Recent studies indicate that cancer-associated fibroblasts (CAFs) are involved in tumor growth, invasion and metastasis, however, the underling mechanisms remain unclear. In the present study, we investigated the role of CAFs on the metastatic potential of lung cancer cells. The stromal fibroblasts we isolated from lung cancer tissues presented CAFs characteristics with high levels of α-smooth muscle actin (α-SMA) and fibroblast-activating protein (FAP). Our data showed that the conditioned medium from cultured CAFs (CAF-CM) dramatically enhanced migration and invasion of lung cancer cells. CAF-CM induced epithelial-mesenchymal transition (EMT) by regulating the expression of EMT-associated markers E-cadherin and vimentin, and also modulated metastasis-related genes MMP-2 and VEGF both in vitro and in vivo. Further mechanistic studies demonstrated that CAFs enhanced the metastatic potential of lung cancer cells by secreting IL-6, subsequently activating of JAK2/STAT3 signaling pathway. Additionally, the inhibition of IL-6/STAT3 signaling pathway by IL-6 neutralizing antibody or specific inhibitors of JAK2/STAT3 reversed CAF-CM induced EMT and migration of lung cancer cells. Taken together, these findings revealed a novel mechanism that CAFs induced EMT and promoted metastasis of lung cancer cells through the IL-6/STAT3 signaling pathway.

The relationship between thyroid dysfunction and metabolic syndrome (MS) is complex. We aimed to explore the impact of gender and age on their association in a large Chinese cohort.This cross-sectional study enrolled 13,855 participants (8532 male, 5323 female), who self-reported as healthy without any known previous diseases. Clinical data including anthropometric measurements, thyroid function, and serum metabolic parameters were collected. The associations between thyroid function and MS of both genders were analyzed separately after dividing thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and age into subgroups. MS risks were calculated by binary logistic regression models.Young males had significantly higher MS prevalence than females, yet after menopause, females had higher prevalence than males. Females had higher incidence of thyroid dysfunction than males. By using TSH quartiles as the categorical variables and the lowest quartile as reference, significantly increased MS risk was demonstrated in quartile 4 for males, yet quartiles 3 and 4 for females. By using FT3 quartiles as the categorical variables, significantly increased MS risk was demonstrated in quartile 2 to 4 for females only. By using age subgroups as the categorical variables, significantly increased MS risk was shown in both genders, with females (4.408–58.455) higher than males (2.588–4.943).Gender and age had substantial influence on thyroid function and MS. Females with high TSH and high FT3 had higher MS risks than males. Aging was a risk for MS, especially for females. Urgent need is necessary to initiate interventional programs.

We aimed to explore correlations between lifestyle choices and hyperuricemia in a large Chinese population, emphasizing the differences from opposite sex. Ten thousand four hundred fifty subjects were randomly recruited from Tianjin municipality in China. Hyperuricemia was defined as serum uric acid >420 μmol/L for men and >360 μmol/L for women. Demographic data, highest education degree, work type, commuting means, smoking and drinking status, exercise frequency, and quantitative assessments of dietary factors were collected. Anthropometric measurements and fasting blood tests were performed. Statistical analyses were conducted. Total hyperuricemic prevalence was 12.89 %, with male significantly higher than female. Body mass index, waist circumference, serum indices, and age displayed high correlation coefficients, and most lifestyle factors also showed significant correlations as well. Binary logistic regression models showed odds ratio of developing hyperuricemia were much greater in males than in females by eating habits. However, physical activity-related lifestyle choices tended to cast much greater influences on the likelihood of hyperuricemia in females. Lifestyle choices and hyperuricemia are closely related. For males, eating habits have greater influences on the likelihood of developing hyperuricemia. For females, lifestyle factors like work type, commuting method, and exercise have such effects.

