Prevalence and risk factors associated with psoriatic arthritis among patients with psoriasis.

INTRODUCTION: Psoriatic arthritis is a chronic, autoimmune inflammatory arthritis that occurs with psoriasis and has profound impact on patients' physical and psychological well-being. This study aims to determine the prevalence and risk factors associated with psoriatic arthritis among patients with psoriasis. METHODS: A single-center, cross-sectional study was conducted over a 12-month period at the Dermatology Clinic, Hospital Pulau Pinang, Malaysia involving all consecutive psoriasis patients. CASPAR (ClASsification of Psoriatic ARthritis) criteria were used to diagnose psoriatic arthritis. RESULTS: A total of 360 patients with psoriasis were recruited, of whom 107 (29.7%) had psoriatic arthritis. Psoriatic arthritis patients had equal gender distribution and the mean age of arthritis onset was 40.7 ± 12.8 years. Psoriasis preceded arthritis in 81.3% of patients (n = 87) with a mean latency interval of 10.5 years. Polyarthropathy was the predominant subtype affecting 46.8% (n = 50) of patients, followed by oligoarthropathy (22.4%, n = 24), axial joint disease (5.6%, n = 6), predominant distal interphalangeal joint disease (2.8%, n = 3), and mixed subtype (22.4%, n = 24). Enthesitis and dactylitis occurred in 12.1% (n = 13) and 20.6% (n = 22) of arthritis patients, respectively, and deformity was present in 37.4% (n = 40). Psoriatic arthritis was significantly associated with being an ever smoker (adjusted odds ratio [aOR] 0.41; 95% confidence interval [CI] 0.18-0.91, p = .029), genital psoriasis (aOR 2.25; 95% CI 1.17-4.33, p = .015), and increased erythrocyte sedimentation rate (ESR) (aOR 1.02; 95% CI 1.01-1.04, p = .005) and C-reactive protein [CRP] (aOR 1.04; 95% CI 1.00-1.08, p = .040). CONCLUSION: Our study showed a high prevalence of psoriatic arthritis among the psoriasis cohort. Genital involvement, and increased ESR and CRP were associated with psoriatic arthritis among patients with psoriasis.

Simplified Rapid Hydration Prevents Contrast-Associated Acute Kidney Injury Among CKD Patients Undergoing Coronary Angiography.

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CAG) are at high risk of contrast-associated acute kidney injury (CA-AKI) and mortality. Therefore, there is a clinical need to explore safe, convenient, and effective strategies for preventing CA-AKI. OBJECTIVES: This study sought to assess whether simplified rapid hydration is noninferior to standard hydration for CA-AKI prevention in patients with CKD. METHODS: This multicenter, open-label, randomized controlled study was conducted across 21 teaching hospitals and included 1,002 patients with CKD. Patients were randomized to either simplified hydration (SH) (SH group, with normal saline from 1 hour before to 4 hours after CAG at a rate of 3 mL/kg/h) or standard hydration (control group, with normal saline 12 hours before and 12 hours after CAG at a rate of 1 mL/kg/h). The primary endpoint of CA-AKI was a ≥25% or 0.5-mg/dL rise in serum creatinine from baseline within 48 to 72 hours. RESULTS: CA-AKI occurred in 29 of 466 (6.2%) patients in the SH group and in 38 of 455 (8.4%) patients in the control group (relative risk: 0.8; 95% CI: 0.5-1.2; P = 0.216). In addition, the risk of acute heart failure and 1-year major adverse cardiovascular events did not differ significantly between the groups. However, the median hydration duration was significantly shorter in the SH group than in the control group (6 vs 25 hours; P < 0.001). CONCLUSIONS: In CKD patients undergoing CAG, SH is noninferior to standard hydration in preventing CA-AKI with a shorter hydration duration.

Altered regional brain white matter in dry eye patients: a brain imaging study.

