Exogenous Injection Research Articles

Food deprivation during active phase induces skeletal muscle atrophy via IGF-1 reduction in mice

Skeletal muscle mass is largely influenced by nutritional status and physical activity. Although feeding at specific times of the day (time-restricted feeding, TRF) modulates obesity and other metabolic functions, its effects on skeletal muscles remain unclear. We explored the effects of feeding mice only during the inactive (daytime feeding, DF) or active (nighttime feeding, NF) phases for one week. Daytime feeding did not abolish the nocturnal activity rhythm, although total daily activity was reduced in these mice. Temporal expression of the circadian clock genes, Per2 and Rev-erbα, became synchronized to the feeding cycle in the liver, but not in skeletal muscle. Skeletal muscle mass, grip strength, and cross-sectional area were significantly lower in DF, than in NF mice, although DF increased body weight gain and lipid accumulation. Expression of the atrophy-related ubiquitin ligases, Atrogin-1 and Murf1 and the autophagy-related genes, Lc3b and Bnip3, was induced during the active phase in the gastrocnemius muscles of DF, compared with those of NF mice. Plasma IGF-1 concentrations and Igf-1 expression in the livers and gastrocnemius muscles during the active phase were lower in DF, than in NF mice. Furthermore, exogenous IGF-1 injection significantly suppressed DF-induced reduction in gastrocnemius muscle mass, which might at least partly explain the association between decreased plasma IGF-1 concentrations and reductions in the skeletal muscle mass of DF mice. These findings suggest that feeding only during the inactive phase reduces skeletal muscle mass via a decrease in plasma IGF-1 concentrations during the active phase.

Stress–glucocorticoid–TSC22D3 axis compromises therapy-induced antitumor immunity

Psychological distress has long been suspected to influence cancer incidence and mortality. It remains largely unknown whether and how stress affects the efficacy of anticancer therapies. We observed that social defeat caused anxiety-like behaviors in mice and dampened therapeutic responses against carcinogen-induced neoplasias and transplantable tumors. Stress elevated plasma corticosterone and upregulated the expression of glucocorticoid-inducible factor Tsc22d3, which blocked type I interferon (IFN) responses in dendritic cell (DC) and IFN-γ+ T cell activation. Similarly, close correlations were discovered among plasma cortisol levels, TSC22D3 expression in circulating leukocytes and negative mood in patients with cancer. In murine models, exogenous glucocorticoid injection, or enforced expression of Tsc22d3 in DC was sufficient to abolish therapeutic control of tumors. Administration of a glucocorticoid receptor antagonist or DC-specific Tsc22d3 deletion reversed the negative impact of stress or glucocorticoid supplementation on therapeutic outcomes. Altogether, these results indicate that stress-induced glucocorticoid surge and Tsc22d3 upregulation can subvert therapy-induced anticancer immunosurveillance.

Advanced oxidation protein products increase TNF-α and IL-1β expression in chondrocytes via NADPH oxidase 4 and accelerate cartilage degeneration in osteoarthritis progression

Interleukin (IL)-1β and tumor necrosis factor (TNF)-α, in particular, control the degeneration of articular cartilage, making them prime targets for osteoarthritis (OA) therapeutic strategies. Advanced oxidation protein products (AOPPs) are prevalent in numerous diseases. Our previous work demonstrates that intra-articular injections of AOPPs accelerate regression of cartilage in OA models. Whether AOPPs exist in the course of OA and their effects on TNF-α and IL-1β expression in chondrocytes are still unclear. This study confirmed that AOPPs levels in human synovial fluid were positively associated with severity of OA. We also found AOPPs deposition in articular cartilage in anterior cruciate ligament transection (ACLT) induced rodent OA models. AOPPs increased expression of TNF-α and IL-1β in chondrocytes in vitro, which was inhibited by pre-treatment with SB202190 (p38-MAPK inhibitor) or apocynin (NADPH oxidase inhibitor) or NOX4 knockdown by siRNAs. Subsequently, we further verified in vivo that exogenous injection of AOPPs in OA mice up-regulated expression of TNF-α and IL-1β in cartilage, which was blocked by treatment with apocynin. In parallel, apocynin attenuated articular cartilage degeneration resulting in substantially lower OARSI scores. Specifically, apocynin reduced NOX4, p-P38, TNF-α and IL-1β and increased collagen II and glycosaminoglycan (GAG). This study demonstrated that AOPPs increased expression of TNF-α and IL-1β in chondrocytes via the NADPH oxidase4-dependent and p38-MAPK mediated pathway, and accelerated cartilage degeneration in OA progression. These findings suggest an endogenous pathogenic role of AOPPs in OA progression. Targeting AOPPs-triggered cellular mechanisms might be a promising therapeutic option for patients with OA.

