Ficus benghalensis as Potential Inhibitor of 5α-Reductase for Hair Growth Promotion: In Vitro, In Silico, and In Vivo Evaluation

The screening of hair follicles, dermal papilla cells, and keratinocytes through in vitro, in vivo, and histology has previously been reported to combat alopecia. Ficus benghalensis has been used conventionally to cure skin and hair disorders, although its effect on 5α-reductase II is still unknown. Currently, we aim to analyze the phytotherapeutic impact of F. benghalensis leaf extracts (FBLEs) for promoting hair growth in rabbits along with in vitro inhibition of the steroid isozyme 5α-reductase II. The inhibition of 5α-reductase II by FBLEs was assessed by RP-HPLC, using the NADPH cofactor as the reaction initiator and Minoxin (5%) as a positive control. In silico studies were performed using AutoDock Vina to visualize the interaction between 5α-reductase II and the reported phytoconstituents present in FBLEs. Hair growth in female albino rabbits was investigated by applying an oral dose of the FBLE formulation and control drug to the skin once a day. The skin tissues were examined by histology to see hair follicles. Further, FAAS, FTIR, and antioxidants were performed to check the trace elements and secondary metabolites in the FBLEs. The results of RP-HPLC and the binding energies showed that FBLEs reduced the catalytic activity of 5α-reductase II and improved cell proliferation in rabbits. The statistical analysis (p 70%) suggested that hydroalcoholic FBLE has more potential in increasing hair growth by elongating hair follicle’s anagen phase. FAAS, FTIR, and antioxidant experiments revealed sufficient concentrations of Zn, Cu, K, and Fe, together with the presence of polyphenols and scavenging activity in FBLE. Overall, we found that FBLEs are potent in stimulating hair follicle maturation by reducing the 5α-reductase II action, so they may serve as a principal choice in de novo drug designing to treat hair loss

Alleviation of drought stress through foliar application of thiamine in two varieties of pea (Pisum sativum L.)

Drought stress poorly impacts many morphological and physio-biochemical processes in plants. Pea (Pisum sativum L.) plants are highly nutritious crops destined for human consumption; however, their productivity is threatened under drought stress. Thiamine (vitamin B1) is well-known essential micronutrient, acting as a cofactor in key metabolic processes. Therefore, this study was designed to examine the protective effect of foliar application of thiamine (0, 250, and 500 ppm) on two varieties of pea plants under drought stress. Here, we conducted the pot experiment at the Government College Women University, Faisalabad, to investigate the physio-biochemical and morphological traits of two pea varieties (sarsabz and metior) grown under drought stress and thiamine treatment. Drought stress was applied to plants after germination period of 1 month. Results showed that root fresh and dry weight, shoot fresh and dry weight, number of pods, leaf area, total soluble sugars, total phenolics, total protein contents, catalase, peroxidase, and mineral ions were reduced against drought stress. However, the application of thiamine (both 250 and 500 ppm) overcome the stress and also enhances these parameters, and significantly increases the antioxidant activities (catalase and peroxidase). Moreover, the performance of sarsabz was better under control and drought stress conditions than metior variety. In conclusion, the exogenous application of thiamine enabled the plants to withstand drought stress conditions by regulating several physiological and biochemical mechanisms. In agriculture, it is a great latent to alleviate the antagonistic impact of drought stress on crops through the foliar application of thiamine

Mosaic BRAF fusions are a recurrent cause of congenital melanocytic naevi targetable by MEK inhibition

Among children with multiple congenital melanocytic naevi (CMN), 25% have no established genetic cause, of which many develop a hyperproliferative and severely pruritic phenotype resistant to treatment. Gene fusions have been reported in individual cases of CMN. Here, we study 169 CMN patients, 38 of whom were double wild-type for NRAS/BRAF mutations. Nineteen of these 38 patients had sufficient tissue to undergo RNAseq, which revealed mosaic BRAF fusions in 11/19 patients and mosaic RAF1 fusions in 1/19. Recurrently, fusions involved the loss of the 5’ regulatory domain of BRAF or RAF1 but preserved the kinase domain. We validated all cases and detected the fusions in two separate naevi in 5/12 patients, confirming clonality. The absence of the fusion in blood in 8/12 patients indicated mosaicism. Primary culture of BRAF-fusion naevus cells from 3/12 patients demonstrated highly increased MAPK activation, despite only mildly increased BRAF expression, suggesting additional mechanisms of kinase activation. Trametinib quenched MAPK hyperactivation in vitro and treatment of two patients caused rapid improvement in bulk tissue, improving bodily movement, and reducing inflammation and severe pruritus. These findings offer a genetic diagnosis to an additional group of patients and trametinib as a treatment option for the severe associated phenotypes

