Infectious disorders drug targets最新文献

Background: Co-infection of SARS-CoV-2 and HIV presents unique challenges for patients, including potential barriers to accessing care and social support. In the present case report, an unexpected revelation of HIV status was made in an asymptomatic individual who was concurrently infected with SARS-CoV-2. There is insufficient information on asymptomatic but SARS-CoV-2-positive carriers, who have been identified only because of contact tracing and surveillance. Asymptomatic individuals co-infected with SARS-CoV-2 and HIV pose a significant challenge, not only for the patients and their families, but also for the broader community, highlighting the need for enhanced awareness, testing, and contact tracing strategies.

Case presentation: This study reports a case of a routine surveillance-based asymptomatic patient who was consistently SARS-CoV-2 positive from June to August 2021 by real-time PCR. Clinical investigations revealed that all vital parameters and laboratory tests were within normal limits, except for a notable elevation in D-dimer levels. The patient was vaccinated with two doses of Covishield, with the second dose administered during the quarantine period. The patient was followed up after six months, and we came to know that the patient's condition deteriorated in the month of November 2021, and he was tested HIV positive during his admission to a tertiary care hospital. Later on, he died in March 2022.

Conclusion: To our knowledge, this is the first study reporting accidental finding of HIV in a SARS-CoV-2 asymptomatic patient who was previously false negative. The persis-tence of SARS-CoV-2 in this case highlights the importance of comprehensive diagnostic workups and careful clinical management in patients with co-infections. This report also highlights the high risk of silent transmission of SARS-CoV-2 by asymptomatic individu-als, emphasizing the need to include such cases in dynamic surveillance strategies to pre-vent further spread. Along with this, the study highlights the need for further investigation into the interplay between HIV co-infection, COVID-19 vaccination outcomes, and the dynamics of SARS-CoV-2 shedding.

Introduction: Concomitant vulval high-grade squamous intraepithelial lesion (HSIL) and cervical intraepithelial neoplasia (CIN) have rarely been associated in a young woman and should prompt investigation for high-risk Human Papillomavirus (HPV). Conservative treatment strategies for vulval HSIL typically range from skinning vulvectomy to topical applications of immunomodu-lator creams. Imiquimod 5% topical application has been associated with local side effects, including itching and burning. Systemic side effects are extremely rare. The authors report a unique case of generalized lymphadenopathy following topical application of imiquimod 5%.

Case presentation: A 32-year-old, nulligravida woman of Asian ethnicity presented with subfertility. Incidentally, her general examination showed the presence of raised, multifocal, maculopapular le-sions (Bowenoid papulosis) with biopsy showing usual-type vulval high-grade squamous intraepi-thelial lesion (HSIL). After a brief application of topical imiquimod 5%, she developed sudden, tender generalized lymphadenopathy. Aspiration cytology showed caseation necrosis, and she was hence started on anti-tubercular therapy. Resolution of lymphadenopathy was observed at the one-month follow-up.

Discussion: This is the first reported case of acute, tender generalized lymphadenopathy with topical imiquimod in a patient with CIN and vulval HSIL. The underlying mechanism involves alteration of cell-mediated immunity, and the resultant likely functional maturation of epidermal Langerhans cells in vivo is hypothesized. This forms an alternative to surgery, as it is a convenient, self-administered modality that does not affect psychosexual health. Additionally, it has been implicated in HPV virus clearance, unlike surgery, and was hence recommended in this case.

Conclusion: This report underscores this rare phenomenon that can pose a significant therapeutic challenge to clinicians, necessitating regular and long-term follow-up.

Introduction: Fungal infections, despite the protective barrier of the human skin, remain a prevalent issue. These infections are often resistant to synthetic antifungal treatments, which can lead to adverse effects. The objective of this review is to explore the potential of bioactive phyto-components derived from herbs, particularly essential oils, in the treatment and management of fungal infections. The study emphasizes the effectiveness of herbal formulations as a viable alternative to chemical treatments.

Methods: A comprehensive review of existing literature on natural remedies for fungal infections was conducted. The review focused on various bioactive components from natural herbs, especially essential oils, and their antifungal properties. Relevant studies examining the use of these phyto-components in topical formulations, such as creams and ointments, were included. The effectiveness of these treatments was evaluated based on their ability to penetrate the skin and exert antifungal effects.

Results: Several natural herbs were identified as effective in combating fungal infections. Essential oils extracted from these herbs demonstrated significant antifungal activity, particularly when used in topical formulations.

Discussion: These bioactive compounds were found to enhance the absorption of the treatment into the skin, thus improving their efficacy in managing fungal infections. Compared to synthetic antifungal agents, herbal treatments showed promising results with minimal side effects.