Lessons learned from intervertebral disc pathophysiology to guide rational design of sequential delivery systems for therapeutic biological factors.

Intervertebral disc (IVD) degeneration has been associated with low back pain, which is a major musculoskeletal disorder and socio-economic problem that affects as many as 600 million patients worldwide. Here, we first review the current knowledge of IVD physiology and physiopathological processes in terms of homeostasis regulation and consecutive events that lead to tissue degeneration. Recent progress with IVD restoration by anti-catabolic or pro-anabolic approaches are then analyzed, as are the design of macro-, micro-, and nano-platforms to control the delivery of such therapeutic agents. Finally, we hypothesize that a sequential delivery strategy that i) firstly targets the inflammatory, pro-catabolic microenvironment with release of anti-inflammatory or anti-catabolic cytokines; ii) secondly increases cell density in the less hostile microenvironment by endogenous cell recruitment or exogenous cell injection, and finally iii) enhances cellular synthesis of extracellular matrix with release of pro-anabolic factors, would constitute an innovative yet challenging approach to IVD regeneration.

Exogenous intrapleural injection of interleukin-27 may improves outcome and prognosis in patients with tuberculous pleural effusion

We hypothesize that exogenous intrapleural injection of interleukin-27 may improve outcome and prognosis in patients with tuberculous pleural effusion (TPE). Studies have found that the balance of Th1/Th2 determines the development trend of TPE. High concentrations of IFN-γ and TNF-α in pleural effusion are associated with pleural adhesion in patients with TPE. Interleukin-27 is a member of the IL-12 family, and IL-27 has a dual regulatory effect on Th1 immunity. On one hand, IL-27 can promote the initial CD4+ T cell proliferation by inducing the expression of T-bet, IL-12Rβ2 and ICAM-1 in the initial CD4+ T cells, and also promote its differentiation into Th1 cells and IFN-γ production in the early infection. On the other hand, in the case of high Th1 polarization, IL-27 induced STAT3 phosphorylation and inhibited TNF and IL-12 production in activated peritoneal macrophages, indicating a novel feedback mechanism by which IL-27 can modulate excessive inflammation, thereby preventing damage to the body caused by excessive immune response. Studies haves confirmed that after stimulation of antigen by mononuclear cells in TPE, the Th1 and Th2 cell subsets and Th1/Th2 ratio markedly increase, and the increase of Th1 is more obvious than that of Th2. Therefore, compared to patients with TPE in the high-level IL-27 group, we hypothesized that pleural effusion is absorbed more slowly, pleural thickening is more obvious, pleural adhesions are more extensive, and the incidence of thoracic collapse is higher in the low-level IL-27 group under the same conditions of anti-tuberculosis treatment. However, exogenous intrapleural injection of IL-27 may induce Stat3 phosphorylation and inhibit TNF and IL-12 production, finally reduces the secretion of IFN-γ and TNF-α. This negative regulation inhibits the excessive inflammatory reaction caused by tuberculosis infection, reduces pleural adhesion, pleural thickening and local pleural tissue damage, thereby improving the prognosis of patients.

FGF9 alters the Wallerian degeneration process by inhibiting Schwann cell transformation and accelerating macrophage infiltration

