RNA polymerase II transcription initiation in holo-TFIID-depleted mouse embryonic stem cells.

The recognition of core promoter sequences by TFIID is the first step in RNA polymerase II (Pol II) transcription initiation. Metazoan holo-TFIID is a trilobular complex, composed of the TATA binding protein (TBP) and 13 TBP-associated factors (TAFs). Why and how TAFs are necessary for the formation of TFIID domains and how they contribute to transcription initiation remain unclear. Inducible TAF7 or TAF10 depletion, followed by comprehensive analysis of TFIID subcomplex formation, chromatin binding, and nascent transcription in mouse embryonic stem cells, result in the formation of a TAF7-lacking TFIID or a minimal core-TFIID complex, respectively. These partial complexes support TBP recruitment at promoters and nascent Pol II transcription at most genes early after depletion, but importantly, TAF10 is necessary for efficient Pol II pausing. We show that partially assembled TFIID complexes can sustain Pol II transcription initiation but cannot replace holo-TFIID over several cell divisions and/or development.

The roles of TAF1 in neuroscience and beyond.

The transcriptional machinery is essential for gene expression and regulation; dysregulation of transcription can result in a range of pathologies, including neurodegeneration, cancer, developmental disorders and cardiovascular disease. A key component of RNA polymerase II-mediated transcription is the basal transcription factor IID, which is formed of the TATA box-binding protein (TBP) and 14 TBP-associated factors (TAFs), the largest of which is the TAF1 protein, encoded on the X chromosome (Xq13.1). TAF1 is dysregulated in X-linked dystonia-parkinsonism and congenital mutations in the gene are causative for neurodevelopmental phenotypes; TAF1 dysfunction is also associated with cardiac anomalies and cancer. However, how TAF1 contributes to pathology is unclear. Here, we highlight the key aspects of the TAF1 gene and protein function that may link transcriptional regulation with disorders of development, growth and adult-onset disorders of motor impairment. We highlight the need to experimentally investigate the full range of TAF1 messenger RNA variants and protein isoforms in human and mouse to aid our understanding of TAF1 biology. Furthermore, the X-linked nature of TAF1-related diseases adds complexity to understanding phenotypes. Overall, we shed light on the aspects of TAF1 biology that may contribute to disease and areas that could be addressed for future research and targeted therapeutics.

PCAF acetylates AIB1 to form a transcriptional coactivator complex to promote glycolysis in endometrial cancer.

Introduction: Despite rapid advances in molecular biology, personalized molecular therapy remains a clinical challenge for endometrial cancer due to its complex and heterogeneous tumor microenvironment.Based on clinical findings, AIB1 is a marker molecule for poor prognosis in endometrial cancer and may serve as a potential therapeutic target. Moreover, it is well known that aerobic glycolysis plays an important role in tumour energy metabolism. It has been previously reported in various hormone-related tumour studies that AIB1 affects glycolysis and promotes tumour development. However, the link between AIB1 and aerobic glycolysis in estrogen-dependent endometrial cancer remains unclear. Methods: We used two endometrial cancer cell lines to validate the high expression of target genes and the effect on the proliferative and invasive capacity of the tumours and verified the pattern of interactions and epigenetic modifications by CHIP and CO-IP techniques. Finally, the conclusions were validated on homozygous mice. Results: In this study, we investigated the transcriptional co-activation functions of AIB1, including its acetylation by PCAF, binding to the c-myc transcription factor, and recruitment of glycolysis-related gene promoters. Discussion: Our findings provide new clues that perturbation of normal homeostatic levels of AIB1 is linked with endometrial cancer. These findings suggest that targeting AIB1-mediated regulation of aerobic glycolysis may offer a novel therapeutic approach for endometrial cancer with high AIB1 expression, opening new avenues for personalized diagnostics and treatment strategies in this disease.

Sheep (Ovis aries) Milk Exosomal miRNAs Attenuate Dextran Sulfate Sodium-Induced Colitis in Mice via TLR4 and TRAF-1 Inhibition.

Mammalian milk exosomal miRNAs play an important role in maintaining intestinal immune homeostasis and protecting epithelial barrier function, but the specific miRNAs and whether miRNA-mediated mechanisms are responsible for these benefits remain a matter of investigation. This study isolated sheep milk-derived exosomes (sheep MDEs), identifying the enriched miRNAs in sheep MDEs, oar-miR-148a, and oar-let-7b as key components targeting TLR4 and TRAF1, which was validated by a dual-luciferase reporter assay. In dextran sulfate sodium-induced colitis mice, administration of sheep MDEs alleviated colitis symptoms, reduced colonic inflammation, and systemic oxidative stress, as well as significantly increased colonic oar-miR-148a and oar-let-7b while reducing toll-like receptor 4 (TLR4) and TNF-receptor-associated factor 1 (TRAF1) level. Further characterization in TNF-α-challenged Caco-2 cells showed that overexpression of these miRNAs suppressed the TLR4/TRAF1-IκBα-p65 pathway and reduced IL-6 and IL-12 production. These findings indicate that sheep MDEs exert gastrointestinal anti-inflammatory effects through the miRNA-mediated modulation of TLR4 and TRAF1, highlighting their potential in managing colitis.

Simulating the Growth of TATA-Box Binding Protein-Associated Factor 15 Inclusions in Neuron Soma.

To the best of the author's knowledge, this paper presents the first attempt to develop a mathematical model of the formation and growth of inclusions containing misfolded TATA-box binding protein associated factor 15 (TAF15). It has recently been shown that TAF15 inclusions are involved in approximately 10% of cases of frontotemporal lobar degeneration (FTLD). FTLD is the second most common neurodegenerative disease after Alzheimer's disease (AD). It is characterized by a progressive loss of personality, behavioral changes, and a decline in language skills due to the degeneration of the frontal and anterior temporal lobes. The model simulates TAF15 monomer production, nucleation and autocatalytic growth of free TAF15 aggregates, and their deposition into TAF15 inclusions. The accuracy of the numerical solution of the model equations is validated by comparing it with analytical solutions available for limiting cases. Physiologically relevant parameter values were used to predict TAF15 inclusion growth. It is shown that the growth of TAF15 inclusions is influenced by two opposing mechanisms: the rate at which free TAF15 aggregates are deposited into inclusions and the rate of autocatalytic production of free TAF15 aggregates from monomers. A low deposition rate slows inclusion growth, while a high deposition rate hinders the autocatalytic production of new aggregates, thus also slowing inclusion growth. Consequently, the rate of inclusion growth is maximized at an intermediate deposition rate of free TAF15 aggregates into TAF15 inclusions.

Factors associated with dietary patterns (DPS) and nutritional status among pregnant women in AM-HDSS, South Ethiopia.

Background: Malnutrition during pregnancy increases the risk of chronic illness later in life and adverse birth outcomes in subsequent generations. In this regard, consumption of diets rich in adequate energy, protein, vitamins, and minerals from a variety of foods is essential. Evidence on the status of maternal dietary pattern is very crucial. Hence, the aim of this study was to assess factors associated with dietary patterns and nutritional status of pregnant women in South Ethiopia. Methods: A community-based cross-sectional study was conducted among 638 randomly selected pregnant women using a validated, a pre-tested, contextualized food frequency questionnaire using interviewer-administered structured questionnaire by digital open-source toolkit. Principal component factor analysis was employed to determine dietary patterns. Bivariable and multivariable ordinal logistic regression analyses were used to identify factors associated with dietary patterns and nutritional status, using STATA version 16. Result: The dietary habits of pregnant women were best explained by three distinct dietary patterns. Urban dwellers (AOR = 2.18; 95% CI: 1.33, 3.59), from high socio-economic status (AOR = 2.43; 95% CI: 1.68, 3.51), from middle socio-economic status (AOR = 1.72; 95% CI: 1.19, 2.48), primigravida mothers (AOR = 1.72; 95% CI: 1.07, 2.78), and multigravida mothers (AOR = 2.08; 95% CI: 1.39, 3.10) were high likelihood to consume the highest tercile of "Cereals-Pulses and Dairy" compared to rural dwellers, from low socio-economic status and grand multigravida, respectively. Attending formal education (AOR = 1.60; 95% CI: 1.02, 2.51), from higher socioeconomic status (AOR = 1.56; 95% CI: 1.02, 2.38), not having food aversion (AOR = 1.98; 95% CI: 1.16, 3.39), and had good dietary knowledge (AOR = 2.16; 95% CI: 1.08, 4.32) were associated with a higher tercile consumption of "Nutrient-Dense" food compared to those without formal education, having food aversion and had poor dietary knowledge, respectively. Not attending formal education (AOR = 2.22; 95% CI: 1.48, 3.36), had decision-making autonomy (AOR = 1.91; 95% CI: 1.26, 2.90), and had good dietary knowledge (AOR = 1.86; 95% CI: 1.13, 3.08) were found to consume the highest tercile of "Leafy local food" compared to their counterpart. Consumption of lower terciles "Nutrient-Dense" food (AOR = 1.63; 95% CI: 1.07, 2.47) and "Leafy local food" (AOR = 2.32; 95% CI: 1.54, 3.51) were found to be factors associated with under nutrition during pregnancy. Conclusion: Three distinct dietary patterns were identified. Factors associated with these major dietary patterns included place of residence, socio-economic status, educational level, dietary knowledge, food aversion, number of pregnancies, and maternal decision-making autonomy. Under nutrition among pregnant women was found to be high and associated with the consumption of 'Nutrient-Dense' and 'Leafy local' foods. Therefore, concerned health authorities should strengthen dietary counseling during pregnancy, provide family planning services, and promote women's education.

