Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation.

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Isorhamnetin Induces Melanoma Cell Apoptosis via the PI3K/Akt and NF-κB Pathways.

Malignant melanoma is characterized by its bad prognosis for aggressiveness, drug resistance, and early metastasis. Isorhamnetin (3'-methoxy-3,4',5,7-tetrahydroxyflavone; IH) is a natural flavonoid that has been investigated for its antitumor effects in breast cancer, colon cancer, and gastric cancer through inducing cell apoptosis. Given its role in tumor inhibition, no research has been conducted concerning its effect against melanoma. In the present study, we found that IH could significantly inhibit B16F10 cell proliferation and migration and induce B16F10 cell apoptosis. The examination on molecular mechanism revealed that IH could suppress the phosphorylation of Akt and the translocation of NF-κB, which are key factors in apoptosis-related pathways. We also detected that this process was related to the bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases 4 (PFKFB4) by PFKFB4 knockdown experiment. In line with in vitro study, we further provided that IH effectively inhibited tumor growth in vivo. Taken together, IH was proven to induce melanoma cell apoptosis in vitro and in vivo, which may serve as a potential agent in malignant melanoma treatment in the future.

The CCN1 (CYR61) protein promotes skin growth by enhancing epithelial-mesenchymal transition during skin expansion.

The skin expansion technique is widely used to induce skin growth for large-scale skin deformity reconstruction. However, the capacity for skin expansion is limited and searching for ways to improve the expansion efficiency is a challenge. In this study, we aimed to explore the possible mechanism of skin expansion and to find a potential therapeutic target on promoting skin growth. We conducted weighted gene coexpression network analysis (WGCNA) of microarray data generated from rat skin expansion and found CCN1 (CYR61) to be the central hub gene related to epithelial-mesenchymal transition (EMT). CCN1 up-regulation was confirmed in human and rat expanded skin and also in mechanically stretched rat keratinocytes, together with acquired mesenchymal phenotype. After CCN1 stimulation on keratinocytes, cell proliferation was promoted and partial EMT was induced by activating ß-catenin pathway. Treatment of CCN1 protein could significantly increase the flap thickness, improve the blood supply and restore the structure in a rat model of skin expansion, whereas inhibition of CCN1 through shRNA interference could dramatically reduce the efficiency of skin expansion. Our findings demonstrate that CCN1 plays a crucial role in skin expansion and that CCN1 may serve as a potential therapeutic target to promote skin growth and improve the efficiency of skin expansion.

CCN1 accelerates re-epithelialization by promoting keratinocyte migration and proliferation during cutaneous wound healing.

Re-epithelialization is an essential part of wound healing and has a prominent influence on the prognosis. CCN family member 1 (CCN1 or Cysteine-rich 61, CYR61), a matricellular protein, has a potential role in the wound healing process. However, its role in re-epithelialization remains unclear. The aim of this study was to determine the expression of CCN1 in the epidermis and its effect on keratinocytes during re-epithelialization. CCN1 expression in the wounded skin was analyzed using microarray data from GEO database and detected by immunofluorescence. The results showed upregulated CCN1 during the early stages of wound healing. Human primary keratinocytes were treated with recombinant human CCN1. The results showed that CCN1 promoted keratinocyte migration and proliferation. Moreover, a full-thickness mouse skin wound model and a superficial second-degree burn mouse model treated intracutaneously with CCN1 were used for in vivo studies. Topical treatment with CCN1 protein accelerated wound closure and re-epithelialization. Additionally, longer newly-formed epithelium tongue and elevated expression of PCNA and Ki67 were detected in the CCN1-treated group 4 days post-burn. These results indicate that CCN1 accelerates re-epithelialization by promoting keratinocyte migration and proliferation, and may serve as a novel target to promote re-epithelialization.

The correlation of plasma omentin-1 with insulin resistance in non-obese polycystic ovary syndrome.

OBJECTIVES: Aberrant circulating adipokines are considered to be related to the pathological mechanism of polycystic ovary syndrome (PCOS). This study aims to evaluate the relationship between plasma omentin-1 levels, metabolic and hormonal parameters in the setting of non-obese Chinese women with PCOS. MATERIAL AND METHODS: This was a case-controlled, cross-sectional study of 153 non-obese (BMI<25kg/m(2)) PCOS and 114 age-matched healthy non-obese control individuals. Levels of plasma omentin-1, fasting blood glucose, insulin and sexual hormones and ovary volume were analyzed in all subjects. RESULTS: Plasma omentin-1 levels of non-obese PCOS individuals were significantly lower than in healthy non-obese controls. Body Mass Index (BMI), homeostasis model of assessment for insulin resistance index (HOMA-IR), levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), LH/FSH ratio and ovary volume (OV) were significantly higher in subjects with PCOS than controls. In the HOMA-IR stratified subgroups, PCOS individuals with insulin resistance had lower omentin-1 than those without insulin resistance after BMI adjustment. Omentin-1 was negatively correlated with BMI, HOMA-IR and fasting insulin. Multiple linear regressions revealed that BMI contributed to omentin-1 levels. Ovary volume was negatively correlated to HOMA-IR but had no correlation with omentin-1. CONCLUSIONS: Plasma omentin-1 concentrations were decreased in the non-obese PCOS group. Insulin resistance could further decrease plasma omentin-1 in non-obese individuals with PCOS independent of BMI status.

Association of vitamin D status of septic patients in intensive care units with altered procalcitonin levels and mortality.

OBJECTIVE: The purpose of this study was to determine whether vitamin D levels correlate with procalcitonin (PCT) levels and mortality in septic patients. METHODS: The following data were collected from 236 patients upon admission to intensive care units (ICUs): demographics; Acute Physiology and Chronic Health Evaluation (APACHE) II score; Sequential Organ Failure Assessment (SOFA) score; 25-hydroxyvitamin D (25OHD), PCT, intact PTH, albumin, creatinine, and ionized calcium (iCa) levels; 25OHD sampling seasonality; fluid load (colloid and crystalloid before 25OHD sampling); mechanical ventilation duration; and length of stay (LOS) in the ICU. The primary endpoint was all-cause mortality 28 days after ICU admission. RESULTS: Patients with 25OHD deficiency had significantly higher APACHE II and SOFA scores, positive blood culture rates, PCT levels, intact PTH levels, and 28-day mortality rates. These patients also had lower iCa levels, longer LOS in the ICU, and longer ventilator durations than patients with 25OHD insufficiency or sufficiency. Age, sex, 25OHD sampling seasonality, serum albumin and creatinine levels, and fluid load did not vary among the 3 groups. Serum 25OHD levels at admission were significantly negatively correlated with PCT levels. PTH responders had significantly higher 28-day mortality rates than did PTH nonresponders. Cox regression showed that a 25OHD level of <20 ng/mL was an independent risk factor for 28-day mortality. CONCLUSIONS: Lower serum 25OHD levels at ICU admission were associated with 28-day mortality in septic patients. Serum 25OHD levels were inversely correlated with PCT levels. Hypovitaminosis D was associated with higher mortality rates in PTH responders than in nonresponders.

Changes in the calcium-parathyroid hormone-vitamin d axis and prognosis for critically ill patients: a prospective observational study.

OBJECTIVE: Vitamin D deficiency is prevalent in critically ill patients and may contribute to suboptimal clinical outcomes, but little is known about alterations of the calcium-parathyroid hormone (PTH)-vitamin D axis and prognosis in these individuals. METHODS: A prospective observational study was conducted on 216 patients admitted to a university-affiliated, tertiary-care medical intensive care unit(MICU) between June 2011 and December 2012. Serum levels of 25-hydroxyvitamin D, ionised calcium and intact PTH were determined within 24 h of MICU admission. The primary end point was all-cause hospital mortality within 90-days of admission. RESULTS: 95 patients (44%) showed 25-hydroxyvitamin D deficiency. Patients deficient in vitamin D showed significantly higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, rate of positive blood culture, incidence of multiple organ dysfunction syndrome, and 90-day mortality rate than did patients with vitamin D insufficiency or sufficiency (P<0.05), as well as lower levels of serum IgG. 25-Hydroxyvitamin D deficiency was identified as an independent risk factor for mortality (OR = 3.018, 95%CI 1.329-6.854, P = 0.008). Hypovitaminosis D in PTH-responders was associated with higher mortality than was the same condition in non-responders (P<0.05). CONCLUSIONS: These results suggest that vitamin D deficiency is prevalent among MICU patients, suggesting a significant derangement of the calcium-PTH-vitamin D axis in critically ill patients. Vitamin D deficiency is an independent risk factor for 90-day mortality, and hypovitaminosis D in PTH-responders is associated with higher mortality than is the same condition in non-responders.