In vitro experiments have proved that Fibroblast Growth Factor 9 (FGF9) was decreased in Schwann cells (SCs) in which Wallerian degeneration (WD) occurred after nerve injury. We hypothesize that FGF9 downregulation in WD has some biological influence on Schwann cells (SCs) and macrophages – the two most important cell components involved in WD. In this study, we employed strategies to regulate FGF9 in sciatic nerve crush by generating a mouse model, wherein Fgf9 was specifically knocked-out in SCs, and an intraneural injection of human FGF9 protein administered to overexpress FGF9 independently. Furthermore, an inhibitor of extracellular-regulated kinases 1/2 (ERK1/2), PD0325901, was used to clarify the underlying downstream mechanism of ERK1/2 activated by FGF9. Analysis of WD revealed the novel features of FGF9: (i) FGF9 was widely expressed in axons and SCs, and was decreased during WD process. (ii) Fgf9 knockout in SCs impaired the debris clearance and eventually impeded the regeneration of nerve fibers after damage. (iii) Fgf9 knockout in SCs promoted the dedifferentiation of SCs and delayed the infiltration of macrophages by decreasing Mcp1, Tnfα, Il1β levels and leaky blood-nerve-barrier (BNB) in WD. (iv) FGF9 injection preserved the nerve fibers, inhibited SCs dedifferentiation and accelerated macrophages infiltration. (v) ERK1/2 phosphorylation was increased by exogenous FGF9 injection. P75, Cyclin D1, Mcp1, Tnfα, Il1β, c-Jun changes by FGF9 intraneural injection were partially reversed by the ERK1/2 inhibitor. Conclusion was that FGF9 inhibited the dedifferentiation of SCs and accelerated the accumulation of macrophages in WD, and exogenous FGF9 took effects partially by ERK1/2.

MiR-21-5p inhibits neuropathic pain development via directly targeting C-C motif ligand 1 and tissue inhibitor of metalloproteinase-3.

MicroRNAs (miRNA) play important roles in neuroinflammation and neuropathic pain development; however, the underlying mechanism requires further investigation. The expression of miR-21-5p was remarkably upregulated in chronic constrictive injury (CCI) rat model. A significant alleviated neuropathic pain development and reduced the expression of cytokines was observed in CCI rat after exogenous injection of miR-21-5p mimic. The dual-luciferase analysis revealed that tissue inhibitor of metalloproteinase-3 (TIMP3) and chemokines C-C motif ligand 1 (CCL1) was direct downstream target of miR-21-5p. Moreover, silencing of TIMP3 and CCL1 could rescue mechanical allodynia, thermal hyperalgesia and cytokine release in CCI rat, suggesting that TIMP3 and CCL1 exert their function by mediating neuroinflammation in neuropathic pain development. Therefore, we have identified a novel miR-21-5p-CCL1/TIMP3-cytokine axis in regulation of neuropathic pain development in CCI rat model, which is valuable for enhancing our understanding of neuropathic pain and developing miRNAs as potential therapeutic options in the future.

Retraction: Muscle-derived Satellite Cells for Treating Type 1 Diabetes in Rats (Rattus norvegicus).

Diabetes mellitus(DM) is a complicated metabolic disease, with the fundamental treatment nowadays being diet control, insulin injections, slet or pancreas transplantation, which is limited because exogenous insulin injections fail to simulate normal insulin secretion in islet beta cells successfully and islet transplantation lacks organ donors. So far, stem cells with highly self-renewal and multi-directional differentiation potential have become a new hope for the treatment of diabetes. In this research, rat Muscle-derived satellite cells *MDSCs*were separated and cultivated in vitro and inducted into insulin-producing cells with observation and identification using dithizone staining and so on. T1D rat model was built with Streptozocin(STZ), then MDSCs and induced insulin-producing cells from MDSCs labeled by Dil were transplanted respectively. Transplantation of MDSCs (group 1) and the induced insulin-producing cells (group 2) into streptozotocin (STZ)-induced diabetic rats resulted in lower blood glucose, lower urine glucose, higher body weight, higher glucose tolerance and less water intake and urine output than control rats (P < 0.05). Among the male rats, the blood glucose levels of 50% of group 1 rats were <16.7 mmol/L, and 40% of group 2 rats yielded similar results (P < 0.01). Among the female rats, the blood glucose levels of 66.67% of group 1 rats were <16.7 mmol/L, and 33.33% of group 2 rats showed similar blood glucose levels (P < 0.01). Histological examination revealed that the transplanted cells reached the pancreas and repaired damaged tissues. The above research conclusions provide theoretical basis, cell selection and good prospect for the treatment of diabetes. This article is protected by copyright. All rights reserved.