This study aimed to investigate the regional changes of brain white matter (WM) in DE patients using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). A total of 25 dry eye patients (PAT) and 25 healthy controls (HC) were recruited. All subjects underwent DTI and NODDI, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), isotropic volume fraction (FISO), intra-cellular volume fraction (FICVF), and orientation dispersion index (ODI) were obtained respectively. Then complete Hospital Anxiety and Depression Scale (HADS), anxiety score (AS) or depression scores (DS) were obtained. Receiver operating characteristic (ROC) curve analysis was used to evaluate the reliability of DTI and NODDI in distinguishing the two groups. DTI revealed that PAT had lower FA in both the left superior longitudinal fasciculus (LSLF) and the corpus callosum (CC), and higher MD in the LSLF, the right posterior limb of the internal capsule and the right posterior thalamic radiation. PAT had significant AD changes in regions including the genu of the CC, the right posterior limb of internal capsule, and the right splenium of the CC. From NODDI, PAT showed increased ODI in the LSLF and increased FISO in the right splenium of the CC. FICVF showed a significant decrease in the LSLF while increased in the left anterior corona radiata and the CC. Furthermore, the average values of MD and FICVF were significantly correlated with DS and AS. Hence the results of this study suggest that there are regional changes in WM in DE patients which may contribute to further understanding of the pathological mechanism of DE.

Circular RNA circ-TNPO3 suppresses metastasis of GC by acting as a protein decoy for IGF2BP3 to regulate the expression of MYC and SNAIL.

Gastric cancer (GC) continues to be the most common gastrointestinal malignancy in China, and tumor metastases are a major reason for poor prognosis. Circular RNAs (circRNAs) are an intriguing type of noncoding RNAs with important regulatory roles. However, the roles of circRNAs in GC metastasis have not been fully elucidated. Here, we reported that circ-transportin 3 (TNPO3) was significantly downregulated in 103 pairs of GC tissues compared with matched noncancerous tissues. The level of circ-TNPO3 expression correlated with differentiation of GC, and plasma circ-TNPO3 could serve as a potential diagnostic biomarker. Functionally, circ-TNPO3 inhibited proliferation and migration of GC in vitro and in vivo. We further verified that circ-TNPO3 competitively interacted with insulin-like growth factor 2 binding protein 3 (IGF2BP3) protein; thus, the role of IGF2BP3 in stabilizing MYC mRNA was weakened, which inhibited the expression of MYC and its target SNAIL. Taken together, circ-TNPO3 acts as a protein decoy for IGF2BP3 to regulate the MYC-SNAIL axis, thereby suppressing the proliferation and metastasis of GC. Therefore, circ-TNPO3 has the potential to serve as a therapeutic target for GC.

High incidence of NMDAR encephalitis among Austronesians: A population-based study in Sabah, Malaysia.

NMDAR encephalitis may be more common among non-Caucasians. A population-based study was conducted to estimate its incidence in Sabah, Malaysia, where the population consists predominantly of Austronesians (84%), and with a Chinese minority. Registries of NMDAR encephalitis at neurology referral centers were reviewed for case ascertainment. The annual incidence was 2.29/million (Austronesians: 2.56/million, Chinese: 1.31/million). Among pediatric population, the incidence was: Austronesians: 3.63/million, Chinese: 2.59/million. Our study demonstrated a higher incidence of NMDAR encephalitis among Austronesians than the predominantly Caucasian populations in Europe (0.5-0.9/million; pediatric: 0.7-1.5/million). Racial and genetic factors may contribute to risks of developing NMDAR encephalitis.

