Glycine tomentella hayata extract and its ingredient daidzin ameliorate cyclophosphamide-induced hemorrhagic cystitis and oxidative stress through the action of antioxidation, anti-fibrosis, and anti-inflammation.

We explored the therapeutic potential of intragastric administration of traditional Chinese medicine Glycine tomentella Hayata (I-Tiao-Gung [ITG]) extract and its major component Daidzin on cyclophosphamide (CYP)-induced cystitis, oxidative stress, fibrosis, inflammation, and bladder hyperactivity in rats. Female Wistar rats were divided into control, CYP (200 mg/kg), CYP+ITG (1.17 g/kg/day), and CYP+Daidzin (12.5 mg/kg/day) groups. We measured the voiding function by the transcystometrogram and evaluated the pathology with the hematoxylin and eosin and Masson stain. We determined the bladder reactive oxygen species (ROS) amount by an ultrasensitive chemiluminescence analyzer, the expression of 3-nitrotyrosine (3-NT) and NADPH oxidase 4 (NOX4) by Western blot and the expression of multiple cytokine profiles, including matrix metalloproteinase (MMP)-8 and tissue inhibitor of metalloproteinase (TIMP)-1 through a cytokine array. ITG extract contains 1.07% of Daidzin through high-performance liquid chromatography. The effect of ITG extract and Daidzin in scavenging hydrogen peroxide activity was more efficient than distilled water. CYP-induced higher urination frequency, shorter intercontraction interval, and lower maximal voiding pressure in the bladders and these symptoms were significantly ameliorated in CYP+ITG and CYP+Daidzin groups. The amount of in vivo bladder ROS and the expression of 3-NT and NOX4 expressions were significantly increased in CYP group but were efficiently decreased in the CYP+ITG and CYP+Daidzin groups. CYP-induced fibrosis, hemorrhage, leukocyte infiltration, and edema in the bladders were significantly attenuated in the CYP+ITG and CYP+Daidzin groups. These results suggested that ITG extract and its active component Daidzin effectively improved CYP-induced oxidative stress, inflammation, and fibrosis through inhibiting the MMP-8, TIMP-1, and oxidative stress.

Abdominal obesity validates the association between elevated alanine aminotransferase and newly diagnosed diabetes mellitus.

To examine how elevated alanine aminotransferase (ALT) could be associated with newly diagnosed diabetes mellitus. We conducted a cross-sectional analysis on a mass health examination. The odds ratios (ORs) for diabetes mellitus and newly diagnosed diabetes mellitus were compared between people with and without abdominal obesity, together with and without elevated ALT levels. 5499 people were included in this study. Two hundred fifty two (4.6%) fulfilled the diagnosis of diabetes mellitus with 178 (3.2%) undiagnosed before. Metabolic syndrome was vigorously associated with diabetes mellitus and newly diagnosed diabetes mellitus (12.4% vs. 1.4% and 9.0% vs. 0.9%), but elevated ALT alone was not. However, coexisting with obesity, elevated ALTs were robustly associated with diabetes mellitus and newly diagnosed diabetes mellitus. For the incidence of newly diagnosed diabetes mellitus, in comparison to non-obese people with normal ALT (1.7%, OR = 1), obese people especially with elevated ALT levels had significantly higher ORs (obese with ALT ≤ 40 U/L: 4.7%, OR 1.73, 95% CI 1.08-2.77, P 0.023; ALT 41-80 U/L: 6.8%, OR 2.06, 95% CI 1.20-3.55, P 0.009; ALT 81-120 U/L: 8.8%, OR 3.07, 95% CI 1.38-6.84, P 0.006; ALT > 120 U/L: 18.2%, OR 7.44, 95% CI 3.04-18.18, P < 0.001). Abdominal obesity validates the association between elevated alanine aminotransferase and diabetes mellitus and newly diagnosed diabetes mellitus. People with abdominal obesity, especially with coexisting elevated ALT levels should be screened for undiagnosed diabetes mellitus.

Intrarenal Arterial Transplantation of Dexmedetomidine Preconditioning Adipose Stem-Cell-Derived Microvesicles Confers Further Therapeutic Potential to Attenuate Renal Ischemia/Reperfusion Injury through miR-122-5p/Erythropoietin/Apoptosis Axis.

Intravenous adipose mesenchymal stem cells (ADSCs) attenuate renal ischemia/reperfusion (IR) injury but with major drawbacks, including the lack of a specific homing effect after systemic infusion, cell trapping in the lung, and early cell death in the damaged microenvironment. We examined whether intrarenal arterial transplantation of dexmedetomidine (DEX) preconditioning ADSC-derived microvesicles (DEX-MVs) could promote further therapeutic potential to reduce renal IR injury. We evaluated the effect of DEX-MVs on NRK-52E cells migration, hypoxia/reoxygenation (H/R)-induced cell death, and reactive oxygen species (ROS) amount and renal IR model in rats. IR was established by bilateral 45 min ischemia followed by 4 h reperfusion. Intrarenal MVs or DEX-MVs were administered prior to ischemia. Renal oxidative stress, hemodynamics and function, western blot, immunohistochemistry, and tubular injury scores were determined. The miR-122-5p expression in kidneys was analyzed using microarrays and quantitative RT-PCR and its action target was predicted by TargetScan. DEX-MVs were more efficient than MVs to increase migration capability and to further decrease H/R-induced cell death and ROS level in NRK-52E cells. Consistently, DEX-MVs were better than MV in increasing CD44 expression, improving IR-depressed renal hemodynamics and renal erythropoietin expression, inhibiting IR-enhanced renal ROS level, tubular injury score, miR-122-5p expression, pNF-κB expression, Bax/caspase 3/poly(ADP-ribose) polymerase (PARP)-mediated apoptosis, blood urea nitrogen, and creatinine levels. The use of NRK-52E cells confirmed that miR-122-5p mimic via inhibiting erythropoietin expression exacerbated Bax-mediated apoptosis, whereas miR-122-5p inhibitor via upregulating erythropoietin and Bcl-2 expression reduced apoptosis. In summary, intrarenal arterial DEX-MV conferred further therapeutic potential to reduce renal IR injury through the miR-122-5p/erythropoietin/apoptosis axis.