General public awareness, knowledge and attitude toward COVID-19 infection and prevention: a cross-sectional study from Pakistan [version 2; peer review: 2 approved]

Background: The aim of this study is to evaluate the knowledge, perceptions, and attitude of the public in Pakistan (using social media) towards COVID-19. Methods: A cross-sectional study was conducted amongst 1120 individuals nationwide. A self-developed, pre-tested questionnaire was used that comprised of sections covering demographic characteristics, medical history, hygiene awareness, COVID-19-related knowledge, and learning attitude. Descriptive statistics were used for frequencies, percentages, averages and standard deviations. Inferential statistics were done using the Student’s t-test and ANOVA. Results: The average age of participants was 31 years (range 18-60 years). In total 56 individuals (5%) had completed primary or secondary school education; 448 (40%) were employed (working from home) and 60% were jobless due to the COVID-19 crisis. Almost all the study subjects (1030 (92%)) were washing their hands multiple times a day. A total of 83% had awareness regarding quarantine time, 82% used face masks whenever they left their homes, 98% were aware of the origin of the disease, and 70% had knowledge regarding the most common symptoms of COVID-19. Conclusion: It can be concluded from the current study that female participants had higher level of education, and more awareness regarding the coronavirus. The majority of the participants followed proper hand washing regimes and washed their faces. Further knowledge and awareness should be promoted

Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients

Background: CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2) is an ultra-rare, neurodegenerative lysosomal storage disease, caused by an enzyme deficiency of tripeptidyl peptidase 1 (TPP1). Lack of disease awareness and the non-specificity of presenting symptoms often leads to delayed diagnosis. These guidelines provide robust evidence-based, expert-agreed recommendations on the risks/benefits of disease-modifying treatments and the medical interventions used to manage this condition. Methods: An expert mapping tool process was developed ranking multidisciplinary professionals, with knowledge of CLN2 disease, diagnostic or management experience of CLN2 disease, or family support professionals. Individuals were sequentially approached to identify two chairs, ensuring that the process was transparent and unbiased. A systematic literature review of published evidence using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance was independently and simultaneously conducted to develop key statements based upon the strength of the publications. Clinical care statements formed the basis of an international modified Delphi consensus determination process using the virtual meeting (Within3) online platform which requested experts to agree or disagree with any changes. Statements reaching the consensus mark became the guiding statements within this manuscript, which were subsequently assessed against the Appraisal of Guidelines for Research and Evaluation (AGREEII) criteria. Results: Twenty-one international experts from 7 different specialities, including a patient advocate, were identified. Fifty-three guideline statements were developed covering 13 domains: General Description and Statements, Diagnostics, Clinical Recommendations and Management, Assessments, Interventions and Treatment, Additional Care Considerations, Social Care Considerations, Pain Management, Epilepsy / Seizures, Nutritional Care Interventions, Respiratory Health, Sleep and Rest, and End of Life Care. Consensus was reached after a single round of voting, with one exception which was revised, and agreed by 100% of the SC and achieved 80% consensus in the second voting round. The overall AGREE II assessment score obtained for the development of the guidelines was 5.7 (where 1 represents the lowest quality, and 7 represents the highest quality). Conclusion: This program provides robust evidence- and consensus-driven guidelines that can be used by all healthcare professionals involved in the management of patients with CLN2 disease and other neurodegenerative disorders. This addresses the clinical need to complement other information available

Lack of association between the eNOS rs1800779 (A/G) polymorphism and the myocardial infarction incidence among the Iraqi Kurdish population

Objectives The genetic polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are strongly associated with several cardiovascular diseases (CVDs) in various populations. The current study aimed to investigate the association of the eNOS rs1800779 (A/G) polymorphism with the progress of myocardial infarction (MI). Methods Eighty-five healthy subjects and 80 patients with MI admitted to the Erbil Cardiac Centre in the Kurdistan Region of Iraq were enrolled in the study. All participants were Kurdish from the same ethnic group. The amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used to determine the rs1800779 (A/G) polymorphism of eNOS, and the nitric oxide (NO) serum level was detected by spectrophotometer. Results The genotypic frequencies of the eNOS rs1800779 AA (wild type), AG, and GG were 58.75%, 33.75%, and 7.50%, respectively, in the MI patients, and 49.41%, 43.53%, and 7.06%, respectively, for the control group. The frequencies of the A and the G alleles were 75.6% and 24.4%, respectively, in the MI group, and 71.2% and 28.8%, respectively, in the control subjects. The results revealed a lack of association of the rs1800779 genotype distribution with the level of NO serum and increased risk of MI. Conclusion The study concluded that there is a lack of association between the genotypes and alleles of the rs1800779 eNOS and susceptibility to MI in the studied population

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts