Antiviral Potential of Traditional Unani Medicine with Special Emphasis on Dengue: A Review.

Dengue fever has become a major public health concern. It is usually related to intravascular leaking, bleeding disorders, and thrombocytopenia and is recognized as a potent threat to humans. The scarcity of anti-dengue medication or vaccine for such a serious disease leads to an upsurge in the usage of traditional medicines for its proper management. India has diverse biodiversity and a long history of using plant-based remedies. Several medicinal plant extracts have been studied for producing anti-dengue viral activity. AYUSH traditional systems provide a plethora of plants that have been reported to be useful in the treatment of fever. Single and compound plant- based formulations in natural form have been used in Unani holistic approaches. This review serves as a new approach to illustrate the most recent evidence regarding the antiviral activity of various plants by providing scientific proof and also to validate the traditional formulations as effective treatments in dengue fever for global acceptance.

Therapeutic Potential of Medicinal Plants against Dengue Infection: A Mechanistic Viewpoint.

Dengue is a tropical disease caused by the Dengue virus (DENV), a positive-sense, single stranded RNA virus of the family Flaviviridae, which is transmitted by Aedes mosquitoes. The occurrence of dengue has grown dramatically around the globe in recent decades, and it is rapidly becoming a global burden. Furthermore, all four DENV serotypes cocirculate and create a problematic hyperendemic situation. Characteristic symptoms range from being asymptomatic, dengue fever to life-threatening complications such as hemorrhagic fever and shock. Apart from the inherent virulence of the virus strain, a dysregulated host immune response makes the condition worse. Currently, there is no highly recommended vaccine or therapeutic agent against dengue. With the advent of virus strains resistant to antiviral agents, there is a constant need for new therapies to be developed. Since time immemorial, human civilization has utilized plants in traditional medicine to treat various diseases, including infectious viral diseases. With the advancement in molecular biology, cell biology techniques, and bioinformatics, recent studies have tried to provide scientific evidence and determine the mechanism of anti-dengue activity of various plant extracts and plant-derived agents. The current Review consolidates the studies on the last 20 years of in vitro and in vivo experiments on the ethnomedicinal plants used against the dengue virus. Several active phytoconstituents like quercetin, castanospermine, α-mangostin, schisandrin-A, hirsutin have been found to be promising to inhibition of all the four DENV serotypes. However, novel therapeutics need to be reassessed in relevant cells using high-throughput techniques. Further, in vivo dose optimization for the immunomodulatory and antiviral activity should be examined on a vast sample size. Such a Review should help take the knowledge forward, validate it, and use medicinal plants in different combinations targeting multiple stages of virus infection for more effective multipronged therapy against dengue infection.

Risk factors and outcomes associated with diabetes mellitus in COVID-19 patients: a meta-analytic synthesis of observational studies.

Purpose: We carried out a meta-analytic synthesis to evaluate the association between diabetes mellitus (DM) and related clinical outcomes, co-morbidities, their risk factors and resource utilization in patients with COVID-19. Methods: The MEDLINE and Web of Science databases were reviewed for identification of eligible studies. Meta-analysis was carried out using Review Manager 5.3. The random- effects model was used to compute the pooled estimates of odds ratio (OR)/mean difference and 95% confidence interval (CI). Results: A total of 14 studies including 3,644 individuals without DM and 1,428 with DM were included in the meta-analysis. Cardiovascular diseases (CVDs) [OR 2.91, 95% CI 2.34, 3.63], hypertension [OR 2.19, 95% CI 1.39, 3.46], acute kidney injury (AKI) [OR 3.59, 95% CI 1.46, 8.84], cerebrovascular disease [OR 2.09, 95% CI 1.22, 3.61], and acute respiratory distress syndrome (ARDS) [OR 3.40, 95% CI 2.09, 5.55] were significantly associated with DM in COVID-19 patients compared with non-DM patients (p < 0.05 for all instances). Mortality was significantly higher among COVID-19 patients with DM [OR 2.46, 95% CI 1.68, 3.58]. Intensive Care Unit (ICU) admission and use of mechanical ventilation were significantly associated with COVID-19 patients with DM [OR 2.79, 95% CI 1.79, 4.34], and [OR 3.33, 95% CI 2.05, 5.42], respectively. No significant difference was observed in the length of stay (LOS) and hospitalization. Conclusions: This meta-analysis shows that CVDs, hypertension, AKI, cerebrovascular disease, and ARDS are significantly higher among DM patients with COVID-19 compared with non-DM patients. Mortality, ICU admission and the use of mechanical ventilation were significantly associated with COVID-19 patients with DM. Further long-term, multinational and large sample size clinical studies are warranted to justify the current findings.

Role of the Serine/Threonine Kinase 11 (STK11) or Liver Kinase B1 (LKB1) Gene in Peutz-Jeghers Syndrome.

Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps and characteristic mucocutaneous freckling. PJS is an autosomal prevailing disease, due to genetic mutation on chromosome 19p, manifested by restricted mucocutaneous melanosis in association with gastrointestinal (GI) polyposis. The gene for PJS has recently been shown to be a serine/threonine kinase, known as LKB1 or STK11, which maps to chromosome subband 19p13.3. This gene has a putative coding region of 1302 bp, divided into nine exons, and acts as a tumor suppressor in the hamartomatous polyps of PJS patients and in the other neoplasms that develop in PJS patients. It is probable that these neoplasms develop from hamartomas, but it remains possible that the LKB1 or STK11 locus plays a role in a different genetic pathway of tumor growth in the cancers of PJS patients. This article focuses on the role of LKB1 or STK11 gene expression in PJS and related cancers.

No association between proton pump inhibitor use and risk of dementia: Evidence from a meta-analysis.

BACKGROUND AND AIM: A growing body of literature suggests the association between dementia risk and proton pump inhibitor (PPI) use. Therefore, we aimed to investigate the association between PPI use and dementia risk. METHODS: An extensive literature search was performed in PubMed, Embase, and Cochrane till March 31, 2019. All the studies (cohort and case-control) assessing the association between PPI use and dementia risk were eligible for inclusion. Articles were selected based on the screening of title and abstract, data were extracted, and risk of bias was assessed using Newcastle-Ottawa scale. The primary outcome was pooled risk of dementia among PPI user as compared with non-PPI user. Secondary outcomes include dementia risk based on subgroups. Statistical analysis was performed using review manager software. RESULTS: Twelve studies (eight cohort and four case-control) were found to be eligible for inclusion. Majority of the studies were of high quality. Dementia was diagnosed based on International Classification of Diseases 9/10 codes in majority of the included studies. PPI use was not associated with the dementia risk, with a pooled relative risk (RR) of 1.05 (95% confidence interval [CI]: 0.96-1.15), P = 0.31. Subgroup analysis based on study design (cohort: P = 0.14; case-control: P = 0.14), sex (RR 1.25 [95% CI: 0.97-1.60], P = 0.08), histamine 2 receptor antagonist blockers (P = 0.93), and Alzheimer's disease (RR 1.00 [95% CI: 0.91-1.09], P = 0.93) revealed no significant association between PPI use and dementia risk. CONCLUSION: We found no significant association between PPI use and the risk of dementia or Alzheimer's disease.

Molecular signaling of G-protein-coupled receptor in chronic heart failure and associated complications.

The well-known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and ß and three distinct subtypes of ß receptor: ß1-, ß2-, and ß3-adrenoceptors. The ß adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin-converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1-7)/Mas receptor axis also shows protective role via Gi ßγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G-protein-coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G-protein-mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart.