Resolvin D1 Inhibits IL-6-Induced Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Targeting IL-6/STAT3 Signaling.

Colorectal cancer (CRC) has emerged as a prevalent malignancy worldwide, exhibiting the high morbidity and mortality rates. Resolvin D1 (RvD1) can exert anti-inflammation and anti-cancer effects on various diseases. This study is aimed to explore the role of RvD1 in CRC cells. HCT15 and SW480 cells were stimulated with IL-6 in our study. A series of assays such as CCK-8, colony formation, wound healing, Transwell, Western blotting, and immunofluorescence staining were designed and conducted to figure out the role of RvD1 in CRC cells. RvD1 suppressed IL-6-induced SW480 and HCT15 cell proliferation. In addition, RvD1 inhibited IL-6-induced SW480 and HCT15 cell migration, invasion, and EMT process. In mechanism, RvD1 inhibited the activation of IL-6/STAT3 signaling in SW480 and HCT15 cells. Angoline strengthened the inhibitive effect of RvD1 on cell malignancy. RvD1 inhibited cell growth, migration, invasion and EMT process by inactivating IL-6/STAT3 signaling in CRC.

Kaempferol Improves Exercise Performance by Regulating Glucose Uptake, Mitochondrial Biogenesis, and Protein Synthesis via PI3K/AKT and MAPK Signaling Pathways.

Kaempferol is a natural flavonoid with reported bioactivities found in many fruits, vegetables, and medicinal herbs. However, its effects on exercise performance and muscle metabolism remain inconclusive. The present study investigated kaempferol's effects on improving exercise performance and potential mechanisms in vivo and in vitro. The grip strength, exhaustive running time, and distance of mice were increased in the high-dose kaempferol group (p < 0.01). Also, kaempferol reduced fatigue-related biochemical markers and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) related to antioxidant capacity. Kaempferol also increased the glycogen and adenosine triphosphate (ATP) content in the liver and skeletal muscle, as well as glucose in the blood. In vitro, kaempferol promoted glucose uptake, protein synthesis, and mitochondrial function and decreased oxidative stress in both 2D and 3D C2C12 myotube cultures. Moreover, kaempferol activated the PI3K/AKT and MAPK signaling pathways in the C2C12 cells. It also upregulated the key targets of glucose uptake, mitochondrial function, and protein synthesis. These findings suggest that kaempferol improves exercise performance and alleviates physical fatigue by increasing glucose uptake, mitochondrial biogenesis, and protein synthesis and by decreasing ROS. Kaempferol's molecular mechanism may be related to the regulation of the PI3K/AKT and MAPK signaling pathways.

Differential Disruption of Glucose and Lipid Metabolism Induced by Phthalates in Human Hepatocytes and White Adipocytes.

Phthalic acid esters (PAEs), commonly used as plasticizers, are pervasive in the environment, leading to widespread human exposure. The association between phthalate exposure and metabolic disorders has been increasingly recognized, yet the precise biological mechanisms are not well-defined. In this study, we explored the effects of monoethylhexyl phthalate (MEHP) and monocyclohexyl phthalate (MCHP) on glucose and lipid metabolism in human hepatocytes and adipocytes. In hepatocytes, MEHP and MCHP were observed to enhance lipid uptake and accumulation in a dose-responsive manner, along with upregulating genes involved in lipid biosynthesis. Transcriptomic analysis indicated a broader impact of MEHP on hepatic gene expression relative to MCHP, but MCHP particularly promoted the expression of the gluconeogenesis key enzymes G6PC and FBP1. In adipocytes, MEHP and MCHP both increased lipid droplet formation, mimicking the effects of the Peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi). Transcriptomic analysis revealed that MEHP predominantly altered fatty acid metabolism pathways in mature adipocytes (MA), whereas MCHP exhibited less impact. Metabolic perturbations from MEHP and MCHP demonstrate shared activation of the PPARs pathway in hepatocytes and adipocytes, but the cell-type discrepancy might be attributed to the differential expression of PPARγ. Our results indicate that MEHP and MCHP disrupt glucose and lipid homeostasis in human liver and adipose through mechanisms that involve the PPAR and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways, highlighting the nuanced cellular responses to these environmental contaminants.

