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3.
ACS Omega ; 9(34): 36066-36075, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39220532

RESUMO

The goal of this study was to use coevaporation to look into how polyether compounds like mephenesin (MEP) can be encapsulated into the host molecule α-cyclodextrin's nanohydrophobic cage. Fourier transform infrared spectroscopy (FT-IR) investigations, powder X-ray diffraction (PXRD), and 1H NMR were among the spectroscopic techniques used to describe the inclusion complex. Additionally, Job's plot has been utilized to illustrate how MEP is encapsulated with α-cyclodextrin (α-CD) at a 1:1 molar ratio. The thermal stability of MEP increased after encapsulation according to thermogravimetric analysis (TGA) and differential thermal analysis (DTA) experiments. Mephenesin fits into the cavity of α-cyclodextrin in a 1:1 ratio, as observed by molecular docking for the inclusion complex to find the most appropriate orientation. This observation is further supported by the Job plot. Furthermore, a comparison was carried out based on a cell viability study between the medication and its inclusion complex.

4.
J Med Virol ; 96(9): e29920, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39283000

RESUMO

Immune profiling of Nipah virus (NiV) infection survivors is essential for advancing our understanding of NiV pathogenesis, improving diagnostic and therapeutic strategies, and guiding public health efforts to prevent future outbreaks. There is currently limited data available on the immune response to NiV infection. We aimed to elucidate the specific immune mechanisms involved in protection against NiV infection by analyzing the immune profiles of survivors of the Nipah outbreak in Kerala, India 2023. Immune cell populations were quantified and compared between survivors (up to 4 months post onset day of illness) and healthy controls. Statistical analysis was performed to explore associations between immune profiles and clinical outcomes. Immune signatures common to all three cases were: a heretofore undescribed persistent lymphopenia including the CD4+ Treg compartment with the relative expansion of memory Tregs; trends indicative of global leukopenic modulation were observed in monocytes and granulocytes including an expansion of putatively immunosuppressive low-density granulocytes described recently in the context of severe COVID-19; altered mucosal homing with respect to integrin beta-7 (ITGB7) expressing subsets; increased mobilization of activated T-cells (CD4+ and CD8+) and plasmablasts in the early phase of infection. Comparative analysis based on clinical presentation and outcome yielded lower initial viremia, increased activated T-cell responses, expanded plasmablasts, and restoration of ITGB7 expressing CD8+ T-cells as possible protective signatures. This longitudinal study delineates putative protective signatures associated with milder NiV disease. It emphasizes the need for the development of immunotherapeutic interventions such as monoclonal antibodies to blunt early viremia and ameliorate pathogenesis.


Assuntos
Surtos de Doenças , Infecções por Henipavirus , Vírus Nipah , Humanos , Índia/epidemiologia , Vírus Nipah/imunologia , Infecções por Henipavirus/imunologia , Infecções por Henipavirus/epidemiologia , Masculino , Adulto , Feminino , Sobreviventes , Linfócitos T CD8-Positivos/imunologia , Pessoa de Meia-Idade
5.
Heliyon ; 10(16): e36090, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39247371

RESUMO

With an emphasis on memory-type approaches, this study presents a class of estimators specifically designed for estimating population variation in simple random sampling (SRS). The term 'memory-type' pertaining to the use of exponentially weighted moving averages (EWMA) statistic for the estimation, which utilizes the current and past information in temporal surveys. The study provides expressions for the bias and mean square error (MSE) of these estimators and establishes conditions under which their efficiency represses the conventional and other memory-type estimators. The theoretical findings are reinforced through a comprehensive simulation study conducted on hypothetically sampled populations. Additionally, the effectiveness of the proposed estimators is demonstrated utilizing real-life population data. The findings of simulation and real data application show the superiority of the proposed memory type estimator over the existing usual and memory type estimators.

