A multifunctional composite, hydrous zirconium hydroxide cross-linked chitosan grafted with beta-cyclodextrin (Zr-CCS-g-beta-CD), was synthesized via a wet precipitation method and thoroughly characterized using FT-IR, XRD, BET, TGA-DTA, XPS, SEM-EDS, and TEM analyses to elucidate its physicochemical, morphological, and surface attributes. The composite exhibited excellent aqueous stability, making it viable for environmental remediation. Optimization of oxytetracycline (OTC) adsorption using central composite design (CCD) integrated with a desirability function revealed a high adsorption capacity (187.52 mg g(-1)) and removal efficiency (98.68%) under optimized conditions (adsorbent dose = 0.01 g, OTC concentration = 90 mg L-1, pH = 6.5, contact time = 45 min). Mechanistic insights were probed using classical isotherms and statistical physics modelling across 298-318 K. The Freundlich model suggested multilayer adsorption on heterogeneous surfaces, while statistical physics model 2 revealed a dominant monolayer adsorption governed by dual energy site interactions (R-2 = 0.9993-0.9998). Energy distribution analysis indicated two interaction regimes: (E-a1 = 21.72-34.87 kJ mol(-1)) attributed to weak forces such as hydrogen bonding and van der Waals interactions, and (E-a2 = 41.33-52.76 kJ mol(-1)) associated with stronger electrostatic and coordination forces. Notably, the statistical physics model revealed that the number of bound molecules per site (n) remained below unity at all temperatures, supporting a multi-docking interaction regime where single OTC molecules simultaneously interact with multiple active sites. This configuration facilitates horizontal alignment of OTC on the surface, stabilized via cooperative weak interactions. Fractal-like pseudo-second-order (FL-PSO) kinetics exhibited superior fitting (R-2 > 0.999), capturing the heterogeneity of the adsorption process, while Weber-Morris analysis confirmed a dual diffusion mechanism: initial film diffusion followed by intraparticle transport. Thermodynamic parameters indicated a spontaneous, endothermic process with positive entropy changes, confirming enhanced affinity and structural reorganization at the solid-liquid interface. Practical utility was validated in real water matrices, achieving high removal efficiencies: 98.20% (tap), 97.10% (river), and 96.95% (wastewater). Remarkably, OTC-loaded Zr-CCS-g-beta-CD demonstrated secondary functionality by efficiently removing As(iii) from aqueous media (>96%) and acid-digested food matrices (91.84-96.26%). The composite retained over 96% efficiency across eleven adsorption-desorption cycles, establishing its reusability and environmental sustainability.
The management of Herpes simplex virus (HSV) and human immunodeficiency virus (HIV) co-infection is severely hindered by the poor oral bioavailability and restricted blood-brain barrier (BBB) penetration of conventional antiviral therapies. In this study, a novel triple drug-loaded nanoemulsion containing saquinavir (SQV), ritonavir (RTV) and acyclovir (ACV) was developed and optimized using a Central Composite Rotatable Design (CCRD) to enhance systemic absorption and brain exposure. The formulation was prepared via ultrasonication and characterized for droplet size, zeta potential, and rheological properties. The optimized nanoemulsion exhibited favorable physicochemical characteristics, including nanometric droplet size, acceptable size distribution, high transparency, and good stability. In vitro release (p < 0.0001) and ex vivo permeation studies (p < 0.05) demonstrated significantly higher drug flux compared to the drug suspension. Pharmacokinetic profiling in Wistar rats confirmed a prominent increase in systemic exposure (p < 0.001). The nanoemulsion also significantly increased drug concentrations in brain tissue compared with the corresponding suspension formulation (p < 0.001), indicating enhanced brain exposure of all three antiviral agents. These findings suggest that the triple drug-loaded nanoemulsion represents a promising oral delivery platform improves the pharmacokinetic performance and brain exposure of antiviral agents, with potential application in the management of HIV-1 and HSV co-infections. Triple-drug nanoemulsion developed for HIV/HSV co-infection management. QbD-optimized formulation achieved an ultra-fine 46.10 nm droplet size. Enhanced oral bioavailability and drug permeation vs. conventional drug suspension. Significant increase in brain exposure of ACV, SQV, and RTV in-vivo. Effective oral nano-platform for enhancing drug exposure in brain tissue.
