Abstract Although decreasing body mass index (BMI) is associated with higher mortality risk in patients undergoing hemodialysis (HD), BMI neither differentiates muscle and fat mass nor provides ...information about the variations of fat distribution. It remains unclear whether changes over time in fat and muscle mass are associated with mortality. We examined the prognostic significance of trajectory in the triceps skinfold (TSF) thickness and mid-upper arm circumference (MUAC). In this multicenter prospective cohort study, 972 outpatients (mean age, 54.5 years; 55.3% men) undergoing maintenance HD at 22 treatment centers were included. We calculated the relative change in TSF and MUAC over a 1-year period. The outcome was all-cause mortality. Kaplan–Meier, Cox proportional hazard analyses, restricted cubic splines, and Fine and Gray sub-distribution hazards models were performed to examine whether TSF and MUAC trajectories were associated with all-cause mortality. During follow-up (median, 48.0 months), 206 (21.2%) HD patients died. Compared with the lowest trajectory group, the highest trajectories of TSF and MUAC were independently associated with lower risk for all-cause mortality (HR = 0.405, 95% CI 0.257–0.640; HR = 0.537; 95% CI 0.345–0.837; respectively), even adjusting for BMI trajectory. Increasing TSF and MUAC over time, measured as continuous variables and expressed per 1-standard deviation decrease, were associated with a 55.7% (HR = 0.443, 95% CI 0.302–0.649), and 97.8% (HR = 0.022, 95% CI 0.005–0.102) decreased risk of all-cause mortality. Reduction of TSF and MUAC are independently associated with lower all-cause mortality, independent of change in BMI. Our study revealed that the trajectory of TSF thickness and MUAC provides additional prognostic information to the BMI trajectory in HD patients.
Background. Adipokines are reported to participate in many common pathologic processes of glucose dysregulation, such as insulin resistance, β-cell dysfunction, and chronic inflammation. Objective. ...To detect the concentrations of plasma asprosin in subjects with impaired glucose regulation (IGR) and newly diagnosed type 2 diabetes (nT2DM) and its relationship to parameters of glucose and lipid metabolism, insulin resistance, and pancreatic β-cell function. Methods. 143 eligible participants were included and were divided into three groups including normal glucose regulation (NGR, n=52), IGR (n=40), and nT2DM group (n=51). The intravenous glucose tolerance test (IVGTT) and clinical and biochemical parameters were measured in all participants. Results. Plasma asprosin levels were higher in IGR (82.40 ± 91.06 ng/mL, P<0.001) and nT2DM (73.25 ± 91.69 ng/mL, P<0.001) groups compared with those in the NGR (16.22 ± 9.27 ng/mL) group, especially in IGR subjects. Correlation analysis showed that plasma asprosin levels were positively correlated with waist circumference (Wc), fasting plasma glucose (FPG), postchallenge plasma glucose (2hPG), HbA1c, triglyceride (TG), and homeostasis model assessment for insulin resistance (HOMA-IR) and negatively correlated with homeostasis model assessment for β-cell function (HOMA-β), area under the curve of the first-phase (0–10 min) insulin secretion (AUC), acute insulin response (AIR), and glucose disposition index (GDI) (all P<0.05). Multiple logistical regression analyses revealed that plasma asprosin concentrations were significantly correlated with IGR and nT2DM after controlling for age, sex, BMI, and WHR. Conclusions. Circulating asprosin might be a predictor of early diagnosis in DM and might be a potential therapeutic target for prediabetes and T2DM.
This study was conducted to evaluate the effects of fermented feed of
(
) on growth performance, oxidative stress, immunity and gastrointestinal microflora of Boer goats under thermal stress.
The ...study was conducted during 45 days using twenty 2 months Boer goats. The goats were randomly allocated into two groups: NPG (
= 10; normal
) and FPG (
= 10; fermented feed of
), and the ratio of concentrates to roughage was 3:2. Both groups of animals were kept in sheds and exposed to summer thermal stress from 10:00 h to 18:00 h (temperature and humidity index, THI > 78). At the end of the study, the animals were slaughtered and assessed for various characteristics.