Correlation of serum vitamin D, adipose tissue vitamin D receptor, and peroxisome proliferator-activated receptor γ in women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Obesity and overweight are closely related to metabolic diseases and diabetes. However, the role of adipose tissue in the pathogenesis of GDM remains to be studied. The aim of this study was to investigate the correlation of vitamin D (VD) levels, VD receptor (VDR), and peroxisome proliferator-activated receptor γ (PPARγ) expression with GDM in overweight or obese women. METHODS: One hundred and forty pregnant women with full-term single-birth cesarean-section were selected as the study subjects and grouped (70 GDM women, including 35 non-overweight/non-obese women [group G1] and 35 women with overweight or obesity [group G2]; 70 pregnant women with normal glucose tolerance, including 35 non-overweight/non-obese women [group N1] and 35 overweight/obese women [group N2]). The levels of serum VD, blood biochemistry, and adiponectin were compared in these women. Subcutaneous adipose tissue was isolated from the abdominal wall incision. VDR and PPARγ messenger RNA (mRNA) transcript levels in these adipose tissues were quantified by real-time polymerase chain reaction. The differences between the levels of PPARγ protein and phosphorylated PPARγ Ser273 were detected by Western blotting. RESULTS: The serum VD level of GDM women was lower in comparison to that of women with normal glucose tolerance (G1 vs. N1: 20.62 ±â€Š7.87 ng/mL vs. 25.85 ±â€Š7.29 ng/mL, G2 vs. N2: 17.06 ±â€Š6.74 ng/mL vs. 21.62 ±â€Š7.18 ng/mL, P < 0.05), and the lowest in overweight/obese GDM women. VDR and PPARγ mRNA expression was higher in the adipose tissues of GDM women in comparison to that of women with normal glucose tolerance (VDR mRNA: G1 vs. N1: 210.00 [90.58-311.46] vs. 89.34 [63.74-159.92], G2 vs. N2: 298.67 [170.84-451.25] vs. 198.28 [119.46-261.23], PPARγ mRNA: G1 vs. N1: 100.72 [88.61-123.87] vs. 87.52 [66.37-100.04], G2 vs. N2: 117.33 [100.08-149.00] vs. 89.90 [76.95-109.09], P < 0.05), and their expression was the highest in GDM + overweight/obese women. VDR mRNA levels positively correlated with the pre-pregnancy body mass index (BMI), pre-delivery BMI, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and PPARγ mRNA while it negatively correlated with the VD and the adiponectin levels (r = 0.395, 0.336, 0.240, 0.190, 0.235, -0.350, -0.294, respectively, P < 0.05). The degree of PPARγ Ser273 phosphorylation increased in obese and GDM pregnant women. PPARγ mRNA levels positively correlated with pre-pregnancy BMI, pre-delivery BMI, FBG, HOMA-IR, serum total cholesterol, triglyceride, free fatty acid, and VDR mRNA, while it negatively correlated with the VD and adiponectin levels (r = 0.276, 0.199, 0.210, 0.230, 0.182, 0.214, 0.270, 0.235, -0.232, -0.199, respectively, P < 0.05). CONCLUSIONS: Both GDM and overweight/obese women had decreased serum VD levels and up-regulated VDR and PPARγ mRNA expression in adipose tissue, which was further higher in the overweight or obese women with GDM. VD may regulate the formation and differentiation of adipocytes through the VDR and PPARγ pathways and participate in the occurrence of GDM.

RGS5 decreases the proliferation of human ovarian carcinoma­derived primary endothelial cells through the MAPK/ERK signaling pathway in hypoxia.

Regulator of G­protein signaling 5 (RGS5), a tissue­specific signal­regulating molecule, plays a key role in the development of the vasculature. It was recently found that RGS5 is abundantly expressed in epithelial ovarian cancer (EOC) compared with the normal ovaries. However, the distribution of RGS5 in EOC and its significance require further investigation. The aim of the present study was to investigate the expression of RGS5 in EOC, as well as its association with cancer differentiation, metastasis and clinicopathological parameters. Immunohistochemistry (IHC), western blotting, RT­PCR, wound­healing, cell proliferation and flow cytometric assays were the methods used in the present study. RGS5 was highly expressed in the cytoplasm of ovarian carcinoma cells and in microvascular structures. The expression of RGS5 in EOC was negatively associated with peritoneal metastasis (P=0.004), but it was not found to be associated with age, tumor size, clinical stage or lymph node metastasis (P>0.05). EOC patients with high RGS5 expression had a prolonged progression­free survival (72.34±8.41 vs. 43.56±5.41 months, P<0.001). High expression of RGS5 was correlated with significantly lower microvascular density (MVD) as indicated by the expression of CD34, whereas the opposite was observed in tissues with low RGS5 expression (P<0.05). Hypoxia increased RGS5 expression in ovarian carcinoma­derived endothelial cells (ODMECs), whereas the proliferative capacity of ODMECs exhibited a significant increase following RNAi­mediated reduction of RGS5 expression. These data indicated that RGS5 plays a key role in angiogenesis in ovarian carcinoma. In addition, RGS5 downregulated the expression of the downstream proteins CDC25A, CDK2 and cyclin E, which are mediated by the mitogen­activated protein kinase/extracellular signal­regulated kinase pathway, causing ODMEC arrest in the G1 phase of the cell cycle under hypoxic conditions. Collectively, our data indicated that RGS5 is crucial for the occurrence and development of ovarian cancer, and that RGS5 and its signaling pathway may serve as anti­angiogenesis targets for the treatment of ovarian cancer.

