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Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Online First
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20 results
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Exploring the Potential Use of Withania somnifera in Leprosy and Lepra Reactions: A Molecular Docking Approach
Available online: 30 December 2024More LessIntroductionWithania somnifera (Ashwagandha) is a traditional herb that is currently commercially available for treating a variety of illnesses. By evaluating and verifying docking affinity scores, it is possible to explore the potential of the plant for treating leprosy and lepra-reaction as off-label use.
MethodsThe sitoindosides were used as ligands along with thalidomide in docking against targets, such as M. leprae, TNF-Alpha, and Interleukin-6 in order to determine the potential for inhibitory concentration and docking affinity.
ResultsAccording to the study, good binding energy values varied from -7 to -11 Kcal/mol. Sitoindoside IX had the highest binding affinity and important binding interactions, such as hydrogen bonding, when compared to Thalidomide and Sitoindoside X against all three receptors.
ConclusionThe present study confirmed that the Sitoindoside IX and X are a better fit for treating patients with leprosy. These findings are highly intriguing and suggest that this herb should be investigated further to validate these findings in leprosy.
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Antioxidant Nutraceuticals: Their Adjunct Role in the Management of COVID-19 Infections and Post-COVID Syndrome
Available online: 30 December 2024More LessThe COVID-19 epidemic in recent years has been produced by various coronavirus strains that nearly destroyed world health policies and economics. Emerging viral strains exacerbated the pandemic. Huge investments have been made in preventative vaccines to combat the disease, but the genetic instability of these viruses has hampered their usefulness. However, in addition to traditional therapeutic approaches, nutraceuticals have been considered efficacious in preventing and or treating COVID-19 and post-COVID syndrome. In this context, nutraceuticals such as vitamins or dietary supplements including multiple vitamins and minerals and propolis have been widely studied for their significant impact on viral respiratory diseases like SARS-CoV-2 and COVID-19. Some of these nutraceuticals having antioxidant, anti-inflammatory, and immune-modulatory properties have been highly recommended for use as an adjunct option to moderate the adverse effects associated with the COVID-19 pandemic. In this review, we intend to present the recent understanding and converse scientific implications for the use of nutraceutical antioxidants such as vitamins, minerals, probiotics, and polyphenols like bee propolis, in the management of viral respiratory diseases and post-COVID-19 syndrome. Future challenges and limitations regarding the use and bioavailability of these ingredients, and dose-response studies are further emphasized.
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Exploration of Phytochemicals as Anti-biofilm Agents Against Pathogenic Bacteria: Their Potential and Challenges
Available online: 30 December 2024More LessMulticellular surface-attached populations of bacteria embedded in the extracellular matrix are known as biofilms. Bacteria generally preferred to grow as biofilms. Quorum sensing (QS), detection of density of cell population through gene regulation, has been found to play an important role in the production of biofilms. Biofilm formation can increase the severity of infections that can lead to morbidity or mortality. Bacteria living within biofilms have a higher pattern of adaptive resistance to antibiotics. Antibiotic resistance is a barrier in the treatment of biofilms-induced acute to chronic infections such as post-surgery infections, surgery-associated wound infections, endocarditis, joint infections, burn-related wound infections occurred, ventilator-associated pneumonia, etc. So it is urgent to discover or find out potent new drugs in fight against infectious diseases such as biofilms-associated infections. Medicinal plants or herbs are a rich source for fighting with biofilms-mediated infections. Phytochemicals have exhibited significant effects in the prevention of biofilms formation against different bacteria that are causing infections. Purified compounds such as berberine, tetrandrine, embelin, xanthorrhizol, bakuchiol, etc., exhibited promising biofilm inhibition actions against different pathogenic bacteria. Plant extracts that contain several phytochemicals are evaluated for its biofilm’s inhibition property, and have shown significant potential in biofilm formation. Antibiofilm agents act by distinct mechanisms such as inhibiting the adherence of biofilms in a surface, preventing the biofilm formations, disrupting the matured biofilms, etc. This study is intended to reiterate about possibilities of plant extracts and purified compounds in the treatment of the prevention of bacterial biofilms-related infections.