Conclusion: Bioactive phyto-components, especially from essential oils of natural herbs, represent a promising alternative for treating fungal infections. They offer several advantages, including improved skin absorption and reduced adverse effects compared to traditional synthetic treatments. Further clinical studies and research are needed to optimize their use and understand their full potential in dermatological applications.

Background: Primary adrenal tuberculosis is a rare but significant cause of adrenal insufficiency (Addison's disease), particularly in regions where tuberculosis remains endemic. The destruction of the adrenal glands due to Mycobacterium tuberculosis leads to hormonal imbalances, which, if undiagnosed, can result in life-threatening adrenal crises.

Case presentation: We report a rare case of a 54-year-old immunocompetent male who presented with progressive weight loss, generalized weakness, and hyperpigmentation over five months. Biochemical investigations revealed hyponatremia, hyperkalemia, low morning cortisol, and elevated adrenocorticotropic hormone (ACTH) levels, confirming primary adrenal insufficiency. Contrast-enhanced computed tomography (CECT) of the abdomen showed bilateral adrenal enlargement with central necrosis. A CT-guided adrenal biopsy revealed caseating granulomas, confirming adrenal TB. The patient was started on a standard anti-tuberculosis treatment (ATT) under the National Tuberculosis Elimination Programme (NTEP) guidelines, along with lifelong hormone replacement therapy.

Conclusion: This case highlights the importance of early diagnosis and prompt intervention in ad-renal TB to prevent complications. Adrenal TB remains a diagnostic challenge due to its nonspecific presentation. A multidisciplinary approach, integrating TB control programs with endocrinology, is vital for improving patient outcomes.

Recent reports indicate an increase in HMPV circulation, which may impact public health systems and have potential implications for India's already burdened healthcare system. HMPV is one of the etiological agents of Acute Respiratory Infections (ARI), especially affecting children, the elderly, and immunocompromised individuals. Its pathophysiology involves epithelial cell infection, cytokine-mediated inflammation, and airway dysfunction, leading to clinical manifestations ranging from mild symptoms to severe respiratory distress. This article outlines strategic directions to address the challenges posed by HMPV in India. Strategic initiatives include enhancing healthcare infrastructure for ARI, integrating HMPV testing into existing surveillance frameworks, and initiating targeted public health campaigns. Working with regional partners and international health organizations helps prioritize the adoption of best practices and enables coordinated responses.

Antimicrobial resistance (AMR) is increasingly threatening the lives of many people, as antibiotics, vital for managing infectious diseases, are no longer as effective. The widespread and inappropriate use of antimicrobial agents in humans, farming, and animal breeding is a major driver of AMR. This study carefully investigates how global cooperation can help control the impact of AMR, primarily by reviewing international policies, partnerships, and strategies against resistant mi-croorganisms. According to our research, global efforts that combine improved surveillance, the pru-dent use of antibiotics, and greater access to healthcare are key to combating the AMR crisis. These efforts underscore the need for increased commitment and action from all countries, particularly those with limited resources. Additionally, the study supports the establishment of robust global monitoring systems, increased funding for research and development of new antimicrobial agents, and raising public awareness. These steps are essential for creating a coordinated and effective global response to the growing challenge of antimicrobial resistance.

Introduction: This study represents the first report of phytochemical investigation and antimicrobial screening of Galium libanoticum endemic to Lebanon. Despite the presence of more than 700 species of the genus Galium, this plant has not been investigated previously. Plants of the genus Galium are well known traditionally for their antioxidant, anti-inflammatory, diuretic, and antimicrobial activities. In this study, we aimed to carry out, for the first time, the phytochemical investigation of G. libanoticum that has not been explored previously.

Methods: Isolation of bioactive compounds was performed using different chromatographic techniques, and the structure identification was achieved using 1H-NMR, 13C-NMR, and 2D NMR spectroscopy.

Results: Results revealed two major components, rutin (1) and asperulosidic acid (2). Both compounds, as well as the crude extract, were evaluated for their antibacterial activity against some common strains. The plant extract showed significant activity against Gram-positive bacteria E. faecalis and S. aureus with MIC of 31.25 μg/mL and 62.5 μg/mL, respectively.

Discussion: This antibacterial activity was higher than that reported from other Galium species, suggesting special chemotypes with different constituents that should be investigated. On the other hand, rutin and asperulosidic acid revealed the highest activity against Gram-negative bacteria.

Conclusion: This study highlighted the medicinal potential of the Galium libanoticum plant and its metabolites and necessitated further studies to isolate the undiscovered constituents that could serve as potential therapeutic remedies, especially in the antimicrobial resistance.

