Colchicine, COVID-19 and hematological parameters: A meta-analysis.

INTRODUCTION: Colchicine has the potential in reducing patient morbidity and mortality in COVID-19 infection owing to its anti-inflammatory properties. This study aims to determine the efficacy of colchicine in optimizing inflammatory hematological biomarker levels among COVID-19 patients. METHODS: In accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement guidelines, a systematic search was conducted using the following keywords: Colchicine, covid*, SARS-CoV-2, anti-inflammatory, trials, clinical, hematological, laboratory. Databases were searched from December 2019 until August 26, 2021: MEDLINE/PubMed, Web of Science, Cochrane, Scopus, and EMBASE. Other sources were located through ClinicalTrials.Gov, manually searching SAGE, Science Direct, Elsevier, and Google Scholar. The meta-analysis was conducted using Review Manager 5.4. RESULTS: In total, six studies were included, of which four reported c-reactive protein (CRP) standardized mean reductions in the colchicine group (N = 165) as opposed to the control (N = 252; SMD = -0.49, p < 0.001). On noting lactate dehydrogenase (LDH) values post treatment, the colchicine group (N = 204) showed significant reductions at the end of treatment compared to control (N = 290; SMD = -0.85, p < 0.001). Finally, the D-dimer values in colchicine groups (N = 129) compared to control (N = 216) also documented a negative effect size (SMD = -0.9, p < 0.001). CONCLUSION: Colchicine has efficacy in reducing inflammatory biomarkers observed in moderate-to-severe COVID-19 patients. It may be worthwhile to consider monitoring the clinical and laboratory parameters of patients in further trials to consider colchicine as a strong candidate for an adjunct to COVID-19 treatment.

Persea americana seeds improve glycosylation and dyslipidemia in fructose-fed streptozotocin-injected type 2 diabetic male rats.

This work explored the in-vitro phytochemical contents and antidiabetic activity of crude seeds powder of Persea americana (CSSPa) and their in-vivo biochemical effects on glycated hemoglobin, lipid profile and other parameters in type 2 diabetic rats (fructose-STZ model). There were 2 groups of over night fasted rats, control (normal diet) and diabetic (35% Fructose for 6 weeks followed with injection (i.p.) of streptozotocin (STZ) (40mg/kg bw). Diabetic group was further divided into diabetic control, positive control (pioglitazone 15mg) and test (CSSPa 500mg) groups. After the appropriate treatments in each group for 2 weeks fasting glucose level (FGL), serum lipids, insulin, alanine aminotransferase (ALT), creatine Kinase (CK) & uric acid were determined. CSPPa showed presence of alkaloids, flavonoids, phenols etc and potent antidiabetic activity with IC50 13.23±0.76µM. CSPPa treatment showed a significant (p<0.01) decline in lipid profile, while HDL showed significant increase (p<0.01) in test group as compared with positive and diabetic control groups. The serum ALT, CK, uric acid, bilirubin & fasting glucose (fbg) showed significant improvements in test group (p<0.01). Coronary risk index (CRI), Fasting insulin resistance index (FIRI), Percent glycemic change (PGC) and HbA1c values also significantly (p<0.01) improved.

Redefining a new frontier in alkaptonuria therapy with AI-driven drug candidate design via in- silico innovation.

A rare metabolic condition called alkaptonuria (AKU) is caused by a decrease in homogentisate 1,2 dioxygenase (HGO) activity due to a mutation in homogentisate dioxygenase (HGD) gene. Homogentisic acid is a byproduct of the catabolism of tyrosine and phenylalanine that darkens the urine and accumulates in connective tissues which causes an agonizing arthritis. Employing the use of deep learning artificial intelligence (AI) drug design, this study aims to alleviate the current toxicity of the AKU drugs currently in use, particularly nitisinone, by utilizing the natural flavanol kaempferol molecule as a 4-hydroxyphenylpyruvate dioxygenase inhibitor. Kaempferol was employed to generate three effective de novo drug candidates targeting the enzyme 4-hydroxyphenylpyruvate dioxygenase using an AI drug design tool. We present novel AIK formulations in the present study. The AIK's (Artificial Intelligence Kaempferol) examination of drug-likeliness among the three led to its choice as a possible target. The toxicity assessment research of AIK demonstrates that it is not only safer to use than other treatments, but also more efficient. The docking of the AIGT with 4-hydroxyphenylpyruvate dioxygenase, which revealed a binding affinity of around -9.099 kcal/mol, highlights the AIK's potential as a therapeutic candidate. An innovative approach to deal with challenging circumstances is thus presented in this study by new formulations kaempferol that have been meticulously designed by AI. The results of the in vitro tests must be confirmed in vivo, even though AI-designed AIK is effective and sufficiently safe as computed.

The natural breakthrough: phytochemicals as potent therapeutic agents against spinocerebellar ataxia type 3.

There is no FDA-approved drug for neurological disorders like spinocerebellar ataxia type 3. CAG repeats mutation in the ATXN3 gene, causing spinocerebellar ataxia type 3 disease. Symptoms include sleep cycle disturbance, neurophysiological abnormalities, autonomic dysfunctions, and depression. This research focuses on drug discovery against ATXN3 using phytochemicals of different plants. Three phytochemical compounds (flavonoids, diterpenoids, and alkaloids) were used as potential drug candidates and screened against the ATXN3 protein. The 3D structure of ATXN3 protein and phytochemicals were retrieved and validation of the protein was 98.1% Rama favored. The protein binding sites were identified for the interaction by CASTp. ADMET was utilized for the pre-clinical analysis, including solubility, permeability, drug likeliness and toxicity, and chamanetin passed all the ADMET properties to become a lead drug candidate. Boiled egg analysis attested that the ligand could cross the gastrointestinal tract. Pharmacophore analysis showed that chamanetin has many hydrogen acceptors and donors which can form interaction bonds with the receptor proteins. Chamanetin passed all the screening analyses, having good absorption, no violation of Lipinski's rule, nontoxic properties, and good pharmacophore properties. Chamanetin was one of the lead compounds with a - 7.2 kcal/mol binding affinity after screening the phytochemicals. The stimulation of ATXN3 showed stability after 20 ns of interaction in an overall 50 ns MD simulation. Chamanetin (Flavonoid) was predicted to be highly active against ATXN3 with good drug-like properties. In-silico active drug against ATXN3 from a plant source and good pharmacokinetics parameters would be excellent drug therapy for SC3, such as flavonoids (Chamanetin).