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A Case Study of Intradural Extramedullary Spinal Schwannoma and Multiple Thoracic Vertebral Haemangiomas Following COVID-19 Infection and Vaccination: Insights from MRI Imaging
Available online: 20 December 2024More LessIntroductionSpinal schwannomas are benign intradural extramedullary tumors of Schwann cells, while hemangiomas are common benign vascular tumors found in the vertebral column.
Case RepresentationThis case study presents a 32-year-old male who developed both a spinal schwannoma and multiple thoracic vertebral haemangiomas following a COVID-19 infection and subsequent vaccination. The patient reported intermittent lumbar and thigh pain over 6-8 months. Magnetic resonance imaging (MRI) confirmed an intradural extramedullary schwannoma at the L5 vertebra and multiple thoracic haemangiomas at the T6-T7 levels. The schwannoma was surgically resected, and pathology confirmed the diagnosis. Postoperatively, the patient’s symptoms improved significantly, with no complications.
ConclusionThis case raises questions about a possible link between COVID-19 and these spinal conditions. Further research is warranted to explore the potential association between viral infection, vaccination, and tumor development.
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Intensification of Invasive Fungal Infections and Exploration of Effective Antifungal Drug Delivery Formulations: A Detailed Review
Authors: Shrikant Mahesh Sharma, Rupali Sharma and Pankaj ChandrateyaAvailable online: 20 December 2024More LessInvasive fungal infections (IFIs) pose a significant global health threat, particularly among immunocompromised individuals. These infections can lead to severe illness and death, placing a significant financial burden on healthcare systems. Fungi were not previously considered a substantial risk to human health, but this perception changed with the rise of the HIV epidemic. The emergence of drug-resistant fungal strains further complicates the management of these infections, highlighting the urgent need for effective antifungal therapies. Innovative approaches in antifungal drug delivery formulations. This article explores the role of effective antifungal drug delivery formulations in combating the rise of IFIs. These formulations, ranging from lipid-based systems like liposomes and lipid emulsions to polymeric nanoparticles and microparticles, offer several advantages over conventional drug delivery methods. Optimizing these formulations may improve drug efficacy, reduce the risk of drug resistance, and enhance patient outcomes. Furthermore, advancements in nanotechnology and targeted drug delivery systems hold promise in overcoming existing limitations and expanding the scope of antifungal therapies.
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Annual SZ: An Alternative Immunotherapy for COVID-19 and Long COVID
Available online: 20 December 2024More LessSince the outbreak of coronavirus disease 2019 (COVID-19) in late 2019 and early 2020, the identification of drugs to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its symptoms has been a pressing focus of research. Cytokine storm and acute respiratory distress syndrome (ARDS) are the leading causes of mortality following infection. In this review, we discuss immune pathogenesis and four medications, including Remdesivir, Tocilizumab, Dexamethasone, and Annual SZ for COVID-19. A comparison of the effectiveness and therapeutic usage of drugs as reported in clinical trials and reports was made at different disease levels as well. Clinical studies indicate that Annual SZ with mild side effects was more affordable and might be more effective than other medications. Additionally, Annual SZ was capable of reducing the levels of pro-inflammatory cytokines as well as viral attachment and RNA replication.