The TATA-box binding protein-associated factor TAF12b facilitates the degradation of type-B response regulators to negatively regulate cytokinin signaling.

Cytokinins (CKs) are one of important classes of plant hormones essential for plant growth and development. The TATA-box binding protein-associated factor 12b (TAF12b) is involved in cytokinin (CK) signaling, but its molecular and biochemical mechanisms remain unclear. In this study, TAF12b of Nicotiana benthamiana (NbTAF12b) was found to mediate CK response by directly interacting with type-B response regulators (B-RRs), which are positive regulators of CK signaling, and inhibiting their transcriptional activities. The co-factor specifically facilitated the proteasomal degradation of non-phosphorylated B-RRs by recruiting the KMD family of F-box proteins. Such interactions between TAF12b and B-RRs also occur in other plant species. Genetic transformation experiments further showed that overexpression of NbTAF12b attenuates the CK-hypersensitive phenotype conferred by NbRR1 overexpression. Taken together, these results suggest a conserved mechanism that TAF12b negatively regulates CK responses through promoting 26S proteasome-mediated degradation of B-RRs degradation in multiple plant species, which provides novel insights into the regulatory network of CK signaling in plants.

C-TERMINAL DOMAIN PHOSPHATASE-LIKE 1 promotes flowering with TAF15b by repressing the floral repressor gene FLOWERING LOCUS C.

Arabidopsis TBP-ASSOCIATED FACTOR15b (TAF15b) is a plant-specific component of the transcription factor IID (TFIID) complex. TAF15b is involved in the autonomous pathway for flowering and represses the transcription of FLOWERING LOCUS C (FLC), a major floral repressor in Arabidopsis. While components of the autonomous flowering pathway have been extensively studied, scant attention has been directed towards elucidating the direct transcriptional regulators responsible for repressing FLC transcription. Here, we demonstrate that C-TERMINAL DOMAIN PHOSPHATASE-LIKE 1 (CPL1) is a physical and functional partner of TAF15b, playing a role for FLC repression. CPL1 is a protein phosphatase that dephosphorylates the C-terminal domain (CTD) of RNA polymerase II (Pol II). Through the immunoprecipitation and mass spectrometry technique, we identified CPL1 as an interacting partner of TAF15b. Similar to taf15b, the cpl1 mutant showed a late-flowering phenotype caused by an increase in FLC levels. Additionally, the increase in cpl1 was correlated with the enrichment of phosphorylated Pol II in the FLC chromatin, as expected. We also discovered that CPL1 and TAF15b share additional common target genes through transcriptome analysis. These results suggest that TAF15b and CPL1 cooperatively repress transcription through the dephosphorylation of Pol II, especially at the FLC locus.

Hyperuricemia and associated factors among hypertensive patients attending an academic hospital of Ethiopia: A cross-sectional study.

