The role of the FACT complex in differentiation of multipotent stem cells

Cellular differentiation is accompanied by dramatic changes in chromatin structure which are associated with the activation of lineage-specific transcriptional programs. Facilitates Chromatin Transcription (FACT) is a histone chaperone complex which is important for chromatin-associated processes such as transcription, DNA replication and DNA repair. However, the role of FACT during differentiation of undifferentiated or stem-cell like cells has not yet been elucidated. We investigated the role of the FACT component Structure Specific Recognition Protein 1 (SSRP1) in adipocyte and osteoblast differentiation. Depletion of SSRP1 in human mesenchymal stem cells (hMSC) elicited lineage-specific effects where the adipocyte-specific genes PPARG, RASD1 and PDK4 were significantly increased while markers of osteoblast differentiation markedly decreased. Consistently, Oil Red O staining was increased during adipocyte differentiation while alkaline phosphatase staining was decreased in osteoblast differentiation following knockdown of SSRP1. Osteoblast differentiation plays a pivotal role in maintenance of bone homeostasis important for different bone-associated diseases including age-related bone loss. Thus this study was further focused on the molecular regulation of SSRP1-mediated effects on osteoblast differentiation. Transcriptome-wide RNA-seq revealed a specific enrichment of down-regulation of the canonical Wnt signaling pathway following SSRP1 depletion in osteoblasts. Furthermore a number of biological processes important for osteoblast differentiation including glycosylation, cell-cell contact, adhesion, extra cellular matrix, ossification, osteoblast differentiation, bone and skeletal development were affected by SSRP1 knockdown. In addition a significant nuclear co-localization of SSRP1 and β-catenin was observed where depletion of SSRP1 diminished accumulation of active β-catenin in the nucleus. Together, our data suggest a previously unknown specific role for SSRP1 in promoting the activation of canonical Wnt signaling during lineage-specific differentiation

Detection of lipoprotein(a)- cholesterol expression in Bangladeshi adults with dyslipidemia

Lipoprotein(a)-cholesterol (Lp(a)-C), a low-density lipoprotein (LDL)-like particle is considered as a risk factor for cardiovascular diseases (CVDs). We aimed to investigate the association of Lp(a)-C expression with dyslipidemia among the Bangladeshi population and assess the relationship with cardiovascular risks. In this cross-sectional comparative study, a total of 180 urban males and females between ages 19-65 years were included who were enrolled in a hospital setting of Bangladesh. Participants were selected based on their total cholesterol (TC) level≥200 mg/dl, high density lipoprotein (HDL)-C<40 mg/dl, LDL-C≥140 mg/dl, and triacylglycerol (TG)≥150 mg/dl regardless of race, religion and socioeconomic status. Venous blood was collected from all participants and analyzed. Further, participants’ socio-demographics and body mass index (BMI) were collected. Expression of Lp(a)-C was detected in 22.86% patients with desirable levels (<14 mg/dL) of serum Lp(a)-C. This study suggests that the prevalence of hyperlipidemia and hypertriglyceridemia is high in the Bangladeshi population. Males were found to have lower HDL-C and higher TG than females. and, similar to other ethnic groups, a negative correlation between BMI and HDL-C was found in this population. In addition, Lp(a)-C had a positive correlation with TG which may recommend routine clinical investigation of Lp(a)-C as a biomarker for CVD risk

Global Prevalence of Zika and Chikungunya Coinfection:A Systematic Review and Meta-Analysis