Correlation of serum vitamin D, adipose tissue vitamin D receptor, and peroxisome proliferator-activated receptor γ in women with gestational diabetes mellitus / 中华医学杂志(英文版)

BACKGROUND@#Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Obesity and overweight are closely related to metabolic diseases and diabetes. However, the role of adipose tissue in the pathogenesis of GDM remains to be studied. The aim of this study was to investigate the correlation of vitamin D (VD) levels, VD receptor (VDR), and peroxisome proliferator-activated receptor γ (PPARγ) expression with GDM in overweight or obese women.@*METHODS@#One hundred and forty pregnant women with full-term single-birth cesarean-section were selected as the study subjects and grouped (70 GDM women, including 35 non-overweight/non-obese women [group G1] and 35 women with overweight or obesity [group G2]; 70 pregnant women with normal glucose tolerance, including 35 non-overweight/non-obese women [group N1] and 35 overweight/obese women [group N2]). The levels of serum VD, blood biochemistry, and adiponectin were compared in these women. Subcutaneous adipose tissue was isolated from the abdominal wall incision. VDR and PPARγ messenger RNA (mRNA) transcript levels in these adipose tissues were quantified by real-time polymerase chain reaction. The differences between the levels of PPARγ protein and phosphorylated PPARγ Ser273 were detected by Western blotting.@*RESULTS@#The serum VD level of GDM women was lower in comparison to that of women with normal glucose tolerance (G1 vs. N1: 20.62 ± 7.87 ng/mL vs. 25.85 ± 7.29 ng/mL, G2 vs. N2: 17.06 ± 6.74 ng/mL vs. 21.62 ± 7.18 ng/mL, P < 0.05), and the lowest in overweight/obese GDM women. VDR and PPARγ mRNA expression was higher in the adipose tissues of GDM women in comparison to that of women with normal glucose tolerance (VDR mRNA: G1 vs. N1: 210.00 [90.58-311.46] vs. 89.34 [63.74-159.92], G2 vs. N2: 298.67 [170.84-451.25] vs. 198.28 [119.46-261.23], PPARγ mRNA: G1 vs. N1: 100.72 [88.61-123.87] vs. 87.52 [66.37-100.04], G2 vs. N2: 117.33 [100.08-149.00] vs. 89.90 [76.95-109.09], P < 0.05), and their expression was the highest in GDM + overweight/obese women. VDR mRNA levels positively correlated with the pre-pregnancy body mass index (BMI), pre-delivery BMI, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and PPARγ mRNA while it negatively correlated with the VD and the adiponectin levels (r = 0.395, 0.336, 0.240, 0.190, 0.235, -0.350, -0.294, respectively, P < 0.05). The degree of PPARγ Ser273 phosphorylation increased in obese and GDM pregnant women. PPARγ mRNA levels positively correlated with pre-pregnancy BMI, pre-delivery BMI, FBG, HOMA-IR, serum total cholesterol, triglyceride, free fatty acid, and VDR mRNA, while it negatively correlated with the VD and adiponectin levels (r = 0.276, 0.199, 0.210, 0.230, 0.182, 0.214, 0.270, 0.235, -0.232, -0.199, respectively, P < 0.05).@*CONCLUSIONS@#Both GDM and overweight/obese women had decreased serum VD levels and up-regulated VDR and PPARγ mRNA expression in adipose tissue, which was further higher in the overweight or obese women with GDM. VD may regulate the formation and differentiation of adipocytes through the VDR and PPARγ pathways and participate in the occurrence of GDM.

Correlation of serum vitamin D, adipose tissue vitamin D receptor, and peroxisome proliferator-activated receptor γ in women with gestational diabetes mellitus / 中华医学杂志(英文版)

Background@#Gestational diabetes mellitus (GDM) is a common complication during pregnancy. Obesity and overweight are closely related to metabolic diseases and diabetes. However, the role of adipose tissue in the pathogenesis of GDM remains to be studied. The aim of this study was to investigate the correlation of vitamin D (VD) levels, VD receptor (VDR), and peroxisome proliferatoractivated receptor γ (PPARγ) expression with GDM in overweight or obese women.@*Methods@#One hundred and forty pregnant women with full-term single-birth cesarean-section were selected as the study subjects and grouped (70 GDM women, including 35 non-overweight/non-obese women [group G1] and 35 women with overweight or obesity [group G2]; 70 pregnant women with normal glucose tolerance, including 35 non-overweight/non-obese women [group N1] and 35 overweight/obese women [group N2]). The levels of serum VD, blood biochemistry, and adiponectin were compared in these women. Subcutaneous adipose tissue was isolated from the abdominal wall incision. VDR and PPARγ messenger RNA (mRNA) transcript levels in these adipose tissues were quantified by real-time polymerase chain reaction. The differences between the levels of PPARγ protein and phosphorylated PPARγ Ser273 were detected by Western blotting.@*Results@#The serum VD level of GDM women was lower in comparison to that of women with normal glucose tolerance (G1 vs. N1: 20.62 ± 7.87 ng/mL vs. 25.85 ± 7.29 ng/mL, G2 vs. N2: 17.06 ± 6.74 ng/mL vs. 21.62 ± 7.18 ng/mL, P < 0.05), and the lowest in overweight/obese GDM women. VDR and PPARγ mRNA expression was higher in the adipose tissues of GDM women in comparison to that of women with normal glucose tolerance (VDR mRNA: G1 vs. N1: 210.00 [90.58-311.46] vs. 89.34 [63.74-159.92], G2 vs. N2: 298.67 [170.84-451.25] vs. 198.28 [119.46-261.23], PPARγ mRNA: G1 vs. N1: 100.72 [88.61-123.87] vs. 87.52 [66.37-100.04], G2 vs. N2: 117.33 [100.08-149.00] vs. 89.90 [76.95-109.09], P < 0.05), and their expression was the highest in GDM+ overweight/obese women. VDR mRNA levels positively correlated with the pre-pregnancy body mass index (BMI), pre-delivery BMI, fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and PPARγ mRNA while it negatively correlated with the VD and the adiponectin levels (r = 0.395, 0.336, 0.240, 0.190, 0.235, -0.350, -0.294, respectively, P < 0.05). The degree of PPARγ Ser273 phosphorylation increased in obese and GDM pregnant women. PPARγ mRNA levels positively correlated with pre-pregnancy BMI, pre-delivery BMI, FBG, HOMA-IR, serum total cholesterol, triglyceride, free fatty acid, and VDR mRNA, while it negatively correlated with the VD and adiponectin levels (r = 0.276, 0.199, 0.210, 0.230, 0.182, 0.214, 0.270, 0.235, -0.232, -0.199, respectively, P < 0.05).@*Conclusions@#Both GDM and overweight/obese women had decreased serum VD levels and up-regulated VDR and PPARγ mRNA expression in adipose tissue, which was further higher in the overweight or obese women with GDM. VD may regulate the formation and differentiation of adipocytes through the VDR and PPARγ pathways and participate in the occurrence of GDM.

Let­7a suppresses cell proliferation via the TGF­ß/SMAD signaling pathway in cervical cancer.

Cervical cancer is the second most commonly diagnosed type of cancer among women after breast cancer. Recent research has addressed the role of microRNAs in cervical cancer. In the present study, we aimed to determine the effect of let­7a on the regulation of the cell proliferation of cervical cancer and the related signaling pathway. Real­time RT­PCR was used to detect the expression of let­7a in the blood of cervical cancer patients and normal controls. The expression of let­7a was also assessed in cervical cancer cell lines: HeLa, SiHa and normal human immortalized keratinocyes HaCaT. Cell proliferation was tested by MTT assay, and cell apoptosis and cell cycle were examined by flow cytometric analysis in HeLa cells. Moreover, bioinformatic analysis, dual­luciferase reporter assay and western blotting were used to confirm the target gene for let­7a. In addition, the expression of TGF­ß1, SMAD4 and p53 were assessed by western blotting and real­time PCR. Our studies showed that the expression of let­7a in cervical cancer was significantly reduced in cervical cancer patients compared with the expression in the normal control group. Cell proliferation of HeLa cells was inhibited by overexpression of let­7a. The cell cycle analysis showed that an increased population was arrested in the G2 phase in the let­7a mimic group when compared with that in the mimic control and untreated groups. In addition, the cell cycle­related factor p53 was increased in the let­7a overexpression group compared with that in the control and untreated groups. Furthermore, TGFBR1 was confirmed to be a target of let­7a. Moreover, the expression of TGF­ß1 and SMAD4 proteins was elevated in cervical squamous carcinoma and cervical adenocarcinoma tissues. However, the expression of TGF­ß1 and SMAD4 was decreased in the let­7a­overexpressing cervical cancer cell lines (HeLa, SiHa and CaSki). Our data suggest that let­7a may play a role in the cell proliferation of cervical cancer by regulating the TGF­ß/SMAD pathway, and may participate in the regulation of the occurrence and development of cervical cancer.