Pilot-scale biomethanation of cattle manure using dense membranes

This study aimed at studying the biomethanation process using a 100 L pilot-scale digester equipped with a dense membrane for hydrogen injection. Hydrogen mass transfer was characterized and the impact of hydrogen flowrate, agitation rate and of the co-injection of CO2, on biogas production and composition, was precisely studied. A linear relationship between H2 flowrate and the CO2 and CH4 rates in biogas was found but no impact on biogas flowrate was shown. It was also noticed that, without exogenous CO2 injection, and for high H2 injection flowrates, residual H2 could be found at the digester outlet due to local CO2 limitation. Thus, this study suggested that biogas production in biomethanation process at the pilot scale was probably rather limited by the dissolved CO2 transport within the liquid phase than by the hydrogen mass transfer itself.

The immunomodulatory function of invertebrate specific neuropeptide FMRFamide in oyster Crassostrea gigas

As one of the most important neuropeptides identified only in invertebrates of Mollusca, Annelida and Arthropoda, FMRFamide (Phe-Met-Arg-Phe-NH2) involves in multiple physiological processes, such as mediating cardiac frequency and contraction of somatic and visceral muscles. However, its modulatory role in the immune defense has not been well understood. In the present study, an FMRFamide precursor (designed as CgFMRFamide) was identified in oyster Crassostrea gigas, which could be processed into nineteen FMRFamide peptides. Phylogenetic analysis revealed that CgFMRFamide shared high similarity with other identified FMRFamides in mollusks. The mRNA of CgFMRFamide was mainly concentrated in the tissues of visceral ganglia, hepatopancreas and hemocytes, and a consistent distribution of FMRFamide peptide was confirmed by immunohistochemistry and immunocytochemistry assays. The mRNA expression level of CgFMRFamide in hemocytes was significantly up-regulated after immune stimulation with lipopolysaccharide (LPS). After the concentration of FMRFamide was increased by exogenous injection, the in vivo expressions of pro-inflammatory cytokine CgIL17-5, as well as the apoptosis-related CgCaspase-1 and CgCaspase-3 in hemocytes were promptly increased (p < 0.05), but the concentration of signal molecule nitric oxide (NO) was significantly down-regulated (p < 0.05). Meanwhile, an increased phosphorylation of p38 MAP kinase in hemocytes was also detected after the FMRFamide injection. These results collectively demonstrated that the conserved FMRFamide could not only respond to immune stimulation, but also regulate the expression of immune effectors and apoptosis-related genes, which might be mediated by p38 MAP kinase pathway, thereby effectively involved in clearing pathogens and maintaining homeostasis in oysters.

Ecdysone inducible gene E75 from black tiger shrimp Penaeus monodon: Characterization and elucidation of its role in molting.

Molting is controlled by ecdysteroids, which are synthesized and secreted by the Y-organ in crustaceans. Ecdysone inducible gene, E75, is an early-response gene in the 20-hydroxyecdysone (20E) signaling pathway, with crucial roles in arthropod development. Complementary DNA (cDNA) encoding Penaeus monodon E75 (PmE75) was cloned using RT-PCR and RACE. PmE75 cDNA was 3526 bp long and encoded a 799-amino acid protein. Tissue distribution analysis showed that PmE75 was expressed ubiquitously in selected tissues, and was relatively abundant in the epidermis, muscle, and hepatopancreas. Developmental expression revealed that PmE75 was expressed throughout its life cycle. Silencing PmE75 significantly decreased PmE75 expression. Shrimps injected with PBS and dsGFP started molting on Day 7 and had almost completed molting on Day 9, whereas dsPmE75-injected shrimp presented no signs of molting. These results suggested that PmE75 might be involved in molting. In situ hybridization results support this hypothesis. To explore the role of 20E and eyestalks in the regulation of molting in P. monodon, exogenous 20E injection and eyestalk ablation (ESA) were performed, and showed that 20E can induce the transcription and expression of PmE75 in the hepatopancreas, epidermis, and muscle, which were significantly elevated after ESA. These results provide further insights into our understanding of molting.