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Repercussion of SARS-CoV-2 on the Sexual Function in Males: An Updated Review
Available online: 20 December 2024More LessSARS-CoV-2, also called coronavirus causes SARS-CoV-2 or severe acute respiratory syndrome, a highly transmissible disease that has rapidly spread worldwide, straining healthcare systems and leading to a substantial number of fatalities. Interestingly, SARS-CoV-2 has revealed a gender difference, with males dying at a greater rate and with more severe cases than women. It's worth noting that the male reproductive system might be particularly susceptible to damage during periods of moderate to severe sickness, which has been linked to cases of orchitis and erectile dysfunction. Furthermore, SARS-CoV-2 virus particles have been found in the tissues of the testes and penile of both living patients who have recovered from the virus and in post-mortem analyses of males who have died from it. For males who have recovered from SARS-CoV-2, sexual transmission is not a big concern, even though moderate to severe infections may have detrimental effects on male reproductive health. This includes the depletion of germ cells and Leydig cells that leads to a decrease in the formation of sperm, potentially decreasing the release of male sex hormones. These adverse effects may result in issues such as infertility and sexual dysfunction, which are of growing concern for couples looking to conceive or those in need of assisted reproduction. Numerous investigations have examined SARS-CoV-2's effects on male reproductive health from a variety of perspectives. The purpose of this review is to give a general summary of how SARS-CoV-2 has affected male reproductive health.
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The Severity of COVID-19 in Systemic Lupus Erythematosus Patient
Authors: Kishor R. Danao, Vijayshri V. Rokde and Ujwala N. MahajanAvailable online: 20 December 2024More LessAs of early October 2020, the COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, resulted in approximately 35 million cases and one million fatalities worldwide. Systemic lupus erythematosus (SLE) is an autoimmune disease marked by the generation of pathogenic autoantibodies and a lack of tolerance to nuclear self-antigens. Hypocomplementemia, or an abnormal blood complement deficit, is a reliable predictor of infection in SLE patients. Moreover, it has been found that immunoglobulin (Ig), particularly IgG and IgM, is lowered in SLE patients, which may be a factor in their heightened susceptibility to infection. Bloodstream autoantibodies, lymphopenia, aberrant T cells, proinflammatory cytokines, and impaired regulatory systems all lead to an immune response that is aberrant in lupus patients. SLE patients exhibit impaired CD8 T cell responses, including abnormal phagocytosis and chemotaxis. Recent study has shown that COVID-19 infections significantly boost type I interferon responses. Patients with SLE and Covid-19 infection typically get immune-suppressing drugs viz corticosteroids, Janus kinase inhibitors (JAK), and tocilizumab, which improve their immune systems and diminution susceptible to Covid-19 infections.
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Therapeutic Potential of Emodin: A Mini-Review of its Anti-Biofilm and Antimicrobial Effects
Authors: Samane Teymouri, Maryam Pourhajibagher and Abbas BahadorAvailable online: 20 December 2024More LessThe resistance of biofilms to antimicrobial agents presents numerous challenges. The formation of biofilms leads to enhanced resistance to adverse environmental conditions, as well as to antimicrobial agents. Natural compounds have been of interest as potential therapeutic agents. Emodin, a natural anthraquinone compound, has recently attracted attention for its potential as a broad-spectrum antimicrobial agent. This ability could potentially help combat biofilm-associated infections and enhance the effectiveness of antimicrobial therapies. This review was carried out to evaluate the effects of emodin on microbial biofilms, determine its effectiveness in inhibiting and reducing biofilm formation, eradicate biofilms, and examine its antimicrobial effects. Our study shows that the use of emodin as an additional therapeutic agent in combating microbial biofilms holds considerable promise. As researchers continue to investigate how emodin interacts with microbial biofilms, there is excitement about the potential applications of this natural compound in addressing biofilm-related issues. However, it is suggested to pay more attention to evaluating the effects of emodin on microbial biofilms in future studies
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In vitro Anti-biofilm and Anti-adhesion Effects of Lactic Acid Bacteria-derived Biosurfactants against Streptococcus mutans
Authors: Maryam Pourhajibagher and Abbas BahadorAvailable online: 20 December 2024More LessIntroductionBiosurfactants are naturally occurring compounds with various applications, biodegradable, non-toxic, and effective in different conditions. This study focuses on the extraction and evaluation of biosurfactants produced by five strains of lactic acid bacteria (LAB) for their potential to inhibit biofilm formation and adhesion by Streptococcus mutans.