Autocrine interleukin-23 promotes self-renewal of CD133+ ovarian cancer stem-like cells.

Cancer stem cells (CSCs) are a group of cells which possess the ability of self-renewing and unlimited proliferation. And these CSCs are thought to be the cause of metastasis, recurrence and resistance. Recent study has found that pro-inflammatory cytokine and chemotactic factor mediate the self-renewing and differentiation of most of CSCs. Thus we speculate that ovarian cancer stem cells (OCSCs) can also maintain the ability of self-renewing and differentiation by releasing inflammatory factor. This report we discuss the biological characteristics and the specific molecular mechanism mediated by interleukin-23 (IL-23) and its receptor on the self-renewing of OCSCs. We found that OCSCs had high expression of IL-23 and IL-23R. IL-23 could promote the self-renewal ability of OCSCs and played a very important role to maintain the stable expression of stem cell markers in vitro. Moreover, we verified that IL-23 could maintain the potential tumorigenic of OCSCs in vivo and mediate the self-renewal ability and the formation of tumor in OCSCs by activating the signal pathways of STAT3 and NF-κB. In addition, human low differentiation tissues showed overexpression of IL-23. And IL-23 positively correlated to the expression level of CD133, Nanog and Oct4. In conclusion, Our discoveries demonstrate that autocrine IL-23 contribute to ovarian cancer malignancy through promoting the self-renewal of CD133+ ovarian cancer stem-like cells, and this suggests that IL-23 and its signaling pathway might serve as therapeutic targets for the treatment of ovarian cancer.

Effect of a complex lutein formula in an animal model for light-induced retinal degeneration.

Several retinal degenerative diseases cause vision loss and retinal cell death. Currently, people face prolonged exposure to digital screens, rendering vision protection from light exposure a critical topic. In this study, we designed a complex lutein formula (CLF) by combining several natural compounds: Calendula officinalis, Lycium barbarum, Vaccinium myrtillus, Cassia obtusifolia, and Rhodiola rosea. In addition, we evaluated the protective effects of the formula on retinal functions in an animal model for light-induced retinal degeneration. We employed electroretinography to analyse retinal function, and conducted a histological examination of the morphological changes in the retina treated under various conditions. We revealed that the retinal function in animals exposed to light for 7 days decreased significantly; however, the retinal function of animals that had received the CLF exhibited superior performance, despite light exposure. In addition, a greater portion of the outer nuclear layer (ONL) (i.e. the nuclei of photoreceptors) in these animals was preserved compared with the animals that had not received the formula after 7 days of light exposure. These results revealed that our dietary CLF supplement attenuated retinal function loss resulting from long-term light exposure.

SH2 domain-containing phosphatase 1 regulates pyruvate kinase M2 in hepatocellular carcinoma.

Pyruvate kinase M2 (PKM2) is known to promote tumourigenesis through dimer formation of p-PKM2Y105. Here, we investigated whether SH2-containing protein tyrosine phosphatase 1 (SHP-1) decreases p-PKM2Y105 expression and, thus, determines the sensitivity of sorafenib through inhibiting the nuclear-related function of PKM2. Immunoprecipitation and immunoblot confirmed the effect of SHP-1 on PKM2Y105 dephosphorylation. Lactate production was assayed in cells and tumor samples to determine whether sorafenib reversed the Warburg effect. Clinical hepatocellular carcinoma (HCC) tumor samples were assessed for PKM2 expression. SHP-1 directly dephosphorylated PKM2 at Y105 and further decreased the proliferative activity of PKM2; similar effects were found in sorafenib-treated HCC cells. PKM2 was also found to determine the sensitivity of targeted drugs, such as sorafenib, brivanib, and sunitinib, by SHP-1 activation. Significant sphere-forming activity was found in HCC cells stably expressing PKM2. Clinical findings suggest that PKM2 acts as a predicting factor of early recurrence in patients with HCC, particularly those without known risk factors (63.6%). SHP-1 dephosphorylates PKM2 at Y105 to inhibit nuclear function of PKM2 and determines the efficacy of targeted drugs. Targeting PKM2 by SHP-1 might provide new therapeutic insights for patients with HCC.

Promoter hypermethylation of let-7a-3 is relevant to its down-expression in diabetic nephropathy by targeting UHRF1.

Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus (DM). Recent researches show that DNA methylation plays a role in DN. However, the exact mechanism is not fully understood. MicroRNAs (miRNAs) are a group of endogenous non-coding small RNAs that are involved in the regulation of the development of DN. We have previously demonstrated that let-7a was down-expressed in DN by microarray, but the mechanism is unclear. In this study, let-7a-3 was found to be the only gene with the CpG island in the promoter region among the three let-7a members (let-7a-1, let-7a-2 and let-7a-3) by bioinformatic methods. Also, the expression levels of three homologues of let-7a were tested by real-time PCR, and DNA methylation of the let-7a-3 gene in the promoter region was analyzed by quantitative methylation-specific PCR (qMSP) in 60 individuals, with 20 cases in the control (CON), DM and DN groups respectively. Additionally, the target gene of let-7a-UHRF1 was proved by bioinformatic analysis and dual-luciferase reporter assay. Results showed that let-7a-3 was down-regulated in DN patients. Moreover, qMSP data showed that the average methylation ratio of the let-7a-3 promoter in the DN group was significantly higher than that in the CON and DM groups (P<0.05). Data also showed that let-7a negatively regulated the mRNA and protein expressions of methylation-related gene-UHRF1 through UHRF1 3'UTR. And the expressions of UHRF1 and DNMT1 were increased in DN patients. Therefore, we concluded that promoter hypermethylation and down-expression of let-7a-3 may play a role in DN by targeting UHRF1.

MiR-451 suppresses cell proliferation and metastasis in A549 lung cancer cells.

Recent study showed that inflammation was related to lung cancer. However, the exact cause of lung inflammation leading to carcinogenesis is unknown. MicroRNAs (miRNAs) are a group of endogenous non-coding small RNAs that regulate the activity of targeted mRNAs by inflammatory response in many diseases. MiR-451 was reported to relate to the development of lung cancer and metastasis of glioma. But the effect of miR-451 on cell proliferation, migration, and invasion of lung cancer is not really clear. In order to explore the molecular mechanism of the occurrence and development of lung cancer, we investigated the effect of human miR-451 on the proliferation, invasion, and metastasis in lung cancer cell line A549. The miR-451 expression construct was generated into pGenesil-1.1 and transfected into A549 cells. Results showed that the recombinant vectors were verified by sequencing. And miR-451 was over-expressed in A549 by real-time RT PCR. Furthermore, the proliferation, invasion, and metastasis of the cells in miR-451 group were inhibited significantly compared with those in control and A549 groups by MTT assay, Transwell invasion assay, and wound-healing assay. And the lung cancer metastasis factors (MMP-2, MMP-9, VEGF, and CXCR4) were decreased in miR-451 group by Western blot. Moreover, it was proved that inflammation-related gene-PSMB8 was a target for miR-451 by bioinformatics analysis and dual-luciferase reporter assay. And the protein expressions of PSMB8 and NOS2 were decreased in miR-451 group compared with those in control and A549 groups. Therefore, our findings indicated that miR-451 related to PSMB8/NOS2 inflammatory factors may suppress the development and migration of lung cancer, providing evidence for the role of miR-451 in lung cancer.

[Establishment of archives of Schistosoma japonicum antibody indirect hemagglutination tests].

OBJECTIVE: To establish written and electronic archives of Schistosoma japonicum antibody indirect hemagglutination (IHA) tests. METHODS: In the process of schistosomiasis screening by IHA, the written records, electronic records, and serum sample bank were combined to make comprehensive archives. RESULTS: The S. japonicum antibody IHA test archives can preserve the schistosomiasis screening data in the long term and even can trace the source of experiments, and the operation was simple. CONCLUSION: The archives of S. japonicum antibody IHA tests are simple and useful, and worth of popularization.

Taurine improves the spatial learning and memory ability impaired by sub-chronic manganese exposure.