Human immunodeficiency virus type 1 (HIV-1) remains a major global public health challenge due to lifelong persistence, latency, and the emergence of drug resistance. Natural bioactive compounds are increasingly being explored as alternative or adjunct antiviral strategies. In this study, we evaluated the antiviral efficacy and cytotoxicity of a synergistic pharmaceutical composition comprising three phycobiliproteins: C-phycocyanin (C-PC), B-phycoerythrin (B-PE), and allophycocyanin (APC), derived from cyanobacteria and marine algae. Individual and combinatorial effects were assessed against HIV-1 using TZM-bl cells and peripheral blood mononuclear cells (PBMCs). A Box–Behnken experimental design was employed to identify optimal synergistic ratios. Among fifteen combinations initially screened at a fixed concentration of 50 µg/mL, five exhibited strong antiviral activity. The optimized formulation (CBA: C2; 73.28
Garlic peel (GP), an abundant agro-waste, remains largely unexplored as a biogenic source for selenium nanoparticle (SeNP) synthesis. This study investigates the antioxidant, anti-inflammatory, and antibacterial properties of GP-SeNPs and GP-extract. GP-SeNPs synthesized via reduction of sodium selenite using GP-extract were confirmed to be crystalline by X-ray diffraction, showing a characteristic absorption peak at 264 nm. Fourier transform infrared spectroscopy verified phytoconstituents responsible for nanoparticle synthesis, interaction, and stabilization. Scanning and transmission electron microscopy revealed predominantly spherical nanoparticles with an average diameter of 14.66 nm. Gas chromatography-mass spectrometry profiling identified multiple bioactive compounds, with palmitic and oleic acids as dominant constituents. GP-SeNPs exhibited markedly higher antioxidant and anti-inflammatory activities than GP-extract alone. Antibacterial assays demonstrated that GP-SeNPs exerted significantly stronger inhibitory effects than GP-extract against multidrug-resistant Staphylococcus aureus and Acinetobacter baumannii. This was evidenced by larger zones of inhibition, effective suppression of bacterial growth, and disruption of bacterial membranes, which caused leakage of proteins and DNA. Molecular docking showed strong binding affinities of palmitic and oleic acids toward bacterial DNA gyrase and topoisomerase IV, enhanced through nanoparticle conjugation. Overall, our findings demonstrate that GP-SeNPs are sustainable, agro-waste-derived bioactive nanomaterials with pronounced antibacterial activity, supported by measurable antioxidant and anti-inflammatory properties.
Phthalates are the emerging environmental toxicants derived from phthalic acid and its constituents, which are moderately present in plastics and many personal care products. Phthalate exposure occurs through various environmental factors, including air, water, and soil, with absorption facilitated via ingestion, inhalation, and dermal contact. Upon exposure, phthalates become bioavailable within the biological systems and undergo biotransformation and detoxification processes in the liver. The physicochemical properties of phthalates indicate their lipophilicity, environmental persistence, and bioaccumulation potential, influencing their absorption, distribution, and hepatic biotransformation. The prolonged exposure to phthalates adversely influences the biological redox system by altering the levels of the enzymatic and non-enzymatic antioxidants, molecular signaling pathways, and causing hepatic pathogenesis. The strategies to combat phthalate-induced toxicity include avoiding exposure to these compounds and using plant-based bioactive molecules such as polyphenols, which possess therapeutic potential as antioxidants, suppress inflammatory cascades, prevent oxidative damage, and stabilize cellular integrity. This review presents a comprehensive and updated account of the chemical, biochemical, immunological, and toxicological properties of phthalates, along with novel plant-based therapeutic strategies to mitigate the phthalate-induced adverse effects on living systems.
