Utilising biosensor-based approaches for identifying neurotropic viruses.

Neurotropic viruses, with their ability to invade the central nervous system, present a significant public health challenge, causing a spectrum of neurological diseases. Clinical manifestations of neurotropic viral infections vary widely, from mild to life-threatening conditions, such as HSV-induced encephalitis or poliovirus-induced poliomyelitis. Traditional diagnostic methods, including polymerase chain reaction, serological assays, and imaging techniques, though valuable, have limitations. To address these challenges, biosensor-based methods have emerged as a promising approach. These methods offer advantages such as rapid results, high sensitivity, specificity, and potential for point-of-care applications. By targeting specific biomarkers or genetic material, biosensors utilise technologies like surface plasmon resonance and microarrays, providing a direct and efficient means of diagnosing neurotropic infections. This review explores the evolving landscape of biosensor-based methods, highlighting their potential to enhance the diagnostic toolkit for neurotropic viruses.

Neurological Implications of Poxvirus Infections: Pathogenesis, Neurotropism, and Clinical Manifestations.

Poxviridae is a diverse family of double-stranded DNA viruses, historically significant for diseases like smallpox caused by variola virus (VARV). These viruses exhibit unique cytoplasmic replication strategies, large genomes encoding numerous proteins, and the ability to cause severe cutaneous and systemic diseases. Recent attention has focused on their neurotropic potential, including mechanisms of CNS invasion, immune-mediated damage, and clinical manifestations such as encephalitis and myelitis. This review synthesises current knowledge on poxvirus neurotropism, highlighting pathophysiological mechanisms and clinical implications.

Neurological manifestations of Flaviviridae, Togaviridae, and Peribunyaviridae as vector-borne viruses.

Vector-borne viruses pose a significant health problem worldwide, as they are transmitted to humans through the bite of infected arthropods such as mosquitoes and ticks. In recent years, emerging and re-emerging vector-borne diseases have gained attention as they can cause a wide spectrum of neurological manifestations. The neurological manifestations of vector-borne viruses encompass a board spectrum of clinical manifestations, ranging from mild and self-limiting symptoms to severe and life-threatening conditions. Common neurological complications include viral encephalitis, acute flaccid paralysis, aseptic meningitis, and various neuromuscular disorders. The specific viruses responsible for these neurological sequelae vary by geographic region and include Orthoflavivirus nilense, Zika virus, dengue virus, chikungunya virus, Japanese encephalitis virus, and tick-borne encephalitis virus. This review focuses on the pathogenesis of these neurologic complications and highlights the mechanisms by which vector-borne viruses invade the central nervous system and trigger neuroinflammatory responses. Diagnostic challenges and strategies for early detection of neurological manifestations are discussed, emphasising the importance of clinical suspicion and advanced laboratory testing.

Overview of reemerging mpox infection with a focus on neurological manifestations.

Mpox, a reemerging zoonotic disease caused by the mpox virus, has garnered increasing attention due to its potential for severe clinical manifestations. While the cutaneous and systemic presentations of mpox have been well-documented, its neurological complications have recently emerged as an area of concern. This review provides a brief overview of the neurological aspects of mpox infection, highlighting the key findings and challenges in understanding and managing these complications. Neurological manifestations in mpox patients range from mild symptoms such as headaches and dizziness to more severe conditions, including encephalitis and seizures. The pathogenesis of neurological involvement is not yet fully elucidated but is thought to involve viral dissemination to the central nervous system. This dissemination may occur through haematogenous or neuronal routes, contributing to the diverse clinical spectrum observed. Early recognition and diagnosis of neurological complications in mpox are crucial for implementing appropriate therapeutic interventions and improving patient outcomes.

Transmission dynamics, complications and mitigation strategies of the current mpox outbreak: A comprehensive review with bibliometric study.

