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Background: Depression is increasingly diagnosed in the general population today. The loss of a limb through amputation, which can result in disfigurement, may also contribute to the development of depression despite pre-operative counselling. Understanding the factors associated with depression in individuals with limb amputation is important to effectively identify and manage this psychological condition. The objective of this study was to identify the factors associated with depression in individuals who have undergone limb amputation., Methods: A descriptive cross-sectional study was conducted in Quetta City from May to July 2018. Data were collected using a structured, respondent-cantered questionnaire based on the Hospital Anxiety and Depression Scale (HADS)., Results: Females were more affected as 5 out of 7 (71.42%) were depressed compared to 32 out of 47 (68%) males. The study found a statistically significant association between depression and marital status (p-value of 0.047) as well as amputation (p-value of 0.039). These results suggest that both sociodemographic factors, such as marital status, and the experience of amputation are associated with the development of depression in individuals with limb amputation., Conclusions: Amputation is significantly associated with the level of depression among amputees, and sociodemographic factors, such as marital status, also play a role in the development of depression. Therefore, it is recommended to conduct yearly screenings for depression following an amputation to effectively identify and manage this psychological condition. Further research and interventions are needed to address the mental health needs of individuals with limb amputation and implement strategies for depression prevention and management in this population.

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma.

Formamidinium lead bromide (FAPbBr 3 ) nanocrystals have emerged as a powerful platform for optoelectronic applications due to their pure green photoluminescence (PL). However, their low colloidal stability under storage and operation reduces the potential use of FAPbBr 3 perovskite nanocrystals (PeNCs) in various applications. In this study, we prepared the poly(L-lactic acid) (PLLA) nanofibrous membrane embedded with FAPbBr 3 perovskite nanocrystals by electrospinning the perovskite and PLLA precursor solution. This is a simple and low-cost technique for the direct confinement of nano-sized functional materials in the continuous polymer nanofibres. PLLA as a polymer matrix provided a high surface framework to fully encapsulate the perovskite NCs. In addition, we found that FAPbBr 3 PeNCs crystallize spontaneously inside the PLLA nanofibre. The resultant PLLA-FAPbBr 3 nanofibrous membranes were stable and remained in the water for about 45 days without any evident decomposition. The results of this research support the idea of new possibilities for the production of air-stable FAPbBr 3 PeNCs by forming a composite with PLLA polymer. The authors believe this study is a new milestone in the development of highly stable metal halide perovskite-based nanofibres, which allow for potential use in lasers, waveguides, and flexible energy harvesters., Competing Interests: The authors declare no conflicts of interest.

In spite of its high effectiveness in the treatment of both leishmaniasis as well as a range of fungal infections, the free form of the polyene antibiotic amphotericin B (AmB) does not entertain the status of the most preferred drug of choice in clinical settings. The high intrinsic toxicity of the principal drug could be considered the main impedance in the frequent medicinal use of this otherwise very effective antimicrobial agent. Taking into consideration this fact, the pharma industry has introduced many novel dosage forms of AmB to alleviate its toxicity issues. However, the limited production, high cost, requirement for a strict cold chain, and need for parenteral administration are some of the limitations that explicitly compel professionals to look for the development of an alternate dosage form of this important drug. Considering the fact that the nano-size dimensions of drug formulation play an important role in increasing the efficacy of the core drug, we employed a green method for the development of nano-assemblies of AmB (AmB-NA). The as-synthesized AmB-NA manifests desirable pharmacokinetics in the treated animals. The possible mechanistic insight suggested that as-synthesized AmB-NA induces necrosis-mediated cell death and severe mitochondrial dysfunction in L. donovani promastigotes by triggering depolarization of mitochondrial membrane potential. In vivo studies demonstrate a noticeable decline in parasite burden in the spleen, liver, and bone marrow of the experimental BALB/c mice host. In addition to successfully suppressing the Leishmania donovani , the as-formed AmB-NA formulation also modulates the host immune system with predominant Th1 polarization, a key immune defender that facilitates the killing of the intracellular parasite., Competing Interests: The authors declare no conflict of interest.

Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future.

Although, zinc oxide nanoparticles (ZRTs) as an anti-cancer agent have been the subject of numerous studies, none of the reports has investigated the impact of the reaction entry time of ion-carriers on the preparation of ZRTs. Therefore, we synthesized variants of ZRTs by extending the entry time of NaOH (that acts as a carrier of hydroxyl ions) in the reaction mixture. The anti-proliferative action, morphological changes, reactive oxygen species (ROS) production, and nuclear apoptosis of ZRTs on human A431 skin carcinoma cells were observed. The samples revealed crystallinity and purity by X-ray diffraction (XRD). Scanning electron microscopy (SEM) images of ZRT-1 (5 min ion carrier entry) and ZRT-2 (10 min ion carrier entry) revealed microtubule like morphology. On prolonging the entry time for ion carrier (NaOH) introduction in the reaction mixture, a relative ascent in the aspect ratio was seen. The typical ZnO band with a slight shift in the absorption maxima was evident with UV-visible spectroscopy. Both ZRT-1 and ZRT-2 exhibited non-toxic behavior as evident by RBC lysis assay. Additionally, ZRT-2 showed better anti-cancer potential against A431 cells as seen by MTT assay, ROS generation and chromatin condensation analyses. At 25 μM of ZRT-2, 5.56% cells were viable in MTT test, ROS production was enhanced to 166.71%, while 33.0% of apoptotic cells were observed. The IC 50 for ZRT-2 was slightly lower (6 μM) than that for ZRT-1 (8 μM) against A431 cells. In conclusion, this paper presents a modest, economical procedure to generate ZRT nano-structures exhibiting strong cytotoxicity against the A431 cell line, indicating that ZRTs may have application in combating cancer., 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 Aljohar, Muteeb, Zia, Siddiqui, Aatif, Farhan, Khan, Alsultan, Jamal, Alshoaibi, Ahmad, Alam, Arshad and Ahamed.)