MethodsThe strains of LAB-producing biosurfactants such as Lactobacillus salivarius, L. acidophilus, L. plantarum, L. casei, and L. rhamnosus were confirmed by the hemolysis test. The presence of biosurfactants derived from LAB strains and their molecular composition were confirmed, and their cellular toxicity, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) were investigated. Ultimately, the anti-biofilm and anti-adhesive activities of LAB-derived biosurfactants against S. mutans were determined. Eventually, the effect of biosurfactants on the changes in gene expression associated with biofilm formation of S. mutans was assessed.
All the LAB strains used in this study were biosurfactant producers. The LAB-derived biosurfactants exhibited no cytotoxicity towards the human gingival fibroblast (HGF) cell line. According to the results, the lowest and highest MIC values were observed in the biosurfactants derived from L. rhamnosus and L. plantarum at 0.78 mg/mL and 6.25 mg/mL, respectively. The MBC values for the biosurfactants derived from L. rhamnosus, L. casei, L. salivarius, L. acidophilus, and L. plantarum were 3.12, 3.12, 6.25, 12.5, and 12.5 mg/mL, respectively. The LAB-derived biosurfactants at MBC concentrations exhibited significant inhibitory effects on biofilm formation and adhesion of S. mutans (P<0.05) The highest anti-biofilm and anti-adhesion activities were attributed to the biosurfactants derived from L. plantarum, which were not significantly different from the 0.2% chlorhexidine as a positive control group (P>0.05). Moreover, all biosurfactants could significantly decrease the gene expression level of gtfB (P>0.05).
ResultsThe study found that LAB-derived biosurfactants exhibit significant anti-adhesion and anti-biofilm activities against S. mutans without any observed cellular toxicity towards HGF cells.
ConclusionThese promising bioactive compounds can be utilized as natural antimicrobial agents and biofilm inhibitors to prevent microbial biofilm formation and adhesion in various dental applications, offering a safe and effective alternative for controlling dental biofilms and improving oral health outcomes.
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Serum microRNA Biomarker Expression in HIV and TB: A Concise Overview
Authors: Shweta Kushwaha, Anjana Goel and Ajay Vir SinghAvailable online: 06 November 2024More LessNon-coding RNAs (ncRNAs), specifically MicroRNAs or miRNAs, are now understood to be essential regulators in the complex field of gene expression. By selectively binding to certain mRNA targets, these tiny RNA molecules control the expression of genes., leading to mRNA degradation or translational repression. The discovery of miRNAs has significantly advanced biomedical research, particularly in elucidating the molecular mechanisms underlying various diseases and exploring innovative therapeutic approaches. Recent progress in miRNA research has provided insights into their biogenesis, functional roles, and potential clinical applications. Despite the absence of established methodologies for clinical implementation, miRNAs show great promise as diagnostic and therapeutic agents for a wide array of diseases. Their distinctive attributes, such as high specificity, sensitivity, and accessibility, position them as ideal candidates for biomarker development and targeted therapy. Achieving a comprehensive understanding of miRNA biology and functionality is crucial to fully harnessing their potential in medicine. Ongoing research efforts aim to unravel the intricate mechanisms of miRNA-mediated gene regulation and to develop novel approaches for utilizing miRNAs in disease diagnosis, prognosis, and treatment. This review provides a comprehensive analysis of current knowledge on miRNAs, focusing on their biogenesis, regulatory mechanisms, and potential clinical applications. By synthesizing existing evidence and highlighting key research findings, this review aims to inspire further exploration into the diverse roles of miRNAs in health and disease. Ultimately, this endeavour could result in the development of innovative miRNA-based diagnostic and therapeutic strategies.
