Association between patterns of biological rhythm and self-harm: evidence from the baoxing youth mental health (BYMH) cohort.

BACKGROUND: Self-harm, a severe mental health concern among children and adolescents, has varying global prevalence rates. Previous studies have suggested potential associations between specific behavioral aspects of biological rhythm and self-harm risk in these populations. OBJECTIVE: Our study aimed to elucidate the relationship between biological rhythm patterns and the propensity of self-harm among Chinese children and adolescents using the Baoxing Youth Mental Health (BYMH) cohort. METHODS: We included 1883 Chinese children and adolescents from the BYMH cohort. The self-report questions used to assess biological rhythm and self-harm. We applied Principal Component Analysis (PCA) to distinguish patterns of biological rhythms. Logistic regression models were conducted to estimate the associations between biological rhythm, as well as biological rhythm patterns and risk of self-harm. RESULTS: Of the participants, 35.0% reported experiencing lifetime self-harm. PCA revealed six significantly predominant biological rhythm patterns. Elevated risks of self-harm were linked with unhealthy eating practices, daytime tiredness, and unhealthy bedtime snacking. Conversely, patterns emphasizing physical exercise, family meals for breakfast, and nutritious diet exhibited decreased self-harm propensities. These trends persisted across varied self-harm attributes, including type, recency, and frequency of self-harm. CONCLUSIONS: This study underscores the critical impact of biological rhythms on self-harm risks among Chinese youth. Targeted lifestyle interventions, focusing on improved sleep and dietary habits, could serve as potent preventive measures. Our findings lay the groundwork for future longitudinal studies to further probe these associations, fostering the creation of tailored interventions to curb self-harm and enhance mental well-being in younger populations.

Associations between intimate partner violence and adverse birth outcomes during pregnancy: a systematic review and meta-analysis.

Background: Intimate partner violence (IPV) has been associated with an elevated risk of multiple adverse birth outcomes, yet little is known about how specific IPV influences adverse birth outcomes. The aim of this study was to examine the association between IPV during pregnancy and adverse birth outcomes (i.e., preterm birth, low birth weight, and stillbirth). Methods: Systematic searches were conducted using four databases: EMBASE, Web of Science, PubMed, and CINAHL for observational studies published from 1 January 2011 to 31 August 2021. Two reviewers independently carried out the literature search, study selection, data extraction, assessment of the study, and risk of bias assessment; disagreements were resolved by a third reviewer. A random-effect model was used to calculate the odds ratio (OR) with a 95% confidence interval (CI) for preterm birth, low birth weight, and stillbirth. I2 statistic accompanied by chi-square p-value was used to assess heterogeneity, and funnel plot and Peter's test were used to assess publication bias. Results: In total, 23 studies met the inclusion criterion. IPV was associated with preterm birth (OR = 1.84; 95% CI: 1.37-2.49; I2 = 88%), low birth weight (OR = 2.73; 95% CI: 1.66-4.48; I2 = 95%), and stillbirth (OR = 1.74; 95% CI: 0.86-3.54; I2 = 64%). We attained comparable results among all specific IPV including physical, sexual, emotional, and mixed. Conclusion: Intimate partner violence and specific IPV during pregnancy were significantly associated with adverse birth outcomes, especially for physical IPV. An urgent need for greater action to prevent or intervene in IPV during pregnancy is warranted. Systematic review registration: CRD42021282936, https://www.crd.york.ac.uk/prospero/.

Mutations in ARHGEF15 cause autosomal dominant hereditary cerebral small vessel disease and osteoporotic fracture.

