Infectious disorders drug targets最新文献

Introduction: Toxoplasma infection is highly prevalent among patients with different autoimmune diseases, including psoriasis patients. Pyrimethamine is an antiparasitic medication that has a variable treatment response in Toxoplasma-infected patients. This study investigates the demographic, biochemical, and genetic factors influencing the response to pyrimethamine treatment in Toxoplasma gondii-infected psoriasis patients.

Methods: We conducted a comprehensive analysis of 73 patients diagnosed with toxoplasmosis. Demographic characteristics, biochemical lab results, and the serum levels of TNF-α detected by ELISA, and MicroRNA-155 expression were analyzed using real-time PCR with the 2^ΔΔCt method.

Results and discussion: Total cholesterol and bilirubin levels were higher in patients with good responses compared to those in the poor response group, while other biochemical parameters did not exhibit any statistically significant differences. Neither MicroRNA-155 expression nor serum TNF-α levels were found to be significantly associated with treatment response. Univariate and multivariate logistic regression analyses were conducted to assess predictors of treatment response to pyrimethamine.

Conclusion: Biochemical markers play a role in determining the response to pyrimethamine treatment; however, other factors may also contribute. Future research should focus on larger longitudinal studies to validate these findings and explore additional biomarkers.

Introduction: Withania 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.

Methods: The 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.

Results: According 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.

Conclusion: The 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.

Background: Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) can cause acute and chronic viral infections. Due to their higher costs, potential side effects and drug interactions, and associated risks, some patients with HCV and HBV infections may not be able to afford conventional antiviral medications.

Objective: The goal of this review paper is to highlight the advantages of Nigella sativa, or black seeds, in the treatment of patients with HCV and HBV infections.

Methods: Medline/Pubmed/PMC, Scopus, Web of Science, Google Scholar, Science Direct, Ebsco, Embase, and reference lists were searched to locate the research studies that assessed the effects of different black seed (N. sativa) preparations on the telltale signs and symptoms of HCV and HBV infections.

Results: Numerous preclinical and clinical investigations have suggested that black seeds (N. sativa) may be effective against HCV and HBV infections. Furthermore, N. sativa, or black seeds, have demonstrated a range of pleiotropic effects, such as antiviral activity against multiple other viruses and anti-inflammatory, antioxidant, and immunomodulatory properties that can lessen the symptoms and indicators of HCV and HBV infections.

Conclusion: Patients with HCV and HBV infections may benefit from using black seeds (N. sativa) as an adjuvant therapy in addition to conventional therapy. Additional randomized controlled clinical trials would confirm the safety and effectiveness of Nigella sativa (black seeds) in treating HCV and HBV infections.

Background: Shiga Toxin-Producing Escherichia coli (E. coli) O157:H7, capable of causing serious food-borne illnesses, is extensively studied and is known to be transmitted through animal reservoirs or person-to-person contact, leading to severe disease outbreaks. The emergence of antibiotic resistance in these strains, coupled with increased adverse effects of existing therapeutics, underscores the urgent need for alternative therapeutic strategies.

Objective: This study aims to evaluate Glutamate Racemase (MurI protein) of the food-pathogenic E. coli O157:H7 (EC MurI) as a novel drug target. Furthermore, the study seeks to identify new compounds with potential inhibitory effects against this protein.

Methods: Using computational tools, the study identified inhibitor binding sites on EC MurI and identified relevant inhibitors capable of binding to these sites. Molecular docking techniques were employed to assess potential hits, and selected compounds were further analyzed for their structural activity and binding affinity to the protein.

Results: The results of the study revealed that Frigocyclinone and Deslanoside, exhibited the best binding affinity with EC-MurI. Subsequent molecular dynamic (MD) simulations of the selected complexes indicated that both compounds were stable. This suggests that Frigocyclinone and Deslanoside have the potential to serve as potent inhibitors of EC-MurI.

Conclusion: In summary, this study highlights the urgent need for alternative therapies against food-pathogenic E. coli, focusing on E. coli O157:H7. Evaluation of Glutamate Racemase as a drug target identified Frigocyclinone and Deslanoside as promising inhibitors. MD simulations indicated their stability, suggesting their potential as lead molecules for further research and treatment development.

This 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, performi ng 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.

SARS-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, SARSCoV- 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.

Ulcerative colitis is a chronic, idiopathic, inflammatory condition affecting the colon, primarily impacting individuals aged 30 to 40. It typically begins in the rectum and gradually progresses to the proximal regions of the colon, characterized by recurrent and remitting mucosal inflammation. Ulcerative colitis is categorized under inflammatory bowel disease, which encompasses various gastrointestinal tract disorders, but its underlying pathophysiology remains unclear. The development of ulcerative colitis is influenced by a combination of genetic, environmental, and inflammatory factors. The severity of the disease guides the management of ulcerative colitis. Restorative strategies include the use of TNF-α (anti-tumor necrosis factor-alpha) monoclonal antibodies. Janus Kinase inhibitors suppress cell signaling of the innate immune system. As ongoing research continues, the treatment options for ulcerative colitis are continually evolving and improving. Various types of dosage forms (tablets, capsules, suppositories, etc.) are available in the market for managing ulcerative colitis, with the primary goal of achieving and maintaining clinical and endoscopic remission of the disease. Ensuring a high level of patient compliance is crucial when considering the formulation of these dosage forms. This review article seeks to offer a comprehensive understanding of ulcerative colitis while highlighting the existing treatment options on various available dosage forms.

Non-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.

Introduction: Over the past four years, SARS-CoV-2 and COVID-19 have become global health crises, spurring extensive research on virus behavior, complications, and treatments. The virus interacts with a component of the renin-angiotensin system (RAS), altering inflammatory, hypertrophic, and hemodynamic responses via binding to ACE2 found in organs like the heart, lungs, and kidneys.

Objective: This review explores the RAS-COVID-19 interplay, focusing on key molecules like ACE2, Ang-(1-7), and Ang-(1-9), influencing susceptibility, severity, and treatments. It seeks to clarify ACE2's dual role in viral entry and protection and assess the therapeutic potential of balancing Ang-(1-7) and Ang-(1-9) to prevent disease progression and related complications.

Methods: Studies were chosen through a systematic search in databases, such as PubMed, Scopus, and Web of Science. The inclusion criteria were centered on peer-reviewed research that explored the relationship between SARS-CoV-2 and important RAS molecules, including ACE2, Ang-(1-7), and Ang-(1-9), seeking information on therapies, severity, and susceptibility. Non-peer-reviewed articles and those lacking focus on RAS-COVID-19 interplay were excluded. Titles and abstracts were screened, followed by full-text assessment and data extraction for analysis.

Results: Some studies indicate that the peptides Ang-(1-7) and Ang-(1-9) could provide protective effects against heart-related complications by counteracting the harmful impacts of the angiotensin II pathway, which is often exacerbated by SARS-CoV-2. Ang-(1-7) and Ang-(1-9) are recognized for promoting vasodilation, reducing inflammation, and preventing fibrosis, which can mitigate the heart damage typically associated with COVID-19.

Discussion: ACE2, a component of the non-canonical RAS, is closely linked to SARS-CoV-2 and plays a pivotal role in the pathophysiology of COVID-19. Ang-(1-9) and Ang-(1-7) are produced by ACE2 and have demonstrated positive cardiovascular effects. In the context of COVID-19, Ang-(1- 7) has shown protective effects in preclinical studies and clinical trials; however, more evidence is needed to support this effect.

Conclusion: Further research, including clinical trials, is vital to understand and develop precise therapies for COVID-19 and similar infectious diseases.