The findings from the study revealed that FPG-feeding significantly increased (
< 0.05) average daily gain (ADG, 48.18 g) and carcass weight (4.38 kg), while decreased (
< 0.01) average daily feed intake (ADFI, 0.74 kg/d;
< 0.01) and the feed:gain (F/G, 15.36) ratio. The CAT, GSH-Px activities and GSH in serum, liver and spleen, and the levels of IgA, IgG, IgM, IL-2, IL-4 and IL-1β in serum of FPG-fed goats were significantly higher (
< 0.05) than those of NPG-feeding goats. Further, we found that FPG feed is rich in nutrients with
(65.83%) and
(17.80%). Results for gastrointestinal microbiota composition showed that FPG-feeding significantly enhanced the abundance of
and
, and reduced
and
. Meanwhile, Spearman's correlation analysis showed that these microbiotas were closely related to the improvement of oxidative stress and immune indexes of goats.
These results demonstrated that FPG-feeding not only reduces oxidative stress and improves ROS clearance to enhance antioxidant defense system, but also improves gastrointestinal microbiota to enhance immune function by overcoming the adverse effects of heat stress, and further improve growth performance of goats.
Increasing evidence indicates that the gut microbiota contributes to the occurrence and development of metabolic diseases. However, little is known about the effects of commonly used antidiabetic ...agents on the gut microbiota. In this study, we investigated the roles of dipeptidyl peptidase-4 inhibitors (DPP-4i) and α-glucosidase inhibitor in modulating the gut microbiota.
16S-rDNA sequencing was performed to analyse the effects of DPP-4i and acarbose on the gut microbiota in mice fed a high-fat diet (HFD). Fecal microbiota transplantation (FMT) from type 2 diabetes patients to germ-free mice was performed to investigate the contribution of the altered microbiome to antidiabetic effects of the drugs. Fecal metabolomics was also analysed by untargeted and targeted GC–MS systems.
Although DPP-4i and α-glucosidase inhibitor both altered the gut microbial composition, only the microbiome modulation of DPP-4i contributed to its hypoglycemic effect. Specifically, the changes of 68.6% genera induced by HFD were rescued by DPP-4i. FMT showed that the DPP-4i-altered microbiome improved glucose tolerance in colonized mice, while acarbose did not. Moreover, DPP-4i increased the abundance of Bacteroidetes, and also promoted a functional shift in the gut microbiome, especially increasing the production of succinate.
Our findings demonstrate an important effect of DPP-4i on the gut microbiota, revealing a new hypoglycemic mechanism and an additional benefit of it. Furthermore, modulating the microbial composition, and the functional shift arising from changes in the microbiome, might be a potential strategy for improving glucose homeostasis.
This work was supported by grants from the National Natural Science Foundation of China (No. 81700757, No. 81471039, No. 81700714 and No. 81770434), the National Key R&D Program of China (No. 2017YFC1309602, No. 2016YFC1101100, No. 2017YFD0500503 and No. 2017YFD0501001), and the Natural Science Foundation of Chongqing (No. cstc2014jcyjjq10006, No. cstc2016jcyjA0093 and No. cstc2016jcyjA0518).
The matrix equation AXBH=E with SX=XR or PX=sXQ constraint is considered, where S, R are Hermitian idempotent, P, Q are Hermitian involutory, and s=±1. By the eigenvalue decompositions of S, R, the ...equation AXBH=E with SX=XR constraint is equivalently transformed to an unconstrained problem whose coefficient matrices contain the corresponding eigenvectors, with which the constrained solutions are constructed. The involved eigenvectors are released by Moore-Penrose generalized inverses, and the eigenvector-free formulas of the general solutions are presented. By choosing suitable matrices S, R, we also present the eigenvector-free formulas of the general solutions to the matrix equation AXBH=E with PX=sXQ constraint.
Objective:
This study aimed to investigate the effect of anti-osteoporosis therapy on plasma aldosterone concentration (PAC), plasma renin concentration (PRC) and the aldosterone/renin ratio (ARR) in ...patients with postmenopausal osteoporosis.
Methods:
In 60 patients with postmenopausal osteoporosis, bone mineral density (BMD), PAC and PRC were measured before and after treatment with alendronate (70 mg/week, n=22) or recombinant human parathyroid hormone (20 μg/day, n=35) for 48 weeks.