Prevalence of both metabolic syndrome (MS) and hyperuricemia are increasing. However, findings regarding their relationships are inconsistent. We aimed to explore correlations between MS and hyperuricemia in a large Chinese population, emphasizing the impacts from gender and age. Data analyses were performed in 17,762 subjects randomly recruited from Tianjin municipality in China. Hyperuricemia was defined as serum uric acid (SUA) >420 μmol/L for men, >360 μmol/L for women. MS was diagnosed by the consensus criterion released in 2009 from a joint collaboration between American Heart Association and other organizations. MS was also diagnosed by Chinese Diabetes Society (CDS) criterion. Total hyperuricemic prevalence was 12.16%, with male significantly higher than female. Total MS prevalence by consensus criterion was much higher than by CDS criterion (25.56% versus 14.09%). Correlation coefficients were much greater in women than in men. SUA was significantly positively related with body mass index and waist circumference. Generally, binary logistic regression models disclosed females with high SUA were twice likely to suffer from MS than males. Young females (≤44 years old) with hyperuricemia had the highest odd ratio of 7.857 by consensus criterion; and after further adjustment by body mass index, this odd ratio was 3.040. SUA and MS were much more closely related in females than in males. Young women with hyperuricemia had the highest risk of MS.

Cancer tissues consist of cancer cells, surrounding stromal cells and the extracellular matrix. Cancer‐associated fibroblasts ( CAF ) are one of the key components of stromal cells. CAF have a great impact on the behavior of cancer cells, including proliferation, invasion, metastasis and chemoresistance in many ways. However, the underlying mechanism had not been fully elucidated. In this study, we investigated the role of CAF in cisplatin resistance of lung cancer cells. By using conditioned medium from CAF ( CAF ‐ CM ), we found that CAF decreased the sensitivity of lung cancer cells to cisplatin. RNA sequencing results showed that CAF expressed a higher level of Annexin A3 ( ANXA 3) than normal fibroblasts ( NF ), and CAF ‐ CM incubation increased the ANXA 3 level in lung cancer cells. Overexpression of ANXA 3 in lung cancer cells increased cisplatin resistance and activated c‐jun N‐terminal kinase ( JNK ), whereas knockdown of ANXA 3 increased cisplatin sensitivity. Further study showed that CAF ‐ CM enhanced cisplatin resistance by inhibiting cisplatin‐induced apoptosis, determined by repression of caspase‐3 and caspase‐8, through activation of the ANXA 3/ JNK pathway. Conversely, suppression of JNK activation by specific inhibitor retarded the effect of CAF ‐ CM and ANXA 3 on cisplatin sensitivity. Taken together, our study demonstrated that CAF potentiated chemoresistance of lung cancer cells through a novel ANXA 3/ JNK pathway both in vitro and in vivo, suggesting ANXA 3 could be a potential therapeutic target for the treatment of chemoresistant cancer.

Vitamin E exerts significant protective effects on the parotid and submandibular glands after I therapy.

Background The associations of different adiposity indicators and short-term adiposity change with diabetes risk are not fully elucidated. Objective We aimed to assess the independent and joint effects of different baseline adiposity indicators and short-term body adiposity change on the risk of type 2 diabetes. Methods We prospectively followed 10,419 Chinese adults aged 20–80 y in 2008–2012. Incident diabetes was diagnosed based on fasting glucose, 2-h glucose, or glycated hemoglobin (HbA1c) after an oral glucose tolerance test using the American Diabetes Association standard. Cox proportional hazard regression models were used to assess the associations of adiposity indicators and adiposity change with diabetes risk. Results During a mean follow-up of 2.8 y, we identified 805 type 2 diabetes cases. Baseline BMI, waist circumference, and waist-height ratio (WHtR) were all positively associated with diabetes risk. The area under the curve was significantly greater for waist circumference (0.624) and WHtR (0.627) than for BMI (0.608) (P <0.05). Compared with subjects with stable adiposity levels (±2 kg or ± 3 cm in changes in body weight or waist circumference) from baseline to Year 1, those subjects with the most weight gain or the most waist circumference gain had a 1.53-fold or 1.37-fold greater risk of diabetes; those with the most weight loss had a 46% lower risk of diabetes. Furthermore, regardless of baseline weight status, weight or waist circumference change in the first year was associated with diabetes risk. Conclusion Abdominal adiposity indicators, waist circumference and its change, are more strongly associated with the risk of type 2 diabetes than general adiposity indicators, BMI, and changes in body weight among Chinese adults.

No abstract