Effect of Dietary Geranylgeraniol and Green Tea Polyphenols on Glucose Homeostasis, Bone Turnover Biomarkers, and Bone Microstructure in Obese Mice.

Previously, we demonstrated that the administration of either geranylgeraniol (GGOH) or green tea polyphenols (GTP) improved bone health. This study examined the combined effects of GGOH and GTP on glucose homeostasis in addition to bone remodeling in obese mice. We hypothesized that GGOH and GTP would have an additive or synergistic effect on improving glucose homeostasis and bone remodeling possibly in part via suppression of proinflammatory cytokines. Forty-eight male C57BL/6J mice were assigned to a high-fat diet (control), HFD + 400 mg GGOH/kg diet (GG), HFD + 0.5% GTP water (TP), or HFD + GGOH + GTP (GGTP) diet for 14 weeks. Results demonstrated that GTP supplementation improved glucose tolerance in obese mice. Neither GGOH nor GTP affected pancreas insulin or bone formation procollagen type I intact N-terminal, bone volume at the lumbar vertebrae, or bone parameters at the trabecular bone and cortical bone of the femur. There was an interactive effect for serum bone resorption collagen type 1 cross-linked C-telopeptide concentrations, resulting in no-GGOH and no-GTP groups having the highest values. GGOH increased trabecular number and decreased trabecular separation at the lumbar vertebrae. GTP increased trabecular thickness at lumbar vertebrae. The GG group produced the greatest connectivity density and the lowest structure model index. Only GTP, not GGOH, decreased adipokines concentrations (resistin, leptin, monocyte chemoattractant protein-1, and interleukin-6). In an obese male mouse model, individual GGOH and GTP supplementation improved glucose homeostasis, serum CTX, and trabecular microstructure of LV-4. However, the combined GGOH and GTP supplementation compromises such osteoprotective effects on serum CTX and trabecular bone of obese mice.

Exploring transitions in care from pulmonary rehabilitation to home for persons with chronic obstructive pulmonary disease: A descriptive qualitative study.

BACKGROUND: Individuals with chronic obstructive pulmonary disease (COPD) often experience high health-care utilization following pulmonary rehabilitation, suggesting suboptimal transitions to home. OBJECTIVE: To understand the experiences of persons with COPD and health-care professionals regarding transitions from pulmonary rehabilitation to home, including factors impacting these transitions. DESIGN: A descriptive qualitative study. SETTING AND PARTICIPANTS: Health-care professionals working at, and persons with COPD who attended, an inpatient or outpatient pulmonary rehabilitation programme at one large, urban health-care centre. The centre is located in Ontario, Canada. MAIN VARIABLE STUDIED: Experiences of participants with care transitions between pulmonary rehabilitation and home. Semi-structured interviews were audio-recorded, transcribed verbatim, and thematically analysed. RESULTS: Ten patients and eight health-care professionals participated. Four main themes were identified around the overall experiences with pulmonary rehabilitation and transitions to home: (a) pulmonary rehabilitation as a safe environment; (b) pulmonary rehabilitation as a highly structured environment; (c) contrasting perceptions of the role of pulmonary rehabilitation; and (d) dependency on pulmonary rehabilitation programmes. Persons with COPD and health-care professionals identified three key factors that influenced this transition: (a) patients' social support, (b) application of self-management strategies prior to discharge, and (c) patients' physical and mental health. CONCLUSION: Participants agreed that some patients with COPD experienced suboptimal transitions from pulmonary rehabilitation to home that were characterized by suboptimal self-management. Further research is needed to develop and evaluate interventions to improve transitions. Such interventions should include strategies to elicit long-term behaviour change to assist patients when they return into the community.

Effects of Hyperbaric (Non-Thermal) Sanitization and the Method of Extracting Pomegranate Juice on Its Antioxidant and Antihypertensive Properties.

