Efficacy of immunotherapy-based immediate cytoreductive nephrectomy vs. deferred cytoreductive nephrectomy in metastatic renal cell carcinoma.

OBJECTIVE: This study was performed to evaluate the efficacy of immediate cytoreductive nephrectomy (CRN) followed by programmed cell death factor-1 (PD-1) inhibitors vs. deferred CRN after the administration of 4 cycles of neoadjuvant therapy using nivolumab preceding the debulking and postoperative chemotherapy in metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: We recruited 84 patients with primary mRCC admitted to our Oncology Department from 2018 to 2020 and randomized them 1:1 to receive either CRN followed by nivolumab (control group) or 4 cycles of neoadjuvant therapy using nivolumab before CRN and postoperative chemotherapy (study group), with 42 patients in each group. The primary clinical endpoints were the clinical efficacy and safety of the PD-1 antibody. Clinical outcomes were assessed 3 months after treatment. RESULTS: Patients were followed-up for 10-52 months, with a median follow-up period of 40.50 months. The control group reported 2 cases of complete remission and 10 cases of partial remission, with an objective response rate (ORR) of 28.57% (12/42). The study group reported 4 cases of complete remission and 14 cases of partial remission with an ORR of 42.86% (18/42). No significant differences in the ORR were identified between the two groups (p > 0.05). Progression-free survival of the patients was significantly extended from 30 months (19-51) to 43 months (38-76) after administrating the PD-1 inhibitors before the debulking (HR = 0.501, 95% CI: 0.266 to 0.942). There were no significant differences in the median survival of patients between the two groups [44 months (38-79) vs. 44 months (32-81)] (HR = 0.814, 95% CI: 0.412 to 1.612). The two protocols had a similar safety profile. CONCLUSIONS: Nivolumab administration preceding delayed CRN provides significant progression-free survival benefits for patients with mRCC, but its impact on overall survival requires further investigations.

Expression and clinical significance of miR-193a-3p in invasive pituitary adenomas.

OBJECTIVE: Our study aimed to investigate miR-193a-3p expression and its clinical significance in pituitary adenomas (PAs). Moreover, the correlation between miR-193a-3p expression and the invasiveness of PAs was explored. PATIENTS AND METHODS: In this study, the relative expression levels of miR-193a-3p were detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlations between miR-193a-3p and tumor size, clinical features, and prolactinomas postoperative prolactin (PRL) levels early remission were further analyzed. RESULTS: Compared with non-invasive PAs, there was a lower miR-193a-3p expression in invasive PAs. MiR-193a-3p expression had reverse relevance to tumor size. A higher risk of postoperative residual and recurrence was found in patients with downregulated miR-193a-3p. Prolactinomas patients with postoperative PRL levels early remission were at lower risk to relapse and patients with high-expression miR-193a-3p had a higher early remission rate, suggesting that miR-193a-3p was a significant prognostic factor for prolactinomas. CONCLUSIONS: MiR-193a-3p could have potential therapeutic value for invasive pituitary adenomas.

Circ-0001801 contributes to cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in glioblastoma by regulating miR-628-5p/HMGB3 axis.

