Background: Inflammatory bowel disease (IBD) patients may be at risk of vitamin B12 and folate insufficiencies, as these micronutrients are absorbed in the small intestine, which is affected by IBD. However, a consensus has not been reached on the association between IBD and serum folate and vitamin B12 concentrations. Methods: In this study, a comprehensive search of multiple databases was performed to identify studies focused on the association between IBD and serum folate and vitamin B12 concentrations. Studies that compared serum folate and vitamin B12 concentrations between IBD and control patients were selected for inclusion in the meta-analysis. Results: The main outcome was the mean difference in serum folate and vitamin B12 concentrations between IBD and control patients. Our findings indicated that the average serum folate concentration in IBD patients was significantly lower than that in control patients, whereas the mean serum vitamin B12 concentration did not differ between IBD patients and controls. In addition, the average serum folate concentration in patients with ulcerative colitis (UC) but not Crohn’s disease (CD) was significantly lower than that in controls. This meta-analysis identified a significant relationship between low serum folate concentration and IBD. Conclusions: Our findings suggest IBD may be linked with folate deficiency, although the results do not indicate causation. Thus, providing supplements of folate and vitamin B12 to IBD patients may improve their nutritional status and prevent other diseases.

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BackgroundAberrant microRNA (miRNA) expression affects biologic processes and downstream genes that are crucial to CKD initiation or progression. The miRNA miR-204-5p is highly expressed in the kidney but whether miR-204-5p plays any role in the development of chronic renal injury is unknown.MethodsWe used real-time PCR to determine levels of miR-204 in human kidney biopsies and animal models. We generated Mir204 knockout mice and used locked nucleic acid–modified anti-miR to knock down miR-204-5p in mice and rats. We used a number of physiologic, histologic, and molecular techniques to analyze the potential role of miR-204-5p in three models of renal injury.ResultsKidneys of patients with hypertension, hypertensive nephrosclerosis, or diabetic nephropathy exhibited a significant decrease in miR-204-5p compared with controls. Dahl salt-sensitive rats displayed lower levels of renal miR-204-5p compared with partially protected congenic SS.13BN26 rats. Administering anti–miR-204-5p to SS.13BN26 rats exacerbated interlobular artery thickening and renal interstitial fibrosis. In a mouse model of hypertensive renal injury induced by uninephrectomy, angiotensin II, and a high-salt diet, Mir204 gene knockout significantly exacerbated albuminuria, renal interstitial fibrosis, and interlobular artery thickening, despite attenuation of hypertension. In diabetic db/db mice, administering anti–miR-204-5p exacerbated albuminuria and cortical fibrosis without influencing blood glucose levels. In all three models, inhibiting miR-204-5p or deleting Mir204 led to upregulation of protein tyrosine phosphatase SHP2, a target gene of miR-204-5p, and increased phosphorylation of signal transducer and activator of transcription 3, or STAT3, which is an injury-promoting effector of SHP2.ConclusionsThese findings indicate that the highly expressed miR-204-5p plays a prominent role in safeguarding the kidneys against common causes of chronic renal injury.

Renalase, a recently discovered secreted flavoprotein, exerts anti-apoptotic and anti-inflammatory effects against renal injury in acute and chronic animal models. However, whether Renalase elicits similar effects in the development of diabetic nephropathy (DN) remains unclear. The studies presented here tested the hypothesis that Renalase may play a key role in the development of DN and may have therapeutic potential for DN. Renalase expression was measured in human kidney biopsies with DN and in kidneys of db/db mice. The role of Renalase in the development of DN was examined using a genetically engineered mouse model: Renalase knockout mice with db/db background. The renoprotective effects of Renalase in DN was evaluated in db/db mice with Renalase overexpression. In addition, the effects of Renalase on high glucose-induced mesangial cells were investigated. Renalase was down-regulated in human diabetic kidneys and in kidneys of db/db mice compared with healthy controls or db/m mice. Renalase homozygous knockout increased arterial blood pressure significantly in db/db mice while heterozygous knockout did not. Renalase heterozygous knockout resulted in elevated albuminuria and increased renal mesangial expansion in db/db mice. Mesangial hypertrophy, renal inflammation, and pathological injury in diabetic Renalase heterozygous knockout mice were significantly exacerbated compared with wild-type littermates. Moreover, Renalase overexpression significantly ameliorated renal injury in db/db mice. Mechanistically, Renalase attenuated high glucose-induced profibrotic gene expression and p21 expression through inhibiting extracellular regulated protein kinases (ERK1/2). The present study suggested that Renalase protected against the progression of DN and might be a novel therapeutic target for the treatment of DN.

