Identification of key claudin genes associated with survival prognosis and diagnosis in colon cancer through integrated bioinformatic analysis

The claudin multigene family is associated with various aberrant physiological and cellular signaling pathways. However, the association of claudins with survival prognosis, signaling pathways, and diagnostic efficacy in colon cancer remains poorly understood.Methods: Through the effective utilization of various bioinformatics methods, including differential gene expression analysis, gene set enrichment analysis protein-protein interaction (PPI) network analysis, survival analysis, single sample gene set enrichment analysis (ssGSEA), mutational variance analysis, and identifying receiver operating characteristic curve of claudins in The Cancer Genome Atlas colon adenocarcinoma (COAD).Results: We found that: CLDN2, CLDN1, CLDN14, CLDN16, CLDN18, CLDN9, CLDN12, and CLDN6 are elevated in COAD. In contrast, the CLDN8, CLDN23, CLDN5, CLDN11, CLDN7, and CLDN15 are downregulated in COAD. By analyzing the public datasets GSE15781 and GSE50760 from NCBI-GEO (https://www.ncbi.nlm.nih.gov/geo/), we have confirmed that CLDN1, CLDN2, and CLDN14 are significantly upregulated and CLDN8 and CLDN23 are significantly downregulated in normal colon, colon adenocarcinoma tumor, and liver metastasis of colon adenocarcinoma tissues from human samples. Various claudins are mutated and found to be associated with diagnostic efficacy in COAD.Conclusion: The claudin gene family is associated with prognosis, immune regulation, signaling pathway regulations, and diagnosis of COAD. These findings may provide new molecular insight into claudins in the treatment of colon cancer

Common Fixed Points for Suzuki-Generalized Nonexpansive Maps

A common fixed point theorem for a pair of maps satisfying condition (C) is proved under certain conditions. We extend the well-knownDeMarr's fixed point theorem to the case of noncommuting family of maps satisfying condition (C). As for an application, an invariant approximation theorem is also derived

The Generalized Weaker (

We introduce the notion of generalized weaker (α-ϕ-φ)-contractive mappings in the context of generalized metric space. We investigate the existence and uniqueness of fixed point of such mappings. Some consequences on existing fixed point theorems are also derived. The presented results generalize, unify, and improve several results in the literature

Therapeutic effect of combination vitamin D3 and siponimod on remyelination and modulate microglia activation in cuprizone mouse model of multiple sclerosis

Stimulation of remyelination is critical for the treatment of multiple sclerosis (MS) to alleviate symptoms and protect the myelin sheath from further damage. The current study aimed to investigate the possible therapeutic effects of combining vitamin D3 (Vit D3) and siponimod (Sipo) on enhancing remyelination and modulating microglia phenotypes in the cuprizone (CPZ) demyelination mouse model. The study was divided into two stages; demyelination (first 5 weeks) and remyelination (last 4 weeks). In the first 5 weeks, 85 mice were randomly divided into two groups, control (n = 20, standard rodent chow) and CPZ (n = 65, 0.3% CPZ mixed with chow for 6 weeks, followed by 3 weeks of standard rodent chow). At week 5, the CPZ group was re-divided into four groups (n = 14) for remyelination stages; untreated CPZ (0.2 ml of CMC orally), CPZ+Vit D3 (800 IU/kg Vit D3 orally), CPZ+Sipo (1.5 mg/kg Sipo orally), and CPZ+Vit D3 (800 IU/kg Vit D3) + Sipo (1.5 mg/kg Sipo orally). Various behavioral tasks were performed to evaluate motor performance. Luxol Fast Blue (LFB) staining, the expression level of myelin basic protein (MBP), and M1/M2 microglia phenotype genes were assessed in the corpus callosum (CC). The results showed that the combination of Vit D3 and Sipo improved behavioral deficits, significantly promoted remyelination, and modulated expression levels of microglia phenotype genes in the CC at early and late remyelination stages. These results demonstrate for the first time that a combination of Vit D3 and Sipo can improve the remyelination process in the cuprizone (CPZ) mouse model by attenuating the M1 microglia phenotype. This may help to improve the treatment of MS patients