OBJECTIVE: Glioblastoma (GBM) is a fast-growing type of central nervous system tumor with high invasiveness and recurrence. Circular RNA (circRNA) circ-0001801 (also named as circPCMTD1) was recognized as a novel biomarker in cancers. However, the pathological mechanism of circ-0001801 in GBM is still largely obscured. To the best of our knowledge, it is the first time to reveal the involvement of circ-0001801/miR-628-5p/HMGB3 axis in the progression of GBM cells. PATIENTS AND METHODS: Expression of circ-0001801, microRNA (miR)-628-5p and high mobility group box 3 (HMGB3) in GBM tumors and cells was detected by quantitative real time-polymerase chain reaction (qRT-PCR). Stability of circ-0001801 was determined by RNase R. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) was performed to analyze cell viability. Cell migration and invasion were assessed using transwell assay. The interaction between miR-628-5p and circ-0001801 or HMGB3 was confirmed by Dual-Luciferase reporter system. Protein expression of HMGB3, N-cadherin, E-cadherin and Vimentin was detected by Western blot. RESULTS: The up-regulation of circ-0001801 and HMGB3 and the down-regulation of miR-628-5p were both observed in GBM tumors and cells compared with the normal ones. Depletion of circ-0001801 reduced GBM cell proliferation, migration, invasion and EMT. In addition, we discovered that circ-0001801 was a sponge of miR-628-5p and HMGB3 was a target of miR-628-5p. Furthermore, miR-628-5p inhibitor abolished circ-0001801 silencing-mediated inhibition of cell progression in GBM. Similarly, HMGB3 restored circ-0001801 silencing-mediated repression on GBM cell progression. We also noticed that circ-0001801 could improve HMGB3 expression by sponging miR-628-5p in GBM. CONCLUSIONS: Overexpression of circ-00018 01 accelerates cell proliferation, migration, invasion and EMT in GBM by absorbing miR-628-5p and facilitating HMGB3 expression, representing promising targeted therapy for GBM.

A meta-analysis of influence of MSMB promoter rs10993994 polymorphisms on prostate cancer risk.

OBJECTIVE: The aim of this meta-analysis was to assess the association between beta-microseminoprotein gene (MSMB) rs10993994 polymorphism and prostate cancer (PCa) risk. MATERIALS AND METHODS: Relevant databases were searched to identify studies investigating the association between rs10993994 polymorphisms and the risk of PCa using allele contrast, recessive, dominant, and additive models. The assessment of the association was used by odds ratios (ORs) with 95% confidence intervals (CIs). Hardy-Weinberg equilibrium (HWE) was checked for each study. The sensitivity analysis and the assessment of publication bias were also performed. RESULTS: Six reports involving 13 eligible studies (a total of 11,385 PCa patients and 9,115 controls) were included in the meta-analysis. Our data revealed that the T allele of MSMB rs10993994 polymorphism was significantly associated with PCa in all subjects (allele contrast: OR=1.24, 95% CI=1.19-1.29, p<0.001). Similarly, for recessive, dominant, and additive genetic models, significant associations were also found (recessive: OR=1.40, 95% CI=1.30-1.51; dominant: OR=1.28, 95% CI=1.21-1.36; and additive: OR=1.56, 95% CI=1.44-1.70). Significant associations were also found in Caucasians. The data for Asians showed significant association in allele contrast and recessive, additive genetic models, whereas no statistical significance was found in the dominant genetic model. CONCLUSIONS: This study demonstrated a significant association between the MSMB rs10993994 polymorphisms and PCa risk. Further large-scale studies are warranted to confirm our findings.

The effects of aflatoxin exposure on Hepatitis B-vaccine induced immunity in Kenyan children.

BACKGROUND: Globally, approximately three million children die each year from vaccine preventable infectious diseases mainly in developing countries. Despite the success of the expanded immunization program, not all infants and children around the world develop the same protective immune response to the same vaccine. A vaccine must induce a response over the basal immune response that may be driven by population-specific, environmental or socio-economic factors. Mycotoxins like aflatoxins are immune suppressants that are confirmed to interfere with both cell-mediated and acquired immunity. The mechanism of aflatoxin toxicity is through the binding of the bio-activated AFB1-8, 9-epoxide to cellular macromolecules. METHODS: We studied Hepatitis B surface antibodies [anti-HBs] levels to explore the immune modulation effects of dietary exposure to aflatoxins in children aged between one and fourteen years in Kenya. Hepatitis B vaccine was introduced for routine administration for Kenyan infants in November 2001. To assess the effects of aflatoxin on immunogenicity of childhood vaccines Aflatoxin B1-lysine in blood serum samples were determined using High Performance Liquid Chromatography with Fluorescence detection while anti-HBs were measured using Bio-ELISA anti-HBs kit. RESULTS: The mean ± SD of AFB1-lysine adducts in our study population was 45.38 ± 87.03 pg/mg of albumin while the geometric mean was 20.40 pg/mg. The distribution of AFB1-lysine adducts was skewed to the right. Only 98/205 (47.8%) of the study population tested positive for Hepatitis B surface antibodies. From regression analysis, we noted that for every unit rise in serum aflatoxin level, anti-HBs dropped by 0.91 mIU/ml (-0.9110038; 95% C.I -1.604948, -0.21706). CONCLUSION: Despite high coverage of routine immunization, less than half of the study population had developed immunity to HepB. Exposure to aflatoxin was high and weakly associated with low anti-HBs antibodies. These findings highlight a potentially significant role for environmental factors that may contribute to vaccine effectiveness warranting further research.

lncRNA HOXB-AS3 promotes hepatoma by inhibiting p53 expression.

OBJECTIVE: We investigate the mechanism of HOXB-AS3 in promoting the development of hepatocellular carcinoma. PATIENTS AND METHODS: The expression of HOXB-AS3 in tumor tissues and adjacent tissues of hepatocellular carcinoma was detected by quantitative real time-polymerase chain reaction (qRT-PCR), and the relationship between the expression of HOXB-AS3 and tumor tissues was analyzed. The effects of HOXB-AS3 and p53 on cell proliferation, cell cycle and apoptosis were detected by plate cloning experiment and flow cytometry. The binding relationship between HOXB-AS3 and DNMT1 and the regulation mechanism of DNMT1 on p53 were tested by RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) experiments, respectively. Western blot was used to detect the expression of p53 after knockdown of HOXB-AS3. The torsion experiment was performed to assess whether HOXB-AS3 regulated the proliferation and apoptosis of hepatoma cells by inhibiting p53 expression. RESULTS: The results of qRT-PCR showed that the expression of HOXB-AS3 was significantly higher in cancerous tissues of patients with hepatocellular carcinoma than in adjacent tissues. The expression of HOXB-AS3 in patients in stage III and IV was significantly higher than that in stage I and II. Inhibition of HOXB-AS3 expression in liver cancer cells including Hep3B and LM3 could promote cell proliferation, inhibit cell apoptosis and induce cell cycle arrest in the G0/G1 phase. The results of RIP and ChIP experiments showed that HOXB-AS3 inhibited the expression of p53 by binding to DNMT1, and overexpression of p53 in Hep3B cells could partially reverse the changes in cell proliferation and apoptosis induced by HOXB-AS3. CONCLUSIONS: Highly expressed HOXB-AS3 was confirmed to promote the proliferation of hepatocellular carcinoma cells and inhibit apoptosis, and the mechanism was related to the regulation role of HOXB-AS3 in p53 expression by binding to DNMT1.

Preliminary study of Bim on the early diagnosis and prognosis of the elderly uremia with gastrointestinal nutrition combined with dialysis.

OBJECTIVE: Elderly uremia frequently refers to the end stage of various chronic kidney diseases that threats the patients' health seriously. Enteral nutrition can reduce complications, while the molecular mechanism is still unclear. Mitochondrial protein Bim plays an essential role in regulating inflammation, restraining oxidative stress, and maintaining the balance of the mitochondrial membrane potential and energy production. This study aims to investigate the effect of Bim on the early diagnosis and prognosis of the elderly uremia with gastrointestinal nutrition combined with dialysis. PATIENTS AND METHODS: Elderly patients with uremia in our hospital were selected and divided into parenteral nutrition group, enteral nutrition group, and regular treatment group. Healthy volunteers were chosen as the control group. Blood oxygen free radicals were tested by flow cytometry. Blood immune function parameter C-reactive protein and IL-6 levels were determined by Western blot. Bim expression in blood was evaluated by RT-PCR and Western blot. Correlation analysis was performed between Bim level and the prognosis of elderly patients with uremia who received gastrointestinal nutrition therapy. RESULTS: Blood oxygen free radical level was significantly higher in parenteral nutrition group and regular treatment group compared with enteral nutrition group (p< 0.05). C-reactive protein and IL-6 contents were significantly reduced in parenteral nutrition group and regular treatment group compared to those in enteral nutrition group (p< 0.05). The expression of Bim at both mRNA and protein levels was declined in elderly patients with uremia after enteral nutrition combined with dialysis therapy to the normal level. The level of Bim was positively correlated with the severity of elderly uremia. CONCLUSIONS: Bim is positively correlated with the severity of elderly uremia, which can be set as a potential specific biomarker, along with reactive oxygen radicals, CRP, IL-6, for the prognosis of elderly uremia.