Enhancement of postprandial endogenous insulin secretion rather than exogenous insulin injection ameliorated insulin antibody-induced unstable diabetes: a case report

BackgroundInsulin injection, especially with insulin analogs, occasionally induces the production of insulin antibodies with high binding capacity and low affinity, similar to the insulin autoantibodies characteristic of insulin autoimmune syndrome (IAS). Production of these “IAS-like” insulin antibodies causes marked glycemic fluctuations with postprandial hyperglycemia and fasting hypoglycemia.Case presentationA 66-year-old man with a 27-year history of diabetes was admitted because of marked glycemic fluctuations. Human insulin treatment had been initiated at age 56, followed by multiple daily injections of insulin analogs 5 years later. After the initial year of insulin analog treatment, the patient began to experience frequent morning hypoglycemic attacks and day-time hyperglycemia. Marked hyperinsulinemia (4500 μU/mL) and high titers of insulin antibodies (80.4%) with high binding capacity and low affinity indicated that IAS-like insulin antibodies were causing severe glucose fluctuations. Altering insulin formulations (insulin aspart → regular human insulin→ insulin lispro) proved to be ineffective. After several therapeutic trials, cessation of exogenous insulin and addition of mitiglinide to liraglutide with voglibose finally attenuated glycemic fluctuations with increased postprandial insulin secretion. Continuous glucose monitoring revealed improvement of morning hypoglycemia and postprandial hyperglycemia with smaller mean amplitude of glycemic excursion. Therefore, compared to exogenously injected insulin, endogenously secreted insulin directly and rapidly acts on hepatocytes and suppresses postprandial glucose output.ConclusionsProper enhancement of postprandial endogenous insulin aimed at suppressing postprandial glucose output without stimulating excessive glucose uptake in the periphery is potentially useful for treating diabetes with insulin antibody-induced glycemic instability.

Effects of exogenous Fibroblast Growth Factor-21 on characteristic parameters related to energy metabolism in dairy cows

Negative energy balance (NEB) is a common pathological foundation of fatty liver and ketosis. Liver and fat tissue are the major organs of lipid metabolism, which is also a key metabolic pathway that regulates NEB development during the perinatal period. Fibroblast growth factor-21 (FGF-21) is a protein hormone that plays an important role in adipose lipid metabolism and liver gluconeogenesis. Our aim was to investigate the effects of exogenous FGF-21 on characteristic parameters related to energy balance in dairy cows. Ten non-pregnant, non-lactating Holstein-Friesian dairy cows were randomly allocated into two groups. The interventions were exogenous FGF-21 injection group received 1 ug/kg BW (body weight) of recombinant bovine FGF-21 by intravenous injection, and control group received physiological saline injections by intravenous injection. In comparison to saline injections, intravenous injections of FGF-21 either increased or tended to increase concentrations of FGF-21 (p &lt; 0.05), BHBA (p &lt; 0.05), adiponectin, leptin and HDL-C. FGF-21 injections decreased or tended to decrease concentrations of insulin, glucose, glucagon (p &lt; 0.05), ALT/GPT (p &lt; 0.05), AST/GOT (p &lt; 0.05), urate, creatinine (p &lt; 0.05), BUN, triglyceride (p &lt; 0.05), T-CHO and LDL-C (p &lt; 0.05). The results indicate that FGF-21 has only negative effects on the metabolites and metabolic hormones related to NEB in serum of dairy cows, but it has more beneficial effects on prominent adipokines, liver function index, renal function index, lipoprotein profiles related to the pathological changes that occurred in NEB.

Poorly-Controlled Type 1 Diabetes Mellitus Impairs LH-LHCGR Signaling in the Ovaries and Decreases Female Fertility in Mice.

PurposeThe aim of this study was to investigate how type I diabetes mellitus (T1D) affects the folliculogenesis and oocyte development, fertilization, and embryo development.Materials and MethodsA comparative animal study was conducted using two different mouse models of T1D, a genetic AKITA model and a streptozotocin-induced diabetes model. Ovarian function was assessed by gross observation, immunoblot, immunohistochemistry, oocyte counting, and ELISA for serum hormones (insulin, anti-Mullerian hormone, estradiol, testosterone, and progesterone). Maturation and developmental competence of metaphase II oocytes from control and T1D animals was evaluated by immunofluorescent and immunohistochemical detection of biomarkers and in vitro fertilization.ResultsAnimals from both T1D models showed increased blood glucose levels, while only streptozotocin (STZ)-injected mice showed reduced body weight. Folliculogenesis, oogenesis, and preimplantation embryogenesis were impaired in both T1D mouse models. Interestingly, exogenous streptozotocin injection to induce T1D led to marked decreases in ovary size, expression of luteinizing hormone/chorionic gonadotropin receptor in the ovaries, the number of corpora lutea per ovary, oocyte maturation, and serum progesterone levels. Both T1D models exhibited significantly reduced pre-implantation embryo quality compared with controls. There was no significant difference in embryo quality between STZ-injected and AKITA diabetic mice.ConclusionThese results suggest that T1D affects folliculogenesis, oogenesis, and embryo development in mice. However, the physiological mechanisms underlying the observed reproductive effects of diabetes need to be further investigated.

