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Epalrestat (EPL) is an aldose reductase inhibitor with poor aqueous solubility that affects its therapeutic efficacy. The research study was designed to prepare epalrestat-cyclodextrins (EPL-CDs) inclusion complexes to enhance the aqueous solubility by using beta-cyclodextrin (β-CD) and sulfobutyl ether₇ β-CD (SBE7 β-CD). Furthermore, polymeric nanoparticles (PNPs) of EPL-CDs were developed using chitosan (CS) and sodium tripolyphosphate (sTPP). The EPL-CDs complexed formulations were then loaded into chitosan nanoparticles (CS NPs) and further characterized for different physico-chemical properties, thermal stability, drug-excipient compatibility and acute oral toxicity studies. In-silico molecular docking of cross-linker with SBE7 β-CD was also carried out to determine the binding site of the CDs with the cross-linker. The sizes of the prepared NPs were laid in the range of 241.5–348.4 nm, with polydispersity index (PDI) ranging from 0.302–0.578. The surface morphology of the NPs was found to be non-porous, smooth, and spherical. The cumulative percentage of drug release from EPL-CDs loaded CS NPs was found to be higher (75–88%) than that of the pure drug (25%). Acute oral toxicity on animal models showed a biochemical, histological profile with no harmful impact at the cellular level. It is concluded that epalrestat-cyclodextrin chitosan nanoparticles (EPL-CDs-CS NPs) with improved solubility are safe for oral administration since no toxicity was reported on vital organs in rabbits.

In today's world, the utilization of electronic devices, particularly mobile phones, has seen a remarkable surge and they are a valuable source of recovery of precious metals. The current study reports on the physical and chemical processing of mobile phone waste into leachate, followed by recovery of precious metals, using ionic liquid functionalized activated carbon (ACF). The recovery process was explored both in batch and column study. The presence of base metals in the final leachate was minimized by employing multi-stage chemical leaching, leading to a more efficient purification process. Moreover, adjustment of HCl concentration in the leachate leads to decreased in other metals interference during adsorption. Following the batch adsorption results, a favorable interaction between IL and metal complexes leads to a quantitative adsorption of the precious metals. In addition, ACF also gave an excellent performance in the column adsorption process with the high bed depth and low flow rate of the leachate as the influential parameter. An increase in the bed depth and a decrease in leachate flow rate proportionally increases the values of kTh (rate constant), qe (adsorption capacity), and KYN (rate constant) and positively increases the 50% breakthrough time (τ). Moreover, the final purification of the adsorbed metals was performed selectively through sequential desorption, employing Na2S2O3, NH4SCN, and HNO3 solutions. Finally, the adsorption capability of ACF shown a negligible change after five repetitive adsorption-desorption cycles. Thus, the current study presents a method to process mobile phone waste and selectively recover the precious metals from the leachate.

The strong demand for biological materials in the food industry places chitosan at the forefront of other biopolymers. The present study aims to evaluate the antifungal properties of chitosan extracted from shrimp shell waste (Parapenaeus longirostris) against post-harvest strawberry (Fragaria × ananassa) spoilage fungi. The physicochemical characteristics (DD, Mw, and solubility) of extracted chitosan were determined. In addition, functional characteristics were studied by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The antifungal effect of chitosan on mycelial growth and spore germination of Aspergillus niger, Botrytis cinerea, Fusarium oxysporum, and Rhizopus stolonifer was evaluated. Yield, degree of deacetylation, molecular weight, and solubility were 21.86%, 83.50%, 180 kDa, and 80.10%, respectively. A degree of deacetylation of 81.27% was calculated from the FTIR spectrum and a crystallinity index of 79.83% was determined from the X-ray diffraction pattern. SEM images of extracted chitosan showed a combination of fibrous and porous structure. At 3% chitosan, mycelial growth inhibition rates of A. niger, B. cinerea, F. oxysporum, and R. stolonifer ranged from 81.37% to 92.70%. At the same chitosan concentration, the percentages of spore germination inhibition of the isolated fungi ranged from 65.47% to 71.48%. The antifungal activity was highly dose-dependent. As a natural polymer, chitosan offers a convincing alternative to synthetic antimicrobials for the post-harvest preservation of strawberries. Its potential lies in its ability to inhibit the growth of spoilage fungi.

Pakistan is endowed with abundant fisheries resources that have significant economic potential. Capture fisheries contribute a comparatively vital role to the national economy. However, poverty, environmental degradation and political instability are major problems for the Pakistani people, and no effective steps have been taken to handle this socio- economically important sector efficiently in the past. Furthermore, the fisheries sector faced its own set of challenges, including the emergence of small-scale artisanal fisheries, the nonexistence of technologies, deficiency of institutional development, an absence of infrastructure, insufficient human resource skill, and a lack of responsiveness among fishing societies, all of which contributed to the sector's demise. The National Fisheries Policy (NFP) was formulated to address these problems in the fisheries sector. Potential efforts have been made by the Government of Pakistan to solve these constraints under various plans of objectives and strategy axes of the policy. Our findings indicate that despite these efforts, the fisheries sector does not show significant growth to achieve the policy goals. So, it is necessary to re-evaluate and re-orient this policy for further development of this sector. It is also essential to achieve the aim of Government of Pakistan Vision 2025 to become one of the 25th largest economies in the world. [ABSTRACT FROM AUTHOR]

