Unraveling the mechanisms of Sofosbuvir resistance in HCV NS3/4A protease: Structural and molecular simulation-based insights.

Current management of HCV infection is based on Direct-Acting Antiviral Drugs (DAAs). However, resistance-associated mutations, especially in the NS3 and NS5B regions are gradually decreasing the efficacy of DAAs. Among the most effective HCV NS3/4A protease drugs, Sofosbuvir also develops resistance due to mutations in the NS3 and NS5B regions. Four mutations at positions A156Y, L36P, Q41H, and Q80K are classified as high-level resistance mutations. The resistance mechanism of HCV NS3/4A protease toward Sofosbuvir caused by these mutations is still unclear, as there is less information available regarding the structural and functional effects of the mutations against Sofosbuvir. In this work, we combined molecular dynamics simulation, molecular mechanics/Generalized-Born surface area calculation, principal component analysis, and free energy landscape analysis to explore the resistance mechanism of HCV NS3/4A protease due to these mutations, as well as compare interaction changes in wild-type. Subsequently, we identified that the mutant form of HCV NS3/4A protease affects the activity of Sofosbuvir. In this study, the resistance mechanism of Sofosbuvir at the atomic level is proposed. The proposed drug-resistance mechanism will provide valuable guidance for the design of HCV drugs.

Fabrication and Characterization of Montmorillonite Clay/Agar-Based Magnetic Composite and Its Biological and Electrical Conductivity Evaluation.

Montmorillonite clay and agar are naturally occurring materials of significant importance in designing biocompatible materials tailored for applications in biotechnology and medicine. The introduction of magnetic properties has the potential to significantly boost their characteristics and expand their applications. In this study, we have successfully synthesized highly intercalated magnetic composites, incorporating magnetic iron oxide nanoparticles (MNPs), montmorillonite clay (MMT), and agar (AG), through a thermo-physicomechanical method. Three samples of MMT-AG with 2, 1.5, and 0.5% MNPs and three sample composites of MNPs-AG with 2, 1, and 0.5% MMT clay are prepared. The synthesized composites were characterized by SEM, XRD, TGA, DTA, and FTIR. SEM analysis revealed a uniform dispersion of MNPs and MMT in the composite. The XRD pattern confirmed the presence of MNPs in the composite site. The TGA and DTA results demonstrated improved thermal stability due to the MNP incorporation. FTIR spectra showed all of the constituents of agar, MNPs, and MMT clay. The swelling ratio was observed to range from 835% to 1739%. The swelling study indicated an increased hydrophobicity with the addition of MNPs to the composite. Antibacterial activities revealed a significant inhibition of Escherichia coli (E. coli) growth by ranging from 10 to 19 nm in the composite. The composite also exhibited a considerable antioxidant action, with IC50 values of 7.96, 46.55, and 57.58 µg/mL, and electrical properties just like conductors.

Structure-guided engineering and molecular simulations to design a potent monoclonal antibody to target aP2 antigen for adaptive immune response instigation against type 2 diabetes.

Introduction: Diabetes mellitus (DM) is recognized as one of the oldest chronic diseases and has become a significant public health issue, necessitating innovative therapeutic strategies to enhance patient outcomes. Traditional treatments have provided limited success, highlighting the need for novel approaches in managing this complex disease. Methods: In our study, we employed graph signature-based methodologies in conjunction with molecular simulation and free energy calculations. The objective was to engineer the CA33 monoclonal antibody for effective targeting of the aP2 antigen, aiming to elicit a potent immune response. This approach involved screening a mutational landscape comprising 57 mutants to identify modifications that yield significant enhancements in binding efficacy and stability. Results: Analysis of the mutational landscape revealed that only five substitutions resulted in noteworthy improvements. Among these, mutations T94M, A96E, A96Q, and T94W were identified through molecular docking experiments to exhibit higher docking scores compared to the wild-type. Further validation was provided by calculating the dissociation constant (KD), which showed a similar trend in favor of these mutations. Molecular simulation analyses highlighted T94M as the most stable complex, with reduced internal fluctuations upon binding. Principal components analysis (PCA) indicated that both the wild-type and T94M mutant displayed similar patterns of constrained and restricted motion across principal components. The free energy landscape analysis underscored a single metastable state for all complexes, indicating limited structural variability and potential for high therapeutic efficacy against aP2. Total binding free energy (TBE) calculations further supported the superior performance of the T94M mutation, with TBE values demonstrating the enhanced binding affinity of selected mutants over the wild-type. Discussion: Our findings suggest that the T94M substitution, along with other identified mutations, significantly enhances the therapeutic potential of the CA33 antibody against DM by improving its binding affinity and stability. These results not only contribute to a deeper understanding of antibody-antigen interactions in the context of DM but also provide a valuable framework for the rational design of antibodies aimed at targeting this disease more effectively.