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Mucormycosis and COVID-19: Unraveling the Interplay of Fungal Infection in a Global Health Crisis: An Overview
Available online: 31 October 2024More LessThe healthcare system has been greatly affected by the COVID-19 pandemic, resulting in an increase in secondary and co-infections among patients. Factors like pulmonary damage and weakened immune systems make patients more susceptible to fungal infections. Mucormycosis, an opportunistic fungal infection, prospers in environments with limited oxygen, and elevated glucose levels due to conditions such as diabetes and steroid use, as well as in acidic environments from metabolic acidosis and diabetic ketoacidosis, where it demonstrates heightened germination ability. Recognizing these complications is critical to minimize harm to patients. The insights gained from this review can improve our understanding of how fungal infections develop in connection to COVID-19, leading to better predictive algorithms, tailored care plans, enhanced antifungal treatments, quicker diagnostics, and improved management strategies.
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The Role of Epigallocatechin Gallate (EGCG) in the Combating and Treatment of Sexually Transmitted Viral Infections
Authors: Ozge Yilmaz and Alev OnderAvailable online: 30 October 2024More LessTea is obtained from the young leaves and shoots of the evergreen perennial plant Camellia sinensis (L.) Kuntze, the most popular and frequently consumed product using a natural beverage worldwide. Some kinds of tea, including green, black, and oolong, have assorted flavors depending on the manufacturing techniques. Green tea has been studied for many years for its important beneficial effects, such as anticancer, antiobesity, antidiabetes, antiinflammatory, neuroprotective, and cardiovascular effects. These effects are primarily associated with tea polyphenols, and regular consumption has been reported to decrease the incidence of some chronic diseases. Current studies support that green tea catechins play an important role in curing and improving the pathology of many diseases. Epigallocatechin-3-gallate (EGCG) is the most highly found polyphenol in the leaves and is of great interest for its protective role in disease prevention. Therefore, this review presents the efficacy and possible mechanisms of EGCG against sexually transmitted viruses. Moreover, EGCG and its derivatives are recognized as safe and bioactive phytochemicals for external and internal use in preventing and treating viral STIs and other concurrent infections. Multidisciplinary studies are essential to discover cheaper, safer, and more effective treatments using EGCG and its derivatives to improve the toxicity and formulations of viral STI medications.
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Structural Prediction and Antigenic Analysis of ROP18, MIC4, and SAG1 Proteins to Improve Vaccine Design against Toxoplasma gondii: An In silico Approach
Available online: 30 October 2024More LessBackgroundToxoplasmosis is a cosmopolitan infectious disease in warm-blooded mammals that poses a serious worldwide threat due to the lack of effective medications and vaccines.
AimsThe purpose of this study was to design a multi-epitope vaccine using several bioinformatics approaches against the antigens of Toxoplasma gondii (T. gondii).
MethodsThree proteins of T. gondii, including ROP18, MIC4, and SAG1 were analyzed to predict the most dominant B- and T-cell epitopes. Finally, we designed a chimeric immunogen RMS (ROP18, MIC4, and SAG1) using some domains of ROP18 (N377-E546), MIC4 (D302-G471), and SAG1 (T130-L299) linked by rigid linker A (EAAAK) A. Physicochemical properties, secondary and tertiary structure, antigenicity, and allergenicity of RMS were predicted utilizing immunoinformatic tools and servers.
ResultsRMS protein had 545 amino acids with a molecular weight (MW) of 58,833.46 Da and a theoretical isoelectric point (IP) of 6.47. The secondary structure of RMS protein contained 21.28% alpha-helix, 24.59% extended strand, and 54.13% random coil. In addition, evaluation of antigenicity and allergenicity showed the protein to be an immunogen and non-allergen. The results of the Ramachandran plot indicated that 76.4%, 12.9%, and 10.7% of amino acid residues were incorporated in the favored, allowed, and outlier regions respectively. ΔG of the best-predicted mRNA secondary structure was −593.80 kcal/mol which indicates a stable loop is not formed at the 5′ end. .