Lignin valorization to produce functionalized materials is challenging. This study harnessed the versatile properties of lignin through a grafting reaction involving the aryl hydroxyl group of alkali lignin (AL) and enzymatically modified-alkali lignin (EMAL) using Bacillus ligninphilus-derived laccase (Lacc) L1 and C. seriivinvornas-derived dye-decolorizing peroxidase (DyP) with keratin (K) amide group. This reaction was executed utilizing an eco-friendly solvent with the aim of generating thin films. A thorough investigation was conducted, focusing on grafting AL and EMAL onto K. The incorporation of EMAL into the films enhanced tensile strength (TS) (14.8±1.8 MPa) and elongation at break (EAB) (23.7±0.3 %). Additionally, it enhanced thermal stability, suppressed the proliferation of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), and mitigated oxidative stress. This study introduces a novel approach for lignin valorization, offering the potential to tailor mechanical properties, antibacterial and antioxidant properties of the final material, making it sustainable substitute for petroleum-based products.

The basic Helix-Loop-Helix (bHLH) superfamily is the most widespread family of transcription factors in eukaryotic organisms, which can activate the expression of genes by interacting with specific promoters in the genes. The bHLH transcription factors direct the development and metabolic process of plants, including flowering initiation and secondary metabolite production, by attaching to specific sites on their promoters. These transcription factors are essential for encouraging plant tolerance or the adjustment to harsh environmental conditions. The involvement of bHLH genes in anthocyanin formation in fleshy fruit-bearing plants, as well as the role of these genes in response to stimuli including drought, salt, and cold stress, are discussed in this article. New concepts and goals for the production of stress-tolerant fruit species are suggested. Furthermore, solid evidence for the critical role of bHLH genes in the growth and development, as well as anthocyanin biosynthesis in fleshy fruit plants, are also presented in this article. This review identifies several future research directions that can shed light on the roles of bHLH genes in fruit-bearing plants and will assist the use of these genes in efforts to breed fruit crop varieties that are more resistant to stress. Generally, there has been little research carried out on the role of bHLHs transcription factor family genes in fleshy fruit-bearing plant species and more in-depth studies are required to fully understand the diverse role of bHLH genes in these species.

Barramundi, (Lates calcarifer) is one of the most commercially important fish species. In Pakistan, farming of this species is relatively new. Article delivers the economic analysis of Barramundi and its fishery resources in Pakistan. The analysis includes the capture production, aquaculture production and market price. The Capture production of Barramundi in Pakistan has shown a declining trend by average at 18 t y-1 from 605 t in 1986 to 121.2 t in 2018. Similarly, wholesale and retail market prices witnessed an increase from 2003 to 2018. During this period, the wholesale price rose to 384.3 PKR/kg from 69 PKR/kg, while the retail price surged to 395.2 PKR/kg from 97 PKR/kg. On the other hand, the increasing operational fishing fleets from 15513 (1990) to 30000 (2018) has reduced Fishery resources of barramundi i.e. from 312 ton to 130 and its body weight from 13.42 kg to 3.5 kg during the period from 1990 to 2018. On the contrary, aquaculture production registered a rising trend by average of 0.5 t y-1 from 05 t in 2009 to 8.2 t in 2018. The rise in aquaculture production of Barramundi is not satisfactory when compared to its growth rate in other countries like Bangladesh, Thailand, Australia, China, India etc. In this study, we find out the major causes of non-satisfactory rise in aquaculture production by the using AGR model. Results show that the main reasons beyond decline in the growth included inaccessibility of Barramundi Seed, unavailability of Barramundi Hatcheries and lack of government Support. [ABSTRACT FROM AUTHOR]

In this study, catch statistics of mullets are first time evaluated to know their exploitation status and ongoing economic implications. Catch and effort (CE) figures of mullets acquired from Sindh, Pakistan was statistically evaluated by employing surplus production models (SPMs), non-equilibrium versions, through two famous fishery related software, viz., catch and effort data analysis (CEDA) and a stock production model incorporating covariates (ASPIC). In total three SPMs, i.e., Fox, Schaefer and Pella-Tomlinson were used to investigate CE statistics, 1995 to 2012. Obtained results reveal that catch per unit effort (CPUE) has considerably dropped from 0.206 (1995) to 0.055 (2012). CEDA estimates of maximum sustainable yield (MSY) remained conservative as they were calculated between 5100 to 6500 t against ASPIC for which estimates of this parameter remained between 5800 and 7600 t. Considering the results, it can be concluded that mullet fishery is experiencing overexploitation (OE). This OE is an indicator of economic losses by increasing costs and decreasing profits. Thus, mullet resource conservation is necessary for its long-term economic utilization. Therefore, it is suggested that the target reference point (TRP) with respect to harvest should be between 5100 to 5500 t. However, this study is a preliminary study, hence; further in-depth studies are suggested before making and implementing any management plan for mullet fishery in Sindh, Pakistan. [ABSTRACT FROM AUTHOR]