Unraveling the genetic variations underlying virulence disparities among SARS-CoV-2 strains across global regions: insights from Pakistan.

Over the course of the COVID-19 pandemic, several SARS-CoV-2 variants have emerged that may exhibit different etiological effects such as enhanced transmissibility and infectivity. However, genetic variations that reduce virulence and deteriorate viral fitness have not yet been thoroughly investigated. The present study sought to evaluate the effects of viral genetic makeup on COVID-19 epidemiology in Pakistan, where the infectivity and mortality rate was comparatively lower than other countries during the first pandemic wave. For this purpose, we focused on the comparative analyses of 7096 amino-acid long polyprotein pp1ab. Comparative sequence analysis of 203 SARS-CoV-2 genomes, sampled from Pakistan during the first wave of the pandemic revealed 179 amino acid substitutions in pp1ab. Within this set, 38 substitutions were identified within the Nsp3 region of the pp1ab polyprotein. Structural and biophysical analysis of proteins revealed that amino acid variations within Nsp3's macrodomains induced conformational changes and modified protein-ligand interactions, consequently diminishing the virulence and fitness of SARS-CoV-2. Additionally, the epistatic effects resulting from evolutionary substitutions in SARS-CoV-2 proteins may have unnoticed implications for reducing disease burden. In light of these findings, further characterization of such deleterious SARS-CoV-2 mutations will not only aid in identifying potential therapeutic targets but will also provide a roadmap for maintaining vigilance against the genetic variability of diverse SARS-CoV-2 strains circulating globally. Furthermore, these insights empower us to more effectively manage and respond to potential viral-based pandemic outbreaks of a similar nature in the future.

Preparation and characterization of sulphur and zinc oxide Co-doped graphitic carbon nitride for photo-assisted removal of Safranin-O dye.

Recently, there has been significant interest in photocatalytic reactions involving graphitic carbon nitride (g-C3N4) due to its sp2-hybridized carbon and nitrogen content and it is an ideal candidate for blending with other materials to enhance performance. Here, we have synthesized and analyzed both doped and undoped g-C3N4 nanoparticles. Specifically, we co-doped sulfur (S) into g-C3N4, integrated it with ZnO particles, and investigated the photocatalytic potential of these nanocomposites to remove Safranin-O dye. The initial step involved the preparation of pure g-C3N4 through calcination of urea. Subsequently, S-g-C3N4 was synthesized by calcining a mixture of urea and thiourea with a 3 : 1 ratio. Finally, the ZnO-S-g-C3N4 composite was synthesized using the liquid exfoliation technique, with distilled water serving as the exfoliating solvent. These samples were characterized by advanced techniques, including UV-Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), energy dispersive X-ray (EDX) and scanning electron microscopy (SEM), to assess their crystallinity, morphology, optical properties, and phase purity. Subsequently, these nanocomposites were employed in catalytic and photocatalytic processes to remove the Safranin-O dye (SO). The results highlighted the formation of Z-scheme junction responsible for ZnO-S-g-C3N4's significant performance improvement. The comparison of results demonstrated that S-g-C3N4 and ZnO-S-g-C3N4 composites revealed an effective removal of Safranin-O dye in the presence of UV-light as compared to pure g-C3N4, as it was attributed to the phenomenon of improved separation of photogenerated charge carriers as a result of heterojunction formation between S-g-C3N4 and ZnO interfaces. In addition to improving photocatalytic performance, this study presents a facile route for producing ZnO-S-g-C3N4 composite with superior adsorption capabilities and selectivity.

Preparation of visible-light active MOFs-Perovskites (ZIF-67/LaFeO3) nanocatalysts for exceptional CO2 conversion, organic pollutants and antibiotics degradation.

