Correction: Association of SNPs within TMPRSS6 and BMP2 genes with iron deficiency status in Saudi Arabia.

[This corrects the article DOI: 10.1371/journal.pone.0257895.].

In Silico Identification of Hub Genes as Observing Biomarkers for Gastric Cancer Metastasis.

Perception of hub genes engaged in metastatic gastric cancer (mGC) promotes novel ways to diagnose and treat the illness. The goal of this investigation is to recognize the hub genes and reveal its molecular mechanism. In order to explore the potential facts for gastric cancer, the expression profiles of two different datasets were used (GSE161533 and GSE54129). The genes were confirmed to be part of the PPI network for gastric cancer pathogenesis and prognosis. In Cytoscape, the CytoHubba module was used to discover the hub genes. Responsible hub genes were identified. Data from Kaplan-Meier plotter confirmed the predictive value of these distinct genes in various stages of gastric malignancy. Upregulated and downregulated genes were identified to utilize for further analysis. Positive regulation by a host of viral process, positive regulation of granulocyte differentiation, negative regulation of histone H3-K9 methylation were found in DEGs analysis. In addition, five KEGG pathways were identified as an essential enhancer that include nucleotide excision repair; base excision repair; DNA replication; homologous recombination; and complement and coagulation cascades. POLE, BUB1B, POLD4, C3, BLM, CCT7, PRPF31, APEX1, PSMA7, and CDC45 were chosen as hub genes after combining the PPI results. Our study recommends that BUB1B, CCT7, APEX1, PSMA7, and CDC45 might be potential biomarkers for gastric cancer. These biomarkers are upregulated genes. Therefore, suppression of these genes will increase the survival rate in gastric cancer patients.

Curcumin-Based Inhibitors of Thrombosis and Cancer Metastasis Promoting Factor CLEC 2 from Traditional Medicinal Species Curcuma longa.

The CLEC-2 receptor protein belongs to the C-type lectin superfamily of transmembrane receptors that have one or more C-type lectin-like domains. CLEC-2 is a physiological binding receptor of podoplanin (PDPN), which is expressed on specific tumour cell types and involved in tumour cell-induced platelet aggregation and tumour metastasis. CLEC-2 and podoplanin-expressing tumour cells interact to increase angiogenesis, tumour development, and metastasis. CLEC-2 is a hemi-immunoreceptor tyrosine-based activation motif (hemi-ITAM) receptor located on platelets and a subset of dendritic cells that are expressed constitutively. This molecule is secreted by activated platelets around tumours and has been shown to inhibit platelet aggregation and tumour metastasis in colon carcinoma by binding to the surface of tumour cells. Pharmacokinetic studies were carried using a DrugLiTo, and molecular docking was performed using AutoDock Tools 1.5.6 (ADT). Twenty-nine bioactive compounds were included in the study, and four of them, namely, piperine, dihydrocurcumin, bisdemethoxycurcumin, and demothoxycurcumin, showed potential antagonist properties against the target. The resultant best bioactive was compared with commercially available standard drugs. Further, validation of respective compounds with an intensive molecular dynamics simulation was performed using Schrödinger software. To the best of our knowledge, this is the first report on major bioactive found on clove as natural antagonists for CLEC-2 computationally. To further validate the bioactive and delimit the screening process of potential drugs against CLEC-2, in vitro and in vivo studies are needed to prove their efficacy.

Association of SNPs within TMPRSS6 and BMP2 genes with iron deficiency status in Saudi Arabia.

