Expression Analysis of Long Noncoding RNA-MALAT1 and Interleukin-6 in Inflammatory Bowel Disease Patients.

 Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1's misregulation has been linked with various autoimmune diseases and regulates proinflammatory cytokines. The role of IL6 in immune-triggered conditions, including IBD, is another focal point. In this research, the expression of MALAT1 and IL6 in IBD patients was meticulously analyzed to uncover potential interactions. The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb. Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6 could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified. This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients.

Conventional Transarterial Chemoembolization Versus Drug-Eluting Beads in Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Hepatocellular carcinoma (HCC) occurs in nearly three-quarters of all primary liver cancers, with the majority not amenable to curative therapies. We therefore aimed to re-evaluate the safety, efficacy, and survival benefits of treating patients with drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE) compared to the conventional transcatheter arterial chemoembolization (C-TACE). Several databases were searched with a strict eligibility criterion for studies reporting on adult patients with unresectable or recurrent HCC. The pooled analysis included 34 studies involving 4841 HCC patients with a median follow-up of 1.5 to 18 months. There were no significant differences between DEB-TACE and C-TACE with regard to complete response, partial response and disease stability. However, disease control (OR: 1.42 (95% CI (1.03,1.96) and objective response (OR: 1.33 (95% CI (0.99, 1.79) were significantly more effective for DEB-TACE treatment with fewer severe complications and all-cause mortality. The pooled-analysis did not find superiority of DEB-TACE in complete or partial response, disease stability, controlling disease progression, and 30 day or end-mortality. However, results showed that DEB-TACE is associated with a better objective response, disease control, and lower all-cause mortality with severe complications compared to C-TACE treatment. Given that the safety outcomes are based on limited studies with a potential for bias, there was no clear improvement of DEB-TACE over C-TACE treatment.

Virus in the pathogenesis of inflammatory bowel disease: role of Toll-like receptor 7/8/3.

The pathogenesis of inflammatory bowel disease (IBD) is influenced by immune system malfunction, particularly innate immune receptors such as toll-like receptors. Furthermore, it is critical to investigate the extremely close association between viruses and IBD incidence. Toll-like receptors (TLRs) 3, 5, and 7 are involved in antiviral immune responses. Finding a relationship between TLR-related virus and IBD is important not only for understanding the disease pathogenesis, but also for developing effective therapies. It has been shown that influenza is expressed more severely in patients with IBD who use immune system inhibitors, and the influenza vaccine is less effective in these patients. In dendritic cells, TLR7 and TLR8 regulate the production of interferons (IFNs) and inflammatory mediators. COVID-19 causes the production of IL-6, possibly due to the induction of TLR pathways. TLR activation by SARS-CoV-2 causes inflammation and IL-1 production, which induces the production of IL-6. Understanding TLR-associated viruses' molecular mechanisms can greatly help improve the quality of life of people with IBD. Therefore, the present study reviewed the role of TLR7, 8, and 3 in inflammatory bowel disease as well as their association with viral infections and evaluated different antagonists for the treatment of IBD.

Effect of COVID-19 on liver abnormalities: a systematic review and meta-analysis.

Emerging evidence suggest association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the development of many liver abnormalities. The overarching aim of this study was therefore to assess the available evidence on the clinical effects of SARS-CoV-2 on the profiles of liver chemistries and coagulation in COVID-19 diagnosed patients. We considered all study designs including epidemiological and observational that reported liver function test abnormalities in patients confirmed with SARS-CoV-2 infection. Medline, Embase databases and Google Scholar as well as relevant reviews were searched to identify appropriate studies from inception to 31st of August 2020. We calculated the pooled mean with 95% confidence intervals (95% CI) through a random-effect model meta-analysis. A total of 35 studies with 10,692 participants were considered for the review from which 23 studies with sufficient quantitative data were included in the meta-analysis. The pooled mean for liver enzymes and coagulation parameters did not significantly change in patients diagnosed with COVID-19 and remained within normal range. Notwithstanding potential bias from confounding factors in interpretation of data in this review, findings from the observational studies and case reports suggest that COVID-19 does not appear to have a significant impact on the transaminases or total bilirubin levels of patients with confirmed SARS-CoV-2 infection. Further controlled studies and larger sample size observational studies are needed with adequate reporting of other liver function parameters are warranted.

Review: The mental health implications for children and adolescents impacted by infectious outbreaks - a systematic review.