Background: Hypertension is a major public health problem in developing countries. Globally, nearly 1.13 billion adults had hypertension in 2015 and this is estimated to increase to 1.56 billion by 2025. Hyperuricemia is an important predictor of the progression of hypertension and is common in hypertensive patients. Hypertensive patients with hyperuricemia are at higher risk of cardiovascular disease. Objective: To assess the prevalence of hyperuricemia and its associated factors among hypertensive patients attending the University of Gondar Comprehensive Specialized Hospital (UGCSH). Method: An institutional-based cross-sectional study was conducted on 248 hypertensive patients attending the University of Gondar Comprehensive Specialized Hospital from January 2020 to February 2021. A convenient sampling technique was employed to select study participants. Socio-demographic and clinical characteristics were collected using a structured questionnaire via face-to-face interviews and reviewing medical records respectively. The biochemical parameters were measured by using a Mindray BS-200E chemistry analyzer. Data was entered using EpiData version 4.6.0.0 and analyzed using STATA vs. 14.0. Bivariable and multivariable binary logistic regression were fitted to identify factors associated with hyperuricemia. The odds ratio and 95 % CI were calculated to assess the strength of the association and a P-value <0.05 in the multivariable was considered statistically significant. Results: A total of 248 patients were enrolled; 140 (56.5 %) were female. The mean age of patients was 57.9 ± 10.5 years. The overall prevalence of hyperuricemia was 42.3 %; males had a prevalence of 36.1 % and females of 47.1 %. High waist circumference, high body mass index, dyslipidemia, low estimated Glomerular Filtration Rate, elevated fasting blood glucose, elevated total cholesterol, elevated triglycerides, elevated Low-Density Lipoprotein cholesterol, and Low High-Density Lipoprotein cholesterol were found to be significantly associated with hyperuricemia. Conclusion: This study demonstrated the predominant existence of hyperuricemia in hypertensive patients. Therefore, early diagnosis and monitoring of hyperuricemia are required before further complications occur.

Aortic isthmus flow reversal in fetal coarctation of the aorta and the associated factors.

INTRODUCTION: The aim of this study was to investigate the presence of aortic isthmus flow reversal and its associated factors in fetuses with positive and false-positive coarctation of the aorta (CoA) compared with normal controls. MATERIAL AND METHODS: Pregnant women with fetuses suspected of CoA and normal control were enrolled, and these women experienced prenatal ultrasound scan and followed up for 6 months after birth to confirm the presence of CoA. All the ultrasound parameters were analyzed. RESULTS: A total of 134 pregnant women were enrolled, with 43 CoA-positive fetuses and 91 CoA false-positive fetuses, and 334 matched pregnant women were enrolled in the control group. Aortic isthmus flow reversal occurred in 28 (65.1%) fetuses in the CoA-positive group, significantly (p < 0.05) more than in the false-positive (37 or 40.7%) or control group (64 or 19.2%). Aortic isthmus flow reversal was mostly in the full systole (n = 17 or 60.7%) or late systole and early-middle diastole (n = 10 or 35.7%) in the CoA-positive fetuses (n = 27 or 96.4%), significantly (p < 0.001) different from that in the false-positive or control group. The aortic isthmus flow reversal peak systolic velocity (PSV), flow volume, and ratio of reversed flow/forward flow were significantly (p < 0.05) increased in the CoA-positive and false-positive groups than in the control group. The aortic isthmus flow reversal incidence was significantly (p < 0.05) correlated with the middle cerebral artery (MCA) PSV in the total three groups or in the false-positive group but was significantly (p < 0001) negatively correlated with the MCA resistance index (RI) in the CoA-positive group. The incidence of the aortic isthmus flow reversal was significantly (p < 0.05) positively correlated with the umbilical artery (UA) RI in the false-positive group and with the UA RI in the total three groups. Independently associated factors for aortic isthmus flow reversal were isthmic flow volume/CCO (combined cardiac output) in the CoA-positive group. CONCLUSIONS: Reversal of flow in the aortic isthmus is much more common in true-positive cases of CoA as compared to controls, and isthmic flow reversal in the full systolic phase only suggests presence of CoA. The aortic isthmic reversed flow volume accounts for over half of the isthmic forward flow volume in the CoA-positive fetuses than in the normal controls.

