The role of the "gut microbiota-mitochondria" crosstalk in the pathogenesis of multiple sclerosis.

Multiple Sclerosis (MS) is a neurologic autoimmune disease whose exact pathophysiologic mechanisms remain to be elucidated. Recent studies have shown that the onset and progression of MS are associated with dysbiosis of the gut microbiota. Similarly, a large body of evidence suggests that mitochondrial dysfunction may also have a significant impact on the development of MS. Endosymbiotic theory has found that human mitochondria are microbial in origin and share similar biological characteristics with the gut microbiota. Therefore, gut microbiota and mitochondrial function crosstalk are relevant in the development of MS. However, the relationship between gut microbiota and mitochondrial function in the development of MS is not fully understood. Therefore, by synthesizing previous relevant literature, this paper focuses on the changes in gut microbiota and metabolite composition in the development of MS and the possible mechanisms of the crosstalk between gut microbiota and mitochondrial function in the progression of MS, to provide new therapeutic approaches for the prevention or reduction of MS based on this crosstalk.

Theoretical calculations and photoluminescence properties of Sr4Al14O25:Mn4+ red phosphors doped with Li.

The absence of high-efficiency oxide red phosphors restricts the development of high-performance solid-state lighting. In this work, a series of Li+ doped Sr4Al14O25:Mn4+ (SAO-Li+) red phosphors were prepared. Theoretical calculation results indicate that Li+ is inclined to occupy the gap 2 position. The low concentration Li+ gap doping has almost no influence on the Sr4Al14O25 structure, and a 0.4 mol Li+-doped sample exhibits a pure phase with regular morphology. With increasing Li+ doping content, the luminescence intensities of phosphors increase first and then decrease. 0.4 mol is found to be the optimal concentration. The fluorescence lifetime continues to decrease with the increase in the Li+ doping content and a mutation occurs at 0.5 mol Li+. Phosphor doping with Li+ can improve the thermal quenching resistance. The WLED device encapsulated with SAO-0.4Li and YAG:Ce3+ phosphors prepared showed a correlated color temperature of 4667 K, a color rendering index of 82, and a light efficiency of 137.34 lm W-1 at a driving current of 20 mA. The above results indicate that the use of a SAO-0.4Li+ phosphor is expected for application in warm WLEDs.

A tree shrew model for steroid-associated osteonecrosis.

Osteonecrosis is a common human disease in orthopedics. It is difficult to treat, and half of patients may need artificial joint replacement, resulting in a considerable economic burden and a reduction in quality of life. Hormones are one of the major causes of osteonecrosis and high doses of corticosteroids are considered the most dangerous factor. Because of the complexity of treatment, we still need a better animal model that can be widely used in drug development and testing. Tree shrews are more closely related to primates than rodents. As such, we constructed a successful tree shrew model to establish and evaluate steroid-associated osteonecrosis (SAON). We found that low-dose lipopolysaccharide (LPS) combined with high-dose methylprednisolone (MPS) over 12 weeks could be used to establish a tree shrew model with femoral head necrosis. Serum biochemical and histological analyses showed that an ideal model was obtained. Thus, this work provides a useful animal model for the study of SAON and for the optimization of treatment methods.

Effects of combined treatment with PD­L1 Ig and CD40L mAb on immune tolerance in the CBA/J x DBA/2 mouse model.

The embryo is a natural allograft and is the only exception to immune rejection, which reflects maternal immune tolerance towards the embryo. However, pregnancy loss is primarily caused by maternal immune rejection of the embryo. The aim of the present study was to explore the effects of combined treatment of programmed death­ligand 1 (PD­L1) immunoglobulin (Ig) and CD40­ligand (CD40L) monoclonal antibody (mAb) on immune tolerance in an abortion­prone mating model. Mice were divided into the normal, spontaneous abortion, PD­L1 Ig, CD40L mAb and the PD­L1 Ig + CD40L mAb groups. On day 14 of gestation, the embryo resorption abortion rates of all the groups was observed. The maternal hypo­responsiveness to paternal antigens was determined using a mixed lymphocyte response and the splenic CD4+CD25+ T­cell population, major histocompatibility complex (MHC)­II+, CD80+ and CD86+ cell populations in pregnant female CBA/J mice were analyzed using flow cytometry. The expression levels of intracellular cytokines in the splenic tissues of pregnant CBA/J female mice were analyzed using western blotting. The PD­L1 Ig + CD40L group displayed the lowest resorption rate compared with the other groups. A significant decrease in the proliferative response of maternal splenic immunocompetent cells against paternal antigens, and a significant increase in the proliferative response of maternal splenic CD4+CD25+ T cells was observed in the PD­L1 Ig + CD40L group compared with the spontaneous abortion group. The number of MHC­II+, CD80+ and CD86+ bone marrow­derived dendritic cells (DCs) generated by female mice, and the levels of tumor necrosis factor­α and interferon­Î³ in the spleens of female mice were significantly decreased in the PD­L1 Ig + CD40L mAb group compared with the spontaneous abortion group. By contrast, interleukin­4 levels were significantly increased in the PD­L1 Ig + CD40L mAb group compared with the spontaneous abortion group. The results suggested that the administration of PD­L1 Ig + CD40L mAb on day 4 of gestation, the period of peri­implantation, may induce paternal antigen­specific immunotolerance, leading to the embryo resorption rate of the abortion­prone model being similar to that of the normal pregnancy model. The results indicate that the combined treatment of PD­L1 Ig and anti­CD40L mAbs may serve as a potential therapeutic for pregnancy loss.

