Recent advances in anti-infective drug discovery最新文献

Multidrug-resistant tuberculosis (MDR-TB) poses a persistent challenge to global health, necessitating continuous efforts to enhance treatment efficacy. Bedaquiline, a cornerstone in MDR-TB management, presents biopharmaceutical challenges that impact its therapeutic potential. This review provides a comprehensive analysis of recent innovations in drug delivery strategies designed to optimize Bedaquiline's efficacy and improve MDR-TB treatment outcomes. Through a systematic examination of various delivery systems, including nanotechnology and formulation advancements, we explore their potential in addressing drug solubility and bioavailability challenges. Emphasizing the integration of Quality by Design (QbD) principles, this review aims to present a cohesive overview of evolving Bedaquiline delivery innovations, providing valuable insights for researchers and healthcare practitioners working towards advancing MDR-TB treatment strategies.

Onychomycosis is regarded as one of the most common and least concerned fungal problems. Although various treatment approaches have been well-established, still treatment strategies suffer from certain drawbacks, so there is a need to discuss novel therapies that could ultimately eliminate all the conventional barriers. It is a nail infection that begins in the toenail and spreads, causing significant negative impacts on patients' quality of life. The purpose of this work was to highlight the limitations of conventional treatments and shed light on novel therapies for managing onychomycosis. A comprehensive review on existing topical and systemic therapies was conducted, with a focus on their drawbacks, such as recurrence and lower efficacy. This review aimed to explore the increasing prevalence of onychomycosis, which poses a serious health issue; however, the advent of nanobased drug delivery systems offers hope for more effective management of this prevalent disease. These systems could potentially overcome the limitations of conventional treatments, thereby improving patient outcomes.

Background: Infestation in greenhouse cucumber with the two-spotted spider mite (Tetranychus urticae Koch) commonly causes severe damage to crop quality and quantity and increases crop production costs.

Objective: This study was conducted to investigate the efficacy of high-abamectinproducing isolates of S. avermitilis against T. urticae-infested cucumber and to assess their impact on biochemical stress markers in these vegetables.

Methods: In this study, 72 non-antagonistic Streptomyces were isolated from rhizospheric soil samples collected from eight different locations in Egypt and screened for their ability to produce the secondary metabolite, abamectin.

Results: The screening process identified two potent abamectin-producing isolates, EW8 and T2, which produced 42.7 and 29.6 μg/L abamectin, respectively, as confirmed by LC-MS/MS analysis. According to DNA sequence analysis of the 16S rRNA gene, these two isolates belong to the species S. avermitilis. The acaricidal activity of either culture suspensions of S. avermitilis strains WE8 and T2, or their extracts containing abamectin, against the mobile stages and egg hatchability of T. urticae was evaluated in the laboratory and the greenhouse. Data on the mortality among the examined female mites and the reduction in their number of eggs point out a potential acaricidal activity of the examined strains of S. avermitilis and their extracts containing abamectin against T. urticaes. Furthermore, the extracts containing abamectin from these two S. avermitilis strains induced oxidative stress in the infested cucumber plants by T. urticaes, as indicated by increased levels of malondialdehyde (MDA). However, the levels of MDA in T. urticae-infested cucumber plants varied depending on the strain and the specific abamectin crude extract used.

Conclusion: S. avermitilis strains T2 or WE8, or their crude extract could be applied in greenhouse cucumber plantations to combat red mite infestation.

Introduction: Recent research has been concentrated on investigating the involvement of Toxoplasma gondii (T. gondii) in the progression of liver disorders. This study aims to investigate the prevalence of T. gondii infection in patients with non-alcoholic fatty liver disease (NAFLD), as well as the effects of toxoplasmosis infection on biological biomarkers such as aspirate transaminase (AST), alanine transaminase (ALT), cholesterol (Chol), and triglyceride (Tg) levels in Sistan, southeast Iran.