L-Theanine-Treated Adipose-Derived Mesenchymal Stem Cells Alleviate the Cytotoxicity Induced by N-Nitrosodiethylamine in Liver.

BACKGROUND: Liver inflammation is the main cause of severe liver diseases, including liver fibrosis, steatohepatitis, cirrhosis and hepatocellular carcinoma. Cell therapy topics are receiving increasingly more attention. The therapeutic applications of mesenchymal stem cells (MSC) have become one of the most discussed issues. While other stem cells have therapeutic effects, they have only one or two clinical applications. MSCs are responsible for repairing a variety of tissue injuries. Moreover, MSCs could be derived from several sources, including adipose tissue. MSCs are usually more abundant and easier to obtain compared to other stem cells. METHODS: To prove the concept that MSCs have homing ability to the injured tissue and assist in tissue repair, we examined the effects of intravenous injected adipose-derived mesenchymal stem cells (ADSCs) in a N-nitrosodiethylamine (DEN)-induced liver injury rat model. RESULTS: The significant repairing ability of ADSCs was observed. The levels of fibrosis, apoptosis, and tumorigenesis in the DEN-injured liver tissues all decreased after ADSC treatment. Furthermore, to enhance the therapeutic effects of ADSCs, we pretreated them with L-theanine, which promotes the hepatocyte growth factor secretion of ADSC, and therefore improved the healing effects on injured liver tissue. CONCLUSION: ADSCs, especially L-theanine-pretreated ADSCs, have anti-inflammation, anti-apoptosis, and anti-tumorigenesis effects on the N-nitrosodiethylamine-induced liver injury rat model.

Negative air ions through the action of antioxidation, anti-inflammation, anti-apoptosis and angiogenesis ameliorate lipopolysaccharide induced acute lung injury and promote diabetic wound healing in rat.

Negative air ions (NAIs) being bioactive and negative charged molecules may confer antioxidant and anti-inflammatory activity. We assessed the effect of NAIs on two inflammatory diseases in animal models including lipopolysaccharide (LPS) induced acute lung injury (ALI) and wound healing in diabetic rats. We used intra-tracheal infusion of LPS to induce ALI and made a full-thickness cutaneous wound in streptozotocin-induced diabetic female Wistar rats. We evaluated NAIs effects on reactive oxygen species amount, leukocyte infiltration, wound healing rate, western blot, and immunohistochemistry in the lungs of ALI and skin sections of wounds. Our data found NAIs exposed saline displayed higher antioxidant activity vs. non-exposed saline. NAIs exposure did not significantly affect arterial blood pressure and respiratory frequency in control and LPS treated groups. LPS increased leukocyte infiltration, caspase 3/Poly-ADP-ribose-polymerase-mediated apoptosis formation and decreased Beclin-1/LC3-II-mediated autophagy in lungs. NAIs exposure conferred pulmonary protection by depressed leukocyte infiltration and caspase 3/Poly-ADP-ribose-polymerase mediated apoptosis and enhanced LC3-II-mediated autophagy in LPS induced ALI. NAIs treatment resulted in a significantly accelerated wound closure rate, decreased erythrocyte accumulation and leukocyte infiltration mediated oxidative stress and inflammation, and upregulated expression of skin collagen, vascular endothelial growth factor receptor-2 (VEGFR-2) and factor transforming growth factor-beta 1 (TGF-ß1) vs non-treated group. Based on these results, it is suggested that NAIs conferred a protection through the upregulating LC3-II-dependent autophagy mechanism and downregulating leukocyte infiltration mediated inflammation and caspase 3/Poly-ADP-ribose-polymerase signaling in the LPS-treated ALI and promoted diabetic wound healing through the enhancing skin collagen synthesis, VEGFR-2 and TGF-ß1 pathways.

Smoking Cessation Carries a Short-Term Rising Risk for Newly Diagnosed Diabetes Mellitus Independently of Weight Gain: A 6-Year Retrospective Cohort Study.

Background. The effects of smoking on human metabolism are complex. Although smoking increases risk for diabetes mellitus, smoking cessation was also reported to be associated with weight gain and incident diabetes mellitus. We therefore conducted this study to clarify the association between smoking status and newly diagnosed diabetes mellitus. Methods. An analysis was done using the data of a mass health examination performed annually in an industrial park from 2007 to 2013. The association between smoking status and newly diagnosed diabetes mellitus was analyzed with adjustment for weight gain and other potential confounders. Results. Compared with never-smokers, not only current smokers but also ex-smokers in their first two years of abstinence had higher odds ratios (ORs) for newly diagnosed diabetes mellitus (never-smokers 3.6%, OR as 1; current smokers 5.5%, OR = 1.499, 95% CI = 1.147-1.960, and p = 0.003; ex-smokers in their first year of abstinence 7.5%, OR = 1.829, 95% CI = 0.906-3.694, and p = 0.092; and ex-smokers in their second year of abstinence 9.0%, OR = 2.020, 95% CI = 1.031-3.955, and p = 0.040). Conclusion. Smoking cessation generally decreased risk for newly diagnosed diabetes mellitus. However, increased odds were seen within the first 2 years of abstinence independently of weight gain.