Schisandrin A ameliorates increased pulmonary capillary endothelial permeability accompanied with sepsis through inhibition of RhoA/ROCK1/MLC pathways.

BACKGROUND: Sepsis is a systemic inflammatory response, and vascular leakage associated with acute lung injury (ALI) is an important pathophysiological process during sepsis. Schisandrin A (SchA) is a bioactive lignan which has been reported to have the anti-inflammatory effects in many studies, while whether SchA can ameliorate ALI-related vascular leakage caused by sepsis is unknown. OBJECTIVE: To evaluate the role and the underlying mechanism of SchA in increase of pulmonary vascular permeability induced by sepsis. METHODS: The effect of SchA on pulmonary vascular permeability was examined in rat acute lung injury model. The effect of SchA on skin vascular permeability of mice was investigated through Miles assay. MTT assay was performed to detect the cell activity, and transwell assay was used to detect the effect of SchA on cell permeability. The effects of SchA on junction proteins and RhoA/ROCK1/MLC signaling pathway were manifested by immunofluorescence staining and western blot. RESULTS: The administration of SchA alleviated rat pulmonary endothelial dysfunction, relieved increased permeability in the mouse skin and HUVECs induced by lipopolysaccharide (LPS). Meanwhile, SchA inhibited the formation of stress fibers, reversed the decrease of expression of ZO-1 and VE-cadherin. Subsequent experiments confirmed that SchA inhibited RhoA/ROCK1/MLC canonical pathway in rat lungs and HUVECs induced by LPS. Moreover, overexpression of RhoA reversed the inhibitory effect of SchA in HUVECs, which suggested that SchA protected the pulmonary endothelial barrier by inhibiting RhoA/ROCK1/MLC pathway. CONCLUSION: In summary, our results indicate that SchA ameliorates the increase of pulmonary endothelial permeability induced by sepsis through inhibition of RhoA/ROCK1/MLC pathway, providing a potentially effective therapeutic strategy for sepsis.

Tubeimoside I induces autophagy in HepG2 cells by activating the AMP-activated protein kinase signaling pathway.

Tubeimoside I (TBMS) is a natural compound with antitumor properties. However, the detailed mechanism underlying the function of TBMS in liver cancer has not been fully elucidated. In the present study, TBMS was shown to suppress cell proliferation and induce S phase cell cycle arrest in HepG2 cells. Furthermore, TBMS treatment induced autophagy, evidenced by autophagosome accumulation, and increased the mRNA expression of Beclin 1 and microtubule-associated protein 1 light chain 3 (LC3)-I. However, flow cytometry analysis demonstrated that TBMS exerted no effect on cell apoptosis. Moreover, TBMS increased the phosphorylation of AMP-activated protein kinase (AMPK) in a concentration-dependent manner, thereby activating the AMPK signaling pathway. A specific AMPK inhibitor, compound C (CC), caused markedly suppressed TBMS-induced accumulation of LC3-II. In addition, the mRNA expression of LC3-I and Beclin 1 was also suppressed in cells treated with TBMS and CC in combination. The results of the present study provide new insights into the role of TBMS in inducing autophagy and support the potential application of TBMS for liver cancer treatment in the clinical setting.

PAK5 facilitates the proliferation, invasion and migration in colorectal cancer cells.