Identification of chronic obstructive pulmonary disease subgroups in 13 Asian cities.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition that can differ in its clinical manifestation, structural changes and response to treatment. OBJECTIVE: To identify subgroups of COPD with distinct phenotypes, evaluate the distribution of phenotypes in four related regions and calculate the 1-year change in lung function and quality of life according to subgroup. METHODS: Using clinical characteristics, we performed factor analysis and hierarchical cluster analysis in a cohort of 1676 COPD patients from 13 Asian cities. We compared the 1-year change in forced expiratory volume in one second (FEV1), modified Medical Research Council dyspnoea scale score, St George's Respiratory Questionnaire (SGRQ) score and exacerbations according to subgroup derived from cluster analysis. RESULTS: Factor analysis revealed that body mass index, Charlson comorbidity index, SGRQ total score and FEV1 were principal factors. Using these four factors, cluster analysis identified three distinct subgroups with differing disease severity and symptoms. Among the three subgroups, patients in subgroup 2 (severe disease and more symptoms) had the most frequent exacerbations, most rapid FEV1 decline and greatest decline in SGRQ total score. CONCLUSION: Three subgroups with differing severities and symptoms were identified in Asian COPD subjects.

Protein kinase Mζ in medial prefrontal cortex mediates depressive-like behavior and antidepressant response.

Neuronal atrophy and alterations of synaptic structure and function in the medial prefrontal cortex (mPFC) have been implicated in the pathogenesis of depression, but the underlying molecular mechanisms are largely unknown. The protein kinase Mζ (PKMζ), a brain-specific atypical protein kinase C isoform, is important for maintaining long-term potentiation and storing memory. In the present study, we explored the role of PKMζ in mPFC in two rat models of depression, chronic unpredictable stress (CUS) and learned helplessness. The involvement of PKMζ in the antidepressant effects of conventional antidepressants and ketamine were also investigated. We found that chronic stress decreased the expression of PKMζ in the mPFC and hippocampus but not in the orbitofrontal cortex. Overexpression of PKMζ in mPFC prevented the depressive-like and anxiety-like behaviors induced by CUS, and reversed helplessness behaviors. Inhibition of PKMζ in mPFC by expressing a PKMζ dominant-negative mutant induced depressive-like behaviors after subthreshold unpredictable stress and increased learned helplessness behavior. Furthermore, stress-induced deficits in synaptic proteins and decreases in dendritic density and the frequency of miniature excitatory postsynaptic currents in the mPFC were prevented by PKMζ overexpression and potentiated by PKMζ inhibition in subthreshold stress rats. The antidepressants fluoxetine, desipramine and ketamine increased PKMζ expression in mPFC and PKMζ mediated the antidepressant effects of ketamine. These findings identify PKMζ in mPFC as a critical mediator of depressive-like behavior and antidepressant response, providing a potential therapeutic target in developing novel antidepressants.

Allopurinol ameliorates cardiac function in non-hyperuricaemic patients with chronic heart failure.