As the mankind counters the ongoing COVID-19 pandemic by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), it simultaneously witnesses the emergence of mpox virus (MPXV) that signals at global spread and could potentially lead to another pandemic. Although MPXV has existed for more than 50 years now with most of the human cases being reported from the endemic West and Central African regions, the disease is recently being reported in non-endemic regions too that affect more than 50 countries. Controlling the spread of MPXV is important due to its potential danger of a global spread, causing severe morbidity and mortality. The article highlights the transmission dynamics, zoonosis potential, complication and mitigation strategies for MPXV infection, and concludes with suggested 'one health' approach for better management, control and prevention. Bibliometric analyses of the data extend the understanding and provide leads on the research trends, the global spread, and the need to revamp the critical research and healthcare interventions. Globally published mpox-related literature does not align well with endemic areas/regions of occurrence which should ideally have been the scenario. Such demographic and geographic gaps between the location of the research work and the endemic epicentres of the disease need to be bridged for greater and effective translation of the research outputs to pubic healthcare systems, it is suggested.

Prevalence of human papillomavirus in head and neck cancer patients in India: a systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations. METHODS: A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3). RESULTS: The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8-42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2-62.4) in the eastern regions and 19.8% (95% CI: 10.8-33.4) in the western regions. No evidence of publication bias was detected. CONCLUSION: The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.

Cynaropicrin, a sesquiterpene lactone, triggers apoptotic cell death in triple negative breast cancer cells.

BACKGROUND: Breast cancer is the most common cancer in the world. Cynaropicrin is a natural sesquiterpene lactone with potential anticancer effects. The present study was conducted to evaluate the effect of cynaropicrin on proliferation and apoptosis in breast cancer cells. METHODS: MDA-MB-231 and MCF-7 cell lines were treated with increasing concentrations of cynaropicrin. The viability of both cell lines was measured using MTT assay. Flowcytometry was used to detect apoptotic cells. The expression levels of apoptosis-related genes were determined using quantitative polymerase chain reaction. The protein expression of apoptosis markers was determined by western blotting. RESULTS: Cynaropicrin significantly diminished the proliferation of MDA-MB-231 and MCF-7 cell lines in a dose-dependent manner. Flowcytometry data uncovered that cynaropicrin augmented early and late apoptosis in MDA-MB-231 cells. Real time-PCR and western blotting results also confirmed the upregulation of pro-apoptotic Bax, caspase-3, -8, and 9 as well as downregulated level of anti-apoptotic marker Bcl-2. Cynaropicrin also remarkably increased the activity of caspase-3, -8, and 9 in MDA-MB-231 cells. However, cynaropicrin neither promoted apoptosis in MCF-7 cells nor altered the expression levels and activity of above mentioned apoptotic markers. CONCLUSION: The present data indicated anti-proliferative properties of cynaropicrin against breast cancer and highlighted apoptosis-inducing effects of this sesquiterpene on triple negative breast cancer (TNBC) cells. These data may suggest cynaropicrin as a potential anti-TNBC agent to tackle therapy resistance in this type of breast cancer.

Repositioning of anti-infective compounds against monkeypox virus core cysteine proteinase: a molecular dynamics study.

Monkeypox virus (MPXV) core cysteine proteinase (CCP) is one of the major drug targets used to examine the inhibitory action of chemical moieties. In this study, an in silico technique was applied to screen 1395 anti-infective compounds to find out the potential molecules against the MPXV-CCP. The top five hits were selected after screening and processed for exhaustive docking based on the docked score of ≤ -9.5 kcal/mol. Later, the top three hits based on the exhaustive-docking score and interaction profile were selected to perform MD simulations. The overall RMSD suggested that two compounds, SC75741 and ammonium glycyrrhizinate, showed a highly stable complex with a standard deviation of 0.18 and 0.23 nm, respectively. Later, the MM/GBSA binding free energies of complexes showed significant binding strength with ΔGTOTAL from -21.59 to -15 kcal/mol. This report reported the potential inhibitory activity of SC75741 and ammonium glycyrrhizinate against MPXV-CCP by competitively inhibiting the binding of the native substrate.