MicroRNAs as Epigenetic Regulators of Obesity.

In obesity, the process of adipogenesis largely determines the number of adipocytes in body fat depots. Adipogenesis is regulated by several adipocyte-selective micro-ribonucleic acids (miRNAs) and transcription factors that modulate adipocyte proliferation and differentiation. However, some miRNAs block the expression of master regulators of adipogenesis. Since the specific miRNAs display different expressions during adipogenesis, in mature adipocytes and permanent obesity, their use as biomarkers or therapeutic targets is feasible. Upregulated miRNAs in persistent obesity are downregulated during adipogenesis. Moreover, some of the downregulated miRNAs in obese individuals are upregulated in mature adipocytes. Induction of adipocyte stress and hypertrophy leads to the release of adipocyte-derived exosomes (AdEXs) that contain the cargo molecules, miRNAs. miRNAs are important messengers for intercellular communication involved in metabolic responses and have very specific signatures that direct the metabolic activity of target cells. While each miRNA targets multiple messenger RNAs (mRNAs), which may coordinate or antagonize each other's functions, several miRNAs are dysregulated in other tissues during obesity-related comorbidities. Deletion of the miRNA-processing enzyme DICER in pro-opiomelanocortin-expressing cells results in obesity, which is characterized by hyperphagia, increased adiposity, hyperleptinemia, defective glucose metabolism, and alterations in the pituitary-adrenal axis. In recent years, RNA-based therapeutical approaches have entered clinical trials as novel therapies against overweight and its complications. Development of lipid droplets, macrophage accumulation, macrophage polarization, tumor necrosis factor receptor-associated factor 6 activity, lipolysis, lipotoxicity, and insulin resistance are effectively controlled by miRNAs. Thereby, miRNAs as epigenetic regulators are used to determine the new gene transcripts and therapeutic targets.

Prevalence and Associated Factors of Paroxysmal Atrial Fibrillation and Atrial Arrhythmias During Hospitalizations for Exacerbation of COPD.

Purpose: This study aimed to investigate the proportion and risk factors of paroxysmal atrial fibrillation (AF) and atrial arrhythmias (AA) in patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Vietnam. Patients and Methods: A prospective observational study was conducted at two major hospitals in Hanoi, Vietnam, from January 2022 to January 2023. A total of 197 AECOPD patients were recruited. ECG and 24-hour Holter ECG were used to diagnose paroxysmal AF and AA. Results: The prevalence of paroxysmal AF and AA were 15.2% and 72.6%, respectively. Factors associated with a higher likelihood of paroxysmal AF included aging 75 years old and above (aOR = 3.15; 95% CI: 1.28 to 8.48), Premature atrial complex (PAC) with 500 or more (aOR = 3.81; 95% CI: 1.48 to 10.97) and severity of COPD as group C and D (aOR = 3.41; 95% CI: 1.28 to 10.50). For AA, aging 75 years old and above (aOR = 2.25; 95% CI: 1.28 to 5.20), smoking (aOR = 2.10; 95% CI: 1.07 to 4.23) and P wave dispersion (PWD) with 40 milliseconds or more (aOR = 3.04; 95% CI: 1.54 to 6.19) were associated with a higher likelihood of AA. Conclusion: Overall, our findings highlight the associated factors with the paroxysmal AF and AA among AECOPD patients. This underscores the importance of a multifaceted approach to risk assessment and management in this vulnerable population, focusing not only on respiratory symptoms but also on comprehensive cardiovascular evaluation and intervention.

Tata-box-binding protein-associated factor 15 as a new potential marker in gastrointestinal tumors.

