Predicting the potential mechanism of Radix Chimonanthi Pracecocis in treating osteoarthritis by network pharmacology analysis combined with experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Chimonanthi Pracecocis(RCP), also known as Tiekuaizi, widely used by the Miao community in Guizhou, exhibits diverse biological activities and holds promise for the treatment of osteoarthritis (OA). However, there is a lack of contemporary pharmacological research in this area. AIMS OF THE STUDY: This study aims to explore the potential of targets and mechanisms of RCP in the treatment of OA. MATERIALS AND METHODS: The chemical components of RCP were identified using UPLC-MS/MS, and active components were determined based on the Lipinski rule. RCP and OA-related targets were retrieved from public databases such as TCMSP and GeneCards. Network pharmacology approaches were employed to identify key genes. The limma package (version 3.40.2) in R 4.3.2 was used to screen for differentially expressed genes (DEGs) between OA and healthy individuals in GSE82107. DEGs were analyzed using an independent sample t-test and receiver operating characteristic analysis in GraphPad Prism 9.5.1. Additionally, molecular docking (SYBYL2.1.1) was used to analyze the binding interactions between the active components and target proteins. Finally, we established a papain-induced osteoarthritis (OA) rat model and treated it with RCP aqueous extract by gavage. We validated relevant indicators using real-time fluorescence quantitative polymerase chain reaction, western blot, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: Seven active components and 53 targets were identified. The results of GO and KEGG enrichment analyses confirmed the significant role of RCP in the regulation of pyroptosis. Hypoxia-inducible factor-1α (HIF-1α) was identified as a key gene involved in the main biological functions. Molecular docking analysis revealed that Praecoxin, Isofraxidin, Esculin, and Naringenin can bind to the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) (T-Score > 5). Additionally, Praecoxin can bind to HIF-1α (T-Score > 5). In vivo experiments demonstrated that RCP significantly affects the NLRP3 inflammasome, which is regulated by the HIF-1α pathway. RCP inhibited pyroptosis and reduced synovial inflammation. CONCLUSIONS: This study confirmed the efficacy of RCP aqueous extract in the treatment of OA and identified seven active components (esculin, dihydrokaempferol, naringenin, praecoxin, carnosol, hydroxyvalerenic acid, isofraxidin) that may play an anti-pyroptosis role in the treatment of OA by downregulating the expression of HIF-1α and NLRP3 inflammasome.

Low platelet count at diagnosis of anti-neutrophil cytoplasmic antibody-associated vasculitis is correlated with the severity of disease and renal prognosis.

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune disease that involves inflammation of blood vessels. There is increasing evidence that platelets play a crucial role not only in hemostasis but also in inflammation and innate immunity. In this study, we explored the relationship between platelet count, clinical characteristics, and the prognosis of patients with AAV. We divided 187 patients into two groups based on their platelet count. Clinicopathological data and prognostic information were retrospectively gathered from medical records. Univariate and multivariate regression analyses were used to identify risk factors for prognosis, including end-stage renal disease (ESRD) and mortality. The cutoff point for platelet count was set at 264.5 × 109/L, as determined by the receiver operating characteristic (ROC) curve for predicting progression to ESRD in patients with AAV. We observed patients with low platelet count (platelets < 264.5 × 109/L) had lower leukocytes, hemoglobin, complement, acute reactants, and worse renal function (P for eGFR < 0.001). They were also more likely to progress to ESRD or death compared to the high platelet count group (platelets > 264.5 × 109/L) (P < 0.0001, P = 0.0338, respectively). Low platelet count was potentially an independent predictor of poor renal prognosis in the multivariate regression analysis [HR 1.670 (95% CI 1.019-2.515), P = 0.014]. Lower platelet count at diagnosis is associated with more severe clinical characteristics and impaired renal function. Therefore, platelet count may be an accessible prognostic indicator for renal outcomes in patients with AAV.

Sympathetic innervation induces exosomal miR-125 transfer from osteoarthritic chondrocytes, disrupting subchondral bone homeostasis and aggravating cartilage damage in aging mice.