Introduction:Herpes Simplex Virus type 2 or HSV-2 is a major cause of genital herpes, contributing to increased susceptibility to HIV, encephalitis, and other severe complications. Despite the availability of antiviral therapies such as acyclovir, their effectiveness is limited due to resistance and side effects, emphasizing the urgent need for an effective vaccine. Methods:This study employed reverse vaccinology and immunoinformatics to design five multivalent, multiepitope mRNA vaccine constructs targeting HSV-2. Four key viral proteins-Glycoprotein B (gB), Ribonucleoside-diphosphate Reductase large subunit (RIR1), Infected Cell Protein 0 (ICP0), and VP23-were selected based on their roles in viral replication and immune evasion. Epitopes for Cytotoxic T Lymphocytes (CD8+), Helper T Lymphocytes (CD4+), and B cells were predicted and rigorously filtered for antigenicity, non-toxicity, and cytokine induction. Vaccine constructs were designed incorporating 50S ribosomal protein, Human β-defensin 3, and PADRE as adjuvants to enhance immune responses. Structural validation, molecular docking, codon optimization, and physiochemical analysis were performed to assess stability and immunogenic potential. Results:The vaccine constructs demonstrated favorable physiochemical properties, structural stability, and high antigenicity. Molecular docking revealed strong binding affinities between the predicted epitopes and their respective MHC class I and class II alleles. Proteasomal cleavage analysis confirmed efficient antigen processing, while codon optimization ensured compatibility with the human translational machinery. Computational immune simulations predicted a strong humoral and cellular immune response, including high IgG and IgM levels, robust CD4+ and CD8+ T-cell activation, and cytokine production. Conclusion:The rationally designed multiepitope mRNA vaccine constructs exhibit strong antigenic potential, structural stability, and immune-stimulatory properties, positioning them as promising candidates for HSV-2 vaccine development. These findings offer a novel, safe, and effective approach to HSV-2 immunization, warranting further experimental validation and preclinical studies.
Exposure to potassium dichromate (K2Cr2O7) is well known for its nephrotoxic effects on humans and animals. This study investigated the protective effects of vitamin C against K2Cr2O7-induced nephrotoxicity, focusing on its impact on altered carbohydrate metabolism, mitochondrial dysfunction, and associated molecular mechanisms in the cortical and medullary kidney segments. Male Wistar rats (n = 8) were divided into four groups: Group I received saline, Group II received a single 250 mg/kg body weight (bwt) intraperitoneal (i.p.) injection of vitamin C, Group III received K2Cr2O7 (15 mg/kg bwt, i.p.), and Group IV received vitamin C 6 h before K2Cr2O7 administration. Vitamin C significantly mitigated K2Cr2O7-induced nephrotoxic effects, restoring normal renal function and histological architecture. It preserved the activities of glycolytic and gluconeogenic enzymes altered by K2Cr2O7. Additionally, vitamin C mitigated K2Cr2O7-induced mitochondrial dysfunction by maintaining tricarboxylic acid (TCA) cycle enzymes, electron transport chain proteins, mitochondrial DNA copy number, and ATP content. It also reduced oxidative stress markers and enhanced antioxidant enzyme activity. The protective mechanism of vitamin C against K2Cr2O7-induced renal damage involved upregulation of the protein expression of peroxisome proliferation-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha), which further elevated the protein expression of nuclear factor erythroid 2-related factor-2 (Nrf-2) and transcription factor A, mitochondrial (TFAM), crucial for protecting cells from oxidative stress, enhancing mitochondrial function, and promoting cellular health. Overall, this study highlights the significant protective role of vitamin C against K2Cr2O7-induced renal damage by preserving carbohydrate metabolism and mitigating mitochondrial dysfunction through the PGC-1 alpha/Nrf-2/TFAM pathway, offering valuable insights into its protective mechanisms in nephrotoxicity.
Novel biomolecules from marine resources are gaining attraction in pharmaceutical industries. Marine macroalgae produce bioactive compounds with antioxidant properties that exhibit high potential in clinical applications. However, the bioactivity of seaweeds originated from India is still unexplored. The effect of such biomolecules is governed by its geographical occurrence and extraction method. In this study the antioxidant capacity of Cystoseira indica was evaluated. The samples were collected from Northern coast (Okha) and Southern coast (Chorwad) of Gujarat, India. The antioxidant activity was evaluated using DPPH, ABTS and reducing power assays. The comparison of two extraction method was also applied, in which soxhlet method gave better results than maceration. This study brings out adequate data on the presence of phytochemical constituents in seaweed using different solvents. The information can contribute to better understanding regarding geographical variation, providing insights into how environmental factors influence the bioactive compound profiles and antioxidant potential of Cystoseira indica.
Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with rising incidence, treatment resistance, and chemotherapy-induced toxicity underscoring the need for safer, more effective therapeutic strategies. Nanotechnology offers a promising approach through targeted drug delivery and enhanced therapeutic efficacy. This study investigates the anticancer potential of quercetin-loaded selenium nanoparticles (Qu-SeNPs) against HCT116 colorectal cancer cells and directly compares their effects with cisplatin (CP). To our knowledge, this is the first study to systematically compare the mechanistic actions of Qu-SeNPs and CP in CRC cells. Comprehensive physicochemical characterization using UV-vis spectroscopy, FTIR, TEM, EDX, zeta potential, and DLS confirmed successful synthesis of stable, well-dispersed Qu-SeNPs, exhibiting a characteristic peak at 410 nm. MTT assays demonstrated that Qu-SeNPs reduced HCT116 cell viability in a dose-dependent manner, with an IC5 0 of 51.19 μg/mL, compared to CP (IC5 0 = 17.6 μg/mL). Morphological analysis revealed distinct apoptotic features in Qu-SeNP-treated cells. In vitro drug release profiles showed rapid CP release under both neutral and acidic conditions, while Qu-SeNPs exhibited a pH-responsive, sustained release pattern. ROS kinetics analysis showed that CP caused a sharp early ROS spike at 6 h, plateauing between 24 and 48 h. In contrast, Qu-SeNPs resulted in a gradual, sustained increase in ROS over 48 h, indicating ongoing oxidative stress. Cell cycle analysis demonstrated that CP induced S and G2/M-phase arrest, consistent with checkpoint-mediated DNA repair, whereas Qu-SeNPs significantly augmented the sub-G0/G1 population, indicating apoptosis induction and checkpoint bypass. Apoptosis assays, comet assay, and DNA fragmentation confirmed extensive cell death with Qu-SeNPs, accompanied by upregulation of Bax and cleaved caspase-3, confirming mitochondrial apoptotic activation. Western blotting revealed that CP significantly upregulated Nrf-2, suggesting activation of antioxidant defenses, while Qu-SeNPs did not induce Nrf-2, implying that persistent ROS overwhelmed cellular antioxidant responses. Collectively, Qu-SeNPs promote checkpoint bypass and sustained ROS-mediated apoptosis while failing to activate Nrf-2 expression, suggesting a more effective strategy for overcoming treatment resistance compared to CP. In conclusion, Qu-SeNPs demonstrate potential anticancer effects against CRC in vitro; however, further in vivo investigations are needed to confirm their effectiveness and safety profile.
Objectives: The objectives of the study are to investigate the anti-cancer properties of quercetin, a widely distributed phytochemical, and assess its potential as a chemopreventive and therapeutic agent for cervical cell carcinoma. Methods: The study employed cell viability assays for cytotoxicity, flow cytometry for cell cycle arrest, comet assays for DNA damage, nuclear morphology to assess apoptosis, and Western blotting to measure caspase 3 expression, a key apoptosis-related marker. Results: Notably, a significantly lower half-maximal inhibitory concentration (25.5 mu M) at 48 h compared to 24 h highlights the time-dependent nature of quercetin's cytotoxic effects. Quercetin significantly (P < 0.001) inhibited human cervix epithelioid carcinoma (HeLa) cell viability compared to the control group, indicating its cytotoxic potential. Morphological changes observed in quercetin-treated cells further supported its cytotoxic effects. Quercetin-induced substantial increase in the percentage of cells in the sub-G0/G1 phase relative to controls (P < 0.001) reveals cell cycle arrest and the initiation of apoptosis. In addition, quercetin caused notable DNA damage, as evidenced by the significant increase (P < 0.001) in the comet tail length, highlighting the genotoxic effects of quercetin. Moreover, quercetin treatment significantly (P < 0.001) upregulated the expression of caspase-3, suggesting the activation of the intrinsic apoptotic pathway. Conclusion: The findings of the current study suggest that quercetin can effectively inhibit HeLa cell viability, induce cell cycle arrest, promote DNA damage, and activate caspase-mediated apoptosis. This underscores quercetin's therapeutic potential against cervical cancer and highlights caspase-mediated apoptosis as a promising strategy. Prolonged exposure may further enhance its efficacy, offering valuable insights into its potential for longterm cancer treatment.
