Catechol estrogens stimulate insulin secretion in pancreatic β-cells via activation of the transient receptor potential A1 (TRPA1) channel

Estrogen hormones play an important role in controlling glucose homeostasis and pancreatic β-cell function. Despite the significance of estrogen hormones for regulation of glucose metabolism, little is known about the roles of endogenous estrogen metabolites in modulating pancreatic β-cell function. In this study, we evaluated the effects of major natural estrogen metabolites, catechol estrogens, on insulin secretion in pancreatic β-cells. We show that catechol estrogens, hydroxylated at positions C2 and C4 of the steroid A ring, rapidly potentiated glucose-induced insulin secretion via a nongenomic mechanism. 2-Hydroxyestrone, the most abundant endogenous estrogen metabolite, was more efficacious in stimulating insulin secretion than any other tested catechol estrogens. In insulin-secreting cells, catechol estrogens produced rapid activation of calcium influx and elevation in cytosolic free calcium. Catechol estrogens also generated sustained elevations in cytosolic free calcium and evoked inward ion current in HEK293 cells expressing the transient receptor potential A1 (TRPA1) cation channel. Calcium influx and insulin secretion stimulated by estrogen metabolites were dependent on the TRPA1 activity and inhibited with the channel-specific pharmacological antagonists or the siRNA. Our results suggest the role of estrogen metabolism in a direct regulation of TRPA1 activity with potential implications for metabolic diseases

Touch and Go: Learning from Human-Collected Vision and Touch

The ability to associate touch with sight is essential for tasks that require physically interacting with objects in the world. We propose a dataset with paired visual and tactile data called Touch and Go, in which human data collectors probe objects in natural environments using tactile sensors, while simultaneously recording egocentric video. In contrast to previous efforts, which have largely been confined to lab settings or simulated environments, our dataset spans a large number of "in the wild" objects and scenes. To demonstrate our dataset's effectiveness, we successfully apply it to a variety of tasks: 1) self-supervised visuo-tactile feature learning, 2) tactile-driven image stylization, i.e., making the visual appearance of an object more consistent with a given tactile signal, and 3) predicting future frames of a tactile signal from visuo-tactile inputs.Comment: Accepted by NeurIPS 2022 Track of Datasets and Benchmark

mTOR Signaling in X/A‐Like Cells Contributes to Lipid Homeostasis in Mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147831/1/hep30229-sup-0001-FigS1-S8.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147831/2/hep30229_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147831/3/hep30229.pd

Mycobacterium tuberculosis Rv1987 protein attenuates inflammatory response and consequently alters microbiota in mouse lung

IntroductionHealthy lung microbiota plays an important role in preventing Mycobacterium tuberculosis (Mtb) infections by activating immune cells and stimulating production of T-helper cell type 1 cytokines. The dynamic stability of lung microbiota relies mostly on lung homeostasis. In our previous studies, we found that Mtb virulence factor, Rv1987 protein, can mediate host immune response and enhance mycobacterial survival in host lung. However, the alteration of lung microbiota and the contribution of lung microbiota dysbiosis to mycobacterial evasion in this process are not clear so far.MethodsM. smegmatis which does not contain the ortholog of Rv1987 protein was selected as a model strain to study the effects of Rv1987 on host lung microbiota. The lung microbiota, immune state and metabolites of mice infected by M. smegmatis overexpressing Rv1987 protein (MS1987) were detected and analyzed.ResultsThe results showed that Rv1987 inhibited inflammatory response in mouse lung and anaerobic bacteria and Proteobacteria, Bacteroidota, Actinobacteriota and Acidobacteriota bacteria were enriched in the lung tissues correspondingly. The immune alterations and microbiota dysbiosis affected host metabolic profiles, and some of significantly altered bacteria in MS1987-infected mouse lung, such as Delftia acidovorans, Ralstonia pickettii and Escherichia coli, led to anti-inflammatory responses in mouse lung. The secretory metabolites of these altered bacteria also influenced mycobacterial growth and biofilm formation directly.ConclusionAll these results suggested that Rv1987 can attenuate inflammatory response and alter microbiota in the lung, which in turn facilitates mycobacterial survival in the host