Modern industries rapid expansion has heightened energy needs and accelerated fossil fuel depletion, contributing to global warming. Additionally, organic pollutants present substantial risks to aquatic ecosystems due to their stability, insolubility, and non-biodegradability. Scientists are currently researching high-performance materials to address these issues. LaFeO3 nanosheets (LFO-NS) were synthesized in this study using a solvothermal method with polyvinylpyrrolidone (PVP) as a soft template. The LFO-NS demonstrate superior performance, large surface area and charge separation than that of LaFeO3 nanoparticles (LFO-NP). The LFO-NS performance is further upgraded by incorporating ZIF-67. Our results confirmed the ZIF-67/LFO-NS nanocomposite have superior performances than pure LFO-NP and ZIF-67. The integration of ZIF-67 has enhanced the charge separation and promote the surface area of LFO-NSwhich was confirmed by various characterization techniques including TEM, HRTEM, DRS, EDX, XRD, FS, XPS, FT-IR, BET, PL, and RAMAN. The 5ZIF-67/LFO-NS sample showed significant activities for CO2 conversion, malachite green degradation, and antibiotics (cefazolin, oxacillin, and vancomycin) degradation. Furthermore, stability tests have confirmed that our optimal sample very active and stable. Furthermore, based on scavenger experiments and the photocatalytic degradation pathways, it has been established that H+ and •O2- are vital in the decomposition of MG and antibiotics. Our research work will open new gateways to prepare MOFs-Perovskites nanocatalysts for exceptional CO2 conversion, organic pollutants and antibiotics degradation.

Network pharmacology, molecular simulation, and binding free energy calculation-based investigation of Neosetophomone B revealed key targets for the treatment of cancer.

In the current study, Neosetophomone B (NSP-B) was investigated for its anti-cancerous potential using network pharmacology, quantum polarized ligand docking, molecular simulation, and binding free energy calculation. Using SwissTarget prediction, and Superpred, the molecular targets for NSP-B were predicted while cancer-associated genes were obtained from DisGeNet. Among the total predicted proteins, only 25 were reported to overlap with the disease-associated genes. A protein-protein interaction network was constructed by using Cytoscape and STRING databases. MCODE was used to detect the densely connected subnetworks which revealed three sub-clusters. Cytohubba predicted four targets, i.e., fibroblast growth factor , FGF20, FGF22, and FGF23 as hub genes. Molecular docking of NSP-B based on a quantum-polarized docking approach with FGF6, FGF20, FGF22, and FGF23 revealed stronger interactions with the key hotspot residues. Moreover, molecular simulation revealed a stable dynamic behavior, good structural packing, and residues' flexibility of each complex. Hydrogen bonding in each complex was also observed to be above the minimum. In addition, the binding free energy was calculated using the MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) and MM/PBSA (Molecular Mechanics/Poisson-Boltzmann Surface Area) approaches. The total binding free energy calculated using the MM/GBSA approach revealed values of -36.85 kcal/mol for the FGF6-NSP-B complex, -43.87 kcal/mol for the FGF20-NSP-B complex, and -37.42 kcal/mol for the FGF22-NSP-B complex, and -41.91 kcal/mol for the FGF23-NSP-B complex. The total binding free energy calculated using the MM/PBSA approach showed values of -30.05 kcal/mol for the FGF6-NSP-B complex, -39.62 kcal/mol for the FGF20-NSP-B complex, -34.89 kcal/mol for the FGF22-NSP-B complex, and -37.18 kcal/mol for the FGF23-NSP-B complex. These findings underscore the promising potential of NSP-B against FGF6, FGF20, FGF22, and FGF23, which are reported to be essential for cancer signaling. These results significantly bolster the potential of NSP-B as a promising candidate for cancer therapy.

Human antigen R: Exploring its inflammatory response impact and significance in cardiometabolic disorders.

RNA-binding proteins (RBPs) play a crucial role in the regulation of posttranscriptional RNA networks, which can undergo dysregulation in many pathological conditions. Human antigen R (HuR) is a highly researched RBP that plays a crucial role as a posttranscriptional regulator. HuR plays a crucial role in the amplification of inflammatory signals by stabilizing the messenger RNA of diverse inflammatory mediators and key molecular players. The noteworthy correlations between HuR and its target molecules, coupled with the remarkable impacts reported on the pathogenesis and advancement of multiple diseases, position HuR as a promising candidate for therapeutic intervention in diverse inflammatory conditions. This review article examines the significance of HuR as a member of the RBP family, its regulatory mechanisms, and its implications in the pathophysiology of inflammation and cardiometabolic illnesses. Our objective is to illuminate potential directions for future research and drug development by conducting a comprehensive analysis of the existing body of research on HuR.