Network-Based Drug Repurposing and Genomic Analysis to Unveil Potential Therapeutics for Monkeypox Virus.

The emergence of the human monkeypox virus (MPXV) and the lack of effective medications have necessitated the exploration of various strategies to combat its infection. This study employs a network-based approach to drug discovery, utilizing the BLASTn and phylogenetic analysis to compare the MPXV genome with those of 18 related orthopoxviruses, revealing over 75% genomic similarity. Through a literature review, 160 human-host proteins linked to MPXV and its relatives were identified, leading to the construction of a human-host protein interactome. Analysis of this interactome highlighted 39 central hub proteins, which were then examined for potential drug targets. The process successfully revealed 15 targets already approved for use with medications. Additionally, the functional enrichment analysis provided insights into potential pathways and disorders connected with these targets. Four medications, namely Baricitinib, Infliximab, Adalimumab, and Etanercept, have been identified as potential candidates for repurposing to combat MPXV. In addition, the pharmacophore-based screening identified a molecule that is comparable to Baricitinib and has the potential to be effective against MPXV. The findings of the study suggest that ZINC22060520 is a promising medication for treating MPXV infection and proposes these medications as potential options for additional experimental and clinical assessment in the battle against MPXV.

Exploration of phytochemical compounds against Marburg virus using QSAR, molecular dynamics, and free energy landscape.

Marburg virus disease (MVD) is caused by the Marburg virus, a one-of-a-kind zoonotic RNA virus from the genus Filovirus. Thus, this current study employed AI-based QSAR and molecular docking-based virtual screening for identifying potential binders against the target protein (nucleoprotein (NP)) of the Marburg virus. A total of 2727 phytochemicals were used for screening, out of which the top three compounds (74977521, 90470472, and 11953909) were identified based on their predicted bioactivity (pIC50) and binding score (< - 7.4 kcal/mol). Later, MD simulation in triplicates and trajectory analysis were performed which showed that 11953909 and 74977521 had the most stable and consistent complex formations and had the most significant interactions with the highest number of hydrogen bonds. PCA (principal component analysis) and FEL (free energy landscape) analysis indicated that these compounds had favourable energy states for most of the conformations. The total binding free energy of the compounds using the MM/GBSA technique showed that 11953909 (ΔGTOTAL = - 30.78 kcal/mol) and 74977521 (ΔGTOTAL = - 30 kcal/mol) had the highest binding affinity with the protein. Overall, this in silico pipeline proposed that the phytochemicals 11953909 and 74977521 could be the possible binders of NP. This study aimed to find phytochemicals inhibiting the protein's function and potentially treating MVD.

Identification of natural potent inhibitors against Mycobacterium tuberculosis isocitrate lyase: an in silico study.

Tuberculosis (TB) is a global burden to humanity due to its adverse effects on health and society since time is not clearly defined. The existence of drug-resistant strains and the potential threat posed by latent tuberculosis act as strong impetuses for developing novel anti-tuberculosis drugs. In this study, various flavonoids were tested against the Mycobacterium tuberculosis (Mtb) Isocitrate Lyase (ICL), which has been identified as an authorised therapeutic target for treating Mtb infection. Using in silico drug discovery approach, a library of 241 flavonoid compounds was virtually screened against the binding pocket of the crystalline ligand, the VGX inhibitor, in the Mtb ICL protein. As a result, the top four flavonoids were selected based on binding score and were further considered for redocking and intermolecular contact profiling analysis. The global and local fluctuations in the protein and ligand structure were analysed using their root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values obtained from the GROMACS generated 100 ns molecular dynamics (MD) simulation trajectories. The end-state binding free energy was also calculated using the MMPBSA approach for all the respective docked complexes. All four selected compounds exhibited considerable stability and affinity compared to control ligands, i.e. VGX inhibitor; however, Vaccarin showed the highest stability and affinity against the Mtb ICL protein active site, followed by the Genistin, Glabridin, and Corylin. Therefore, this study recommends selected flavonoids for in vitro and in vivo experimental studies to check their potency and efficacy against Mtb.