INTRODUCTION: Osteoarthritis (OA) is a progressive disease that poses a significant threat to human health, particularly in aging individuals: Although sympathetic activation has been implicated in bone metabolism, its role in the development of OA related to aging remains poorly understood. Therefore, this study aimed to investigate how sympathetic regulation impacts aging-related OA through experiments conducted both in vivo and in vitro. METHODS: To analyze the effect of sympathetic regulation on aging-related OA, we conducted experiments using various mouse models. These models included a natural aging model, a medial meniscus instability model, and a load-induced model, which were used to examine the involvement of sympathetic nerves. In order to evaluate the expression levels of ß1-adrenergic receptor (Adrß1) and sirtuin-6 (Sirt6) in chondrocytes of naturally aging OA mouse models, we performed assessments. Additionally, we investigated the influence of ß1-adrenergic receptor knockout or treatment with a ß1-adrenergic receptor blocker on the progression of OA in aging mice and detected exosome release and detected downstream signaling expression by inhibiting exosome release. Furthermore, we explored the impact of sympathetic depletion through tyrosine hydroxylase (TH) on OA progression in aging mice. Moreover, we studied the effects of norepinephrine(NE)-induced activation of the ß1-adrenergic receptor signaling pathway on the release of exosomes and miR-125 from chondrocytes, subsequently affecting osteoblast differentiation in subchondral bone. RESULTS: Our findings demonstrated a significant increase in sympathetic activity, such as NE levels, in various mouse models of OA including natural aging, medial meniscus instability, and load-induced models. Notably, we observed alterations in the expression levels of ß1-adrenergic receptor and Sirt6 in chondrocytes in OA mouse models associated with natural aging, leading to an improvement in the progression of OA. Critically, we found that the knockout of ß1-adrenergic receptor or treatment with a ß1-adrenergic receptor blocker attenuated OA progression in aging mice and the degraded cartilage explants produced more exosome than the nondegraded ones, Moreover, sympathetic depletion through TH was shown to ameliorate OA progression in aging mice. Additionally, we discovered that NE-induced activation of the ß1-adrenergic receptor signaling pathway facilitated the release of exosomes and miR-125 from chondrocytes, promoting osteoblast differentiation in subchondral bone. CONCLUSION: In conclusion, our study highlights the role of sympathetic innervation in facilitating the transfer of exosomal miR-125 from osteoarthritic chondrocytes, ultimately disrupting subchondral bone homeostasis and exacerbating cartilage damage in aging mice. These findings provide valuable insights into the potential contribution of sympathetic regulation to the pathogenesis of aging-related OA.

Social Change and Race-Specific Homicide Trajectories: An Age-Period-Cohort Analysis.

Objectives: Social change and the aging process are racially bifurcated in the United States, where Black and White populations have long lived in divergent social worlds. This study examines the cohort patterns and life-course trajectories of Black and White homicide involvement over the past four decades. Data and Methods: The study uses data from the Supplemental Homicide Reports and Age-Period-Cohort-Interaction (APC-I) models to analyze race-specific trends of (alleged) homicide offending and victimization between 1976 and 2018 in the U.S. Results: Results reveal similar patterns in the age, period, and cohort effects on Black and White homicide involvement. However, while the shapes of these trajectories are comparable, the volatility in cohort effects on homicide is much more accentuated for Black cohorts than White cohorts. We also find racial differences for cohorts born after 1990, with a downward cohort pattern among the White group but a flat cohort trend among the Black group. Conclusions: Findings suggest that Black cohorts' homicide involvement is more susceptible than White cohorts' to the influence of external social changes (e.g., economic downturn, the crack epidemic). In addition, an increasing racial gap between Black and White populations is found among the recent birth cohorts. Possible mechanisms are discussed.

Trends in sleep duration in the U.S. from 2004 to 2018: A decomposition analysis.

