Treadmill intervention attenuates motor deficit with 6-OHDA-induced Parkinson's disease rat via changes in lipid profiles in brain and muscle.

One of the key hallmarks of Parkinson's disease is the disruption of lipid homeostasis in the brain, which plays a critical role in neuronal membrane integrity and function. Understanding how treadmill training impacts lipid restructuring and its subsequent influence on motor function could provide a basis for developing targeted non-pharmacological interventions for individuals living with early stage of PD. This study aims to investigate the effects of a treadmill training intervention on motor deficits induced by 6-OHDA in rats model of PD.

Rationally designed febuxostat-based hydroxamic acid and its pH-Responsive nanoformulation elicits anti-tumor activity.

Attempts to furnish antitumor structural templates that can prevent the occurrence of drug-induced hyperuricemia spurred us to generate xanthine oxidase inhibitor-based hydroxamic acids and anilides. Specifically, the design strategy involved the insertion of febuxostat (xanthine oxidase inhibitor) as a surface recognition part of the HDAC inhibitor pharmacophore model. Investigation outcomes revealed that hydroxamic acid 4 elicited remarkable antileukemic effects mediated via HDAC isoform inhibition.

Supplementation with subsp. MH-022 for remission of motor impairments in a 6-OHDA-induced Parkinson's disease rat model by reducing inflammation, reshaping the gut microbiome, and fostering specific microbial taxa.

Inflammation significantly influences the degeneration of dopaminergic neurons in Parkinson's disease (PD), which is potentially intensified by associated gut dysbiosis. The therapeutic potential of probiotics, due to their antioxidant, anti-inflammatory, and gut microbiota modulatory properties, is explored herein as a means to improve gut health and influence the gut-brain-microbiota axis in the context of PD. In this study, we investigated the role and possible mechanism of subsp.

Leveraging a rationally designed veliparib-based anilide eliciting anti-leukemic effects for the design of pH-responsive polymer nanoformulation.

Careful recruitment of the components of the HDAC inhibitory template culminated in veliparib-based anilide 8 that elicited remarkable cell growth inhibitory effects against HL-60 cell lines mediated via dual modulation of PARP [(IC (PARP1) = 0.02 nM) and IC (PARP2) = 1 nM)] and HDACs (IC value = 0.05, 0.

Small molecule tractable PARP inhibitors: Scaffold construction approaches, mechanistic insights and structure activity relationship.

Diverse drug design strategies viz. molecular hybridization, substituent installation, scaffold hopping, isosteric replacement, high-throughput screening, induction and separation of chirality, structure modifications of phytoconstituents and use of structural templates have been exhaustively leveraged in the last decade to load the chemical toolbox of PARP inhibitors. Resultantly, numerous promising scaffolds have been pinpointed that in turn have led to the resuscitation of the credence to PARP inhibitors as cancer therapeutics.

Prudent tactics to sail the boat of PARP inhibitors as therapeutics for diverse malignancies.

Introduction: PARP inhibitors block the DNA-repairing mechanism of PARP and represent a promising class of anti-cancer therapy. The last decade has witnessed FDA approvals of several PARP inhibitors, with some undergoing advanced-stage clinical investigation. Medicinal chemists have invested much effort to expand the structure pool of PARP inhibitors.

Mangosteen Pericarp Extract Supplementation Boosts Antioxidant Status via Rebuilding Gut Microbiota to Attenuate Motor Deficit in 6-OHDA-Induced Parkinson's Disease.

Oxidative stress and gut dysbiosis have been known to precede Parkinson's disease (PD). An antioxidant-rich product, mangosteen pericarp (MP), has the ability to counterbalance excessive free radicals and the imbalanced gut microbiota composition, suggesting the MP's capacity to delay PD progression. In this study, we explored the effects of two doses of MP extract in a unilateral 6-hydroxydopamine (6-OHDA)-induced PD rat model.

and Extracts Improved Lipid Metabolism and Inflammation in High-Energy Diet-Induced Hyperlipidemia Rats.

and both contain unique polyphenols called phlorotannins. Phlorotannins reportedly possess various pharmacological activities. A previous study reported that the activity of phlorotannin is strongly correlated with the normalization of metabolic function, and phlorotannins are extremely promising nutrients for use in the treatment of metabolic syndrome.