Pomegranate (Punica granatum L.) is considered a functional food due to its polyphenol content that benefits the body. The type of processing the fruit undergoes is important, as this also influences the concentrations of these compounds. The pomegranate juice was extracted by two methods: manual extraction using a manual juicer through heat treatment in a water bath (Man-P), and extraction through mechanical pressing using Good Nature X-1 equipment and hyperbaric sanitization (Mech-Hyp). Bromatological analyses showed significant differences (p ≤ 0.05) between the two treatments. When subjected to hyperbaric sanitization, the juice showed higher concentrations of moisture, soluble solids, protein, and carbohydrates. In an antioxidant analysis, the ABTS radical showed no significant difference in the treatments, with 96.99% inhibition. For the DPPH radical, the sample with the highest inhibition was Man-P with 98.48%. The determination of phenols showed that there was a higher concentration in juice that underwent pasteurization (104.566 mg GAE/mL). However, the Mech-Hyp treatment exhibited a minor concentration of phenols with 85.70 mg GAE/mL. FTIR spectra revealed that the functional groups were mainly associated with carbohydrates. Regarding ACE inhibition, it was observed that the Man-P and Mech-Hyp juices showed greater inhibition of enzyme in hypertensive patients compared to normotensive patients. This activity can be attributed to the mechanisms of action of antioxidant compounds. Both extraction methods manual and mechanical pressing resulted in increased antioxidant and antihypertensive activity. The antioxidant compounds accompanied by adequate sanitation were decisive in an antimicrobial analysis, since no pathogenic microorganisms were observed in the juices.

B cell-specific knockout of AID protects against atherosclerosis.

Antigen-naive IgM-producing B cells are atheroprotective, whereas mature B cells producing class-switched antibodies promote atherosclerosis. Activation-induced cytidine deaminase (AID), which mediates class switch recombination (CSR), would thus be expected to foster atherosclerosis. Yet, AID also plays a major role in the establishment of B cell tolerance. We sought to define whether AID affects atherosclerotic plaque formation. We generated Ldlr-/- chimeras transplanted with bone marrow from Aicda-/- or wild-type (WT) mice, fed a HFD for 14 weeks. Decreased B cell maturation in Ldlr-/-Aicda-/- mice was demonstrated by 50% reduction in splenic and aortic BAFFR expression, a key signaling component of B2 cell maturation. This was associated with increased plasma IgM in Ldlr-/-Aicda-/- compared with Ldlr-/-WT animals. Importantly, Ldlr-/-Aicda-/- mice had reduced atherosclerotic lesion area (0.20 ± 0.03mm2) compared with Ldlr-/-WT (0.30 ± 0.04mm2, P < 0.05), although no differences in plaque composition were noted between groups. In addition, immunofluorescence analysis revealed increased splenic B and T cell areas independent of cell number. AID depletion directly inhibits atherosclerotic plaque formation.

Sertoli Cells Express Accommodation, Survival, and Immunoregulatory Factors When Exposed to Normal Human Serum.

Transplantation is a clinical procedure that treats a variety of diseases yet is unattainable for many patients due to a nationwide organ shortage and the harsh side effects of chronic immune suppression. Xenografted pig organs are an attractive alternative to traditional allografts and would provide an endless supply of transplantable tissue, but transplants risk rejection by the recipient's immune system. An essential component of the rejection immune response is the complement system. Sertoli cells, an immunoregulatory testicular cell, survive complement as xenografts long term without any immune suppressants. We hypothesized that exposure to the xenogeneic complement influences Sertoli cell gene expression of other accommodation factors that contribute to their survival; thus, the purpose of this study was to describe these potential changes in gene expression. RNA sequencing of baseline neonatal pig Sertoli cells (NPSC) as compared to NPSC after exposure to normal human serum (NHS, containing complement) revealed 62 significantly differentially expressed genes (DEG) that affect over 30 pathways involved in immune regulation, cell survival, and transplant accommodation. Twelve genes of interest were selected for further study, and Sertoli cell protein expression of CCL2 and the accommodation factor A20 were confirmed for the first time. Functional pathway analyses were conducted in NPSC and three biological clusters were revealed as being considerably affected by NHS exposure: innate immune signaling, cytokine signaling, and T cell regulation. Better understanding of the interaction of Sertoli cells with complement in a xenograft environment may reveal the mechanisms behind immune-privileged systems to increase graft viability.

