Introduction: Dysbiosis of gut microbiota impairs the homeostasis of immune and metabolic systems. Although previous studies have revealed the correlation between gut microbiota and various diseases, the function between gut microbiota and diabetic nephropathy (DN) has not been discovered distinctly. In this study, we tried to investigate the profile and function of gut microbiota in DN. Methods: A total of 100 people were enrolled in this study. Twenty were healthy people, 20 were diabetes patients, and 60 were DN patients. The DN patients were divided into three stages including stage III, IV, and V. We conducted taxonomic analyses in different groups. The distributions of phyla, classes, orders, families, and genera in different groups and samples were investigated. We also evaluated the correlations between clinical parameters and gut microbiota in 60 DN patients. Results: The gut microbiota in the healthy group, diabetes group, and DN group had 1764 operational taxonomic units (OTUs) in total. The healthy group had 1034 OTUs, the diabetes group had 899 OTUs, and the DN group had 1602 OTUs. The diversity of gut microbiota in the stage III DN group was smaller than that in the other groups. 24-h urinary protein was positively correlated with Alistipes and Subdoligranulum, cholesterol was positively correlated with Bacteroides and Lachnoclostridium, and estimated glomerular filtration rate was negatively correlated with Ruminococcus torques group. Discussion: The gut microbiota might play an important role in the development and pathogenesis of DN. A change in gut microbiota diversity is correlated with disease progression. Some kinds of gut microbiota including Alistipes, Bacteroides, Subdoligranulum, Lachnoclostridium, and Ruminococcus torques group might be detrimental factors in DN.

Myasthenia gravis (MG) and neuromyelitis optica (NMO) are autoimmune channelopathies of the peripheral neuromuscular junction (NMJ) and central nervous system (CNS) that are mainly mediated by humoral immunity against the acetylcholine receptor (AChR) and aquaporin-4 (AQP4), respectively. The diseases share some common features, including genetic predispositions, environmental factors, the breakdown of tolerance, the collaboration of T cells and B cells, imbalances in T helper 1 (Th1)/Th2/Th17/regulatory T cells, aberrant cytokine and antibody secretion, and complement system activation. However, some aspects of the immune mechanisms are unique. Both targets (AChR and AQP4) are expressed in the periphery and CNS, but MG mainly affects the NMJ in the periphery outside of CNS, whereas NMO preferentially involves the CNS. Inflammatory cells, including B cells and macrophages, often infiltrate the thymus but not the target—muscle in MG, whereas the infiltration of inflammatory cells, mainly polymorphonuclear leukocytes and macrophages, in NMO, is always observed in the target organ—the spinal cord. A review of the common and discrepant characteristics of these two autoimmune channelopathies may expand our understanding of the pathogenic mechanism of both disorders and assist in the development of proper treatments in the future.

The enteric nervous system (ENS) consists of neurons and enteric glial cells (EGCs) that reside within the smooth muscle wall, submucosa and lamina propria. EGCs play important roles in gut homeostasis through the release of various trophic factors and contribute to the integrity of the epithelial barrier. Most studies of primary enteric glial cultures use cells isolated from the myenteric plexus after enzymatic dissociation. Here, a non-enzymatic method to isolate and culture EGCs from the intestinal submucosa and lamina propria is described. After manual removal of the longitudinal muscle layer, EGCs were liberated from the lamina propria and submucosa using sequential HEPES-buffered EDTA incubations followed by incubation in commercially available non-enzymatic cell recovery solution. The EDTA incubations were sufficient to strip most of the epithelial mucosa from the lamina propria, allowing the cell recovery solution to liberate the submucosal EGCs. Any residual lamina propria and smooth muscle was discarded along with the myenteric glia. EGCs were easily identified by their ability to express glial fibrillary acidic protein (GFAP). Only about 50% of the cell suspension contained GFAP+ cells after completing tissue incubations and prior to plating on the poly-D-lysine/laminin substrate. However, after 3 days of culturing the cells in glial cell-derived neurotrophic factor (GDNF)-containing culture media, the cell population adhering to the substrate-coated plates comprised of >95% enteric glia. We created a hybrid mouse line by breeding a hGFAP-Cre mouse to the ROSA-tdTomato reporter line to track the percentage of GFAP+ cells using endogenous cell fluorescence. Thus, non-myenteric enteric glia can be isolated by non-enzymatic methods and cultured for at least 5 days.