Introduction: In Saudi Arabia, the epidemiology of rheumatoid arthritis (RA) is not well studied and is marked by inconsistencies in clinical diagnosis. Therefore, in this study, we explored the prevalence, clinical characteristics, and diagnostic validity of a prediction score based upon disease markers in orthropedic clinics' patients in the Madinah region of Saudi Arabia., Method: The clinical data for this retrospective cross-sectional study were retrieved from the database registry of orthopedic clinics in selected hospitals of the Medinah province of Saudi Arabia. Sociodemographic features, disease markers and the clinical characteristics were collected for a period of 6 months, from December 1, 2020, to May 31, 2021. The prediction score was generated from the sum of disease markers, coded as dichotomous variables., Results: The total sample size of our study was 401. The prevalence of RA in the study subjects ( n = 401) was 14.46% ( n = 58). Among RA patients, the majority were females (60.3%). Painful joints (69%) and swollen joints (51.7%) were the most common clinical complaints among RA patients. RA patients suffered from arthritis (51.7%) and experienced fatigue (46.6%), weight loss (44.8%), and loss of appetite (41.4%). Diabetes (55.2%) was the most common comorbidity in the RA patients. The sensitivity and specificity of the prediction score at the criterion score of 2.5 were 67.3% and 63.0%, respectively. The area under the curve was 0.69 (95% CI [0.62-0.76])., Conclusion: There was a moderately high prevalence of RA in patients visiting the orthropedic clinics of the selected hospitals of Madinah region of Saudi Arabia. The diagnostic validity of the prediction score, though promising, was slightly lower than the acceptable range., Competing Interests: The authors declare that they have no competing interests., (© 2022 Mir et al.)

Acute hypokalemic paralysis (AHP) is a life-threatening emergency. It is exceptionally unusual for hypothyroidism to present with AHP. This association can be either primary or secondary through distal renal tubular acidosis. We report two cases who presented with acute quadriplegia. The succeeding investigations revealed severe hypokalemia and autoimmune hypothyroidism. The second case was found to have Sjogren's syndrome additionally. The underlying aetiology of hypokalemia in both cases was found to be dRTA. The combination of such conditions is reported sporadically. Here we also discuss the potential association of AHP with autoimmune conditions by proxy through dRTA.

The sol-gel technique was used to fabricate ZnO Nano-swirlings (ZNsw) at a predetermined agitation rate (of >> 1900 rpm), with around 21.94 gm of zinc acetate dihydrate and 0.2 g cetyltrimethylammoniumbromide (CTAB) and a cationic surfactant (drop-wise). The impact of the predetermined agitation condition on the molecular size and morphology of ZNsw is examined, and the outcomes are dissected by useful characterization tools and techniques viz. XRD, SEM embedded with EDS, TEM, FT-IR and UV-visible. The SEM and TEM results suggest that the product formed into a big cluster of adequate ZNsw, containing a significant quantity of folded long thread-lengths. Each group indicated a fair amount of the volume of these lengths. The photocatalytic process of ZNsw was carried out as a result of the irradiation time due to the deterioration of Azo Dye AR183, resulting in approximately 79 percent dye discoloration following an 80-min UV light irradiation in the presence of ZNsw. Additionally, the synthesized ZNsw was tested for antagonistic activity, and the growth hindrance of two plant pathogenic fungal strains found. Per cent inhibition in growth of Rhizoctonia solani and Alternaria alternata were observed in response to ZNsw., (© 2022. The Author(s).)

Alzheimer's disease (AD) is a neurodegenerative disease and the most prevalent form of dementia. The generation of oxygen free radicals and oxidative damage is believed to be involved in the pathogenesis of AD. It has been suggested that date palm, a plant rich in phenolic compounds and flavonoids, can provide an alternative treatment to fight memory loss and cognitive dysfunction due to its potent antioxidant activity. Thus, we studied the effect of flavonoids present in date palm on Aβ 1-40 amyloid formation using molecular docking and molecular dynamics simulation. AutoDock. Myricetin was used as a positive control drug. The flavonoids Diosmetin, Luteolin, and Rutin were found to be potent inhibitors of aggregation (docking energies ≤ -8.05 kcal mol -1 ) targeting Aβ 1-40 fibrils (both 2LMO and 6TI5), simultaneously. Further screening by physicochemical properties and drug-likeness analysis suggested that all flavonoids except Rutin followed Lipinski's rule of five. Rutin was, thus, taken as a negative control (due to its violation of Lipinski's rule) to compare its dynamics with Diosmetin. Diosmetin exhibited the highest positive scores for drug likeness. Since Luteolin exhibited moderate drug-likeness and better absorption properties, it was also included in molecular dynamics simulation. Molecular dynamics of shortlisted compounds (Rutin, Diosmetin, and Luteolin) were performed for 200 ns, and the results were analyzed by monitoring root mean square deviations (RMSD), root mean square fluctuation (RMSF) analysis, the radius of gyration (Rg), and solvent accessible surface area (SASA). The results proved the formation of a stable protein-compound complex. Based on binding energies and non-bonded interactions, Rutin and Luteolin emerged as better lead molecules than Diosmetin. However, high MW (610.5), lowest absorption rate (16.04%), and more than one violation of Lipinski's rule make Rutin a less likely candidate as an anti-amyloidogenic agent. Moreover, among non-violators of Lipinski's rule, Diosmetin exhibited a greater absorption rate than Luteolin as well as the highest positive scores for drug-likeness. Thus, we can conclude that Diosmetin and Luteolin may serve as a scaffold for the design of better inhibitors with higher affinities toward the target proteins. However, these results warrant in-vitro and in-vivo validation before practical use., 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 Zia, Rehman, Hashmi, Siddiqui, Bin Dukhyil, Ahmed, Jamal, Banawas, Almalki, Owais, Aldhafeeri, Ibrahim, Alturaiki, AlAjmi, Alsieni and Alqurashi.)

Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer's disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in silico studies, through molecular docking and molecular dynamics simulation experiments, various flavonoids and alkaloids from Bauhinia variegata were utilised as inhibitors to target the protein (CALHM1). The sequence of CALHM1 was retrieved from UniProt and the secondary structure prediction of CALHM1 was done through CFSSP, GOR4, and SOPMA methods. The structure was identified through LOMETS, MUSTER, and MODELLER and finally, the structures were validated through Rampage. Bauhinia variegata plant was used to check the interaction of alkaloids and flavonoids against CALHM1. The protein and protein-ligand complex were also validated through molecular dynamics simulations studies. The model generated through MODELLER software with 6VAM A was used because this model predicted the best results in the Ramachandran plot. Further molecular docking was performed, quercetin was found to be the most appropriate candidate for the protein molecule with the minimum binding energy of -12.45 kcal/mol and their ADME properties were analysed through Molsoft and Molinspiration. Molecular dynamics simulations showed that CALHM1 and CALHM1-quercetin complex became stable at 2500 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. With the help of an in silico study, it was easier to analyse the 3D structure of the protein, which may be scrutinized for the best-predicted model. Quercetin may work as a good inhibitor for treating Alzheimer's disease, according to in silico research using molecular docking and molecular dynamics simulations, and future in vitro and in vivo analysis may confirm its effectiveness.

Therapeutic drugs based on natural products for the treatment of SARS-CoV-2 are currently unavailable. This study was conducted to develop an anti-SARS-CoV-2 herbal medicine to face the urgent need for COVID-19 treatment. The bioactive components from ethanolic extract of Moringa oleifera fruits (MOFs) were determined by gas chromatography-mass spectroscopy (GC-MS). Molecular-docking analyses elucidated the binding effects of identified phytocomponents against SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) and human ACE2 receptor (PDB ID: 1R42) through the Glide module of Maestro software. GC-MS analysis unveiled the presence of 33 phytocomponents. Eighteen phytocomponents exhibited good binding affinity toward ACE2 receptor, and thirteen phytocomponents had a high affinity with spike glycoprotein. This finding suggests that the top 11 hits (Docking score ≥ -3.0 kcal/mol) could inhibit SARS-CoV-2 propagation. Intriguingly, most of the phytoconstituents displayed drug-likeness with no predicted toxicity. However, further studies are needed to validate their effects and mechanisms of action. PRACTICAL APPLICATIONS: Moringa oleifera (MO) also called "drumstick tree" has been used as an alternative food source to combat malnutrition and may act as an immune booster. GC-MS analysis unveiled that ethanolic extract of Moringa oleifera fruits (MOFs) possessed 33 active components of pyridine, aromatic fatty acid, oleic acid, tocopherol, methyl ester, diterpene alcohol, triterpene and fatty acid ester and their derivatives, which have various pharmacological and medicinal values. Virtual screening study of phytocomponents of MOF with human ACE2 receptor and SARS-CoV-2 spike glycoprotein exhibited good binding affinity. Based on molecular docking, the top 11 hits (Docking score ≥-3.0 kcal/mol) might serve as potential lead molecules in antiviral drug development. Intriguingly, most of the phytoconstituents displayed drug-likeness with no predicted toxicity. Thus, MOF might be used as a valuable source for antiviral drug development to combat COVID-19, an ongoing pandemic., (© 2022 Wiley Periodicals LLC.)

Neurodegenerative disorders involve various pathophysiological pathways, and finding a solution for these issues is still an uphill task for the scientific community. In the present study, a combination of molecular docking and dynamics approaches was applied to target different pathways leading to neurodegenerative disorders such as Alzheimer's disease. Initially, abrineurin natural inducers were screened using physicochemical properties and toxicity assessment. Out of five screened compounds, a pentacyclic triterpenoid, i.e., Soyasapogenol B appeared to be the most promising after molecular docking and simulation analysis. Soyasapogenol B showed low TPSA (60.69), high absorption (82.6%), no Lipinski rule violation, and no toxicity. Docking interaction analysis revealed that Soyasapogenol B bound effectively to all of the targeted proteins (AChE, BuChE MAO-A, MAO-B, GSK3β, and NMDA), in contrast to other screened abrineurin natural inducers and inhibitors. Importantly, Soyasapogenol B bound to active site residues of the targeted proteins in a similar pattern to the native ligand inhibitor. Further, 100 ns molecular dynamics simulations analysis showed that Soyasapogenol B formed stable complexes against all of the targeted proteins. RMSD analysis showed that the Soyasapogenol B-protein complex exhibited average RMSD values of 1.94 Å, 2.11 Å, 5.07 Å, 2.56 Å, 3.83 Å and 4.07 Å. Furthermore, the RMSF analysis and secondary structure analysis also indicated the stability of the Soyasapogenol B-protein complexes.

Bioplastics, synthesized by several microbes, accumulates inside cells under stress conditions as a storage material. Several microbial enzymes play a crucial role in their degradation. This research was carried to test the biodegradability of poly-β-hydroxybutyrate (PHB) utilizing PHB depolymerase, produced by bacteria isolated from sewage waste soil samples. Potent PHB degrader was screened based on the highest zone of hydrolysis followed by PHB depolymerase activity. Soil burial method was employed to check their degradation ability at different incubation periods of 15, 30, and 45 days at 37±2°C, pH 7.0 at 60% moisture with 1% microbial inoculum of Aeromonas caviae Kuk1-(34) (MN414252). Without optimized conditions, 85.76% of the total weight of the PHB film was degraded after 45 days. This degradation was confirmed with Fourier-transform infrared spectroscopy (FTIR) and Scanning electron microscope (SEM) analysis. The presence of bacterial colonies on the surface of the degraded film, along with crest, holes, surface erosion, and roughness, were visible. Media optimization was carried out in statistical mode using Plackett Burman (PB) and Central Composite Design (CCD) of Response Surface Methodology (RSM) by considering ten different factors. Analysis of Variance (ANOVA), Pareto chart, response surface plots, and F-value of 3.82 implies that the above statistical model was significant. The best production of PHB depolymerase enzyme (14.98 U/mL) was observed when strain Kuk1-(34) was grown in a media containing 0.1% PHB, K2HPO4 (1.6 gm/L) at 27 ℃ for seven days. Exploiting these statistically optimized conditions, the culture was found to be a suitable candidate for the management of solid waste, where 94.4% of the total weight of the PHB film was degraded after 45 days of incubation., Competing Interests: The authors have declared that no competing interests exist.