Average sleep duration in the United States declined in recent years, and the decline may be linked with many biopsychosocial factors. We examine how a set of biopsychosocial factors have differentially contributed to the temporal trends in self-reported sleep duration across racial groups between 2004-2005 and 2017-2018. Using repeated nationally representative cross-sections from the National Health Interview Survey, we decompose the influence of biopsychosocial factors on sleep duration trends into two components. One component corresponds to coefficient changes (i.e., changes in the associations between behaviors or exposures and sleep duration) of key biopsychosocial factors, and the other part accounts for the compositional changes (i.e., changes in the distributions of exposures) in these biopsychosocial factors during the study period. We reveal that changes in the coefficients of some biopsychosocial factors are more important than compositional changes in explaining the decline in sleep duration within each racial/ethnic group. Our findings highlight racial differences manifest across multiple biopsychosocial domains that are shifting in terms of association and composition. Methodologically, we note that the standard regression approach for analyzing temporal trends neglects the role of coefficient changes over time and is thus insufficient for fully capturing how biopsychosocial factors may have influenced the temporal patterns in sleep duration and related health outcomes.

Isolation, identification, and induced differentiation of satellite cells from skeletal muscle of adult tree shrews.

A method for the in vitro isolation, purification, identification, and induced differentiation of satellite cells from adult tree shrew skeletal muscle was established. The mixed enzyme digestion method and differential adhesion method were used to obtain skeletal muscle satellite cells, which were identified and induced to differentiate to verify their pluripotency. The use of a mixture of collagenase II, hyaluronidase IV, and DNase I is an efficient method for isolating adult tree shrew skeletal muscle satellite cells. The P3 generation of cells had good morphology, rapid proliferation, high viability, and an "S"-shaped growth curve. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining indicated that marker genes or proteins were expressed in skeletal muscle satellite cells. After myogenic differentiation was induced, multiple-nucleated myotubes were observed, and the MyHC protein was expressed. The expression of myogenic marker genes changed with the differentiation process. After the induction of adipogenic differentiation, orange-red lipid droplets were observed, and the expression of adipogenic marker genes increased gradually with the differentiation process. In summary, satellite cells from adult tree shrew skeletal muscle were successfully isolated using a mixed enzyme digestion method, and their potential for differentiation into myogenic and adipogenic cells was confirmed, laying a foundation for further in vitro study of tree shrew muscle damage.

Pipecolic acid mitigates ferroptosis in diabetic retinopathy by regulating GPX4-YAP signaling.

Diabetic retinopathy (DR) is currently recognized as the leading cause of end-stage eye disease. Pipecolic acid, a metabolite, has a significant regulatory effect on several pathological processes. However, the exact mechanism by which it causes damage in diabetic retinopathy is unknown. Between September 2021 and December 2022, 40 patients were retrospectively examined and divided into two groups: the healthy group (n = 20) and the DR group (n = 20). Metabolomic analysis found that pipecolic acid plays an important role in this process. Streptozotocin-induced diabetic mice and high-glucose cultured human retinal capillary endothelial cells (HRCECs) were then treated with pipecolic acid. Several oxidative stress measurements and RNA sequencing of retinal cells were tested. A gene interaction study was conducted using bioinformatics. Comparison of serological metabolites between healthy volunteers and DR patients showed that pipecolic acid was significantly lower in DR patients, and there was a negative correlation between the level of pipecolic acid with blood glucose and glycated hemoglobin. Yes-associated protein (YAP) mRNA, Malondialdehyde (MDA), and reactive oxygen species (ROS) levels were significantly higher in diabetic mice, but glutathione peroxidase (GSH-Px) levels were significantly lower. Pipecolic acid significantly alleviated oxidative stress and YAP expression. The number of vascular tubes was significantly higher in the DR group, and pipecolic acid treatment significantly reduced tube formation. RNA-Sequencing analysis revealed that YAP and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4) expression was reduced, and functional enrichment analysis revealed that ferroptosis and Hippo signaling pathways play an important role in this process. Additionally, pipecolic acid's ability to improve DR is diminished after YAP and GPX4 ablation. This study found that pipecolic acid, as a metabolite, may impede the progression of DR by inhibiting the YAP-GPX4 signaling pathway.

C5a enhances Vδ1 T cells recruitment via the CCL2-CCR2 axis in IgA nephropathy.