Background: The interaction between HIV-1 and host immune cells, particularly macrophages, is crucial in understanding viral persistence and pathogenesis. This study aims to explore the impact of HIV-1 infection on macrophage microRNA (miRNA) expression profiles using a systems biology approach to uncover the potential role of miRNAs in modulating macrophage functionality and identify key miRNA targets that may serve as therapeutic avenues. Methods: PMA-differentiated THP-1 cells were used to model macrophage infection with HIV-1. A custom miRNA microarray was performed to identify dysregulated miRNAs following infection. miRTarBase was utilized for miRNA target identification, revealing gene targets associated with the dysregulated miRNAs. A protein-protein interaction (PPI) map of miRNA targets and their first interactors was constructed, with key nodes identified based on a calculated disease score, which considered degree, betweenness centrality, average shortest path length, and clustering coefficient. Gene Ontology molecular function analysis was also conducted on the identified targets. Results: The miRNA microarray identified 23 dysregulated miRNAs in HIV-1-infected macrophages, with 8 upregulated and 15 downregulated. Among these, the top 10 dysregulated miRNAs targeted over 2000 unique genes. PPI analysis revealed key nodes in the upregulated miRNA network, including APP, MYC, ESR2, RAF1, and HIST1H4A, while ZRANB1, HSPA8, TGOLN2, HSPA5, and BRD4 were prominent in the downregulated miRNA network. Notably, KRAS, CUL3, TP53, ESR1, and PARP1 were influenced by both upregulated and downregulated miRNAs. Gene Ontology analysis indicated that the targeted genes were involved in processes such as protein and RNA binding, ATPase activity, and ribosomal function. Conclusions: HIV-1 infection induces significant dysregulation of miRNAs in macrophages, impacting a wide array of gene targets and molecular functions. These findings suggest that miRNA-mediated regulation may play a crucial role in HIV-1 pathogenesis within macrophages and present potential targets for miRNA-based therapeutic strategies.
The aim of this study was to improve the therapeutic efficacy, drug delivery and physicochemical features of antimicrobial peptides (AMPs) L-Lysine, for chronic obstructive pulmonary disease (COPD) by developing a glycosylated self-nanoemulsifying drug delivery system (SNEDDS). Roflumilast (Rof) a phosphodiesterase 4 (PDE4) inhibitor, was entrapped within the SNEDDS system (Glucolysinated Rof SNEDDS) for targeted COPD treatment. The Glucolysinated Rof SNEDDS were successfully formulated and characterized in terms of physicochemical properties, in vitro as well as in vivo efficacy. Conjugation chemistry was confirmed using FTIR spectroscopy, mean droplet size of SNEDDS was 222 +/- 0.46 nm, with 0.42 +/- 0.11 PDI and-24.3 +/- 1.20 mV zeta potential. The formulation demonstrated outstanding mucoadhesion capabilities, with a 95 % improvement in drug entrapment efficiency and 80 % sustained drug release over 12 h. Toxicity assessments were conducted by Pharmacokinetics approaches, which confirmed the formulation's safety. Strong antibacterial action was revealed against Pseudomonas aeruginosa, which disrupt bacterial membrane integrity as demonstrated with SEM imaging. PDE4 inhibition was confirmed by strong binding energy in docking analysis. Serum biochemistry analysis remained constant throughout treatment, and histopathological investigations indicated the shielding effect of excipients used. These results presented, highlight the potential of Glucolysinated Rof SNEDDS as a novel and effective drug delivery system for targeted COPD therapy, synergizing therapeutic efficacy with biocompatibility.