The prospective of using plant polyphenols as functional food ingredients

In this review we briefly discuss the publications dedicated to experimental evaluation of hypoglycemic, hypolipidemic and antioxidant properties of different plant polyphenols. The stages of preclinical studies of their efficacy are presented: in silico studies with molecular docking methods and in vivo studies with the use of genetic and medicamental models of type 2 diabetes. The results of own studies present the substantiation of prospects of using the plant polyphenol extracts as functional food ingredients for diet therapy and treatment of patients with type 2 diabetes. It was shown using genetic fatty Zucker rats model that extract consumption led to lower blood glucose level, had beneficial effect on glucose sensitivity and also improved the reaction of insulin-sensitive tissues on exogenous injection of glucose and insulin. Hypoglycemic and hypolipidemic properties of bilberry leaves extract were characterized on male Wistar rats model of carbohydrate metabolism disorder (streptozotocin injection accompanied with consumption of 10% fructose solution). The results of previous studies showed the beneficial effects of bilberry leaves extract on carbohydrate metabolism and determined the task to enhance the efficacy of developed polyphenol ingredient by the way of sorption on protein food matrix - brown buckwheat flour. Thus, a brief review of presented in this article results of foreign and domestic experimental studies shows the prospect of using the individual plant polyphenols and polyphenol plant extracts as phytonutrients for diet therapy and treatment of diseases associated with disorders of carbohydrate and lipid metabolism.

A short periconceptional exposure to maternal type-1 diabetes is sufficient to disrupt the feto-placental phenotype in a rabbit model

Tight metabolic control of type-1 diabetes is essential during gestation, but it could be crucial during the periconception period. Feto-placental consequences of maternal type-1 diabetes around the time of conception need to be explored.Using a rabbit model, type-1 diabetes was induced by alloxan 7 days before mating. Glycemia was maintained at 15–20 mmol/L with exogenous insulin injections to prevent ketoacidosis. At 4 days post-conception (dpc), embryos were collected from diabetic (D) or normoglycemic control (C) dams, respectively, and transferred into non-diabetic recipients. At 28dpc, D- and C-feto-placental units were collected for biometry, placental analyses and lipid profiles.D-fetuses were growth-retarded, hyperglycemic and dyslipidemic compared to C-fetuses. The efficiency of D-placentas was associated with an increased gene expression related to nutrient supply and lipid metabolism whereas volume density of fetal vessels decreased.Fetal plasma, placental and fetal liver membranes had specific fatty acid signatures depending on embryonic origin. Tissues from D-fetuses contained more omega-6 polyunsaturated fatty acids. The concentrations of docosahexaenoic acid decreased while linoleic acid increased in the heart of D-fetuses.This study demonstrates that a short exposure to maternal type-1 diabetes in the periconception window, until the blastocyst stage, is able to irreversibly malprogram the feto-placental phenotype, through precocious and persistent structural and molecular adaptations of placenta.