Glutathione S-transferase (GST) is vital in oxidative stress. Keeping in view the importance of this enzyme, present study was conducted for partial characterization of GST from hepatocytes of Cyprinus carpio. The inferences showed higher (GST) activity in liver of C. carpio collected from Chashma Barrage (144.33±1.15) as compared to Trimmu Head works (128.66.3±0.577) and Rasul Barrage (111.66±0.577) sampling sites. The highest GST activity was 128±0.333 U mL-1 from the crude extract fraction of liver as compared to other fractions of appraisal fish liver. Whereas the lowest activity (109±0.666 U mL-1) was from desalted fraction. Optical density was recorded by spectrophotometer at 280 nm, the fractions that showed high optical density were subjected to enzyme assay. Highest specific activity was 183.63, 153.84 and 162.50 U mg-1 for purified liver GST of C. carpio captured from Trimmu Head works, Rasul Barrage and Chashma Barrage, respectively. Whereas, fold purification was 2.86, 2.69 and 2.10 while, percent recovery was 78.90, 72.07 and 63.19 %, respectively for purified liver GST. The optimum pH was 6.5, 6.0 and 6.8 whereas, temperature was 30.5 °C, 31 °C and 30 °C followed by substrate concentration 40.3 mM, 40 mM and 41 mM, for purified liver GST of C. carpio captured from Trimmu Head works, Rasul Barrage and Chashma Barrage, respectively. It should be noted that detailed studies can be beneficial in the fields of physiology, biochemistry and toxicology. [ABSTRACT FROM AUTHOR]

Serum biochemical assessment is an important tool to provide information about the internal organs, metabolic and nutritional parameters and electrolytes. Present study was conducted to determine the serum biochemistry of Channa marulius in hatchery and riverine populations. For this purpose blood samples were collected by caudal vein puncture. Inferences of the study showed non-significantly (p ≥ 0.05) higher values of calcium 10.24 mmol/L as compared to lower 9.66 mmol/L whereas, significantly (p ≤ 0.05) higher values of serum globulin 21.06 g/L, total protein 53.0 g/L, albumin 14.87 g/L, cholesterol 6.116 mmol/L, alanine transaminase 530 U/L and alkaline phosphatase 398 µ/L were observed in cultured populations as compared to lower 20.40 g/L, 44.84 g/L, 12.30 g/L, 5.084 mmol/L, 453 U/L and 255 µ/L in riverine populations. On the other side, non-significantly (p ≥ 0.05) higher values of serum triglyceride 0.674 mmol/L as compared to lower 0.604 mmol/L, while significantly (p ≤ 0.05) higher values of glucose 28.43 g/L, urea 2.541 mmol/L, bilirubin 28.20 µmol/L, chlorine 70.3 mmol/L, potassium 13.43 mmol/L, sodium 126.5 mmol/L and aspartate transaminase 1169 U/L in riverine populations as compared to lower 23.89 g/L, 2.17 mmol/L, 26.23 µmol/L, 61.9 mmol/L, 12.08 mmol/L, 111.2 mmol/L and 1029 U/L were recorded in cultured populations, respectively. Findings of the study will be helpful in the field of biochemistry, physiology and toxicology as well as to enhance the management and rearing potential of the Chnanna marulius. [ABSTRACT FROM AUTHOR]

USA is the major export market destination for Indian fish and fishery products especially for crustaceans. The present study analyzed the status, export performance and competitiveness of Indian fish export to USA based on data (2000-2017) collected from UNCOMTRADE statistical database of United Nations. Trade balance revealed that the net trade for Indian fish export to USA was positive and the export has always been far greater than the imports. Compound Growth Rate (CGR) revealed that the seafood export grew at 18.22 % in terms of value with instability of 0.1 from 2000-2017. The average Unit Value Realization (UVR) was found highest in live fishes (15.62) followed by crustaceans (6.89) and others. Commodity wise Revealed Comparative Advantage (RCA) revealed that it is highly positive for crustaceans (7.87) followed by molluscs (2.74) and frozen fish (2.12) indicating that India has a strong comparative advantage in exporting these commodities to USA. [ABSTRACT FROM AUTHOR]

Nitrogen (N) is one of the most crucial elements for plant growth. However, a deficiency of N affects plant growth and development. Wedelia trilobata is a notorious invasive plant species that exhibits superior tolerance to adapt to environmental stresses. Yet, research on the growth and antioxidant defensive system of invasive Wedelia under low N stress, which could contribute to understanding invasion mechanisms, is still limited. Therefore, this study aims to investigate and compare the tolerance capability of invasive and native Wedelia under low and normal N conditions. Native and invasive Wedelia species were grown in normal and low-N conditions using a hydroponic nutrient solution for 8 weeks to assess the photosynthetic parameters, antioxidant activity, and localization of reactive oxygen species (ROS). The growth and biomass of W. trilobata were significantly (p < 0.05) higher than W. chinensis under low N. The leaves of W. trilobata resulted in a significant increase in chlorophyll a, chlorophyll b, and total chlorophyll content by 40.2, 56.2, and 46%, respectively, compared with W. chinensis. W. trilobata significantly enhanced antioxidant defense systems through catalase, peroxidase, and superoxide dismutase by 18.6%, 20%, and 36.3%, respectively, providing a positive response to oxidative stress caused by low N. The PCA analysis showed that W. trilobata was 95.3% correlated with physiological traits by Dim1 (79.1%) and Dim2 (16.3%). This study provides positive feedback on W. trilobata with respect to its comprehensive invasion mechanism to improve agricultural systems via eco-friendly approaches in N deficit conditions, thereby contributing to the reclamation of barren land.