Results:
PAC was negatively correlated with the T-score of lumbar spine BMD and femoral neck BMD (lumbar r=−0.386, p<0.01; femoral neck r=−0.262, p<0.05). With the improvement in lumbar BMD after anti-osteoporosis treatment (T-score −3.4±0.5 vs. –3.1 ±0.4, p<0.0001), PAC decreased from 182.8±53.2 to 143.7±68.6 pg/mL (p<0.0001), PRC increased from 7.8±11.6 to 39.2±50.0 μIU/mL (p<0.0001) and the ARR decreased from 74.8±75.2 to 13.1±17.1 pg/μIU (p<0.0001). At baseline, 58% (35/60) of the patients had an ARR >37 pg/μIU, and the proportion decreased to 8% (5/57) after treatment.
Conclusion:
Treatment with alendronate or parathyroid hormone causes decreased PAC and increased PRC, resulting in a decreased ARR in postmenopausal women with osteoporosis.
Four new N-acylated aminoalkanoic acids, namely clonoroseins E−H (1−4), together with three previously identified analogs, clonoroseins A, B, and D (5−7), were identified from the endophytic fungus ...Clonostachys rosea strain 15020 (CR15020), using Feature-based Molecular Networking (FBMN). The elucidation of their chemical structures, including their absolute configurations, was achieved through spectroscopic analysis combined with quantum chemical calculations. Bioinformatics analyses suggested that an iterative type I HR-PKS (CrsE) generates the polyketide side chain of these clonoroseins. Furthermore, a downstream adenylate-forming enzyme of the PKS (CrsD) was suspected to function as an amide synthetase. CrsD potentially facilitates the transformation of the polyketide moiety into an acyl-AMP intermediate, followed by nucleophilic substitution with either β-alanine or γ-aminobutyric acid to produce amide derivatives. These findings significantly expand our understanding of PKS-related products originating from C. rosea and also underscore the powerful application of FBMN analytical methods in characterization of new compounds.
Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus (T2D). Metformin exerts its glucose-lowering effect primarily through decreasing hepatic glucose production (HGP). However, ...the precise molecular mechanisms of metformin remain unclear due to supra-pharmacological concentration of metformin used in the study. Here, we investigated the role of Foxo1 in metformin action in control of glucose homeostasis and its mechanism via the transcription factor Foxo1 in mice, as well as the clinical relevance with co-treatment of aspirin. We showed that metformin inhibits HGP and blood glucose in a Foxo1-dependent manner. Furthermore, we identified that metformin suppresses glucagon-induced HGP through inhibiting the PKA→Foxo1 signaling pathway. In both cells and mice, Foxo1-S273D or A mutation abolished the suppressive effect of metformin on glucagon or fasting-induced HGP. We further showed that metformin attenuates PKA activity, decreases Foxo1-S273 phosphorylation, and improves glucose homeostasis in diet-induced obese mice. We also provided evidence that salicylate suppresses HGP and blood glucose through the PKA→Foxo1 signaling pathway, but it has no further additive improvement with metformin in control of glucose homeostasis. Our study demonstrates that metformin inhibits HGP through PKA-regulated transcription factor Foxo1 and its S273 phosphorylation.
The matrix equation AX=B with PX=XP and XH=sX constraints is considered, where P is a given Hermitian involutory matrix and s=±1. By an eigenvalue decomposition of P, we equivalently transform the ...constrained problem to two well-known constrained problems and represent the solutions in terms of the eigenvectors of P. Using Moore–Penrose generalized inverses of the products generated by matrices A, B and P, the involved eigenvectors can be released and eigenvector-free formulas of the general solutions are presented. Similar strategy is applied to the equations AX=B, XC=D with the same constraints.
The least squares solutions to the equations
AX
=
B
,
XC
=
D
with some constraints such as orthogonality, symmetric orthogonality, symmetric idempotence are considered. By one time singular value ...decomposition or eigenvalue decomposition of the matrix product generated by the coefficient matrices
A
,
C
and right hand side matrices
B
,
D
, the constrained solutions are constructed simply. Similar strategy is applied to the equations with corresponding
P-commuting constraints with given symmetric matrix
P. Numerical examples that show the efficiency of the proposed methods are presented.
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