6.
Int J Cardiol ; 414: 132418, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39121919

RESUMO

For many years, clopidogrel has been a commonly utilised antiplatelet drug in the management of coronary artery disease (CAD). It's thought that the CYP2C19 loss of function (LoF) polymorphism causes clopidogrel's poor metabolism, which eventually leads to resistance. Previous research produced extremely divergent and inconsistent results, making it impossible to draw definitive conclusions. Therefore, current, investigation was carried out to obtain definitive evidence from an updated meta-analysis on the connection between CYP2C19 LoF polymorphism and coronary artery event in patients treated with clopidogrel. 52,542 individuals with coronary artery disease who were receiving clopidogrel treatment were included in 87 carefully chosen trials from reliable databases that we used for our meta-analysis. According to our data, those who carry one or more CYP2C19 LoF alleles worldwide are much more likely to experience composite events and coronary artery events than people who do not carry these alleles, especially in Asian populations. Our meta-analysis observed that the global population, particularly Asians receiving clopidogrel treatment, is at risk of recurrent coronary artery events and composite events if they carry the CYP2C19 LoF alleles. Additional research is essential on alternative antiplatelet therapies for individuals who exhibit poor or intermediate metabolic activity. OBJECTIVES: 1.To systematically analyze the current evidence regarding the association of CYP2C19 variants with coronary artery disease (CAD). 2.To conduct a meta-analysis to investigate the association between loss of function (LoF) CYP2C19 modifications and CAD.


Assuntos
Clopidogrel , Doença da Artéria Coronariana , Citocromo P-450 CYP2C19 , Inibidores da Agregação Plaquetária , Humanos , Citocromo P-450 CYP2C19/genética , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Resultado do Tratamento , Mutação com Perda de Função
7.
Clin Exp Dermatol ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141798

RESUMO

INTRODUCTION: Epidermolysis bullosa (EB) encompasses rare hereditary skin conditions marked by skin fragility, nail dystrophy, and minor trauma-induced skin blisters. This study aims to identify genetic variants in Indian EB patients and examine the relationship between genotypic and phenotypic manifestations. MATERIAL AND METHOD: EB patients seen consecutively over a period of 5 years at Outpatient Department of Dermatology. Baseline demographic data, birth history, family history, skin manifestation at birth, past medical history, current cutaneous manifestations, and the evolution of the disease were assessed and recorded. Genetic variants were identified using targeted gene panel sequencing of 23 EB-related genes, and a genetic-phenotype analysis was performed. RESULTS: Our study included 65 patients with EB. Among 65 EB patients, 38 dystrophic EB cases (58.46%), 12 junctional EB (18.46%), 12 epidermolysis bullosa simplex (18.46%), and 3 Kindler EB (4.62%) were reported. Dominant and recessive forms of dystrophic EB accounted for 16.92% and 41.4%, respectively. We identified 75 unique genetic variants, 58.67% newly discovered and 41.33% previously reported. Compound heterozygous variations were more frequent (55.55%) than homozygous ones (44.44%) in recessive dystrophic EB patients. Junctional EB patients harboured LAMB3 gene mutations more frequently, while epidermolysis bullosa simplex patients showed KRT5 and KRT14 gene missense heterozygous mutations. Kindler EB patients had homozygous mutations in the FERTM1 gene. CONCLUSION: Our study unveiled several novel genetic variants; severe phenotypes associated with nonsense genetic variants. These findings offer valuable insights for future clinical assessments and tailored management strategies.

8.
Front Microbiol ; 15: 1388754, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39144223

RESUMO

Integrated pest management (IPM) is a comprehensive approach to managing diseases, focusing on combining various strategies to reduce pathogen populations effectively and in an environmentally conscious way. We investigated the effects of IPM on beneficial microbial populations and its relationship with pathogen populations in both direct-seeded rice (DSR) and transplanted rice (TR) systems. This study demonstrates that IPM practices have significantly higher populations of beneficial microbes, such as Trichoderma harzianum and Pseudomonas fluorescens, and lower level of the pathogen Fusarium verticillioides compared to non-IPM (farmer practices). The average mean population of T. harzianum was 6.38 × 103 CFU/g in IPM compared to 3.22 × 103 CFU/g in non-IPM during 2019 in TR at Bambawad. P. fluorescens mean population in 2019 was significantly higher in IPM (4.67 × 103 CFU/g) than in non-IPM (3.82 × 103 CFU/g) at the Karnal location in DSR. The F. verticillioides populations were significantly lower in IPM fields (9.46 × 103 CFU/g) compared to non-IPM fields (11.48 × 103 CFU/g) during 2017 at Haridwar in TR. Over three years, a significant increase in the populations of beneficial microbes in IPM plots was observed in all three locations of both TR and DSR, highlighting the sustainable impact of IPM practices. Disease dynamics analysis revealed that IPM effectively managed key diseases in both DSR and TR systems, with significant correlations between microbial density and disease severity. A significant positive correlation was recorded between F. verticillioides population and bakanae incidence at all three locations. Sheath blight incidence was negatively correlated with P. fluorescens population in both TR and DSR. In DSR, bacterial blight and brown spot diseases are reduced with the increased population of T. harzianum. Bioagents T. harzianum and P. fluorescens reduced disease incidence, underscoring the role of beneficial microbes in disease suppression and their importance for sustainable production using IPM practices.

