HTR1A Gene Polymorphism in Type 2 Diabetes Mellitus Comorbid with Major Depressive Disorder in a Chinese Population.

Background: Major depressive disorder is a frequent mental illness, which is common in patients with type 2 diabetes. Type 2 diabetes comorbid with depression has a worse prognosis. There are multiple risk factors for depression, and genetic studies have shown that gene polymorphism may play an important role in the pathogenesis of depression. Methods: A total of 874 patients with type 2 diabetes were recruited for this study and divided into two groups: depressive group (DDM group, n = 234) and non-depressive group (NDDM group, n = 640). HTR1A gene polymorphisms (rs6295, rs878567, rs1800044) genotyping work was performed using a custom by design 48-Plex SNPscanTM Kit. Results: The rs6295, rs878567, and rs1800044 SNPs were not associated with type 2 diabetes comorbid with depression. Female sex, age, and FBG level increased the risk of depression in patients with type 2 diabetes. Conclusion: HTR1A rs6295, rs878567, and rs1800044 SNPs polymorphism is not associated with type 2 diabetes comorbid with depression. Rather, female sex, age, and FBG level are risk factors for depression among patients with type 2 diabetes. Larger studies are needed to further confirm our findings.

Human papillomavirus infection correlates with inflammatory Stat3 signaling activity and IL-17 level in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a major burden of public health and healthcare worldwide. Microbiota has been suggested in promoting chronic inflammation in the intestine which, in turn, promotes tumor development. This study focuses on possible correlations of human papillomavirus (HPV) infection with proinflammatory Stat3 signaling activities and the resulting levels of its downstream proinflammatory cytokine IL-17 in CRC patients. METHODS: HPV was examined using HPV Genotyping Chip technology and constitutively active Stat3 (p-Stat3) and IL-17 levels were tested using immunohistochemistry (IHC) in paraffin-embedded cancerous and adjacent normal tissues (ANT) from a cohort of 95 CRC patients. Correlation analyses were performed between HPV infection and clinicopathological characteristics, Stat3 activities and IL-17 levels among these CRC patients. RESULTS: Three major findings were observed: (1) HPV infection existed in a high rate of CRC cases (48.4%, 46/95), of which 45 cases (45/46, 97.8%) were high-risk HPV16-positive and only one case was HPV53-positive. (2) HPV infection correlated with poorer clinical stages (III+IV) of CRC. (3) HPV infection strongly correlated with both constitutively higher Stat3 activities (P<0.01) and higher IL-17 levels (P<0.01) only in CRC tissues but not in ANT tissues. CONCLUSIONS: HPV infection is common in CRC patients suggesting potentially preventive effectiveness of HPV vaccination among high-risk young individuals. We have for the first time revealed a tri-lateral relationship among HPV infection, constitutive Stat3 activity and IL-17 level, whose collaborative act may orchestrate a proinflammatory microenvironment in the colorectum that, in turn, may promote carcinogenesis and possibly facilitate progression of CRC.

Overweight and obesity among low-income Muslim Uyghur women in far western China: correlations of body mass index with blood lipids and implications in preventive public health.

BACKGROUND: The pandemic of obesity is a global public health concern. Most studies on obesity are skewed toward high-income and urban settings and few covers low-income populations. This study focused on the prevalence of overweight and obesity and their correlations with blood lipids/metabolites/enzymes (bio-indicators) in a rural community typical of low-income in remote western China. METHODS: This study was performed in a Muslim ethnic Uyghur rural community in Kashi Prefecture of Xinjiang, about 4,407 km (2,739 miles) away from Beijing. Body mass index (BMI) and major blood bio-indicators (25 total items) were measured and demographic information was collected from 1,733 eligible healthy women aged 21 to 71 yrs, of whom 1,452 had complete data for analysis. More than 92% of the women lived on US$1.00/day or less. According to the Chinese criteria, overweight and obesity were defined as BMI at 24 to <28 kg/m(2) and at ≥ 28 kg/m(2), respectively. RESULTS: The average BMI among these low-income women was 24.0 ± 4.0 (95% CI, 17.5-33.7) kg/m(2). The prevalence of obesity and overweight was high at 15.1% and 28.9%, respectively. Among 25 bio-indicators, BMI correlated positively with the levels of 11 bio-indicators including triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TCHOL), glucose (GLU), and uric acid (UA); but negatively with the levels of 5 bio-indicators including high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A/B (APO A/B). CONCLUSIONS: This is the first investigation reporting overweight and obesity being common in low-income Muslim Uyghur women, whose BMI correlates with several important blood bio-indicators which are risk factors for diabetes and cardiovascular diseases. These findings may help make preventive public health policies in Uyghur communities. To prevent diabetes and cardiovascular diseases in low-income settings, we therefore propose a cost-effective, two-step strategy first to screen for obesity and then to screen persons with obesity for diabetes and cardiovascular diseases.

Implementing a cervical cancer awareness program in low- income settings in Western China: a community-based locally affordable intervention for risk reduction.