BACKGROUND: This systematic review synthesized available research on the psychological implications for children and adolescents who either were directly or indirectly exposed to an infectious outbreak. On this basis, the current paper aims to provide recommendations for future research, practice and policy regarding children during pandemics. METHOD: A total of 2195 records were retrieved from the PsycINFO, SCOPUS and MEDLINE databases, and three from Google Scholar. RESULTS: Including only those papers that focused on children or adolescent's mental health in association with respiratory infectious outbreaks, 11 articles were identified. The majority of research utilized qualitative or retrospective hospital record data. Children and adolescents reported fear and anxiety, as well as disruptions to their day to day routines as a result of outbreaks. However, children were also able to demonstrate resilience during outbreaks with the right support. CONCLUSIONS: Children's psychological response to the outbreak appeared to be largely attributed to how their parents, healthcare providers and the media communicated the event. Recommendations for policy, practitioners and researchers concerning the current COVID-19 outbreak concludes the paper.

Cannabinoids and Prostate Cancer: A Systematic Review of Animal Studies.

Prostate cancer is a major cause of death among men worldwide. Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and differentiation, as well as potential anti-cancer agents. The aim of this review was to evaluate the effect of cannabinoids on in vivo prostate cancer models. The databases searched included PubMed, Embase, Scopus, and Web of Science from inception to August 2020. Articles reporting on the effect of cannabinoids on prostate cancer were deemed eligible. We identified six studies that were all found to be based on in vivo/xenograft animal models. Results: In PC3 and DU145 xenografts, WIN55,212-2 reduced cell proliferation in a dose-dependent manner. Furthermore, in LNCaP xenografts, WIN55,212-2 reduced cell proliferation by 66-69%. PM49, which is a synthetic cannabinoid quinone, was also found to result in a significant inhibition of tumor growth of up to 90% in xenograft models of LNCaP and 40% in xenograft models of PC3 cells, respectively. All studies have reported that the treatment of prostate cancers in in vivo/xenograft models with various cannabinoids decreased the size of the tumor, the outcomes of which depended on the dose and length of treatment. Within the limitation of these identified studies, cannabinoids were shown to reduce the size of prostate cancer tumors in animal models. However, further well-designed and controlled animal studies are warranted to confirm these findings.

Roles of Cannabinoids in Melanoma: Evidence from In Vivo Studies.

Melanoma is the fourth most common type of cancer diagnosed in Australians after breast, prostate, and colorectal cancers. While there has been substantial progress in the treatment of cancer in general, malignant melanoma, in particular, is resistant to existing medical therapies requiring an urgent need to develop effective treatments with lesser side effects. Several studies have shown that "cannabinoids", the major compounds of the Cannabis sativaL. plant, can reduce cell proliferation and induce apoptosis in melanoma cells. Despite prohibited use of Cannabis in most parts of the world, in recent years there have been renewed interests in exploiting the beneficial health effects of the Cannabis plant-derived compounds. Therefore, the aim of this study was in the first instance to review the evidence from in vivo studies on the effects of cannabinoids on melanoma. Systematic searches were carried out in PubMed, Embase, Scopus, and ProQuest Central databases for relevant articles published from inception. From a total of 622 potential studies, six in vivo studies assessing the use of cannabinoids for treatment of melanoma were deemed eligible for the final analysis. The findings revealed cannabinoids, individually or combined, reduced tumor growth and promoted apoptosis and autophagy in melanoma cells. Further preclinical and animal studies are required to determine the underlying mechanisms of cannabinoids-mediated inhibition of cancer-signaling pathways. Well-structured, randomized clinical studies on cannabinoid use in melanoma patients would also be required prior to cannabinoids becoming a viable and recognized therapeutic option for melanoma treatment in patients.