BACKGROUND: Mucosal immune-associated γδ T cells have been implicated in IgA nephropathy (IgAN). However, the involvement of Vδ1 T cells, the major γδ T cells subtype, in renal damage and the mechanism underlying their migration from peripheral blood to kidney in IgAN remain unclear. METHODS: Clinical data from IgAN patients and healthy controls (HC) were analyzed. Phenotypes and chemokine receptors of γδ T cell were compared between IgAN patients and HC. Immunohistochemistry and immunofluorescence were performed to assess the infiltration of γδ T cell subsets and the expression of chemokine in renal tissues. In vitro, C5a was used to stimulate the human glomerular mesangial cells (HMCs) and chemotaxis experiment was used to examine Vδ1 T cells migration. Correlation between Vδ1 T cells and related clinical indicators were analyzed. RESULTS: IgAN patients exhibited decreased Vδ1 T cell in blood but increased levels in kidneys compared to HC. Increased CCR2-expressing Vδ1 T cells and serum level of CCL2 were observed in IgAN patients. CCL2 co-localized with CCR2 in HMCs of IgAN. In vitro, C5a enhanced Vδ1 T cells recruitment by HMCs through CCL2-CCR2 axis. Importantly, circulating Vδ1 T cell levels showed a negatively correlated with both the urinary protein creatinine ratio (UACR) and 24-hour urine protein (UP). Moreover, kidney infiltration of Vδ1 cells positively correlated with UACR, UP, mesangial hyperplasia and renal tubule atrophy/interstitial fibrosis in IgAN. CONCLUSIONS: C5a-induced production of CCL2 by HMCs facilitates Vδ1 T cells recruitment via the CCL2-CCR2 axis, contributing to renal damage in IgAN.

Preliminary Validation of the Revised Illness Perception Questionnaire for Patients with Nasopharyngeal Carcinoma in China.

Nasopharyngeal carcinoma is a common and highly malignant cancer in southern China. It is important to accurately assess the illness perception of nasopharyngeal carcinoma according to the common-sense model of self-regulation. The purpose was to validate the Chinese version of the Revised Illness Perception Questionnaire for patients with Nasopharyngeal carcinoma. A cross-sectional survey of 631 patients with Nasopharyngeal carcinoma was conducted in Guangzhou, China. The reliability of the scale was evaluated using Cronbach's alpha. The factor structure was assessed using exploratory factor analysis (EFA) of each dimension. The EFA revealed that the 29-item self-rated scale has a seven-factor structure consistent with the original scale and explained 67.3% of the variance after extraction and rotation. The scale showed satisfactory reliability. The item-total correlations ranged from -0.16 to 0.64 (p < 0.05). The item-subscale correlations ranged from 0.46 to 0.91 (p < 0.05). The item-other subscale correlations ranged from -0.38 to 0.51 and from -0.21 to 0.56 (p < 0.05). Significant correlations were found between the timeline (acute/chronic) (r = 0.224, r = 0.166), consequences (r = 0.415, r = 0.338), timeline cyclical (r = 0.366, r = 0.284), emotional representations (r = 0.497, r = 0.465), personal control (r = -0.122, r = -0.134), treatment control (r = -0.135, r = -0.148), and illness coherence (r = -0.261, r = -0.213) subscales, and depression, anxiety (p < 0.05). The scale revealed acceptable reliability, factorial validity, and construct validity. It could be used to assess the illness representations of Chinese patients with nasopharyngeal carcinoma.

Urinary isomorphic red blood cells for the prediction of disease severity and renal outcomes in MPO-ANCA-associated vasculitis: a retrospective cohort study.