ConclusionFinally, the accuracy and precision of the in silico analysis must be confirmed by successful heterologous expression and experimental studies. .
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Significant Microbial Pathogenesis Perspective of Biliary Diseases
Available online: 29 October 2024More LessThis review explores various biliary tract diseases caused by different organisms, including cholelithiasis, hepatolithiasis, and choledocholithiasis. The biliary tract's primary functions include collecting, storing, concentrating, and delivering bile juice produced by the liver. Neurohormonal systems involving the vagus and splanchnic nerves, alongside cholecystokinin, regulate gallbladder movement during fasting and digestion. Under normal conditions, bile acids play a crucial role, with approximately 95% being reabsorbed by the intestinal epithelium and returned to the liver via the portal vein system. The liver, often hailed as a miracle worker, detoxifies, purifies, and regenerates, performing essential functions in the body. Recent research indicates that the gallbladder, akin to the intestine, harbors a diverse microbiota. Additionally, the biliary mucosa features chemical, mechanical, and immunological barriers that promote immunological tolerance. Hepatotoxicity remains a significant global health concern and a leading cause of mortality. Providing clear and accurate information on liver toxicity is critical, especially in the context of medication safety and public health. By refining these elements, this review can effectively convey the complexity and importance of biliary tract diseases and liver function in health and disease contexts.
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Acute Febrile Illness in India: An Epidemiological Retrospective Study
Available online: 28 October 2024More LessIntroductionAcute febrile illness (AFI) is a frequent occurrence in India, often complicated by a multitude of pathogenic and etiological factors. In this context, it is important to analyze the biochemical, hematological, and epidemiological clinical parameters of AFI patients in the North Indian population.
MethodsThis study included 1,819 patients of various ages who presented with new-onset acute febrile illness (AFI) between 2017 and 2021. Among these patients, 211, with a median age of 40 years (ranging from 2 to 85 years), were selected for further analysis. At enrollment, clinical examination involved collecting respiratory tract specimens, blood, and urine samples for biochemical analysis, with subsequent data analysis conducted using statistical methods.
Results and DiscussionThe following biochemical parameters were analyzed: C-reactive protein (CRP), alkaline phosphatase (ALP), serum glutamate-pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transpeptidase (GGT), and total protein serum. The hematological parameters included total leukocyte count (TLC), lymphocyte count, monocyte count, eosinophil count, red blood cell count (RBCs), packed cell volume (PCV), erythrocyte sedimentation rate (ESR), hematocrit value, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Additionally, clinical parameters such as phosphorus, urea, calcium, sodium, uric acid, bilirubin, and potassium were measured. Specific values observed were: SGPT (~113 IU/L in 2018), SGOT (~81 U/L in 2019), GGT (~148 g/L in 2018), and total protein serum (~7 g/L in 2020). The hematological parameters (TLC, lymphocyte, monocyte, RBCs, PCV, ESR, MCV, and MCH). The regression analysis was conducted to explore the temperature recorded at the time of admission, the duration of hospital stays, and biochemical as well as hematological variables of patients suffering from AFI. Karl-Pearson's correlation coefficient and variance inflation factor for each variable mentioned above.
ConclusionBiochemical and hematological parameters were analyzed over different years of intake in patients with Acute Febrile Illness (AFI). Further investigation is required to explore the mechanistic pathways of infection, and preventive measures will be implemented using natural products and other therapeutic interventions. Our data will offer the first systematic assessment of the etiological factors, along with regression analysis and the Karl-Pearson correlation coefficient for each variable in AFI patients.