9.
Chem Biodivers ; : e202401756, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146235

RESUMO

Diploknema butyracea (Roxb) H.J Lam, also referred as " Kalpavriksha", is commonly known as Gophal, Cheura, or Indian butter tree. It is a deciduous tree with straight trunks of 15-20m in height and white-yellow-coloured fragile flowers with fragrance, found at altitudes of 300-1500 m in the sub-Himalayan region of India, China, Nepal, and Bhutan. Diploknema have 11 taxa and 8 species, out of which 3 species are found in Uttarakhand hills, Sikkim, Darjeeling, Arunachal Pradesh, and Assam. The tree holds significant economic importance, serving various purposes within ethnic communities. Its high lipid content makes it valuable for food, medicine, construction, and the production of various value-added products. The ethno-pharmacological applications encompass treating rheumatism, burns, asthma, and skin conditions. The plant's different components-bark, leaves, flowers, seeds, and fruits-contain  diverse array of phytoconstituents, including alkaloids, tannins, flavonoids, steroids, terpenoids, and palmitic acid, along with essential nutrients like sodium, calcium, potassium, iron, magnesium, zinc, and various sugars which shows diverse pharmacological and therapeutic activities. Beyond traditional uses, Diploknema is important for diverse industrial application in pharmaceuticals, confectionery, nutraceuticals, and cosmetics. Present paper is an attempt to understand comprehensive details on different aspects of this plant to explore new avenues for various value-added products.

10.
Cureus ; 16(7): e64839, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39156446

RESUMO

Introduction Peritrochanteric fractures are defined as extra-articular fractures involving the trochanter and frequent extension into the subtrochanteric region. These fractures exhibit a bimodal distribution in terms of age. These fractures commonly happen in young individuals who experience high-energy trauma, often in combination with other injuries. In contrast, elderly individuals with osteopenia are more prone to fractures caused by low-energy trauma. Methods This study is a prospective investigation that was carried out over 30 months. The study focused on peritrochanteric fractures that were treated using proximal femoral nail antirotation-2 (PFNA-2) as a fixation device. A range of criteria were examined and documented, encompassing the mean duration of surgical procedures, blood loss, the duration of hospitalization, mobility, and any potential post-operative problems. Subsequent assessments were conducted at fixed intervals of two weeks, six weeks, three months, six months, and two years. The functional outcome analysis for all patients involved the utilization of the modified Harris hip score (HHS). Results The study involved 60 cases of peritrochanteric fractures. The average age was 56 years. The most common mode of trauma was trivial fall/slip (46.66%), followed by road traffic accidents (RTA) (31.66%) and falls from height (21.66%). The average operating time was 53.03±5.66 minutes. The average modified Harris hip score was 84.78 with 26.66% excellent, 70% good, and 3.33% fair results. Complications included superficial wound infection (5%), knee stiffness (11.66%), hip pain (8.33%), and shortening (1.66%). Conclusion PFNA-2 is a safe and easy implant option for treating peritrochanteric fractures as it preserves periosteal covering, minimizes blood loss, has a short operative time, and helps in early mobilization. PFNA-2 provides excellent outcomes in patients with peritrochanteric fractures with minimum complication rates compared to all other open methods and is highly recommendable.

11.
Heliyon ; 10(12): e32011, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39183875

RESUMO

This article proposes and discusses a novel approach for generating trigonometric G-families using hybrid generalizers of distributions. The proposed generalizer is constructed by utilizing the tangent trigonometric function and distribution function of base model G ( x ) . The newly proposed family of uni-variate continuous distributions is named the "Lomax Tangent Generalized Family of Distributions (LT-G)" and structural-mathematical-statistical properties are derived. Some special and sub-models of the proposed family are also presented. A Weibull-based model, 'The Lomax Tangent Weibull (LT-W) Distribution," is discussed and the plots of density (pdf) and hazard (hrf) functions are also explained. Model parameter estimates are estimated by employing the maximum likelihood estimation (MLE) procedure. The accuracy of the MLEs is evaluated through Monte Carlo simulation. Last but not least, to demonstrate the flexibility and potential of the proposed distribution, two actual hydrological and strength data sets are analyzed. The obtained results are compared with well-known, competitive, and related existing distributions.