AbstractIn this instigation, the heat and mass transfer pattern on Eyring-Powell nanofluid with suspension of dust particles is focused. For heat transfer phenomenon, the Eyring-Powell nanofluid capturing the variable thermal conductivity. Furthermore, the variable and mass diffusivity assumptions are entertained for summarizing the observations chemical reaction phenomenon. The flow is endorsed to magnetic force impact. The additional impact of Brownian motion and thermophoresis consequences have been adopted. The numerical computations with shooting technique are performed. The physical aspects of parameters have been observed graphically. Based on depicted observations, it is examined that the fluid velocity reduces due to interaction velocity parameter which reverse trend is noted for dust particles velocity. The temperature profile for dusty fluid particles enhanced due to interaction parameter for temperature. Furthermore, the concentration profile reduces due to concentration interaction parameter. Current results present applications in solar energy, thermal processes, heat transform devices cooling systems, plasma, manufacturing processes, energy systems, etc. [ABSTRACT FROM AUTHOR]

We report microwave synthesis of seven unique pyrimidine anchored derivatives (1–7) incorporating multifunctional amino derivatives along with their in vitro anticancer activity and their activity against COVID-19 in silico. 1–7 were characterized by different analytical and spectroscopic techniques. Cytotoxic activity of 1–7 was tested against HCT116 and MCF7 cell lines, whereby 6 exhibited highest anticancer activity on HCT116 and MCF7 with EC50 values of 89.24 ± 1.36 µM and 89.37 ± 1.17 µM, respectively.Molecular docking was performed for derivatives (1–7) on main protease for SARS-CoV-2 (PDB ID: 6LU7). Results revealed that most of the derivatives had superior or equivalent affinity for the 3CLpro, as determined by docking and binding energy scores. 6 topped the rest with highest binding energy score of −8.12 kcal/mol with inhibition constant reported as 1.11 µM. ADME, drug-likeness, and pharmacokinetics properties of 1–7 were tested using Swiss ADME tool. Toxicity analysis was done with pkCSM online server.All derivatives showed high GI absorption. Except 1 and 3, all derivatives showed blood brain barrier permeability. Most derivatives showed negative logKp values suggesting derivatives are less skin permeable and bioavailability score of all derivatives was 0.55. The toxicity analysis demonstrated that all derivatives have no skin sensitization properties. 6 and 7 showed maximum tolerated dose (Human) values of −0.03 and −0.018, respectively and absence of AMES toxicity.

Pluronics are amphiphilic triblock copolymers composed of two hydrophilic poly (ethylene oxide) (PEO) chains linked via a central hydrophobic polypropylene oxide (PPO). Owing to their low molecular weight polymer and greater number of PEO segments, Pluronics induce micelle formation and gelation at critical micelle concentrations and temperatures. Pluronics F-68 and F-127 are the only United States (U.S.) FDA-approved classes of Pluronics and have been extensively used as materials for living bodies. Owing to the fascinating characteristics of Pluronics, many studies have suggested their role in biomedical applications, such as drug delivery systems, tissue regeneration scaffolders, and biosurfactants. As a result, various studies have been performed using Pluronics as a tool in nanomedicine and targeted delivery systems. This review sought to describe the delivery of therapeutic cargos using Pluronic F-68 and F-127-based cancer nanomedicines and their composites for combination therapy.

The design and synthesis of three new 1,8-naphthalimide-based fluorescent sensors (1–3) for the detection of Zn2+ in aqueous solution is described. The structural architect of these sensors contains 1,8-naphthalimide scaffold as a fluorophore attached to 2,2′-dipicolylamine (DPA) and bis(2-quinolinylmethyl)amine (DQA) receptors through an amide linkage. The addition of Zn2+ to the solutions of sensors (1–3) led to enhanced fluorescence intensity, ranging between 2.5 and 14 folds. At physiological pH (pH = 7.4), these sensors exhibited high selectivities for Zn2+ over a wide range of competing metal cations, displaying high sensitivities with a limit of detections of 120, 81.7 and 79.2 nM, respectively. This suggests that these sensors can detect chronic Zn2+ concentration for freshwater (>1.84 μM), designated by the U.S. Environmental Protection Agency. DFT simulations performed on the more stable stacked conformations of unbound and Zn2+ bounded states suggested that the latter display higher density of excited states than the unbound sensors. Moreover, the stacked conformer of sensor 3 was significantly more stable as compared to sensors 1 and 2, which was attributed to a stronger Van Der Waals (VDW) interaction between DQA and 1,8-naphthalimide. The Zn2+ binding leads to enhanced electronic coupling between the HOMOs and LUMOs, making excited states more populated which then undergoes geometric relaxation before emitting light and relaxing back to the ground states. The lower energy separation (5.0 eV) between the HOMO and the first Zn2+ d-orbital in sensor 3 as compared to sensors 1 and 2 results in enhanced density of the generated states and subsequently higher intensity upon binding with Zn2+.

