Bifidobacterium animalis ssp. lactis MG741 Reduces Body Weight and Ameliorates Nonalcoholic Fatty Liver Disease via Improving the Gut Permeability and Amelioration of Inflammatory Cytokines

Diet-induced obesity is one of the major causes of the development of metabolic disorders such as insulin resistance and nonalcoholic fatty liver disease (NAFLD). Recently, specific probiotic strains have been found to improve the symptoms of NAFLD. We examined the effects of Bifidobacterium animalis ssp. lactis MG741 (MG741) on NAFLD and weight gain, using a mouse model of high-fat-diet (HFD)-induced obesity. HFD-fed mice were supplemented daily with MG741. After 12 weeks, MG741-administered mice exhibited reduced fat deposition, and serum metabolic alterations, including fasting hyperinsulinemia, were modulated. In addition, MG741 regulated Acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), sterol regulatory element-binding protein 1 (SREBP-1), and carbohydrate-responsive element-binding protein (ChREBP) expression and lipid accumulation in the liver, thereby reducing the hepatic steatosis score. To determine whether the effects of MG741 were related to improvements in gut health, MG741 improved the HFD-induced deterioration in gut permeability by reducing toxic substances and inflammatory cytokine expression, and upregulating tight junctions. These results collectively demonstrate that the oral administration of MG741 could prevent NAFLD and obesity, thereby improving metabolic health.     

Surgical Outcomes of Sphenoid Wing Meningioma with Periorbital Invasion

ObjectiveThe aim of this study was to evaluate the clinical outcome of sphenoid wing meningioma with periorbital invasion (PI) after operation. MethodsSixty one patients with sphenoid wing meningioma were enrolled in this study. Their clinical conditions were monitored after the operation and followed up more than 5 years at the outpatient clinic of a single institution. Clinical and radiologic information of the patients were all recorded including the following parameters : presence of PI, presence of peri-tumor structure invasion, pathologic grade, extents of resection, presence of hyperostosis, exophthalmos index (EI), and surgical complications. We compared the above clinical parameters of the patients with sphenoid wing meningioma in the presence or absence of PI (non-PI), then linked the analyzed data with the clinical outcome of the patients. ResultsOf 61 cases, there were 14 PI and 47 non-PI patients. PI group showed a significantly higher score of EI (1.37±0.24 vs. 1.00±0.01, p<0.001), more frequent presence of hyperostosis (85.7% vs. 14.3%, p<0.001), and lower rate of gross total resection (GTR) (35.7% vs. 68.1%, p=0.032). The lower score of pre-operative EI, the absence of both PI and hyperostosis, smaller tumor size, and the performance of GTR were associated with lower recurrence rates in the univariate analysis. However, in the multivariate analysis, the performance of GTR was the only significant factor to determine the recurrence rate (p=0.043). The incidences of surgical complications were not statistically different between the subtotal resection (STR) and GTR groups, but it was strongly associated tumor size (p=0.017). ConclusionThe GTR group showed lower recurrence rate than the STR group without differences in the surgical complications. Therefore, the GTR is strongly recommended to treat sphenoid wing meningioma with PI for the better clinical outcome.     

Pancreatic Atrophy Relative to External Versus Internal Drainage of the Pancreatic Duct After Pylorus-Preserving Pancreaticoduodenectomy

Background

Atrophy of the pancreatic parenchyma, which occurs frequently after pylorus-preserving pancreaticoduodenectomy (PPPD), is often associated with pancreatic exocrine insufficiency. Many surgeons prefer to insert a drainage tube into the remnant pancreatic duct primarily to prevent pancreatic leakage at the pancreaticojejunostomy (PJ) after PPPD. Drainage methods vary widely but can be roughly classified as internal or external drainage. This study intended to evaluate their effects on pancreatic parenchymal atrophy following PPPD.

Methods

Fifty-seven patients who underwent PPPD were retrospectively divided into two groups, 28 who underwent external and 29 who underwent internal pancreatic drainage. External drainage tubes were removed 4 weeks after PPPD. The volume of the pancreatic parenchyma was serially measured on abdominal computed tomography (CT) scans before PPPD, as well as 7 days and 3, 6, and 12 months after surgery. Degree of pancreatic parenchymal atrophy was determined by calculating pancreatic volume relative to that on day 7.

Results

Univariate analysis showed that patient sex, age, body mass index, concurrent pancreatitis, pathology, and types of PJ did not significantly affect changes in pancreatic volume following PPPD. The degree of pancreatic volume atrophy did not differ significantly in the external and internal drainage groups. No patient in the external drainage group experienced drainage-related surgical complications. The incidence of PJ leak was comparable in the two groups. Postoperative pancreatic atrophy did not induce new-onset diabetes mellitus at 1 year.

Conclusions

Both external and internal pancreatic drainage methods showed similar atrophy rate of the pancreatic parenchyma following PPPD.     

