166 results on '"Zafar MN"'
Search Results
2. HLA-MATCHING BY DNA METHODS: IMPACT ON A LIVING-RELATED RENAL TRANSPLANTATION PROGRAMME
- Author
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Zafar, MN, primary, Ahmed, N, additional, Abbas, Y, additional, Abbas, K, additional, Naqvi, SAA, additional, and Rizvi, SAH, additional
- Published
- 2002
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3. DFT and comparative adsorption study of NiO, MnO, and Mn 2 NiO 4 nanomaterials for the removal of amaranth dye from synthetic water.
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Ahmad M, Riaz Q, Tabassum M, Shafqat SS, Ayesha AT, Zubair M, Xiong Y, Syed A, Al-Shwaiman HA, Nadeem MA, Jia X, Xu G, and Zafar MN
- Abstract
In the current study, NiO nanoparticles, MnO nanoparticles, and Mn
2 NiO4 nanocomposites (Ni-NPs, Mn-NPs and MN-NCs, respectively) were synthesized using a facile hydrothermal method, and their performance in the removal of amaranth (AM) dye from synthetic wastewater was compared. XRD, FTIR spectroscopy, SEM, BET analysis, and TGA were performed to characterize the produced catalysts. The effect of pertinent parameters, including pH, dosage of catalysts, temperature, and shaking speed on the uptake of AM was investigated through batch experiments. The MN-NCs showed ultrafast and high efficiency for AM removal compared to their counter parts Mn-NPs and Ni-NPs. Under ideal conditions, the highest adsorption efficiencies of AM onto Ni-NPs, Mn-NPs, and MN-NCs were calculated to be 80.50%, 93.85%, and 98.50%, respectively. The Langmuir isotherm fitted the experimental data of AM removal better as shown by the higher values of r , compared to the Freundlich isotherm, indicating monolayer type adsorption of AM. According to kinetic analyses, the adsorption of AM was best described by the pseudo-second-order kinetic model. Further, regeneration/recycling studies showed that MN-NCs retained 79% adsorption efficiency after four cycles. DFT experiments were also conducted to gain a deeper understanding of the process and behavior of AM adsorption. In conclusion, as Ni-NPs, Mn-NPs, and MN-NCs adsorb AM predominantly2 , compared to the Freundlich isotherm, indicating monolayer type adsorption of AM. According to kinetic analyses, the adsorption of AM was best described by the pseudo-second-order kinetic model. Further, regeneration/recycling studies showed that MN-NCs retained 79% adsorption efficiency after four cycles. DFT experiments were also conducted to gain a deeper understanding of the process and behavior of AM adsorption. In conclusion, as Ni-NPs, Mn-NPs, and MN-NCs adsorb AM predominantly via electrostatic interaction, they can be applied for the removal of both cationic and anionic dyes by controlling the pH factor., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)- Published
- 2024
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4. Recent advancements in modifications of metal-organic frameworks-based materials for enhanced water purification and contaminant detection.
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Truong HB, Le VN, Zafar MN, Rabani I, Do HH, Nguyen XC, Hoang Bui VK, and Hur J
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- Adsorption, Environmental Restoration and Remediation methods, Catalysis, Nanocomposites chemistry, Metal-Organic Frameworks chemistry, Water Purification methods, Water Pollutants, Chemical analysis, Water Pollutants, Chemical chemistry
- Abstract
Metal-organic frameworks (MOFs) have emerged as a key focus in water treatment and monitoring due to their unique structural features, including extensive surface area, customizable porosity, reversible adsorption, and high catalytic efficiency. While numerous reviews have discussed MOFs in environmental remediation, this review specifically addresses recent advancements in modifying MOFs to enhance their effectiveness in water purification and monitoring. It underscores their roles as adsorbents, photocatalysts, and in luminescent and electrochemical sensing. Advancements such as pore modification, defect engineering, and functionalization, combined synergistically with advanced materials, have led to the development of recyclable MOF-based nano-adsorbents, Z-scheme photocatalytic systems, nanocomposites, and hybrid materials. These innovations have broadened the spectrum of removable contaminants and improved material recyclability. Additionally, this review delves into the creation of multifunctional MOF materials, the development of robust MOF variants, and the simplification of synthesis methods, marking significant progress in MOF sensor technology. Furthermore, the review addresses current challenges in this field and proposes potential future research directions and practical applications. The growing research interest in MOFs underscores the need for an updated synthesis of knowledge in this area, focusing on both current challenges and future opportunities in water remediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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5. Design and Fabrication of Biomass Derived Black Carbon Modified g-C 3 N 4 /FeIn 2 S 4 Heterojunction as Highly Efficient Photocatalyst for Wastewater Treatment.
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Arif N, Ma Y, Zafar MN, Humayun M, Bououdina M, Zhang SY, Zhang Q, Yang X, Liang H, and Zeng YJ
- Abstract
The environmental deterioration caused by dye wastewater discharge has received considerable attention in recent decades. One of the most promising approaches to addressing the aforementioned environmental issue is the development of photocatalysts with high solar energy consumption efficiency for the treatment of dye-contaminated water. In this study, a novel low-cost π-π biomass-derived black carbon modified g-C
3 N4 coupled FeIn2 S4 composite (i.e., FeInS/BC-CN) photocatalyst is successfully designed and fabricated that reveals significantly improved photocatalytic performance for the degradation of Eosin Yellow (EY) dye in aqueous solution. Under dark and subsequent visible light irradiation, the amount optimized composite reveals 99% removal performance for EY dye, almost three-fold compared to that of the pristine FeInS and BC-CN counterparts. Further, it is confirmed by means of the electron spin resonance spectrometry, quenching experiments, and density functional theory (DFT) calculations, that the hydroxyl radicals (• OH) and superoxide radicals (• O2 - ) are the dominant oxidation species involved in the degradation process of EY dye. In addition, a systematic photocatalytic degradation route is proposed based on the resultant degradation intermediates detectedduring liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. This work provides an innovative idea for the development of advanced photocatalysts to mitigate water pollution., (© 2023 Wiley‐VCH GmbH.)- Published
- 2024
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6. Encapsulation and release of calcein from herceptin-conjugated eLiposomes.
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Zafar MN, Pitt WG, and Husseini GA
- Abstract
Achieving an optimal therapeutic level is crucial in effectively eradicating cancer cells during treatment. However, conventional chemotherapy-associated systemic administration of anticancer agents leads to many side effects. To achieve the desired control over the target site, active targeting of HER2-positive breast cancer cells can be achieved by conjugating liposomal vesicles with Human Epidermal growth factor Receptor 2 (HER2) and inducing release of the encapsulated drug using ultrasound. To further enhance the delivery efficiency, nanoemulsion droplets exhibiting responsiveness to low-frequency ultrasound are encapsulated within these lipid vesicles. In this study, we prepared four different liposomal formulations, namely pegylated liposomes, emulsion liposomes (eLiposomes), HER-conjugated liposomes, and HER-conjugated eLiposomes, each loaded with calcein and subjected to a thorough characterization process. Their sizes, phospholipid concentration, and amount of antibody conjugation were compared and analyzed. Cryogenic transmission electron microscopy was used to confirm the encapsulation of nanoemulsion droplets within the liposomes. The drug-releasing performance of Herceptin-conjugated eLiposomes was found to surpass that of other liposomal formulations with a notably higher calcein release and established it as a highly effective nanocarrier. The study showcases the efficacy of calcein-loaded and Herceptin-conjugated eLiposomes, which demonstrate rapid and efficient drug release among other liposomal formulations when subjected to ultrasound. This discovery paves the way for a more targeted, efficient, and humane approach to cancer therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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7. Correlation of lymphocyte subsets and inflammatory biomarkers with disease severity in COVID-19 patients.
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Abbas K, Musharraf W, Zafar MN, Lal J, Dodani S, and Rizvi SAH
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- Humans, Male, Female, Middle Aged, Retrospective Studies, Lymphocyte Subsets, Lymphocyte Count, Biomarkers, Cytokines, Patient Acuity, COVID-19
- Abstract
Objective: To determine the correlation of lymphocyte subsets and soluble serum inflammatory biomarkers with disease severity in coronavirus disease-2019 infection., Methods: The retrospective study was conducted at the Department of Immunology, Sindh Institute of Urology and Transplantation (SIUI), Karachi, Pakistan from September 1 to November 30, 2021, and comprised data of patients admitted from June to July 2021 who tested positive for coronavirus disease-2019 on the basis of reverse transcription-polymerase chain reaction of nasopharyngeal swab specimens. The patients were categorised into severe group A and non-severe group B. Initial investigations included complete blood count, neutrophil-to-lymphocytes ratio, C-reactive protein, D-Dimers and serum ferritin levels. Lymphocyte subsets included cluster of differentiation-3+, cluster of differentiation-4+/ cluster of differentiation-3+, cluster of differentiation-8+ T lymphocytes, cluster of differentiation-19+B lymphocytes, cluster of differentiation-16+ cluster of differentiation-56+ Natural Killer cells and serum cytokine levels of interleukin-2, interleukin- 4, interleukin-6, interleukin-10, tumour necrosis factor-alpha and interferon gamma. They were correlated with disease severity. Data was analysed using SPSS 20., Results: Of the 54 patients, 33(61.1%) were males and 21(38.9%) were females. There were 29(53.70%) patients in group A with median age 52 years (interquartile range: 43.5-65 years), and 25(46.29%) in group B with median age 50 years (interquartile range: 36.5-59 years) (p=0.241). Disease was significantly more severe in male patients compared to female (p=0.002). In group A, cluster of differentiation-3+ T cells were reduced in 21(72.4%) patients, cluster of differentiation-8+ T cells in 16(55.2%), cluster of differentiation-4+ T cells in 23(79.3%) and cluster of differentiation-19+ B cells in 8(27.6%). In group B, cluster of differentiation-3+ T cells were reduced in 10(40%) subjects, cluster of differentiation-8+ T cells in 7(28%), cluster of differentiation-4+ T cells in 12(48%) and cluster of differentiation-19+ B cells in 4(16%) patients. Serum cytokine levels were not significantly different between the groups (p>0.05). In group A, 7(24.13%) patients died, and in such cases, the neutrophil-to-lymphocytes ratio was significantly higher (p=0.037)., Conclusion: Pro-inflammatory markers and cytokine levels increased, while lymphocyte subsets decreased with increasing severity of the disease.
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- 2024
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8. Preliminary anticancer evaluation of new Pd(II) complexes bearing NNO donor ligands.
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Hussain S, Hussain S, Zafar MN, Hussain I, Khan F, Mughal EU, and Tahir MN
- Abstract
In this study we presented a novel series of NNO tridentate ligands generating imino, amido and oxo donor pocket for Pd(II) coordination. All the compounds were meticulously characterized by elemental analysis and advanced spectroscopic techniques, including FTIR, proton and carbon NMR. The synthesized compounds underwent rigorous evaluation for their potential as anti-cancer agents, utilizing the aggressive breast cancer cell lines MDA-MB (ATCC) and MCF-7 as a crucial model for assessing growth inhibition in cancer cells. Remarkably, the MTT assay unveiled the robust anti-cancer activity for all palladium complexes against MDA-MB-231 and MCF-7 cells. Particularly, complex [Pd(L
1 )(CH3 CN)] exhibited exceptional potency with an IC50 value of 25.50 ± 0.30 µM (MDA-MB-231) and 20.76 ± 0.30 µM (MCF-7), compared to respective 27.00 ± 0.80 µM and 24.10 ± 0.80 µM for cisplatin, underscoring its promising therapeutic potential. Furthermore, to elucidate the mechanistic basis for the anti-cancer effects, molecular docking studies on tyrosine kinases, an integral target in cancer research, were carried out. The outcome of these investigations further substantiated the remarkable anticancer properties inherent to these innovative compounds. This research offers a compelling perspective on the development of potent anti-cancer agents rooted in the synergy between ligands and Pd(II) complexes and presenting a promising avenue for future cancer therapy endeavors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)- Published
- 2024
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9. Construction of Host Plant Insect-Resistance Mutant Library by High-Throughput CRISPR/Cas9 System and Identification of A Broad-Spectrum Insect Resistance Gene.
