In-silico characterization of phytochemicals identified from Vitex negundo (L) extract as potential therapy for Wnt-signaling proteins

Background Colorectal cancer is the third most diagnosed disease in the world population and current chemotherapy has been used for targeting the cell proliferation and metastasizing ability of tumor cells. Potent chemotherapeutic drugs for colorectal cancer are capecitabine, fluorouracil, irinotecan, etc. which have toxic effects in normal tissues and adverse effects in multiple organs leading to major obstacles in clinical use. The aim of the study is the use of plant-derived compounds that improve the effectiveness of chemotherapeutics with lower and alleviate toxic side effects and reduce the risk of tumor progression. Results The current study is performed using Vitex negundo leaf which has been demonstrated to have positive effects against colorectal cancer. The use of computational approaches will help improve the identification and screening of lead molecules using AutoDock 4.2 and AutoDock Vina. Using computational approaches will help to improve lead identification and screening. Herein, we have retrieved six phytochemicals from published literature and investigated their inhibitory effect with Wnt-associated signaling proteins. Authentication of phytocompounds and Wnt-associated signaling proteins was done using AutoDock.4.2. Conclusions The results are screened based on the number of hydrogen bonds, binding energy, and interacting amino acids. The Isoorientin, luteolin, and Chrysophanol get the highest binding energy with target receptors. The binding energy is calculated with all target receptors from the range of − 6.0 to − 8.9 kcal/mol. The In-silico drug likeliness properties are predicted to be the best interacting compounds based on Lipinski Rule of 5 and ADMET analysis. Hence, we propose that Isoorientin, luteolin, and Chrysophanol are the potential inhibitors of Wnt signaling inhibitors, and preclinical studies are needed to confirm the promising therapeutic ability of colorectal cancer.

Role of eNOS and TGFβ1 gene polymorphisms in the development of diabetic nephropathy in type 2 diabetic patients in South Indian population

Background Diabetic nephropathy is known to be a leading complication of diabetes mellitus, characterized by diverse aspects such as high urinary albumin level, elevated blood pressure, and genetic susceptibility leading to end-stage renal disease. The current study was carried out to investigate the association of eNOS and TGFβ1 gene polymorphisms in the progression of diabetic nephropathy among type 2 diabetic patients in the South Indian population. The eNOS and TGFβ1 genetic variants were genotyped in 280 T2DM patients, 140 with DN, 140 without DN, and 140 controls. Genotyping was performed using ARMS PCR and the genomic variants were confirmed by the Sanger sequencing method. Results A significant (p < 0.05) association was observed in the genotypic frequencies of eNOS (G > T) polymorphism in the T2DM patients with diabetic nephropathy when compared to controls. The frequency of TT (heterozygous) genotype was observed to increase in patients with type 2 diabetes and DN when compared to the diabetic patients without DN and controls. This indicates that diabetic patients with TT genotype are at an increased risk to develop DN. However, TGFβ1 (G > C) polymorphism did not show any association in the allele and genotypic frequencies with DN when compared with T2DM and controls. Conclusion The results of the study propose a strong influence of TT genotype of eNOS gene be significantly linked with diabetic nephropathy in T2DM patients. Whereas no association was examined concerning TGFβ1 gene polymorphism and DN. Nevertheless, large sample size studies are required to confirm the part of these genetic variants in the development of DN.

Oral cavity infection by the SARS-CoV-2: emphasizing the essence of masking and peptide therapeutics

The SARS-CoV-2 has infected many people globally with the ravaging COVID-19; a disease, which has become challenging for every aspect of modern healthcare. The saliva and oral mucosa are sites of high risk for increased viral loads, and aside from the usual epithelial functions like lining and protection, the oral mucosa is also specialized for crucial functions, such as secretion, mastication, sensory perception, and taste perception. The human ACE2 receptor has been extensively studied for its essential role in the regulation of blood pressure homeostasis. However, scRNA-Seq studies have revealed high expression levels of the protein in keratinized epithelial surfaces of the oral cavity. The SARS-CoV-2 have access to the host’s body by binding to the ACE2 receptor, leading to the cleavage and major conformational changes in the viral spike glycoprotein for the release of its nucleocapsid into the cellular cytoplasm. This proteolytic cleavage is carried out by the TMPRSS2 and cathepsin L. In this study, we harnessed the information from the binding interface of TMPRSS2 and PAI-1 (a protease inhibitor known to inhibit the TMPRSS2 and several other proteases) to design a potential therapeutic peptide for the inhibition of the TMPRSS2, while also emphasizing the need for preventive masking.