Zika virus (ZIKV) and chikungunya virus (CHIKV) are arthropod-borne viruses with significant pathogenicity, posing a substantial health and economic burden on a global scale. Moreover, ZIKV-CHIKV coinfection imposes additional therapeutic challenges as there is no specific treatment for ZIKV or CHIKV infection. While a growing number of studies have documented the ZIKV-CHIKV coinfection, there is currently a lack of conclusive reports on this coinfection. Therefore, we performed a systematic review and meta-analysis to determine the true statistics of ZIKV-CHIKV coinfection in the global human population. Relevant studies were searched for in PubMed, Scopus, and Google Scholar without limitation in terms of language or publication date. A total of 33 studies containing 41,460 participants were included in this meta-analysis. The study protocol was registered with PROSPERO under the registration number CRD42020176409. The pooled prevalence and confidence intervals of ZIKV-CHIKV coinfection were computed using a random-effects model. The study estimated a combined global prevalence rate of 1.0% [95% CI: 0.7–1.2] for the occurrence of ZIKV-CHIKV coinfection. The region of North America (Mexico, Haiti, and Nicaragua) and the country of Haiti demonstrated maximum prevalence rates of 2.8% [95% CI: 1.5–4.1] and 3.5% [95% CI: 0.2–6.8], respectively. Moreover, the prevalence of coinfection was found to be higher in the paediatric group (2.1% [95% CI: 0.0–4.2]) in comparison with the adult group (0.7% [95% CI: 0.2–1.1]). These findings suggest that the occurrence of ZIKV-CHIKV coinfection varies geographically and by age group. The results of this meta-analysis will guide future investigations seeking to understand the underlying reasons for these variations and the causes of coinfection and to develop targeted prevention and control strategies

Prevalence of Anemia among Children and Adolescents of Bangladesh:A Systematic Review and Meta-Analysis

© 2023 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/ijerph20031786The prevalence of anemia is high among children and adolescents in low- and middle-income countries because of undernutrition resulting from their poor socioeconomic status and lack of knowledge on proper nutrition. We conducted a systematic review and meta-analysis to determine the prevalence of anemia among children and adolescents aged between 6 months and 19 years in Bangladesh. Databases such as PubMed, Scopus, and Google Scholar were searched to identify the studies that reported the prevalence of anemia among children and adolescents. A total of 24 studies, including the data of 14,062 cases, were included in the systematic review and meta-analysis of the time period between 1997 and 2019. The random-effects model was used to calculate the summary estimates. The protocol was registered with PROSPERO (CRD42021246960). The pooled prevalence of anemia, iron deficiency anemia (IDA), and non-severe and severe anemia were 46.8% [95% CI: 36.0–57.6], 13.6% [95% CI: 8.0–19.2], 56.4% [95% CI: 39.6–73.1] and 0.7% [95% CI: 0.1–1.4], respectively. Prevalence of anemia exhibited the highest among the children aged ≤2 years. Briefly, 91.67% of the studies were of high quality. No significant publication bias was found; however, two outlier studies were detected. The prevalence of anemia among children and adolescents was estimated as high in Bangladesh.Published versio

Prevalence and characteristics of fever in adult and paediatric patients with coronavirus disease 2019 (COVID-19):a systematic review and meta-analysis of 17515 patients

BackgroundCoronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 started to spread globally since December 2019 from Wuhan, China. Fever has been observed as one of the most common clinical manifestations, although the prevalence and characteristics of fever in adult and paediatric COVID-19 patients is inconclusive. We aimed to conduct a systematic review and meta-analysis to estimate the overall pooled prevalence of fever and chills in addition to fever characteristics (low, medium, and high temperature) in both adult and paediatric COVID-19 patients.MethodsThe protocol of this systematic review and meta-analysis was registered with PROSPERO (CRD42020176327). PubMed, Scopus, ScienceDirect and Google Scholar databases were searched between 1st December 2019 and 3rd April 2020 without language restrictions. Both adult (≥18 years) and paediatric (ResultsWe identified 2055 studies, of which 197 studies (n = 24266) were included in the systematic review and 167 studies with 17142 adults and 373 paediatrics were included in the meta-analysis. Overall, the pooled prevalence of fever in adult and paediatric COVID-19 patients were 79.43% [95% CI: 77.05-81.80, I2 = 95%] and 45.86% [95% CI: 35.24-56.48, I2 = 78%], respectively. Besides, 14.45% [95% CI: 10.59-18.32, I2 = 88%] of the adult COVID-19 patients were accompanied with chills. In adult COVID-19 patients, the prevalence of medium-grade fever (44.33%) was higher compared to low- (38.16%) and high-grade fever (14.71%). In addition, the risk of both low (RR: 2.34, 95% CI: 1.69-3.22, pConclusionsThe prevalence of fever in adult COVID-19 patients was high, however, 54.14% of paediatric COVID-19 patients did not exhibit fever as an initial clinical feature. Prevalence and risk of low and medium-grade fevers were higher compared to high-grade fever

Mesenchymal Stem Cell Therapy in Multiple Sclerosis:A Systematic Review and Meta-Analysis