OBJECTIVE: This study sought to observe the effects of allopurinol on the cardiac function of non-hyperuricaemic patients with chronic heart failure and determine the safety of allopurinol for clinical applications. PATIENTS AND METHODS: A group of 125 consecutive cases of non-hyperuricaemic patients with chronic heart failure who were treated at Chongqing Emergency Medical Centre between July 2011 and June 2012 were enrolled and were randomly divided into allopurinol (300 mg/day) group (n=62) and control group (n=63). During the six months treatment period, levels of cardiac function, brachial artery endothelial function, inflammatory cytokines, and biochemical markers were routinely examined. RESULTS: After three months of allopurinol treatment, patients exhibited an increase in flow-mediated vasodilatation (FMD) of brachial artery, whereas, after six months of treatment, the cardiac function classification was improved; plasma levels of brain natriuretic peptide and tumour necrosis factor-a were decreased; left ventricular internal diameter was diminished; and the ejection fraction was increased (p<0.01 for all the parameters) in patients. Serum uric acid level was decreased during the treatment period for both groups, with no significant difference between the two groups. Liver and kidney dysfunction was not observed among the study participants, and no significant increase in creatine kinase level was detected for either treatment group. CONCLUSIONS: For non-hyperuricaemic patients with chronic heart failure, the addition of six months of allopurinol therapy was safe and effective. Moreover, in these patients, allopurinol treatment not only can significantly ameliorate the left ventricular function and reduce the level of inflammatory factors but could also improve endothelial function.

Proapoptotic effects of heme oxygenase-1 inhibitor on Kasumi-1 cells via the ATF4/CHOP/Ire-1α pathway.

We evaluated the effects of down-regulated heme oxygenase (HO)-1 expression on the proliferation of the acute myelocytic leukemia Kasumi-1 cell line by using the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) in combination with daunorubicin (DNR), and evaluated the mechanism. The proliferation rates of cells treated with 10 mg/mL DNR and 10 mM ZnPPIX individually or in combination for different time periods were detected using the MTT assay. The apoptotic outcomes of the blank control, ZnPPIX, DNR, and ZnPPIX groups in combination with the DNR group were detected by flow cytometry. The expression of HO-1, activating transcription factor 4, CCAAT-enhancer-binding protein homologous protein, and inositol-requiring enzyme-α mRNA and proteins were detected by fluorescent quantitative real-time polymerase chain reaction and western blotting, respectively. Combined administration inhibited the cells most potently and time-dependently, decreased the expression of HO-1, and significantly increased the expression of activating transcription factor 4, CCAAT-enhancer-binding protein homologous protein, and inositol-requiring enzyme-α expression levels. The cell apoptotic rates in the blank control, DNR, ZnPPIX, and combined administration groups were 8.32 ± 0.53, 39.16 ± 1.46, 10.46 ± 0.88, and 56.26 ± 2.24%, respectively. Inhibiting HO-1 expression can enhance the damaging effects of DNR on Kasumi-1 cells, providing experimental evidence for the improvement of therapeutic effects on acute myelocytic leukemia in clinical practice.

Therapeutic effects of tibial support braces on posterior stability after posterior cruciate ligament reconstruction with autogenous hamstring tendon graft.

BACKGROUND: In the patients who have to be in supine position for most of the time after posterior cruciate ligament (PCL) reconstruction, the tibia tends to shift backwards due to the gravity of the lower leg and the tensed hamstring muscle. AIM: To observe the effects of tibial support braces on rehabilitation after PCL reconstruction. DESIGN: Retrospective study. SETTING: Inpatients. POPULATION: Thirty-nine patients were divided into regular brace (N.=18) and tibial support brace (N.=21) groups according to using different types of braces after PCL reconstruction. METHODS: The follow-up time was more than 2 years in all patients. The function of the affected knee joint was evaluated with International Knee Documentation Committee (IKDC) score, Lysholm knee score, Tegner activity rating, range of motion (ROM) and kneelax arthrometer before and after PCL reconstruction, respectively. RESULTS: The function of the affected knee joint was significantly improved in both groups after PCL reconstruction. Compared with regular brace group, postoperative Lysholm and IKDC scores were significantly increased in tibial support brace group (P<0.05). However, there were no statistical differences in Tegner activity rating and ROM between regular brace group and tibial support brace group (P<0.05). CONCLUSION: Tibial support brace can obtain better therapeutic effects for PCL reconstruction. CLINICAL REHABILITATION IMPACT: This study suggests that compared with regular brace, tibial support brace can significantly improve the mechanical stability and functional outcomes of the affected knee after PCL reconstruction.