A critical review on metal-organic frameworks (MOFs) based nanomaterials for biomedical applications: Designing, recent trends, challenges, and prospects.

Nanomaterials (NMs) have garnered significant attention in recent decades due to their versatile applications in a wide range of fields. Thanks to their tiny size, enhanced surface modifications, impressive volume-to-surface area ratio, magnetic properties, and customized optical dispersion. NMs experienced an incredible upsurge in biomedical applications including diagnostics, therapeutics, and drug delivery. This minireview will focus on notable examples of NMs that tackle important issues, demonstrating various aspects such as their design, synthesis, morphology, classification, and use in cutting-edge applications. Furthermore, we have classified and outlined the distinctive characteristics of the advanced NMs as nanoscale particles and hybrid NMs. Meanwhile, we emphasize the incredible potential of metal-organic frameworks (MOFs), a highly versatile group of NMs. These MOFs have gained recognition as promising candidates for a wide range of bio-applications, including bioimaging, biosensing, antiviral therapy, anticancer therapy, nanomedicines, theranostics, immunotherapy, photodynamic therapy, photothermal therapy, gene therapy, and drug delivery. Although advanced NMs have shown great potential in the biomedical field, their use in clinical applications is still limited by issues such as stability, cytotoxicity, biocompatibility, and health concerns. This review article provides a thorough analysis offering valuable insights for researchers investigating to explore new design, development, and expansion opportunities. Remarkably, we ponder the prospects of NMs and nanocomposites in conjunction with current technology.

Structural vaccinology, molecular simulation and immune simulation approaches to design multi-epitopes vaccine against John Cunningham virus.

The JCV (John Cunningham Virus) is known to cause progressive multifocal leukoencephalopathy, a condition that results in the formation of tumors. Symptoms of this condition such as sensory defects, cognitive dysfunction, muscle weakness, homonosapobia, difficulties with coordination, and aphasia. To date, there is no specific and effective treatment to completely cure or prevent John Cunningham polyomavirus infections. Since the best way to control the disease is vaccination. In this study, the immunoinformatic tools were used to predict the high immunogenic and non-allergenic B cells, helper T cells (HTL), and cytotoxic T cells (CTL) epitopes from capsid, major capsid, and T antigen proteins of JC virus to design the highly efficient subunit vaccines. The specific immunogenic linkers were used to link together the predicted epitopes and subjected to 3D modeling by using the Robetta server. MD simulation was used to confirm that the newly constructed vaccines are stable and properly fold. Additionally, the molecular docking approach revealed that the vaccines have a strong binding affinity with human TLR-7. The codon adaptation index (CAI) and GC content values verified that the constructed vaccines would be highly expressed in E. coli pET28a (+) plasmid. The immune simulation analysis indicated that the human immune system would have a strong response to the vaccines, with a high titer of IgM and IgG antibodies being produced. In conclusion, this study will provide a pre-clinical concept to construct an effective, highly antigenic, non-allergenic, and thermostable vaccine to combat the infection of the John Cunningham virus.

Designing State-of-the-Art Gas Sensors: From Fundamentals to Applications.

Gas sensors are crucial in environmental monitoring, industrial safety, and medical diagnostics. Due to the rising demand for precise and reliable gas detection, there is a rising demand for cutting-edge gas sensors that possess exceptional sensitivity, selectivity, and stability. Due to their tunable electrical properties, high-density surface-active sites, and significant surface-to-volume ratio, nanomaterials have been extensively investigated in this regard. The traditional gas sensors utilize homogeneous material for sensing where the adsorbed surface oxygen species play a vital role in their sensing activity. However, their performance for selective gas sensing is still unsatisfactory because the employed high temperature leads to the poor stability. The heterostructures nanomaterials can easily tune sensing performance and their different energy band structures, work functions, charge carrier concentration and polarity, and interfacial band alignments can be precisely designed for high-performance selective gas sensing at low temperature. In this review article, we discuss in detail the fundamentals of semiconductor gas sensing along with their mechanisms. Further, we highlight the existed challenges in semiconductor gas sensing. In addition, we review the recent advancements in semiconductor gas sensor design for applications from different perspective. Finally, the conclusion and future perspectives for improvement of the gas sensing performance are discussed.