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Poly-GLP-1 promotes angiogenesis to accelerate bone formation via BMSC differentiation and M2 polarization.

As fleeting facial expressions which reveal the emotion that a person tries to conceal, micro-expressions have great application potentials for fields like security, national defense and medical treatment. However, the physiological basis for the recognition of these facial expressions is poorly understood. In the present research, we utilized a double-blind, placebo-controlled, mixed-model experimental design to investigate the effects of oxytocin on the recognition of micro-expressions in three behavioral studies. Specifically, in Studies 1 and 2, participants were asked to perform a laboratory-based standardized micro-expression recognition task after self-administration of a single dose of intranasal oxytocin (40 IU) or placebo (containing all ingredients except for the neuropeptide). In Study 3, we further examined the effects of oxytocin on the recognition of natural micro-expressions. The results showed that intranasal oxytocin decreased the recognition speed for standardized intense micro-expressions of surprise (Study 1) and decreased the recognition accuracy for standardized subtle micro-expressions of disgust (Study 2). The results of Study 3 further revealed that intranasal oxytocin administration significantly reduced the recognition accuracy for natural micro-expressions of surprise and disgust. The present research is the first to investigate the effects of oxytocin on micro-expression recognition. It suggests that the oxytocin mainly plays an inhibiting role in the recognition of micro-expressions and there are fundamental differences in the neurophysiological basis for the recognition of micro-expressions and macro-expressions.

Background Diabetes mellitus (DM) is considered to be an important factor for bone degeneration disorders such as bone defect nonunion, which is characterized by physical disability and tremendous economy cost to families and society. Exosomal miRNAs of BMSCs have been reported to participate in osteoblastogenesis and modulating bone formation. However, their impacts on the development of bone degeneration in DM are not yet known. The role of miRNAs in BMSCs exosomes on regulating hyperglycemia bone degeneration was investigated in the present study. Results The osteogenic potential in bone defect repair of exosomes derived from diabetes mellitus BMSCs derived exosomes (DM-Exos) were revealed to be lower than that in normal BMSCs derived exosomes (N-Exos) in vitro and in vivo. Here, we demonstrate that miR-140-3p level was significantly altered in exosomes derived from BMSCs, ADSCs and serum from DM rats. In in vitro experiments, upregulated miR-140-3p exosomes promoted DM BMSCs differentiation into osteoblasts. The effects were exerted by miR-140-3p targeting plxnb1, plexin B1 is the receptor of semaphoring 4D(Sema4D) that inhibited osteocytes differentiation, thereby promoting bone formation. In DM rats with bone defect, miR-140-3p upregulated exosomes were transplanted into injured bone and accelerated bone regeneration. Besides, miR-140-3p in the exosomes was transferred into BMSCs and osteoblasts and promoted bone regeneration by targeting the plexin B1/RohA/ROCK signaling pathway. Conclusions Normal-Exos and miR-140-3p overexpressed-Exos accelerated diabetic wound healing by promoting the osteoblastogenesis function of BMSCs through inhibition plexin B1 expression which is the receptor of Sema4D and the plexin B1/RhoA/ROCK pathway compared with diabetes mellitus-Exos. This offers a new insight and a new therapy for treating diabetic bone unhealing. Graphical Abstract