Clonorchiasis is a parasitic disease caused by Clonorchis sinensis, a trematode that inhabits the intrahepatic bile ducts of humans and mammals. C. sinensis is one of common foodborne trematodes, prevalent in East Asia including Korea. The International Agency for Research on Cancer reclassified C. sinensis as the Group 1 biological carcinogen of human cholangiocarcinoma (CCA). Evidence supporting the carcinogenicity of C. sinensis includes epidemiological studies showing increased prevalence and odds ratio (OR) of CCA in clonorchiasis patients, the development of CCA in experimental animals, and molecular studies. Approximately 10% of CCA in Korea are believed to be solely caused by clonorchiasis, with an OR of 4.7 for CCA risk among clonorchiasis patients. All hamsters exposed to both of C. sinensis and N-nitrosodimethylamine (NDMA) developed CCA while those exposed to either C. sinensis or NDMA alone did not. In vitro studies using cell models investigated carcinogenetic changes of the intracellular molecules and genes following stimulation with a soluble extract of C. sinensis. The in vitro stimulated cells showed a significant shift to G2/M phage, produced oncogenic molecules, changed expression of oncogenes, increased cell proliferation and suppressed apoptosis. Additionally, the gap-junction proteins between cells, such as connexin (Cx) 43, Cx 26, and Cx 32, were changed significantly, disrupting intercellular homeostasis. These findings suggest that C. sinensis and nitrogen compounds synergistically stimulate the cholangiocytes to become neoplastic. C. sinensis is a biological carcinogen of human CCA, and the World Health Organization guidelines enlist food-borne trematodes as one of target neglected tropical diseases to be eliminated by 2030. The present article reviews and updates perspectives on clonorchiasis, focusing on carcinogenesis.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Clonorchiasis is a parasitic disease caused by Clonorchis sinensis, a trematode that inhabits the intrahepatic bile ducts of humans and mammals. C. sinensis is one of common foodborne trematodes, prevalent in East Asia including Korea. The International Agency for Research on Cancer reclassified C. sinensis as the Group 1 biological carcinogen of human cholangiocarcinoma (CCA). Evidence supporting the carcinogenicity of C. sinensis includes epidemiological studies showing increased prevalence and odds ratio (OR) of CCA in clonorchiasis patients, the development of CCA in experimental animals, and molecular studies. Approximately 10% of CCA in Korea are believed to be solely caused by clonorchiasis, with an OR of 4.7 for CCA risk among clonorchiasis patients. All hamsters exposed to both of C. sinensis and N-nitrosodimethylamine (NDMA) developed CCA while those exposed to either C. sinensis or NDMA alone did not. In vitro studies using cell models investigated carcinogenetic changes of the intracellular molecules and genes following stimulation with a soluble extract of C. sinensis. The in vitro stimulated cells showed a significant shift to G2/M phage, produced oncogenic molecules, changed expression of oncogenes, increased cell proliferation and suppressed apoptosis. Additionally, the gap-junction proteins between cells, such as connexin (Cx) 43, Cx 26, and Cx 32, were changed significantly, disrupting intercellular homeostasis. These findings suggest that C. sinensis and nitrogen compounds synergistically stimulate the cholangiocytes to become neoplastic. C. sinensis is a biological carcinogen of human CCA, and the World Health Organization guidelines enlist food-borne trematodes as one of target neglected tropical diseases to be eliminated by 2030. The present article reviews and updates perspectives on clonorchiasis, focusing on carcinogenesis.

Clonorchiasis is a parasitic disease caused by Clonorchis sinensis, a trematode that inhabits the intrahepatic bile ducts of humans and mammals. C. sinensis is one of common foodborne trematodes, prevalent in East Asia including Korea. The International Agency for Research on Cancer reclassified C. sinensis as the Group 1 biological carcinogen of human cholangiocarcinoma (CCA). Evidence supporting the carcinogenicity of C. sinensis includes epidemiological studies showing increased prevalence and odds ratio (OR) of CCA in clonorchiasis patients, the development of CCA in experimental animals, and molecular studies. Approximately 10% of CCA in Korea are believed to be solely caused by clonorchiasis, with an OR of 4.7 for CCA risk among clonorchiasis patients. All hamsters exposed to both of C. sinensis and N-nitrosodimethylamine (NDMA) developed CCA while those exposed to either C. sinensis or NDMA alone did not. In vitro studies using cell models investigated carcinogenetic changes of the intracellular molecules and genes following stimulation with a soluble extract of C. sinensis. The in vitro stimulated cells showed a significant shift to G2/M phage, produced oncogenic molecules, changed expression of oncogenes, increased cell proliferation and suppressed apoptosis. Additionally, the gap-junction proteins between cells, such as connexin (Cx) 43, Cx 26, and Cx 32, were changed significantly, disrupting intercellular homeostasis. These findings suggest that C. sinensis and nitrogen compounds synergistically stimulate the cholangiocytes to become neoplastic. C. sinensis is a biological carcinogen of human CCA, and the World Health Organization guidelines enlist food-borne trematodes as one of target neglected tropical diseases to be eliminated by 2030. The present article reviews and updates perspectives on clonorchiasis, focusing on carcinogenesis.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

To explore the anti-depression effect of Suanzaoren Decoction(SZRD), the regulatory effects on endogenous metabolites in the liver of rats with depression induced by chronic unpredictable mild stress(CUMS) were analyzed by using LC-MS metabolomics. The rats were randomly divided into normal control group, model group, low-dose SZRD group, high-dose SZRD group, and positive drug group. The CUMS depression model was replicated by applying a variety of stimuli, such as fasting and water deprivation, ice water swimming, hot water swimming, day and night reversal, tail clamping, and restraint for rats. Modeling and treatment were conducted for 56 days. The behavioral indexes of rats in each group, including body weight, open field test, sucrose preference test, and tail suspension test, were observed. Plasma samples and liver tissue samples were collected, and the contents of 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) in plasma were measured using enzyme-linked immunosorbent assay(ELISA). Meanwhile, the regulatory effects of SZRD on the liver metabolic profile of CUMS model rats were analyzed by the LC-MS metabolomics method. The results show that SZRD can significantly improve the depression-like behavior of CUMS model rats and increase the neurotransmitter levels of 5-HT, DA, and NE in plasma. A total of 24 different metabolites in the rats' liver are identified using the LC-MS metabolomics method, and SZRD can reverse 13 of these metabolites. Metabolic pathway analysis indicates that nine metabolic pathways are found to be significantly associated with depression, and in the low-dose SZRD group, four pathways can be regulated, including pentose phosphate pathway, purine metabolism, inositol phosphate metabolism, and sphingolipid metabolism. In the high-dose SZRD group, two metabolic pathways can be regulated, including sphingolipid metabolism and glycerol glycerophospholipid metabolism. Sphingolipid metabolism is a metabolic pathway that can be regulated by SZRD at different doses, so it is speculated that it may be the primary pathway through which SZRD can alleviate metabolic disturbances in the liver of CUMS model rats.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Metabolomics ; Depression/metabolism* ; Male ; Liver/drug effects* ; Rats, Sprague-Dawley ; Antidepressive Agents/administration & dosage* ; Serotonin/blood* ; Humans ; Disease Models, Animal ; Behavior, Animal/drug effects*