Accommodation of ring C expanded deoxyvasicinone in the HDAC inhibitory pharmacophore culminates into a tractable anti-lung cancer agent and pH-responsive nanocarrier.

A fragment recruitment process was conducted to pinpoint a suitable fragment for installation in the HDAC inhibitory template to furnish agents endowed with the potential to treat lung cancer. Resultantly, Ring C expanded deoxyvasicinone was selected as an appropriate surface recognition part that was accommodated in the HDAC three-component model. Delightfully, fused quinazolinone 6 demonstrating a magnificent anticancer profile against KRAS and EGFR mutant lung cancer cell lines (IC = 0.

Probiotic supplementation attenuates age-related sarcopenia via the gut-muscle axis in SAMP8 mice.

Background: Age-related muscle dysfunctions are common disorders resulting in poor quality of life in the elderly. Probiotic supplementation is a potential strategy for preventing age-related sarcopenia as evidence suggests that probiotics can enhance muscle function via the gut-muscle axis. However, the effects and mechanisms of probiotics in age-related sarcopenia are currently unknown.

The immunomodulatory effects of long-term supplementation with Lactobacillus casei Shirota depend on ovalbumin presentation in BALB/c mice.

Immunomodulation is an ability of several particular probiotics. However, it still remains unclear whether the immunomodulatory effects of specific probiotics vary for different antigen presentation models with the same antigen. To investigate this matter, six groups of BALB/c mice (n = 10) were exposed to one of two antigen presentation models: ovalbumin (OVA) by injection alone, or injection plus intranasal administration.

Pathological Role of Phosphoglycerate Kinase 1 in Balloon Angioplasty-Induced Neointima Formation.

Restenosis is a common vascular complication after balloon angioplasty. Catheter balloon inflation-induced transient ischemia (hypoxia) of local arterial tissues plays a pathological role in neointima formation. Phosphoglycerate kinase 1 (PGK1), an adenosine triphosphate (ATP)-generating glycolytic enzyme, has been reported to associate with cell survival and can be triggered under hypoxia.

Preventive Effect and Mechanism of Extract on Balloon Angioplasty-Induced Neointimal Hyperplasia.

Balloon angioplasty-induced neointimal hyperplasia remains a clinical problem that must be resolved. The bioactivities of the extract (CCE) have demonstrated potential in preventing the progression of restenosis. The present study evaluated whether CCE can suppress balloon angioplasty-induced neointima formation and elucidated its possible pharmacological mechanisms.

PS23 Effectively Modulates Gut Microbiota Composition and Improves Gastrointestinal Function in Aged SAMP8 Mice.

Probiotics are reported to improve gastrointestinal (GI) function via regulating gut microbiota (GM). However, exactly how probiotics influence GM and GI function in elders is poorly characterized. Therefore, in this study, we assessed the effect of the probiotic PS23 (LPPS23) on the GM and GI function of aged mice.

Sclareol ameliorated ERCC1-mediated cisplatin resistance in A549 human lung adenocarcinoma cells and a murine xenograft tumor model by suppressing AKT-GSK3β-AP1/Snail and JNK-AP1 pathways.

Cisplatin-based chemotherapy is a common first-line regimen for treating non-small cell lung cancer (NSCLC). However, drug resistance is still a major problem. The purposes of this study were to evaluate whether sclareol can reverse cisplatin resistance and to investigate its possible mechanisms.

Edible Mushrooms: Novel Medicinal Agents to Combat Metabolic Syndrome and Associated Diseases.

