Journal of Biomedical Research最新文献

Silicosis is an occupational lung disease caused by prolonged exposure to silica dust in the workplace. It has a complex pathogenesis and currently lacks effective treatments. Homoharringtonine(HHT), a natural compound approved for the treatment of acute myeloid leukemia, but its effects on silicosis are unclear. In the present study, we constructed a mouse model of silica (SiO ₂)-induced pulmonary fibrosis and evaluated the preventive and therapeutic capacity of HHT. The results showed that HHT attenuated the progression of SiO ₂-induced pulmonary fibrosis in mice. We then used MRC-5, a human lung fibroblast cell line to explore the mechanisms underlying HHT's inhibitory effects in vitro and found that HHT significantly inhibited the activation and migratory capacity of MRC-5 cells. Mechanistically, the effects were mediated by enhanced ubiquitination and degradation of the CCR1 protein. Furthermore, HHT exhibited favorable biocompatibility in vivo, and its preventive and therapeutic effects were validated in SiO ₂-treated mice. This study demonstrates that HHT holds significant potential as a therapeutic agent for silicosis by targeting CCR1 and the PI3K/AKT/mTOR signaling pathway, highlighting it as a promising candidate for clinical development in silicosis treatment.

Mutation in oxysterol-binding protein-like 2 ( OSBPL2) has been identified as the genetic cause of autosomal dominant nonsyndromic hearing loss (DFNA67, OMIM No. 616340). However, the pathogenesis of the OSBPL2 mutation in DFNA remains unclear. Our previous work showed that OSBPL2 deficiency impaired cell adhesion in auditory HEI-OC1 cells. In addition, loss of hair cells (HCs) and morphological abnormalities of HC stereocilia were detected in OSBPL2-disrupted pigs, suggesting that OSBPL2 plays an important role in the regulation of the actin cytoskeleton in auditory cells. In the present study, we found that OSBPL2 deficiency inhibited the Rho/ROCK2 signaling pathway and downregulated phosphorylated Ezrin-Radixin-Moesin (p-ERM), resulting in abnormal F-actin morphology in HEI-OC1 cells and stereociliary defects in mouse HCs. The present study demonstrates the underlying mechanism of OSBPL2 in the regulation of the actin cytoskeleton in HCs, which contributes to a deeper understanding of the pathogenesis of OSBPL2 mutations in DFNA.

Prenatal maternal psychological distress, particularly depression, has been increasingly recognized as a factor that influences fetal growth; however, its impact on early childhood development remains less well understood. The present study investigated the association between prenatal depression and children's growth trajectories, as well as the odds of overweight and obesity from 1 to 36 months, while also accounting for maternal anxiety and stress. We analyzed data from 4710 mother-child dyads in the Jiangsu Birth Cohort, assessing maternal psychological distress across trimesters and categorizing participants into groups with mild, moderate, and severe depressive symptomatology. Children's weight-for-length z-scores (WLZ) were used to assess overweight/obesity prevalence, and growth patterns were identified through trajectory models. The results from the generalized estimating equations analysis showed that greater depressive symptomatology during pregnancy was associated with a 28% to 41% increase in the odds of childhood overweight/obesity across all three trimesters, compared with mild depressive symptomatology. We identified five distinct WLZ growth trajectory patterns, and found that mothers with greater depressive symptomatology were 39%-47% more likely to have children who followed a very-high-stable growth trajectory, compared with mothers with mild depressive symptomatology. These findings highlight the significant impact of prenatal depression on adverse growth patterns and childhood overweight/obesity, underscoring the need for early intervention.

Circular RNAs (circRNAs) are key regulators of reproductive biology. However, limited information is available regarding circRNA expression profiles in seminal plasma samples from individuals with male infertility. The present study aimed to identify circRNAs associated with infertility in seminal plasma samples and to clarify their potential as biomarkers, as well as the possible molecular mechanisms underlying their functions. Next-generation RNA sequencing was conducted to analyze circRNA profiles in seminal plasma from healthy controls, oligoasthenospermia (OAZ) patients, and non-obstructive azoospermia (NOA) patients. Bioinformatics analysis revealed that 637 circRNAs were differentially expressed between OAZ and control subjects, and 272 circRNAs were differentially expressed between NOA and control subjects. The expression of key circRNAs ( hsa-SAP130_0002, hsa-TRPC1_0001, hsa-FBRS_0001, hsa-ACACA_0025, hsa-UTRN_0042, and hsa-ZNF532_0023) was then validated by qPCR, and their diagnostic accuracy for infertility was confirmed through receiver operating characteristic curve analysis. Additionally, a possible circRNA-miRNA-mRNA regulatory network was constructed for these candidate biomarkers. Collectively, this study identifies a novel set of circRNAs with potential as diagnostic biomarkers for male infertility and provides molecular insights that may facilitate both diagnostic and therapeutic efforts.