The title compounds, 8-{1-[3-(cyclopent-1-en-1-yl)benzyl]piperidin-4-yl}-2-methoxyquinoline, C27H30N2O (I), and 8-{4-[3-(cyclopent-1-en-1-yl)benzyl]piperazin-1-yl}-2-methoxyquinoline, C26H29N3O (II), differ only in the nature of the central six-membered ring: piperidine in I and piperazine in II. They are isoelectronic (CH cf. N) and isotypic; they both crystallize in the triclinic space group P\overline{1} with very similar unit-cell parameters. Both molecules have a curved shape and very similar conformations. In the biaryl group, the phenyl ring is inclined to the cyclopentene mean plane (r.m.s. deviations = 0.089 Å for I and 0.082 Å for II) by 15.83 (9) and 13.82 (6)° in I and II, respectively, and by 67.68 (6) and 69.47 (10)°, respectively, to the mean plane of the quinoline moiety (r.m.s. deviations = 0.034 Å for I and 0.038 Å for II). The piperazine ring in I and the piperidine ring in II have chair conformations. In the crystals of both compounds, molecules are linked by C—H...π interactions, forming chains in I and ribbons in II, both propagating along the b-axis direction. The principal contributions to the overall Hirshfeld surfaces involve H...H contacts at 67.5 and 65.9% for I and II, respectively. The major contribution to the intermolecular interactions in the crystals is from dispersion forces (Edis), reflecting the absence of classical hydrogen bonds.

Cancer remains a major global health challenge. Traditional chemotherapy often results in side effects and drug resistance, necessitating the development of alternative treatment strategies such as gene therapy. Mesoporous silica nanoparticles (MSNs) offer many advantages as a gene delivery carrier, including high loading capacity, controlled drug release, and easy surface functionalization. MSNs are biodegradable and biocompatible, making them promising candidates for drug delivery applications. Recent studies demonstrating the use of MSNs for the delivery of therapeutic nucleic acids to cancer cells have been reviewed, along with their potential as a tool for cancer therapy. The major challenges and future interventions of MSNs as gene delivery carriers for cancer therapy are discussed.

The amine 8-{4-[(6-phenylpyridin-3-yl)methyl]piperazin-1-yl}-3,4-dihydroquinolin-2(1H)-one was crystallized as the hydrochloride salt, 4-(2-oxo-1,2,3,4-tetrahydroquinolin-8-yl)-1-[(6-phenylpyridin-3-yl)methyl]piperazin-1-ium chloride, C25H27N4+·Cl− (I·HCl). The conformation of the organic cation is half-moon in shape enclosing the chloride anion. The piperidine ring of the 3,4-dihydroquinolin-2(1H)-one moiety has a screw-boat conformation, while the piperazine ring has a chair conformation. In the biaryl group, the pyridine ring is inclined to the phenyl ring by 40.17 (7) and by 36.86 (8)° to the aromatic ring of the quinoline moiety. In the crystal, the cations are linked by pairwise N—H...O hydrogen bonds, forming inversion dimers enclosing an R22(8) ring motif. The Cl− anion is linked to the cation by an N—H...Cl hydrogen bond. These units are linked by a series of C—H...O, C—H...N and C—H...Cl hydrogen bonds, forming layers lying parallel to the ab plane.

Herein, we report novel macromolecular prodrugs (MPDs) of flurbiprofen (FLB) onto a cellulose ether, hydroxypropylcellulose (HPC). The FLB was activated with a powerful acylation reagent carbonyldiimadazole (CDI) in N,N′ dimethylacetamide (DMAc) solvent at room temperature. Imidazolide of FLB generated in situ reacts at 80 °C for 24 h with pre-dissolved HPC to prepare HPC-FLB conjugates. The resultant MPDs of FLB showed moderate to high degree of substitution (DS: 0.35–1.3) with good yield (70–82%). Structures were thoroughly characterized using FTIR, UV and NMR spectroscopic analyses. The pharmacokinetic studies showed that the t1/2 and tmax values of FLB from HPC-FLB conjugate were increased substantially as compare to standard FLB indicates enhanced bioavailability of drug after conjugate formation. Remarked anti-inflammatory activity of the HPC-FLB conjugate was also observed.

Abstract In this study, 5-amino-nicotinic acid derivatives (1–13) have been designed and synthesized to evaluate their inhibitory potential against α-amylase and α-glucosidase enzymes. The synthesized compounds (1–13) exhibited promising α-amylase and α-glucosidase activities. IC50 values for α-amylase activity ranged between 12.17 ± 0.14 to 37.33 ± 0.02 µg/mL ± SEM while for α-glucosidase activity the IC50 values were ranged between 12.01 ± 0.09 to 38.01 ± 0.12 µg/mL ± SEM. In particular, compounds 2 and 4–8 demonstrated significant inhibitory activities against α-amylase and α-glucosidase and the inhibitory potential of these compounds was comparable to the standard acarbose (10.98 ± 0.03 and 10.79 ± 0.17 µg/mL ± SEM, respectively). In addition, the impact of substituent on the inhibitory potential of these compounds was assessed to establish structure activity relationships. Studies in molecular simulations were conducted to better comprehend the binding properties of the compounds. All the synthesized compounds were extensively characterized with modern spectroscopic methods including 1H-NMR, 13C–NMR, FTIR, HR-MS and elemental analysis.