Colorectal cancer (CRC) is the third-most common cancer around the world, accounting for approximately 10% of cancer-related mortality. Deeper molecular understanding of colorectal carcinogenesis will provide evidences for identification of early diagnostic indicators and novel therapeutic strategies for CRC treatment. The p21cdc42/rac1 -activated kinase 5 (PAK5) has been reported to be involved in a variety of tumor-promoting behaviors, whereas the underlying mechanisms of PAK5 in CRC progression are still obscure. Our current study revealed an upregulated expression of PAK5 in human CRC tissues as compared with normal adjacent biopsies, which was associated with tumor progression and metastasis. We further unraveled that inhibition of PAK5 was correlated with restrained proliferation, migration, and invasion of CRC cells in vitro and in vivo. Moreover, we showed an indispensable role of PAK5 in interacting with Cdc42 and Integrin ß1, ß3, thus, to facilitate the migration and invasion of CRC cells. Collectively, we pointed out a potential of PAK5 to serve as a novel therapeutic target in restricting CRC proliferation and metastasis. The uncovered mechanisms will deepen the comprehension with regard to the mechanisms of CRC progression, as well as providing new insights for therapeutic intervention in colorectal cancer.

Bidirectional relationships between retention and health-related quality of life in Chinese mainland patients receiving methadone maintenance treatment.

This study aimed to explore the bidirectional relationships between retention and health-related quality of life (HRQoL) in patients from mainland China receiving methadone maintenance treatment (MMT). This prospective cohort study recruited 1,212 eligible MMT patients from the two largest MMT clinics (one privately and another publicly funded) in Xi'an. This study started in March 2012 with a 2-year follow-up until March 2014. Retention was assessed by repeated terminations, past treatment duration, premature terminations, and follow-up treatment duration. HRQoL was evaluated using the Chinese (simple) short-form 36 health survey version 2 (SF-36v2) and the quality of life scale for drug addicts (QOL-DAv2.0). Linear and Cox regression analyses were used to explore relationships between retention and HRQoL. A general linear model was used to further examine the global effect of past treatment duration on HRQoL. Multivariate analyses showed that repeated terminations had no significant impact on HRQoL scores in MMT patients; however, past treatment time (year) influenced the SF-36v2PCS (P = 0.004): treatment for ≥4 years showed a lower SF-36v2PCS score (regression coefficient: -2.39; 95% confidence interval [CI]: -3.80, -0.97; P = 0.001) than treatment for <1 year. In addition, patients with an SF-36v2PCS score > 49 (hazard ratio: 0.83; 95% CI: 0.69, 0.98; P = 0.03) were 17% less likely to terminate MMT than those with scores of ≤49. In conclusion, retention and HRQoL tended to have a bidirectional relationship, which should be considered in the development of retention and health-management programs for patients with MMT.

Relationships between received and perceived social support and health-related quality of life among patients receiving methadone maintenance treatment in Mainland China.

BACKGROUND: Social support has been considered one of the most important factors of health-related quality of life (HRQoL) evaluations among different populations; however, few studies have explored the relationships of both received and perceived social support to HRQoL among patients undergoing methadone maintenance treatment (MMT). Thus, the purpose of this cross-sectional study was to clarify these relationships. METHODS: Participants were patients admitted at the two largest privately and publicly funded MMT clinics in Xi'an. The main explanatory variable was social support, both received (i.e., social network support and professional support services) and perceived (Multidimensional Scale of Perceived Social Support). The outcome was HRQoL, which was evaluated using the Short-Form 36 Health Survey version 2 (SF-36v2) and the Quality of Life Scale for Drug Addicts (QOL-DAv2.0). We carried out independent samples t-tests and multiple linear regression analysis to examine the relationships between received and perceived social support and HRQoL. RESULTS: The study findings revealed that patients with good social support had significantly higher scores on the SF-36v2 and QOL-DAv2.0 (p < 0.05). After controlling for individual characteristics, the significant factors predicting HRQoL were good family relationships, usually communicating with others, a convenient service time, appropriate treatment charges, and good perceived social support (p < 0.05). CONCLUSIONS: Our results suggest that received and perceived social support influences HRQoL among individuals receiving MMT. Thus, these variables should be considered during health management efforts and interventions directed at this patient population.

Reliability and validity of the multidimensional scale of perceived social support in Chinese mainland patients with methadone maintenance treatment.