Anti-tubercular activity evaluation of natural compounds by targeting Mycobacterium tuberculosis resuscitation promoting factor B inhibition: An in silico study.

Tuberculosis (TB), an infectious disease caused by the Mycobacterium tuberculosis (Mtb), has been responsible for the deaths of millions of individuals around the globe. A vital protein in viral pathogenesis known as resuscitation promoting factor (RpfB) has been identified as a potential therapeutic target of anti-tuberculosis drugs. This study offered an in silico process to examine possible RpfB inhibitors employing a computational drug design pipeline. In this study, a total of 1228 phytomolecules were virtually tested against the RpfB of Mtb. These phytomolecules were sourced from the NP-lib database of the MTi-OpenScreen server, and five top hits (ZINC000044404209, ZINC000059779788, ZINC000001562130, ZINC000014766825, and ZINC000043552589) were prioritized for compute intensive docking with dock score ≤ - 8.5 kcal/mole. Later, molecular dynamics (MD) simulation and principal component analysis (PCA) were used to validate these top five hits. In the list of these top five hits, the ligands ZINC000044404209, ZINC000059779788, and ZINC000043552589 showed hydrogen bond formation with the functional residue Glu292 of the RpfB protein suggesting biological significance of the binding. The RMSD study showed stable protein-ligand complexes and higher conformational consistency for the ligands ZINC000014766825, and ZINC000043552589 with RMSD 3-4 Å during 100 ns MD simulation. The overall analysis performed in the study suggested promising binding of these compounds with the RpfB protein of the Mtb at its functional site, further experimental investigation is needed to validate the computational finding.

Effect of Achillea fragrantissima Extract on Excision Wound Biofilms of MRSA and Pseudomonas aeruginosa in Diabetic Mice.

Achillea fragrantissima, a desert plant commonly known as yarrow, is traditionally used as an antimicrobial agent in folklore medicine in Saudi Arabia. The current study was undertaken to determine its antibiofilm activity against methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug-resistant Pseudomonas aeruginosa (MDR-P. aeruginosa) using in vitro and in vivo studies. A biofilm model induced through an excision wound in diabetic mice was used to evaluate its effect in vivo. The skin irritation and cytotoxic effects of the extract were determined using mice and HaCaT cell lines, respectively. The Achillea fragrantissima methanolic extract was analyzed with LC-MS to detect different phytoconstituents, which revealed the presence of 47 different phytoconstituents. The extract inhibited the growth of both tested pathogens in vitro. It also increased the healing of biofilm-formed excision wounds, demonstrating its antibiofilm, antimicrobial, and wound-healing action in vivo. The effect of the extract was concentration-dependent, and its activity was stronger against MRSA than MDR-P. aeruginosa. The extract formulation was devoid of a skin irritation effect in vivo and cytotoxic effect on HaCaT cell lines in vitro.

A Review of the Resistance Mechanisms for ß-Lactams, Macrolides and Fluoroquinolones among Streptococcus pneumoniae.

Streptococcus pneumoniae (S. pneumoniae) is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of S. pneumoniae as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like ß-lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of S. pneumoniae infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in S. pneumoniae against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes ß-lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of S. pneumoniae may aid researchers in developing a more efficacious antibiotic in future endeavors.

Variants of SARS-CoV-2: Influences on the Vaccines' Effectiveness and Possible Strategies to Overcome Their Consequences.