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Antimicrobial Resistance of Environmental V. cholerae Non-O1/O139 Isolates: Systematic Review and Meta-analysis
Available online: 22 October 2024More LessBackgroundThe understanding of the antibiotic resistance status of environmental nonO1/nonO139 V. cholerae [NOVC] in relation to other illnesses, which can vary in severity from mild to life-threatening, is limited. However, it is important to note that NOVC-related infections are increasing and serve as a significant illustration of emerging human diseases associated with climate change. The primary objective of the present study was to assess the rates of resistance observed in environmental NOVC isolates across various years, and regions, and their resistance rates.
MethodsWe performed a systematic search of Scopus, PubMed, Web of Science, and EMBASE databases [until May 2024] following PRISMA guidelines. All statistical analyses were carried out using the statistical package R.
ResultsOur analysis included a total of 34 studies. According to the meta-regression, chloramphenicol, rifampicin, ciprofloxacin, nalidixic acid, cotrimoxazole, kanamycin, trimethoprim, amoxicillin/clavulanic acid, and tetracycline resistance rate increased over time. The lowest resistance rates were observed in Austria [amoxicillin; 0.6%], the United States [kanamycin; 0.1% and tetracycline; 0.1%], Morocco [polymyxin B; 12%], and Spain [trimethoprim; 0.3%]. Conversely, the highest resistance rates were found in Spain [amoxicillin; 61%], Indonesia [kanamycin and tetracycline; 94.9%], India [polymyxin B; 97.8%], and Morocco [trimethoprim; 48.9%].
ConclusionThe meta-analysis showed significant variability in antibiotic resistance patterns among environmental NOVC isolates across time and regions, emphasizing the need for targeted, time-specific, and country-specific approaches to address antibiotic resistance globally.
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Unveiling the Threat: Battling the Resurgence of Western Equine Encephalitis (WEE)
Authors: Balram Singh, Rajesh Gour and Akhlesh Kumar SinghaiAvailable online: 14 October 2024More Less
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The Relationship among SARS-CoV-2, Vaccine Spike Protein, Renin-Angiotensin System, and Epilepsy
Authors: Ziad Fajloun, Layla Tajer, Hervé Kovacic and Jean-Marc SabatierAvailable online: 22 September 2024More Less
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Design of RNA Polymerase Inhibitors as Therapeutics for Tuberculous Meningitis
Authors: Varalakshmi Vummidi and Sekhar TalluriAvailable online: 02 September 2024More LessBackgroundTuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The current treatment protocols for pulmonary tuberculosis are quite effective, even though the treatment requires 3-6 months. The current treatment protocols for extrapulmonary tuberculosis are based on the same drugs that are used for pulmonary tuberculosis. However, the success rates are much lower for certain types of extrapulmonary tuberculosis, such as tuberculous meningitis. Tuberculous meningitis is one of the very few diseases attributable to bacteria that have a very high short-term mortality rate among diagnosed patients, even after treatment with antibiotics that are effective for pulmonary tuberculosis. For example, rifampicin is highly effective for the treatment of pulmonary tuberculosis, but its effectiveness for the treatment of tuberculous meningitis is much lower. The reason for the lower effectiveness of rifampicin against tuberculous meningitis is that it has low Blood-Brain Barrier (BBB) permeability, which results in lower concentrations of the drug at the required sites in the central nervous system.
MethodsIn this work, ligands having increased BBB permeability and pharmacokinetic and pharmacodynamic properties, either similar to or better than that of rifampicin, have been designed. The BBB permeability of the designed molecules was assessed by using pkCSM, a machine-learning model. Pharmacokinetic properties, drug-likeness, and synthesizability were assessed by using SWISS-MODEL. The binding affinity of the designed drugs was assessed by using AutoDock Vina. A customized scoring function, StWN score, was used for a quantitative weighted assessment of all the properties of interest to rank the designed molecules.
ResultsIn this study, drug-like ligands have been designed that have been predicted to have high BBB permeability as well as high affinity for RNA polymerase β of Mycobacterium tuberculosis.
ConclusionThe best ligands generated by the tools employed were selected as potential drugs to address the current need for better options for the treatment of tuberculous meningitis.
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