Ginger Root Extract Improves GI Health in Diabetic Rats by Improving Intestinal Integrity and Mitochondrial Function.

Background Emerging research suggests hyperglycemia can increase intestinal permeability. Ginger and its bioactive compounds have been reported to benefit diabetic animals due to their anti-inflammatory and antioxidant properties. In this study, we revealed the beneficial effect of gingerol-enriched ginger (GEG) on intestinal health (i.e., barrier function, mitochondrial function, and anti-inflammation) in diabetic rats. Methods Thirty-three male Sprague Dawley rats were assigned to three groups: low-fat diet (control group), high-fat-diet (HFD) + streptozotocin (single low dose 35 mg/kg body weight (BW) after 2 weeks of HFD feeding) (DM group), and HFD + streptozotocin + 0.75% GEG in diet (GEG group) for 42 days. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were conducted at baseline and prior to sample collection. Total pancreatic insulin content was determined by ELISA. Total RNA of intestinal tissues was extracted for mRNA expression using qRT-PCR. Results Compared to the DM group, the GEG group had improved glucose tolerance and increased pancreatic insulin content. Compared to those without GEG (DM group), GEG supplementation (GEG group) increased the gene expression of tight junction (Claudin-3) and antioxidant capacity (SOD1), while it decreased the gene expression for mitochondrial fusion (MFN1), fission (FIS1), biogenesis (PGC-1α, TFAM), mitophagy (LC3B, P62, PINK1), and inflammation (NF-κB). Conclusions Ginger root extract improved glucose homeostasis in diabetic rats, in part, via improving intestinal integrity and mitochondrial dysfunction of GI health.

Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells.

The acute cell-mediated immune response presents a significant barrier to xenotransplantation. Immune-privileged Sertoli cells (SC) can prolong the survival of co-transplanted cells including xenogeneic islets, hepatocytes, and neurons by protecting them from immune rejection. Additionally, SC survive as allo- and xenografts without the use of any immunosuppressive drugs suggesting elucidating the survival mechanism(s) of SC could be used to improve survival of xenografts. In this study, the survival and immune response generated toward neonatal pig SC (NPSC) or neonatal pig islets (NPI), nonimmune-privileged controls, was compared after xenotransplantation into naïve Lewis rats without immune suppression. The NPSC survived throughout the study, while NPI were rejected within 9 days. Analysis of the grafts revealed that macrophages and T cells were the main immune cells infiltrating the NPSC and NPI grafts. Further characterization of the T cells within the grafts indicated that the NPSC grafts contained significantly more cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) regulatory T cells (Tregs) at early time points than the NPI grafts. Additionally, the presence of increased amounts of interleukin 10 (IL-10) and transforming growth factor (TGF) ß and decreased levels of tumor necrosis factor (TNF) α and apoptosis in the NPSC grafts compared to NPI grafts suggests the presence of regulatory immune cells in the NPSC grafts. The NPSC expressed several immunoregulatory factors such as TGFß, thrombospondin-1 (THBS1), indoleamine-pyrrole 2,3-dioxygenase, and galectin-1, which could promote the recruitment of these regulatory immune cells to the NPSC grafts. In contrast, NPI grafts had fewer Tregs and increased apoptosis and inflammation (increased TNFα, decreased IL-10 and TGFß) suggestive of cytotoxic immune cells that contribute to their early rejection. Collectively, our data suggest that a regulatory graft environment with regulatory immune cells including CD4 and CD8 Tregs in NPSC grafts could be attributed to the prolonged survival of the NPSC xenografts.