Anxiety among adolescents and young adults during COVID-19 pandemic: A multi-country survey

(1) Background: Adolescents-and-young-adults (AYA) are prone to anxiety. This study assessed AYA's level of anxiety during the COVID-19 pandemic; and determined if anxiety levels were associated with country-income and region, socio-demographic profile and medical history of individuals. (2) Methods: A survey collected data from participants in 25 countries. Dependent-variables included general-anxiety level, and independent-variables included medical problems, COVID-19 infection, age, sex, education, and country-income-level and region. A multilevel-multinomial-logistic regression analysis was conducted to determine the association between dependent, and independent-variables. (3) Results: Of the 6989 respondents, 2964 (42.4%) had normal-anxiety, and 2621 (37.5%), 900 (12.9%) and 504 (7.2%) had mild, moderate and severe-anxiety, respectively. Participants from the African region (AFR) had lower odds of mild, moderate and severe than normal-anxiety compared to those from the Eastern-Mediterranean-region (EMR). Also, participants from lower-middle-income-countries (LMICs) had higher odds of mild and moderate than normal-anxiety compared to those from low-income-countries (LICs). Females, older-adolescents, with medical-problems, suspected-but-not-tested-for-COVID-19, and those with friends/family-infected with COVID-19 had significantly greater odds of different anxiety-levels. (4) Conclusions: One-in-five AYA had moderate to severe-anxiety during the COVID-19-pandemic. There were differences in anxiety-levels among AYAs by region and income-level, emphasizing the need for targeted public health interventions based on nationally-identified priorities

Hemorrhagic fever in Saudi Arabia: challenge to public health, effective management and future considerations

Background: Viral hemorrhagic fevers (VHF) refers to a group of febrile illnesses caused by different viruses that result in high mortality in animals and humans. Many risk factors like increased human-animal interactions, climate change, increased mobility of people and limited diagnostic facility have contributed to the rapid spread of VHF. Materials: The history of VHFs in the Saudi Arabian Peninsula has been documented since the 19th century, in which many outbreaks have been reported from the southwestern region of Saudi Arabia. Despite presence of regional network of experts and technical organizations, which expedite support and respond during outbreaks, there are some more challenges that need to be addressed immediately. Gaps in funding, exhaustive and inclusive response plans and improved surveillance systems are some areas of concern in the region which can be dealt productively. This review primarily focusses on the hemorrhagic fevers that are caused by three most common viruses namely, the Alkhurma hemorrhagic fever virus, Rift valley fever virus, and Dengue fever virus. Conclusion: In summary, effective vector control, health education, possible use of vaccine and concerted synchronized efforts between different government organizations and private research institutions will help in planning effective outbreak-prevention and response strategies in future

Effect of growth techniques on the structural, optical and electrical properties of indium doped TiO2thin films

We have investigated the effect of the growth techniques on the structural, the electrically and optically active defects in Indium doped TiO2 thin films grown by pulsed laser deposition (PLD) and sputtering techniques. X-ray diffraction (XRD) and Raman spectroscopy patterns revealed both rutile and anatase phases for the sputtering samples. On the other hand, only the anatase phase was observed for the PLD samples. The photoluminescence (PL) spectra have unveiled several peaks which were explained by defect related optical transitions. Particularly, the PL bands are fully consistent with anatase/rutile TiO2 phases and the formation of In2O3 during the preparation of our samples. It was also observed that at −4 V reverse bias, the PLD samples have lower leakage currents (∼1.4 × 10−7 A) as compared to the sputtering samples (∼5.9 × 10−7 A). In addition, the PLD samples exhibited lower ideality factors and higher barrier heights as compared to those grown by sputtering. Finally, the Deep Level Transient Spectroscopy (DLTS) measurements have shown only one defect in the PLD samples whereas five defects have been detected in the sputtering samples. Therefore, our results provide strong evidence that the PLD technique is better suited for the growth of In-doped TiO2 thin films