Immunoinformatics-driven In silico vaccine design for Nipah virus (NPV): Integrating machine learning and computational epitope prediction.

The Nipah virus (NPV) is a highly lethal virus, known for its significant fatality rate. The virus initially originated in Malaysia in 1998 and later led to outbreaks in nearby countries such as Bangladesh, Singapore, and India. Currently, there are no specific vaccines available for this virus. The current work employed the reverse vaccinology method to conduct a comprehensive analysis of the entire proteome of the NPV virus. The aim was to identify and choose the most promising antigenic proteins that could serve as potential candidates for vaccine development. We have also designed B and T cell epitopes-based vaccine candidate using immunoinformatics approach. We have identified a total of 5 novel Cytotoxic T Lymphocytes (CTL), 5 Helper T Lymphocytes (HTL), and 6 linear B-cell potential antigenic epitopes which are novel and can be used for further vaccine development against Nipah virus. Then we performed the physicochemical properties, antigenic, immunogenic and allergenicity prediction of the designed vaccine candidate against NPV. Further, Computational analysis indicated that these epitopes possessed highly antigenic properties and were capable of interacting with immune receptors. The designed vaccine were then docked with the human immune receptors, namely TLR-2 and TLR-4 showed robust interaction with the immune receptor. Molecular dynamics simulations demonstrated robust binding and good dynamics. After numerous dosages at varied intervals, computational immune response modeling showed that the immunogenic construct might elicit a significant immune response. In conclusion, the immunogenic construct shows promise in providing protection against NPV, However, further experimental validation is required before moving to clinical trials.

Improving the substrate binding of acetyl-CoA carboxylase (AccB) from Streptomyces antibioticus through computational enzyme engineering.

Malonyl-CoA serves as the main building block for the biosynthesis of many important polyketides, as well as fatty acid-derived compounds, such as biofuel. Escherichia coli, Corynebacterium gultamicum, and Saccharomyces cerevisiae have recently been engineered for the biosynthesis of such compounds. However, the developed processes and strains often have insufficient productivity. In the current study, we used enzyme-engineering approach to improve the binding of acetyl-CoA with ACC. We generated different mutations, and the impact was calculated, which reported that three mutations, that is, S343A, T347W, and S350W, significantly improve the substrate binding. Molecular docking investigation revealed an altered binding network compared to the wild type. In mutants, additional interactions stabilize the binding of the inner tail of acetyl-CoA. Using molecular simulation, the stability, compactness, hydrogen bonding, and protein motions were estimated, revealing different dynamic properties owned by the mutants only but not by the wild type. The findings were further validated by using the binding-free energy (BFE) method, which revealed these mutations as favorable substitutions. The total BFE was reported to be -52.66 ± 0.11 kcal/mol for the wild type, -55.87 ± 0.16 kcal/mol for the S343A mutant, -60.52 ± 0.25 kcal/mol for T347W mutant, and -59.64 ± 0.25 kcal/mol for the S350W mutant. This shows that the binding of the substrate is increased due to the induced mutations and strongly corroborates with the docking results. In sum, this study provides information regarding the essential hotspot residues for the substrate binding and can be used for application in industrial processes.

Analysis of E2F1 single-nucleotide polymorphisms reveals deleterious non-synonymous substitutions that disrupt E2F1-RB protein interaction in cancer.

Cancer is a medical condition that is caused by the abnormal growth and division of cells, leading to the formation of tumors. The E2F1 and RB pathways are critical in regulating cell cycle, and their dysregulation can contribute to the development of cancer. In this study, we analyzed experimentally reported SNPs in E2F1 and assessed their effects on the binding affinity with RB. Out of 46, nine mutations were predicted as deleterious, and further analysis revealed four highly destabilizing mutations (L206W, R232C, I254T, A267T) that significantly altered the protein structure. Molecular docking of wild-type and mutant E2F1 with RB revealed a docking score of -242 kcal/mol for wild-type, while the mutant complexes had scores ranging from -217 to -220 kcal/mol. Molecular simulation analysis revealed variations in the dynamics features of both mutant and wild-type complexes due to the acquired mutations. Furthermore, the total binding free energy for the wild-type E2F1-RB complex was -64.89 kcal/mol, while those of the L206W, R232C, I254T, and A267T E2F1-RB mutants were -45.90 kcal/mol, -53.52 kcal/mol, -55.67 kcal/mol, and -61.22 kcal/mol, respectively. Our study is the first to extensively analyze E2F1 gene mutations and identifies candidate mutations for further validation and potential targeting for cancer therapeutics.