The net action of ruminal bacteria and endogenous bovine enzymes are responsible for cow's milk having the most complex fatty acid profiles among common foods. About 40 monounsaturated fatty acids below 1.5% w/w are known. Analysis of trace and ultratrace fatty acids is a challenge to the highest resolution chromatography even with prior fractionation. We employ solvent-mediated covalent adduct chemical ionization (CACI) tandem mass spectrometry (MS/MS) to enable rapid, unambiguous identification of unsaturated fatty acid methyl esters (FAME) at high sensitivity. Fifty-four monounsaturated fatty acids (C 10−24 ) were completely characterized, with the discovery of 15 novel fatty acids including nine at ultratrace levels 10−100 ppm, g/10 6 g fatty acids (lowest concentration 19:1n-6 (10 ± 11 ppm, w/w (0.001%, w/w))). Ultratrace monoenes were typically odd chain lengths and all analyzed in a single 20 min analysis. These data establish the abundance of 15 new monoene fatty acids in bovine milkfat and a strategy for rapid unambiguous analysis of ultratrace monounsaturated fatty acids.

The present study was performed to investigate whether the markedly 2-deoxy-2-(fluorine-18) fluoro-D-glucose (18F-FDG) uptake in the bone marrow (BM) is a presentation of malignant infiltration (MI).Super bone marrow uptake (super BMU) was used to name the markedly 18F-FDG uptake on BM, which was similar to or higher than that of the brain. From April 2008 to December 2015, 31 patients with such presentation were retrospectively reviewed. The 18F-FDG uptake was semiquantified using SUVmax and BM to cerebellum (BM/C) ratio. The origin of super BMU was diagnosed by pathology. Some blood parameters, as well as fever, were also collected and analyzed. For comparison, 106 patients with mildly and moderately uptake in BM and 20 healthy subjects were selected as the control group.Bone marrow MI was diagnosed in 93.5% (29/31) patients with super BMU, which mostly originated from acute leukemia and highly aggressive lymphoma. The super BMU group had markedly higher 18F-FDG uptake in the BM than those of mildly and moderately uptake, and the control subjects (all P = 0.000) and the BM/C ratio reached a high of 1.24 ± 0.36. The incidence of bone marrow MI in the super BMU group was markedly higher than that of mildly and moderately uptake (93.5% vs 36.8%, P = 0.000). Based on the receiver operating characteristic analysis, when cut-off values of BM/C and SUVmax were set at 0.835 and 6.560, the diagnostic specificity for bone marrow MI reached the high levels of 91.4% and 95.7%, respectively. In 15 patients with bone marrow MI, the extra-BM malignant lesions were simultaneously detected by 18F-FDG PET/CT. The liver and the nasal cavity involvements were only found in the patients with lymphoma, but not in those with leukemia. A decrease of leukocyte, hemoglobin, and platelet counts was noted in 48.4%, 86.2%, and 51.5% of patients with bone marrow MI, respectively.The present study revealed that super BMU was a highly potent indicator for the bone marrow MI.

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This study sought to evaluate the infiltration tendency of retroperitoneal liposarcoma (RPLS) from a new pathological angle by exploring the infiltration characteristics, which could provide helpful information to facilitate surgical decision-making and prognosis prediction. Concurrently, we aim to identify significant indicators of infiltration. A total of 61 consecutive patients with RPLS at our institution were retrospectively analyzed. All patients received extended surgery. The tumor infiltration characteristics and influencing factors were studied based on the pathological diagnosis. Univariate and multivariate analyses of organ infiltration (OI) and surrounding fat infiltration (SFI) were performed. OI was found in 95 (28.5%) resected organs from 39 (60.7%) patients, and SFI was found in 119 (35.7%) resected organs from 47 (77%) patients. The tumor infiltrated the serosal layer of 13 organs (13/37, 35.1%), the muscularis layer of 18 organs (18/37, 48.6%) and the submucosa of 6 organs (6/37, 16.2%). The percentage of lipoblasts and the rates of necrosis and mitosis were all significantly higher in high-grade tumors (dedifferentiated, round cell, and pleomorphic). A high lipoblast percentage (≥ 20%) was the only independent risk factor for OI. A recurrent tumor and a high-grade tumor were independent risk factors for SFI. In conclusion, RPLS has a high infiltration tendency, such that it frequently infiltrates organs and surrounding fat tissue. Therefore, extended resection of the tumor and the adjacent organs is recommended. The percentage of lipoblasts was associated with the tumor grade and infiltration characteristics; thus, lipoblast percentage may become a new grading factor for RPLS.

A major hurdle for effective stem cell therapy is ongoing inflammation in the target organ. Reconditioning the lesion microenvironment may be an effective way to promote stem cell therapy. In this study, we showed that engineered neural stem cells (NSCs) with complement factor H-related protein 1, a complement inhibitor protein, can attenuate inflammatory infiltration and immune-mediated damage of astrocytes, an important pathogenic progress in patients with neuromyelitis optica spectrum disorders. Furthermore, we demonstrated that transplantation of the complement factor H-related protein 1-modified NSCs effectively blocked the complement activation cascade and inhibited formation of the membrane attack complex, thus contributing to the protection of endogenous and transplanted NSC-differentiated astrocytes. Therefore, manipulation of the lesion microenvironment contributes to a more effective cell replacement therapeutic strategy for autoimmune diseases of the CNS.