Popular Trend of Electronic Cigarettes and Their Adverse Effects on Oral Health.

Electronic cigarettes were originally promoted as a possible tool to assist individuals in quitting smoking, particularly for those who had been tobacco users for an extended period. Compared with traditional tobacco use, these devices were promoted as a safer option. Over the years, it has been proven that conventional cigarettes adversely affect almost all body systems. Owing to the constantly evolving nature of the products and the difficulties in identifying potential e-cigarette effects in traditional tobacco users including combustible and noncombustible forms, studying the impact of e-cigarette usage on oral health is challenging. Although the existing scientific evidence is limited, it indicates that e-cigarette use may have negative effects on oral health. Moreover, the adoption of vaping among young people has increased globally. There is still a lack of awareness regarding the use of e-cigarettes and their associated health complications, especially in developing countries. We aim to sensitize the readers to the pertinent issue, which has clinical and public health significance.

Incidence, predictors, and outcomes of DAPT non-compliance in planned vs. ad hoc PCI in chronic coronary syndrome.

OBJECTIVE: The disruption of dual antiplatelet therapy (DAPT) causes more adverse events after percutaneous coronary intervention (PCI). However, incidence and predictors of DAPT non-compliance are unknown in chronic coronary syndrome patients when compared between planned and ad hoc PCI. METHODS: This investigation was aimed to assess the incidence, predictors, outcomes, and primary mode of non-compliance of DAPT in patients with chronic coronary syndrome undergoing their first PCI. We analyzed the patients between planned (group 1) and ad hoc (group 2) PCI. RESULTS: There were a total of 628 participants in this investigation (370 were in planned PCI and 270 in the ad hoc PCI group). Out of 628 patients, by one month, 10% left DAPT in planned PCI group and 19.7% in ad hoc PCI group (aOR: 0.451, 95% CI: 0.285-0.713, p = 0.001). At 12 months, DAPT non-compliance was significantly more in ad hoc PCI group (52.7% vs. 47.8%; aOR: 0.647 95% CI: 0.470-0.891, p = 0.008). Age > 65 years (p < 0.001), low education status (p = 0.012), residents of rural areas (p < 0.001), ad hoc PCI group (p = 0.036), and angina class II (p = 0.038) were predictors for DAPT non-compliance in this cohort. CONCLUSION: Approximately 5 out of 10 patients disrupt DAPT due to non-compliance. This investigation provides an insight on additional predictors of non-compliance to DAPT, helping us to identify and address specific patient-related factors for disruption.

Comparison of Metformin and Repaglinide Monotherapy in the Treatment of New-Onset Type 2 Diabetes Mellitus.

Objectives We intend to investigate the feasibility of using repaglinide as initial therapy in patients with newly diagnosed type 2 diabetes mellitus naive to the oral anti-hyperglycemic agents by validating the effects of repaglinide on glycemic control (HbA1c) in comparison with metformin monotherapy. Methodology This parallel-controlled, randomized study was carried at the outpatient department of a tertiary care hospital. Two-hundred patients of both genders with newly diagnosed type 2 diabetes mellitus were included. After taking relevant history and physical examination, we drew venous blood samples of each patient and sent them to the institutional laboratory for analysis of fasting blood sugar (FBS) levels, HbA1c, and lipid profile. We divided the patients into two subgroups based on the lottery method. Group A was prescribed metformin, and group B was prescribed repaglinide, while the dosages were adjusted according to the blood sugar levels. All data were analyzed using SPSS Software 25.0 (SPSS Inc., Chicago, USA). We reported the data as means along with the standard error. Results All patients completed the study. There was a decline in fasting blood glucose levels after three months of therapy, both in the metformin (135 mg/dl ± 6 mg/dl versus 115 mg/dl ± 7 mg/dl, p < 0.01) and repaglinide groups (145 ± 6 mg/dl versus 122 ± 6 mg/dl, p < 0.01). Similarly, significant reductions in HbA1c were seen in both metformin (7.12 ± 0.15% versus 6.67 ± 0.06%, p < 0.01) and repaglinide treatment groups (7.83 ± 0.67% versus 6.81 ± 0.07%, p < 0.01). After three months of treatment, body mass index (BMI) was significantly decreased in the metformin group (26.87±1.1 kg/m2 versus 25.11 ± 0.44 kg/m2, p < 0.05). However, the patients in repaglinide group demonstrated a very slight decrease in BMI (27.11 ± 1.6 kg/m2 versus 26.47 ± 0.40 kg/m2). On follow-up, we found a significant decrease in triglyceride levels in both groups (p < 0.01 and p < 0.05. respectively). We also found that only the patients in metformin group showed some improvements in total cholesterol and low-density lipoprotein (LDL) levels (p < 0.05). Conclusion Our study concluded that both metformin and repaglinide have similar anti-hyperglycemic effects. Repaglinide can be prescribed as an alternative drug to metformin in patients with new-onset diabetes mellitus.