Background: Phoenix dactylifera L. has a diverse set of pharmacological properties due to its distinct phytochemical profile. The purpose of this study was to investigate the anticancer potential of Phoenix dactylifera seed extract (PDSE) in human breast cancer MDA-MB-231 and MCF-7 cells, as well as liver cancer HepG2 cells, and to investigate the anticancer efficacy in triple-negative MDA-MB-231 cells, followed by in silico validation of the molecular interaction between active components of PDSE and caspase-3, an apoptosis executioner protein ., Methods: In this study, human cancer cell lines were cultured and subsequently treated with 10 to 100 μg/mL of PDSE. MTT test was performed to determine the cell viability, MMP was measured using fluorescent probe JC-1, nuclear condensation was determined by Hoechst 33258 dye, Annexin V-FITC & PI staining and cell cycle analysis were evaluated through flow cytometer, and apoptotic markers were detected using western blotting. The bioactive agents in PDSE were identified using high-performance liquid chromatography (HPLC) analysis. The binding affinity was validated using molecular docking tools AutoDock Vina and iGEMDOCK v2.1., Results: Cell viability data indicated that PDSE inhibited cell proliferation in both breast cancer cells and liver cancer cells. MDA-MB-231 cells showed maximum growth inhibition with an IC 50 value of 85.86 μg/mL for PDSE. However, PDSE did not show any significant toxicity against the normal Vero cell line. PDSE induced MMP loss and formation of apoptotic bodies, enhanced late apoptosis at high doses and arrested cells in the S phase of cell cycle. PDSE activated the enzymatic activity of cleaved caspase-3 and caused the cleavage of poly-ADB ribose polymerase (PARP) protein. PDSE upregulated pro-apoptotic Bax protein markedly but  no significant effect on tumor suppressor protein p53, while it downregulated the anti-apoptotic Bcl-2 protein expression. HPLC analysis showed the presence of rutin and quercetin bioactive flavonols in ethanolic extract of PDS. Interestingly, both active components revealed a strong binding interaction with amino acid residues of caspase-3 (PDB ID: 2XYP; Hetero 4-mer - A2B2) protein., Conclusion: PDS could serve as a potential medicinal source for apoptotic cell death in human breast cancer cells and, thus, could be used as a promising and crucial candidate in anticancer drug development. This study warrants further in vivo research, followed by clinical investigation., (© 2022. The Author(s).)

The study aimed to assess the proficiency of secondary metabolites (SMs) synthesized by actinobacteria isolated from the rhizospheric soil of Rauwolfia serpentina for its antimicrobial and anti-biofilm activity. After morphological and biochemical identification of actinobacteria, primary and secondary screening was done for specific metabolite production. The secondary metabolites were then tested for their antioxidant, antibacterial, and antibiofilm potential. Out of 29 bacterial colonies isolated, only one emerged as a novel isolate, Microbacterium LA2(R). Partial 16S rRNA gene sequence of the isolate LA2(R) was deposited in NCBI GenBank with accession number MN560041. The highest antioxidant capacity of the methanolic extract the novel isolate was found to be 474.183 µL AAE/mL and 319.037 µL AAE/mL by DPPH assay and ABTS assay respectively; three folds higher than the control. These results were further supported by the high total phenolic (194.95 gallic acid equivalents/mL) and flavonoid contents (332.79 µL quercetin equivalents/mL) of the methanolic extract. GC-MS analysis revealed the abundance of antibacterial compounds; where, n-Hexadecanoic acid was found to be the major compound present with a peak of 14 min retention time (RT) and 95% similarity index. MIC value of the metabolite was noted to be around 132.28 ± 84.48 μg/mL. The IC 50 value was found to be 74.37, 71.33, 66.28 and 84.48 μg/mL against Escherichia coli , Staphylococcus aureus , Klebsiella pneumonia , and Salmonella abony , respectively. Treatment with IC 50 of the extract decreased the biofilm formation up to 70%-80% against pathogenic strains viz. Escherichia coli , Staphylococcus aureus , Klebsiella pneumoniae and Salmonella abony . These significant activities of Microbacterium sp. LA2(R) suggests that it could be utilized for antibiotic production for human welfare and in various important industrial applications., 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., (© 2021 The Authors.)

Since the outbreak of coronavirus disease (COVID-19) in Wuhan, China, triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2) in late November 2019, spreading to more than 200 countries of the world, the ensuing pandemic to an enormous loss of lives, mainly the older population with comorbidities, like diabetes, cardiovascular disease, chronic obstructive pulmonary disease, obesity, and hypertension. Amongst these immune-debilitating diseases, SARS-CoV-2 infection is the most common in patients with diabetes due to the absence of a normal active immune system to fight the COVID-19. Recovery of patients having a history of diabetes from COVID-19 encounters several complications, and their management becomes cumbersome. For control of coronavirus, antiviral medications, glucose-lowering agents, and steroids have been carefully evaluated. In the present review, we discuss the crosstalk between SARS-CoV-2 infection and patients with a history of diabetes. We mainly emphasize the molecular factors that are involved in diabetic individuals recently infected by SARS-CoV-2 and developed COVID-19 disease. Lastly, we examine the medications available for the long-term management of diabetic patients with SARS-CoV-2 infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The emergence and spread of SARS-CoV-2 throughout the world has created an enormous socioeconomic impact. Although there are several promising drug candidates in clinical trials, none is available clinically. Thus, the drug repurposing approach may help to overcome the current pandemic., Methods: The main protease (M pro ) of SARS-CoV-2 is crucial for cleaving nascent polypeptide chains. Here, FDA-approved antiviral and anti-infection drugs were screened by high-throughput virtual screening (HTVS) followed by re-docking with standard-precision (SP) and extra-precision (XP) molecular docking. The most potent drug's binding was further validated by free energy calculations (Prime/MM-GBSA) and molecular dynamics (MD) simulation., Results: Out of 1397 potential drugs, 157 showed considerable affinity toward M pro . After HTVS, SP, and XP molecular docking, four high-affinity lead drugs (Iodixanol, Amikacin, Troxerutin, and Rutin) with docking energies -10.629 to -11.776kcal/mol range were identified. Among them, Amikacin exhibited the lowest Prime/MM-GBSA energy (-73.800kcal/mol). It led us to evaluate other aminoglycosides (Neomycin, Paramomycin, Gentamycin, Streptomycin, and Tobramycin) against M pro . All aminoglycosides were bound to the substrate-binding site of M pro and interacted with crucial residues. Altogether, Amikacin was found to be the most potent inhibitor of M pro . MD simulations of the Amikacin-M pro complex suggested the formation of a complex stabilized by hydrogen bonds, salt bridges, and van der Waals interactions., Conclusion: Aminoglycosides may serve as a scaffold to design potent drug molecules against COVID-19. However, further validation by in vitro and in vivo studies is required before using aminoglycosides as an anti-COVID-19 agent., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this study, a versatile method for the manufacturing of chitosan-grafted porous poly (L-lactic acid) (P-PLLA) nanofibrous membrane by using polydopamine (PDA) as an intermediate layer has been developed. P-PLLA fibres were electrospun and collected as nano/micro fibrous membranes. Highly porous fibres could serve as a substrate for chitosan to adsorb heavy metal ions. Moreover, PDA was used to modify P-PLLA surface to increase the coating uniformity and stability of chitosan. Due to the very high surface area of P-PLLA membranes and abundant amine groups of both PDA and chitosan, the fabricated membranes were utilized as adsorbent for removal of copper (Cu 2+ ) ions from the wastewater. The adsorption capability of Cu 2+ ions was examined with respect to the PDA polymerization times, pH, initial metal ion concentration and time. Finally, the equilibrium adsorption data of chitosan-grafted membranes fitted well with the Langmuir isotherm with the maximum adsorption capacity of 270.27 mg/g., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Cervical cancer is the second leading cause of cancer in women, which necessitates safe and potential therapeutic agents., Objective: This study was designed to investigate the antiproliferative effect of ethanolic extract of Cissus quadrangularis L. (CQ) against human cervical adenocarcinoma HeLa cell line and in silico analysis of selected active agents against apoptosis executioner enzyme caspase-3., Methods: Cell viability was analyzed in HeLa cells at different concentrations (25-300 μg/ml) of CQ extract. Reactive oxygen species (ROS) generation, cellular apoptosis, cell cycle analysis and caspases-3 activation were evaluated. In silico, structure-based virtual screening analysis was carried out using AutoDock Vina and iGEMDOCK., Results: Cell viability of HeLa cells was reduced significantly (p < 0.05) in a dose-dependent manner, however, CQ extract showed non-toxic to normal kidney epithelial NRK-52E cells. CQ extract induced the intracellular ROS level, nuclear condensation and reduced the mitochondrial membrane potential (MMP) with the induction of annexin V-FITC positive cells. CQ extract arrested cells in G0/G1 and G2/M checkpoints and activated caspase-3 activity significantly in HeLa cells. The molecular docking study showed a strong binding affinity of CQ phytocomponents against the caspase-3 (PDB ID: 1GFW) protein of human apoptosis. PASS analyses of selected active components using Lipinski's Rule of five showed promising results. Further, drug-likeness and toxicity assessment using OSIRIS Data Warrior V5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity., Conclusion: This study suggested that active constituents in CQ extract can be considered as potential chemotherapeutic candidates in the management of cervical cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study evaluates the impact of two separate incubation periods (4 and 6 weeks) on the morphology of sol-gel-fabricated ZnO nanospikes (ZNs), that is, ZN1 and ZN2, respectively. We further analyzed the inhibitory effects of ZN1 and ZN2 on quorum sensing (QS) and biofilm formation in Pseudomonas aeruginosa (PAO1) and Chromobacterium violaceum (strains 12472 and CVO26). The size of the synthesized ZNs was in the range of 40-130 nm, and finer nanoparticles were synthesized after an incubation period of 6 weeks. Treatment with ZNs decreased the production of violacein in the pathogen without affecting the bacterial growth, which indicated that ZNs inhibited the QS signaling regulated by N -acyl homoserine lactone. ZN2 had a higher inhibitory action on the virulence factor productivity than ZN1. Furthermore, ZN2-treated cells displayed a substantial decrease in azocasein-degrading protease activity (80%), elastase activity (83%), and pyocyanin production (85%) relative to untreated P. aeruginosa PAO1 cells. Treatment with ZN2 decreased swarming motility and exopolysaccharide production by 89 and 85%, respectively. ZN2 was effective against both the las & pqs systems of P. aeruginosa and exhibited broad-spectrum activity. Additionally, ZN2 was more efficient in inhibiting the biofilm formation at the attachment stage than ZN1. These findings revealed that in P. aeruginosa , ZN2 demonstrated inhibitory effects on QS as well as on the development of biofilms. Thus, ZN2 can be potentially used to treat drug-resistant P. aeruginosa infections., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

Authentication of meat products is critical in the food industry. Meat adulteration may lead to religious apprehensions, financial gain and food-toxicities such as meat allergies. Thus, empirical validation of the quality and constituents of meat is paramount. Various analytical methods often based on protein or DNA measurements are utilized to identify meat species. Protein-based methods, including electrophoretic and immunological techniques, are at times unsuitable for discriminating closely related species. Most of these methods have been replaced by more accurate and sensitive detection methods, such as DNA-based techniques. Emerging technologies like DNA barcoding and mass spectrometry are still in their infancy when it comes to their utilization in meat detection. Gold nanobiosensors have shown some promise in this regard. However, its applicability in small scale industries is distant. This article comprehensively reviews the recent developments in the field of analytical methods used for porcine identification., 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.)

