METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry.
RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores.
INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.
METHODS: Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent 1H-cardiovascular magnetic resonance spectroscopy (1H-CMRS) to measure MTG (lipid/water, %), 31P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.
RESULTS: When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45 ± 0.25% vs. 0.64 ± 0.16%, p = 0.009) and reduced PCr/ATP (1.60 ± 0.09 vs. 2.00 ± 0.10, p = 0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO2 max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO2 max.
CONCLUSIONS: Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.
METHODS: In this study, anti-diabetic effect of ML extract is investigated in vivo to evaluate the biochemical changes, potential serum biomarkers and alterations in metabolic pathways pertaining to the treatment of HFD/STZ induced diabetic rats with ML extract using 1H NMR based metabolomics approach. Type 2 diabetic rats were treated with different doses (200 and 400 mg/kg BW) of Melicope lunu-ankenda leaf extract for 8 weeks, and serum samples were examined for clinical biochemistry. The metabolomics study of serum was also carried out using 1H NMR spectroscopy in combination with multivariate data analysis to explore differentiating serum metabolites and altered metabolic pathways.
RESULTS: The ML leaf extract (400 mg/kg BW) treatment significantly increased insulin level and insulin sensitivity of obese diabetic rats, with concomitant decrease in glucose level and insulin resistance. Significant reduction in total triglyceride, cholesterol and low density lipoprotein was also observed after treatment. Interestingly, there was a significant increase in high density lipoprotein of the treated rats. A decrease in renal injury markers and activities of liver enzymes was also observed. Moreover, metabolomics studies clearly demonstrated that, ML extract significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism, and amino acid metabolism.
CONCLUSION: ML leaf extract exhibits potent antidiabetic properties, hence could be a useful and affordable alternative option for the management of T2DM.
MATERIALS AND METHODS: In this study, we focus on two important drugs used for TB treatment - rifampicin (RIF) and isoniazid (INH) - and report a detailed study of RIF-loaded poly lactic-co-glycolic acid (PLGA) NPs and INH modified as INH benz-hydrazone (IH2) which gives the same therapeutic effect as INH but is more stable and enhances the drug loading in PLGA NPs by 15-fold compared to INH. The optimized formulation was characterized using particle size analyzer, scanning electron microscopy and transmission electron microscopy. The drug release from NPs and stability of drug were tested in different pH conditions.
RESULTS: It was found that RIF and IH2 loaded in NPs release in a slow and sustained manner over a period of 1 month and they are more stable in NPs formulation compared to the free form. RIF- and IH2-loaded NPs were tested for antimicrobial susceptibility against Mycobacterium tuberculosis H37Rv strain. RIF loaded in PLGA NPs consistently inhibited the growth at 70% of the minimum inhibitory concentration (MIC) of pure RIF (MIC level 1 µg/mL), and pure IH2 and IH2-loaded NPs showed inhibition at MIC equivalent to the MIC of INH (0.1 µg/mL).
CONCLUSION: These results show that NP formulations will improve the efficacy of drug delivery for TB treatment.
METHODS: Four different solvent extracts of OS, namely aqueous, ethanolic, 50% aqueous ethanolic and methanolic, at a dose of 500 mg/kg body weight (bw) were orally administered for 14 days to diabetic rats induced via intraperitoneal injection of 60 mg/kg bw STZ. NMR metabolomics approach using pattern recognition combined with multivariate statistical analysis was applied in the rat urine to study the resulted metabolic perturbations.
RESULTS: OS aqueous extract (OSAE) caused a reversal of DM comparable to that of 10 mg/kg bw glibenclamide. A total of 15 urinary metabolites, which levels changed significantly upon treatment were identified as the biomarkers of OSAE in diabetes. A systematic metabolic pathways analysis identified that OSAE contributed to the antidiabetic activity mainly through regulating the tricarboxylic acid cycle, glycolysis/gluconeogenesis, lipid and amino acid metabolism.
CONCLUSIONS: The results of this study validated the ethnopharmacological use of OS in diabetes and unveiled the biochemical and metabolic mechanisms involved.