BACKGROUND: Some 60 years after introduction of the Papanicolaou smear worldwide, cervical cancer remains a burden in developing countries where >85% of world new cases and deaths occur, suggesting a failure to establish comprehensive cervical-cancer control programs. Effective interventions are available to control cervical cancer but are not all affordable in low-income settings. Disease awareness saves lives by risk-reduction as witnessed in reducing mortality of HIV/AIDS and smoking-related cancers. SUBJECTS AND METHODS: We initiated a community-based awareness program on cervical cancer in two low-income Muslim Uyghur townships in Kashi (Kashgar) Prefecture, Xinjiang, China in 2008. The education involved more than 5,000 women from two rural townships and awareness was then evaluated in 2010 and 2011, respectively, using a questionnaire with 10 basic knowledge questions on cervical cancer. Demographic information was also collected and included in an EpiData database. A 10-point scoring system was used to score the awareness. RESULTS: The effectiveness and feasibility of the program were evaluated among 4,475 women aged 19-70 years, of whom >92% lived on/ below US$1.00/day. Women without prior education showed a poor average awareness rate of 6.4% (164/2,559). A onetime education intervention, however, sharply raised the awareness rate by 4-fold to 25.5% (493/1,916). Importantly, low income and illiteracy were two reliable factors affecting awareness before or after education intervention. CONCLUSIONS: Education intervention can significantly raise the awareness of cervical cancer in low-income women. Economic development and compulsory education are two important solutions in raising general disease awareness. We propose that implementing community-based awareness programs against cervical cancer is realistic, locally affordable and sustainable in low-income countries, which may save many lives over time and, importantly, will facilitate the integration of comprehensive programs when feasible. In this context, adopting this strategy may provide one good example of how to achieve "good health at low cost".

Stat6 activity-related Th2 cytokine profile and tumor growth advantage of human colorectal cancer cells in vitro and in vivo.

Signal transducer and activator of transcription 6 (Stat6) is critical in Th2 polarization of immune cells and active Stat6 activity has been suggested in anti-tumor immunity in animal models. The present study aims at investigating the impact of natural Stat6 activity on tumor microenvironment in human colorectal cancer cells in vitro and in vivo. Using colorectal cancer cell lines HT-29 and Caco-2 whose IL-4/Stat6 activities were known and nude mice as a model, we examined correlative relationships between Stat6 activities and gene expression profiles together with cellular behaviors in vitro and in vivo. HT-29 cells carrying active Stat6 signaling displayed spontaneous expression profiles favoring Th2 cytokines, cell cycle promotion, anti-apoptosis and pro-metastasis with increased mRNA levels of IL-4, IL-13, GATA-3, CDK4, CD44v6 and S100A4 using RT-PCR. In contrast, Caco-2 cells carrying defective Stat6 signaling exhibited spontaneous expression profiles favoring Th1 and Th17 cytokines, cell cycle inhibition, pro-apoptosis and anti-metastasis with elevated mRNA expression of IFNγ, TNFα, IL-12A, IL-17, IL-23, T-bet, CDKN1A, CDKNIB, CDKN2A and NM23-H1. Xenograft tumors of Stat6-active HT-29 cells showed a growth advantage over those of Stat6-defective Caco-2 cells. Furthermore, mice bearing HT-29 tumors expressed increased levels of Th2 cytokines IL-4 and IL-5 in the blood and pro-growth and/or pro-metastasis proteins CDK4 and CD44v6 in the tumor. To the contrary, mice bearing Caco-2 tumors expressed heightened levels of Th1 cytokines IFNγ and TNF in the blood and pro-apoptosis and anti-metastatic proteins p53 and p27(kip1) in the tumor. Colorectal cancer cells carrying active Stat6 signaling may create a microenvironment favoring Th2 cytokines and promoting expression of genes related to pro-growth, pro-metastasis and anti-apoptosis, which leads to a tumor growth advantage in vivo. These findings may imply why Stat6 pathway is constitutively activated in a number of human malignancies.

Natural resistance to apoptosis correlates with resistance to chemotherapy in colorectal cancer cells.

Defects in apoptotic machinery vary among individual cancer cells, and the efficacy of chemotherapy in killing cancer cells depends on the successful induction of apoptosis. This study tested the hypothesis that the intrinsic ability of a cancer cell's natural resistance to apoptosis would indicate its ability in resistance to chemotherapy. Four widely studied human colorectal cancer cell lines, SW480, HT-29, LoVo and Caco-2, were examined for their apoptotic fates in spontaneous cultures for up to 6 days using flowcytometry. Chemoresponse of these cells was tested against anti-colorectal cancer drugs 5-fluorouracil (5-FU) and oxaliplatin (OXP) at different peak plasma concentrations (PPCs) using MTT assay. Apoptosis analyses demonstrated that, from Day 2 to Day 6 in spontaneous cultures, SW480 and HT-29 lines showed resistance to apoptosis by having much less average early and late apoptotic cells than LoVo and Caco-2 lines with differences of 3.2- to 5.2-fold. Interestingly, apoptosis-resistant SW480 and HT-29 exhibited higher chemoresistance to both 5-FU (P < 0.01 at 5×, 10×, and 50× PPC) and OXP (P < 0.01 at 5× and 10× PPC, and P < 0.05 at 50× PPC) than LoVo and Caco-2. Colorectal cancer cells' natural resistance to apoptosis is an intrinsic ability that correlates with resistance to chemotherapeutic drugs 5-FU and OXP. Cancer cells' natural apoptotic phenotypes may help predict the outcome of chemotherapy in colorectal cancers.