Cerebral small vessel disease (CSVD) is a prominent cause of ischemic and hemorrhagic stroke and a leading cause of vascular dementia, affecting small penetrating vessels of the brain. Despite current advances in genetic susceptibility studies, challenges remain in defining the causative genes and the underlying pathophysiological mechanisms. Here, we reported that the ARHGEF15 gene was a causal gene linked to autosomal dominant inherited CSVD. We identified one heterozygous nonsynonymous mutation of the ARHGEF15 gene that cosegregated completely in two families with CSVD, and a heterozygous nonsynonymous mutation and a stop-gain mutation in two individuals with sporadic CSVD, respectively. Intriguingly, clinical imaging and pathological findings displayed severe osteoporosis and even osteoporotic fractures in all the ARHGEF15 mutation carriers. In vitro experiments indicated that ARHGEF15 mutations resulted in RhoA/ROCK2 inactivation-induced F-actin cytoskeleton disorganization in vascular smooth muscle cells and endothelial cells and osteoblast dysfunction by inhibiting the Wnt/ß-catenin signaling pathway in osteoblast cells. Furthermore, Arhgef15-e(V368M)1 transgenic mice developed CSVD-like pathological and behavioral phenotypes, accompanied by severe osteoporosis. Taken together, our findings provide strong evidence that loss-of-function mutations of the ARHGEF15 gene cause CSVD accompanied by osteoporotic fracture.

Organic extracts in PM2.5 are the major triggers to induce ferroptosis in SH-SY5Y cells.

As a major air pollutant, PM2.5 can induce apoptosis of nerve cells, causing impairment of the learning and memory capabilities of humans and animals. Ferroptosis is a newly discovered way of programmed cell death. It is unclear whether the neurotoxicity induced by PM2.5 is related to the ferroptosis of nerve cells. In this study, we observed the changes in ferroptosis hallmarks of SH-SY5Y cells after exposure to various doses (40, 80, and 160 µg/mL PM2.5) for 24 h, exposure to 40 µg/mL PM2.5 for various times (24, 48, and 72 h), as well as exposure to various components (Po, organic extracts; Pw, water-soluble extracts; Pc, carbon core component). The results showed that PM2.5 reduced the cell viability, the content of GSH, and the activity of GSH-PX and SOD in SH-SY5Y cells with exposure dose and duration increasing. On the other hand, PM2.5 increased the content of iron, MDA, and the level of lipid ROS in SH-SY5Y cells with exposure dose and duration increasing. Additionally, PM2.5 reduced the expression levels of HO-1, NRF2, SLC7A11, and GPX4. The ferroptosis inhibitors Fer-1 and DFO significantly increase the cells viabilities and significantly reversed the changes of other above ferroptosis hallmarks. We also observed the different effects on ferroptosis hallmarks in the SH-SY5Y cells exposed to PM2.5 (160 µg/mL) and its various components (organic extracts, water-soluble extracts, and carbon core) for 24 h. We found that only the organic extracts shared similar results with PM2.5 (160 µg/mL). This study demonstrated that PM2.5 induced ferroptosis of SH-SY5Y cells, and organic extracts might be the primary component that caused ferroptosis.

Brain-gut-liver axis: Chronic psychological stress promotes liver injury and fibrosis via gut in rats.

Background: The effect of chronic psychological stress on hepatitis and liver fibrosis is concerned. However, its mechanism remains unclear. We investigated the effect and mechanism of chronic psychological stress in promoting liver injury and fibrosis through gut. Methods: Sixty male SD rats were randomly assigned to 6 groups. Rat models of chronic psychological stress (4 weeks) and liver fibrosis (8 weeks) were established. The diversity of gut microbiota in intestinal feces, permeability of intestinal mucosa, pathologies of intestinal and liver tissues, collagen fibers, protein expressions of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa ß (NF-κß), tumor necrosis factor α (TNF-α) and interleukin 1 (IL-1) in liver tissue, liver function and coagulation function in blood and lipopolysaccharide (LPS) in portal vein blood were detected and analyzed. Results: The diversities and abundances of gut microbiota were significant differences in rats among each group. The pathological lesions of intestinal and liver tissues, decreased expression of occludin protein in intestinal mucosa, deposition of collagen fibers and increased protein expression of TLR4, MyD88, NF-κß, TNF-α and IL-1 in liver tissue, increased LPS level in portal vein blood, and abnormalities of liver function and coagulation function, were observed in rats exposed to chronic psychological stress or liver fibrosis. There were significant differences with normal rats. When the dual intervention factors of chronic psychological stress and liver fibrosis were superimposed, the above indicators were further aggravated. Conclusion: Chronic psychological stress promotes liver injury and fibrosis, depending on changes in the diversity of gut microbiota and increased intestinal permeability caused by psychological stress, LPS that enters liver and acts on TLR4, and active LPS-TLR4 pathway depend on MyD88. It demonstrates the possibility of existence of brain-gut-liver axis.

Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide induces ferroptosis in neuroblastoma cells through redox imbalance.

As a widespread environmental pollutant, benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE)-induced neurotoxicity has received increasing attention. Studies have shown that BPDE-induced neurodegeneration is due partly to neuronal apoptosis. Unlike apoptosis, ferroptosis is a non-apoptotic form of programmed cell death, but its specific role in the neurotoxicity of BPDE remains unclear. In this work, we investigated the ferroptosis in BPDE-induced cell death in human neuroblastoma cell line SH-SY5Y using a specific pharmacological inhibitor. Lipid peroxides, malondialdehyde production, glutathione / glutathione peroxidase activity, superoxide dismutase activity, and iron content were evaluated. Consistent with previous studies, our data showed that 0.5 µM BPDE poisoning for 24 hr could induce cell apoptosis and that cell survival could be improved by using apoptosis inhibitors. But with prolonged exposure time (72 hr) or increased exposure dose (1.0 µM), we have elucidated and validated that BPDE triggered ferroptosis in human SH-SY5Y cells. We also revealed that suppression of ferroptosis by specific inhibitors, ferrostatin-1 and deferoxamine, significantly rescued the phenotypes of ferroptosis induced by BPDE. BPDE downregulated Nrf2 and its target genes related to redox regulation, GPX4 and SLC7A11, but upregulated HO-1. Our results first demonstrated that BPDE caused cytotoxic effects on cell death via apoptosis and ferroptosis. Most notably, long-term environmental exposure to BPDE becomes a concern due to ferroptosis. Redox imbalance is controlled by the Nrf2, SLC7A11, and HO-1, through which lipid peroxides and ferrous ion accumulation cause ferroptosis after BPDE treatment. These findings highlight that targeting ferroptosis could serve as an effective protective strategy for neurotoxicity of BPDE.

Instability of decoupling livestock greenhouse gas emissions from economic growth in livestock products in the Tibetan highland.

Livestock production is the major livelihood for a growing local population on the Tibetan plateau. However, government policy is to reduce the number of livestock due to the large quantities of greenhouse gasses (GHG), in particular methane, produced by ruminants and the degradation of the grasslands. For this policy to be effective, with little effect on livelihoods, there should be a decoupling of GHG emissions from economic growth of livestock products. This study examined the synergetic effects of policies, extreme climate events and GHG emissions from livestock at the headwater region of the Yellow River since 1980. Optimization models of GHG emissions efficiency and drivers were developed and parameterized. Trade-offs between GHG emissions from livestock and economic growth from livestock, determined by the decoupling model, showed that from 1980 to 2015: 1) the GHG emissions decreased by 39%; (2) CH4 emissions from livestock decreased by 33%, and yaks emitted the most (accounted for 99.6%) among livestock; (3) N2O emissions decreased by 34%; (4) trade-offs between livestock GHG emissions and grassland uptake indicated that the grazing livestock system functioned as a net carbon sink; (5) the efficiency factor, especially technical efficiency, was the main driver of GHG emissions; and (6) GHG emissions from livestock were in a decoupling state from economic growth from livestock. However, decoupling has not been stable as inter-annual fluctuations have been large mainly due to extreme climatic events, such as snowstorm disasters, which indicates that the grazing system was still relatively fragile. The GHG emissions can be reduced further by mitigating CH4 emissions, and enhancing CO2 sequestration on grazed pastureland. The ongoing transformation of livestock industry development on the Tibetan plateau is associated with uncertainty under the background of global GHG mitigation.

Climate warming benefits alpine vegetation growth in Three-River Headwater Region, China.