A hybrid systems biology and systems pharmacology investigation of Zingerone’s effects on reconstructed human epidermal tissues

Background As individuals live longer, elderly populations can be expected to face issues. This pattern urges researchers to investigate the aging concept further to produce successful anti-aging agents. In the current study, the effects of Zingerone (a natural compound) on epidermal tissues were analyzed using a bioinformatics approach. Methods For this purpose, we chose the GEO dataset GSE133338 to carry out the systems biology and systems pharmacology approaches, ranging from identifying the differentially expressed genes to analyzing the gene ontology, determining similar structures of Zingerone and their features (i.e., anti-oxidant, anti-inflammatory, and skin disorders), constructing the gene–chemicals network, analyzing gene–disease relationships, and validating significant genes through the evidence presented in the literature. Results The post-processing of the microarray dataset identified thirteen essential genes among control and Zingerone-treated samples. The procedure revealed various structurally similar chemical and herbal compounds with possible skin-related effects. Additionally, we studied the relationships of differentially expressed genes with skin-related diseases and validated their direct connections with skin disorders the evidence available in the literature. Also, the analysis of the microarray profiling dataset revealed the critical role of interleukins as a part of the cytokines family on skin aging progress. Conclusions Zingerone, and potentially any constituents of Zingerone (e.g., their similar compound scan functionality), can be used as therapeutic agents in managing skin disorders such as skin aging. However, the beneficial effects of Zingerone should be assessed in other models (i.e., human or animal) in future studies.

Prevalence of enterotoxin genes (SEA to SEE) and antibacterial resistant pattern of Staphylococcus aureus isolated from clinical specimens in Assiut city of Egypt

Background Infections in communities and hospitals are mostly caused by Staphylococcus aureus strains. This study aimed to determine the prevalence of five genes (SEA, SEB, SEC, SED and SEE) encoding staphylococcal enterotoxins in S. aureus isolates from various clinical specimens, as well as to assess the relationship of these isolates with antibiotic susceptibility. Traditional PCR was used to detect enterotoxin genes, and the ability of isolates expressing these genes was determined using Q.RT-PCR. Results Overall; 61.3% (n = 46) of the samples were positive for S. aureus out of 75 clinical specimens, including urine, abscess, wounds, and nasal swabs. The prevalence of antibiotic resistance showed S. aureus isolates were resistant to Nalidixic acid, Ampicillin and Amoxicillin (100%), Cefuroxime (94%), Ceftriaxone (89%), Ciprofloxacin (87%), Erythromycin and Ceftaxime (85%), Cephalexin and Clarithromycin (83%), Cefaclor (81%), Gentamicin (74%), Ofloxacin (72%), Chloramphenicol(59%), Amoxicillin/Clavulanic acid (54%), while all isolates sensitive to Imipinem (100%). By employing specific PCR, about 39.1% of isolates were harbored enterotoxin genes, enterotoxin A was the most predominant toxin in 32.6% of isolates, enterotoxin B with 4.3% of isolates and enterotoxin A and B were detected jointly in 2.1% of isolates, while enterotoxin C, D and E weren’t detected in any isolate. Conclusion This study revealed a high prevalence of S. aureus among clinical specimens. The isolates were also multidrug resistant to several tested antibiotics. Enterotoxin A was the most prevalent gene among isolates. The presence of antibiotic resistance and enterotoxin genes may facilitate the spread of S. aureus strains and pose a potential threat to public health.