INTRODUCTION: The multidimensional scale of perceived social support (MSPSS) is a valid tool for assessing perceived support from family, friends and significant others. However, evidence about reliability and validity of the MSPSS in Chinese mainland patients with methadone maintenance treatment (MMT) is lacking. METHODS: The patients (n=1212) being admitted to the first two largest MMT clinics in Xi'an were recruited in the study. Reliability was estimated with Cronbach's α and intra-class correlation (ICC). Convergent and discriminant validity was assessed using item-subscale correlation. Factorial validity was examined using exploratory and confirmatory factor analysis. The patients answered the questions of MSPSS at baseline and re-test after 6months, respectively. RESULTS: Cronbach's α of the overall MSPSS was 0.92 (subscales range: 0.84-0.89). ICC of the overall MSPSS was 0.65 (subscales range: 0.57-0.64). Better convergent validity (r≥0.40) was demonstrated by the satisfactory hypothesized item-subscale correlation. All of the hypothesized item-subscale correlations were higher than the correlations between the hypothesized items and other subscales, indicating better discriminant validity. Two factors were extracted from the 12 items, with factor 1 mainly covering friends and significant others subscales (explained 55.56% variance) and factor 2 mainly covering family subscale (explained 11.77% variance). In comparison with the proposed three-subscale model, the two-factor observed model did not fit well in this sample according to model fit indices. CONCLUSIONS: The MSPSS has acceptable reliability and convergent/discriminant validity in Chinese mainland MMT patients. The proposed three-factor model of MSPSS is much better fit than the two-factor observed model in this study. Findings of the study will provide evidence of psychometric properties of the MSPSS in MMT patient population and expand the use of the MSPSS in clinical MMT context.

Knowledge of HIV and willingness to conduct oral rapid HIV testing among dentists in Xi'an China.

INTRODUCTION: China is considered a country of low HIV prevalence (780,000 people living with HIV), however, HIV infections among high-risk populations continue to grow at alarming rates. Voluntary Counseling and Testing services were first implemented in 2003, and oral rapid HIV testing (ORHT) began in 2012. Dentists, as oral health experts, would be well placed to conduct ORHT. We assessed willingness of dentists to undertake ORHT in their clinical practice. METHODS: A cross-sectional, paper-based survey of dentists from the Xi'an region of China was conducted from April to June 2013. Dentists were recruited from Shaanxi Stomatological Association using a stratified sampling methodology. A 40-item survey was used to measure knowledge of HIV, attitudes toward people living with HIV and willingness to conduct ORHT. RESULTS: 477 dentists completed the survey with a mean HIV knowledge test score of 13.2/18 (SD 1.9). If made available in the dental setting, 276 (57.9%) preferred to use blood to diagnose HIV, only 190 (39.8%) preferred saliva or both. Four hundred and thirty-five (91.2%) thought that ORHT was needed in dental clinics. Female dentists felt more accepting of ORHT than males (93.8% vs. 87.8%; χ2=5.145; p<0.05). 42.6% of the participants who responded thought that lack of education on ORHT for dentists was the most urgent problem to solve for ORHT, 144 (31.3%) thought that lack of support for ORHT from patients was the most urgent problem. There was statistically significant difference among dental hospital, dentistry and department of dentistry (χ2=24.176; p<0.05). CONCLUSIONS: The majority of Chinese dentists thought that ORHT was needed in the dental setting. Providing opportunities for dentists and dental students to learn about HIV testing guidelines and practices is needed as well as feasibility and implementation science research.

[Survey of Hepatitis B infection and vaccination status among drug users in Xi'an].