Viral myocarditis is a rare but life-threatening complication in patients with ulcerative colitis. Management of myocarditis is primarily supportive, because there are currently no established targeted therapies. Recent studies have increasingly highlighted the association between the gut microbiota and myocarditis. Here, we report a case of acute severe ulcerative colitis complicated by cytomegalovirus and Epstein-Barr virus co-infections that led to viral myocarditis. The patient experienced rapid remission of both intestinal and cardiac symptoms following washed microbiota transplantation, suggesting this intervention may serve as a potential alternative treatment for these life-threatening conditions.

Primordial germ cells (PGCs), the precursors of oocytes or spermatozoa, are highly pluripotent. In recent years, the in vitro induction of human primordial germ cell-like cells (hPGCLCs) has advanced significantly. However, the stability and efficacy of obtaining hPGCLCs in vitro still require further improvement. In the current study, we identified a novel induction system by using Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F-12) as the basal medium supplemented with B27 and N2 (referred to as N2B27) in combination with four cytokines: bone morphogenetic protein 4 (BMP4), stem cell factor (SCF), epidermal growth factor (EGF), and leukemia inhibitory factor (LIF). The hPGCLCs induced under these conditions closely resemble PGCs from 4 to 5-week-old embryos at the transcriptome level. Compared with traditional GK15 (GMEM supplemented with 15% Knockout™ SR)-based induction conditions, the N2B27 system significantly increased the speed and efficacy of hPGCLC induction. RNA sequencing analysis revealed that this improvement resulted from an increased cell capacity to cope with hypoxic stress and avoid apoptosis. The N2B27 medium promoted an increase in mitochondrial activity, enabling cells to better cope with hypoxic stress while also reducing the production of reactive oxygen species. Moreover, by gradient concentration experiments, we demonstrated that addition of the common antioxidant N-acetyl-L-cysteine at an optimized concentration further enhanced the efficiency of PGCLC induction under GK15 conditions. Thus, our study established an optimized induction system that enhances the efficiency of hPGCLC differentiation by improving cellular resilience to hypoxic stress and apoptosis.

The study examined the association between weekly mean temperature and influenza cases across 122 countries/regions (2014-2019) using a distributed lag non-linear model (DLNM). We analyzed 3145206 cases of overall influenza (Flu-All), with influenza A (Flu-A) and influenza B (Flu-B) accounting for 73.49% and 26.51%, respectively. Within a lag of 2 weeks, Flu-All incidence demonstrated a bimodal temperature relationship, with peak relative risks (RR) of 6.02 (95% CI: 1.92-20.77) at -8 ℃ and 3.08 (95% CI: 1.27-7.49) at 22 ℃. Flu-A exhibited a similar bimodal pattern, with RRs of 3.76 (95% CI: 2.39-5.91) at -8 ℃ and 2.08 (95% CI: 1.55-2.80) at 22 ℃. Flu-B demonstrated a single risk peak at 1 ℃ (RR = 4.48, 95% CI: 1.74-11.55). Subgroup analyses of climate zones revealed variations: tropical zones peaked at 12 ℃ (RR = 1.37, 95% CI: 1.08-1.74), while dry and temperate zones exhibited the highest risk at -5 ℃, with RRs of 4.49 (95% CI: 2.46-7.15) and 5.23 (95% CI: 3.17-8.64), respectively. Cold zones peaked at 1 ℃ (RR = 5.96, 95% CI: 3.76-9.43). Subgroup analyses of influenza transmission zones (ITZs) revealed variations: Africa showed higher risk between 6 ℃-14 ℃, Asia showed higher risk below 3 ℃, and Europe exhibited distinct risks of influenza peaks at -1 ℃ (Eastern), 1 ℃ (Southwest), and -20 ℃ (Northern). Elevated risks above 11 ℃ were identified in the Americas and Oceania. These findings establish a predictive framework for influenza outbreak preparedness by integrating regional temperature patterns with global climate variability.

Parvalbumin-positive (PV ⁺) interneuron dysfunction is believed to be linked to autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by social deficits and stereotypical behaviors. However, the mechanisms behind PV ⁺ interneuron dysfunction remain largely unclear. Here, we found that a deficiency of Biorientation Defective 1 ( Bod1) in PV ⁺ interneurons led to an ASD-like phenotype in Pvalb-Cre; Bod1 ^f/f mice. Mechanistically, we observed that Bod1 deficiency induced hypoactivity of PV ⁺ interneurons and hyperactivity of calcium/calmodulin-dependent protein kinase Ⅱ alpha (CaMKⅡα) neurons in the medial prefrontal cortex, as determined by whole-cell patch-clamp recording. Additionally, Bod1 deficiency decreased the power of high-gamma oscillation, assessed by in vivo multi-channel electrophysiological recording. Furthermore, we found that Bod1 deficiency enhanced the inwardly rectifying K ⁺ current, leading to an increase in the resting membrane potential of PV ⁺ interneurons. Importantly, the gain-of-function of Bod1 improved social deficits and stereotypical behaviors in Pvalb-Cre; Bod1 ^f/f mice. These findings provide mechanistic insights into the PV ⁺ interneuron dysfunction and suggest new strategies for developing PV ⁺ interneuron-targeted therapies for ASD.