Leptin impairs the therapeutic efficacy of adipose-derived mesenchymal stem cells by inducing apoptosis through NLRP3 inflammasomes activation.

Mesenchymal stem cells (MSC) have been widely applied for regenerative medicine and the treatment of immune-disorders due to their multilineage differentiation and potent immunomodulatory properties. The therapeutic application of MSC post transplantation are influenced by various endogenous modulators. Leptin, a hormone primarily derived from adipose tissue, exerts a variety of physiological functions, in addition to the metabolic effects.

Discovery of novel theophylline derivatives bearing tetrazole scaffold for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is associated with AChE and BACE1 enzymes. Designing inhibitors for preventing these enzymes can be benefit for AD treatment. In this context, theophylline derivatives were generated to prevent the biological activity of AChE and BACE1.

NLRP3 inflammasome activation contributes to the development of the pro-fibrotic phenotype of lung fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is an irreversible progressive interstitial lung disease of unknown cause. The poorly understood pathophysiology of IPF poses substantial challenges to the development of effective anti-lung fibrotic drugs. The NLRP3 inflammasome, a key component of the innate immune system, has recently been linked to the pathogenesis of lung fibrosis.

Mimosa pudica L. extract ameliorates pulmonary fibrosis via modulation of MAPK signaling pathways and FOXO3 stabilization.

Ethnopharmacological Relevance: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing pulmonary disorder that has a poor prognosis and high mortality. Although there has been extensive effort to introduce several new anti-fibrotic agents in the past decade, IPF remains an incurable disease. Mimosa pudica L.

Adiponectin restores the obesity-induced impaired immunomodulatory function of mesenchymal stromal cells glycolytic reprogramming.

Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells (MSC). However, it remains unclear what drives the compromised potency of obese MSC. In this study, we examined the involvement of adiponectin, an adipose tissue-derived hormone, in obesity-induced impaired therapeutic function of MSC.

Liposomal co-delivery of toll-like receptors 3 and 7 agonists induce a hot triple-negative breast cancer immune environment.

Triple-negative breast cancer (TNBC) is highly aggressive and has no standard treatment. Although being considered as an alternative to conventional treatments for TNBC, immunotherapy has to deal with many challenges that hinder its efficacy, particularly the poor immunogenic condition of the tumor microenvironment (TME). Herein, we designed a liposomal nanoparticle (LN) platform that delivers simultaneously toll-like receptor 7 (imiquimod, IQ) and toll-like receptor 3 (poly(I:C), IC) agonists to take advantage of the different toll-like receptor (TLR) signaling pathways, which enhances the condition of TME from a "cold" to a "hot" immunogenic state.

Adipokines at the crossroads of obesity and mesenchymal stem cell therapy.

Mesenchymal stem cell (MSC) therapy is an emerging treatment strategy to counteract metabolic syndromes, including obesity and its comorbid disorders. However, its effectiveness is challenged by various factors in the obese environment that negatively impact MSC survival and function. The identification of these detrimental factors will provide opportunities to optimize MSC therapy for the treatment of obesity and its comorbidities.

Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation.

Immunomodulation is an essential consideration for cell replacement procedures. Unfortunately, lifelong exposure to nonspecific systemic immunosuppression results in immunodeficiency and has toxic effects on nonimmune cells. Here, we engineered hybrid spheroids of mesenchymal stem cells (MSCs) with rapamycin-releasing poly(lactic--glycolic acid) microparticles (RAP-MPs) to prevent immune rejection of islet xenografts in diabetic C57BL/6 mice.

Anti-inflammatory effect of a triterpenoid from : results of bioactivity-guided isolation.

, a medicinal plant traditionally used to treat fever, pain, and inflammation in Vietnam, has been reported to possess prominent anti-inflammatory activity. This study examined the active constituents and molecular mechanisms underlying these anti-inflammatory effects using bioactivity-guided isolation in combination with cell-based assays and animal models of inflammation. Among the isolated compounds, the triterpenoid (21α)-22-hydroxyhopan-3-one () showed the most potent inhibitory effect on COX-2 expression in LPS-stimulated Raw 264.

Mitophagy Induction and Aryl Hydrocarbon Receptor-Mediated Redox Signaling Contribute to the Suppression of Breast Cancer Cell Growth by Taloxifene Regulation of Inflammasomes Activation.