The immune response elicited by the current COVID-19 vaccinations declines with time, especially among the immunocompromised population. Furthermore, the emergence of novel SARS-CoV-2 variants, particularly the Omicron variant, has raised serious concerns about the efficacy of currently available vaccines in protecting the most vulnerable people. Several studies have reported that vaccinated people get breakthrough infections amid COVID-19 cases. So far, five variants of concern (VOCs) have been reported, resulting in successive waves of infection. These variants have shown a variable amount of resistance towards the neutralising antibodies (nAbs) elicited either through natural infection or the vaccination. The spike (S) protein, membrane (M) protein, and envelope (E) protein on the viral surface envelope and the N-nucleocapsid protein in the core of the ribonucleoprotein are the major structural vaccine target proteins against COVID-19. Among these targets, S Protein has been extensively exploited to generate effective vaccines against COVID-19. Hence, amid the emergence of novel variants of SARS-CoV-2, we have discussed their impact on currently available vaccines. We have also discussed the potential roles of S Protein in the development of novel vaccination approaches to contain the negative consequences of the variants' emergence and acquisition of mutations in the S Protein of SARS-CoV-2. Moreover, the implications of SARS-CoV-2's structural proteins were also discussed in terms of their variable potential to elicit an effective amount of immune response.

New-onset and relapsed liver diseases following COVID-19 vaccination: a systematic review.

BACKGROUND: Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines. OBJECTIVES: To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination. METHODS: For this systematic review, we searched Proquest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA guideline for studies on the incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction. RESULTS: Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n = 4, 50%), portal vein thrombosis (n = 25, 48.1%), splanchnic vein thrombosis (n = 6, 42.8%), jaundice (n = 1, 12.5%), raised liver enzymes (n = 2, 7.7%), and autoimmune hepatitis (n = 3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy. CONCLUSION: Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.

Designing mRNA- and Peptide-Based Vaccine Construct against Emerging Multidrug-Resistant Citrobacter freundii: A Computational-Based Subtractive Proteomics Approach.

Background and Objectives: Citrobacter freundii (C. freundii) is an emerging and opportunistic Gram-negative bacteria of the human gastrointestinal tract associated with nosocomial and severe respiratory tract infections. It has also been associated with pneumonia, bloodstream, and urinary tract infections. Intrinsic and adaptive virulence characteristics of C. freundii have become a significant source of diarrheal infections and food poisoning among immune-compromised patients and newborns. Impulsive usage of antibiotics and these adaptive virulence characteristics has modulated the C. freundii into multidrug-resistant (MDR) bacteria. Conventional approaches are futile against MDR C. freundii. Materials and Methods: The current study exploits the modern computational-based vaccine design approach to treat infections related to MDR C. freundii. A whole proteome of C. freundii (strain: CWH001) was retrieved to screen pathogenic and nonhomologous proteins. Six proteins were shortlisted for the selection of putative epitopes for vaccine construct. Highly antigenic, nonallergen, and nontoxic eleven B-cell, HTL, and TCL epitopes were selected for mRNA- and peptide-based multi-epitope vaccine construct. Secondary and tertiary structures of the multi-epitope vaccine (MEVC) were designed, refined, and validated. Results: Evaluation of population coverage of MHC-I and MHC-II alleles were 72% and 90%, respectively. Docking MEVC with TLR-3 receptor with the binding affinity of 21.46 (kcal/mol) occurred through the mmGBSA process. Further validations include codon optimization with an enhanced CAI value of 0.95 and GC content of about 51%. Immune stimulation and molecular dynamic simulation ensure the antibody production upon antigen interaction with the host and stability of the MEVC construct, respectively. Conclusions: These interpretations propose a new strategy to combat MDR C. freundii. Further, in vivo and in vitro trials of this vaccine will be valuable in combating MDR pathogens.

Dermal derived matrix hydrogel loaded with curcumin improved wound healing in a diabetic rat model.

