Effect of probiotics on children with autism spectrum disorders: a meta-analysis.

BACKGROUND: Researches have found that alteration of intestinal flora may be closely related to the development of autism spectrum disorder (ASD). However, whether probiotics supplementation has a protective effect on ASD remains controversial. This meta-analysis aimed to analyze the outcome of probiotics in the treatment of ASD children. METHODS: The Pubmed, Cochrane Library, Web of Science and Embase were searched until Sep 2022. Randomized controlled trials (RCTs) relevant to the probiotics and placebo treatment on ASD children were screened. Quality assessment of the included RCTs was evaluated by the Cochrane collaboration's tool. The primary outcomes were ASD assessment scales, including ABC (aberrant behavior checklist) and CBCL (child behavior checklist) for evaluating the behavior improvement, SRS (social responsiveness scale) for social assessment, DQ (developmental quotient) for physical and mental development and CGI-I (clinical global impression improvement) for overall improvement. The secondary outcome was total 6-GSI (gastrointestinal severity index). RESULTS: In total, 6 RCTs from 6 studies with 302 children were included in the systemic review. Total 6-GSI (MD=-0.59, 95%CI [-1.02,-0.17], P < 0.05) decreased significantly after oral administration of probiotics. Whereas, there was no statistical difference in ABC, CBCL, SRS, DQ and CGI-I between probiotics and placebo groups in ASD children. CONCLUSION: Probiotics treatment could improve gastrointestinal symptoms, but there was no significant improvement in ASD.

Association of Oxidative Stress on Cognitive Function: A Bidirectional Mendelian Randomisation Study.

The purpose of this study was to investigate the relationship between oxidative stress and cognitive function, encompassing cognitive performance, intelligence, memory, reaction time, speech and vision by a bidirectional Mendelian randomisation study. Independent genetic variants associated with glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPX), peroxiredoxin (PRDX), sulfhydryl oxidase (SOX) and thyroid peroxidase (TPO) were explored using a genome-wide association study (GWAS). The inverse variance weighted (IVW) or Wald ratio method was employed to ascertain the relationship between antioxidant enzymes and cognitive function. The MR analyses indicated that the MR effect estimates of GST (ß = 0.0352, P = 0.0047, FDR = 0.0164) and TPO (ß = 0.0531, P = 0.0003, FDR = 0.0021) were significantly associated with cognitive performance elevation. Furthermore, genetically predicted GST (ß = 0.0334, P = 0.0043, FDR = 0.0151) and TPO (ß = 0.0496, P = 0.0031, FDR = 0.0151) were found to be associated with high intelligence. Additionally, there were also some associations of SOX (ß = 0.0243, P = 0.0283, FDR = 0.066) on high cognitive performance, TPO (ß = 0.1189, P = 0.0315, FDR = 0.2205) on larger maximum digits remembered correctly, and SOX (ß = - 0.2435, P = 0.0395, FDR = 0.1185) on reaction time. Nevertheless, the associations between antioxidant enzymes and speech and linguistic disorders, as well as visual disturbances, were not significant. We did not find reverse causation between antioxidant enzymes and cognitive function traits. This study provides evidence of potential causal relationships between oxidative stress and cognitive function.

RP105 Attenuates Ischemia/Reperfusion-Induced Oxidative Stress in the Myocardium via Activation of the Lyn/Syk/STAT3 Signaling Pathway.