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Sun L, Alariqi M, Wang Y, Wang Q, Xu Z, Zafar MN, Yang G, Jia R, Hussain A, Chen Y, Ding X, Zhou J, Wang G, Wang F, Li J, Zou J, Zhu X, Yu L, Sun Y, Liang S, Hui F, Chen L, Guo W, Wang Y, Zhu H, Lindsey K, Nie X, Zhang X, and Jin S
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- Humans, Animals, Reactive Oxygen Species metabolism, Plants, Genetically Modified genetics, Plants, Genetically Modified metabolism, Insecta, CRISPR-Cas Systems genetics, RNA, Guide, CRISPR-Cas Systems
- Abstract
Insects pose significant challenges in cotton-producing regions. Here, they describe a high-throughput CRISPR/Cas9-mediated large-scale mutagenesis library targeting endogenous insect-resistance-related genes in cotton. This library targeted 502 previously identified genes using 968 sgRNAs, generated ≈2000 T0 plants and achieved 97.29% genome editing with efficient heredity, reaching upto 84.78%. Several potential resistance-related mutants (10% of 200 lines) their identified that may contribute to cotton-insect molecular interaction. Among these, they selected 139 and 144 lines showing decreased resistance to pest infestation and targeting major latex-like protein 423 (GhMLP423) for in-depth study. Overexpression of GhMLP423 enhanced insect resistance by activating the plant systemic acquired resistance (SAR) of salicylic acid (SA) and pathogenesis-related (PR) genes. This activation is induced by an elevation of cytosolic calcium [Ca
2+ ]cyt flux eliciting reactive oxygen species (ROS), which their demoted in GhMLP423 knockout (CR) plants. Protein-protein interaction assays revealed that GhMLP423 interacted with a human epidermal growth factor receptor substrate15 (EPS15) protein at the cell membrane. Together, they regulated the systemically propagating waves of Ca2+ and ROS, which in turn induced SAR. Collectively, this large-scale mutagenesis library provides an efficient strategy for functional genomics research of polyploid plant species and serves as a solid platform for genetic engineering of insect resistance., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)- Published
- 2024
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10. Palladium-anchored donor-flexible pyridylidene amide (PYA) electrocatalysts for CO 2 reduction.
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Khurshid A, Tanveer T, Hafeez K, Ahmed M, Akhtar Z, and Zafar MN
- Abstract
The conversion of CO
2 into CO as a substitute for processing fossil fuels to produce hydrocarbons is a sustainable, carbon neutral energy technology. However, the electrochemical reduction of CO2 into a synthesis gas (CO and H2 ) at a commercial scale requires an efficient electrocatalyst. In this perspective, a series of six new palladium complexes with the general formula [Pd(L)(Y)]Y, where L is a donor-flexible PYA, N2 , N6 -bis(1-ethylpyridin-4(1 H )-ylidene)pyridine-2,6-dicarboxamide, N2 , N6 -bis(1-butylpyridin-4(1 H )-ylidene)pyridine-2,6-dicarboxamide, or N2 , N6 -bis(1-benzylpyridin-4(1 H )-ylidene)pyridine-2,6-dicarboxamide, and Y = OAc or Cl- , were utilized as active electrocatalysts for the conversion of CO2 into a synthesis gas. These palladium(ii) pincer complexes were synthesized from their respective H-PYA proligands using 1,8-diazobicyclo[5.4.0]undec-7-ene (DBU) or sodium acetate as a base. All the compounds were successfully characterized by various physical methods of analysis, such as proton and carbon NMR, FTIR, CHN, and single-crystal XRD. The redox chemistry of palladium complexes toward carbon dioxide activation suggested an evident CO2 interaction with each Pd(ii) catalyst. [Pd( N2 , N6 -bis(1-ethylpyridin-4(1 H )-ylidene)pyridine-2,6-dicarboxamide)(Cl)]Cl showed the best electrocatalytic activity for CO2 reduction into a synthesis gas under the acidic condition of trifluoracetic acid (TFA) with a minimum overpotential of 0.40 V, a maximum turnover frequency (TOF) of 101 s-1 , and 58% FE of CO. This pincer scaffold could be stereochemically tuned with the exploration of earth abundant first row transition metals for further improvements in the CO2 reduction chemistry., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)- Published
- 2023
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11. Benzimidazol-2-ylidene ruthenium complexes for C-N bond formation through alcohol dehydrogenation.
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Nawaz Z, Gürbüz N, Zafar MN, Özdemir N, Çetinkaya B, and Özdemir İ
- Abstract
A low temperature hydrogen borrowing approach to generate secondary amines using benzimidazole-based N -heterocyclic carbene (BNHC) ruthenium complexes is reported. A series of the piano-stool complexes of the type [(η
6 - p -cymene)(BNHC)RuCl2 ] ( 1a - g ) were synthesized via one-pot reaction of the NHC salt precursor, Ag2 O, and [RuCl2 (p-cymene)]2 and characterized using conventional spectroscopic techniques. The geometry of two precursors, [(η6 - p -cymene)(Me4Bn Me2 BNHCCH2OxMe )RuCl2 ] ( 1f ) and [(η6 - p -cymene)(Me5Bn Me2 BNHCCH2OxMe )RuCl2 ] ( 1g ), was studied by single crystal X-ray diffraction. These catalysts were found to dehydrogenate alcohols efficiently at temperatures as low as 50 °C to allow Schiff-base condensation and subsequent imine hydrogenation to afford secondary amines. Notably, this ruthenium-based procedure enables the N -alkylation of aromatic and heteroaromatic primary amines with a wide range of primary alcohols in excellent yields of up to 98%. The present methodology is green and water is liberated as the sole byproduct., (© TÜBİTAK.)- Published
- 2023
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12. Bacterial isolates and their antimicrobial susceptibility profile of superficial and deep-seated skin and soft tissue infections.
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Abid Khan RM, Dodani SK, Nadeem A, Jamil S, and Zafar MN
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Background: Skin and soft tissue infections (SSTIs) are caused by microbial invasion of healthy or damaged skin. SSTIs are difficult to manage and contribute to chronicity and emergence of antimicrobial resistance., Objectives: To ascertain the prevalence of bacteria causing SSTIs and their antimicrobial susceptibility patterns., Methods: A prospective study between November 2020 and May 2021. A total of 447 samples from SSTIs were analyzed., Results: A total of 347 samples revealed mono-bacterial growth, of which 67% were male. SSTIs are common among patients aged 21-50 years with the dominance (78%) of gram-negative rods (GNRs). Escherichia coli (36%), Klebsiella spp. (22%), Staphylococcus aureus (16%), and Pseudomonas aeruginosa (11%) were predominant organisms. GNRs were highly resistant (>65%) to ciprofloxacin and trimethoprim-sulfamethoxazole. For injectable antibiotics, the highest resistance was determined against ceftriaxone, and the least resistance was determined against amikacin. Resistance against carbapenem was the highest among P. aeruginosa (53%) and Klebsiella spp. (32%). S. aureus showed the highest resistance against ciprofloxacin, and the least resistance was determined against clindamycin. Of 57 S. aureus isolates, 86% isolates were methicillin-resistant Staphylococcus aureus (MRSA). All isolates of P. aeruginosa and S. aureus were sensitive to polymyxin B and vancomycin, respectively. The prevalence of multidrug-resistant E. coli and Klebsiella spp. was higher among deep-seated SSTIs (dSSTIs)., Conclusions: The predominant etiology of SSTIs is GNR. Currently, there is very high resistance against oral antibiotics. Antimicrobial resistance against carbapenem has also increased. Moreover, there is a high frequency of MRSA. MDR E. coli and Klebsiella spp. isolates are frequently involved in dSSTIs., (© 2023 Rao Muhammad Abid Khan et al., published by Sciendo.)
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- 2023
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13. Optimization of the photocatalytic degradation of phenol using superparamagnetic iron oxide (Fe 3 O 4 ) nanoparticles in aqueous solutions.
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Bazrafshan E, Mohammadi L, Zarei AA, Mosafer J, Zafar MN, and Dargahi A
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The present work was carried out to remove phenol from aqueous medium using a photocatalytic process with superparamagnetic iron oxide nanoparticles (Fe
3 O4 ) called SPIONs. The photocatalytic process was optimized using a central composite design based on the response surface methodology. The effects of pH (3-7), UV/SPION nanoparticles ratio (1-3), contact time (30-90 minutes), and initial phenol concentration (20-80 mg L-1 ) on the photocatalytic process were investigated. The interaction of the process parameters and their optimal conditions were determined using CCD. The statistical data were analyzed using a one-way analysis of variance. We developed a quadratic model using a central composite design to indicate the photocatalyst impact on the decomposition of phenol. There was a close similarity between the empirical values gained for the phenol content and the predicted response values. Considering the design, optimum values of pH, phenol concentration, UV/SPION ratio, and contact time were determined to be 3, 80 mg L-1 , 3, and 60 min, respectively; 94.9% of phenol was eliminated under the mentioned conditions. Since high values were obtained for the adjusted R2 (0.9786) and determination coefficient ( R2 = 0.9875), the response surface methodology can describe the phenol removal by the use of the photocatalytic process. According to the one-way analysis of variance results, the quadratic model obtained by RSM is statistically significant for removing phenol. The recyclability of 92% after four consecutive cycles indicates the excellent stability of the photocatalyst for practical applications. Our research findings indicate that it is possible to employ response surface methodology as a helpful tool to optimize and modify process parameters for maximizing phenol removal from aqueous solutions and photocatalytic processes using SPIONs., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)- Published
- 2023
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14. Providing "Free" Access to Dialysis and Transplant to the Disfranchised. A Sustainable Model for Low and Low Middle Income Countries (LMICs).
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Zafar MN and Rizvi SAH
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- Child, Humans, Renal Dialysis, Developing Countries, Renal Replacement Therapy, Registries, Kidney Transplantation methods, Kidney Failure, Chronic surgery
- Abstract
Pakistan is a low-middle income country where incidence of End Stage Kidney Disease (ESKD) is 100-150 per million population (pmp). Paucity and high costs of renal replacement therapy (RRT) renders the majority disfranchised, since the dialysis rate is 15 pmp and the transplant rate is 4-5 pmp. In view of this, our center started an integrated dialysis and transplant program where all treatment is provided "Free of Cost" to all patients, with lifelong follow-up and medications. The model is based on the concept of community-government partnership funded by both partners. The annual contribution in 2021 was $37.4 million. >1,500 patients were dialyzed daily, and 6-8 received transplants weekly. Of the 6,553 transplants performed between 1985-2021, 988 (15%) were children. Overall, the 1 and 5-year graft survival rate was 97% and 88%. The donor clinic has 3,786 donors in regular yearly follow-up for up to 30-35 years where ESKD prevalence is 0.29%. Access to dialysis was increased by establishing six satellite centers reducing patient time and travel costs. Cost reductions by dialyzer reuse and generic drugs resulted in an annual saving of $5.8 m. This sustainable model has overcome the inherent socio-economic, logistic, cultural, and gender biases in RRT in LMICs. It has provided RRT with equity to the disfranchised in Pakistan and can be replicated in other LMICs with community-government support., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zafar and Rizvi.)