In this editorial, the roles of tata-box-binding protein-associated factor 15 (TAF15) in oncogenesis, tumor behavior, and as a therapeutic target in cancers in the context of gastrointestinal (GI) tumors are discussed concerning the publication by Guo et al. TAF15 is a member of the FET protein family with a comprehensive range of cellular processes. Besides, evidence has shown that TAF15 is involved in many diseases, including cancers. TAF15 contributes to carcinogenesis and tumor behavior in many tumors. Besides, its relationship with the mitogen-activated protein kinases (MAPK) signaling pathway makes TAF15 a new target for therapy. Although, the fact that there is few studies investigating the expression of TAF15 constitutes a potential limitation in GI system, the association of TAF15 expression with aggressive tumor behavior and, similar to other organ tumors, the influence of TAF15 on the MAPK signaling pathway emphasize that this protein could serve as a new molecular biomarker to predict tumor behavior and target therapeutic intervention in GI cancers. In conclusion, more studies should be performed to better understand the prognostic and therapeutic role of TAF15 in GI tumors, especially in tumors resistant to therapy.

Epidemiological features of suicidal ideation among the elderly in China based meta-analysis.

BACKGROUND: Studies on the prevalence of suicidal ideation (SI) and its associated factors among the elderly in China show considerable variability. This meta-analysis aims to clarify the epidemiological features of SI in this population. METHODS: We systematically searched English and Chinese databases for relevant literature up to September 15, 2022. The extracted data facilitated the calculation of prevalence and odds ratios (ORs) for factors associated with SI among China's elderly. RESULTS: We analyzed 31 cross-sectional studies, comprising a total of 79,861 participants from over 20 provinces and municipalities. The pooled prevalence of SI was found to be 11.47% [95% confidence interval (CI): 7.82-15.71%]. Significant variations in prevalence were influenced by residence, physical health (including chronic diseases and daily living capabilities), mental health (depressive symptoms and life satisfaction), economic status, and time-specific assessment tools. Notably, the prevalence from 2011-2020 (15.59%, 95% CI: 9.08-23.44%) was almost double that of 2001-2010 (7.85%, 95% CI: 5.08-11.16%). The SI prevalence in the eastern region (8.06%, 95% CI 5.59-10.94%) was significantly lower than in the central and western regions (16.97%, 95% CI 12.04-22.53%). Fourteen factors exhibited a significant pooled OR greater than 1 (p < 0.05), and two factors had ORs less than 1 (p < 0.05), indicating notable association with SI among the elderly. CONCLUSION: SI among China's elderly showed relatively high prevalence and considerable heterogeneity across different characteristics and associated factors. This underscores the need for targeted intervention strategies and standardized temporal assessments of SI to effectively address suicide risk in this population.

Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury.

Spinal cord injury (SCI) is a serious, disabling injury to the central nervous system that can lead to motor, sensory, and autonomic dysfunction below the injury plane. SCI can be divided into primary injury and secondary injury according to its pathophysiological process. Primary injury is irreversible in most cases, while secondary injury is a dynamic regulatory process. Secondary injury involves a series of pathological events, such as ischemia, oxidative stress, inflammatory events, apoptotic pathways, and motor dysfunction. Among them, oxidative stress is an important pathological event of secondary injury. Oxidative stress causes a series of destructive events such as lipid peroxidation, DNA damage, inflammation, and cell death, which further worsens the microenvironment of the injured site and leads to neurological dysfunction. The nuclear factor erythrocyte 2-associated factor 2 (Nrf2) is considered to be a key pathway of antioxidative stress and is closely related to the pathological process of SCI. Activation of this pathway can effectively inhibit the oxidative stress process and promote the recovery of nerve function after SCI. Therefore, the Nrf2 pathway may be a potential therapeutic target for SCI. This review deeply analyzed the generation of oxidative stress in SCI, the role and mechanism of Nrf2 as the main regulator of antioxidant stress in SCI, and the influence of cross-talk between Nrf2 and related pathways that may be involved in the pathological regulation of SCI on oxidative stress, and summarized the drugs and other treatment methods based on Nrf2 pathway regulation. The objective of this paper is to provide evidence for the role of Nrf2 activation in SCI and to highlight the important role of Nrf2 in alleviating SCI by elucidating the mechanism, so as to provide a theoretical basis for targeting Nrf2 pathway as a therapy for SCI.

Assessment of impaired glomerular filtration rate and associated factors in South West Ethiopia: a cross-sectional study.