Polysaccharides are beneficially used as drug carriers via prodrug formation and offer a mechanism for better effectiveness and delivery of the drug. The unique geometry of hydroxypropylcellulose (HPC), a polysaccharide, allows the attachment of drug molecules with a higher degree of substitution because the hydroxyls groups are projected outside the HPC chains. Therefore HPC-Naproxen conjugates, i.e., macromolecular prodrugs, were synthesized using a powerful acylation reagent carbonyldiimadazole (CDI) in N,N' dimethylacetamide (DMAc) solvent. The reactions were carried out at 80 °C under stirring for 24 h and inert environment. This reaction strategy appeared efficient to obtain a high degree of drug substitution (DS = 0.88–1.40) on the polymer parent chain as calculated by UV–visible spectrophotometry after hydrolysis of the samples. The method provides high efficacy as product yields were high (77–81%). Macromolecular prodrugs (MPDs) with different DS of naproxen designed were found soluble in organic solvents.

Bioactive compounds are widely used in the bio-industry because of their antioxidant and antibacterial activities. Because of excessive oxidative stress, which causes various diseases in humans, and because preservatives used in bioproducts cause allergies and contact dermatitis, it is important to use natural bioactive compounds in bioproducts to minimize oxidative stress. α-bisabolol (ABS) is a natural compound with both antioxidant and antibacterial properties. However, its water-insolubility makes its utilization in bioproducts difficult. In this study, ABS-loaded polyglyceryl-4 caprate nanoparticles (ABS@NPs) with improved aqueous stability and ABS loading were fabricated using an encapsulation method. The long-term stability of the ABS@NPs was analyzed with dynamic light scattering and methylene blue-staining to determine the optimized ABS concentration in ABS@NPs (10 wt%). The ABS@NPs exhibited excellent antioxidant activity, according to the 2,2-diphenyl-1-picrylhydrazyl assay and in vitro reactive oxygen species generation in NIH-3T3 fibroblast cells, and an outstanding antibacterial effect, as determined using the Staphylococcus aureus colony-counting method. Furthermore, we evaluated the biocompatibility of the ABS@NPs in vitro. This study suggests that ABS@NPs with improved antioxidant and antibacterial properties can be used to treat diseases related to various oxidative stresses and can be applied in many fields, such as pharmaceuticals, cosmetics, and foods.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that causes coronavirus-19 disease (COVID-19), a severe respiratory damaging syndrome with serious health complications worldwide. SARS-CoV-2 was unfamilar before the epidemic started in Wuhan, China, in December 2019. COVID-19 is currently a pandemic influencing several countries worldwide. One of the mysteries of the new coronavirus is that it is deadlier for men than women with the male mortality rate is twice as high as that of females.

An enhanced acetylcholinesterase (AChE) activity is a hallmark in early stages of Alzheimer's ailment that results in decreased acetylcholine (ACh) levels, which in turn leads to cholinergic dysfunction and neurodegeneration. Consequently, inhibition of both AChE and butyrylcholinesterase (BChE) is important to prolong ACh activity in synapses for the enhanced cholinergic neurotransmission. In this study, a series of new fluoroquinolone derivatives (7a-m) have synthesized and evaluated for AChE and BChE inhibitory activities. The screening results suggested that 7 g bearing ortho fluorophenyl was the most active inhibitor against both AChE and BChE, exhibiting IC50 values of 0.70 ± 0.10 µM and 2.20 ± 0.10 µM, respectively. The structure–activity relationship (SAR) revealed that compounds containing electronegative functions (F, Cl, OMe, N and O) at the ortho position of the phenyl group exhibited higher activities as compared to their meta- and/or para substituted counterparts. Molecular docking studies of synthesized compounds 7a, 7g, 7j and 7l docked into the active site of AChE and 7a-f docked into the active site of BChE revealed that these compounds exhibited conventional H-bonding along with π-π interaction with the active residues of AChE through their electronegative functions and phenyl ring, respectively. All the synthesized compounds are characterized by spectroscopic methods including FT-IR, 1H- and 13C NMR as well as elemental analysis. This is the first example of fluoroquinolone-based cholinesterase inhibitors.

Meningococcal infection caused by Neisseria meningitidis causes epidemics especially in the ‘’Meningitis Belt’’ of Sub-Saharan Africa with a case fatality of 5.9% and attack rate 1%. We report a localized outbreak of Meningococcal disease in a Liberian county (a West African country) where our Pakistan Army Military Hospital was working under United Nations (UN) Mission. It began suddenly as a cluster of cases who had all attended a funeral. Patients developed sudden headache, vomiting and abdominal pain with petechial rash in a few but without fever in the majority. It caused much diagnostic confusion until the illness was diagnosed by Centres for disease control (CDC) as Meningococcal septicemia due to Neisseria meningitidis group C.