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- 2023
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15. Impact of pre-transplant donor specific antibodies detected by Luminex with negative microlymphocytotoxicity assay and flow crossmatch in live-related renal transplant recipients.
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Abbas K, Aziz T, Musharaf W, Mubarak M, and Zafar MN
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- Humans, Retrospective Studies, Antibodies, Tissue Donors, Transplant Recipients, Antilymphocyte Serum, Graft Survival, Graft Rejection etiology, HLA Antigens, Histocompatibility Testing, Isoantibodies, Kidney Transplantation adverse effects
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Introduction/aim: The Luminex assay, where beads are coated with a single HLA antigen, has been shown to detect HLA antibodies with more sensitivity and specificity as compared to microlymphocytotoxicity (CDC) assay and flow cross match (FCXM). We report the impact of low Mean Flourescence intensity (MFI) pre-transplant DSA by Luminex with negative CDC and FCXM on acute rejection, graft function, and survival., Methods: In this retrospective study between January 2015 to December 2021, 45 recipients had pre-transplant anti-HLA donor-specific antibodies (DSAs) detected by Luminex. Two control groups of 45 patients each matched for age and gender, first with non-DSA HLA antibodies and second with no antibodies by Luminex were selected to compare outcomes with DSA group., Results: In the DSA group of 45, 22 (48.8%) had class I (MFI mean 4043 ± 1909, range: 1096-7111), 20 (44.4%) class II (MFI mean 3601 ± 2310, range: 1031-9259), and 3 (6.6%) both class I (MFI mean 4746 ± 1922) and class II (MFI mean 3940 ± 2312) antibodies. Acute rejection episodes were reported in 15.6%, DSA group, 17.8% in non-DSA, and 24.4% in no antibody group (p = .538). Death censored graft survival at 1 and 5 years was 98% and 93% in DSA group, 100% and 95% in non-DSA and 93% and 85% in the no antibody group (p = .254)., Conclusions: Patients with low MFI DSA pre-transplant, with a negative CDC and FCXM under ATG induction, have similar graft outcomes at 1 and 5 years when compared to non-DSA and no antibody groups., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2023
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16. Metal organic frameworks as promising sensing tools for electrochemical detection of persistent heavy metal ions from water matrices: A concise review.
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Shafqat SS, Rizwan M, Batool M, Shafqat SR, Mustafa G, Rasheed T, and Zafar MN
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- Humans, Water, Ions, Metal-Organic Frameworks, Metals, Heavy, Environmental Pollutants
- Abstract
Water bodies are being polluted rapidly by disposal of toxic chemicals with their huge entrance into drinking water supply chain. Among these pollutants, heavy metal ions (HMIs) are the most challenging one due to their non-biodegradability, toxicity, and ability to biologically hoard in ecological systems, thus posing a foremost danger to human health. This can be addressed by robust, sensitive, selective, and reliable sensing of metal ions which can be achieved by Metal organic frameworks (MOF) based electrochemical sensors. In the present era, MOFs have caught greater interest in a variety of applications including sensing of hazardous pollutants such as heavy metal ions. So, in this review article, types, synthesis and working mechanism of MOF based sensors is explained to give general overview with updated literature. First time, detailed study is done for sensing of metal ions such as chromium, mercury, zinc, copper, manganese, palladium, lead, iron, cadmium and lanthanide by MOFs based electrochemical sensors. The use of MOFs as electrochemical sensors has attractive success story along with some challenges of the area. Considering these challenges, we attempted to highlight the milestone achieved and shortcomings along with future prospective of the MOFs for employing it in electrochemical sensing devices for HMIs. Finally, challenges and future prospects have been discussed to promote the development of MOFs-based sensors in future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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17. Acoustically-Activated Liposomal Nanocarriers to Mitigate the Side Effects of Conventional Chemotherapy with a Focus on Emulsion-Liposomes.
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Zafar MN, Abuwatfa WH, and Husseini GA
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To improve currently available cancer treatments, nanomaterials are employed as smart drug delivery vehicles that can be engineered to locally target cancer cells and respond to stimuli. Nanocarriers can entrap chemotherapeutic drugs and deliver them to the diseased site, reducing the side effects associated with the systemic administration of conventional anticancer drugs. Upon accumulation in the tumor cells, the nanocarriers need to be potentiated to release their therapeutic cargo. Stimulation can be through endogenous or exogenous modalities, such as temperature, electromagnetic irradiation, ultrasound (US), pH, or enzymes. This review discusses the acoustic stimulation of different sonosensitive liposomal formulations. Emulsion liposomes, or eLiposomes, are liposomes encapsulating phase-changing nanoemulsion droplets, which promote acoustic droplet vaporization (ADV) upon sonication. This gives eLiposomes the advantage of delivering the encapsulated drug at low intensities and short exposure times relative to liposomes. Other formulations integrating microbubbles and nanobubbles are also discussed.
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- 2023
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18. Rice Nutraceuticals and Bioactive Compounds: Extraction, Characterization and Antioxidant Activity: A Review.
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Zubair M, Anwar F, Arshad I, Malik S, and Zafar MN
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Rice ( Oryza sativa L.), a cereal grass, belongs to the genus Oryza from the family Poaceae, which encompasses twenty-five species cultured in many countries of Asia, and partly in the rest of the world. From these species, two viz . Oryza sativa ( O. sativa ) Asian rice and Oryza glaberrima ( O. glaberrima ) African rice are commonly found and the most widely consumed staple food by a large part of the human population in the world, especially in Asia due to their nutritional and nutraceutical prospects. Rice, a popular source of carbohydrates, also contains a good amount of dietary fiber, minerals (Ca, Zn, Se, P, K, Mg, Fe, and Mn), protein and vitamin B along with several other medicinally important bioactives such as tocols (α-tocopherols and α-tocotrienols) (ßsitosterol) phenolic acids, flavonoids (apiginine), and oryzanol (24-Methylenecylcoartanyl transferulate). Rice bran is a byproduct of the rice polishing industry and is valuable in terms of containing 15-20% high-value oil. Because of the natural antioxidants present in rice, several medicinal benefits and biological properties can be attributed to rice consumption. The nutrient profile of rice varies based on several factors, such as grains (white, brown, red, and black/purple), the extent of polishing, and the preparation method. Considering the importance of rice as a traditional diet rich in high-value bioactives, together with the existing gap of related information, it is worthwhile to assemble a comprehensive review that focuses on the detailed profile of valuable nutrients and high-value phytochemicals and biological activities of rice to explore its functional food and nutraceutical applications. This review attempts to provide collective information on the essential rice cereal for its nutritional and antioxidant potential., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
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- 2023
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19. Primary hyperoxaluria: Comprehensive mutation screening of the disease causing genes and spectrum of disease-associated pathogenic variants.
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Abid A, Raza A, Khan AR, Firasat S, Shahid S, Hashmi S, Zafar MN, Sultan S, Khaliq S, and Rizvi SA
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- Humans, Child, Mutation, Hyperoxaluria, Primary diagnosis, Hyperoxaluria, Primary genetics
- Abstract
The primary hyperoxalurias are rare disorders of glyoxylate metabolism. Accurate diagnosis is essential for therapeutic and management strategies. We conducted a molecular study on patients suffering from recurrent calcium-oxalate stones and nephrocalcinosis and screened primary hyperoxaluria causing genes in a large cohort of early-onset cases. Disease-associated pathogenic-variants were defined as missense, nonsense, frameshift-indels, and splice-site variants with a reported minor allele frequency <1% in controls. We found pathogenic-variants in 34% of the cases. Variants in the AGXT gene causing PH-I were identified in 81% of the mutation positive cases. PH-II-associated variants in the GRHPR gene are found in 15% of the pediatric PH-positive population. Only 3% of the PH-positive cases have pathogenic-variants in the HOGA1 gene, responsible to cause PH-III. A population-specific AGXT gene variant c.1049G>A; p.Gly350Asp accounts for 22% of the PH-I-positive patients. Pathogenicity of the identified variants was evaluated by in-silico tools and ACMG guidelines. We have devised a rapid and low-cost approach for the screening of PH by using targeted-NGS highlighting the importance of an accurate and cost-effective screening platform. This is the largest study in Pakistani pediatric patients from South-Asian region that also expands the mutation spectrum of the three known genes., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2023
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20. Efficient and tunable enhancement of NLO performance for indaceno-based donor moiety in A-π-D-π-D-π-A type first DSSC design by end-capped acceptors.
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Hassan AU, Sumrra SH, Mustafa G, Nazar MF, and Zafar MN
- Subjects
- Density Functional Theory
- Abstract
Background: The organic dyes with non-fullerene acceptors (NFAs) have aided in the creation of competitive organic solar cells (OSCs) with long-term sustainability. A series of NFA dyes (IDIC-R1-IDIC-R9) have been designed by varying the end-capped fluorinated moieties (PD1-PD6) at indaceno (IDIC) core., Methods: All the calculations were performed by density functional theory (DFT) and time-dependent DFT (TD-DFT)-based approaches. All the geometries were optimized at B3LYP/6-31G + (d,p) of DFT level at their ground state energies. Out of several density functionals, the CAM-B3LYP with 6-31G + (d,p) basis sets was selected after a benchmark study to carry out further calculations. All the dyes had their bandgaps in 0.11-3.12 eV while their starting reference dye had a bandgap value of 2.01 eV., Results: Their ionization potential (IP) implied that these dyes have strong tendency to lose electrons. The λ
max of the dyes was slightly redshifted from the IDIC (476 nm) and IDIC-R (479 nm) when changing solvent polarity from methanol to DCM and then chloroforms. The natural bond orbital (NBO) analysis showed the (S63)LP → (C61-C62)π* with highest stabilization energy. Their electron injection analysis showed that these dyes can be a good anode material against the aluminum and gold electrodes. The intramolecular charge transfer (ICT) process and stability of the dyes were investigated using frontier molecular orbital (FMO) and natural bond orbital (NBO) analysis., Conclusion: Among all dyes, IDIC-R8 has the highest linear polarizability and second-order hyperpolarizability (βtotal ). All the dyes demonstrated promising non-linear optical (NLO) properties due to their low charge transfer barriers. Scientists would be able to exploit these properties to identify the best NLO materials for existing applications., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)- Published
- 2022
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21. Recurrent Urinary Tract Infections in Renal Transplant Recipients: Risk Factors and Outcomes in Low-resource Settings.