INTRODUCTION: Currently, kidney disease is an increasing major health problem worldwide. It is expected to be the 5th ranked cause of death by 2040. If it is early detected, further complication caused by kidney disease will be minimized. An assessment of impaired glomerular filtration rate (eGFR) has potential aids in early identification and treatment of kidney disease. However, in hospital practice instead of using eGFR, direct measurement of serum creatinine level is used for assessing renal function. Hence, this study is aimed to assess the magnitude and associated factors of impaired glomerular filtration rate among admitted patients in Wolkite University Specialized Teaching Hospital (WKUSTH). OBJECTIVE: To assess the magnitude and associated factors of impaired glomerular filtration rate in WKUSTH, Ethiopia 2023. METHOD: Institutional based cross-sectional study with secondary data was conducted. 338 participants were selected by a convenient sampling technique. Epidata 3.1 version for data entry and SPSS version 20 for data analysis was used. Bivariate analysis was used to screen candidate variables for multivariate analysis. In the multivariate analysis a P-value < 0.05 were considered statistically significant. RESULTS: The study enrolled 338 patients admitted to WUSTH. Seventy (20.7%) (95% CI: 16.6-25.4%) of them had impaired eGFR according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and Modification of Diet in Renal Disease (MDRD-4). older age (AOR 3.38, 95% CI; 1.31, 8.71), hypertension (AOR 17.8, 95% CI; 7.75, 41.22), anemia (AOR 2.51, 95% CI; 1.11, 5.83) DM (AOR 11.2, 95% CI; 4.11, 30.73), and high BMI (AOR 7.56, 95% CI; 3.16, 18.08), were independently associated with impaired eGFR. CONCLUSIONS: The magnitude of impaired eGFR was prevalent among adult patients admitted to WKUSTH medical ward with different medical conditions. Old age, Hypertension, Diabetes, high body mass index, and Anemia were significantly associated with impaired eGFR both in CKD-EPI and MDRD-4 equation. Estimation of GFR for all hospitalized adults with known CKD risk factors might help in early detection of CKD and prevent complications.

Inhibition of TRAF6 alleviates secondary brain injury by reducing neuronal pyroptosis after intracerebral hemorrhage.

Secondary brain injury (SBI) is one of the main causes of high mortality and disability rates following intracerebral hemorrhage (ICH). TRAF6 plays a crucial role in the process of pyroptosis, and modulating its expression may present a novel therapeutic strategy for mitigating brain injury. This study aims to explore the mechanisms of TRAF6 in pyroptosis after ICH. C57BL/6J mice were used to establish the ICH model. Brain was collected at different time points for q-PCR and western blot to detect the level of TRAF6. After the C25-140 (the TRAF6 inhibitor) was administrated, the mice were divided into four groups. Then, the neurological deficit, brain water content, and blood-brain barrier (BBB) ​​damage were detected. Immunofluorescence and western blot were used to detect the level of pyroptosis proteins, and enzyme-linked immunosorbent assay (ELISA) and q-PCR were used to detect the levels of IL-18 and IL-1ß. TRAF6 expression was upregulated after ICH and was mainly expressed in neurons. Inhibition of TRAF6 expression with C25-140 alleviated neurological deficits and reduced brain edema after ICH. In addition, inhibition of TRAF6 also reduced the expression of pyroptosis inflammasomes such as GSDMD, NLRP3, and ASC, as well as neurological damage caused by IL-18 and IL-1ß after ICH. TRAF6 regulates neuronal pyroptosis in SBI after ICH. Inhibition of TRAF6 may be a potential target for alleviating inflammatory damage after ICH.

Resilience and mental health among perinatal women: a systematic review.

Objective: This review aimed to assess the current evidence on the relationship between resilience and mental health employed in response to the impacts of mental health. Method: This review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA). The protocol of this review was registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023470966). Three authors searched peer-reviewed articles using several electronic databases, including Scopus, PubMed/MEDLINE, Psych Info, EMBASE, and Web of Science, from September to October 2023 and included all the studies from any time until November 1, 2023. The review included all eligible quantitative observational and qualitative studies, irrespective of geographical boundaries. Result: Depression, anxiety, and post-traumatic stress disorders were found to be the most common, but not the only, mental health disorders during the perinatal period, and higher maternal resilience during perinatal periods was found to reduce mental health disorders. It was also found that pregnant women were more resilient to mental health disorders than postpartum women. Tolerance of uncertainty and a positive cognitive appraisal, women's self-behavior and family functioning, and protective psychosocial resources such as dispositional optimism, parental sense of mastery, self-esteem, gratitude, and forgiveness were found to be the most common mechanisms of resilience among perinatal women. Older age, having an adolescent partner, family income, and distress were found to affect resilience. Conclusion: Noting that women's resilience is an important tool to prevent perinatal mental health disorders, maternal healthcare providers need to counsel perinatal women on resilience-boosting mechanisms, such as applying self-behavior and having social support or close family relationships. It is recommended to counsel or provide psychosocial interventions for the woman's companion or partner to give strong support for the woman in each of the perinatal periods. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=470966, identifier CRD42023470966.