Structural and molecular investigation of the impact of S30L and D88N substitutions in G9R protein on coupling with E4R from Monkeypox virus (MPXV).

Understanding the pathogenesis mechanism of the Monkeypox virus (MPXV) is essential to guide therapeutic development against the Monkeypox virus. In the current study, we investigated the impact of the only two reported substitutions, S30L, D88N, and S30L-D88N on the G9R of the replication complex in 2022 with E4R using structural modeling, simulation, and free energy calculation methods. From the molecular docking and dissociation constant (KD) results, it was observed that the binding affinity did not increase in the mutants, but the interaction paradigm was altered by these substitutions. Molecular simulation data revealed that these mutations are responsible for destabilization, changes in protein packing, and internal residue fluctuations, which can cause functional variance. Additionally, hydrogen bonding analysis revealed that the estimated number of hydrogen bonds are almost equal among the wild-type G9R and each mutant. The total binding free energy for the wild-type G9R with E4R was -85.00 kcal/mol while for the mutants the TBE was -42.75 kcal/mol, -43.68 kcal/mol, and -48.65 kcal/mol respectively. This shows that there is no direct impact of these two reported mutations on the binding with E4R, or it may affect the whole replication complex or any other mechanism involved in pathogenesis. To explore these variations further, we conducted PCA and FEL analyses. Based on our findings, we speculate that within the context of interaction with E4R, the mutations in the G9R protein might be benign, potentially leading to functional diversity associated with other proteins.Communicated by Ramaswamy H. Sarma.

Structural basis for the mechanism of interaction of SARS-CoV-2 B.1.640.2 variant RBD with the host receptors hACE2 and GRP78.

The inflicted chaos instigated by the SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) globally continues with the emergence of novel variants. The current global outbreak is aggravated by the manifestation of novel variants, which affect the effectiveness of the vaccine, attachment with hACE2 (human Angiotensin-converting enzyme 2) and immune evasion. Recently, a new variant named University Hospital Institute (IHU) (B.1.640.2) was reported in France in November 2021 and is spreading globally affecting public healthcare. The B.1.640.2 SARS-CoV-2 strain revealed 14 mutations and 9 deletions in spike protein. Thus, it is important to understand how these variations in the spike protein impact the communication with the host. A protein coupling approach along with molecular simulation protocols was used to interpret the variation in the binding of the wild type (WT) and B.1.640.2 variant with hACE2 and Glucose-regulating protein 78 (GRP78) receptors. The initial docking scores revealed a stronger binding of the B.1.640.2-RBD with both the hACE2 and GRP78. To further understand the crucial dynamic changes, we looked at the structural and dynamic characteristics and also explored the variations in the bonding networks between the WT and B.1.640.2-RBD (receptor-binding domain) in association with hACE2 and GRP78, respectively. Our findings revealed that the variant complex demonstrated distinct dynamic properties in contrast to the wild type due to the acquired mutations. Finally, to provide conclusive evidence on the higher binding by the B.1.640.2 variant the TBE was computed for each complex. For the WT with hACE2 the TBE was quantified to be-61.38 ± 0.96 kcal/mol and for B.1.640.2 variant the TBE was estimated to be -70.47 ± 1.00 kcal/mol. For the WT-RBD-GRP78 the TBE -was computed to be 32.32 ± 0.56 kcal/mol and for the B.1.640.2-RBD a TBE of -50.39 ± 0.88 kcal/mol was reported. This show that these mutations are the basis for higher binding and infectivity produced by B.1.640.2 variant and can be targeted for drug designing against it.Communicated by Ramaswamy H. Sarma.

Green synthesis of silver nanoparticles from plant Fagonia cretica and evaluating its anti-diabetic activity through indepth in-vitro and in-vivo analysis.