Rare dosage abnormalities flanking the SHOX gene

Background Transcriptional regulation of the SHOX gene is highly complex. Much of our understanding has come from the study of copy number changes of conserved non-coding sequences both upstream and downstream of the gene. Downstream deletions have been frequently reported in patients with Leri–Weill dyschondrosteosis or idiopathic short stature. In contrast, there are only four cases in the literature of upstream deletions that remove regulatory elements. Although duplications flanking the SHOX gene have also been reported, their pathogenicity is more difficult to establish. To further evaluate the role of flanking copy number variants in SHOX-related disorders, we describe nine additional patients from a large SHOX diagnostic cohort. Results The nine cases presented here include five with duplications (two upstream of SHOX and three downstream), one with a downstream triplication and three with upstream deletions. Two of the deletions remove a single conserved non-coding element (CNE-3) while the third does not remove any known regulatory element but is just 4 kb upstream of SHOX, and the deleted region may be important in limb bud development. We also describe six families with novel sequence gains flanking SHOX. Three families had increased dosage of a proposed regulatory element approximately 380 kb downstream of SHOX (X:970,000), including one family with the first ever reported triplication of this region. One family had two in cis downstream duplications co-segregating with LWD, and the two others had a duplication of just the upstream SHOX regulatory element CNE-5. Conclusions This study further extends our knowledge of the range of variants that may potentially cause SHOX-related phenotypes and may aid in determining the clinical significance of similar variants.

The effect of cytokine leukemia-inhibitory factor (LIF) and interleukin-11 (IL-11) gene expression on the primary infertility related to polycystic ovary syndrome, Tubal factor, and Unexplained infertility in Turkish women

Background Successful implantation of blastocysts is indeed an important path in mammalian reproduction that is governed by a complicated web of cytokines interactions. Leukemia inhibitory factor (LIF) and interleukin-11 (IL-11) part of the interleukin (IL)-6 groups are cytokines that are needed for effective implantation and prevent infertility symptoms. This study aimed to determine the expression level (LIF, IL-11) genes in patients with primary infertility related to polycystic ovary syndrome (PCOS), tubal factor infertility (TFI), and unexplained infertility (UI). Results In this study, 75 infertility women and 40 controls were involved. The expressions of LIF and IL-11 genes were evaluated by quantitative real-time polymerase chain reaction qRT–PCR Light Cycler in patients and healthy controls. PCOS, TFI, and UI groups showed promising results regarding LIF gene, which appeared at very small levels compared to the control (p < 0.0001). Regarding IL-11, the two groups TFI and UI were significantly linked to the lower level of gene expression, while the PCOS group has no significant difference when it is compared to the control group (p < 0.0001, < 0.05, 0.19), respectively. Conclusion The current findings show that low levels of LIF and IL-11 gene expression are linked to various primary infertility conditions, including PCOS, tubal factor, and unexplained infertility since they play a fundamental role in embryo implantation.

TaqI polymorphism of the VDR gene: aspects related to the clinical behavior of COVID-19 in Cuban patients

Purpose To determine the relationship between the genotypes of the TaqI polymorphism of VDR gene and the clinical forms of COVID-19 in Cuban patients. Methods TaqI polymorphism was determined by the PCR in 104 Cuban patients, who suffered different clinical forms of COVID-19. Results There was a greater possibility of presenting symptomatic forms [OR = 2.081, 95% CI: 0.243–17.842], even severe [OR = 1.200, 95% CI: 0.217–6.638], related to the tt genotype. Conclusion There are signs of association between the risk of developing COVID-19 and the genotypes of the TaqI polymorphism of the VDR gene in the studied Cuban patients.

Coronavirus disease 19 and risk of hyperglycemia among Iraqi patients

A cross-sectional observational study was conducted on 213 patients with COVID-19 who did not have a clinical history of diabetes at hospital admission. One week after hospitalization, they were stratified by random blood glucose levels. It was found that 25.4, 22.5 and 52.1% of COVID-19 patients were classified as normoglycemia, prediabetes and diabetes, respectively. The study indicated that diabetes may be a risk factor for COVID-19 or the disease may be associated with an increased risk of developing diabetes.