Raloxifene, a selective estrogen receptor (ER) modulator, has been reported to exert the tumor-suppressive effects in both ER-positive and ER-negative cancer cells; however, the mechanisms underlying its ER-independent anti-cancer effects are poorly understood. The NLRP3 inflammasome, a critical component of the innate immune system, has recently received growing attention owing to its multifaceted roles in various aspects of cancer development. The present study aimed at examining the involvement of NLRP3 inflammasomes in the anti-breast cancer effects of raloxifene and its underlying mechanisms.

Adiponectin triggers breast cancer cell death via fatty acid metabolic reprogramming.

Background: Adiponectin, the most abundant adipokine derived from adipose tissue, exhibits a potent suppressive effect on the growth of breast cancer cells; however, the underlying molecular mechanisms for this effect are not completely understood. Fatty acid metabolic reprogramming has recently been recognized as a crucial driver of cancer progression. Adiponectin demonstrates a wide range of metabolic activities for the modulation of lipid metabolism under physiological conditions.

Sestrin2 induction contributes to anti-inflammatory responses and cell survival by globular adiponectin in macrophages.

Adiponectin, an adipose tissue-derived hormone, exhibits a modulatory effect on cell death/survival and possesses potent anti-inflammatory properties. However, the underlying molecular mechanisms remain elusive. Sestrin2, a stress-inducible metabolic protein, has shown cytoprotective and inflammation-modulatory effects under stressful conditions.

Tumor Metabolic Reprogramming by Adipokines as a Critical Driver of Obesity-Associated Cancer Progression.

Adiposity is associated with an increased risk of various types of carcinoma. One of the plausible mechanisms underlying the tumor-promoting role of obesity is an aberrant secretion of adipokines, a group of hormones secreted from adipose tissue, which have exhibited both oncogenic and tumor-suppressing properties in an adipokine type- and context-dependent manner. Increasing evidence has indicated that these adipose tissue-derived hormones differentially modulate cancer cell-specific metabolism.

Autophagy activation and SREBP-1 induction contribute to fatty acid metabolic reprogramming by leptin in breast cancer cells.

Leptin, a hormone predominantly derived from adipose tissue, is well known to induce growth of breast cancer cells. However, its underlying mechanisms remain unclear. In this study, we examined the role of reprogramming of lipid metabolism and autophagy in leptin-induced growth of breast cancer cells.

Recent insights on modulation of inflammasomes by adipokines: a critical event for the pathogenesis of obesity and metabolism-associated diseases.

Aberrant production of adipokines, a group of adipocytes-derived hormones, is considered one of the most important pathological characteristics of obesity. In individuals with obesity, beneficial adipokines, such as adiponectin are downregulated, whereas leptin and other pro-inflammatory adipokines are highly upregulated. Hence, the imbalance in levels of these adipokines is thought to promote the development of obesity-linked complications.

Globular Adiponectin Inhibits Breast Cancer Cell Growth through Modulation of Inflammasome Activation: Critical Role of Sestrin2 and AMPK Signaling.

Adiponectin, an adipokine predominantly derived from adipose tissue, exhibits potent antitumor properties in breast cancer cells. However, its mechanisms of action remain elusive. Inflammasomes-intracellular multimeric protein complexes-modulate cancer cell growth in a complicated manner, as well as playing a role in the innate immune system.

Formulation and biopharmaceutical evaluation of supersaturatable self-nanoemulsifying drug delivery systems containing silymarin.

The first objective of this study was to optimize a supersaturatable self-nanoemulsifying drug delivery system (S-SNEDDS) containing silymarin through the investigation of the single and synergistic effect of either SNEDDS or a precipitation inhibitor on dissolution efficiency (DE) of silymarin. The bioavailability and hepatoprotective activity of S-SNEDDS were then compared to those of a branded product (Legalon®, Meda). SNEDDS containing silymarin was developed by titration technique, and Poloxamer 407 was selected as the optimal precipitation inhibitor by using casting film and solvent-shift method.

Xanthine oxidase inhibitors from Archidendron clypearia (Jack.) I.C. Nielsen: Results from systematic screening of Vietnamese medicinal plants.

Objective: To screen Vietnamese medicinal plants for xanthine oxidase (XO) inhibitory activity and to isolate XO inhibitor(s) from the most active plant.

Methods: The plants materials were extracted by methanol. The active plant materials were fractionated using different organic solvents, including n-hexane, ethyl acetate, and n-butanol.