Spinal sample showing p-JNK and P38 associated with the pain signaling transduction of glial cell in neuropathic pain.

OBJECTIVE: To investigate the signaling pathways after astrocytes were activated in neuropathic pain. METHODS: Thirty-six Sprague Dawley (s.d.) rats were randomly divided into two groups (each group with 18 s.d. rats) including chronic constriction injury (CCI) of the sciatic nerve model group and sham operation group. Operation was perform ed on the right leg in all rats. The lumbar spin al cord (L4 and L5) was taken to make paraffin slices on the 1st day before operation and the 1st, 3rd, 7th, 14th and 28th day after operation in each group. Paraffin slices were labeled with p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) by immunofluorescence staining, and then were co-labeled with hexaribonucleotide binding protein-3 (NeuN), glial fibrillary acidic protein (GFAP) and anti-integrin αM (CD11b) antibody (OX-42) to explore the associations of p38MAPK and JNK with nerve cells or glial cell. RESULTS: Compared with sham group, the pain threshold was significantly decreased, and astrocyte-activated markers, GFAP and vimentin were significantly increased in CCI group. The mean fluorescence intensities of p38MAPK and JNK were increased in the right spinal dorsal horn of CCI group. The coexpression of JNK and GFAP was found in astrocytes of the spinal dorsal horn in CCI group. CONCLUSION: JNK signal transduction pathway is involved in the pain signaling transduction of astrocytes.

Dexmedetomidine protects against ischemia/reperfusion injury in rat kidney.

OBJECTIVES: Ischemia/reperfusion (I/R) injury in the kidney during perioperative period remains the leading cause of acute renal failure. The purpose of this experimental study was to determine the role of dexmedetomidine (Dex) on renal I/R injury in rats. MATERIALS AND METHODS: Male Wistar rats, subjected to renal ischemia for 45 min, were either untreated or treated with dexmedetomidine 30 min prior to renal ischemia. A sham-operated group served as the control. Renal function [serum creatinine, blood urea nitrogen, serum Cystatin C and neutrophil gelatinase-associated lipocalin (NGAL)], histology, apoptosis and expression of the phosphorylations of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) were assessed. RESULTS: The animals treated with dexmedetomidine improved renal functional recovery, especially reducing the level of serum Cystatin C and NGAL at early time after ischemia, attenuated histological lesions, reduced tubular epithelial apoptosis and inhibited the phosphorylation of JAK2 and its downstream molecule STAT3, contributing to ameliorating renal I/R injury. CONCLUSIONS: Our data suggest that anti-apoptosis effect contributes to the renoprotection of dexmedetomidine, via inhibiting JAK2/STAT3 signaling pathway partially.

Characterization of the ß-1,3-glucanase gene in peanut (Arachis hypogaea L.) by cloning and genetic transformation.

Plant ß-1,3-glucanases are commonly involved in disease resistance. This report describes the cloning and genetic transformation of a ß-1,3-glucanase gene from peanut. The gene was isolated from both the genomic DNA and cDNA of peanut variety Huayu20 by polymerase chain reaction (PCR) and reverse transcription PCR (RT-PCR), respectively. The DNA sequence contained 1471 bp including two exons and one intron, and the coding sequence contained 1047 bp that coded for a 348-amino acid protein with a calculated molecular weight of 38.8 kDa. The sequence was registered in NCBI (GenBank accession No. JQ801335) and was designated as Ah-Glu. As determined by BLAST analysis, the Ah-Glu protein has 42-90% homology with proteins from Oryza sativa (BAC83070.1), Zea mays (NP_001149308), Arabidopsis thaliana (NP_200470.1), Medicago sativa (ABD91577.1), and Glycine max (XP_003530515.1). The over-expression vector pCAMBIA1301-Glu containing Ah-Glu was constructed, confirmed by PCR and restriction enzyme digestion, and transformed into peanut variety Huayu22 by Agrobacterium EHA105-mediated transformation. The putative transformed plants (T0) were confirmed by PCR amplification. RT-PCR analysis and ß-glucuronidase (GUS) staining showed that the transferred Ah-Glu was expressed as mRNA and protein. In a laboratory test, the transgenic plants were found to be more resistant to the fungal pathogen Cercospora personata than the non-transgenic plants were.

Genome-wide association study in a Chinese population with diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of preventable blindness in adults. To identify genetic contributions in DR, we studied 2071 type 2 diabetics. We first conducted a genome-wide association study of 1007 individuals, comparing 570 subjects with ≥8 years duration without DR (controls) with 437 PDR (cases) in the Chinese discovery cohort. Cases and controls were similar for HbA1c, diabetes duration and body mass index. Association analysis with imputed data identified three novel loci: TBC1D4-COMMD6-UCHL3 (rs9565164, P = 1.3 × 10(-7)), LRP2-BBS5 (rs1399634, P = 2.0 × 10(-6)) and ARL4C-SH3BP4 (rs2380261, P = 2.1 × 10(-6)). Analysis of an independent cohort of 585 Hispanics diabetics with or without DR though did not confirm these signals. These genes are still of particular interest because they are involved in insulin regulation, inflammation, lipid signaling and apoptosis pathways, all of which are possibly involved with DR. Our finding nominates possible novel loci as potential DR susceptibility genes in the Chinese that are independent of the level of HbA1c and duration of diabetes and may provide insight into the pathophysiology of DR.

Effect of green tea and Tai Chi on bone health in postmenopausal osteopenic women: a 6-month randomized placebo-controlled trial.

UNLABELLED: Postmenopausal women with osteopenia received green tea polyphenols (GTP) supplement and/or Tai Chi exercise for 6 months. Bone turnover biomarkers, calcium metabolism, and muscle strength were measured. This study showed that GTP supplementation and Tai Chi exercise increased bone formation biomarkers and improved bone turnover rate. Tai Chi exercise increased serum parathyroid hormone. GTP supplementation, Tai Chi exercise, and the combination of the two all improved muscle strength in postmenopausal women with osteopenia. INTRODUCTION: This study evaluated the effect of GTP supplementation and Tai Chi (TC) exercise on serum markers of bone turnover (bone-specific alkaline phosphatase, BAP, and tartrate-resistant acid phosphatase, TRAP), calcium metabolism, and muscle strength in postmenopausal osteopenic women. METHODS: One hundred and seventy-one postmenopausal osteopenic women were randomly assigned to four groups: (1) placebo (500 mg starch/day), (2) GTP (500 mg GTP/day), (3) placebo + TC (placebo plus TC training at 60 min/session, three sessions/week), and (4) GTP + TC (GTP plus TC training). Overnight fasting blood and urine samples were collected at baseline, 1, 3, and 6 months for biomarker analyses. Muscle strength was evaluated at baseline, 3, and 6 months. One hundred and fifty subjects completed the 6-month study. RESULTS: Significant increases in BAP level due to GTP intake (at 1 month) and TC (at 3 months) were observed. Significant increases in the change of BAP/TRAP ratio due to GTP (at 3 months) and TC (at 6 months) were also observed. Significant main effect of TC on the elevation in serum parathyroid hormone level was observed at 1 and 3 months. At 6 months, muscle strength significantly improved due to GTP, TC, and GTP + TC interventions. Neither GTP nor TC affected serum TRAP, serum and urinary calcium, and inorganic phosphate. CONCLUSION: In summary, GTP supplementation and TC exercise increased BAP and improved BAP/TRAP ratio. TC exercise increased serum parathyroid hormone. GTP supplementation, TC exercise, and the combination of the two all improved muscle strength in postmenopausal women with osteopenia.

Socio-demographic determinants of aflatoxin B1-lysine adduct levels among pregnant women in Kumasi, Ghana.