One of the most widespread metabolic diseases, Type-2 Diabetes Mellitus (T2DM) is defined by high blood sugar levels brought on by decreased insulin secretion, reduced insulin action, or both. Due to its cost-effectiveness and eco-friendliness, plant-mediated green synthesis of nanomaterials has become more and more popular. The aim of the study is to synthesize AgNPs, their characterizations and further in-vitro and in-vivo studies. Several methods were used to morphologically characterise the AgNPs. The AgNPs were crystalline, spherical, and clustered, with sizes ranging from 20 to 50 nm. AgNPs were found to contain various functional groups using Fourier transform infrared spectroscopy. This study focuses on the green-synthesis of AgNPs from Fagonia cretica (F. cretica) leaves extract to evaluate their synthesized AgNPs for in-vitro and in-vivo anti-diabetic function. For the in-vivo tests, 20 male Balb/C albino-mice were split up into four different groups. Anti-diabetic in-vivo studies showed significant weight gain and a decrease in all biochemical markers (pancreas panel, liver function panel, renal function panel, and lipid profile) in Streptozotocin (STZ)-induced diabetic mice. In vitro anti-diabetic investigations were also conducted on AgNPs, comprising α-amylase, α-glucosidase inhibitions, and antioxidant assays. AgNPs showed antioxidant activity in both the DPPH and ABTS assays. The research showed that the isolated nanoparticles have powerful antioxidant and enzyme inhibitory properties, especially against the main enzymes involved in T2DM.

WGX50 mitigates doxorubicin-induced cardiotoxicity through inhibition of mitochondrial ROS and ferroptosis.

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major impediment to its clinical application. It is indispensable to explore alternative treatment molecules or drugs for mitigating DIC. WGX50, an organic extract derived from Zanthoxylum bungeanum Maxim, has anti-inflammatory and antioxidant biological activity, however, its function and mechanism in DIC remain unclear. METHODS: We established DOX-induced cardiotoxicity models both in vitro and in vivo. Echocardiography and histological analyses were used to determine the severity of cardiac injury in mice. The myocardial damage markers cTnT, CK-MB, ANP, BNP, and ferroptosis associated indicators Fe2+, MDA, and GPX4 were measured using ELISA, RT-qPCR, and western blot assays. The morphology of mitochondria was investigated with a transmission electron microscope. The levels of mitochondrial membrane potential, mitochondrial ROS, and lipid ROS were detected using JC-1, MitoSOX™, and C11-BODIPY 581/591 probes. RESULTS: Our findings demonstrate that WGX50 protects DOX-induced cardiotoxicity via restraining mitochondrial ROS and ferroptosis. In vivo, WGX50 effectively relieves doxorubicin-induced cardiac dysfunction, cardiac injury, fibrosis, mitochondrial damage, and redox imbalance. In vitro, WGX50 preserves mitochondrial function by reducing the level of mitochondrial membrane potential and increasing mitochondrial ATP production. Furthermore, WGX50 reduces iron accumulation and mitochondrial ROS, increases GPX4 expression, and regulates lipid metabolism to inhibit DOX-induced ferroptosis. CONCLUSION: Taken together, WGX50 protects DOX-induced cardiotoxicity via mitochondrial ROS and the ferroptosis pathway, which provides novel insights for WGX50 as a promising drug candidate for cardioprotection.

Hemolytic Anemia-Related Acute Kidney Injury: A Case Report With Complications Including Posterior Reversible Encephalopathy Syndrome.

INTRODUCTION: The condition known as posterior reversible encephalopathy syndrome (PRES) is characterized by symptoms such as headaches, seizures, and vision problems due to brain swelling, which often can be seen in brain scans. While there have been some cases of PRES linked to conditions such autoimmune diseases and high blood pressure, we're sharing a unique case here. Our case involves severe kidney damage caused by idiopathic hemolytic anaemia. The patient also experienced loss of consciousness, seizures, and headache. Brain scans confirmed the signs of PRES. We managed to help the patient recover fully through careful treatment, including fluids, managing seizures, and transfusions. CASE DETAILS: Our patient was dealing with severe kidney damage from idiopathic hemolytic anaemia. They had episodes of loss of consciousness, seizures, and headaches. Brain scans showed that they had PRES. DIAGNOSIS AND TREATMENT: We found out that the patient had severe kidney damage because of hemolytic anaemia, and she also had PRES. We treated her by giving fluids, managing her seizures, and doing blood transfusions, along with other supportive care. CONCLUSIONS: With our treatment, the patient got better, her neurological symptoms improved, and her brain scans showed fewer signs of PRES. This case tells us something interesting - sometimes, anaemia can lead to rare neurological problems like PRES. We need to be aware of these possibilities to help patients better. Our successful treatment in this case emphasizes how important quick and comprehensive care can be for good outcomes.