BACKGROUND: Hematuria is common in myeloperoxidase anti-neutrophil cytoplasmic antibody associated vasculitis (ANCA-MPO). Previous studies have mainly focused on urinary dysmorphic red blood cells and few have reported the clinical significance of isomorphic urinary red blood cells. Therefore, the main aim of this study was to assess the predictive yield  of urinary isomorphic red blood cells for disease severity and renal outcomes in patients with ANCA-MPO associated vasculitis. METHODS: A total of 191 patients with ANCA-MPO associated vasculitis with hematuria were retrospectively selected and were divided into two groups (with isomorphic red blood cells versus dysmorphic red blood cells) according to the percentage of isomorphic red blood cells on urinary sediment analysis. Clinical, biological and pathological data at diagnosis were compared. Patients were followed up for a median of 25 months and progression to end-stage kidney disease and death were regarded as main outcome events. Additionally, univariate and multivariate Cox regression models were used to estimate the risk factors for end-stage kidney disease. RESULTS: Out of 191 patients, 115 (60%) had ≥ 70% and 76 (40%) had < 30% urine isomorphic red blood cells. Compared with patients in the dysmorphic red blood cell group, patients in the isomorphic red blood cell group had a significantly lower estimated glomerular filtration rate (eGFR) [10.41 mL/min (IQR 5.84-17.06) versus 12.53 (6.81-29.26); P = 0.026], higher Birmingham Vasculitis Activity Score [16 (IQR 12-18) versus 14 (10-18); P = 0.005] and more often received plasma exchange [40.0% versus 23.7% (P = 0.019)] at diagnosis. Kidney biopsies revealed a higher proportion of patients with glomerular basement membrane fracture in the isomorphic red blood cell group [46.3% versus 22.9% (P = 0.033)]. Furthermore, patients with predominant urinary isomorphic red blood cells were more likely to progress to end-stage kidney disease [63.5% versus 47.4% (P = 0.028)] and had a higher risk of death [31.3% versus 19.7% (P = 0.077)]. The end-stage kidney disease-free survival was lower in patients in the isomorphic red blood cell group (P = 0.024). However, urine isomorphic red blood cells ≥ 70% could not predict the presence of end-stage kidney disease in multivariate Cox analysis. CONCLUSION: Myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis patients with predominant urinary isomorphic red blood cells at diagnosis had more severe clinical manifestations and a higher risk of poor renal outcomes. In this respect, urinary isomorphic red blood cells could be viewed as a promising biomarker of ANCA_MPO vasculitis severity and progression.

Describing and explaining age, period, and cohort trends in Americans' vocabulary knowledge.

For a quarter of a century researchers have been documenting and trying to explain trends in Americans' vocabulary knowledge using data from the General Social Survey (GSS) and its WORDSUM test. Trends in Americans' vocabulary knowledge have important practical implications-for example, for educational policy and practice-and speak to the American workforce's competitiveness in the global knowledge economy. We contribute to this debate by analyzing 1978-2018 GSS data using an improved analytical approach that is consistent with theoretical notions of cohort effects and that permits simultaneously estimating inter-cohort average differences and intra-cohort life-course changes. We find that WORDSUM scores peak around age 35 and gradually decline in older ages; the scores were significantly lower in the 1980s and higher in the late 2000s and 2010s; and the 1940-1954 birth cohorts and the 1965 and later birth cohorts had notably higher and lower scores, respectively, than the expectation based on age and period main effects. We provide new evidence that such cohort differences tend to persist over the life course. Interestingly, the effects of increasing educational attainment and decreasing reading behaviors seemed to cancel out, leading to a relatively flat overall period trend. Trends in television viewing and word obsolescence did not appear to affect age, period, or cohort trends in WORDSUM scores. Supplementary Information: The online version contains supplementary material available at 10.1007/s11113-023-09771-5.

Cross-sectional association between neighborhood socioeconomic status and sleep duration among Black and white men and women: The Southern Community Cohort Study.

OBJECTIVE: To examine the association of neighborhood socioeconomic status (SES) with sleep duration among a large cohort of Black and white men and women in the United States. METHODS: We used data from the Southern Community Cohort Study (SCCS, N = 75,248). Neighborhood SES was based on census data and sleep duration was measured by self-report. Multinomial logistic regression analysis was performed to assess the association between neighborhood SES and short (<7 hours) and long (≥9 hours) sleep in the overall sample and according to race-sex subgroups. RESULTS: In the total sample, when compared with the highest quintile of neighborhood SES, the lowest quintile was associated with higher odds of both short (adjusted ORQ5 vs. Q1 [95% CI], 1.10 [1.03, 1.17]) and long sleep (1.37 [1.24, 1.52]). In race-sex specific analysis, the association between lower neighborhood SES and short sleep was only observed among white women (1.21 [1.05, 1.40]), but not in other subgroups. On the other hand, the association between lower neighborhood SES and long sleep duration was primarily observed among Black women (1.31 [1.06, 1.60]). CONCLUSIONS: The association between neighborhood SES and sleep duration varied among race-and-sex subgroups. These findings provide new evidence on the importance of considering individual sociodemographic characteristics in understanding the potential effects of neighborhood socioeconomic context on sleep health.