12.
Sci Rep ; 14(1): 18027, 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39098844

RESUMO

Ranked set sampling (RSS) is known to increase the efficiency of the estimators while comparing it with simple random sampling. The problem of missingness creates a gap in the information that needs to be addressed before proceeding for estimation. Negligible amount of work has been carried out to deal with missingness utilizing RSS. This paper proposes some logarithmic type methods of imputation for the estimation of population mean under RSS using auxiliary information. The properties of the suggested imputation procedures are examined. A simulation study is accomplished to show that the proposed imputation procedures exhibit better results in comparison to some of the existing imputation procedures. Few real applications of the proposed imputation procedures is also provided to generalize the simulation study.

13.
Heliyon ; 10(14): e33839, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39092266

RESUMO

This article considers the issue of domain mean estimation utilizing bivariate auxiliary information based enhanced direct and synthetic logarithmic type estimators under simple random sampling (SRS). The expressions of mean square error (MSE) of the proposed estimators are provided to the 1 s t order approximation. The efficiency criteria are derived to exhibit the dominance of the proposed estimators. To exemplify the theoretical results, a simulation study is conducted on a hypothetically drawn trivariate normal population from R programming language. Some applications of the suggested methods are also provided by analyzing the actual data from the municipalities of Sweden and acreage of paddy crop in the Mohanlal Ganj tehsil of the Indian state of Uttar Pradesh. The findings of the simulation and real data application exhibit that the proposed direct and synthetic logarithmic estimators dominate the conventional direct and synthetic mean, ratio, and logarithmic estimators in terms of least MSE and highest percent relative efficiency.

14.
J Ethnopharmacol ; 335: 118655, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39097211

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Abutilon indicum, a shrub of the Malvaceae family, is found abundantly in tropical countries like India. A. indicum is widely used for its high medicinal properties. Traditionally, A. indicum seed powder is consumed to treat piles, constipation, chronic cystitis, gonorrhea, gleet, and pregnancy-related problems. Despite having numerous medicinal properties and widespread traditional use of A. indicum seeds, scientific validation, and toxicity studies have yet to be documented. AIMS OF THE STUDY: The primary objective of this study is to conduct a comprehensive study on phytochemical profiling, in-vitro cytotoxicity, mutagenicity, and in-vivo acute and sub-acute toxicity, and genotoxicity on animal models of methanolic extract of A. indicum seed (MAS). MATERIALS AND METHODS: The qualitative analysis of MAS was explored through FTIR and HR LC-MS. For in-vitro cytotoxicity, the HEK-293 cell line was used, and the TA100 (Staphylococcus typhimurium) bacterial strain was used for the Ames mutagenicity test. A single oral dose of 250, 500, 1000, or 2000 mg/kg body weight of MAS was given to each male and female rat for acute toxicity study and observed for 14 days for any toxicity signs. In the sub-acute toxicity study, 250, 500, or 1000 mg/kg body weight of MAS was administered orally to each rat for 28 days. The experimental animals were weighed weekly, and general behavior was monitored regularly. After 28 days of the experiment, the rats were sacrificed, and different serum biochemical, hematological, and histological analyses were performed. The blood samples of different doses of MAS were used for genotoxicity study through comet assay. RESULTS: FTIR analysis found different functional groups, which indicated the presence of phenolics, flavonoids, and alkaloids. HR LC-MS analysis depicts several components with different biological functions. The cell cytotoxicity and Ames mutagenicity results showed minimal toxicity and mutagenicity up to a certain dose. The acute toxicity study conducted in Wistar albino rats demonstrated zero mortality among the animals, and the LD50 value for seed extract was determined to be 2000 mg/kg body weight. Sub-acute toxicity assessments indicated that the administration of seed extract resulted in no adverse effects at dosages of 250 and 500 mg/kg body weight. However, at higher doses, specifically 1000 mg/kg body weight, the liver of the experimental rats exhibited some toxic effects. In the genotoxicity study, minimal DNA damage was found in 250 and 500 mg/kg doses, respectively, but slightly greater DNA damage was found in 1000 mg/kg doses in both male and female rats. CONCLUSIONS: The consumption of A. indicum seed powder is deemed safe; however, doses exceeding 500 mg/kg body weight may raise concerns regarding use. These findings pave the path for the creation of innovative medicines with improved efficacy and safety profiles.