Metabolic syndrome is an aggregation of conditions and associated with an increased risk of developing diabetes, obesity and cardiovascular diseases (CVD). Edible mushrooms are widely consumed in many countries and are valuable components of the diet because of their attractive taste, aroma, and nutritional value. Medicinal mushrooms are higher fungi with additional nutraceutical attributes having low-fat content and a transisomer of unsaturated fatty acids along with high fiber content, biologically active compounds such as polysaccharides or polysaccharide β-glucans, alkaloids, steroids, polyphenols and terpenoids.

PS128 Improves Physiological Adaptation and Performance in Triathletes through Gut Microbiota Modulation.

A triathlon is an extremely high-intensity exercise and a challenge for physiological adaptation. A triathlete's microbiome might be modulated by diet, age, medical treatments, lifestyle, and exercise, thereby maintaining aerobiosis and optimum health and performance. Probiotics, prebiotics, and synbiotics have been reported to have health-promoting activities (e.

Oxidative stress-induced cellular senescence desensitizes cell growth and migration of vascular smooth muscle cells through down-regulation of platelet-derived growth factor receptor-beta.

The relationship between aging and restenosis are unclear. The purposes of this study were to investigate the possible pathological role and mechanism of aging on formation of restenosis. Our data indicated that cell proliferation and migration of the oxidative stress-induced senescent vascular smooth muscle cells were obviously desensitized to stimulation by platelet-derived growth factor (PDGF)-BB, which may have been caused by suppression of promoter activity, transcription, translation, and activation levels of PDGF receptor (PDGFR)-β.

Suppression of Cell Growth, Migration and Drug Resistance by Ethanolic Extract of Antrodia cinnamomea in Human Lung Cancer A549 Cells and C57BL/6J Allograft Tumor Model.

The purpose of this study was to investigate the inhibitory activities of ethanolic extracts from (EEAC) on lung cancer. Cell proliferation and cell cycle distribution were analyzed using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay and flow cytometry, respectively. Wound-healing assay, Western blotting, and a murine tumor model were separately used to examine cell migration, protein expression, and tumor repression.

Suppressive activities and mechanisms of ugonin J on vascular smooth muscle cells and balloon angioplasty-induced neointimal hyperplasia.

Neointimal hyperplasia (or restenosis) is primarily attributed to excessive proliferation and migration of vascular smooth muscle cells (VSMCs). In this study, we investigated the inhibitory effects and mechanisms of ugonin J on VSMC proliferation and migration as well as neointimal formation. Cell viability and the cell-cycle distribution were, respectively, analyzed using an MTT assay and flow cytometry.

Toxicological effects of NCKU-21, a phenanthrene derivative, on cell growth and migration of A549 and CL1-5 human lung adenocarcinoma cells.

Background: Chemotherapy insensitivity continues to pose significant challenges for treating non-small cell lung cancer (NSCLC). The purposes of this study were to investigate whether 3,6-dimethoxy-1,4,5,8-phenanthrenetetraone (NCKU-21) has potential activity to induce effective toxicological effects in different ethnic NSCLC cell lines, A549 and CL1-5 cells, and to examine its anticancer mechanisms.

Methods: Mitochondrial metabolic activity and the cell-cycle distribution were analyzed using an MTT assay and flow cytometry in NCKU-21-treated cells.

Methyl Protodioscin, a Steroidal Saponin, Inhibits Neointima Formation in Vitro and in Vivo.

Restenosis (or neointimal hyperplasia) remains a clinical limitation of percutaneous coronary angioplasty. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are known to be involved in the development of restenosis. The present study aimed to investigate the ability and molecular mechanisms of methyl protodioscin (1), a steroidal saponin isolated from the root of Dioscorea nipponica, to inhibit neointimal formation.

Anti-Restenotic Roles of Dihydroaustrasulfone Alcohol Involved in Inhibiting PDGF-BB-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells.

Dihydroaustrasulfone alcohol (DA), an active compound firstly isolated from marine corals, has been reported to reveal anti-cancer and anti-inflammation activities. These reported activities of DA raised a possible application in anti-restenosis. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) and the stimulation of platelet-derived growth factor (PDGF)-BB play major pathological processes involved in the development of restenosis.