Environmental factors that drive vegetation change in the Three River Headwater Region (TRHR) on Qinghai-Tibetan Plateau are largely unknown. In particular, the response of alpine grasslands in the TRHR to changing climate and ecological compensations is still poorly understood. Here, we present data on vegetation trends of the TRHR from 1982 to 2015 by employing multiple high-resolution satellite data to determine the mean annual normalized difference vegetation index (NDVI). In addition, spatio-temporal changes in climate were monitored by long-term climate data collection and by using the distributed modeling system. It emerged that: 1) there was a weak increasing trend, albeit not significant, in overall TRHR NDVI, ranging between 0.23 and 0.27; whereas, grassland NDVI ranged between 0.43 and 0.50, and displayed a significant (r2adj = 0.46; P = 0.004) linear increase with year; 2) annual average temperature was below 0 °C and increased linearly (r2adj = 0.60; P = 0.01) at a rate of 0.06 °C/yr from 2000 to 2015, which was almost four times faster than the rate of global warming; and 3) average rainfall was 493 mm/yr, with no significant yearly trend. In conclusion, climate warming enhanced vegetation growth and recovery in the TRHR since 2000; whereas, rainfall did not show a trend. However, vegetation changes on the spatial scale demonstrated zoning and segmentation effects. Consequently, for restoration of degraded lands in the TRHR, effective one-to-one ecological conservation projects, which are particular to an eco-fragile area, should be implemented. In addition, these results are important for regional planning of livestock stocking rates and animal husbandry systems, which can have great impact on the livelihood of the people in the area.

MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2.

This study aimed to understand the exact function and potential mechanism of miR-4500 in colorectal cancer (CRC). In this study, the expression of miR-4500 was decreased in both CRC cells and tissues, and downregulated miR-4500 indicated advanced tumor stage and poor survival. By bisulfite sequencing analysis, we found that the CpG island in the promoter region of miR-4500 was hypermethylated in CRC cells and tissues compared with normal control cells and non-tumor tissues, respectively. Functionally, gain- and loss-of-function analyses indicated the tumor suppressor role of miR-4500: it suppressed cell proliferation, cell cycle progression, migration, and invasion. Predictive algorithms and experimental analyses identified HMGA2 as a direct target of miR-4500. Reintroducing HMGA2 impaired the inhibitory effects of miR-4500 on cell growth and motility. Clinically, higher HMGA2 protein expression in CRC tissues was associated with advanced tumor stage and poor survival. An inverse correlation was found between miR-4500 levels and HMGA2 protein expression. Taken together, this study provides the first evidence that miR-4500 functions as a novel tumor suppressor in the miR-4500/HMGA2 axis in colorectal carcinogenesis, and restoring miR-4500 expression might represent a promising therapeutic strategy for CRC.

A critical role of mir-199a in the cell biological behaviors of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancer and the leading causes of cancer mortality worldwide. The critical role of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) are important in the cancer development. METHODS: The purpose of this study was to investigate the association of miR-199a expression in CRC and non-tumor tissues as well as assessed the effect of miR-199a on biological behaviors including cell proliferation, apoptosis, migration and invasion of CRC cells. The expression of miR-199a was distinctly decreased in colorectal cancer tissues compared with non-neoplastic colorectal tissues. RESULTS: In this study, we found that miR-199a down-regulation was associated with the CRC and metastasis incidence. Advanced study showed that miR-199a up-regulation would lead to decreased CRC proliferation, migration and invasion. However, no significant association of miR-199a treatment and apoptosis rate and cell-cycle were detected in this study. The detection for the mechanisms of miR-199a on the development of CRC showed that the anticarcinogenic effect of miR-199a might be produced through HIF-1α/VEGF pathway. CONCLUSION: It was found that miR-199a would reduce the proliferation, migration and invasion. However, overexpression of miR-199a on the apoptosis rate and cell cycles showed no significant results. The potential functionary mechanism of miR-199a might through HIF-1α/VEGF pathway. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9806714131513041 .

CD4+CD29+T cells are blamed for the persistent inflammatory response in ulcerative colitis.