Assuntos
Malvaceae , Testes de Mutagenicidade , Extratos Vegetais , Sementes , Animais , Extratos Vegetais/toxicidade , Extratos Vegetais/administração & dosagem , Feminino , Sementes/química , Masculino , Humanos , Ratos , Células HEK293 , Malvaceae/química , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Metanol/química , Testes de Toxicidade Aguda , Relação Dose-Resposta a Droga , Sobrevivência Celular/efeitos dos fármacos , Ratos Wistar , Ratos Sprague-Dawley
15.
J Family Med Prim Care ; 13(6): 2354-2356, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39027845

RESUMO

Background: Alpha-1 antitrypsin (AAT) deficiency is a genetic risk factor for chronic obstructive pulmonary disease (COPD) but prevalence data in acutely exacerbated Indian patients is limited. This study determined AAT deficiency rates and correlations with inflammation and lung function among hospitalized patients with COPD. Methods: A total of 106 patients hospitalized for acute COPD exacerbations were prospectively enrolled from June 2016 to February 2018 in Kerala, India, excluding any with known AAT deficiency. Serum AAT levels were quantified and correlated with C-reactive protein (CRP) levels as well as postbronchodilator spirometry. Results: Mean serum AAT level was 1.48 ± 0.27 g/L. No AAT deficiency cases were identified, although AAT and CRP both significantly increased during flares. AAT levels positively correlated with FEV1, FVC, and FEV1/FVC ratios. Patients with lower AAT had worse pulmonary status. Conclusion: Despite finding no AAT deficiency in this regional Indian cohort, further studies across expanded, more diverse populations are warranted to definitively establish prevalence nationwide. Temporal monitoring of AAT kinetics could help gauge exacerbation trajectories.

16.
Mol Neurobiol ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898199

RESUMO

Depression is one of the predominant common mental illnesses that affects millions of people of all ages worldwide. Random mood changes, loss of interest in routine activities, and prevalent unpleasant senses often characterize this common depreciated mental illness. Subjects with depressive disorders have a likelihood of developing cardiovascular complications, diabesity, and stroke. The exact genesis and pathogenesis of this disease are still questionable. A significant proportion of subjects with clinical depression display inadequate response to antidepressant therapies. Hence, clinicians often face challenges in predicting the treatment response. Emerging reports have indicated the association of depression with metabolic alterations. Metabolomics is one of the promising approaches that can offer fresh perspectives into the diagnosis, treatment, and prognosis of depression at the metabolic level. Despite numerous studies exploring metabolite profiles post-pharmacological interventions, a quantitative understanding of consistently altered metabolites is not yet established. The article gives a brief discussion on different biomarkers in depression and the degree to which biomarkers can improve treatment outcomes. In this review article, we have systemically reviewed the role of metabolomics in depression along with current challenges and future perspectives.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38847252

RESUMO

BACKGROUND: Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin receptor agonists (lasmiditan) in the management of migraine. However, the exact safety and efficacy profile of these drugs is unclear so far. METHODS: The study's primary objective was to determine the exact safety and efficacy profile. The overall estimate was calculated in terms of risk ratios using a suitable model. The subgroup analysis was also performed to check the effect of individual drugs on the outcome, whereas sensitivity analysis was performed to check the effects of outliers on the outcome. All the analyses were performed using Rev Man 5. The drugs have shown significant improvement in efficacy parameters (pain freedom, most bothersome symptoms, phonophobia, nausea, and photophobia). RESULTS: The subgroup analysis results have shown significant improvement in all efficacy parameters in the rimegepant and ubrogepant groups. The effect of ubrogepant on safety parameters was found to be non-significant, indicating a better safety profile of ubrogepant than lasmiditan. CONCLUSION: The sensitivity analysis results have shown no effect of outliers on the efficacy parameters. Based on the available evidence, recently approved drugs are effective in the treatment of migraine, however, associated with few adverse drug reactions.

