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PPARγ activation ameliorates postoperative cognitive decline probably through suppressing hippocampal neuroinflammation in aged mice.

Neuroinflammation plays a key role in many neurodegenerative disorders, including postoperative cognitive decline (POCD). Growing evidence h … 1β, IBA1-positive cells, and GFAP-positive cells in the hippocampus. As expected, the PPARγ agonist pioglitazone attenuated the surgery-induced inflammatory changes and rescued the associated cognitive impairment. However, these beneficial effects were abolished by the PPARγ specific antagonist GW9662, suggesting a pivotal role of the PPARγ pathway in the path …

A clinical risk score for heart failure in patients with type 2 diabetes and macrovascular disease: an analysis of the PROactive study.

BACKGROUND: Diabetes mellitus is associated with a high risk for heart failure, which is further increased in the presence of coronary heart … eart rate, right and left bundle branch block, microalbuminuria, previous myocardial infarction and pioglitazone treatment were independent predictors of heart failure. The risk score showed a good calibration and moderate discrimination (AUC 0.75). Patients were accurately stratified with an actual risk of 1.0%, 3.2% and 9.7% in the bottom, middle and top ter …

Repurposing Drugs for Cancer Prevention.

Development of agents for cancer prevention has been particularly challenging for two main reasons. One is the inherent difficulty in identi … are the current focus of much interest in the field of cancer prevention - aspirin, metformin, and pioglitazone.

Разработка доклинической платформы человека для идентификации нетронутых охранных соединений.

Множественный склероз (MS) является наиболее распространенным воспалительным и демиелинизирующим заболеванием, влияющим на центральную нервную систему (КНС). В то время как иммуномодилизующие препараты могут предотвратить новые повреждения, реагируя на лимфоцитную активность, лечение не зависящих от рецидива заболеваний по-прежнему сопряжено с трудностями. Продолжительная воспаление CNS, приводящее к аксоновому и нейронному повреждению, а также к отсутствию компенсационных механизмов, таких, как пластичность мозга и воспаление, стимулирует развитие болезни. Таким образом, срочно необходимо иде

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is the most common inflammatory and demyelinating disease affecting the central nervous system (CNS). While immune-m … r mechanisms. Findings were validated in an acute cuprizone (CPZ) mouse model. We demonstrated that pioglitazone and minocycline protected against glutamate-induced axonal injury, rotenone-induced neuronal death and promoted oligodendrocyte differentiation. Proteomic analyses suggest that pioglitazone's neuroprotective effect may involve reducing mitochondrial …

Tumor cell derived osteopontin and prostaglandin E2 synergistically promote the expansion of myeloid derived suppressor cells during the tumor immune escape phase.

The immune escape stage in cancer immunoediting is a pivotal feature, transitioning immune-controlled tumor dormancy to progression, and aug … potentiated by the presence of OPN but not IL-17. Finally, in vitro treatment of EL4luc2 cells with pioglitazone, a modulator of OPN and cyclooxygenase 2 (COX-2) resulted in a significant reduction in cell proliferation in EL4luc2 cells. Our findings highlight the significant role played by tumor cell-derived OPN and PGE2 in fostering the expansion of medullar …

The downregulation of miR-129-5p relieves the inflammatory response in acute respiratory distress syndrome by regulating PPARγ-mediated autophagy.

BACKGROUND: The peroxisome proliferator-activated receptor γ (PPARγ) promotes autophagy and regulates the inflammatory response. However, the effects of the PPARγ on inflammation in acute respiratory distress syndrome (ARDS) are unclear. This study sought to explore the mechanism by which the downregulation of microRNA-129-5p (miR-129-5p) attenuates the inflammatory response in ARDS patients by regulating PPARγ-mediated autophagy. METHODS: Lipopolysaccharide (LPS) was used to establish an acute lung injury (ALI) mice model to simulate ARDS. GW9662 and pioglitazone were applied to inhibit and …

Role of activation of 5'-adenosine monophosphate-activated protein kinase in gastric ulcer healing in diabetic rats.