Ulcerative colitis (UC) is a chronic gastrointestinal disorder eliciting occurrence of colorectal cancer, the third most common human malignancy. The diagnosis of UC is based on clinical symptoms combined with typical findings on endoscopy, radiology, and ultimately pathology. We investigated the variation trend of CD4+CD29+T cells together with MPO, VCAM-1 in different periods of rat UC model and UC patients. We also evaluated the relationship between CD4+CD29+T cells and disease severity. UC model was induced by administering DNCB liquid and acetate solution. We found upregulated expression of CD4+CD29+T cells in both peripheral blood and colon from rats, and a similar trend for MPO and VCAM-1 in colon (P<0.05); the expression was especially enhanced in UC rats at two weeks after the model was established (P<0.01). Such upregulation was also indicated in active and remission UC patients as compared to the healthy and enteritis groups (P<0.05), with the highest expression level detected in the active UC patients (P<0.01). Pearson correlation analysis showed a positive correlation of CD4+CD29+T cells in rat and human peripheral blood with DAI score (rrat=0.712, rhuman=0.677, P<0.01), and MPO in colon (rrat=0.514, rhuman=0.682, P<0.05). These results suggest that CD4+CD29+T cells may act as major effector cell subsets in persistent inflammatory responses for UC and that infiltration into colon inflammation may be induced by the combination of VCAM-1 and CD29.

Short-term effect and adverse events of adalimumab versus placebo in inducing remission for moderate-to-severe ulcerative colitis: a meta-analysis.

BACKGROUND: Adalimumab is used in an attempt to maintain remission for Ulcerative colitis. This study was to evaluate the efficacy and adverse events of adalimumab compared with placebo in inducing remission of Ulcerative colitis. METHODS: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, OVID, BIOSIS, CNKI, and Google were searched. All randomized trials comparing adalimumab with placebo in inducing remission of moderate-to-severe ulcerative colitis were included. RESULTS: Two randomized controlled trials with a total of 754 participants met the inclusion criteria. The pooled risk ratio (RR) of clinical remission was 1.85 (95% confidence interval (CI) 1.26 to 2.72) following adalimumab treatment. RR of clinical response was 1.40 (95% CI 1.19 to 1.65) while that of mucosal healing was 1.23 (95% CI 1.03 to 1.47). RR of any adverse events was 1.00 (95% CI 0.93 to 1.09). CONCLUSION: Compared with placebo, administration of adalimumab may increase the proportion of patients with moderate-to-severe ulcerative colitis attaining clinical remission, clinical response and mucosal healing. Adalimumab is also tolerated well in these patients.

Ulcerative colitis with inflammatory polyposis in a teenage boy: a case report.

Ulcerative colitis in addition to inflammatory polyposis is common. The benign sequel of ulcerative colitis can sometimes mimic colorectal carcinoma. This report describes a rare case of inflammatory polyposis with hundreds of inflammatory polyps in ulcerative colitis which was not easy to distinguish from other polyposis syndromes. A 16-year-old Chinese male suffering from ulcerative colitis for 6 mo underwent colonoscopy, and hundreds of polyps were observed in the sigmoid, causing colonic stenosis. The polyps were restricted to the sigmoid. Although rectal inflammation was detected, no polyps were found in the rectum. A diagnosis of inflammatory polyposis and ulcerative colitis was made. The patient underwent total colectomy and ileal pouch anal anastomosis. The patient recovered well and was discharged on postoperative day 8. Endoscopic surveillance after surgery is crucial as ulcerative colitis with polyposis is a risk factor for colorectal cancer. Recognition of polyposis requires clinical, endoscopic and histopathologic correlation, and helps with chemoprophylaxis of colorectal cancer, as the drugs used postoperatively for colorectal cancer, ulcerative colitis and polyposis are different.

Ginsenoside Rh2 alleviates dextran sulfate sodium-induced colitis via augmenting TGFß signaling.