There is a need in clinical practice for new wound healing techniques to address full thickness skin injuries, particularly in individuals with diabetes. Herein we investigated whether dermal derived matrix hydrogel (DMH) loaded with curcumin (Cur) could promote healing in diabetic rats. Sixty diabetic rats were randomly assigned into the non-treated group, DMH group, Cur group, and DMH+Cur group. According to the phases of wound healing, sampling was done on days 7, 14, and 21 for further assessments. Our results indicated that the wound contraction rate, new epidermal length and thickness, number of fibroblasts and vascular length, collagen deposition, and strength properties of the healed wounds were meaningfully increased in the treatment groups than in the non-treated group, and these changes were more obvious in the DMH+Cur ones. In addition, the expression of VEGF and IL-10 genes were meaningfully upregulated in all treatment groups compared to the non-treated group and were greater in the DMH+Cur group. This is while the number of neutrophils and expression levels of TNF-α and IL-1ß genes decreased more significantly in the DMH+Cur group compared to the other groups. In conclusion, it was found that using both DMH and curcumin has a greater impact on diabetic wound healing.

Suppression of glomerular damage, inflammation, apoptosis, and oxidative stress of acute kidney injury induced by cyclophosphamide toxicity using resveratrol in rat models.

Cyclophosphamide (CP) is a chemotherapy drug that can be used to treat different types of cancers, but its nephrotoxicity effects restrict its usage in clinical settings. Currently, we examined whether the polyphenolic antioxidant and anti-inflammatory compound, resveratrol (RES), can protect against CP-induced nephrotoxicity. Twenty male mature Sprague-Dawley rats were divided into 4 groups of equal size: control group, RES group which received RES (20 mg/kg) for 15 consecutive days, CP group which received CP as a single dose (150 mg/kg) on day 16, and CP+RES group which was similar of the RES and CP groups. Tissue samples were obtained for the stereological, immunohistochemical, biochemical, and molecular evaluations. Findings showed that the numerical density of glomerulus, total volumes and interstitial tissue volumes of kidney, antioxidative biomarkers concentrations (CAT, GSH, SOD), and expression levels of OCT2 gene were notably greater in the CP+RES group than the CP group (P<0.05). During treatment, there was a significant decrease in the serum levels of the urea and creatinine, the densities of apoptotic and inflammatory cells, as well as levels of MDA and proinflammatory cytokines (IL-1ß, TNF-α, and PFN1) in the CP+RES group than the CP group (P<0.05). We deduce that giving RES can suppress of glomerular damage, inflammation, apoptosis, and oxidative stress of acute kidney injury induced by CP toxicity.

Utilization of nanotechnology and experimental design in the development and optimization of a posaconazole‒calendula oil nanoemulgel for the treatment of mouth disorders.

Introduction: Essential oil‒based nanoemulsions (NEs) are the subjects of extensive investigation due to their potential to address a variety of oral health issues. NEs are delivery systems that improve lipid medicine solubility and distribution to intended sites. The goal of the current study was to create and enhance a self-nanoemulsifying drug delivery paradigm based on calendula oil (CO) and decorated with chitosan (CS) that could deliver posaconazole (PSZ) for the treatment of gingivitis. Method: Employing a response-surface Box‒Behnken design, PSZ-CO-CS NEs were created with varying amounts of PSZ (10, 15, and 20 mg), percentages of CO (6%, 12%, and 18%), and percentages of CS (0.5%, 1.5%, and 2.5%). Results and conclusion: The optimized formulation resulted in a 22-mm bacterial growth suppression zone, 25-mm fungal growth inhibition zone, droplet sizes of 110 nm, and a viscosity of 750 centipoise (cP). Using the appropriate design, the ideal formulation was produced; it contained 20 mg of PSZ, 18% of CO, and 1.35% of CS. Furthermore, the optimal formulation had a more controlled drug release, larger inhibition zones of bacterial and fungal growth, and desirable rheologic properties. Additionally, the optimized formulation substantially lowered the ulcer index in rats when tested against other formulations. Thus, this investigation showed that PSZ-CO-CS NEs could provide efficient protection against microbially induced gingivitis.