18.
Indian J Otolaryngol Head Neck Surg ; 76(3): 2660-2674, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38883502

RESUMO

Salivary gland tumors are relatively rare and can exhibit various clinical behaviors. The study aims to understand the natural history, pathology, diagnostic workup, and treatment strategies for these tumors to improve patient outcomes. The audit included patients with salivary gland tumors detected through radiology or cytology. Patients underwent surgery, with some receiving adjuvant treatment. Demographic information, treatment interventions, and survival outcomes were analyzed using SPSS software. A total 89 as malignant salivart gland tumours were audited Malignant tumors were predominantly found in the parotid gland, with fewer cases in the minor salivary gland and submandibular gland.The median age of presentation was 47 years, and the majority of patients were male. The study examined various pathological and clinical factors, including tumor stage, nodal status, and the presence of facial palsy. Surgical procedures and histological types of tumors were documented. Adverse histological features like positive margins, lymph node positivity, lympho-vascular invasion, extracapsular spread, and perineural invasion were noted. POSTOP RT was administered to high-risk patients. Most malignant salivary gland tumors were found in the parotid gland, while minor salivary gland tumors were underrepresented in the audit. Surgical practices were diverse. Radiotherapy protocols were relatively standardized. The study found that certain histological features, such as lymph node positivity, margin positivity, lympho-vascular invasion, perineural invasion, and extracapsular spread, were associated with adverse effects on DFS and OS. The findings suggest that specific histological features, including LVI and ECE have emerged as independent prognostic factors for DFS and OS.

19.
Vaccines (Basel) ; 12(5)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38793710

RESUMO

Understanding the antibody response to SARS-CoV-2, the virus responsible for COVID-19, is crucial to comprehending disease progression and the significance of vaccine and therapeutic development. The emergence of highly contagious variants poses a significant challenge to humoral immunity, underscoring the necessity of grasping the intricacies of specific antibodies. This review emphasizes the pivotal role of antibodies in shaping immune responses and their implications for diagnosing, preventing, and treating SARS-CoV-2 infection. It delves into the kinetics and characteristics of the antibody response to SARS-CoV-2 and explores current antibody-based diagnostics, discussing their strengths, clinical utility, and limitations. Furthermore, we underscore the therapeutic potential of SARS-CoV-2-specific antibodies, discussing various antibody-based therapies such as monoclonal antibodies, polyclonal antibodies, anti-cytokines, convalescent plasma, and hyperimmunoglobulin-based therapies. Moreover, we offer insights into antibody responses to SARS-CoV-2 vaccines, emphasizing the significance of neutralizing antibodies in order to confer immunity to SARS-CoV-2, along with emerging variants of concern (VOCs) and circulating Omicron subvariants. We also highlight challenges in the field, such as the risks of antibody-dependent enhancement (ADE) for SARS-CoV-2 antibodies, and shed light on the challenges associated with the original antigenic sin (OAS) effect and long COVID. Overall, this review intends to provide valuable insights, which are crucial to advancing sensitive diagnostic tools, identifying efficient antibody-based therapeutics, and developing effective vaccines to combat the evolving threat of SARS-CoV-2 variants on a global scale.

20.
Drug Dev Res ; 85(4): e22211, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38807372

RESUMO

The World Health Organization (WHO) has published a list of priority pathogens that urgently require research to develop new antibiotics. The main aim of the current study is to identify potential marketed drugs that can be repurposed against bacterial infections. A pharmacovigilance-based drug repurposing approach was used to identify potential drugs. OpenVigil 2.1 tool was used to query the FDA Adverse Event Reporting System database. The reporting odds ratio (ROR) < 1, ROR95CI upper bound <1, and no. of cases ≥30 were used for filtering and sorting of drugs. Sunburst plot was used to represent drugs in a hierarchical order using the Anatomical Therapeutic Chemical classification. Molecular docking and dynamics were performed using the Maestro and Desmond modules of Schrodinger 2023 software respectively. A total of 40 drugs with different classes were identified based on the pharmacovigilance approach which has antibacterial potential. The molecular docking results have shown energetically favored binding conformation of lisinopril against 3-deoxy-manno-octulosonate cytidylyltransferase, UDP-2,3-diacylglucosamine hydrolase, and penicillin-binding protein 3 (PBP3) of Pseudomonas aeruginosa; olmesartan, atorvastatin against lipoteichoic acids flippase LtaA and rosiglitazone and varenicline against  d-alanine ligase of Staphylococcus aureus; valsartan against peptidoglycan deacetylase (SpPgdA) and atorvastatin against CDP-activated ribitol for teichoic acid precursors of Streptococcus pneumoniae. Further, molecular dynamic results have shown the stability of identified drugs in the active site of bacterial targets except lisinopril with PBP3. Lisinopril, olmesartan, atorvastatin, rosiglitazone, varenicline, and valsartan have been identified as potential drugs for repurposing against bacterial infection.


Assuntos
Antibacterianos , Infecções Bacterianas , Mineração de Dados , Reposicionamento de Medicamentos , Simulação de Acoplamento Molecular , Farmacovigilância , Humanos , Antibacterianos/farmacologia , Antibacterianos/efeitos adversos , Antibacterianos/química , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Sistemas de Notificação de Reações Adversas a Medicamentos
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