Timing of Tracheostomy in Pediatric Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Tracheostomy is a very common clinical intervention in critically ill adult patients. The indications for tracheostomy procedures in pediatric patients with complex conditions have increased dramatically in recent years, but there are currently no guidelines on the optimal timing of tracheostomy in pediatric patients undergoing prolonged ventilation. DATA SOURCES: We performed a systematic search of the existing literature in MEDLINE via PubMed and Embase databases and the Cochrane Library to identify clinical trials, observational studies, and cohort studies that compare early and late tracheostomy in children. The date of the last search was August 27, 2018. Included articles were subjected to manual searching. STUDY SELECTION: Studies in mechanically ventilated children that compared early with late tracheostomy were included. DATA EXTRACTION: Data were extracted into a spreadsheet and copied into Review Manager 5.3 (The Cochrane Collaboration, Copenhagen, Denmark). DATA SYNTHESIS: Data were meta-analyzed using an inverse variance, random effects model. Continuous outcomes were calculated as mean differences with 95% CIs, and dichotomous outcomes were calculated as Mantel-Haenszel risk ratios with 95% CIs. We included eight studies (10 study arms). These studies were all retrospective cohort studies. Early tracheostomy was associated with significant reductions in mortality, days on mechanical ventilation, and length of intensive care and total hospital stay, although the lack of randomized, controlled trials limits the validity of these findings. Although variance was imputed for some studies, these conclusions did not change after removing these studies from the analysis. CONCLUSIONS: In children on mechanical ventilation, early tracheostomy may improve important medical outcomes. However, our data demonstrate the urgent need for high-quality, randomized controlled trials in the pediatric population.

Acute effects of dietary plant nutrients on transcriptome profiles: evidence from human studies.

The health benefits of long-term dietary plant ingestion are well-established. However, literature on acute nutritional challenges is very limited. This study aimed to identify available evidence on transcriptomics responses to acute ingestion of plants or plant extracts and identify signature gene profiles that may serve as biomarkers of health status. We systematically searched electronic databases and extracted information based-on inclusion criteria such as human clinical studies, single plant-based nutrients and outcomes reported on acute transcriptome responses. A total of 11 studies reported on acute intake of plant dietary interventions. Four studies investigating natural oil extracts with three reporting on whole plants and two studies on natural plant-derived extracts. Gene expression was found to be associated with immune response (7 studies), inflammation (9 studies), metabolism (8 studies), cellular processes and cancer. The finding of this systematic review suggests that acute ingestion may significantly impact diverse physiological and pathological pathways including inflammatory, immune, cancer and oxidative stress pathways. Transcriptomics approach is proven to be an effective strategy in discovery of these anticipated mechanisms. Further studies are now required to validate and continue exploring the short-term health impact of dietary plants and their bioactive phytochemicals on gene expression and function.

The Clinical Efficacy and Safety of Tulsi in Humans: A Systematic Review of the Literature.

Tulsi, also known as holy basil, is indigenous to the Indian continent and highly revered for its medicinal uses within the Ayurvedic and Siddha medical systems. Many in vitro, animal and human studies attest to tulsi having multiple therapeutic actions including adaptogenic, antimicrobial, anti-inflammatory, cardioprotective, and immunomodulatory effects, yet to date there are no systematic reviews of human research on tulsi's clinical efficacy and safety. We conducted a comprehensive literature review of human studies that reported on a clinical outcome after ingestion of tulsi. We searched for studies published in books, theses, conference proceedings, and electronic databases including Cochrane Library, Google Scholar, Embase, Medline, PubMed, Science Direct, and Indian Medical databases. A total of 24 studies were identified that reported therapeutic effects on metabolic disorders, cardiovascular disease, immunity, and neurocognition. All studies reported favourable clinical outcomes with no studies reporting any significant adverse events. The reviewed studies reinforce traditional uses and suggest tulsi is an effective treatment for lifestyle-related chronic diseases including diabetes, metabolic syndrome, and psychological stress. Further studies are required to explore mechanisms of action, clarify the dosage and dose form, and determine the populations most likely to benefit from tulsi's therapeutic effects.

Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence.

Pierre Robin sequence (PRS) is an important subgroup of cleft palate. We report several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06-1.23 Mb upstream of SOX9, and microdeletions both approximately 1.5 Mb centromeric and approximately 1.5 Mb telomeric of SOX9. We have also identified a heterozygous point mutation in an evolutionarily conserved region of DNA with in vitro and in vivo features of a developmental enhancer. This enhancer is centromeric to the breakpoint cluster and maps within one of the microdeletion regions. The mutation abrogates the in vitro enhancer function and alters binding of the transcription factor MSX1 as compared to the wild-type sequence. In the developing mouse mandible, the 3-Mb region bounded by the microdeletions shows a regionally specific chromatin decompaction in cells expressing Sox9. Some cases of PRS may thus result from developmental misexpression of SOX9 due to disruption of very-long-range cis-regulatory elements.