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Jamil S, Zafar MN, Siddiqui S, Ayub S, and Rizvi AU
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- Humans, Retrospective Studies, Kidney, Risk Factors, Escherichia coli, Transplant Recipients, Kidney Transplantation adverse effects, Urinary Tract Infections diagnosis, Urinary Tract Infections epidemiology, Urinary Tract Infections drug therapy
- Abstract
Recurrent urinary tract infections (UTIs) after kidney transplantation are a common problem adversely affecting graft outcomes. This retrospective study aimed to report the frequency and risk factors of recurrent UTI and their impact on graft and patient outcomes in kidney transplant recipients at the Sindh Institute of Urology and Transplantation, Karachi, Pakistan, in January-December 2015. Five-year graft and patient survival rates were compared among different groups using Kaplan-Meier analysis. Of the 251 recipients, 67 developed one episode of UTI. Of these 67, 29 had 76 episodes of recurrent UTI. Out of the 76 episodes of recurrent UTI, Escherichia coli was the most common pathogen in 32 cases. Organisms causing recurrent UTI showed resistance to carbapenem in 19 cases versus 2 in the non-recurrent UTI group (P = 0.006). The estimated glomerular filtration rate at 1 year was 57.8 ± 16.23 mL/min/1.73 m2 in the recurrent UTI group vs. 61.9 ± 15.7 mL/min/1.73 m2 in the non-recurrent UTI group (P = 0.001). Graft survival in the recurrent UTI group at 5 years was significantly lower (76%) than in the non-recurrent UTI (95%) and no UTI groups (93%) (log-rank P = 0.006), with no significant effect on patient survival in these groups (P = 0.429). The presence of double-J stent (P = 0.036) and cytomegalovirus infections (P = 0.013) independently predicted recurrent UTI. Recurrent UTIs are common in low-resource settings and adversely affect graft outcomes. Appropriate prophylaxis and treatment are important to reduce recurrent UTI to improve graft outcomes., (Copyright © 2022 Copyright: © 2022 Saudi Journal of Kidney Diseases and Transplantation.)
- Published
- 2022
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22. Primary hyperoxaluria and genetic linkages: an insight into the disease burden from Pakistan.
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Hashmi S, Abid A, Sultan S, Shekhani SS, Lanewala AA, and Zafar MN
- Subjects
- Child, Cost of Illness, Female, Genetic Linkage, Humans, Male, Pakistan epidemiology, Retrospective Studies, Hyperoxaluria complications, Hyperoxaluria, Primary complications, Hyperoxaluria, Primary epidemiology, Hyperoxaluria, Primary genetics, Kidney Calculi complications, Nephrocalcinosis epidemiology, Nephrocalcinosis genetics
- Abstract
Autosomal recessive disorders are prevalent in Pakistan, a developing South Asian country where consanguineous marriages are common. This study seeks to determine the prevalence of monogenic causes in children presenting with nephrocalcinosis and nephrolithiasis at a dialysis and transplant center in Karachi, Pakistan. A retrospective analysis was conducted in children aged 1-18 years presenting with nephrocalcinosis, between 2010 and 2019. Demographic information, clinical profile, laboratory parameters and stone analysis were collected, on a pre-designed questionnaire. One hundred and twenty-six children were included, with 11 and 3 diagnosed with renal tubular acidosis and Bartter's syndrome respectively. Next-generation sequencing and Sanger sequencing was performed on 112 children. Eighty-seven patients were diagnosed with primary hyperoxaluria, with mutations in alanine-glyoxylate-aminotransferase gene found in 73, followed by glyoxylate reductase/hydroxy-pyruvate reductase in 13, and 4-hydroxy-2-oxaloglutarate aldolase in 1. Twenty-five patients reported negative for mutations. Sixty-four percent were males, with a statistically significant difference (p < 0.05). History of parental consanguineous marriage was found in 98% of the cohort. Fifty-four and 40 patients presented to the clinic with Chronic Kidney Disease Stage 1 and Stage 5, respectively, with a statistically significant difference p = 0.007. Mutations noted in our cohort are different and more severe than those reported in the developed world. The disease poses a major disease burden in developing world context with the only treatment option of combined liver-kidney transplantation not available in Pakistan., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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23. Surfactant stabilized gold nanomaterials for environmental sensing applications - A review.
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Najeeb J, Farwa U, Ishaque F, Munir H, Rahdar A, Nazar MF, and Zafar MN
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- Colorimetry, Gold chemistry, Surface-Active Agents, Metal Nanoparticles chemistry, Nanostructures chemistry
- Abstract
Surfactant stabilized Gold (Au) nanomaterials (NMs) have been documented extensively in recent years for numerous sensing applications in the academic literature. Despite the crucial role these surfactants play in the sensing applications, the comprehensive reviews that highlights the fundamentals associated with these assemblies and impact of these surfactants on the properties and sensing mechanisms are still quite scare. This review is an attempt in organizing the vast literature associated with this domain by providing critical insights into the fundamentals, preparation methodologies and sensing mechanisms of these surfactant stabilized Au NMs. For the simplification, the surfactants are divided into the typical and advanced surfactants and the Au NMs are classified into Au nanoparticles (NPs) and Au nanoclusters (NCs) depending upon the complexity in structure and size of the NMs respectively. The preparative methodologies are also elaborated for enhancing the understanding of the readers regarding such assemblies. The case studies regarding surfactant stabilized Au NMs were further divided into colorimetric sensors, surface plasmonic resonance (SPR) based sensors, luminescence-based sensors, and electrochemical/electrical sensors depending upon the property utilized by the sensor for the sensing of an analyte. Future perspectives are also discussed in detail for the researchers looking for further progress in that particular research domain., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2022
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24. Enhanced Antifungal and Wound Healing Efficacy of Statistically Optimized, Physicochemically Evaluated Econazole-Triamcinolone Loaded Silica Nanoparticles.
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Maheen S, Younis H, Khan HU, Salman Shafqat S, Ali S, Rehman AU, Ilyas S, Zafar MN, Shafqat SR, Kalam A, and Al-Ghamdi AA
- Abstract
Co-encapsulated econazole nitrate-triamcinolone acetonide loaded biocompatible, physically stable, and non-irritating mesoporous silica nanoparticles (EN-TA-loaded MSNs) were prepared and optimized by using a central composite rotatable design (CCRD) for providing better therapeutic efficacy against commonly prevailed resistant fungal infections. These drugs loaded MSNs can significantly overcome the deficiencies and problems like short duration of action, requirement of frequent administration, erythema, and burning sensation and irritation associated with conventional drug delivery systems. The stability of optimized drugs loaded MSNs prepared with 100 gm of oil at pH 5.6 with a stirring time of 2 h was confirmed from a zeta potential value of -25 mV. The remarkable compatibility of formulation ingredients was depicted by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) spectra while scanning electron microscopy (SEM) and size analysis represented a very fine size distribution of nanoparticles ranging from 450-600 nm. The CCRD clearly predicted that the optimized parameters of drugs loaded MSNs have better values of percentage yield (85%), EN release (68%), and TA release (70%). Compared to pure drugs, the decreased cytotoxicity of EN-TA-loaded MSNs was quite evident because they showed a cell survival rate of 90%, while in the case of pure drugs, the survival rate was 85%. During in vivo antifungal testing against Candida albicans performed on three different groups, each consisting of six rabbits, the EN-TA-loaded MSNs were relatively superior in eradicating the fungal infection as a single animal exhibited a positive culture test. Rapid recovery of fungal infection and a better therapeutic effect of EN-TA-loaded MSN were quite evident in wound healing and histopathology studies. Likewise, on the 14th day, a larger inhibitory zone was measured for optimized nanoparticles (15.90 mm) compared to the suspension of pure drugs (13.90 mm). In skin irritation studies, MSNs did not show a grade of erythema compared to pure drugs, which showed a four-fold grade of erythema. As a result, MSNs loaded with combination therapy seem to have the potential of improving patient compliance and tolerability by providing enhanced synergistic antifungal effectiveness at a reduced dose with accelerated wound healing and reduced toxicity of therapeutics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maheen, Younis, Khan, Salman shafqat, Ali, Rehman, Ilyas, Zafar, Shafqat, Kalam and Al-Ghamdi.)
- Published
- 2022
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25. Application of Green Gold Nanoparticles in Cancer Therapy and Diagnosis.
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Sargazi S, Laraib U, Er S, Rahdar A, Hassanisaadi M, Zafar MN, Díez-Pascual AM, and Bilal M
- Abstract
Nanoparticles are currently used for cancer theranostics in the clinical field. Among nanoparticles, gold nanoparticles (AuNPs) attract much attention due to their usability and high performance in imaging techniques. The wide availability of biological precursors used in plant-based synthesized AuNPs allows for the development of large-scale production in a greener manner. Conventional cancer therapies, such as surgery and chemotherapy, have significant limitations and frequently fail to produce satisfying results. AuNPs have a prolonged circulation time, allow easy modification with ligands detected via cancer cell surface receptors, and increase uptake through receptor-mediated endocytosis. To exploit these unique features, studies have been carried out on the use of AuNPs as contrast agents for X-ray-based imaging techniques (i.e., computed tomography). As nanocarriers, AuNPs synthesized by nontoxic and biocompatible plants to deliver therapeutic biomolecules could be a significant stride forward in the effective treatment of various cancers. Fluorescent-plant-based markers, including AuNPs, fabricated using Medicago sativa , Olax Scandens , H. ambavilla , and H. lanceolatum , have been used in detecting cancers. Moreover, green synthesized AuNPs using various extracts have been applied for the treatment of different types of solid tumors. However, the cytotoxicity of AuNPs primarily depends on their size, surface reactivity, and surface area. In this review, the benefits of plant-based materials in cancer therapy are firstly explained. Then, considering the valuable position of AuNPs in medicine, the application of AuNPs in cancer therapy and detection is highlighted with an emphasis on limitations faced by the application of such NPs in drug delivery platforms.
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- 2022
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26. New organosulfur metallic compounds as potent drugs: synthesis, molecular modeling, spectral, antimicrobial, drug likeness and DFT analysis.
- Author
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Hassan AU, Sumrra SH, Zafar MN, Nazar MF, Mughal EU, Zafar MN, and Iqbal M
- Subjects
- Acetylcholinesterase, Butyrylcholinesterase, Ligands, Microbial Sensitivity Tests, Schiff Bases chemistry, Spectroscopy, Fourier Transform Infrared, Anti-Infective Agents pharmacology, Pharmaceutical Preparations
- Abstract
During the present investigation, two new sulfonamide-based Schiff base ligands, 4-{[(2-hydroxy-3-methoxyphenyl)methylidene]amino}-N-(1,3-thiazol-2-yl)benzene-1-sulfonamide (L
1 ) and 4-{[1-(2-hydroxyphenyl)ethylidene]amino}-N-(1,3-thiazol-2-yl)benzene-1-sulfonamide (L2 ), have been synthesized and coordinated with the transition metals (V, Fe, Co, Ni, Cu and Zn). The ligands were characterized by their physical (color, melting point, yield and solubility), spectral (UV-Vis, FT-IR, LC-MS,1 H NMR and13 C NMR) and elemental data. The structures of the metal complexes (1)-(12) were evaluated through their physical (magnetic and conductance), spectral (UV-Vis, FT-IR and LC-MS) and elemental data. The molecular geometries of ligands and their selected metal complexes were optimized at their ground state energies by B3LYP level of density functional theory (DFT) utilizing 6-311+G (d, p) and LanL2DZ basis set. The first principle study has been discussed for the electronic properties, the molecular electrostatic possibilities as well as the quantum chemical identifiers. An obvious transition of intramolecular charge had been ascertained from the occupied to the unoccupied molecular orbitals. The UV-Vis analysis was performed through time-dependent density functional theory (TD-DFT) by CAM-B3LYP/6-311+G (d, p) function. The in vitro antimicrobial activity was studied against two fungal (Aspergillus niger and Aspergillus flavus) and four bacterial (Staphylococcus aureus, Klebsiela pneumoniae, Escherichia coli and Bacillus subtilis) species. The antioxidant activity was executed as antiradical DPPH scavenging activity (%), total iron reducing power (%) and total phenolic contents (mg GAE g-1 ). Additionally, enzyme inhibition activity was done against four enzymes (Protease, α-Amylase, Acetylcholinesterase and Butyrylcholinesterase). All the synthetic products exhibited significant bioactivity which were found to enhance upon chelation due to phenomenon of charge transfer from metal to ligand., (© 2021. Springer Nature Switzerland AG.)- Published
- 2022
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27. Heating effect on quality characteristics of mixed canola cooking oils.