OBJECTIVE: To explore seroepidemiological status and vaccine coverage of hepatitis B among drug users in Xi'an. METHODS: 545 drug users in the Xi'an Compulsory Detoxification Center were asked to answer questionnaire and provide blood sample (3-5 ml) for test of HBsAg, anti-HBc and anti-HBs from March to June 2013. Totally, 545 subjects were surveyed and tested. All of them effectively completed the survey. RESULTS: The positive rates of HBsAg, anti-HBc and anti-HBs were 29.4% (160/545), 60.0% (327/545) and 56.1% (306/545), respectively. Eighty five subjects (15.6%) were negative for all of the three markers. The prevalence of HBsAg and anti-HBc among injection drug users were 40.0% (94/235) and 65.6% (154/235), which was significantly higher than non- injection drug users' (21.6% (52/241), 58.5% (141/241)) and mixed non-injection and injection drug users ((20.3% (14/69), 46.4% (32/69)) (χ(2) = 23.518 and 9.017, respectively, P < 0.05) . The HBsAg positive rate (30.6% (153/500)) of subjects with more than once per day of drug using within one year was significantly higher than those who used drugs for 2-3 times per week (15.6% (7/45)) (χ(2) = 4.51, P < 0.05). Only 11.7% (64/545) of drug users had a clear history of hepatitis B vaccination. The vaccination rate of subjects (3.5% (5/141)) with primary education or below was significantly lower than those with high school (16.3% (45/276)) (χ(2) = 26.61, P < 0.05). The vaccination rate of subjects (7.8% (12/153)) over 45 years old was significantly lower than that of subjects below 30 years old (15.9% (21/132)) and 30-44 years old (11.9% (31/260)) (χ(2) = 30.36, P < 0.05). The vaccinees had a significantly higher positive rate of anti-HBs (73.4% (47/64)) than those who without vaccination (53.8% (259/481)) (χ(2) = 8.81, P = 0.003), but the positive rates of HBsAg (16.7% (11/64)) were lower than those who without vaccination (31.0% (149/481)) (χ(2) = 23.52 and 9.02, respectively;P > 0.05). CONCLUSION: The HBV infection status among drug users in Xi'an was in serious condition, while a low vaccination rate was also discovered among them.

Psychometrics of the Short Form 36 Health Survey version 2 (SF-36v2) and the Quality of Life Scale for Drug Addicts (QOL-DAv2.0) in Chinese mainland patients with methadone maintenance treatment.

OBJECTIVE: To test psychometrics of the Short Form 36 Health Survey version 2 (SF-36v2) and the Quality of Life Scale for Drug Addicts (QOL-DAv2.0) in Chinese mainland patients with methadone maintenance treatment (MMT). METHODS: A total of 1,212 patients were recruited from two MMT clinics in Xi'an, China. Reliability was estimated with Cronbach's α and intra-class correlation (ICC). Convergent and discriminant validity was assessed using multitrait-multimethod correlation matrix. Sensitivity was measured with ANOVA and relative efficiency. Responsiveness was evaluated by pre-post paired-samples t-test and standardized response mean based on the patients' health status changes following 6-month period. RESULTS: Cronbach's α of the SF-36v2 physical and mental summary components were 0.80 and 0.86 (eight scales range 0.73-0.92) and the QOL-DAv2.0 was 0.96 (four scales range: 0.80-0.93). ICC of the SF-36v2 two components were 0.86 and 0.85 (eight scales range: 0.72-0.87) and the QOL-DAv2.0 was 0.94 (four scales range: 0.88-0.92). Convergent validity was lower between the two instruments (γ <0.70) while discriminant validity was acceptable within each instrument. Sensitivity was satisfied in self-evaluated health status (both instruments) and average daily methadone dose (SF-36v2 physical functioning and vitality scales; QOL-DAv2.0 except psychology scale). Responsiveness was acceptable in the improved health status change (SF-36v2 except vitality scale; QOL-DAv2.0 except psychology and symptoms scales) and deteriorated health status change (SF-36v2 except vitality, social functioning and mental health scales; QOL-DAv2.0 except society scale). CONCLUSIONS: The SF-36v2 and the QOL-DAv2.0 are valid tools and can be used independently or complementary according to different emphases of health-related quality of life evaluation in patients with MMT.