Response to pretransplant hypomethylating agents influences the outcome of allogeneic hematopoietic stem cell transplantation in adults with myelodysplastic syndromes

This study describes a retrospective analysis on the transplant outcome of 56 consecutive patients with myelodysplastic syndrome (MDS) according to their response to hypomethylating agents (HMA). While 2‐yr disease‐free survival (DFS) of patients who transformed to acute myeloid leukemia (n = 12) was 25%, that of the remaining patients with MDS according to response to HMA was 73.1%, 68.1%, 50.0%, and 20.8% in G‐COR (group of continuous response, n = 19), G‐NoC (group of no change, n = 15), G‐LOR (group of loss of response, n = 6), and G‐DP (group of disease progression, n = 4), respectively. When dichotomized as G‐COR/G‐NoC versus G‐LOR/G‐DP, significantly different 2‐yr DFS (71.0% vs. 33.3%; P = 0.004) and relapse (14.1% vs. 46.7%; P = 0.016) were demonstrated. On multivariate analysis, G‐LOR/G‐DP [hazard ratio (HR), 3.91; P = 0.008] and poor karyotype at transplantation (HR, 2.69; P = 0.017) were the significant predictors for poor DFS, as G‐LOR/G‐DP was for relapse (HR, 6.28; P = 0.011). DFS was significantly poor in patients with any of the two predictors in all MDS (81.5% vs. 34.9%; P = 0.001) or higher‐risk MDS (HrMDS) at the time of HMA (80.7% vs. 29.2%; P = 0.005). G‐COR showed a trend of better DFS compared with G‐NoC among HrMDS (74.6% vs. 36.5%; P = 0.090). These results implicate the significance of response to HMA on hematopoietic stem cell transplantation (HSCT) outcomes and support the need for future study to verify the suggested strategy of proceeding to transplantation before LOR or DP, especially for HrMDS.     

A Case of Nonalcoholic Steatohepatitis and Small Intestinal Bacterial Overgrowth with Peripheral Edema Caused by Intestinal Bypass Surgery and Relieved by Repair

Intestinal bypass surgery, particularly jejuno-ileal bypass surgery, performed for the purpose of weight reduction may cause an unexpected exacerbation of nonalcoholic steatohepatitis (NASH). Here, we report a case of NASH caused by small intestinal bacterial overgrowth, which developed after jejuno-colic bypass surgery and resolved dramatically after surgical correction.     

Effect of PRX-1 Downregulation in the Type 1 Diabetes Microenvironment

Type 1 diabetes (T1D) is caused by dysregulation of the immune system in the pancreatic islets, which eventually leads to insulin-producing pancreatic β-cell death and destabilization of glucose homeostasis. One of the major characteristics of T1D pathogenesis is the production of inflammatory mediators by macrophages that result in destruction or damage of pancreatic β-cells. In this study the inflammatory microenvironment of T1D was simulated with RAW264.7 cells and MIN6 cells, acting as macrophages and pancreatic β-cells respectably. In this setting, peroxiredoxin-1, an anti-oxidant enzyme was knocked down to observe its functions in the pathogenesis of T1D. RAW264.7 cells were primed with lipopolysaccharide and co-cultured with MIN6 cells while PRX-1 was knocked down in one or both cell types. Our results suggest that hindrance of PRX-1 activity or the deficiency of this enzyme in inflammatory conditions negatively affects pancreatic β-cell survival. The observed decrease in viability of MIN6 cells seems to be caused by nitric oxide production. Additionally, it seems that PRX-1 affects previously reported protective activity of IL-6 in pancreatic β cells as well. These results signify new, undiscovered roles for PRX-1 in inflammatory conditions and may contribute toward our understanding of autoimmunity.     

Acute Hypoxia Activates an ENaC-like Channel in Rat Pheochromocytoma (PC12) Cells

Cells can resist and even recover from stress induced by acute hypoxia, whereas chronic hypoxia often leads to irreversible damage and eventually death. Although little is known about the response(s) to acute hypoxia in neuronal cells, alterations in ion channel activity could be preferential. This study aimed to elucidate which channel type is involved in the response to acute hypoxia in rat pheochromocytomal (PC12) cells as a neuronal cell model. Using perfusing solution saturated with 95% N₂ and 5% CO₂, induction of cell hypoxia was confirmed based on increased intracellular Ca²⁺ with diminished oxygen content in the perfusate. During acute hypoxia, one channel type with a conductance of about 30 pS (2.5 pA at -80 mV) was activated within the first 2~3 min following onset of hypoxia and was long-lived for more than 300 ms with high open probability (P_o, up to 0.8). This channel was permeable to Na⁺ ions, but not to K⁺, Ca⁺, and Cl^- ions, and was sensitively blocked by amiloride (200 nM). These characteristics and behaviors were quite similar to those of epithelial sodium channel (ENaC). RT-PCR and Western blot analyses confirmed that ENaC channel was endogenously expressed in PC12 cells. Taken together, a 30-pS ENaC-like channel was activated in response to acute hypoxia in PC12 cells. This is the first evidence of an acute hypoxia-activated Na⁺ channel that can contribute to depolarization of the cell.     

CTLA-4-Tg/CD-28-KO Mice Exhibit Reduced T Cell Proliferation in vivo Compared to CD-28-KO Mice in a Graft-versus-host Disease Model

Activated T cells express inhibitory receptors such as CTLA-4 that can downregulate immune responses. Blockade of or genetic deficiency in CTLA-4 can result in autoimmunity. Therefore, strategies to increase the inhibitory function of CTLA-4 may be attractive in settings of undesirable T cell responses such as autoimmunity or transplant rejection. We have tested the hypothesis that transgenic constitutive expression of CTLA-4 can further attenuate immune responses when compared with normal inducible expression. Our results indicate that transgenic expression of CTLA-4 in mouse T cells (CTLA-4-Tg T cells) results in reduced cell cycle progression and increased apoptosis of TCR-stimulated T cells. CTLA-4-Tg T cells display reduced T cell proliferation in an in vivo model of graft versus host disease (GVHD). These results further our understanding of how CTLA-4 can be manipulated to inhibit immune responses and may help development of new therapeutic strategies for clinical settings of autoimmunity and transplantation.