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Baig A, Zubair M, Sumrra SH, Nazar MF, Zafar MN, Jabeen K, Hassan MB, and Rashid U
- Abstract
Background: The subcontinent is famous for its variety of seasonal foods cooked in vegetable seed cooking oils at elevated heating. Oils are often of poor quality that effect to consumer health. The work, therefore, planned to examine the effects of heat on the quality of mixed canola cooking oils (MCCOs). MCCOs were analyzed by preparing volatile fatty acid methyl esters (FAMEs) and for physiochemical properties., Results: A major change was observed in the FAs composition of various MCCOs as coded K-1 to K-5. MCCOs were found rich in unsaturated 9-octadecanoic acid (oleic acid C
18:1 ) and 9, 12-octadecadienoic acid (linoleic acid C18:2 ) along saturated octadecanoic acid (stearic acid C18:0 ). Results reveals that canola oil samples are mixed in the range of 4-30% with other vegetable oils and animal fats. The quality of canola cooking oils further reduced after heating to 100 °C, 200 °C and 350 °C, respectively. Quality parameters of MCCOs were significantly altered after heating and found as color (510-520 nm to 570-600 nm), mass 220-237 g to 210-225 g, volume 250 mL to 239 mL, pH (6.76-6.89), specific gravity (0.87-0.92), refractive index (1.471-1.475), saponification value (SV) (0.7-2.5), un-saponifiable matter (2.4-9.8%) and acid value (AV) (1.20-5.0 mg KOH)., Conclusion: Heating of oils at elevated temperature have shown a significant effect on pH, specific gravity and un-saponifiable matter (p-value < 0.05). Large changes in the physicochemical parameters and FAs composition help to develop a conclusion that cooking at high temperatures affects the quality of mixed canola cooking oils., (© 2022. The Author(s).)- Published
- 2022
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28. Multivariate Investigation of Toxic and Essential Metals in the Serum from Various Types and Stages of Colorectal Cancer Patients.
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Mahmood MHR, Qayyum MA, Yaseen F, Farooq T, Farooq Z, Yaseen M, Irfan A, Muddassir K, Zafar MN, Qamar MT, Abbasi AM, and Liu HY
- Subjects
- Humans, Metals, Smoking, Spectrophotometry, Atomic, Colorectal Neoplasms, Trace Elements analysis
- Abstract
Colorectal cancer (CRC) is currently one of the most frequent malignant neoplasms, ranking 3rd in incidence and 2nd in mortality both in the USA and across the world. The pathogenesis of CRC is a complex interaction between genetic susceptibility and environmental factors such as exposure to metals. Therefore, the present study was intended to assess the imbalances in the concentrations of selected essential/toxic elements (Pb, Cr, Fe, Zn, As, Cd, Cu, Se, Ni, and Hg) in the serum of newly diagnosed colorectal carcinoma patients (n = 165) in comparison with counterpart controls (n = 151) by atomic absorption spectrometry after wet-acid digestion method. Serum carcinoembryonic antigen (CEA) of the CRC patients was determined using immunoradiometric method. Body mass index (BMI) which is an established risk factor for CRC was also calculated for patients and healthy controls. Conversely, average Ni (2.721 μg/g), Cd (0.563 μg/g), As (0.539 μg/g), and Pb (1.273 μg/g) levels were significantly elevated in the serum of CRC patients compared to the healthy donors, while the average Se (7.052 μg/g), Fe (15.67 μg/g), Cu (2.033 μg/g), and Zn (8.059 μg/g) concentrations were elevated in controls. The correlation coefficients between the elements in the cancerous patients demonstrated significantly dissimilar communal relationships compared with the healthy subjects. Significant differences in the elemental levels were also showed for CRC types (primary colorectal lymphoma, gastrointestinal stromal tumor, and adenocarcinoma) and CRC stages (stage-I, stage-II, stage-III, and stage-IV) among the patients. Majority of the elements demonstrated perceptible disparities in their levels based on dietary, habitat, gender, and smoking habits of the malignant patients and healthy subjects. Multivariate methods revealed noticeably divergent apportionment among the toxic/essential elements in the cancerous patients than the healthy counterparts. Overall, the study showed significantly divergent distribution and associations of the essential and toxic elemental levels in the serum of the CRC patients in comparison with the healthy donors., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)
- Published
- 2022
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29. Pd(II) complexes with chelating N-(1-alkylpyridin-4(1H)-ylidene)amide (PYA) ligands: Synthesis, characterization and evaluation of anticancer activity.
- Author
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Zafar MN, Butt AM, Chaudhry GE, Perveen F, Nazar MF, Masood S, Dalebrook AF, Mughal EU, Sumrra SH, Sung YY, Muhammad TST, and Wright LJ
- Subjects
- Antineoplastic Agents chemistry, Apoptosis drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Crystallography, X-Ray methods, DNA chemistry, HeLa Cells, Humans, Ligands, Molecular Structure, Quantitative Structure-Activity Relationship, Amides chemistry, Antineoplastic Agents pharmacology, Coordination Complexes chemistry, Palladium chemistry, Pyridinium Compounds chemistry
- Abstract
The bidentate N-(1-Alkylpyridin-4(1H)-ylidene)amide (PYA) pro-ligands [H
2 LBn ][Cl]2 (2), and [H2 LMe ][TfO]2 (3) were prepared by simple alkylation reactions of the known compound, N,N-di(pyridin-4-yl)oxalamide (H2 L, 1). The Pd(II) complexes, [Pd(LBn )2 ][Cl]2 (4), [Pd(LMe )2 ][Cl][TfO] (5), Pd(LBn )Cl2 (6) and Pd(LMe )Cl2 (7) were synthesized through reactions between these pro-ligands and suitable Pd(II) substrates in the presence of base. The molecular structures of 3 and 6 were obtained by single crystal X-ray structure determinations. Studies of the experimental and computational DNA binding interactions of the compounds 1-7 revealed that overall 4 and 6 have the largest values for the binding parameters Kb and ΔGb o . The results showed a good correlation with the steric and electronic parameters obtained by quantitative structure activity relationship (QSAR) studies. In-vitro cytotoxicity studies against four different cell lines showed that the human breast cancer cell lines MCF-7, T47D and cervical cancer cell line HeLa had either higher or similar sensitivities towards 4, 6 and 2, respectively, compared to cisplatin. In general, the cytotoxicity of the compounds, represented by IC50 values, decreased in the order 4 > 6 > 2 > 5 > 3 > 1 > 7 in cancer cell lines. Apoptosis contributed significantly to the cytotoxic effects of these anticancer agents as evaluated by apoptosis studies., (Copyright © 2021. Published by Elsevier Inc.)- Published
- 2021
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30. Exploring 3-hydroxyflavone scaffolds as mushroom tyrosinase inhibitors: synthesis, X-ray crystallography, antimicrobial, fluorescence behaviour, structure-activity relationship and molecular modelling studies.
- Author
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Ashraf J, Mughal EU, Sadiq A, Bibi M, Naeem N, Ali A, Massadaq A, Fatima N, Javid A, Zafar MN, Khan BA, Nazar MF, Mumtaz A, Tahir MN, and Mirzaei M
- Subjects
- Crystallography, X-Ray, Dose-Response Relationship, Drug, Enzyme Inhibitors pharmacology, Molecular Docking Simulation, Molecular Structure, Monophenol Monooxygenase metabolism, Structure-Activity Relationship, Agaricales, Anti-Infective Agents pharmacology, Flavonoids chemistry, Monophenol Monooxygenase antagonists & inhibitors
- Abstract
To explore new scaffolds as tyrosinase enzyme inhibitors remain an interesting goal in the drug discovery and development. In due course and our approach to synthesize bioactive compounds, a series of varyingly substituted 3-hydroxyflavone derivatives ( 1-23 ) were synthesized in one-pot reaction and screened for in vitro against mushroom tyrosinase enzyme. The structures of newly synthesized compounds were unambiguously corroborated by usual spectroscopic techniques (FTIR, UV-Vis,
1 H-,13 C-NMR) and mass spectrometry (EI-MS). The structure of compound 15 was also characterized by X-ray diffraction analysis. Furthermore, the synthesized compounds ( 1-23 ) were evaluated for their antimicrobial potential. Biological studies exhibit pretty good activity against most of the bacterial-fungal strains and their activity is comparable to those of commercially available antibiotics i.e. Cefixime and Clotrimazole. Amongst the series, the compounds 2, 4, 5, 6, 7, 10, 11, 14 and 22 exhibited excellent inhibitory activity against tyrosinase, even better than standard compound. Remarkably, the compound 2 (IC50 = 0.280 ± 0.010 μg/ml) was found almost sixfold and derivative 5 (IC50 = 0.230 ± 0.020 μg/ml) about sevenfold more active as compared to standard Kojic acid (IC50 =1.79 ± 0.6 μg/ml). Moreover, these synthetic compounds ( 1-23 ) displayed good to moderate activities against tested bacterial and fungal strains. Their emission behavior was also investigated in order to know their potential as fluorescent probes. The molecular modelling simulations were also performed to explore their binding interactions with active sites of the tyrosinase enzyme. Limited structure-activity relationship was established to design and develop new tyrosinase inhibitors by employing 2-arylchromone as a structural core in the future. Communicated by Ramaswamy H. Sarma.- Published
- 2021
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31. 2-Benzylidenebenzofuran-3(2 H )-ones as a new class of alkaline phosphatase inhibitors: synthesis, SAR analysis, enzyme inhibitory kinetics and computational studies.
- Author
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Ashraf J, Mughal EU, Alsantali RI, Sadiq A, Jassas RS, Naeem N, Ashraf Z, Nazir Y, Zafar MN, Mumtaz A, Mirzaei M, Saberi S, and Ahmed SA
- Abstract
The excelling role of organic chemistry in the medicinal field continues to be one of the main leads in the drug development process. Particularly, this industry requires organic chemists to discover small molecular structures with powerful pharmacological potential. Herein, a diverse range of chalcone (1-11) and aurone (12-22) derivatives was designed and synthesized and for the first time, and both motifs were evaluated as potent inhibitors of alkaline phosphatases (APs). Structural identification of the target compounds (1-22) was accomplished using common spectroscopic techniques. The effect of the nature and position of the substituent was interestingly observed and justified based on the detailed structure-activity relationship (SAR) of the target compounds against AP. It was concluded from the obtained results that all the newly synthesized compounds exhibit high inhibitory potential against the AP enzyme. Among them, compounds 12 (IC
50 = 2.163 ± 0.048 μM), 15 (IC50 = 2.146 ± 0.056 μM), 16 (IC50 = 2.132 ± 0.034 μM), 18 (IC50 = 1.154 ± 0.043 μM), 20 (IC50 = 1.055 ± 0.029 μM) and 21 (IC50 = 2.326 ± 0.059 μM) exhibited excellent inhibitory activity against AP, and even better/more active than KH2 PO4 (standard) (IC50 = 2.80 ± 0.065 μM). Remarkably, compound 20 (IC50 = 1.055 ± 0.029 μM) may serve as a lead structure to design more potent inhibitors of alkaline phosphatase. To the best of our knowledge, these synthetic compounds are the most potent AP inhibitors with minimum IC50 values reported to date. Furthermore, a molecular modeling study was performed against the AP enzyme (1EW2) to check the binding interaction of the synthesized compounds 1-22 against the target protein. The Lineweaver-Burk plots demonstrated that most potential derivative 20 inhibited h-IAP via a non-competitive pathway. Finally, molecular dynamic (MD) simulations were performed to evaluate the dynamic behavior, stability of the protein-ligand complex, and binding affinity of the compounds, resulting in the identification of compound 20 as a potential inhibitor of AP. Accordingly, excellent correlation was observed between the experimental and theoretical results. The pharmacological studies revealed that the synthesized analogs 1-22 obey Lipinski's rule. The assessment of the ADMET parameters showed that these compounds possess considerable lead-like characteristics with low toxicity and can serve as templates in drug design., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)- Published
- 2021
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32. Green photosensitisers for the degradation of selected pesticides of high risk in most susceptible food: A safer approach.
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Baig A, Zubair M, Sumrra SH, Rashid U, Zafar MN, Ahmad F, Nazar MF, Farid M, Bilal M, Alharthi FA, and Giannakoudakis DA
- Subjects
- Humans, Pest Control, Photosensitivity Disorders, Nitriles chemistry, Pesticide Residues analysis, Pesticides chemistry, Photosensitizing Agents, Pyrethrins chemistry
- Abstract
Pesticides are the leading defence against pests, but their unsafe use reciprocates the pesticide residues in highly susceptible food and is becoming a serious risk for human health. In this study, mint extract and riboflavin were tested as photosensitisers in combination with light irradiation of different frequencies, employed for various time intervals to improve the photo-degradation of deltamethrin (DM) and lambda cyhalothrin (λ-CHT) in cauliflower. Different source of light was studied, either in ultraviolet range (UV-C, 254 nm or UV-A, 320-380 nm) or sunlight simulator (> 380-800 nm). The degradation of the pesticides varied depending on the type of photosensitiser and light source. Photo-degradation of the DM and λ-CHT was enhanced by applying the mint extracts and riboflavin and a more significant degradation was achieved with UV-C than with either UV-A or sunlight, reaching a maximum decrement of the concentration by 67-76%. The light treatments did not significantly affect the in-vitro antioxidant activity of the natural antioxidants in cauliflower. A calculated dietary risk assessment revealed that obvious dietary health hazards of DM and λ-CHT pesticides when sprayed on cauliflower for pest control. The use of green chemical photosensitisers (mint extract and riboflavin) in combination with UV light irradiation represents a novel, sustainable, and safe approach to pesticide reduction in produce., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2021
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33. Exploring 3-Benzyloxyflavones as new lead cholinesterase inhibitors: synthesis, structure-activity relationship and molecular modelling simulations.
- Author
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Mughal EU, Sadiq A, Ayub M, Naeem N, Javid A, Sumrra SH, Zafar MN, Khan BA, Malik FP, and Ahmed I
- Subjects
- Acetylcholinesterase metabolism, Molecular Docking Simulation, Structure-Activity Relationship, Butyrylcholinesterase metabolism, Cholinesterase Inhibitors pharmacology
- Abstract
In this protocol, a series of 3-benzyloxyflavone derivatives have been designed, synthesized, characterized and investigated in vitro as cholinesterase inhibitors. The findings showed that all the synthesized target compounds ( 1-10 ) are potent dual inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes with varying IC
50 values. In comparison, they are more active against AChE than BChE. Remarkably, amongst the series, the compound 2 was identified as the most active inhibitor of both AChE (IC50 = 0.05 ± 0.01 μM) and BChE (IC50 = 0.09 ± 0.02 μM) relative to the standard Donepezil (IC50 = 0.09 ± 0.01 for AChE and 0.13 ± 0.04 μM for BChE). Moreover, the derivatives 5 (IC50 = 0.07 ± 0.02 μM) and 10 (0.08 ± 0.02 μM) exhibited the highest selective inhibition against AChE as compared to the standard. Preliminary structure-activity relationship was established and thus found that cholinesterase inhibitory activities of these compounds are highly dependent on the nature and position of various substituents on Ring-B of the 3-Benzyloxyflavone scaffolds. In order to find out the nature of binding interactions of the compounds and active sites of the enzymes, molecular docking studies were carried out.[Formula: see text]HIGHLIGHTS3-benzyloxyflavone analogues were designed, synthesized and characterized.The target molecules ( 1-10 ) were evaluated for their inhibitory potential against AChE and BChE inhibitory activities.Limited structure-activity relationship was developed based on the different substituent patterns on aryl part.Molecular docking studies were conducted to correlate the in vitro results and to identify possible mode of interactions at the active pocket site of the enzyme.Communicated by Ramaswamy H. Sarma.- Published
- 2021
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34. Breast Cancer: A Global Concern, Diagnostic and Therapeutic Perspectives, Mechanistic Targets in Drug Development.
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Chaudhry GE, Jan R, Akim A, Zafar MN, Sung YY, and Muhammad TST
- Abstract
Cancer is a complex multifactorial process, unchecked and abrupt division, and cell growth-conventional chemotherapy, along with radiotherapy, is used to treat breast cancer. Due to reduce efficacy and less survival rate, there is a particular need for the discovery of new active anticancer agents. Natural resources such as terrestrial/marine plants or organisms are a promising source for the generation of new therapeutics with improving efficacy. The screening of natural plant extracts and fractions, isolations of phytochemicals, and mechanistic study of those potential compounds play a remarkable role in the development of new therapeutic drugs with increased efficacy. Cancer is a multistage disease with complex signaling cascades. The initial study of screening whole extracts or fractions and later the isolation of secondary compounds and their mechanism of action study gives a clue of potential therapeutic agents for future drug development. The phytochemicals present in extracts/fractions produce remarkable effects due to synergistically targeting multiple signals. In this review, the molecular targets of extracts/ fractions and isolated compounds highlighted. The therapeutic agent's mechanistic targets in drug development focused involves; i) Induction of Apoptosis, ii) modulating cell cycle arrest, iii) Inhibition or suppression of invasion and metastasis and iv) various other pro-survival signaling pathways. The phytochemicals and their modified analogs identified as future potential candidates for anticancer chemotherapy., (© 2021 The Authors.)
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- 2021
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35. Silencing of a LIM gene in cotton exhibits enhanced resistance against Apolygus lucorum.
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Liang S, Luo J, Alariqi M, Xu Z, Wang A, Zafar MN, Ren J, Wang F, Liu X, Xin Y, Xu H, Guo W, Wang Y, Ma W, Chen L, Lindsey K, Zhang X, and Jin S
- Subjects
- Animals, Plants parasitology, Gossypium parasitology, Heteroptera genetics, Insecta genetics, RNA Interference immunology
- Abstract
Plant bugs (Miridae species) have become major agricultural pests that cause increasing and severe economic damage. Plant-mediated RNA interference (RNAi) is emerging as an eco-friendly, efficient, and reliable strategy for pest management. In this study, we isolated and characterized a lethal gene of Apolygus lucorum and named it Apolygus lucorum LIM (AlLIM), which produced A. lucorum mortality rates ranging from 38% to 81%. Downregulation of the AlLIM gene expression in A. lucorum by injection of a double-stranded RNA (dsRNA) led to muscle structural disorganization that resulted in metamorphosis deficiency and increased mortality. Then we constructed a plant expression vector that enabled transgenic cotton to highly and stably express dsRNA of AlLIM (dsAlLIM) by Agrobacterium-mediated genetic transformation. In the field bioassay, dsAlLIM transgenic cotton was protected from A. lucorum damage with high efficiency, with almost no detectable yield loss. Therefore, our study successfully provides a promising genetically modified strategy to overpower A. lucorum attack., (© 2021 Wiley Periodicals LLC.)
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- 2021
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36. Induction of Apoptosis by Acanthaster planci sp., and Diadema setosum sp., Fractions in Human Cervical Cancer Cell Line, HeLa.
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Chaudhry GE, Islamiah M, Zafar MN, Bakar K, Aziz N, Saidin J, Sung YY, and Tengku Muhammad TS
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- Animals, Cell Proliferation, Female, HeLa Cells, Humans, Uterine Cervical Neoplasms pathology, Antineoplastic Agents pharmacology, Apoptosis, Sea Urchins chemistry, Starfish chemistry, Tissue Extracts pharmacology, Uterine Cervical Neoplasms drug therapy
- Abstract
Cancer is an uncontrolled multiplication of cells. The desire efficacy and severe toxicity of current anticancer drugs urge exploring and investigating a better alternative to existing chemotherapeutics. Natural products of marine origin are excellent sources of potential new drugs of enhanced biological activities., Objectives: Thus, the cytotoxic effects along with investigating the mode of cell death exerted by fractions, AP-9, AP-THR, DS-8 and DS-9 fraction of Acanthaster planci, Diadema setosum sp., on the human cervical cancer cell line, HeLa., Methods: The cytotoxicity of fractions has determined by using an MTS assay. The early and late apoptosis was studied by using the High content Screening (HCS) instrument., Results: The four fractions produced effective cytotoxicity effects with IC50 values at 72hr of less than 20 μg/ml in the order of AP-9 > DS-9 > APTHR-9 > DS-8. The fraction s exhibited cytotoxicity via mediating apoptotic mode of cell death. The early apoptosis by exposure of phosphatidylserine to the outer leaflet of the plasma membrane and late apoptosis due to the presence of green stain (DNA fragmentation) in treated cells., Conclusion: The potent bioactive compounds might be responsible for inducing apoptosis in cancer cells and, thus, the potential to be a successful candidate for exploring upcoming chemotherapeutic drugs.
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- 2021
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37. Structure-based designing and synthesis of 2-phenylchromone derivatives as potent tyrosinase inhibitors: In vitro and in silico studies.
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Ashraf J, Mughal EU, Alsantali RI, Obaid RJ, Sadiq A, Naeem N, Ali A, Massadaq A, Javed Q, Javid A, Sumrra SH, Zafar MN, and Ahmed SA
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- Chromones chemical synthesis, Chromones chemistry, Dose-Response Relationship, Drug, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Humans, Models, Molecular, Molecular Structure, Monophenol Monooxygenase metabolism, Structure-Activity Relationship, Chromones pharmacology, Drug Design, Enzyme Inhibitors pharmacology, Monophenol Monooxygenase antagonists & inhibitors
- Abstract
The present study describes the discovery of novel inhibitors of mushroom tyrosinase enzyme. For that purpose, a series of varyingly substituted 2-phenylchromone analogues 1-28 were synthesized and characterized in detail by various spectroscopic techniques (UV-Vis, FTIR,
1 H NMR,13 C NMR) and mass spectrometry. All the derivatives (1-28) were screened in vitro for their inhibitory potential against mushroom tyrosinase enzyme. Interestingly, all the synthetic compounds displayed good to excellent inhibitory activity with IC50 values ranging from 0.093 ± 0.003 μg/ml to 23.58 ± 0.94 μg/ml for brominated 3-hydroxy-2-phenylchromones and 0.22 ± 0.017 μg/ml to 22.22 ± 1.1 μg/ml for brominated 2-phenylchromones against tyrosinase in comparison to the standard kojic acid (IC50 = 1.79 ± 0.64 μg/ml). Remarkably, the bromine atoms attached on ring A attribute to increases the inhibitory potential of 2-phenylchromone moiety and anti-tyrosinase assay demonstrated that compound 10 (IC50 = 0.093 ± 0.003 µg/ml) was found almost nineteenfold, 11 (IC50 = 0.126 ± 0.015 µg/ml) fourteenfold and 26 (IC50 = 0.22 ± 0.017 µg/ml) about eightfold more active than the positive control. Notably, among the already literature reported tyrosinase inhibitors, these analogues have been found the most active inhibitors of mushroom tyrosinase with the lowest possible IC50 values. To design and develop novel tyrosinase inhibitors using 2-phenylchromone as a structural motif in the future, a limited structure-activity relationship was established. Moreover, in silico studies were carried out to rationalize the binding mode of interactions of all the targeted compounds (1-28) with the active site of enzymes. The experimental and theoretical results are in parallel with one another. In addition, molecular description was performed with the drug-likeness and bioactivity scores. Computational analysis predicted that few compounds are in a linear correlation with Lipinski's RO5 indicating superb drug-likeness and bioactivity score for drug targets., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
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38. Pharmaco-Technical Evaluation of Statistically Formulated and Optimized Dual Drug-Loaded Silica Nanoparticles for Improved Antifungal Efficacy and Wound Healing.
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Masood A, Maheen S, Khan HU, Shafqat SS, Irshad M, Aslam I, Rasul A, Bashir S, and Zafar MN
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The current research aimed at designing mesoporous silica nanoparticles (MSNs) for a controlled coadministration of salicylic acid (SA) and ketoconazole (KCZ) to effectively treat highly resistant fungal infections. The sol-gel method was used to formulate MSNs, which were further optimized using central composite rotatable design (CCRD) by investigating mathematical impact of independent formulation variables such as pH, stirring time, and stirring speed on dependent variables entrapment efficiency (EE) and drug release. The selected optimized MSNs and pure drugs were subjected to comparative in vitro/in vivo antifungal studies, skin irritation, cytotoxicity, and histopathological evaluations. The obtained negatively charged (-23.1), free flowing spherical, highly porous structured MSNs having a size distribution of 300-500 nm were suggestive of high storage stability and improved cell proliferation due to enhanced oxygen supply to cells. The physico-chemical evaluation of SA/KCZ-loaded MSNs performed through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) indicates absolute lack of any interaction between formulation components and successful encapsulation of both drugs in MSNs. The EE
SA , EEKCZ , SA release, and KCZ release varied significantly from 34 to 89%, 36 to 85%, 39 to 88%, and 43 to 90%, respectively, indicating the quadratic impact of formulation variables on obtained MSNs. For MSNs, the skin tolerability and cell viability percentage rate were also having an extraordinary advantage over suspension of pure drugs. The optimized SA/KCZ-loaded MSNs demonstrated comparatively enhanced in vitro / in vivo antifungal activities and rapid wound healing efficacy in histopathological evaluation without any skin irritation impact, suggesting the MSNs potential for the simultaneous codelivery of antifungal and keratolyic agents in sustained release fashion., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)- Published
- 2021
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39. Assessment of SnFe 2 O 4 Nanoparticles for Potential Application in Theranostics: Synthesis, Characterization, In Vitro, and In Vivo Toxicity.
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Sargazi S, Hajinezhad MR, Rahdar A, Zafar MN, Awan A, and Baino F
- Abstract
In this research, tin ferrite (SnFe
2 O4 ) NPs were synthesized via hydrothermal route using ferric chloride and tin chloride as precursors and were then characterized in terms of morphology and structure using Fourier-transform infrared spectroscopy (FTIR), Ultraviolet-visible spectroscopy (UV-Vis), X-ray power diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), and Brunauer-Emmett-Teller (BET) method. The obtained UV-Vis spectra was used to measure band gap energy of as-prepared SnFe2 O4 NPs. XRD confirmed the spinel structure of NPs, while SEM and TEM analyses disclosed the size of NPs in the range of 15-50 nm and revealed the spherical shape of NPs. Moreover, energy dispersive X-ray spectroscopy (EDS) and BET analysis was carried out to estimate elemental composition and specific surface area, respectively. In vitro cytotoxicity of the synthesized NPs were studied on normal (HUVEC, HEK293) and cancerous (A549) human cell lines. HUVEC cells were resistant to SnFe2 O4 NPs; while a significant decrease in the viability of HEK293 cells was observed when treated with higher concentrations of SnFe2 O4 NPs. Furthermore, SnFe2 O4 NPs induced dramatic cytotoxicity against A549 cells. For in vivo study, rats received SnFe2 O4 NPs at dosages of 0, 0.1, 1, and 10 mg/kg. The 10 mg/kg dose increased serum blood urea nitrogen and creatinine compared to the controls (P < 0.05). The pathology showed necrosis in the liver, heart, and lungs, and the greatest damages were related to the kidneys. Overall, the in vivo and in vitro experiments showed that SnFe2 O4 NPs at high doses had toxic effects on lung, liver and kidney cells without inducing toxicity to HUVECs. Further studies are warranted to fully elucidate the side effects of SnFe2 O4 NPs for their application in theranostics.- Published
- 2021
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40. Xylocarpus Moluccensis Induces Cytotoxicity in Human Hepatocellular Carcinoma HepG2 Cell Line via Activation of the Extrinsic Pathway.
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Chaudhry GE, Sohimi NKA, Mohamad H, Zafar MN, Ahmed A, Sung YY, and Muhammad TST
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- Apoptosis Regulatory Proteins genetics, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular metabolism, Cell Proliferation, Humans, Liver Neoplasms drug therapy, Liver Neoplasms metabolism, Tumor Cells, Cultured, Apoptosis, Apoptosis Regulatory Proteins metabolism, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology, Meliaceae chemistry, Plant Extracts pharmacology
- Abstract
Objective: Liver cancer is one of the most common causes of cancer death, with reduced survival rates. The development of new chemotherapeutic agents is essential to find effective cytotoxic drugs that give minimum side effects to the surrounding healthy tissues. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the crude and diethyl ether extract of Xylocarpus mouccensis on the human hepatocellular carcinoma cell line., Methods: The cytotoxicity activity was measured using the MTS assay. The mode of cell death determined by the apoptosis study, DNA fragmentation analysis done by using the TUNEL system. The pathway study or mechanism of apoptosis observed by study caspases 8, 9, 3/7 Glo-caspases method., Results: In this study, the methanol extracts prepared from leaf Xylocarpus mouccensis leaf produced cytotoxicity effect with IC50 (72hr) < 30µg/ml. The IC50 value at 72 hours exerted by diethyl ether extract of Xylocarpus moluccensis leaf was 0.22 µg/ml, which was more cytotoxic than to that of crude methanol extract. The results obtained by the colorimetric TUNEL system suggest that methanol crude extract of Xylocarpus moluccensis (leaf), diethyl ether extract of Xylocarpus moluccensis (leaf) and methanol extract of Xylocarpus granatum (bark) induced DNA fragmentation in the HepG2 cell line. Besides, the caspase-Glo assay demonstrated that diethyl ether leaf extract of Xylocarpus moluccensis triggered apoptotic cell death via activation of caspases -8, and -3/7 However, no visible activation was noticed for caspase -9. Furthermore, TLC indicates the presence of potential metabolites in an extract of Xylocarpus moluccensis., Conclusion: Thus, the present study suggests the remarkable potential of active metabolites in the extract of Xylocarpus moluccensis as a future therapeutic agent for the treatment of cancer., .
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- 2021
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41. Terpyridine-metal complexes: effects of different substituents on their physico-chemical properties and density functional theory studies.
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Mughal EU, Mirzaei M, Sadiq A, Fatima S, Naseem A, Naeem N, Fatima N, Kausar S, Altaf AA, Zafar MN, and Khan BA
- Abstract
A series of different substituted terpyridine (tpy)-based ligands have been synthesized by Kröhnke method. Their binding behaviour was evaluated by complexing them with Co(II), Fe(II) and Zn(II) ions, which resulted in interesting coordination compounds with formulae, [Zn(tpy)
2 ]PF6 , [Co(tpy)2 ](PF6 )2 , [Fe(tpy)2 ](PF6 )2 and interesting spectroscopic properties. Their absorption and emission behaviours in dilute solutions were investigated in order to explain structure-property associations and demonstrate the impact of different aryl substituents on the terpyridine scaffold as well as the role of the metal on the complexes. Photo-luminescence analysis of the complexes in acetonitrile solution revealed a transition from hypsochromic to bathochromic shift. All the compounds displayed remarkable photo-luminescent properties and various maximum emission peaks owing to the different nature of the functional groups. Furthermore, the anti-microbial potential of ligands and complexes was evaluated with docking analyses carried out to investigate the binding affinity of terpyridine-based ligands along with corresponding proteins (shikimate dehydrogenase and penicillin-binding protein) binding sites. To obtain further insight into molecular orbital distributions and spectroscopic properties, density functional theory calculations were performed for representative complexes. The photophysical activity and interactions between chromophore structure and properties were both investigated experimentally as well as theoretically., Competing Interests: There are no conflicts of interest to declare., (© 2020 The Authors.)- Published
- 2020
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42. Induction of cytotoxicity by Bruguiera gymnorrhiza in human breast carcinoma (MCF-7) cell line via activation of the intrinsic pathway.
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Chaudhry GE, Rahman NH, Sevakumaran V, Ahmad A, Mohamad H, Zafar MN, Sung YY, and Tengku Muhammad TS
- Abstract
Breast cancer is among the frequently occurring cancer worldwide. The foremost underline aim of this study was to determine the growth inhibitory effect along with mechanistic study of a Bruguiera gymnorrhiza extract on MCF-7. The cytotoxicity activity was determined by using the MTS assay. Butanol extract exhibited the maximum cytotoxicity activity against the MCF-7 cells with IC
50 of 3.39 μg/mL, followed by diethyl ether and methanol extract (IC50 at 16.22 μg/mL and 37.15 μg/mL, respectively) at 72 h. The DeadEndTM Colorimetric Apoptosis Detection System confirmed the induction of apoptosis (via DNA fragmentation) in MCF-7 cells. Both butanol and diethyl ether extracts of B. gymnorrhiza significantly increase the caspase-3 level. However, the diethyl ether extract induced higher caspase-9 levels compared to caspase-8, suggesting that the intrinsic pathway was the major route in the process of apoptosis. Thin-layer chromatography profiling demonstrated the presence of phenolic, terpene, and alkaloid compounds in crude methanol, diethyl ether, and butanol extracts. The phytochemicals present in the extracts of B. gymnorrhiza might have the potential to be a future therapeutic agent against breast cancer., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Advanced Pharmaceutical Technology & Research.)- Published
- 2020
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43. Statistical Assessment of Toxic and Essential Metals in the Serum of Female Patients with Lung Carcinoma from Pakistan.
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Qayyum MA, Farooq Z, Yaseen M, Mahmood MH, Irfan A, Zafar MN, Khawaja M, Naeem K, and Kisa D
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- Female, Humans, Lung, Pakistan, Carcinoma, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Metals, Heavy
- Abstract
Lung cancer (LC) is the number one cancer killer of women both in the USA and around the world. Besides cigarette smoking, an important feature in the etiology of LC is its strong association with exposure of toxic metals. The primary objective of the present investigation was to assess the concentrations of toxic/essential elements (Ni, Ca, Se, Zn, Co, K, Cr, As, Cu, Na, Fe, Hg, Cd, Mg, Mn, and Pb) in the serum samples of LC female patients with female controls by atomic absorption spectrometry after wet-acid digestion procedure. Carcinoembryonic antigen (CEA) was also measured in the serum of the patients using immunoradiometric method. Comparative appraisal of the data revealed that concentrations of Cr, Mg, Cd, Pb, Hg, As, and Ni were noted to be high significantly in serum of LC female patients, while the average Fe, Co, Mn, Na, K, Zn, Ca, and Se were observed at higher levels in female controls (p < 0.05). The correlation study revealed significantly different mutual associations among the elements in the both donor groups. Markedly, variations in the elemental levels were also noted for different types (non-small cell lung cancer and small cell lung cancer) and stages (I, II, III, & IV) of LC patients. Multivariate analyses showed substantially diverse apportionment of the metals in the female patients and female controls. Hence, present findings suggest that the toxic and essential metals accumulated in the body may pose a high risk for LC progression in Pakistani females.