The involvement of tumor necrosis factor receptor-associated factor 6 in regulating immune response by NF-κB at pre-molt stage of Chinese mitten crab (Eriocheir sinensis).

Molting is a crucial biological process of crustaceans. Crustaceans go through three separate stages throughout their molting process, including pre-molt, post-molt and inter-molt. However, the exact mechanism of immunological modulation during molting remains unclear. Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been extensively documented to participate in immune defense. In the present study, a TRAF6 gene with two TRAF-type zinc finger domains was identified from Eriocheir sinensis (designed as EsTRAF6), and its role in regulating immune response during molting process was explored. The mRNA expression level of EsTRAF6 at pre-molt stage was higher than that at post-molt stage and inter-molt stage. After Aeromonas hydrophila stimulation, the expression levels of EsTRAF6, EsRelish and anti-lipopolysaccharide factors (ALFs) genes exhibited a considerable increase at three molting stages. Subsequently, the expression patterns of EsTRAF6 and EsRelish in response to the treatment with 20-hydroxyecdysone (20E) were examined. The mRNA expression of EsTRAF6 and EsRelish were significantly increased at 12 h after 20E injection. Additionally, the protein expression level of TRAF6 was also up-regulated in 20E group compared to control group. Furthermore, the role of EsTRAF6 in regulating the anti- ALFs expression at pre-molt stage post A. hydrophila stimulation was investigated. Following the inhibition of the EsTRAF6 transcript using RNAi or the injection of inhibitor (TMBPS), there was a notable decrease of the EsALF1, EsALF2 and EsALF3 transcripts. Moreover, a significant reduction in the phosphorylation level of NF-κB at pre-molt stage was observed after A. hydrophila stimulation in TRAF6-inhibited crabs. Collectively, our results suggest that EsTRAF6 could be induced by 20E and promoted the EsALFs expression by activating NF-κB at pre-molt stage, which provides a novel insight into the research of immune regulatory mechanism during the process of molting of crustaceans.

Effects of novel lactoferrin peptides on LPS-induced alveolar bone destruction in a rat model.

To develop novel bovine lactoferrin (bLF) peptides targeting bLF-tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6) binding sites, we identified two peptides that could target bLF-TRAF6 binding sites using structural analysis. Moreover, another peptide that could bind to the TRAF6 dimerization area was selected from the bLF sequence. The effects of each peptide on cytokine expression in lipopolysaccharide (LPS)-stimulated osteoblasts (ST2) and on osteoclastogenesis were examined using an LPS-treated co-culture of primary bone marrow cells (BMCs) with ST2 cells and a single culture of osteoclast precursor cells (RAW-D) treated with soluble receptor activator of NF-κB ligand. Finally, the effectiveness of these peptides against LPS-induced alveolar bone destruction was assessed. Two of the three peptides significantly suppressed LPS-induced TNF-α and interleukin-1ß expression in ST2 cells. Additionally, these peptides inhibited and reversed LPS-induced receptor activator of NF-κB ligand (RANKL) upregulation and osteoprotegerin (OPG) downregulation, respectively. Furthermore, both peptides significantly reduced LPS-induced osteoclastogenesis in the BMC-ST2 co-culture and RANKL-induced osteoclastogenesis in RAW-D cells. In vivo, topical application of these peptides significantly reduced the osteoclast number by downregulating RANKL and upregulating OPG in the periodontal ligament. It is indicated that the novel bLF peptides can be used to treat periodontitis-associated bone destruction.