© 2024 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/jcm12196311The assurance of safety and effectiveness is a significant focal point in all therapeutic approaches. Although mesenchymal stem cells (MSCs) have been identified as a potential novel therapeutic strategy for multiple sclerosis (MS), existing evidence regarding the effectiveness and safety of this strategy remains inconclusive. Thus, the primary aim of this systematic review and meta-analysis (SRMA) was to comprehensively assess the effectiveness and safety of MSC therapy in individuals diagnosed with MS. A comprehensive search was conducted using appropriate keywords in the PubMed, Scopus, Cochrane, ScienceDirect, and Google Scholar databases to determine the eligible studies. The change in the expanded disability status scale (EDSS) score from baseline to follow-up was used to assess MSC efficacy. The effectiveness of the therapy was assessed using a random-effects model, which calculated the combined prevalence and 95% confidence intervals (CIs) for MS patients who experienced improvement, stability, or worsening of their condition. The protocol was registered in PROSPERO (CRD42020209671). The findings indicate that 40.4% (95% CI: 30.6–50.2) of MS patients exhibited improvements following MSC therapy, 32.8% (95% CI: 25.5–40.1) remained stable, and 18.1% (95% CI: 12.0–24.2) experienced a worsening of their condition. Although no major complications were observed, headaches 57.6 [37.9–77.3] and fever 53.1 [20.7–85.4] were commonly reported as minor adverse events. All of the results reported in this meta-analysis are consistent and credible according to the sensitivity analyses. Regardless of different individual studies, our meta-analysis provides a comprehensive overview showing the potential of MSC therapy as a possible effective treatment strategy for patients with MS.This research received no external funding.Published versio

Vitamin D Status in Patients with Primary Antiphospholipid Syndrome (PAPS):A Systematic Review and Meta-Analysis

Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder, characterised by consistently high levels of antiphospholipid antibodies, thrombosis, and/or pregnancy morbidity. Due to various suspected causes, deficient or insufficient levels of vitamin D in the serum have been reported in patients with PAPS; however, the reports have been sporadic and inconclusive. This systematic review and meta-analysis aimed to comprehensively evaluate the serum vitamin D levels in patients with PAPS compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42019132128) and a systematic literature search was conducted through Google Scholar, PubMed, Web of Science, Scopus, and ScienceDirect databases without restricting language and year. Pooled prevalence, mean difference (MD), and odds ratio (OR) along with 95% confidence intervals (CI) were determined by using a random effects model. Study quality was assessed by the Joana Brigg’s Institute (JBI) protocol and publication bias was evaluated by a trim and fill funnel plot, Begg’s, and Egger’s tests. The pooled prevalence of vitamin D deficiency and insufficiency was found to be 32.2% [95% CI: 16.3–48.2] and 61.5% [95% CI: 40.2–82.8], respectively. Serum levels of vitamin D were considerably lower in the PAPS patients compared to controls (MD: −5.75, 95% CI: −9.73 to −1.77; p = 0.005). Multiple sensitivity analyses showed that the results remained statistically significant, demonstrating the robustness of this meta-analysis. No significant publication bias was detected in determining the MD of serum vitamin D levels in PAPS and controls. In conclusion, PAPS patients had greater rates of vitamin D deficiency or insufficiency, higher frequency of thrombosis, and lower serum vitamin D levels than healthy individuals

BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire

Proper temporal epigenetic regulation of gene expression is essential for cell fate determination and tissue development. The Bromodomain-containing Protein-4 (BRD4) was previously shown to control the transcription of defined subsets of genes in various cell systems. In this study we examined the role of BRD4 in promoting lineage-specific gene expression and show that BRD4 is essential for osteoblast differentiation. Genome-wide analyses demonstrate that BRD4 is recruited to the transcriptional start site of differentiation-induced genes. Unexpectedly, while promoter-proximal BRD4 occupancy correlated with gene expression, genes which displayed moderate expression and promoter-proximal BRD4 occupancy were most highly regulated and sensitive to BRD4 inhibition. Therefore, we examined distal BRD4 occupancy and uncovered a specific co-localization of BRD4 with the transcription factors C/EBPb, TEAD1, FOSL2 and JUND at putative osteoblast-specific enhancers. These findings reveal the intricacies of lineage specification and provide new insight into the context-dependent functions of BRD4