Although our previous studies have established the crucial role of RP105 in myocardial ischemia/reperfusion injury (MI/RI), its involvement in regulating oxidative stress induced by MI/RI remains unclear. To investigate this, we conducted experiments using a rat model of ischemia/reperfusion (I/R) injury. Adenovirus carrying RP105 was injected apically at multiple points, and after 72 h, the left anterior descending coronary artery was ligated for 30 min followed by 2 h of reperfusion. In vitro experiments were performed on H9C2 cells, which were transfected with recombinant adenoviral vectors for 48 h, subjected to 4 h of hypoxia, and then reoxygenated for 2 h. We measured oxidative stress markers, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, as well as malondialdehyde (MDA) concentration, using a microplate reader. The fluorescence intensity of reactive oxygen species (ROS) in myocardial tissue was measured using a DHE probe. We also investigated the upstream and downstream components of the signal transducer and activator of transcription 3 (STAT3). Upregulation of RP105 increased SOD and GSH-Px activities, reduced MDA concentration, and inhibited ROS production in response to I/R injury in vivo and hypoxia reoxygenation (H/R) stimulation in vitro. The overexpression of RP105 led to a decrease in the myocardial enzyme LDH in serum and cell culture supernatant, as well as a reduction in infarct size. Additionally, left ventricular fraction (LVEF) and fractional shortening (LVFS) were improved in the RP105 overexpression group compared to the control. Upregulation of RP105 promoted the expression of Lyn and Syk and further activated STAT phosphorylation, which was blocked by PP2 (a Lyn inhibitor). Our findings suggest that RP105 can inhibit MI/RI-induced oxidative stress by activating STAT3 via the Lyn/Syk signaling pathway.

The emerging role of DOT1L in cell proliferation and differentiation: Friend or foe.

Cell proliferation and differentiation are the basic physiological activities of cells. Mistakes in these processes may affect cell survival, or cause cell cycle dysregulation, such as tumorigenesis, birth defects and degenerative diseases. In recent years, it has been found that histone methyltransferase DOT1L is the only H3 lysine 79 methyltransferase, which plays an important role in the process of cell fate determination through monomethylation, dimethylation and trimethylation of H3K79. DOT1L has a pro-proliferative effect in leukemia cells; however, loss of heart-specific DOT1L leads to increased proliferation of cardiac tissue. Additionally, DOT1L has carcinogenic or tumor suppressive effects in different neoplasms. At present, some DOT1L inhibitors for the treatment of MLL-driven leukemia have achieved promising results in clinical trials, but completely blocking DOT1L will also bring some side effects. Thus, this uncertainty suggests that DOT1L has a unique function in cell physiology. In this review, we summarize the primary findings of DOT1L in regulating cell proliferation and differentiation. Correlations between DOT1L and cell fate specification might suggest DOT1L as a therapeutic target for diseases.

Trends and influence factors in the prevalence, awareness, treatment, and control of hypertension among US adults from 1999 to 2018.

OBJECTIVE: We aimed to describe the trends and influence factors in the prevalence, awareness, treatment, and control of hypertension among US Adults from 1999 to 2018. METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning ten survey cycles (n = 53,496). Prevalence, awareness, treatment, and control of hypertension were calculated using survey weights. Joinpoint regression and survey-weighted generalized linear models were used to analyze trends and influence factors, respectively. RESULTS: The estimated prevalence of hypertension increased significantly from 33.53% to 40.58% (AAPC = 0.896, P = 0.002) during 1999-2018 with dropping rate of newly diagnosed hypertension from 8.62% to 4.82% before 2014 (APC = -4.075, P = 0.001), and then rose to 7.51% in 2018 (APC = 12.302, P = 0.126). Despite modest improvements or stability in the awareness, treatment, and control since 1999, the latter two remained inadequate in 2018 at 59.52% and 51.71%. There was an uptrend in the use of angiotensin-converting enzyme inhibitors (from 24.02% to 45.71%) and angiotensin receptor blockers (from 20.22% to 38.38%), and downtrend in ß-blocker (from 12.71% to 4.21%). Men were at higher risk of incidence, un-awareness, un-treatment, and un-control for hypertension. Lower income and education were associated with susceptibility to hypertension, while being married was favorable for treatment and control. Optimal health reduced the incidence of hypertension, and increased the awareness and treatment. CONCLUSION: Although the rate of newly diagnosed hypertension has declined slightly since 2010 in the US, the prevalence of hypertension is increasing, and treatment and control rates remain inadequate. To manage hypertension effectively, we need to focus on screening and prevention for high-risk populations, while advocating for optimal health to improve the burden of hypertension.

Comparison of the Efficacy of ECMO With or Without IABP in Patients With Cardiogenic Shock: A Meta-Analysis.