Abstract Background This study contributes to the current ethnomedicinal knowledge of the Swat Valley, Pakistan. District Swat possesses remarkable biodiversity owing to its varied topographical and climatic conditions, prompting a distinct human-plant association. Our hypothesis is that the presence of such a great biodiversity has shaped into a formal ethnobotanical culture in the area transmitted through generations. We suspect that the versatility of some plant species has greater influence on the culture. Therefore, the prime objective of the study is to understand this unique human-plant relationship in the valley and to create scientific roots for the selection and practice of herbs in the ethnobotanical domain of the district. Methods Primary data were collected using questionnaires and face-to-face interviews with the locals. The data collected were used for calculating some important indices, i.e. relative frequency of citation (RFC), participant agreement ratio (PAR), frequency of citation (FC), Smith’s Salience Index (SI), Relative Importance Index (RII), Cultural Value Index (CVI) and a newly proposed, Ali’s Conservation Priority Index (CPI). Index scores were used as key identifier of the ethnobotanically important plants of the area. Results Residents of the Swat Valley have listed plant uses in 15 use categories. Around 9% of the respondents have a common consensus on the selection and use of plants for the treatment of evil eye with similar results for body cuts (8.2%) followed by psychological/neural ailments (8.0%). Respondents agree that Berberis lyceum Royle. dominates in all five indices. Skimmia laureola Franch. also constitutes one of the central plants of the ethnobotanical domain, ranking second in the SI, fifth in the RII, seventh in CVI, and third in the Cultural Importance Index. It holds the thirty-fifth position in the CPI. Over 80% of the population treat different diseases with herbal remedies. In the common ethnobotanical domain of the area, plants like Mentha longifolia L., Berberis lyceum, and Skimmia laureola are very important and have high salience and importance values, thus suggesting these plants are versatile for their uses in the study area. Conclusion In conclusion, only some plant species are prioritised for their use in the ethnobotanical domain of the community. Medicinal and aromatic plant (MAP) usage is widespread in the Swat Valley. The ethnobotanical knowledge could be used as a tool to understand the adaptability of a specific taxon in the area and the possible conservation risk to their existence.

Abstract Effect of Trichoderma harzianum was investigated on plant growth and inhibitory activity against Phythium ultimum and Phytopthora capsici under laboratory and greenhouse conditions. Data under lab conditions revealed that mycelial growth of both pathogens were inhibited by T. harzianum in vitro. The effect of T. harzianum on different plant growth parameters was assessed in the presence of P. ultimum and P. capsici. Fresh and dry shoot weight was reduced by both fungal strains. The fresh shoot weight was decreased by 38.8 and 44.4% in case of P. capsici and P. ultimum, respectively. T. harzianum improved the overall plant growth in the presence of P. ultimum and P. capsici. Histopathological observation of P. ultimum and P. capsici infected tissue of the root clearly indicated that both severely affected the epidermis and vascular bundle of the host plant. T. harzianum reduced the size of lesions caused by the two pathogens. Observation of hyphae interaction of the T. harzianum with pathogens demonstrated that it inhibited the entry of both pathogens to the vascular bundle of the host tissue. Furthermore, no effect was observed on the vascular bundle, pith and cortex of treated host plant inoculated with T. harzianum and pathogens.

Carissa edulis is a plant used in the management of oxidative stress and inflammatory related disorders such as malaria, rheumatism inflammation, and cardiovascular diseases. The present study evaluates the total phenolic content, antioxidant capacity (DPPH, ABTS, and FRAP), and the bioactive compounds present in the various extracts of C. edulis (HEC, MEC, AEC, and PC). An HPLC analysis determined the different compounds present in the extracts. High concentration of total phenolic content was observed in aqueous and methanolic extracts more than in the hydroethanolic extract though not significantly different. Flavonoids were higher in the hydroethanolic and methanolic extracts, respectively, with 14.84 mg RE/g extract and 12.02 mg RE/g extract. Tannins were also found in large amounts in the same two extracts with 26.76 mg TAE/g extract and 34.67 mg TEE/g extract. The percentage radical scavenging activity DPPH ranged between 58.63% and 94.67% for aqueous extract and for ABTS between 51.39% and 94.12% for the methanolic extract. The highest FRAP was obtained in the methanolic extract (6.73 g AAE/100 g extract). HPLC analysis revealed the presence of quercetin, rutin, and gallic acid in the different extracts. C. edulis represents a potential source of bioactive components with antioxidant capacity.