BACKGROUND: Excessive manganese exposure induced cognitive deficit. Several lines of evidence have demonstrated that taurine improves cognitive impairment induced by numerous neurotoxins. However, the role of taurine on manganese-induced damages in learning and memory is still elusive. This goal of this study was to investigate the beneficial effect of taurine on learning and memory capacity impairment by manganese exposure in an animal model. RESULTS: The escape latency in the Morris Water Maze test was significantly longer in the rats injected with manganese than that in the rats received both taurine and manganese. Similarly, the probe trial showed that the annulus crossings were significantly greater in the taurine plus manganese treated rats than those in the manganese-treated rats. However, the blood level of manganese was not altered by the taurine treatment. Interestingly, the exposure of manganese led to a significant increase in the acetylcholinesterase activity and an evidently decrease in the choline acetyltransferase activity, which were partially restored by the addition of taurine. Additionally, we identified 9 differentially expressed proteins between the rat hippocampus treated by manganese and the control or the manganese plus taurine in the proteomic analysis using the 2-dimensional gel electrophoresis followed by the tandem mass spectrometry (MS/MS). Most of these proteins play a role in energy metabolism, oxidative stress, inflammation, and neuron synapse. CONCLUSIONS: In summary, taurine restores the activity of AChE and ChAT, which are critical for the regulation of acetylcholine. We have identified seven differentially expressed proteins specifically induced by manganese and two proteins induced by taurine from the rat hippocampus. Our results support that taurine improves the impaired learning and memory ability caused by excessive exposure of manganese.

A potentially functional polymorphism in the regulatory region of let-7a-2 is associated with an increased risk for diabetic nephropathy.

Diabetic nephropathy (DN) is a major diabetic complication. However, the initiating molecular events triggering DN are unknown. MicroRNAs (miRNAs) have recently been identified as regulators that modulate the target gene expression and are involved in DN. However, the evidence of the mechanism is still insufficient in human samples. In this study, microRNA microarray assay was used to study gene differential expression profiles in DN and diabetes mellitus (DM) patients. One of the specific differentially expressed microRNAs, let-7a, was down-expressed in DN. Additionally, the expression of let-7a was also decreased in DN by real-time RT PCR in the patients' samples. Moreover, single nucleotide polymorphism (SNP) analysis was used to evaluate the relationship between three SNPs in the regulatory region of let-7a-2 gene and the risk of DN in the Chinese Han population by means of PCR-restriction fragment length polymorphism (RFLP-PCR). Also, the genotype and allele frequencies of let-7a-2 polymorphism were tested in 274 individuals, including 108 DN, 104 DM patients and 62 health control individuals (CON). It was found that a variant rs1143770 and the distributions of CT/TT genotypes were significantly different in three groups, and the CT+TT genotypes frequencies were significantly higher in DN and DM groups than that in CON group. In conclusion, let-7a-2 might participate in the regulation of the occurrence of DN, and a potential variant rs1143770 was significantly associated with the increased risk for DN.

A blind area of family planning services in China: unintended pregnancy among unmarried graduate students.

BACKGROUND: Status of premarital sex, unintended pregnancy and associated factors among Chinese graduate students remain unclear. And unmarried graduate students' needs of family planning services seem to be ignored. In the present study, we ascertained the prevalence rate of premarital sex and unintended pregnancy, as well as estimated the possible factors associated with unintended pregnancy among unmarried Chinese graduate students, and evaluated their reproductive health needs. METHODS: We obtained the representative sample of graduate students using a multistage, stratified, cluster design, and collected data using a questionnaire. RESULTS: We obtained 11936 responders. Premarital sexual intercourse was acknowledged by 24.2% of responders; unintended pregnancy was acknowledged by 4.8% of responders (19.8% of students active in premarital sex); and abortion was acknowledged by 4.6% of responders (96.7% of pregnant students). In multivariate analysis, the identified risk factors for unintended pregnancy among both genders that were active in premarital sex were: (1) having no steady lover [for males: odds ratio (OR), 1.96, 95% confidence interval (CI), 1.41-2.70; for females: OR, 2.65; 95%CI, 1.56-4.84]; (2) younger age at the first sexual intercourse (for males: OR, 1.62, 95% CI, 1.22-2.15; for females: OR, 2.57; 95% CI, 1.64-4.02); (3) lack of condom use at the first sex (for males: OR, 1.13, 95% CI, 1.09-1.37; for females: OR, 2.81; 95% CI, 1.81-4.39); (4) unaware of the conditions of conception (for males: OR, 1.69, 95% CI, 1.31-2.19; for females: OR, 1.75; 95% CI, 1.16-2.65); and (5) unaware that abortion endangers women's future pregnancy (for males: OR, 2.98, 95% CI, 2.15-4.14; for females: OR, 2.34; 95% CI, 1.23-4.46). Medical graduates were not less likely to have unintended pregnancy than nonmedical graduates for both genders. CONCLUSIONS: The avoidable risk of being unintended pregnancy among graduate students in China indicates that an urgent need to take action on how to delay the age of first sex, promote condom use at first sex, and acquire accurate contraceptive information, as well as improve skills to use reliable contraception among graduate students.