Association between dietary inflammatory index and risk of endometriosis: A population-based analysis

Background and aimsChronic inflammation plays a significant role in the etiology of endometriosis, which might be affected by dietary intake. This study aimed to investigate the association between dietary inflammatory index (DII) and the risk of endometriosis.MethodsA cross-sectional analysis using data from the National Health and Nutrition Examination Survey (1999–2006) was conducted on 3,410 American participants, among whom 265 reported a diagnosis of endometriosis. DII scores were calculated based on the dietary questionnaire. The association of DII scores with endometriosis was evaluated by adjusted multivariate logistic regression analyzes, which were further investigated in the subgroups.ResultsIn the fully adjusted models, the odds ratio (OR) for endometriosis participants in the highest and middle tertiles of DII scores were 1.57 [95% confidence interval (CI): 1.14–2.17] and 1.18 (95% CI: 0.84–1.65), compared to the lowest tertile (Ptrend = 0.007). In subgroup analyzes, the significant positive association between DII scores and the endometriosis risk was also observed in non-obese women (ORtertile3vs1: 1.69, 95% CI: 1.12–2.55; Ptrend = 0.012), women without diabetes (ORtertile3vs1: 1.62, 95% CI: 1.16–2.27; Ptrend = 0.005), women with hypertension (ORtertile3vs1: 2.25, 95% CI: 1.31–3.87; Ptrend = 0.003), parous women (ORtertile3vs1: 1.55, 95% CI: 1.11–2.17; Ptrend = 0.011), and women using oral contraceptives (ORtertile3vs1: 1.63, 95% CI: 1.15–2.30; Ptrend = 0.006).ConclusionThis nationally representative study found that increased intake of the pro-inflammatory diet, as a higher DII score, was positively associated with endometriosis risk among American adults. Our results suggested anti-inflammatory dietary interventions may be promising in the prevention of endometriosis. Further prospective studies are necessary to confirm these findings

Unraveling the microbial puzzle: exploring the intricate role of gut microbiota in endometriosis pathogenesis

Endometriosis (EMs) is a prevalent gynecological disorder characterized by the growth of uterine tissue outside the uterine cavity, causing debilitating symptoms and infertility. Despite its prevalence, the exact mechanisms behind EMs development remain incompletely understood. This article presents a comprehensive overview of the relationship between gut microbiota imbalance and EMs pathogenesis. Recent research indicates that gut microbiota plays a pivotal role in various aspects of EMs, including immune regulation, generation of inflammatory factors, angiopoietin release, hormonal regulation, and endotoxin production. Dysbiosis of gut microbiota can disrupt immune responses, leading to inflammation and impaired immune clearance of endometrial fragments, resulting in the development of endometriotic lesions. The dysregulated microbiota can contribute to the release of lipopolysaccharide (LPS), triggering chronic inflammation and promoting ectopic endometrial adhesion, invasion, and angiogenesis. Furthermore, gut microbiota involvement in estrogen metabolism affects estrogen levels, which are directly related to EMs development. The review also highlights the potential of gut microbiota as a diagnostic tool and therapeutic target for EMs. Interventions such as fecal microbiota transplantation (FMT) and the use of gut microbiota preparations have demonstrated promising effects in reducing EMs symptoms. Despite the progress made, further research is needed to unravel the intricate interactions between gut microbiota and EMs, paving the way for more effective prevention and treatment strategies for this challenging condition

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

HGF-Modified Dental Pulp Stem Cells Mitigate the Inflammatory and Fibrotic Responses in Paraquat-Induced Acute Respiratory Distress Syndrome

Paraquat (PQ) poisoning can cause acute lung injury and progress to pulmonary fibrosis and eventually death without effective therapy. Mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) have been shown to partially reverse this damage. MSCs can be derived from bone marrow (BM-MSCs), adipose tissue (AD-MSCs), umbilical cord (UC-MSCs), dental pulp (DPSCs), and other sources. The biological characteristics of MSCs are specific to the tissue source. To develop an effective treatment for PQ poisoning, we compared the anti-inflammatory and antifibrotic effects of UC-MSCs and DPSCs and chose and modified a suitable source with HGF to investigate their therapeutic effects in vitro and in vivo. In this study, MSCs’ supernatant was beneficial to the viability and proliferation of human lung epithelial cell BEAS-2B. Inflammatory and fibrosis-related cytokines were analyzed by real-time PCR. The results showed that MSCs’ supernatant could suppress the expression of proinflammatory and profibrotic cytokines and increase the expression of anti-inflammatory and antifibrotic cytokines in BEAS-2B cells and human pulmonary fibroblast MRC-5. Extracellular vesicles (EVs) derived from MSCs performed more effectively than MSCs’ supernatant. The effect of DPSCs was stronger than that of UC-MSCs and was further strengthened by HGF modification. PQ-poisoned mice were established, and UC-MSCs, DPSCs, and DPSCs-HGF were administered. Histopathological assessments revealed that DPSCs-HGF mitigated lung inflammation and collagen accumulation more effectively than the other treatments. DPSCs-HGF reduced lung permeability and increased the survival rate of PQ mice from 20% to 50%. Taken together, these results indicated that DPSCs can suppress inflammation and fibrosis in human lung cells better than UC-MSCs. The anti-inflammatory and antifibrotic effects were significantly enhanced by HGF modification. DPSCs-HGF ameliorated pulmonitis and pulmonary fibrosis in PQ mice, effectively improving the survival rate, which might be mediated by paracrine mechanisms. The results suggested that DPSCs-HGF transplantation was a potential therapeutic approach for PQ poisoning

Exploring Piezo1, Piezo2, and TMEM150C in human brain tissues and their correlation with brain biomechanical characteristics

Abstract Unraveling the intricate relationship between mechanical factors and brain activity is a pivotal endeavor, yet the underlying mechanistic model of signaling pathways in brain mechanotransduction remains enigmatic. To bridge this gap, we introduced an in situ multi-scale platform, through which we delineate comprehensive brain biomechanical traits in white matter (WM), grey-white matter junctions (GW junction), and the pons across human brain tissue from four distinct donors. We investigate the three-dimensional expression patterns of Piezo1, Piezo2, and TMEM150C, while also examining their associated histological features and mechanotransduction signaling networks, particularly focusing on the YAP/β-catenin axis. Our results showed that the biomechanical characteristics (including stiffness, spring term, and equilibrium stress) associated with Piezo1 vary depending on the specific region. Moving beyond Piezo1, our result demonstrated the significant positive correlations between Piezo2 expression and stiffness in the WM. Meanwhile, the expression of Piezo2 and TMEM150C was shown to be correlated to viscoelastic properties in the pons and WM. Given the heterogeneity of brain tissue, we investigated the three-dimensional expression of Piezo1, Piezo2, and TMEM150C. Our results suggested that three mechanosensitive proteins remained consistent across different vertical planes within the tissue sections. Our findings not only establish Piezo1, Piezo2, and TMEM150C as pivotal mechanosensors that regulate the region-specific mechanotransduction activities but also unveil the paradigm connecting brain mechanical properties and mechanotransduction activities and the variations between individuals

Yoda1 Enhanced Low-Magnitude High-Frequency Vibration on Osteocytes in Regulation of MDA-MB-231 Breast Cancer Cell Migration

Low-magnitude (≤1 g) high-frequency (≥30 Hz) (LMHF) vibration has been shown to enhance bone mineral density. However, its regulation in breast cancer bone metastasis remains controversial for breast cancer patients and elder populations. Yoda1, an activator of the mechanosensitive Piezo1 channel, could potentially intensify the effect of LMHF vibration by enhancing the mechanoresponse of osteocytes, the major mechanosensory bone cells with high expression of Piezo1. In this study, we treated osteocytes with mono- (Yoda1 only or vibration only) or combined treatment (Yoda1 and LMHF vibration) and examined the further regulation of osteoclasts and breast cancer cells through the conditioned medium. Moreover, we studied the effects of combined treatment on breast cancer cells in regulation of osteocytes. Combined treatment on osteocytes showed beneficial effects, including increasing the nuclear translocation of Yes-associated protein (YAP) in osteocytes (488.0%, p < 0.0001), suppressing osteoclastogenesis (34.3%, p = 0.004), and further reducing migration of MDA-MB-231 (15.1%, p = 0.02) but not Py8119 breast cancer cells (4.2%, p = 0.66). Finally, MDA-MB-231 breast cancer cells subjected to the combined treatment decreased the percentage of apoptotic osteocytes (34.5%, p = 0.04) but did not affect the intracellular calcium influx. This study showed the potential of stimulating Piezo1 in enhancing the mechanoresponse of osteocytes to LMHF vibration and further suppressing breast cancer migration via osteoclasts

Non-cleavable talin rescues defect in the T-cell conjugation of T-cells deficient in the immune adaptor SKAP1.

While the cytoskeletal protein talin binds to the β-chain of LFA-1, the immune cell adaptor SKAP1 (SKAP-55) binds to the α-chain of the same integrin via RapL. Whereas calpain protease cleavage of talin is important for LFA-1 activation, it has been unclear whether SKAP1 can alter the function of talin or its associated adaptor RIAM in T-cells. In this paper, we report that Skap1-/- T-cells showed a reduction in the translocation of talin and RIAM to the contact interface of T-cells with antigenic beads or dendritic cells (DCs) presenting OVA peptide to OT-1 T-cells. In addition, Skap1-/- T-cells show an altered pattern of talin cleavage, while the expression of a cleavage resistant form of talin (L432G) restored the impaired adhesion of OT1 transgenic Skap1-/- T-cells with DCs. SKAP1 therefore can affect the function of talin in T-cells needed for optimal T-cell/DC conjugation.Wellcome TrustThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.imlet.2016.02.00