Objective: Studies on extracorporeal membrane oxygenation (ECMO) with and without an intra-aortic balloon pump (IABP) for cardiogenic shock (CS) have been published, but there have been no meta-analyses that compare the efficacy of these two cardiac support methods. This meta-analysis evaluated the outcomes of these two different treatment measures. Methods: The PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials databases were searched until March 2022. Studies that were related to ECMO with or without IABP in patients with CS were screened. Quality assessments were evaluated with the methodological index for nonrandomized studies (MINORS). The primary outcome was in-hospital survival, while the secondary outcomes included duration of ECMO, duration of ICU stay, infection/sepsis, and bleeding. Revman 5.3 and STATA software were used for this meta-analysis. Results: In total, nine manuscripts with 2,573 patients were included in the systematic review. CS patients who received ECMO in combination with IABP had significantly improved in-hospital survival compared with ECMO alone (OR = 1.58, 95% CI = 1.26-1.98, P < 0.0001). However, there were no significant differences in the duration of ECMO (MD = 0.36, 95% CI = -0.12-0.84, P = 0.14), duration of ICU stay (MD = -1.95, 95% CI = -4.05-0.15, P = 0.07), incidence of infection/sepsis (OR = 1.0, 95% CI = 0.58-1.72, P = 1.0), or bleeding (OR = 1.28, 95% CI = 0.48-3.45, P = 0.62) between the two groups of patients with CS. Conclusion: ECMO combined with IABP can improve in-hospital survival more effectively than ECMO alone in patients with CS.

ATF3 and its emerging role in atherosclerosis: a narrative review.

Background and Objective: Atherosclerosis (AS), is characterized by the subintima lipid accumulation and chronic inflammation inside the arterial wall, causing much mortality and morbidity worldwide. Activating transcription factor 3 (ATF3) is a member of ATF/cAMP-responsive element-binding (CREB) family of transcription factors, which acts as a master regulator of adaptive response. Recent studies have indicated the implicated role of ATF3 in atherogenesis and AS progression due to its impact on metabolic disorder, vascular injury, plaque formation, and stability. In this review, we summarize the current advances in the mechanism of ATF3 activation and the contribution of ATF3 in AS, highlighting vascular intrinsic and extrinsic mechanisms of how ATF3 influences the pathology of AS. Methods: The relevant literature (from origin to March 2022) was retrieved through PubMed research to explore the regulatory mechanism of ATF3 and the specific role of ATF3 in AS. Only English publications were reviewed in this paper. Key Content and Findings: ATF3 acts as a key regulator of AS progression, which not only directly affects atherosclerotic lesions by regulating vascular homeostasis, but also gets involved in AS through systemic glucolipid metabolism and inflammatory response. The two different promoters, transcript variants, and post-translational modification in distinct cell types partly contribute to the regulatory diversity of ATF3 in AS. Conclusions: ATF3 is a crucial transcription regulatory factor during atherogenesis and AS progression. Gaining a better understanding of how ATF3 affects vascular, metabolic, and immune homeostasis would advance the progress of ATF3-targeted therapy in AS.

miR-24 Alleviates MI/RI by Blocking the S100A8/TLR4/MyD88/NF-kB Pathway.

ABSTRACT: Although inflammation plays an important role in myocardial ischemia/reperfusion injury (MI/RI), an anti-inflammatory treatment with a single target has little clinical efficacy because of the multifactorial disorders involved in MI/RI. MicroRNAs (miR-24) can achieve multitarget regulation in several diseases, suggesting that this factor may have ideal effects on alleviation of MI/RI. In the present study, bioinformatics method was used to screen potential therapeutic targets of miR-24 associated with MI/RI. Three days before ischemia/reperfusion surgery, rats in the ischemia/reperfusion, miR-24, and adenovirus-negative control groups were injected with saline, miR-24, and adenovirus-negative control (0.1 mL of 5 × 109 PFU/mL), respectively. Myocardial enzymes, myocardial infarct size, cardiac function, and the possible molecular mechanism were subsequently analyzed. In contrast to the level of S100A8, the level of miR-24 in myocardial tissue was significantly reduced after 30 minutes of ischemia followed by reperfusion for 2 hours. Overexpression of miR-24 reduced the myocardial infarction area and improved the heart function of rats 3 days after MI/RI. Moreover, miR-24 inhibited infiltration of inflammatory cells in the peri-infarction area and decreased creatine kinase myocardial band and lactate dehydrogenase release. Interestingly, miR-24 upregulation reduced S100A8 expression, followed by inhibition of toll-like receptor 4/MyD-88/nuclear factor-k-gene binding signaling activation. In conclusion, miR-24 can alleviate MI/RI via inactivation of the S100A8/toll-like receptor 4/MyD-88/nuclear factor-k-gene binding signaling pathway.