The gut microbiota metabolite capsiate regulate SLC2A1 expression by targeting HIF-1α to inhibit knee osteoarthritis-induced ferroptosis.

Ferroptosis is an iron-dependent cell death that has been found to aggravate the progression of osteoarthritis (OA) and gut microbiota- OA axis refers to the bidirectional information network between the gut microbiota and OA, which may provide a new way to protect the OA. However, the role of gut microbiota-derived metabolites in ferroptosis-relative osteoarthritis remains unclear. The objective of this study was to analyze the protective effect of gut microbiota and its metabolite capsiate (CAT) on ferroptosis-relative osteoarthritis in vivo and in vitro experiments. From June 2021 to February 2022, 78 patients were evaluated retrospectively and divided into two groups: The health group (n = 39) and the OA group (n = 40). Iron and oxidative stress indicators were determined in peripheral blood samples. And then in vivo and in vitro experiments, a surgically destabilized medial meniscus (DMM) mice model was established and treated with CAT or Ferric Inhibitor-1 (Fer-1). Solute Carrier Family 2 Member 1 (SLC2A1) short hairpin RNA (shRNA) was utilized to inhibit SLC2A1 expression. Serum iron was increased significantly but total iron binding capacity was decreased significantly in OA patients than healthy people (p < 0.0001). The least absolute shrinkage and selection operator clinical prediction model suggested that serum iron, total iron binding capacity, transferrin, and superoxide dismutase were all independent predictors of OA (p < 0.001). Bioinformatics results suggested that SLC2A1, Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), and HIF-1α (Hypoxia Inducible Factor 1 Alpha)-related oxidative stress signaling pathways play an important role in iron homeostasis and OA. In addition, gut microbiota 16s RNA sequencing and untargeted metabolomics were used to find that gut microbiota metabolites CAT in mice with osteoarthritis were negatively correlated with Osteoarthritis Research Society International (OARSI) scores for chondrogenic degeneration (p = 0.0017). Moreover, CAT reduced ferroptosis-dependent osteoarthritis in vivo and in vitro. However, the protective effect of CAT against ferroptosis-dependent osteoarthritis could be eliminated by silencing SLC2A1. SLC2A1 was upregulated but reduced the SLC2A1 and HIF-1α levels in the DMM group. HIF-1α, MALAT1, and apoptosis levels were increased after SLC2A1 knockout in chondrocyte cells (p = 0.0017). Finally, downregulation of SLC2A1 expression by Adeno-associated Virus (AAV) -SLC2A1 shRNA improves osteoarthritis in vivo. Our findings indicated that CAT inhibited HIF-1a expression and reduced ferroptosis-relative osteoarthritis progression by activating SLC2A1.

Identification of kukoamine a as an anti-osteoporosis drug target using network pharmacology and experiment verification.

BACKGROUND: Osteoporosis (OP) is a major and growing public health problem characterized by decreased bone mineral density and destroyed bone microarchitecture. Previous studies found that Lycium Chinense Mill (LC) has a potent role in inhibiting bone loss. Kukoamine A (KuA), a bioactive compound extract from LC was responsible for the anti-osteoporosis effect. This study aimed to investigate the anti-osteoporosis effect of KuA isolated from LC in treating OP and its potential molecular mechanism. METHOD: In this study, network pharmacology and molecular docking were investigated firstly to find the active ingredients of LC such as KuA, and the target genes of OP by the TCMSP platform. The LC-OP-potential Target gene network was constructed by the STRING database and network maps were built by Cytoscape software. And then, the anti-osteoporotic effect of KuA in OVX-induced osteoporosis mice and MC3T3-E1 cell lines were investigated and the potential molecular mechanism including inflammation level, cell apoptosis, and oxidative stress was analyzed by dual-energy X-ray absorptiometry (DXA), micro-CT, ELISA, RT-PCR, and Western Blotting. RESULT: A total of 22 active compounds were screened, and we found KuA was identified as the highest active ingredient. Glycogen Phosphorylase (PYGM) was the target gene associated with a maximum number of active ingredients of LC and regulated KuA. In vivo, KuA treatment significantly increased the bone mineral density and improve bone microarchitecture for example increased BV/TV, Tb.N and Tb.Th but reduced Tb.Sp in tibia and lumber 4. Furthermore, KuA increased mRNA expression of osteoblastic differentiation-related genes in OVX mice and protects against OVX-induced cell apoptosis, oxidative stress level and inflammation level. In vitro, KuA significantly improves osteogenic differentiation and mineralization in cells experiment. In addition, KuA also attenuated inflammation levels, cell apoptosis, and oxidative stress level. CONCLUSION: The results suggest that KuA could protect against the development of OP in osteoblast cells and ovariectomized OP model mice and these found to provide a better understanding of the pharmacological activities of KuA again bone loss.

The mobility effects hypothesis: Methods and applications.

We discuss hypotheses researchers have put forth to explain how outcomes of socially mobile and immobile individuals might differ and/or how mobility experiences are related to outcomes of interest. Next, we examine the methodological literature on this topic, culminating in the development of the diagonal mobility model (DMM, also called the diagonal reference model in some studies), the primary tool of use since the 1980's. We then discuss some of the many applications of the DMM. Although the model was proposed to examine the effects of social mobility on outcomes of interest, the estimated relationships between mobility and outcomes that researchers have called mobility effects are more appropriately regarded as partial associations. When mobility is not associated with outcomes, as is often found in empirical work, the outcomes of movers from origin o to destination d are a weighted average of the outcomes of individuals who remained in states o and d respectively, and the weights capture the relative salience of origins and destinations in the acculturation process. In light of this attractive feature of the model, we briefly develop several generalizations of the current DMM that future researchers should also find useful. Finally, we propose new estimands of mobility effects, based on the explicit notion that a unit effect of mobility is a comparison of an individual with herself under two conditions, one in which she is mobile, the other in which she is immobile, and we discuss some of the challenges in identifying such effects.

Temperature-related mortality in China from specific injury.

Injury poses heavy burden on public health, accounting for nearly 8% of all deaths globally, but little evidence on the role of climate change on injury exists. We collect data during 2013-2019 in six provinces of China to examine the effects of temperature on injury mortality, and to project future mortality burden attributable to temperature change driven by climate change based on the assumption of constant injury mortality and population scenario. The results show that a 0.50% (95% confident interval (CI): 0.13%-0.88%) increase of injury mortality risk for each 1 °C rise in daily temperature, with higher risk for intentional injury (1.13%, 0.55%-1.71%) than that for unintentional injury (0.40%, 0.04%-0.77%). Compared to the 2010s, total injury deaths attributable to temperature change in China would increase 156,586 (37,654-272,316) in the 2090 s under representative concentration pathways 8.5 scenario with the highest for transport injury (64,764, 8,517-115,743). Populations living in Western China, people aged 15-69 years, and male may suffer more injury mortality burden from increased temperature caused by climate change. Our findings may be informative for public health policy development to effectively adapt to climate change.

Explaining obesity disparities by urbanicity, 2006 to 2016: A decomposition analysis.