Ziziphus nummularia is an important source of valuable phytoconstituents, which are widely used in traditional medicine system of Indo-Pak sub-continent. In this study we investigated the distribution of phenolic compounds in the fruit pericarps of six different genotypes (ZNP01-06) of Z. nummularia growing in the unexplored hilly areas of Pakistan. The methanolic extracts of these genotypes were screened for total phenolic content (TPC), total flavonoid content (TFC), antioxidant, and cholinesterase inhibitory potentials. The observed biological potentials were explained in terms of the outcome of molecular docking and HPLC analyses. Among them, genotype ZNP02 displayed high TPC (88.50 ± 1.23 μg/mL) and showed potent scavenging activity against DPPH (67.03 ± 1.04 μg/mL) and ABTS (65.3 ± 1.74 μg/mL) in comparison to ascorbic acid (68.7 ± 0.47 μg/mL). Moreover, genotypes ZNP01, ZNP02, and ZNP04 displayed potent inhibition against acetyl and butyryl cholinesterases (AChE and BChE) with IC50 values of 21.2, 20.5, and 23.7 μg/mL (AChE) and 22.7, 24.4, and 33.1 μg/mL (BChE), respectively. Furthermore, the individual compounds in the most potent species ZNP01 responsible for potent enzyme inhibition (identified through HPLC-UV analysis), were computed via docking simulation software to the enzyme structures. Among these compounds rutin exhibited significant binding affinity with value of −9.20 kcal/mol. The differences amongst the phytochemical compositions of the selected genotypes highlighted the genotypic variations in them. Based on our results it was concluded that the selected plant can be used as remedy of oxidative stress and neurodegenerative diseases. However, further studies are needed to isolate responsible compounds and test the observed potential in vivo, along with toxicological evaluations in animal models.

PURPOSE: The purpose of this study was to investigate the ability of a self-nano-emulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of a BCS class IV drug, etoposide (VP-16). METHOD: A series of SNEDDS formulations with VP-16 were prepared consisting of medium chain triglycerides, polysorbate 80, diethylene glycol monoethyl ether and propylene glycol monolaurate type-1. Based on an obtained ternary phase diagram, an optimum formulation was selected and characterized in terms of size, zeta potential, loading, morphology and in vitro drug release. The pharmacokinetic parameters and oral bioavailability of VP-16 suspension and VP-16 in SNEDDS was assessed using 30 Male Sprague–Dawley rats and compared with the commercial product (VePesid®). RESULTS: Pharmacokinetic data showed that the mean values for AUC0-t of VP-16 in SNEDDS was 6.4 fold higher compared to a drug suspension and 2.4-folds higher than VePesid®. Similarly, the mean value for Cmax of VP-16 in SNEDDS (1.13± 0.07 µg/ml µg.h/mL) was higher than VePesid® (0.62± 0.09 µg/mL) and drug suspension (0.13± 0.07 µg/mL). CONCLUSION: The SNEDDS formulation was able to enhance the oral bioavailability of the BCS Class IV chemotherapeutic agent VP-16 by increasing the dissolution and absorption of the drug. A good in vitro in vivo correlation was found between the in vitro dissolution and in vivo absorption data of VP-16 SNEDDS preparation. Therefore, SNEDDS formulations might be a very promising approach for BCS Class IV drugs.

ABSTRACTFlurbiprofen, a potent nonsteroidal anti-inflammatory drug, is widely used for relief of pain in patients suffering from rheumatic diseases, migraine, sore throat and primary dysmenorrheal. However, this drug has many gastrointestinal side effects produced by its oral administration, such as gastric bleeding and peptic ulcer. These effects were responsible for non-compliance among patients, which ultimately results in treatment failure. The physicochemical properties of flurbiprofen, make it a suitable candidate for transdermal drug delivery, which can overcome the drawbacks of oral administration. In this sense, microemulsions have been proved to increase the cutaneous absorption of lipophilic drugs when compared to conventional drug delivery systems. The purpose of this study was to formulate and characterize gel based microemulsions, for topical delivery of flurbiprofen. Different gel bases, containing microemulsion and hydro-alcoholic solution of flurbiprofen, were developed and compared. In vitro study showed that gels containing microemulsion had a higher permeation rate than those containing hydro-alcoholic solutions. Additionally, formulation of Carbopol-I (microemulsion) showed higher percent of inhibition of inflammation than others bases. Further, skin irritation study demonstrated that Carbopol-I was none irritating. Flurbiprofen microemulsion incorporated on Carbopol-I showed physicochemical, in vitro and in vivo characteristics suitable for the development of alternative transdermal delivery formulation.

Two new DTPA-bis(amide) based ligands conjugated with the arylpiperazinyl moiety were synthesized and subsequently transformed into their corresponding Gd(III) complexes 1 and 2 of the type [Gd(L)H2O]·nH2O. The relaxivity (R1) of these complexes was measured, which turned out to be comparable with that of Omniscan®, a commercially available MRI contrast agent. The cytotoxicity studies of these complexes indicated that they are non-toxic, which reveals their potential and physiological suitability as MRI contrast agents. All the synthesized ligands and complexes were characterized with the aid of analytical and spectroscopic methods, including elemental analysis, 1H-NMR, FT-IR, XPS and fast atom bombardment (FAB) mass spectrometry.

In recent years, it has become apparent that cancer nanomedicine’s reliance on synthetic nanoparticles as drug delivery systems has resulted in limited clinical outcomes. This is mostly due to a poor understanding of their “bio−nano” interactions. Protein-based nanoparticles (PNPs) are rapidly emerging as versatile vehicles for the delivery of therapeutic and diagnostic agents, offering a potential alternative to synthetic nanoparticles. PNPs are abundant in nature, genetically and chemically modifiable, monodisperse, biocompatible, and biodegradable. To harness their full clinical potential, it is important for PNPs to be accurately designed and engineered. In this review, we outline the recent advancements and applications of PNPs in cancer nanomedicine. We also discuss the future directions for PNP research and what challenges must be overcome to ensure their translation into the clinic.