BACKGROUND: Globally, iron-deficiency anemia (IDA) remains a major health obstacle. This health condition has been identified in 47% of pre-school students (aged 0 to 5 years), 42% of pregnant females, and 30% of non-pregnant females (aged 15 to 50 years) worldwide according to the WHO. Environmental and genetic factors play a crucial role in the development of IDA; genetic testing has revealed the association of a number of polymorphisms with iron status and serum ferritin. AIM: The current study aims to reveal the association of TMPRSS6 rs141312 and BMP2 rs235756 with the iron status of females in Saudi Arabia. METHODS: A cohort of 108 female university students aged 18-25 years was randomly selected to participate: 50 healthy and 58 classified as iron deficient. A 3-5 mL sample of blood was collected from each one and analyzed based on hematological and biochemical iron status followed by genotyping by PCR. RESULTS: The genotype distribution of TMPRSS6 rs141312 was 8% (TT), 88% (TC) and 4% (CC) in the healthy group compared with 3.45% (TT), 89.66% (TC) and 6.89% (CC) in the iron-deficient group (P = 0.492), an insignificant difference in the allelic distribution. The genotype distribution of BMP2 rs235756 was 8% (TT), 90% (TC) and 2% (CC) in the healthy group compared with 3.45% (TT), 82.76% (TC) and 13.79% (CC) in iron-deficient group (P = 0.050) and was significantly associated with decreased ferritin status (P = 0.050). In addition, TMPRSS6 rs141312 is significantly (P<0.001) associated with dominant genotypes (TC+CC) and increased risk of IDA while BMP2 rs235756 is significantly (P<0.026) associated with recessive homozygote CC genotypes and increased risk of IDA. CONCLUSION: Our finding potentially helps in the early prediction of iron deficiency in females through the genetic testing.

Prostate cancer and therapeutic challenges.

Prostate cancer (PC) is the most prevalent type of cancer in men worldwide. In Saudi Arabia, the rate of PC is increasing annually. The sex steroid hormones androgens and their receptors have critical roles in PC development and progression. Additionally, apoptosis-related proteins such as heat-shock proteins are vital molecules in PC development. Steroid hormone-deprivation therapies remain the essential treatment for patients with metastatic PCs; however, acquired resistance to hormone deprivation and the transition to PC androgen independence is a major health obstacle. In this review, we aim to detail the roles of androgens, androgen receptors and sex steroid hormones in inducing apoptosis in PC.

Study the association of transmembrane serine protease 6 gene polymorphisms with iron deficiency status in Saudi Arabia.

BACKGROUND: Intheclinical setting, iron deficiencyanaemia(IDA) represents a majorglobalhealthconcern. This health condition is reported in 30% of non-pregnant women, 42% of pregnant women (aged 15-50 years), 12.7% of men (15 years or older) and in 47% of preschool children (aged 0 to 5 years). Several genetic polymorphisms associated with iron status havebeen identified by using genome-wide association studies. AIM: This study aimed to identify the functional polymorphismsrs855791 and rs2111833 in the transmembrane serine protease 6 (TMPRSS6) gene in female university students with IDA inthe Kingdom of Saudi Arabia. METHODS: About 108 female students, aged from 18 to 25 years, were randomly selected and included to this study. Fifty-eightparticipants were iron deficient, and fifty participants were healthy. Blood samples were collected from all participants andassessed based on theirhaematologicaland biochemical iron status indices. Genotyping was carried out byusing PCR. RESULTS: The genotype distribution oftheTMPRSS6rs855791 region in female studentsfromTabuk University,northern Saudi Arabia,was0% (CC), 77.6% (CT) and 22.4% (TT) in the iron-deficient students compared to 2% (CC), 96% (CT) and 2% (TT) in the healthy students,indicating significant differences in the allelic distribution betweentheiron-deficient group andthehealthy group. The genotype distribution of theTMPRSS6rs2111833 polymorphism was 8.6% (GG), 89.7% (GA) and 1.7% (AA) inthe iron-deficient students compared to 6% (GG), 92% (GA) and 2% (AA) in the healthy students,respectively,showing no differences between the iron-deficient group andthehealthy group in allelic distribution. CONCLUSION: Our data demonstrated that theTMPRSS6 polymorphism rs855791 is significantly associated with decreased iron status, whereasTMPRSS6 polymorphismrs2111833 is not linked with iron deficiency status in female university students innorthern Saudi Arabia.