Objective: To evaluate the levels of serum rare earth elements (REEs): lutetium [Lu], praseodymium [Pr], samarium [Sm], dysprosium [Dy], and cerium [Ce] in pregnant women with recurrent pregnancy loss (RPL) and evaluate their relationship with total antioxidant capacity (TAC) and 8-hydroxy-2 '-deoxyguanosine (8-OHdG), a marker of DNA damage. Methods: A case-controlled study was conducted on a cohort of 60 female participants, with first-trimester healthy pregnant women as the control group and pregnant women with a history of consecutive abortions as the recurrent pregnancy loss (RPL) group. Following blood collection, serum concentrations of Lu, Pr, Sm, Dy, and Ce were measured using an inductively coupled plasma mass spectrophotometer (ICP-MS). Oxidative stress and DNA damage were evaluated through TAC and DNA damage marker (8-OHdG). Results: Serum levels of Lu, Pr, Sm, Dy, and Ce were higher in women with RPL compared with control (P < 0.001). Intriguingly, a strong significant negative correlation was observed between TAC and REEs (P < 0.05). Lu, Dy, and Ce demonstrated a significant positive correlation with increased DNA damage in the RPL group (P < 0.05). Contrary, there was no evidence of a correlation between 8-OHdG and Pr and Sm. Conclusion: The study highlights a potential association between Lu, Sm, Dy, and Ce and an increased risk of RPL, highlighting REE-induced toxicity as a major risk factor for RPL. The outcome of the study is to advance our understanding of the interplay between rare earth elements and RPL, with potential implications for reproductive medicine, environmental health, and the development of preventive strategies for individuals at risk of RPL.
Seaweeds are sources of bioactive compounds with medicinal properties, which make them attractive candidates for natural therapeutic agents. Marine brown algae are known to possess anti-inflammatory, hepatoprotective, anticancer properties, etc. Present study was carried out to identify the phytochemical constituents, antioxidant and cytotoxic activities of Sargassum prismaticum in two different solvents viz., chloroform and methanol. Chloroform was found to be the superior solvent for phenol and flavonoid extraction. Antioxidant activity was determined using DPPH and ABTS assays; however, the methanolic extract demonstrated better antioxidant potential. The highest cell cytotoxicity with an IC50 value of 7.6 ± 0.02 μg/mL was observed in methanolic extract, while the chloroform extract had an IC50 value of 9.6 ± 0.03 μg/mL against U937 cell line. These finding suggest that Sargassum prismaticum possesses potent antioxidant and cytotoxic properties, making it a potential candidate for further study as a novel antioxidant drug source.
Among all the heavy metals, Pb, Cd, and As are the most harmful pollutants in the environment. They reach into the organisms via various levels of food chains i.e. air and water. Glutathione-s-transferase (GST, E.C. 2.5.1.18), a key enzyme of xenobiotics metabolism, plays an important role in the removal of several toxicants. The present study aimed to evaluate any inhibitory action of these heavy metals on the GST enzyme isolated from the hepatic tissues of rats. A 10 % (w/v) homogenate of rat liver was prepared in cold and centrifuged at 4 degrees C at 9000xg for 30 min. The supernatant was collected and kept frozen at -20 degrees C or used fresh for carrying out different experiments. The activity of GST was monitored spectrophotometrically at 340 nm using 220 mu g of soluble protein with varying equal substrate concentrations (0.125-2 mM) in phosphate buffer (50 mM, pH 6.5). To assess the impact of heavy metals on the enzyme activity, different concentrations of Cd (0-0.6 mM) and Pb (0-2 mM) were added to the reaction mixture followed by monitoring the residual activity. The optimum temperature and pH of rat liver GST were found to be 37 degrees C and 6.5, respectively. The K-m value for GST was 0.69 mM and the V-max was found to be 78.67 U/mg. The Cd and Pb significantly altered the kinetic behaviour of the enzyme. The V-max and K-cat/K-m parameters of GST were recorded to be decreased after interaction with Cd and Pb individually and showed a mixed type of inhibition pattern suggesting that these inhibitors may have a greater binding affinity either for the free enzyme or the substrate-enzyme complex. These metals showed a time-dependent enzyme inhibition profile. Cd was found to be the most potent inhibitor when compared to other treated metals; the order of inhibitory effect of metal ions was Cd>Pb>As. The in silico ion docking analysis for determining the probable interactions of Cd and Pb with fragmented GST validated that Cd exhibited higher inhibition potential for the enzyme as compared to Pb. The results of the present study indicated that exposure of both the Cd and Pb may cause significant inhibition of hepatic GST; the former with higher inhibitory potential than the later. However, As proved to be least effective against the enzyme under the aforesaid experimental conditions.
Human Lymphatic filariasis is caused by parasitic nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Protein disulfide isomerase (PDI), a redox-active enzyme, helps to form and isomerize the disulfide bonds, thereby acting as a chaperone. Such activity is essential for activating many essential enzymes and functional proteins. Brugia malayi protein disulfide isomerase (BmPDI) is crucial for parasite survival and an important drug target. Here, we used a combination of spectroscopic and computational analysis to study the structural and functional changes in the BmPDI during unfolding. Tryptophan fluorescence data revealed two well-separated transitions during the unfolding process, suggesting that the unfolding of the BmPDI is non-cooperative. The binding of the fluorescence probe 8-anilino-1-naphthalene sulfonic acid dye (ANS) validated the results obtained by the pH unfolding. The dynamics of molecular simulation performed at different pH conditions revealed the structural basis of BmPDI unfolding. Detailed analysis suggested that under different pH, both the global structure and the conformational dynamics of the active site residues were differentially altered. Our multiparametric study reveals the differential dynamics and collective motions of BmPDI unfolding, providing insights into its structure-function relationship.Communicated by Ramaswamy H. Sarma
Pesticide exposure can pose a serious risk to nontarget animals. Cartap is being broadly used in agricultural fields. The toxic effects of cartap on the levels of hepatotoxicity and neurotoxicity have not been properly studied in mammalian systems. Therefore, the present work focused on the effect of cartap on the liver and brain of Wistar rats and made an assessment of the ameliorating potential of A. vera. The experimental animals were divided into 4 groups, comprising six rats in each: Group 1-Control; Group 2-A. vera; Group 3-Cartap; and Group 4-A. vera + Cartap. The animals orally given cartap and A. vera were sacrificed after 24 h of the final treatment and histological and biochemical investigations were conducted in liver and brain of Wistar rats. Cartap at sublethal concentrations caused substantial decreases in CAT, SOD, and GST levels in the experimental rats. The activity levels of transaminases and phosphatases in cartap group were also found to be substantially altered. The AChE activity was recorded as decreasing in RBC membrane and brain of the cartap-treated animals. The TNF-α and IL-6 level in serum were increased expressively in the cartap challenged groups. Histological investigation of liver showed disorganized hepatic cords and severely congested central veins due to cartap. However, the A. vera extract was observed to significantly protect against the effects of cartap toxicity. The protective impact of A. vera against cartap toxicity may be due to the existence of antioxidants in it. These findings suggest that A. vera may be developed as a potential supplement to the appropriate medication in the treatment of cartap toxicity.
The corona virus disease 2019 (COVID-19), caused by severe acute respiratory syndrome corona virus type 2 (SARS-CoV-2), belongs to emerging and reemerging diseases, which was first identified and reported in Wuhan, China, during December 2019. The genetic sequence of SARS-CoV-2 was similar to SARS virus, a β-corona virus. The epidemiologicalstudies suggest that the transmission of SARS-CoV-2 mainly occurs from an infected person to others through close contact with the respiratory droplets or by having contact with SARS-CoV-2adhering toobjects and surfaces. The incubation period ranges from 5 to14 days. During COVID-19, the occurrence of fever, dry cough, tiredness, aches, chest pain, conjunctivitis, diarrhea, headache, difficulty in breathing or short breath, loss of taste, smell, rashes on the skin,andsore throat.Some reports indicated that males exhibited lower scores than females, the younger populations displayed increased symptoms, Chinese/Taiwanese people registered only scarce symptoms and Canadians experienced more symptoms. The results of some studiesindictaed that COVID-19 significantly impacted on depression whereas job insecurity impacted on anxiety and depression. The risk factors of COVID-19 pandemic include steep rise in the degree of fear, worry, mainly the health care providers, infants, pregnant ladies, older adults, patients receiving treatment in hospitals, development of psychosomatic disorders including depression with serious immunological consequences in infectedindividuals. The diagnostics to detect the presence of corona virus involves ELISA and RT-PCR. There is no specific treatment available to eradicate COVID-19. The therapeutics used to treat COVID 19 exhibited severe side effects. Recently, some Indian traditional medicinal plants have shown promises to reduce the risk of viral infection and also boost immunity of an invidual.This paper presents an overview of the current status of depression in the SARS CoV2 infected people and the measures required to overcome COVID-19 induced depression in patients even after recovery.