Introduction: Acute respiratory distress syndrome (ARDS) is a severe and life-threatening complication of COVID-19, for which no specific antiviral treatment currently exists. Shenfu Injection (SFI), a traditional Chinese medicine formulation, has shown clinical promise in improving respiratory function and reducing mortality in ARDS patients. However, its underlying molecular mechanisms remain poorly understood.

Methods: A combined network pharmacology and bioinformatics approach was used to elucidate the potential mechanisms of SFI against COVID-19-induced ARDS. SFI-related targets were identified through multiple public databases, followed by Gene Ontology (GO) and KEGG pathway enrichment analyses. Gene expression data from GEO datasets (GSE171110 and GSE273149) were used to identify differentially expressed genes in COVID-19-induced ARDS, which were then intersected with SFI targets. Molecular docking was performed to evaluate the binding affinities between major active compounds in SFI and core viral proteins, including 3CLpro, RdRp, and ACE2.

Results: A total of 398 SFI-associated targets were identified, with key targets including SRC, MAPK1, MAPK3, PIK3R1, and STAT3. Active compounds such as Gomisin B, Deoxyharringtonine, Ginsenoside-Rh4_qt, Suchilactone, and Celabenzine were highlighted. Enrichment analyses identified 2,883 GO terms and 219 KEGG pathways (P < 0.05), primarily involving the PI3K-Akt, MAPK, TNF, NF-κB, and apoptosis signaling pathways. GEO data analysis confirmed the involvement of these pathways in COVID-19-induced ARDS. Molecular docking showed strong binding affinities, particularly between Ginsenoside-Rh4_qt and 3CLpro/ACE2, and Celabenzine with RdRp.

Discussion: The findings suggest that SFI exerts therapeutic effects through modulation of key inflammatory and immune pathways and by direct interaction with SARS-CoV-2 viral proteins. This multi-target mechanism aligns with the pharmacological characteristics of traditional Chinese medicine. However, further experimental validation is required to confirm these computational predictions and assess clinical relevance.

Conclusion: This study provides mechanistic insights into how SFI may alleviate COVID-19-induced ARDS via modulation of critical signaling pathways and interaction with viral targets, offering a theoretical foundation for its clinical application in the management of severe COVID-19 cases.

The Food and Drug Administration (FDA) authorized the topical gel Zelsuvmi on Jan-uary 5, 2024, to treat molluscum contagiosum in children and adults over the age of one. This is the first licensed prescription medication for this highly infectious viral skin illness, primarily af-fecting youngsters. Zelsuvmi produces nitric oxide, which has antiviral properties. The specific treatment method is unclear, but it is believed to involve processes affecting inflammation, immu-nological control, and viral replication. Clinical studies have shown Zelsuvmi to significantly de-crease the number of lesions and be easily tolerated when applied daily. Clinical trials in Phase 3, such as B-SIMPLE 4 and B-SIMPLE 2, were the basis for the FDA's clearance of Zelsuvmi. The treatment is given topically once daily for a maximum duration of 12 weeks. The product is sup-plied in two separate tubes: one contains berdazimer gel and the other contains hydrogel. The most common negative effects of Zelsuvmi are usually experienced in the applied area, such as distress-ing burning, itching, redness, and irritation. Zelsuvmi is anticipated to be commercially accessible in the United States by late 2024, broadening the spectrum of treatment choices for molluscum contagiosum.

Introduction: Dental caries is a prevalent chronic infectious disease primarily associated with Streptococcus mutans. Natural compounds with antimicrobial properties, such as licorice (Glycyrrhiza glabra), offer promising alternatives for oral health care.

Methods: Licorice roots were authenticated by a botanist and processed into an extract. The extract was formulated into an oral gel (100 μg/mL) and sterilized using gamma irradiation. The minimum inhibitory concentration (MIC) of the gel against S. mutans was determined by the agar dilution method. Sub-MIC concentrations were used in a time-kill assay to assess antibacterial efficacy. A reduction of ≥3 log10 CFU/mL was considered indicative of antibacterial activity. Data were ana-lyzed using the Shapiro-Wilk test, Kruskal-Wallis, and Tukey's post hoc test (SPSS v25, p < 0.05).

Results: The MIC of the gel was found to be 1260 μg/mL. Time-kill assays using concentrations of 1.4 and 1.8 μg/mL showed a significant reduction in bacterial count over time, demonstrating effec-tive antibacterial action against S. mutans.

Discussion: The results suggest that even sub-MIC levels of licorice gel can significantly inhibit S. mutans, highlighting its potential for incorporation into preventive or therapeutic oral health products.

Conclusion: Licorice extract gel exhibits promising antimicrobial activity against S. mutans and may be considered a potential natural agent in oral formulations targeting dental caries.