PO-220 HIIT prescription and diabetes

Objective To clarify the effect of HIIT prescription on diabetic mellitus (DM) and provide reliable exercise advise for DM patients. Method: Through literature &#x0D; Methods Through literature method to collect studies by key words: HIIT, diabetic mellitus, T1DM , T2DM. And through data analyze method to organize the related studies to make a conclusion.&#x0D; Results As a non-infectious metabolic disease，the incidence of DM is increasingly continuing in recent years. The epidemiological studies show that the global incidence of DM in the population aged 20-79 was 8.8% in 2015, and the total number reached 415 million. It is predicted that by 2040, the number of DM patients in this age group will reach 642 million with the prevalence rate rose to 10.4%. Insulin secretion and insulin signal transduction disorders are the main mechanisms of the onset of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) respectively. The inducers of DM are complex, such as obesity, inactivity, insomnia and heredity. The current interventions for DM are mainly drugs, diet, exercise, self-monitoring and education. Among them, exercise is accepted by the majority of diabetic patients because of its economic, fewer side effects and obvious effects.&#x0D; The occurrence of T1DM is closely related to heredity with the majority of adolescence patients. Due to insufficient insulin secretion, the clinical treatment of T2DM is mainly exogenous insulin injections. However, long-term insulin injections on the one hand leads to a continuous decline in the effect of insulin action, and are also a painful process for T1DM patients. Regular exercise can increase insulin sensitivity, decrease insulin resistance, promote the glucose uptake of skeletal muscle and regulate the blood glucose. However, the occurrence of exercise hypoglycemia makes it difficult for T1DM patients to insist exercise. The mechanism for the occurrence of exercise hypoglycemia is not clear, but studies show that it may related to insulin regulation change, counter-regulatory response decline and energy substrate metabolism disorder. Studies have shown that high intensity interval training (HIIT) prescription can avoid the occurrence of exercise-induced hypoglycemia caused by long-term moderate-intensity exercise to a certain extent. Therefore, the relationship between HIIT exercise and T1DM patients requires more research to prove. The occurrence of T2DM is accompanied by obesity. Obesity leads to the development of insulin resistance. A large number of studies have confirmed that exercise has a good intervention effect on obesity and T2DM. Compared with the traditional moderate intensity continuous training (MICT), HIIT has a better effect on reducing abdominal fat in the obesity. T2DM is often accompanied by many complications, such as diabetes cognitive dysfunction, diabetic Cardiomyopathy, diabetic liver disease and so on. The intervention effect of the HIIT prescription on these complications has also been confirmed by numerous studies.&#x0D; Conclusions As a non-pharmaceutical treatment of diabetes, exercise has obvious effects on diabetes intervention. The HIIT has gradually become one of the exercise intervention prescription because of its short time-consuming and obvious effects. However, the HIIT exercise prescription for DM patients of different ages, types, and complications remains to be further clarified.&#x0D;

Taxifolin is a rat and human 11β-hydroxysteroid dehydrogenase 1 inhibitor as a possible drug to treat the metabolic syndrome

11β-Hydroxysteroid dehydrogenase 1 (HSD11B1) is an NADPH-dependent oxidoreductase that elevates cortisol (in human beings) or corticosterone (in rats) locally via metabolically activating 11 keto-glucocorticoids. Taxifolin is a flavonoid in food plants. The present study investigated the effects of taxifolin on rat and human liver microsomal HSD11B1. Taxifolin competitively inhibited rat and human HSD11B1 against steroid cortisone or 11-dehydrocorticosterone, with IC50 values of 37,833 and 4981 nM, respectively. Oral administration of 5 and 10 mg/kg taxifolin for 30 min significantly inhibited rat liver HSD11B1 ex vivo and suppressed cortisone metabolism as shown by the significant increase of T1/2, Cmax, Tmax, and the area under curve (AUC) after exogenous injection of cortisone in vivo. This result shows that taxifolin is a potent inhibitor of both rat and human HSD11B1, being a possible supplement to treat the metabolic syndrome.

Leptin alleviates intestinal mucosal barrier injury and inflammation in obese mice with acute pancreatitis.