Porous poly(L-lactic acid) (PLLA) nanofibrous membrane with the high surface area was developed by electrospinning and post acetone treatment and used as a substrate for deposition of chitosan. Chitosan was coated onto porous nanofibrous membrane via direct immersion coating method. The porous PLLA/chitosan structure provided chitosan a high surface framework to fully and effectively adsorb heavy metal ions from water and showed higher and faster ion adsorption. The composite membrane was used to eliminate copper ions from aqueous solutions. Chitosan acts as an adsorbent due to the presence of aminic and hydroxide groups which are operating sites for the capture of copper ions. The maximum adsorption capacity of copper ions reached 111.66 ± 3.22 mg/g at pH (7), interaction time (10 min) and temperature (25 °C). The adsorption kinetics of copper ions was established and was well agreed with the second-order model and Langmuir isotherm. Finally, the thermodynamic parameters were studied., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ultrafine particulate aerosols less than 100 nm diffuse randomly in the air and are hazardous to the environment and human health. However, no technical standards or commercial products are available for filtering particle sizes under 100 nm yet. Here, we report the development of a porous poly(l-lactic acid) (PLLA) nanofibrous membrane filter with an ultra-high specific surface area via electrospinning and a post-treatment process. After PLLA fibres were electrospun and collected, they were treated by acetone to generate a blossoming porous structure throughout each individual fibre. Characterizations of morphology, crystallinity, and mechanical and thermal properties demonstrated that the porous structure can be attributed to the nonsolvent-induced spinodal phase separation during electrospinning and solvent-induced recrystallization during post treatment. The blossoming porous structure with high specific surface area contributed to excellent filtration efficiency (99.99%) for sodium chloride (NaCl) ultrafine aerosol particles (30-100 nm) with a low pressure drop (110-230 Pa). Notably, under 7.8 cm/s air flow rate, the membrane samples performed better for filtering smaller-sized aerosol particles than the larger ones when evaluated by the quality factor (0.07). Finally, this finding demonstrates that the electrospun membrane with a hierarchical pore structure and high specific surface area hold great potential in applications as air-filtering materials.

Background: Nanotechnology exploits materials and devices with a functional organization that has been engineered at the nanometre scale. The application of nanotechnology in neuroscience involves specific interactions with neurons and glial cells. This property is used for delivering drugs and other small molecules (such as genes, oligonucleotides and contrasting agents) across the blood brain barrier (BBB), an important requirement for delivering the drug successfully to the brain., Objective: Nanotechnology based approaches (NBA) favours transcytosis-mediated delivery of nanoparticles to the brain by crossing the BBB. The last five years have witnessed the successful applications of NBA to treat neurological disorders. It is expected that the development of novel NBA will result in important insights on the brain mechanisms, and eventually provide better medical care to patients suffering from neurological disorders., Conclusion: This review introduces the emerging work in this area and summarizes the successful NBA used in recent past for treating various neurological disorders ike Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, meningitis and glioblastoma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Higher animals, especially the human beings have the privilege of employing advanced central nervous system (CNS) as well as the evolved immune system to ward off various onslaughts throughout their life. Alterations in inflammatory and neural regulatory pathways lead to several disorders that are now becoming the cause of concern across the world. Deregulation in bidirectional network, particularly in aging population, leads to several neurodegenerative diseases such as dementia as a one of the major characteristics., Objective: Interestingly, research updates have signified the role of abrupt immune regulation in several brain diseases, establishing a link between altered immune system and CNS related diseases. In the later period of life, the altered immune response in the pathogenesis of major psychiatric disorders, has become more visible. In the present manuscript, we present a synopsis on the linkage of CNS and immune system with respect to psychology, with the aim to further understand the biological machinery of psychoneuroimmunological disorders. The immune system of human being plays an important role in keeping pathogen onslaughts on bay., Conclusion: Our manuscript concludes a close relationship between emotion and psychology to diseases and immunology, proclaiming the need of providing enhanced attention on mechanistic aspect of psychoneuroimmunological disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: For design of a subunit vaccine for tuberculosis, identification of antigenic Tcell epitope is of utmost importance. Several MHC prediction server are available that can accurately predict antigenic peptide of variable lengths. However, peptides predicted from one server not necessarily are predicted form another server, thus creating a confusing situation for scientists to choose a best epitope., Method: Keeping the above problem in mind, we developed a comprehensive database of peptides of Mycobacterial proteins. Each protein was taken from PubMed and was run through different MHC prediction servers, with the results being compiled into one database., Results: For each protein, PeMtb generates a set of three different mers of variable lengths (12 mer or 13-mer) based on their ranking; with each mer being predicted for a plethora of MHC alleles. Researcher can choose the peptide (mers) that gives best binding affinity from most of the servers., Conclusion: The database relieves the investigators of the painstaking task of searching various MHC prediction servers for the right epitope (T-cell epitope) for a particular Mycobacterial antigen. We trust and anticipate that PeMtb will be a practical platform for trial and computational analyses of antigenic peptides for Mycobacterium tuberculosis. All the resources and information can be accessed by PeMtb home page www.pemtb-amu.org., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Biomimetic synthesis of nanoparticles offers a convenient and bio friendly approach to fabricate complex structures with sub-nanometer precision from simple precursor components. In the present study, we have synthesized nanoparticles of Amphotericin B (AmB), a potent antifungal agent, using Aloe vera leaf extract. The synthesis of AmB nano-assemblies (AmB-NAs) was established employing spectro-photometric and electron microscopic studies, while their crystalline nature was established by X-ray diffraction. AmB-nano-formulation showed much higher stability in both phosphate buffer saline and serum and exhibit sustained release of parent drug over an extended time period. The as-synthesized AmB-NA possessed significantly less haemolysis as well as nephrotoxicity in the host at par with Ambisome ® , a liposomized AmB formulation. Interestingly, the AmB-NAs were more effective in killing various fungal pathogens including Candida spp. and evoked less drug related toxic manifestations in the host as compared to free form of the drug. The data of the present study suggest that biomimetically synthesized AmB-NA circumvent toxicity issues and offer a promising approach to eliminate systemic fungal infections in Balb/C mice.

Antibodies occupy a central position when it comes to binding proteins with desired antigenic specificities. During the past decade, a plethora of recombinant or humanized versions of antibodies have entered clinical settings with outstanding accomplishments. Yet, they suffer from several drawbacks such as high molecular weight, limited tissue penetration, instability, high production cost, requirement for large doses and potential cytotoxicity. As a result, new generation of receptor proteins has been developed, that are derived from small and robust immunoglobulin (Ig) or non-immunoglobulin based "scaffolds". Combinatorial protein engineering has tremendous scope in the development of these protein scaffolds with immunoglobulin like specificity and/or prescribed binding functions. The advancement made in this regard can boast of developing various validated Ig based and non-Ig protein scaffolds with desirable therapeutic potential. The newly emerging technology has profound scope in translational biology and offer matching replacement for existing immunotherapeutic agents. Only few data from early clinical studies are available yet, but many more are likely to come in the near future. Here, we provide a glimpse of recent clinical advances in the field of existing protein scaffolds., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Commercially available amphotericin B (AmB) formulations are limited by cytotoxicities, lower efficacies, shelf-life related issues and high production costs. In this study, AmB complexes based on poly(gamma-glutamic acid) (PGGA) were prepared and evaluated for their efficacies against AmB-deoxycholate (Fungizone ® ) and liposomal AmB (AmBisome ® ). Physical characterizations showed that AmB/PGGA complexes are nanoscopic (20-40 nm) with a negative zeta potential (-45.5 to -51.0 mV), water-soluble, stable in solution (up to 4 weeks, at 4 °C and 25 °C), and have a high drug loading (up to 35% w/w). In vitro, AmB/PGGA complexes exhibited a more favorable cytotoxicity profile than Fungizone ® but comparable to AmBisome ® , with respect to the hemolytic activity and the modulation of pro-inflammatory cytokines (TNF-α and IL-1ß). In-vivo, AmB/PGGA complexes were significantly more efficacious than both Fungizone ® and AmBisome ® against experimental murine candidiasis. These results provide strong evidence that AmB/PGGA complexes display better efficacy and safety features than the currently approved AmB products., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Therapeutic proteins are engineered proteins produced in the laboratory for pharmaceutical use. With the advent of recombinant DNA technology, the proteins can be generated in specific host cells under defined conditions. In the process of production of genetically engineered animals, the gene of interest can be added at a single cell stage to produce a cloned animal from genetically engineered cells. Several recombinant cytokines, clotting factors etc have been licensed and are currently being utilized for the treatment of cancer, infectious diseases, hemophilia, anemia, multiple sclerosis, and hepatitis B/C. Therapeutic proteins that are useful for human are successfully produced in poultry as well as in livestock animals. However, the fastest growing class of therapeutic proteins are antibodies especially monoclonal antibodies (mAb), the most important class of therapeutic protein with the potential to generate significant revolution in terms of clinical success rate. Here, we review the most recent clinical advances in the field of emerging and existing therapeutic proteins., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: The renewable feedstock derived biodegradable plastics are important in various industries such as packaging, agricultural, paper coating, garbage bags and biomedical implants. The increasing water and waste pollution due to the available decomposition methods of plastic degradation have led to the emergence of biodegradable plastics and biological degradation with microbial (bacteria and fungi) extracellular enzymes. The microbes utilize biodegradable polymers as the substrate under starvation and in unavailability of microbial nutrients. Microbial enzymatic degradation is suitable from bioremediation point of view as no waste accumulation occurs., Methods: It is important to understand the microbial interaction and mechanism involved in the enzymatic degradation of biodegradable plastics under the influence of several environmental factors such as applied pH, thermo-stability, substrate molecular weight and/or complexity. To study the surface erosion of polymer film is another approach for hydrolytic degradation characteristion., Results: The degradation of biopolymer is associated with the production of low molecular weight monomer and generation of carbon dioxide, methane and water molecule. This review reported the degradation study of various existing biodegradable plastics along with the potent degrading microbes (bacteria and fungi). Patents available on plastic biodegradation with biotechnological significance is also summarized in this paper., Conclusion: This paper assesses that new disposal technique should be adopted for the degradation of polymers and further research is required for the economical production of biodegradable plastics along with their enzymatic degradation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The effect of mechanical stirring on sol-gel synthesis of thorn-like ZnO nanoparticles (ZnO-NPs) and antimicrobial activities is successfully reported in this study. The in-house synthesized nanoparticles were characterized by XRD, SEM, TEM, FTIR, TGA, DSC and UV-visible spectroscopy. The X-Ray Diffraction analysis revealed the wurtzite crystal lattice for ZnO-NPs with no impurities present. The diametric measurements of the synthesized thorn-like ZnO-NPs (morphology assessed by SEM) were well accounted to be less than 50 nm with the help of TEM. Relative decrease in aspect ratio was observed on increasing the agitation speed. The UV-visible spectroscopy showed the absorption peaks of the ZnO-NPs existed in both UVA and UVB region. A hypsochromic shift in λmax was observed when stirring pace was increased from 500 rpm to 2000 rpm. The FTIR spectroscopy showed the absorption bands of the stretching modes of Zn-O between 500 cm(-1) to 525 cm(-1). The Thermal analysis studies revealed better stability for ZnO-NPs prepared at 2000 rpm (ZnO-2000 rpm). TGA revealed the weight loss between two main temperatures ranges viz. around (90 °C-120 °C) and (240 °C-280 °C). Finally, the effect of ZnO-NPs prepared at different stirring conditions on the growth of Gram-positive (Bacillus subtilis), Gram-negative (Escherichia coli) bacteria and a fungi (Candida albicans) were examined; which showed good antibacterial as well as antifungal properties. These findings introduce a simple, inexpensive process to synthesize ZnO-NPs using conventional methods without the use of sophisticated equipments and its application as a potent nano-antibiotic.