Ginsenoside Rh2 (GRh2) has been reported to have therapeutic effects on various diseases. However, whether it may also affect the recovery from ulcerative colitis remains unknown. Here we induced colitis in mice by dextran sulfate sodium (DSS) administration, and then treated the mice with GRh2. We found that GRh2-treated mice showed significant alleviation of the DSS-induced colitis. Moreover, significant increase in the activity of TGFß signaling was detected in the GRh2-treated colon that had received DSS. To investigate whether there is a causative link among GRh2 treatment, TGFß signaling augment and the cure of colitis, we gave the DSS-treated mice a combination of GRh2 and a specific TGFß receptor I inhibitor, SB431542. SB431542 significantly decreased the activation of TGFß signaling in the colon from the GRh2-administrated mice, and consequently attenuated the therapeutic effect of GRh2. Our data thus demonstrate that GRh2 may alleviate DSS-induced colitis via augmenting TGFß signaling.

Baicalin down regulates the expression of TLR4 and NFkB-p65 in colon tissue in mice with colitis induced by dextran sulfate sodium.

BACKGROUND: Baicalin is one of flavonoid extracts from Scutellaria baicalensis, which has several functions including anti-inflammation, anti-bacteria, antitumor and et al. However, the mechanisms of anti-inflammatory of baicalin in ulcerative colitis is not clear. METHODS: Mice colitis models were established by dextran sodium sulfate, Mice administrated with baicalin (100 mg/kg) and mesalazine (100 mg/kg) twice daily by intragastric injection for 7 days after colitis induced were defined as treated group. Then the mice were sacrificed and the colon samples were collected. Toll-like receptor-2, 4, 9 were detected by immunohistochemistry. Signaling proteins such as TLR4, MyD88, and NF-κB p65 were analyzed by western blotting. Cytokine's mRNA include TNF-α, IL-6 IL-10 and IL-13 were measured by reverse transcription polymerase chain reaction. Modified disease activity index were used to analyse the severity of the disease by assessed of diarrhea, stool (occult) blood and body weight loss of the mice. RESULTS: Compared with control and model groups, modified disease activity index in baicalin and mesalazine treated, mice decreased gradually. Immunohistochemistry analysis showed the expression of TLR4, but not TLR2 and TLR9, in the mucosa of mice colon were decreased. Western blot analysis showed that in colitis model, the expression of NF-κB p65 and TLR4 decreased (P < 0.05), while the expression of MyD88 increased significantly compared to control group, and MyD88 expression can not be repressed by baicalin (P < 0.05). Baicalin and mesalazine treatment suppressed the expression of TNF-α, IL-6 and IL-13 mRNA (P < 0.05), yet up-regulated the expression of IL-10 mRNA (P < 0.05), compared to the DDS and control groups. CONCLUSIONS: Baicalin administration by intragastric injection ameliorates the severity of colon inflammation. The possible mechanism of anti-inflammatory response by baicalin may involve in the blocking of the TLR4/NF-κB-p65/IL-6 signaling pathway.

Serum IL-17 and IL-6 increased accompany with TGF-ß and IL-13 respectively in ulcerative colitis patients.

PURPOSES: To explorer the serum level of pro- and anti-inflammatory cytokines in the patients of ulcerative colitis and irritable bowel disease. And analyze the correlation between the cytokine's levels and disease's activity of ulcerative colitis patients. METHODS: Serum cytokines of ulcerative colitis and irritable bowel syndrome with diarrhea patients including IL-6, IL-10, IL-13, IL-17, TNF-α and TGF-ß were analyzed by enzyme linked immunosorbent assay, and ulcerative colitis activity were assessed by Mayo scoring system. The correlation of the serum level of cytokines and ulcerative colitis activity were analyzed by the SPSS 19.0 software. RESULTS: Compared with healthy people, the serum level of IL-6, IL-10, IL-13, IL-17, TNF-α and TGF-ß were elevated in ulcerative colitis patients. There is no direct correlation between each cytokines analyzed and the Mayo score. And the level of IL-6 is relevant to IL-13 (r=0.364, P=0.029), and the level of IL-17 is relevant to TGF-ß (r=0.336, P=0.045). CONCLUSION: When the pro-inflammatory cytokines increase in the serum of ulcerative colitis, the anti-inflammatory cytokines were increased concomitantly, Some cytokines are positive correlated, such as IL-6 and IL-13, IL-17 and TGF-ß, the mechanism of which is complex and needs further investigation.