Obesity is an independent risk factor for severe acute pancreatitis (AP). Leptin plays an important role in energy homeostasis. It has been reported that leptin might also participate in the regulation of the intestinal mucosal barrier and inflammatory response. This study aimed to evaluate the effects of leptin on the intestinal mucosal barrier and inflammatory injury in obese mice with AP. AP was induced in leptin-deficient (ob/ob) or wild type (WT) mice by peritoneal injection of caerulein. The animals were divided into 4 groups: WT mice with or without exogenous leptin injection and ob/ob mice with or without leptin treatment. The inflammatory scoring of the pancreas and intestine were evaluated. Intestinal permeability, ileal interleukin (IL)-6 and IL-1β, proliferation, apoptosis and intestinal expression levels of claudin-1 and occludin were measured. Pancreatic pathologic scores (8.50 ± 0.96 vs. 3.78 ± 1.35, p < 0.001), pancreatic levels of IL-6 (8.34 ± 3.21 ng/mg vs. 4.99 ± 0.53 ng/mg, p = 0.022), intestinal oedema scores (2.25 ± 0.46 vs. 1.14 ± 0.69, p = 0.001) and intestinal permeability to FD4 (0.78 ± 0.06 μg/ml vs. 0.53 ± 0.11 μg/ml, p < 0.001) were significantly higher in ob/ob mice than those in WT mice. Leptin replacement in ob/ob mice greatly improved the intestinal permeability (FD4 0.66 ± 0.03 μg/ml, vs. 0.78 ± 0.06 μg/ml, p = 0.012), increased the ileal expression of claudin-1(1.07 ± 0.08 vs. 0.83 ± 0.07 relative densitometry, p = 0.001) and reduced intestinal IL-6 and IL-1β to levels comparable to those in WT mice. The pancreatic level of IL-6 in ob/ob mice treated with leptin was also significantly decreased relative to that of untreated ob/ob mice (4.45 ± 1.71 ng/mg vs. 8.34 ± 3.21 ng/mg, p = 0.010). Obesity may aggravate intestinal inflammation and increase intestinal permeability under the condition of acute pancreatitis. Exogenous leptin supplementation was in favour of anti-inflammation and improvement of intestinal mucosal barrier.

ANTI-INFLAMMATORY FACTOR DEL-1 PROTECTS FROM ANGIOTENSIN II-DEPENDENT VASCULAR REMODELING AND HYPERTENSION

Objective: Hypertension is the leading cause of mortality worldwide. Critical contributor to pathophysiology of hypertension is vascular remodeling, which is mediated by angiotensin II (ANGII) driven T-cell inflammation and production of interleukin 17 (IL-17). Thus, anti-inflammatory approaches have been proposed as a potential therapeutic strategy. We tested the role of an endogenous anti-inflammatory factor, developmental endothelial locus-1 (Del-1), in prevention of ANGII-induced vascular remodeling and hypertension. Design and method: Mice overexpressing endothelial Del-1 (Del1 Tg) and WT mice which were repetitively injected with soluble Del-1 (50 μg/per injection) were used. Hypertension and vascular remodeling were induced with ANGII infusion using osmotic minipumps (Alzet®) for 4-weeks. Systolic blood pressure (SBP) was measured via tail-cuff method. Aortic remodeling was assessed by quantification of adventitial fibrosis, elastin and medial thickness. Aortic inflammatory cells were quantified with flow cytometry, whereas endothelial dysfunction was assessed using Mulvany myography. Results: After 4-weeks of ANGII infusion, Del-1 Tg mice had lower (P < 0.01) SBP compared to WT littermates. Del-1 Tg mice had less (P < 0.01) aortic medial thickness, less adventitial collagen (P < 0.01) and more elastin (P < 0.01) area compared to WT mice. MMP2 activity was significantly (P < 0.01) less in Del-1 Tg mice than in WT. Endothelium-dependent relaxation of aorta was stronger (P < 0.01) in Del-1 Tg mice than in WT. Del-1 Tg mice had less (P < 0.05) CD45+ leukocytes, TCRβ+ T-cells, as well as CD4+ T-helper and CD8+ T-cytotoxic cells in aorta compared to WT mice. TCRβ+/IL-17+ double positive T-cell count was also less (P < 0.05) in Del-1 Tg than in WT mice. Injections of soluble Del-1 in WT completely protected from ANGII-induced development of hypertension and aortic remodeling. Del-1 injected mice had lower (P < 0.05) SBP compared to vehicle treated mice. Del-1 injections resulted in less aortic medial thickness (P < 0.05) and adventitial collagen area (P < 0.05), as well as lower MMP2 (P < 0.05) activity. Endothelium-dependent relaxation was stronger (P < 0.01) in Del-1 injected mice. Conclusions: Our findings demonstrate that Del-1 protects from ANGII-dependent development of hypertension and vascular remodeling via limitation of inflammation and maintaining of endothelial function. Its proof of efficacy via exogenous injections presents Del-1 as a potential therapeutic agent.