Amphotericin B (AmB)-deoxycholate micellar formulation, Fungizone®, is the drug of choice for the treatment of unidentified mycotic infections. However, it usage has been marred by long therapeutic regimes and severe side effects. The less toxic lipid associated AmB formulations have been limited by their high expense, with some loss in activity. The quest for decreasing AmB cytotoxicity as well as production cost has resulted in the development of AmB super-aggregate as an alternative to its existing lipid formulations. AmB super-aggregate is spectroscopically distinct from the aggregate present in Fungizone, displaying enhanced thermodynamic stability. The poly-aggregated form of AmB exhibits reduced toxicity in mammalian cells in vitro and to mice in vivo, while maintaining its 'gold standard' antifungal activity. Poly-aggregated AmB interacts predominantly with serum albumin and also attenuates its ability to induce potentially harmful cytokines. Bio-distribution studies have demonstrated that the self-associated AmB shows greater accumulation in reticulo-endothelial organs while sparing kidney, one of the principal organs where its toxic effects are seen. The super-aggregated AmB can thus be used to improve the therapeutic index of AmB against a plethora of fungal infections including candidiasis and cryptococcosis, thus providing a fitting solution to growing demand of an active, less toxic substitute of AmB.

Drug-induced photosensitivity of the skin is drawing increasing attention. In past few decades, photosensitivity has been reported with an array of drugs, and is now recognized as a noteworthy medical problem by clinicians, regulatory authorities and pharmaceutical industry. The photosensitivity is of two types i.e., phototoxicity and photoallergy. Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent in human population. Several hundred substances, chemicals, or drugs may invoke phototoxic and photoallergic reactions. In order to avoid photosensitive reactions, it is essential to understand the mechanism behind the photosensitizing properties of such substances before these drugs are introduced in clinical settings. Photosensitization is inter-related to photochemical reaction, through the knowledge of which the photosensitivity of a drug can be anticipated. This review highlights the current research status on photosensitizing drugs and its correlation to phototoxicity. Different mechanisms of photodegradation of photolabile drugs have also been discussed.

The development of prophylactic anti-candidal vaccine comprising the Candida albicans cytosolic proteins (Cp) as antigen and plasma beads (PB) prepared from plasma as sustained delivery system, is described. The immune-prophylactic potential of various PBs-based dual antigen delivery systems, co-entrapping Cp pre-entrapped in PLGA microspheres were tested in the murine model. Induction of cell mediated immunity was measured by assaying DTH and NO production as well as in vitro proliferation of lymphocytes derived from the immunized animals. Expression of surface markers on APCs (CD80, CD86) and T-cells (CD4+, CD8+) was also evaluated. Humoral immune response was studied by measuring circulating anti-Cp antibodies and their subclasses. When the prophylactic efficacy of the vaccines was tested in mice challenged with virulent C. albicans, the PB-based formulation (PB-PLGA-Cp vaccine) was found to be most effective in the generation of desirable immune response, in terms of suppression of fungal load and facilitating the survival of the immunized animals., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In the current study, a novel niosome based formulation of diallyl disulfide (DADS) was evaluated for its potential to treat disseminated candidiasis in mouse model. Among various non-ionic surfactants tested, niosome formulation prepared using Span 80 was found to be most efficient in the entrapment of DADS. The DADS loaded niosomes had size dimensions in the range of 140 ± 30 nm with zeta potential of -30.67 ± 4.5. Liver/kidney function tests as well as histopathologic studies suggested that noisome-based DADS formulations are safe at the dose investigated. When administered to Candida albicans infected animals, the DADS bearing niosomal formulation cleared the fungal burden and increased their survival much efficiently than its free form., From the Clinical Editor: In this study, a novel niosomal formulation of the antifungal DADS was utilized in a murine candidiasis model, resulting in more efficient fungal clearance compared to the free formulation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Doxorubicin (DOX) binding to hemoglobin (Hb) was studied to investigate the drug induced protein dysfunction. The features of anti-tumor drug doxorubicin infused structural perturbation of human Hb were studied by circular dichroism (CD). The mechanism of DOX-Hb binding was elucidated by steady-state and synchronous fluorescence spectroscopy. The Stern-Volmer analysis indicated that the binding of Hb to DOX is characterized by more than one high affinity binding site with the association constants of the order of 10(5). Hydrophobic probe ANS was employed to elucidate the drug binding site. Binding mode expounded by thermodynamic parameters implied the role of hydrogen bonding, electrostatic and hydrophobic interaction in stabilizing the complex. The molecular distance between donor (Hb) and acceptor (DOX) was calculated according to Förster's theory of energy transfer. Fourier transform infrared (FT-IR) spectroscopy provides an insight to the changes occurring in protein on DOX binding. Treatment of Hb with DOX resulted in a dose dependent fragmentation of protein. The quantitative analysis revealed the release of acid soluble amino groups from the photoexcited Hb-DOX mixture. The free radical mediated degradation was suggested by its rescue on mannitol and superoxide dismutase (SOD) appliance. The loss of protein band further corroborates the concentration dependent Hb fragmentation. The molecular modeling complies with the thermodynamic data of forces involved in DOX binding and depicts its interaction in the proximity of oxygen binding pocket of Hb. Thus, this study enriches our understanding of the interaction dynamics of anticancer drugs to the physiologically important protein Hb.