Efficacy and safety of colchicine for secondary prevention of coronary heart disease: a systematic review and meta-analysis.

To evaluate the efficacy and safety of colchicine for secondary prevention of coronary heart disease (CHD), relevant randomized controlled trials (RCTs) were identified by searching several databases from the creation date to August 31, 2020 and were reviewed. Eight eligible trials of colchicine therapy involving a total of 11, 463 patients were included (5, 776 subjects received colchicine, while 5, 687 subjects were in the respective control arms), and the outcome was reported as risk ratio (RR) and 95% confidence interval (CI), as the relative measure of association. Overall, the incidences of major adverse cardiovascular events (MACEs) (RR 0.70; 95% CI 0.61-0.80), myocardial infarction (MI) (RR 0.77; 95% CI 0.64-0.94), emergency readmission due to CHD (RR 0.70; 95% CI 0.58-0.86), and ischemic stroke (RR 0.49; 95% CI 0.30-0.79) were lower in the colchicine group than in the placebo arm. We did not find a significant reduction in the incidence of all-cause mortality (RR 1.03; 95% CI 0.80-1.32). Although the incidence of diarrhea in the colchicine treatment group was higher than that in the placebo arms (RR 2.53; 95% CI 1.17, 5.48), the symptoms disappeared rapidly after drug withdrawal, and no serious adverse reactions occurred. In summary, colchicine is an accessible, safe, and effective drug that could be successfully utilized for the secondary prevention of CHD. The tolerability and benefits should be confirmed in in-depth clinical trials.

Analysis of influencing factors related to elevated serum troponin I level for COVID-19 patients in Yichang, China.

BACKGROUND: Cardiac injury is a common condition among hospitalized coronavirus disease 2019 (COVID-19) patients, and is associated with a higher risk of mortality. However, the mechanism of myocardial injury in COVID-19 remains unclear. In this retrospective study, we compared the clinical characteristics of COVID-19 patients with different troponin I (TnI) levels during hospitalization to provide a clinical reference for the identification of those at high-risk. METHODS: In total, 218 patients diagnosed with COVID-19 in Yichang Central People's Hospital and Yichang Third People's Hospital between January 23 and February 19, 2020 were initially included. Of these patients, 89 underwent TnI testing during hospitalization and were finally included in the study. The medical history, clinical signs and symptoms at the time of admission, and laboratory test results were recorded. The patients were assigned to the normal TnI group (TnI <0.01 µg/L; n=67) or the elevated TnI group (TnI >0.01 µg/L; n=22). RESULTS: The incidence of elevated TnI in our patient cohort was 24.7%. There were significant differences between the two groups in the following factors: history of coronary heart disease (CHD), age, lymphocyte count, prothrombin time (PT), activated partial thromboplastin time (APTT), and levels of interleukin (IL)-6, C-reactive protein (CRP), myoglobin (MYO), lactate dehydrogenase (LDH), and albumin (all P<0.05). Binary logistic analysis showed that a history of CHD, age, lymphocyte count, IL-6, APTT, and MYO were influencing factors of elevated serum TnI. CONCLUSIONS: A history of CHD, advanced age, decreased lymphocyte count, increased IL-6, increased MYO, and prolonged APTT were independent influencing factors of elevated TnI in COVID-19 patients. COVID-19 patients with these characteristics are prone to myocardial injury.