BACKGROUND: The potential utility of 5'-adenosine monophosphate-activated protein kinase (AMPK)-activating agents, such as metformin, in ind … in-injected rats treated with metformin or metformin and an inhibitor of AMPK, namely compound C or pioglitazone) for 7 days following acetic acid application. RESULTS: Administration of metformin, but not pioglitazone, resulted in a significant decrease in the gastric ulcer area, a significant increase in epithelial regeneration assessed histologically, a si …

[Glycemic control and cardiovascular benefit: What do we know today?].

It is still a much debated question whether antidiabetic therapy to target normal glycated hemoglobin levels would reduce cardiovascular eve … riod of 1 - 2 decades. For the first time, the cardiovascular benefit of an antidiabetic substance (pioglitazone) could be verified in the large-scale outcome-trial PROactive for patients with advanced diabetes and multiple manifestations of macroangiopathy. The results provide strong support for a beneficial influence on macrovascular complications just under …

Juanbi Lijieqing Decoction Inhibits TLR4/NF-κB Signaling Pathway by Promoting PPARγ Expression to Relieve Acute Gouty Arthritis.

INTRODUCTION: This study aimed to investigate the mechanism of Juanbi Lijieqing Decoction (JLD) in alleviating acute gouty arthritis (AGA) b … medium-dose group (Group D), the low-dose group (Group E), the etoricoxib group (Group F), and the pioglitazone group (Group G), with 12 rats per group. The acute gouty arthritis model was established by intraperitoneal injection of potassium oxonate, followed by monosodium urate (MSU) injection into the ankle joint, and then by pharmacological intervention i …

Treatment of Mitochondrial Diabetes with a Peroxisome Proliferator-activated Receptor (PPAR)-gamma Agonist.

The 3243 A>G mutation in mitochondrial DNA is the most common cause of monogenic diabetes mellitus in Japan. A 45-year-old woman with mitochondrial diabetes and significant insulin resistance presented with hypoadiponectinemia despite a normal amount of visceral fat. Three months of treatment with pioglitazone (PIO) improved her blood glucose profile and response to the 75-g oral glucose tolerance test. These changes were accompanied by the amelioration of her insulin resistance and the impairment of early-phase insulin secretion. Her serum adiponectin levels increased to the normal range. In …

EMPA-REG and Other Cardiovascular Outcome Trials of Glucose-lowering Agents: Implications for Future Treatment Strategies in Type 2 Diabetes Mellitus.

During the last decade, the armamentarium for glucose-lowering drugs has increased enormously by the development of DPP-4 inhibitors, GLP-1 … esistance Intervention after Stroke) study documented a significant reduction in stroke and MI when pioglitazone instead of placebo was given to nondiabetic patients presenting with both stroke/transient ischemic attack and insulin resistance, confirming results from the PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events) study in patie …

Observational studies on the association of outpatient antidiabetic medication use and COVID-19 outcomes: are the findings more relevant to diabetes management than to COVID-19 pathology? A mini-review.

At the start of the COVID-19 pandemic, there were concerns that some antidiabetic medications might worsen outcomes, though anti-inflammatory properties suggested possible benefits. Many observational studies examined antidiabetic medications use and COVID-19 outcomes. Meta-analyses showed that insulin was linked to worse outcomes, while metformin, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, and glucagon-like peptide-1 (GLP-1) agonists were associated with better outcomes. Findings on dipeptidyl peptidase-4 (DPP-4) inhibitors, pioglitazone, and sulfonylureas were mixed-showing neutral,…

Hepatoprotective effects of Shilajit on high fat-diet induced non-alcoholic fatty liver disease (NAFLD) in rats.

Background Non-alcoholic fatty liver disease (NAFLD) is the main common cause of chronic liver disease. The aim of this study is to evaluate the effect of Shilajit, a medicine of Ayurveda, on the liver damage caused by NAFLD. Materials and methods Forty male Wistar rats, after being established as fatty liver models by feeding a high-fat diet (HFD, 12 weeks), were divided randomly into five groups as follows: control (standard diet), vehicle (HFD + distilled water), high-dose Shilajit (HFD + 250 mg/kg Shilajit), low-dose Shilajit (HFD + 150 mg/kg Shilajit) and pioglitazone (HFD + 10 mg/kg piog…

Activation of PGC-1α and Mitochondrial Biogenesis Protects Against Prenatal Hypoxic-ischemic Brain Injury.