OBJECTIVE: A large, and potentially growing, disparity in obesity prevalence exists between large central metros and less urban United States counties. This study examines its key predictors. METHODS: Using a rich county-year data set spanning 2006 to 2016, the authors conducted a Gelbach decomposition to examine the relative importance of demographic, socioeconomic, environmental, and behavioral factors in shaping the baseline obesity gap and the growth rate over time between large central metros and other counties. RESULTS: Predictors included in this model explain almost the entire obesity gap between large central metros and other counties in the baseline year but can explain only ~32% of the growing gap. At baseline, demographic predictors explain more than half the obesity gap, and socioeconomic and behavioral predictors explain the other half. Behavioral and socioeconomic predictors explain more than half the growing gap over time whereas controlling for environmental and demographic predictors decreases the obesity gap by urbanicity over time. CONCLUSIONS: Results suggest policy makers should prioritize interventions targeting health behaviors of residents in non-large central metros to slow the growth of the obesity gap between large central metros and other counties. However, to fundamentally eliminate the obesity gap, in addition to improving health behaviors, policies addressing socioeconomic inequalities are needed.

Individual and neighborhood socioeconomic status and long-term individual trajectories of sleep duration among Black and White adults: the Southern Community Cohort Study.

STUDY OBJECTIVES: Sleep duration can change over the life course; however, previous studies rarely investigated the association between socioeconomic status (SES) and individual sleep trajectories over time. We examined the association between baseline socioeconomic characteristics and long-term sleep trajectories among Black and White adults. METHODS: This study used data from the Southern Community Cohort Study (N = 45 035). Diverse trajectories of sleep duration were constructed using self-reported sleep duration at baseline and after ~10 years of follow-up. The associations between baseline socioeconomic characteristics and sleep trajectories were examined using multinomial logistic regression. RESULTS: Both Black and White participants experienced similar long-term individual sleep trajectories for baseline educational attainment and employment status albeit the associations appeared stronger among White participants. Lower education and unemployment were associated with higher odds of various suboptimal sleep trajectories suggesting worsening long-term sleep patterns among both racial groups. However, there were some racial differences in the experience of long-term sleep trajectories for household income and neighborhood SES. Household income was notably more important among White than Black individuals; lower household income was associated with higher odds of more suboptimal long-term sleep trajectories for White than Black individuals. Also, neighborhood SES was slightly more important among White than Black individuals; lower neighborhood SES was associated with higher odds of a few suboptimal long-term sleep trajectories for both racial groups. CONCLUSIONS: Lower socioeconomic characteristics were associated with various suboptimal long-term sleep trajectories among Black and White participants. Substantial improvements in socio-economic characteristics may contribute to improved sleep patterns.

The role of TGR5 as an onco-immunological biomarker in tumor staging and prognosis by encompassing the tumor microenvironment.

The relationship between G protein-coupled bile acid receptor 1 (TGR5, GPBAR1) and, specifically, cancer has been studied in in vivo and in vitro experiments, but there is still a lack of pan-cancer analysis to understand the prognostic significance and functioning mechanism of TGR5 in different cancer-driving oncogenic processes. Here, we used Gene Expression Integration, Human Protein Atlas, and The Cancer Genome Atlas (TCGA) to perform a pan-cancer analysis of the role of TGR5 in all 33 tumors. In all TCGA tumors, the TGR5 gene expression has been assessed, and we found that the high TGR5 gene expression in most cancers is associated with poor prognosis of overall survival for cancers such as glioblastoma multiforme (p = 0.0048), kidney renal papillary cell carcinoma (p = 0.033), lower grade glioma (p = 0.0028), thymoma (p = 0.048), and uveal melanoma (p = 0.004), and then the lower expression of TGR5 was linked with poor prognosis in cervical squamous cell carcinoma and endocervical adenocarcinoma (p = 0.014), malignant mesothelioma (MESO) (p = 0.048), sarcoma (p = 0.018), and skin cutaneous melanoma (p = 0.0085). The TGR5 expression was linked with the immune infiltration level of the macrophage M2_TIDE and was also associated with DNA methylation in ovarian and breast cancers. The regulation of hormone secretion, Rap1 pathway, osteoclast differentiation, and bile acid pathway was involved in the functional mechanism of TGR5. Besides, gene expressions were different in different tumors detected by RT-PCR, and cell activity experiments have also found that TGR5 can increase the activity of renal cell carcinoma and reduce the activity of skin cancer and osteosarcoma cells. In this investigation, the aim was to assess the comprehensive overview of the oncogenic roles of TGR5 in all TCGA tumors using pan-analysis.