Dissection of the mechanism of traditional Chinese medical prescription-Yiqihuoxue formula as an effective anti-fibrotic treatment for systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue fibrotic disease for which there is no effective treatment. Traditional Chinese Medicine (TCM), such as the Yiqihuoxue formula used in Shanghai TCM-integrated Hospital, has shown the efficacy of anti-fibrosis in clinical applications. This study was aiming to dissect the anti-fibrotic mechanism of Yiqihuoxue treatment for SSc. METHODS: Bleomycin-induced mice and SSc dermal fibroblasts were treated with Yiqihuoxue decoction; NIH-3T3 fibroblasts were exposed to exogenous TGF-β1, and then cultured with or without Yiqihuoxue decoction. Luciferase reporter gene assay was used to determine the activity of Smad binding element (SBE). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the mRNA levels of extracellular matrix (ECM) genes. The protein levels of type I collagen, Smad3 and phosphorylated-Smad3 (p-Smad3) were detected by western blotting. Student’s t-tests were used to determine the significance of the results. RESULTS: Bleomycin-induced mice, SSc dermal fibroblasts and TGF-β1-induced NIH/3T3 fibroblasts showed higher levels of ECM gene transcriptions and collagen production. In addition, the phosphorylation level of Smad3 and activity of SBE were significantly increased after exogenous TGF-β1 induction. Whereas, Yiqihuoxue treatment could obviously attenuate fibrosis in bleomycin-induced mice, down regulate ECM gene expressions and collagen production in SSc dermal fibroblasts and TGF-β1-induced NIH/3T3 fibroblasts. Furthermore, the aberrantly high phosphorylation level of Smad3 and activity of SBE in the TGF-β1-induced NIH/3T3 fibroblasts were also dramatically decreased by Yiqihuoxue treatment. CONCLUSIONS: Yiqihuoxue treatment could effectively reduce collagen production via down-regulating the phosphorylation of Smad3 and then the activity of SBE, which are involved in the TGF-β pathway and constitutively activated in the progression of SSc

A potential relationship between MMP-9 rs2250889 and ischemic stroke susceptibility

PurposeIschemic stroke (IS), a serious cerebrovascular disease, greatly affects people's health and life. Genetic factors are indispensable for the occurrence of IS. As a biomarker for IS, the MMP-9 gene is widely involved in the pathophysiological process of IS. This study attempts to find out the relationship between MMP-9 polymorphisms and IS susceptibility.MethodsA total of 700 IS patients and 700 healthy controls were recruited. The single nucleotide polymorphism (SNP) markers of the MMP-9 gene were genotyped by the MassARRAY analyzer. Multifactor dimensionality reduction (MDR) was applied to generate SNP–SNP interaction. Furthermore, the relationship between genetic variations (allele and genotype) of the MMP-9 gene and IS susceptibility was analyzed by calculating odds ratios (ORs) and 95% confidence intervals (CIs).ResultsOur results demonstrated that rs2250889 could significantly increase the susceptibility to IS in the codominant, dominant, overdominant, and log-additive models (p < 0.05). Further stratification analysis showed that compared with the control group, rs2250889 was associated with IS risk in different case groups (age, female, smoking, and non-drinking) (p < 0.05). Based on MDR analysis, rs2250889 was the best model for predicting IS risk (cross-validation consistency: 10/10, OR = 1.56 (1.26–1.94), p < 0.001).ConclusionOur study preliminarily confirmed that SNP rs2250889 was significantly associated with susceptibility to IS

The rates and the determinants of hypertension according to the 2017 definition of hypertension by ACC/AHA and 2014 evidence-based guidelines among population aged ≥40 years old

Background : In November 2017, the American College of Cardiology/American Heart Association (ACC/AHA) updated their definition of hypertension from 140/90 mm Hg to 130/80 mm Hg. Objectives : We sought to assess the situation of hypertension and the impact of applying the new threshold to a geographically and ethnically diverse population. Methods : We analyzed selected data on 237,142 participants aged ≥40 who had blood pressure taken for the 2014 China National Stroke Screening and Prevention Project. Choropleth maps and logistic regression analyses were performed to estimate the prevalence, geographical distribution and risk factors of hypertension using both 2017 ACC/AHA guidelines and 2014 evidence-based guidelines. Results : The present cross-sectional study showed the age- and sex-standardized prevalence of hypertension was 37.08% and 58.52%, respectively, according to 2014 evidence-based guidelines and 2017 ACC/AHA guidelines. The distribution of hypertension and risk factors changed little between guidelines, with data showing a high prevalence of hypertension around Bohai Gulf and in south central coastal areas using either definition. The age- and sex-standardized prevalence of newly labeled as hypertensive was 21.44%. Interestingly, the high prevalence region of newly labeled as hypertensive was found in the north China. Conclusion : The prevalence of hypertension increased significantly on 2017 ACC/AHA guidelines compared to the prevalence when using 2014 evidence-based guidelines, with high prevalence areas of newly labeled as hypertensive now seen mainly in north China. There need to be correspondingly robust efforts to improve health education, health management, and behavioral and lifestyle interventions in the north

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat