Associations of Nutritional,Environmental, and Metabolic Biomarkers with Diabetes-Related Mortality in U.S. Adults: The Third National Health and Nutrition Examination Surveys between 1988–1994 and 2016

Background: Nutritional, environmental, and metabolic status may play a role in affecting the progression and prognosis of type 2 diabetes. However, results in identifying prognostic biomarkers among diabetic patients have been inconsistent and inconclusive. We aimed to evaluate the associations of nutritional, environmental, and metabolic status with disease progression and prognosis among diabetic patients. Methods: In a nationally representative sample in the NHANES III (The Third National Health and Nutrition Examination Survey, 1988–1994), we analyzed available data on 44 biomarkers among 2113 diabetic patients aged 20 to 90 years (mean age: 58.2 years) with mortality data followed up through 2016. A panel of 44 biomarkers from blood and urine specimens available from NHANES III were included in this study and the main outcomes as well as the measures are mortalities from all-causes. We performed weighted logistic regression analyses after controlling potential confounders. To assess incremental prognostic values of promising biomarkers beyond traditional risk factors, we compared c-statistics of the adjusted models with and without biomarkers, separately. Results: In total, 1387 (65.2%) deaths were documented between 1988 and 2016. We observed an increased risk of all-cause mortality associated with higher levels of serum C-reactive protein (p for trend = 0.0004), thyroid stimulating hormone (p for trend = 0.04), lactate dehydrogenase (p for trend = 0.02), gamma glutamyl transferase (p for trend = 0.02), and plasma fibrinogen (p for trend = 0.03), and urine albumin (p for trend < 0.0001). In contrast, higher levels of serum sodium (p for trend = 0.005), alpha carotene (p for trend = 0.006), and albumin (p for trend = 0.005) were associated with a decreased risk of all-cause mortality. In addition, these significant associations were not modified by age, sex, or race. Inclusion of thyroid stimulating hormone (p = 0.03), fibrinogen (p = 0.01), and urine albumin (p < 0.0001), separately, modestly improved the discriminatory ability for predicting all-cause mortality among diabetic patients. Conclusions: Our nationwide study findings provide strong evidence that some nutritional, environmental, and metabolic biomarkers were significant predictors of all-cause mortality among diabetic patients and may have potential clinical value for improving stratification of mortality risk.     

Phenolic constituents in dried flowers of aloe vera (Aloe barbadensis) and their in vitro antioxidative capacity

The dried flowers from Aloe vera (L.) Burm. f. (Aloe barbadensis Mill.) (Asphodelaceae) were analysed by means of HPLC-DAD and HPLC-MS/MS, verifying chlorogenic, caffeic, 5-P-coumaroylquinic, caffeoylshikimic, 5-feruloylquinic, 5-P-CIS-coumaroylquinic, P-coumaric and ferulic acid as well as luteolin, apigenin, quercetin, kaempferol, isoorientin, isovitexin and their 7-O-glucosides, saponarin and lutonarin. On searching for anthranoids in the flower extract, aloe-emodin as well as the glycosylchromone aloeresin B could be identified. Aloin A and B, the laxative principle of the drug Cura?ao-Aloes, are not accumulated in the dried flowers. The polyphenol content of three different batches was 0.73 - 1.01% (+/- 0.05%) and the flavonoid content 0.24 - 0.34% (+/- 0.01%). The hydrophilic antioxidative capacity amounted to 85.7 - 94.9 (+/- 0.5) micromol TEAC/g dried Aloe vera flower and was directly correlated with the polyphenol and flavonoid contents.     

Estrogen receptor–β activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNFα mediated

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are androgen-dependent diseases commonly treated by inhibiting androgen action. However, androgen ablation or castration fail to target androgen-independent cells implicated in disease etiology and recurrence. Mechanistically different to castration, this study shows beneficial proapoptotic actions of estrogen receptor–β (ERβ) in BPH and PCa. ERβ agonist induces apoptosis in prostatic stromal, luminal and castrate-resistant basal epithelial cells of estrogen-deficient aromatase knock-out mice. This occurs via extrinsic (caspase-8) pathways, without reducing serum hormones, and perturbs the regenerative capacity of the epithelium. TNFα knock-out mice fail to respond to ERβ agonist, demonstrating the requirement for TNFα signaling. In human tissues, ERβ agonist induces apoptosis in stroma and epithelium of xenografted BPH specimens, including in the CD133⁺ enriched putative stem/progenitor cells isolated from BPH-1 cells in vitro. In PCa, ERβ causes apoptosis in Gleason Grade 7 xenografted tissues and androgen-independent cells lines (PC3 and DU145) via caspase-8. These data provide evidence of the beneficial effects of ERβ agonist on epithelium and stroma of BPH, as well as androgen-independent tumor cells implicated in recurrent disease. Our data are indicative of the therapeutic potential of ERβ agonist for treatment of PCa and/or BPH with or without androgen withdrawal.     

CD4+ follicular regulatory T cells optimize the influenza virus–specific B cell response

CD4⁺ follicular regulatory T (Tfr) cells control B cell responses through the modulation of follicular helper T (Tfh) cells and germinal center development while suppressing autoreactivity; however, their role in the regulation of productive germinal center B cell responses and humoral memory is incompletely defined. We show that Tfr cells promote antigen-specific germinal center B cell responses upon influenza virus infection. Following viral challenge, we found that Tfr cells are necessary for robust generation of virus-specific, long-lived plasma cells, antibody production against both hemagglutinin (HA) and neuraminidase (NA), the two major influenza virus glycoproteins, and appropriate regulation of the BCR repertoire. To further investigate the functional relevance of Tfr cells during viral challenge, we used a sequential immunization model with repeated exposure of antigenically partially conserved strains of influenza viruses, revealing that Tfr cells promote recall antibody responses against the conserved HA stalk region. Thus, Tfr cells promote antigen-specific B cell responses and are essential for the development of long-term humoral memory.     

Androgen receptor gene and sex-specific Alzheimer's disease

Women are at a 2-fold risk of developing late-onset Alzheimer's disease (AD) (onset at 65 years of age or older) compared with men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular, and inflammatory changes. These all together have been suggested as risk factors for late-onset AD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the Androgen Receptor gene (AR) in a clinical cohort of male and female AD patients and normal control subjects by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, sex, and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex-specific phenotypic effect.     

Osteoarticular complications of brucellosis in Hamedan, an endemic area in the west of Iran.

OBJECTIVE: To determine the frequency and clinical characteristics of osteoarticular complications of brucellosis in an endemic region in Iran. METHODS: In a prospective study we evaluated 245 patients with brucellosis diagnosed between January 2004 and December 2005. Patients included were those older than 8 years of age and who had clinical features suggestive of brucellosis and specific antibodies at significant titers, and/or positive blood or body fluid culture for Brucella species. A bone scan was performed in those with a clinical suspicion of osteoarticular involvement. RESULTS: Seventy patients (28.6%) had osteoarticular complications. Sacroiliitis was the most common complication (75.7%), followed by spondylitis (21.4%) and peripheral arthritis (8.6%). Spondylitis was the most common osteoarticular complication in the elderly. Relapses occurred in five (2%) patients, three of them with spondylitis. CONCLUSIONS: Osteoarticular disease is the most common complication of brucellosis in Western Iran. Sacroiliitis is the most common form of osteoarticular complication. With the use of a proper treatment regimen, the prospect for recovery is good.