Methods: A case-control study was conducted between December 2021 and September 2022. The study included 225 patients diagnosed with NAFLD as the case group and 225 healthy blood donors as the control group. The controls were selected from the same region and were matched with the patients based on gender and age. We collected serum samples from all patients and utilized an enzyme-linked immunosorbent assay to analyze them for the existence of anti-T. gondii IgG antibodies. A questionnaire and medical records were utilized to gather data on the patient's demographic factors.

Results: The prevalence of anti-T. gondii IgG antibodies were 68 (30.2%) in patients with NAFLD, whereas it was 11 (4.88%) in the control group. The seroprevalence of T. gondii in NAFLD patients increased in correlation with age (P < 0.001). The prevalence of NAFLD was significantly greater in the seropositive group compared to the seronegative group (P < 0.001). In addition, the levels of the metabolic markers Chol and Tg were significantly higher in T. gondii seropositive NAFLD patients compared to T. gondii seronegative NAFLD patients.

Conclusion: The findings of this study indicate a high seroprevalence of T. gondii in patients with NAFLD. Further studies are warranted to investigate the underlying mechanisms and potential therapeutic implications of this association.

Background: Tinea infections are superficial fungal infections caused by three species of fungi (i.e. Epidermophyton, Microsporum, and Trichophyton) collectively termed dermatophytes. Dermatophytes are fungi that cause skin, nail bed, and hair infections. These infections are classified based on infection site, including tinea pedis (foot), tinea corporis (body), tinea capitis (head), and tinea cruris (groin). Dermatophytes can spread by direct contact with other people (anthropophilic organisms), animals (zoophilic organisms), and soil (geophilic organisms), as well as indirectly from fomities.

Objective: This review aims to summarize the allopathic drugs along with their mechanism of action and herbal drugs including their parts of the plant used for the treatment of tinea infections.

Methods: The literature review was performed using the following databases: PubMed (https://pubmed.ncbi.nlm.nih.gov/), and Google Scholar (https://scholar.google.com/), to identify the various drugs involved in the treatment of dermatophytosis along with their mechanisms.

Results: The following keywords were applied in the search strategy: "Tinea", "Dermatophytosis", "Ringworm infection", "Pathogenesis of tinea", "Tinea pedis", and "Tinea capitis". This article also reviews several formulations that are available in the market for treating ringworm infection.

Conclusion: The current review provides information about the classification of dermatophytosis based on infection site and environmental habitat, pathogenesis, immunopathogenesis of dermatophytes, and herbals and allopathic drugs used for their treatment.

This review discusses the use of hydrogel systems for intravaginal drug delivery, specifically antibacterial, anti-trichomonas, and anti-fungal regimens for managing and treating gynecological infections, particularly vaginal candidiasis. Nearly 80% of females worldwide have encountered Candida albicans, the root cause of vaginal candidiasis (VC). This infection is manifested by inflammation, itching, erythema, dyspareunia, and pain in the infected vaginal mucosal area. Long-term use of antibiotics, immunosuppressants, contraceptive pills, use of intra-uterine devices, vaginal douching, unprotected sexual intercourse, pregnancy, and hyperglycemic condition are the major factors that affect vaginal flora and may cause VC. Conventional dosage forms, such as creams, ointment, powder, pessaries, etc., are used in VC treatment; however, they have some serious limitations, such as short mucosal contact, rapid vaginal flush or discharge, or poor mucosal absorption. Researchers have developed several novel hydrogel preparations, such as mucoadhesive, pH or temperature-sensitive, or other polymeric hydrogels, to overcome these limitations. Thus, the objective of this study is to provide information on the pathophysiology and diagnosis of VC, and recently developed hydrogels for its treatment, which utilize a sol-gel system where gel formation takes place in vaginal conditions. Drug-exempted systems exhibiting antifungal problems are overcome by hydrogel, which also facilitates their wardship and proper distribution in the vaginal mucosa.

Background: The emergence of resistance to multiple drugs has posed a multitude of difficulties that demand immediate attention and solutions. Multiple drug resistance arises from the accumulation of numerous genes within a single cell, each conferring resistance to a specific drug, and from the heightened expression of genes responsible for multidrug efflux pumps. These pumps effectively expel a diverse array of drugs from the cell.

Objective: The multi-drug-resistant organisms, including methicillin-resistant Staphylococcus aureus, are the hub of numerous diseases, from minute ailments to fatal diseases, like catheter infections. Nowadays, a combination of many antibiotics is given together as a multimodality therapy to cure MRSA infections. However, researchers are exploring novel approaches to find better solutions.

Methods: De novo designing of the peptide sequences has been done through an in silico tool. The peptides were further screened using different computational methods. Following this, the selection was conducted utilizing physicochemical properties as criteria. Molecular docking of the selected peptide sequence was carried out. Based on the highest docking score, the model complex was chosen for validation purposes by conducting studies through molecular dynamics simulations.

Results: A total of fifty-two novel antimicrobial peptides were designed and evaluated based on various parameters, targeting MRSA-specific proteins PBP2a and PVL toxin. Among these designed peptides, the peptide sequence VILRMFYHWAVKTNGP emerged as the optimal candidate, satisfying all the necessary parameters to be an effective antimicrobial peptide.

Conclusion: Molecular docking and MD simulation results showed that the designed peptide sequence could be the possible solution for MRSA treatment.

Medicinal plants are an integral part of the medical system in many countries around the world. Natural products have been used as important biological sources for drug discovery over the past half-century. Alkaloids are a group of natural compounds that contain a basic nitrogen atom. Oxoglaucine is a phytochemical of the oxoaporphines class phytochemical isolated from Aquilegia ecalcarata Maxim, Corydalis yanhusuo, Chasmanthera dependens, and Xylopia aethiopica. The purpose of this study is to analyze all the scientific information about oxoglaucine in order to know the health-beneficial potential of oxoglaucine in medicine. The detailed pharmacological activities of oxoglaucine are analyzed and discussed in this review. The scientific data of the present review about oxoglaucine were collected from PubMed, Scopus, Science Direct, and Google using the terms oxoglaucine, oxoaporphines, alkaloid, phytochemical, pharmacological, and herbal medicine. The scientific findings of the present review article describe the biological importance and therapeutic effectiveness of oxoglaucine in medicine. The present article scientific data signified the biological potential of oxoglaucine against inflammatory diseases, arthritis, osteoarthritis, immune response, enterovirus, and poliovirus. Furthermore, its anticancer, antiaggregation, antifungal, antiprotozoal, and cytotoxic potential are also described in this review article. The scientific information in this article will be helpful to all the scientific peoples of biological science to understand the therapeutic potential of oxoglaucine in medicine.

Background: The recent COVID-19 wave showed a significant rise in mucormycosis, changing its prevalence, particularly in India. Sadly, the total risk of mortality due to COVID-19 associated mucormycosis (CAM) remains high. It may be better to introduce a combination of drugs rather than unacceptable poor outcomes with Amphotericin B monotherapy.

Aim: The aim of this study is to assess the proportion of mucormycosis patient's clinical outcomes with antifungal agent (Amphotericin B of any forms alone) or combination drug therapy (Amphotericin B of any form and Posaconazole).

Methods: It was a retrospective cohort study conducted between April 1st, 2021 and July 31st, 2021 at the tertiary care teaching hospital All India Institutes of Medical Sciences (AIIMS), Raipur.

Results: Out of 271 medical records of CAM patients, 211 records were included in the study. Among them, 46 patients (21.8%) received group 1 treatment i.e. Amphotericin only and 165 patients (78.2%) received group 2 treatment, i.e. Amphotericin B with Posaconazole. Group 2 was associated with a longer time to event, having a higher survival rate. The Hazard Ratio (HR) was 0.22 (95% CI - 0.13-0.36, p-value 0.000).

Conclusion: Our findings will support the need for future studies to determine the efficacy of AMB and posaconazole combination therapy in the treatment of mucormycosis and to produce an evidence-based standard treatment regimen.