OBJECTIVES: Aflatoxins are fungal metabolites that contaminate staple food crops in many developing countries. Although studies have linked these toxins to adverse birth outcomes and poor infant development, no study has investigated the socio-demographic and economic determinants of aflatoxin levels among pregnant women living in sub-Saharan Africa. DESIGN: A cross-sectional study was conducted among 785 pregnant women in Kumasi. Aflatoxin B1 lysine adduct levels (AF-ALB) were determined by High Performance Liquid Chromatography. Analysis of variance was used to determine mean log AF-ALB levels and significance of differences in these levels according to socio-demographic variables. Logistic regression was used to identify independent associations of socio-demographics with having AF-ALB levels (≥ 11.34 pg/mg; upper quartile). RESULTS: AF-ALB levels ranged from 0.44 pg/mg to 268.73 pg/mg albumin with a median level of 5.0 pg/mg. Bivariate analyses indicates that mean ln AF-ALB as well as the percent of women having high AF-ALB levels (≥ 11.34 pg/mg; upper quartile) were inversely associated with indices of higher socioeconomic status: higher education and income, being employed and having a flush toilet. Higher income, being employed, having one child (verses no children) and having a flush toilet (verses no toilet facilities) were each independently associated with a 30-40% reduced odds of high AF-ALB levels. CONCLUSIONS: Additional research is needed to investigate how socio-demographic and economic factors interact to influence aflatoxin ingestion by individuals in regions with high aflatoxin crop contamination. This knowledge can be used to formulate and implement policies that will reduce exposure of women and their unborn children to these toxins.

Association of high viral load and abnormal liver function with high aflatoxin B1-albumin adduct levels in HIV-positive Ghanaians: preliminary observations.

We examined the association between certain clinical factors and aflatoxin B(1)-albumin adduct (AF-ALB) levels in HIV-positive people. Plasma samples collected from 314 (155 HIV-positive and 159 HIV-negative) people were tested for AF-ALB levels, viral load, CD4+ T-cell count, liver function profile, malaria parasitaemia, and hepatitis B and C virus infections. HIV-positive participants were divided into high and low groups based on their median AF-ALB of 0.93 pmol mg(-1) albumin and multivariable logistic and linear regression methods used to assess relationships between clinical conditions and AF-ALB levels. Multivariable logistic regression showed statistically significant increased odds of having higher HIV viral loads (OR=2.84; 95% CI=1.17-7.78) and higher direct bilirubin levels (OR=5.47; 95% CI=1.03-22.85) among HIV-positive participants in the high AF-ALB group. There were also higher levels of total bilirubin and lower levels of albumin in association with high AF-ALB. Thus, aflatoxin exposure may contribute to high viral loads and abnormal liver function in HIV-positive people and so promote disease progression.

Reversal of multidrug resistance in human breast cancer cells by Curcuma wenyujin and Chrysanthemum indicum.

The emergence of multidrug resistance (MDR) is a big challenge to cancer chemotherapy. Plant-derived agents have great potential to prevent onset or delay progression of the carcinogenic process, and enhance the efficacy of mainstream antitumor agents. In this study, fractionated extracts of Curcuma wenyujin and Chrysanthemum indicum were tested for their potential to modulate the MDR phenotype and function of P-gp in MCF-7/ADR and A549/Taxol cells in vitro. Fractions C. wenyujin C10, E10 from Curcuma wenyujin, and C. indicum E10 from Chrysanthemum indicum, exhibited significant effects in sensitization of these resistant cancer cells at non-toxic concentration to doxorubicin and docetaxel by MTT method. They also increased the intracellular doxorubicin accumulation and retention in MCF-7/ADR cells. In mechanism study, an increase of Rh123 accumulation and a decrease of Rh123 efflux were observed in MCF-7/ADR cells treated with these fractions, indicating a blockage of the activity of P-gp. Furthermore, C. wenyujin C10 had the ability to down-regulate the expression of P-gp. All these fractions could enhance the apoptosis induced by doxorubicin in MCF-7/ADR cells, and restore the effect of docetaxel on the induction of G2/M arrest in A549/Taxol cells. C. wenyujin C10 and E10 also owned the ability to induce S phase arrest. These results showed the therapeutic value of the three fractions as potential MDR-reversing agents and warranted further investigations.