Sitagliptin/Metformin Versus Insulin Glargine Combined With Metformin in Obese Subjects With Newly Diagnosed Type 2 Diabetes.

To compare the therapeutic effects of different regimens in Chinese obese type 2 diabetic mellitus (T2DM) patients. From October 2013 to July 2014, a total of 166 T2DM outpatients who attended the Shanghai Changhai Hospital and the Yijishan Hospital of Wannan Medical College were randomly assigned into an experimental sitagliptin/metformin combined with low caloric diet group (n = 115) and an insulin glargine combined with metformin control group (n = 51). Inclusion criteria were body mass index (BMI) ≥ 25 kg/m and diagnosed with T2DM with glycosylated hemoglobin (glycated hemoglobin A1C [HbA1c]) >9%. Main outcome parameters were fasting plasma glucose, postprandial plasma glucose, BMI, HbA1c, fasting C-peptide, 2-h postprandial C-peptide, triglyceride (TG), total cholesterol (TC), high-density cholesterol (HDL-C), and low-density cholesterol (LDL-C), which were determined by the 75 g steamed-bun meal tolerance test before and 4, 8, 12, and 24 weeks after the treatment started. Treatment costs and life quality were also assessed. BMI, HbA1C, TG, TC, and LDL were significantly more reduced (P < 0.000) and HbA1c significantly better improved in the experimental group than in the control group (<6.5% in 24 [20.87%] vs 2 [3.92%], P < 0.001; <7% in 65 [56.52%] vs 12 [23.53%], P < 0.001). Quality of life scores in the experimental group increased more than in the control group (P < 0.001). The costs for the experimental group medication were less than for other regimens. For obese T2DM patients diagnosed with a glycosylated hemoglobin level >9%, oral sitagliptin/metformin combined with a low caloric diet effectively and economically maintained glycemic control and significantly improved life quality.

TM7SF1 (GPR137B): a novel lysosome integral membrane protein.

In the previous proteomic study of human placenta, transmembrane 7 superfamily member 1 (TM7SF1) was found enriched in lysosome compartments. TM7SF1 encodes a 399-amino acid protein with a calculated molecular mass of 45 kDa. Bioinformatic analysis of its amino acid sequence showed that it is a multipass transmembrane protein containing a potential dileucine-based lysosomal targeting signal and four putative N-glycosylation sites. By percoll-gradient centrifugation and further subfraction ways, the lysosomal solute and membrane compartments were isolated respectively. Immunoblotting analysis indicated that TM7SF1 was co-fractioned with lysosome associated membrane protein 2 (LAMP2), which was only detected in lysosomal membrane compartments whereas not detected in the solute compartments. Using specific anti-TM7SF1 antibody and double-immunofluorescence with lysosome membrane protein LAMP1 and Lyso-Tracker Red, the colocalisations of endogenous TM7SF1 with lysosome and late endosome markers were demonstrated. All of this indicated that TM7SF1 is an integral lysosome membrane protein. Rat ortholog of TM7SF1 was found to be strongly expressed in heart, liver, kidney and brain while not or low detected in other tissues. In summary, TM7SF1 was a lysosomal integral membrane protein that shows tissue-specific expression. As a G-protein-coupled receptor in lysosome membrane, TM7SF1 was predicted function as signal transduction across lysosome membrane.

catena-Poly[[tetra-aqua-cobalt(II)]-µ-2,2'-dihydroxy-5,5'-diazenediyldibenzoato].

In the title compound, [Co(C(14)H(8)N(2)O(6))(H(2)O)(4)](n), each 5,5'-diazenediylbis(2-hydroxy-benzoato) ligand acts as a dicarboxyl-ate bridge, leading to the formation of polymeric chains running in the [10] direction. The Co atom is hexa-coordinated in a distorted octa-hedral geometry by six O atoms [Co-O = 2.039 (4)-2.115 (4) Å] from two ligands and four water mol-ecules. Inter-molecular O-H⋯O and O-H⋯N hydrogen bonds build up a three-dimensional supra-molecular structure.