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- 2020
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44. Impact of One-Year Serum Creatinine on Long-term Renal Graft Survival in a Living-Related Renal Transplant Program.
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Nawaz SH, Zafar MN, Afzal M, Anwar Naqvi SA, Mubarak M, and Hasan Rizvi SA
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- Adult, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult, Creatinine blood, Graft Survival physiology, Kidney Transplantation adverse effects, Kidney Transplantation statistics & numerical data
- Abstract
This study was carried out to determine the impact of one-year posttransplant serum creatinine (SCr) levels on the long-term outcomes of living-related donor kidney transplants. A retrospective cohort study included 773 adult living-related renal transplant recipients from 2010 to 2012, with a minimum follow-up period of five years. Demographics and posttransplantation follow-up data including immunosuppression regimens, rejection episodes, and survival rates were evaluated. Patients were divided into four cohorts (G1, G2, G3, and G4 based on SCr at the end of the 1
st year: G1, SCr <88.4 μ mol/L; G2, 88.5≤ SCr ≤ 132.6 μmol/L; G3, 132.7≤ SCr ≤176.8 mol/L; and G4, SCr ≥176.9 μ mol/L). Comparisons between the groups used the Chi-square test for qualitative parameters and analysis of variance for continuous variables. Five-year graft survival for G1 was 98% as compared to 76% in G4 (P <0.001). Recipients of G4 encountered more acute rejection episodes in 21% of the cases as compared to 7.3% in G1 (P = 0.001). Donors were older in G4 (42.07 ± 10.4 years) as compared to G1 (30.1 ± 8.5 years) (P = 0.001). A third of the donors in G1 were HLA identical as compared to 7% in G4. Prediction of long-term graft survival is possible by the SCr level at one year post transplant. This can be of great importance, especially to identify those patients who require close monitoring in follow-up. Donor age, HLA, and acute rejection impact SCr at one year and hence graft outcome.- Published
- 2020
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45. Application of Fusarium sp. immobilized on multi-walled carbon nanotubes for solid-phase extraction and trace analysis of heavy metal cations.
- Author
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Moallaei H, Bouchara JP, Rad A, Singh P, Raizada P, Tran HN, Zafar MN, Giannakoudakis DA, and Hosseini-Bandegharaei A
- Subjects
- Adsorption, Cations chemistry, Cells, Immobilized chemistry, Copper analysis, Fresh Water analysis, Hydrogen-Ion Concentration, Lead analysis, Lead isolation & purification, Limit of Detection, Metals, Heavy isolation & purification, Metals, Heavy standards, Osmolar Concentration, Reference Standards, Spectrophotometry standards, Fusarium chemistry, Metals, Heavy analysis, Nanotubes, Carbon chemistry, Solid Phase Extraction, Spectrophotometry methods
- Abstract
In the present work, for the first time, the filamentous fungus Fusarium sp. was utilized for devising a novel method for pre-concentration and determination of trace amounts of Pb(II), Cu(II), Cd(II), and Zn(II) ions, using a mini-column packed with Fusarium-coated multi-walled carbon nanotubes and inductively coupled plasma-optical emission spectrometry. Optimal analytical conditions including pH, ionic strength, elution solution, sample and eluent flow rates, and sample volume were determined. The detection limits were 0.39, 0.060, 0.021, and 0.025 ng mL
-1 for Pb(II), Cu(II), Cd(II), and Zn(II) cations, respectively. This new method demonstrated a high performance for the analytes, and their adsorption was not affected by the different co-existing ions. The present procedure was validated by the analysis of standard reference materials, since the obtained data were in close agreement with reference values. Finally, this new procedure was successfully applied to analysis of heavy metal cations in natural food and water samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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46. Induction of apoptosis and role of paclitaxel-loaded hyaluronic acid-crosslinked nanoparticles in the regulation of AKT and RhoA.
- Author
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Chaudhry GE, Akim A, Zafar MN, Abdullah MA, Sung YY, and Muhammad TST
- Abstract
Cancer is a complex multifactorial disease and leading causes of death worldwide. Despite the development of many anticancer drugs, there is a reduced survival rate due to severe side effects. The nontargeted approach of convention drugs is one of the leading players in context to toxicity. Hyaluronan is a versatile bio-polymer and ligand of the receptor (CD44) on cancer cells. The MCF-7 and HT-29 cancer cell lines treated with hyaluronic acid-paclitaxel (HA-PTX) showed the distinguishing morphological features of apoptosis. Flow cytometric analysis showed that HA-PTX induces apoptosis as a significant mode of cell death. The activation level of tumor suppressor protein (p53) increased after PTX treatment in MCF-7, but no changes observed in HT-29 might be due to hereditary mutations. The lack of suppression in AKT and Rho A protein suggest the use of possible inhibitors in future studies which might could play a role in increasing the sensitivity of drug towards mutated cells line and reducing the possibilities for cancer cell survival, migration, and metastasis., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Advanced Pharmaceutical Technology & Research.)
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- 2020
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47. Effective Adsorptive Removal of Methylene Blue from Water by Didodecyldimethylammonium Bromide-Modified Brown Clay.
- Author
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Munir M, Nazar MF, Zafar MN, Zubair M, Ashfaq M, Hosseini-Bandegharaei A, Khan SU, and Ahmad A
- Abstract
In the present investigation, brown clay (BC) was modified with didodecyldimethylammonium bromide (DDAB) to produce a sorbent (DDAB-BC), which was characterized and applied for sorption of methylene blue (MB) from aqueous media. BC was functionalized using DDAB by cation exchange of the DDAB moiety with positive ions existing inside the interlayer spaces of the BC. X-ray diffraction (XRD) studies confirmed that the d -spacing of DDAB-BC became wider (3.39 Å) than that of BC (3.33 Å). Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were exploited to explore the functional groups and morphological structure of sorbents, respectively. The Brunauer-Emmett-Teller (BET) surface area, pore volume, and pore diameter of DDAB-BC were determined as 124.6841 m
2 /g, 0.316780 cm3 /g, and 8.75102 nm, respectively. Batch sorption investigations were carried out to determine the optimum experimental conditions, using the one-factor one-time procedure. The sorption of MB on DDAB-BC strongly obeyed the Langmuir isotherm and agreed well with pseudo-second-order kinetics. Sorption of MB onto DDAB-BC showed maximum efficiency (∼98%) and maximum sorption capacity (∼164 mg/g) at optimal values of pertinent factors: dye concentration (100 mg/L), pH (7), and temperature (55 °C). Sorption isothermal studies predicted that removal of MB on DDAB-BC follows multilayer sorption at higher MB dye concentrations and monolayer sorption at lower MB dye concentrations., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)- Published
- 2020
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48. Turn-on fluorescent glutathione detection based on lucigenin and MnO 2 nanosheets.
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Halawa MI, Wu F, Zafar MN, Mostafa IM, Abdussalam A, Han S, and Xu G
- Subjects
- Humans, Manganese Compounds chemical synthesis, Molecular Structure, Oxides chemical synthesis, Particle Size, Surface Properties, Acridines chemistry, Fluorescent Dyes chemistry, Glutathione blood, Manganese Compounds chemistry, Nanoparticles chemistry, Oxides chemistry
- Abstract
In this work, a glutathione (GSH) sensing nano-platform using lucigenin as a fluorescent probe in the presence of MnO2 nanosheets was reported for the first time. Unlike the earlier fluorescent detection systems based on MnO2 nanosheets, which depend on Förster resonance energy transfer (FRET) or the dynamic quenching effect (DQE), the mechanism of the quenching process of MnO2 nanosheets on lucigenin fluorescence was attributed mainly to a static quenching effect (SQE) with a minor contribution of the inner filter effect (IFE). A double exponential fluorescence decay of lucigenin was obtained in various MnO2 nanosheet concentrations as a result of their SQE and IFE. Based on this phenomenon and taking advantage of the redox reaction between GSH and MnO2 nanosheets, we have developed a switch-on sensitive fluorescent method for GSH via the recovery of the MnO2 nanosheet-quenched fluorescence of lucigenin. A good linearity range of 1.0-150.0 μM with a low limit of detection (S/N = 3) of 180.0 nM was achieved, revealing the higher sensitivity for GSH determination in comparison with the previously reported MnO2 nanosheet-based turn-on fluorescent methods. The developed fluorescent nano-platform exhibits excellent selectivity with successful application for GSH detection in human serum plasma, indicating its good practicability for GSH sensing in biological and clinical applications.
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- 2020
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49. Highly sensitive and selective non-enzymatic glucose detection based on indigo carmine/hemin/H 2 O 2 chemiluminescence.
- Author
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Fereja TH, Kitte SA, Zafar MN, Halawa MI, Han S, Zhang W, and Xu G
- Abstract
A new chemiluminescence (CL) system, indigo carmine/glucose/hemin/H2O2, has been found and developed for non-enzymatic detection of indigo carmine (IC) and glucose. The CL response increases linearly with IC concentrations from 3.2 μM to 10 mM and glucose concentrations from 0.06 μM to 3.5 mM. The detection limits are 1.45 μM and 15.0 nM for IC and glucose, respectively. This method allows the determination of glucose in blood and urine after simple dilution. The recoveries for the determination of glucose are between 98.5% and 101.0% in blood and between 98.5% and 101.3% in urine. This method shows good sensitivity, selectivity, simplicity, and is low cost, suggesting its promising broad applications.
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- 2020
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50. Synthesis of new Pro-PYE ligands as co-catalysts toward Pd-catalyzed Heck-Mizoroki cross coupling reactions.
- Author
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Munir N, Masood S, Liaqat F, Tahir MN, Yousuf S, Kalsoom S, Mughal EU, Sumrra SH, Maalik A, and Zafar MN
- Abstract
The present research work describes the synthesis of five new ligands containing pyridinium amine, [H
2 L1 ][OTf]2 -[H2 L5 ][I]2 from two new precursors, [P3 Et ][I] and [P2 Me ][CF3 SO3 ]. The structure elucidations of the compounds were confirmed by multinuclear NMR (1 H,13 C), FT-IR and by single crystal XRD techniques. Theoretical DFT studies were carried out to get better insight into the electronic levels and structural features of all the molecules. These synthesized new Pro-PYE ligands [H2 L1 ][OTf]2 -[H2 L5 ][I]2 were found to be significantly active as co-catalysts for Pd(CH3 CO2 )2 toward Heck-Mizoroki coupling reactions with wide substrate scope in the order of [H2 L1 ][OTf]2 ≫ [H2 L2 ][OTf]2 > [H2 L3 ][OTf]2 > [H2 L4 ][OTf]2 > [H2 L5 ][I]2. , Competing Interests: There are no conflicts of interest among authors to declare., (This journal is © The Royal Society of Chemistry.)- Published
- 2019
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