METHODS: We therefore conducted a cluster analysis of the Autism Diagnostic Interview-Revised (ADI-R) scores from 85 individuals with ASD to predict subgroups and subsequently identified dysregulated genes by reanalyzing the transcriptome profiles of individuals with ASD and unaffected individuals. Proteome profiling of lymphoblastoid cell lines from these individuals was performed via 2D-gel electrophoresis, and then mass spectrometry. Disrupted proteins were identified and compared to the dysregulated transcripts and reported dysregulated proteins from previous proteome studies. Biological functions were predicted using the Ingenuity Pathway Analysis (IPA) program. Selected proteins were also analyzed by Western blotting.
RESULTS: The cluster analysis of ADI-R data revealed four ASD subgroups, including ASD with severe language impairment, and transcriptome profiling identified dysregulated genes in each subgroup. Screening via proteome analysis revealed 82 altered proteins in the ASD subgroup with severe language impairment. Eighteen of these proteins were further identified by nano-LC-MS/MS. Among these proteins, fourteen were predicted by IPA to be associated with neurological functions and inflammation. Among these proteins, diazepam-binding inhibitor (DBI) protein was confirmed by Western blot analysis to be expressed at significantly decreased levels in the ASD subgroup with severe language impairment, and the DBI expression levels were correlated with the scores of several ADI-R items.
CONCLUSIONS: By subgrouping individuals with ASD based on clinical phenotypes, and then performing an integrated transcriptome-proteome analysis, we identified DBI as a novel candidate protein for ASD with severe language impairment. The mechanisms of this protein and its potential use as an ASD biomarker warrant further study.
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.
MATERIALS & METHODS: A total of 50 participants with T2DM with peripheral neuropathy were included. Age group of 30-75 years were selected for the study. Participants with a known history of neurological disease, locomotor disability, and pregnancy were excluded from the study. Demographic details of the participants like duration of diabetes mellitus, age, Fasting Blood Glucose, Fasting Insulin, HOMA-IR, Glycated Haemoglobin (HBA1c), Neuropathy and Blood pressure values were noted. We measured Basal Metabolic Rate (BMR) by using Mifflin-St Jeor predictive equation in T2DM with peripheral neuropathy.
RESULTS: The mean age of the participants is 60.16 ± 10.62. The mean duration of T2DM 13.44 ± 11.92. In the present study we found a statistical significant correlation between BMR and HOMA IR (r = 0.913*; p = 0.000), BMR & Fasting blood sugar (FBS) (r = 0.281*; p = 0.048), BMR and Visceral fat (VF) (r = 0.332*; p = 0.018).
CONCLUSION: Basal metabolic rate is correlated to Homa-IR, visceral fat, fasting blood sugar and musculoskeletal mass among T2DM with peripheral neuropathy.
MATERIAL AND METHODS: Forty-eight subjects (23 complicated mTBI [cmTBI] patients, 12 uncomplicated mTBI [umTBI] patients, and 13 controls) underwent magnetic resonance imaging scan with additional single voxel spectroscopy sequence. Magnetic resonance imaging scans for patients were done at an average of 10 hours (standard deviation 4.26) post injury. The single voxel spectroscopy adjacent to side of injury and noninjury regions were analysed to obtain absolute concentrations and ratio relative to creatine of the neurometabolites. One-way analysis of variance was performed to compare neurometabolite concentrations of the three groups, and a correlation study was done between the neurometabolite concentration and Glasgow Coma Scale.
RESULTS: Significant difference was found in ratio of N-acetylaspartate to creatine (NAA/Cr + PCr) (χ2(2) = 0.22, P
MATERIALS AND METHODS: We identified differentially expressed mitochondrial proteins in 50 infertile men with varicocele and in 10 fertile controls by secondary liquid chromatography-tandem mass spectroscopy data driven in silico analysis. Identified proteins were validated by Western blot and immunofluorescence. Seminal oxidation-reduction potential was measured.
RESULTS: We identified 22 differentially expressed proteins related to mitochondrial structure (LETM1, EFHC, MIC60, PGAM5, ISOC2 and import TOM22) and function (NDFSU1, UQCRC2 and COX5B, and the core enzymes of carbohydrate and lipid metabolism). Cluster analysis and 3-dimensional principal component analysis revealed a significant difference between the groups. All proteins studied were under expressed in infertile men with varicocele. Liquid chromatography-tandem mass spectroscopy data were corroborated by Western blot and immunofluorescence. Impaired mitochondrial function was associated with decreased expression of the proteins (ATPase1A4, HSPA2, SPA17 and APOA1) responsible for proper sperm function, concomitant with elevated seminal oxidation-reduction potential in the semen of infertile patients with varicocele.
CONCLUSIONS: Impaired mitochondrial structure and function in varicocele may lead to oxidative stress, reduced ATP synthesis and sperm dysfunction. Mitochondrial differentially expressed proteins should be explored for the development of biomarkers as a predictor of infertility in patients with varicocele. Antioxidant therapy targeting sperm mitochondria may help improve the fertility status of these patients.
MATERIAL AND METHODS: Eighty-seven individuals (42 individuals consuming NW and 45 controls) were included. Clinical (plaque index, bleeding on probing, probing depth and clinical attachment loss) and radiographic (marginal bone loss) periodontal parameters were compared among NW and control groups. Gingival specimens were taken from subjects in NW and control groups, assessed for ICTP and CTX levels (using ELISA) and analyzed using micro-Raman spectroscopy. The significance of differences in periodontal parameters between the groups was determined using Kruskal-Wallis and Mann-Whitney U tests. The percent loss of dry mass over exposure time and the rate of release of ICTP and CTX from all groups were compared using the paired t-test to examine the effects of exposure time.
RESULTS: Clinical and radiographic periodontal parameters were significantly higher in the NW group than the control group (P
METHODS: This study was designed to investigate the effect of SynacinnTM and its individual biomarkers on drug metabolizing enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam), CYP3A4 (Testosteron)), to assess its herb-drug interaction potential through cytochrome P450 inhibition assay. This study was conducted using liquid chromatography- tandem mass spectroscopy (LC-MS/MS) using probe substrates using human liver microsomes against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4 (Testosteron).
RESULTS: Result showed that SynacinnTM at maximum concentration (5000 µg/ml) 100% inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4 (Testosteron). IC50 values determined were 0.23, 0.60, 0.47, 0.78, 1.23, 0.99, 1.01, and 0.91 mg/ml for CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4 (midazolam) and 3A4 (testosterone), respectively. Meanwhile, all individual biomarkers showed no, less or moderate inhibitory effect towards all the tested CYP450 except for curcumin that showed inhibition of CYP2C8 (91%), CYP2C9 (81%) and CYP2C19 (72%) at 10µM.
CONCLUSION: Curcumin was found to be an active constituent that might contribute to the inhibition of SynacinnTM against CYP2C8, CYP2C9 and CYP2C19. It can be suggested that SynacinnTM can be consumed separately from a drug known to be metabolized by all tested CYP450 enzymes.