Survivals after prenatal hypoxia-ischemia (HI) usually suffer long-lasting cognitive defects. Reduced blood-oxygen supplies and the followin … HI induced both mitochondrial impairment and mitochondrial biogenesis. Postnatal administration of pioglitazone further promoted PGC-1α and mitochondrial biogenesis, alleviated hippocampal injury, and improved performance in the behavioral tasks after intrauterine HI. Our investigation implicated activation of PGC-1α, and mitochondrial biogenesis is a neuropr …

Role of Vitamin E for Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes: A Randomized Controlled Trial.

OBJECTIVE: While vitamin E has shown to improve nonalcoholic steatohepatitis (NASH) in patients without diabetes, information on patients with type 2 diabetes mellitus (T2DM) is lacking. The aim of this study was to determine whether vitamin E, alone or combined with pioglitazone, improves histology in patients with T2DM and NASH. RESEARCH DESIGN AND METHODS: This was a proof-of-concept, randomized, double-blind, placebo-controlled trial conducted from 2010 to 2016. Patients with T2DM and biopsy-proven NASH (n = 105) were randomized to vitamin E 400 IU b.i.d., vitamin E 400 IU b.i.d. plus pio…

Increased peroxisome proliferator-activated receptor γ activity reduces imatinib uptake and efficacy in chronic myeloid leukemia mononuclear cells.

Imatinib is actively transported by organic cation transporter-1 (OCT-1) influx transporter, and low OCT-1 activity in diagnostic chronic myeloid leukemia blood mononuclear cells is significantly associated with poor molecular response to imatinib. Herein we report that, in diagnostic chronic myeloid leukemia mononuclear cells and BCR-ABL1+ cell lines, peroxisome proliferator-activated receptor γ agonists (GW1929, rosiglitazone, pioglitazone) significantly decrease OCT-1 activity; conversely, peroxisome proliferator-activated receptor γ antagonists (GW9662, T0070907) increase OCT-1 activity. I…

Case Report: The long-term effects of the empagliflozin therapy on glycemia and renal function in a patient with Rabson-Mendenhall syndrome caused by two heterozygous variants in INSR gene.

We present a patient with Rabson-Mendenhall syndrome with unsatisfactory glycemic control of diabetes despite the use of metformin, pioglitazone, and sitagliptin. We investigated the long-term effects of treatment with an empagliflozin. After one year of empagliflozin therapy, an improvement in metabolic control of diabetes was detected. However, eleven months after implementation of empagliflozin, the patient was diagnosed with an early form of nephrocalcinosis. The empagliflozin dose was reduced, maintaining metabolic control and reducing hypercalciuria. We discuss the probable causes of nep…

Novel PIK3R1 mutation of SHORT syndrome: A case report with a 6-month follow up.

SHORT syndrome (short stature, hyperextensibility, ocular depression [deeply set eyes], Rieger anomaly and teething delay) is very rare, with a few cases reported in the literature. We report a case of SHORT syndrome with a novel PIK3R1 mutation (c.2008delT) and complicated with severe insulin resistance. Although no treatment guidelines are available to relieve insulin resistance in SHORT syndrome, our treatment plans, including lifestyle intervention combined with metformin and pioglitazone, were carried out for this patient. After the intervention, insulin resistance and hyperinsulinemia in…

Stress-coping phenotypes shape adipose tissue function and plasticity and modulate metabolic resilience.

Our previous findings demonstrated that stress resilience confers metabolic protection in high-fat diet (HFD)-fed mice. Recognizing the central role of adipose tissue in the pathogenesis of obesity comorbidities, this study aimed to define how stress resilience shapes adipose tissue function. Stress-resilient (Dominant, Dom) and stress-vulnerable (Submissive, Sub) mice were examined under standard (STD) or HFD. Metabolic, molecular, and transcriptomic analyses were performed in epididymal and inguinal white adipose tissue (eWAT and iWAT), and the effects of PPARgamma activator (pioglitazone) a…