Search

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation (> 5% of liver tissue) in the absence of alcohol abuse or other chronic liver diseases. NAFLD can progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This study aimed to assess the efficacy of probiotic (lactobacillus) supplementation on NAFLD fibrosis score., Methodology: A double-arm randomized controlled trial was conducted in the family medicine clinic of a tertiary hospital, enrolling patients with sonographic evidence of NAFLD. Fifty patients were divided into two groups: the Probiotic group received lifestyle modification instructions along with daily probiotic supplementation for twelve weeks, with regular monthly follow-up visits. The Standard Treatment group received low-fat diet and lifestyle modification instructions only., Results: The mean age of participants was 46.10 years (SD 10.11), with 70% females and 30% males. The study found a statistically significant difference in liver enzymes (ALT and AST) and BMI in the probiotic group before and after intervention. However, there was no significant difference in NAFLD fibrosis score between the two groups., Conclusion: Short-term probiotic treatment resulted in improvements in ALT, AST, and BMI in the probiotic group, but did not significantly affect NAFLD fibrosis score. Further research with larger sample sizes and longer follow-up periods is warranted., Trial Registration: The clinical trial was registered at Protocol Registration and Results System with number NCT06074094 (12/09/2021)., (© 2024. The Author(s).)

Background: Genomic copy number alterations commonly occur in prostate cancer and are one measure of genomic instability. The clinical implication of copy number change in advanced prostate cancer, which defines a wide spectrum of disease from high-risk localised to metastatic, is unknown., Methods: We performed copy number profiling on 688 tumour regions from 300 patients, who presented with advanced prostate cancer prior to the start of long-term androgen deprivation therapy (ADT), in the control arm of the prospective randomised STAMPEDE trial. Patients were categorised into metastatic states as follows; high-risk non-metastatic with or without local lymph node involvement, or metastatic low/high volume. We followed up patients for a median of 7 years. Univariable and multivariable Cox survival models were fitted to estimate the association between the burden of copy number alteration as a continuous variable and the hazard of death or disease progression., Results: The burden of copy number alterations positively associated with radiologically evident distant metastases at diagnosis (P=0.00006) and showed a non-linear relationship with clinical outcome on univariable and multivariable analysis, characterised by a sharp increase in the relative risk of progression (P=0.003) and death (P=0.045) for each unit increase, stabilising into more modest increases with higher copy number burdens. This association between copy number burden and outcome was similar in each metastatic state. Copy number loss occurred significantly more frequently than gain at the lowest copy number burden quartile (q=4.1 × 10 -6 ). Loss of segments in chromosome 5q21-22 and gains at 8q21-24, respectively including CHD1 and cMYC occurred more frequently in cases with higher copy number alteration (for either region: Kolmogorov-Smirnov distance, 0.5; adjusted P<0.0001). Copy number alterations showed variability across tumour regions in the same prostate. This variance associated with increased risk of distant metastases (Kruskal-Wallis test P=0.037)., Conclusions: Copy number alteration in advanced prostate cancer associates with increased risk of metastases at diagnosis. Accumulation of a limited number of copy number alterations associates with most of the increased risk of disease progression and death. The increased likelihood of involvement of specific segments in high copy number alteration burden cancers may suggest an order underlying the accumulation of copy number changes., Trial Registration: ClinicalTrials.gov NCT00268476 , registered on December 22, 2005. EudraCT  2004-000193-31 , registered on October 4, 2004., (© 2022. The Author(s).)

Background: People with type 2 diabetes mellitus (T2DM) are best managed by a chronic care model that is associated with enhanced quality of care and improved patient outcome. Assessing patients' perceived quality of care is crucial in improving the healthcare delivery system. Hence, this study determined the perceived quality of care among people with T2DM and explored its associations with (i) sociodemographic and clinical characteristics and (ii) types of healthcare clinics to guide future planning., Methods: A cross-sectional study involving 20 primary healthcare clinics in the North East Region of Peninsular Malaysia and people with T2DM as the sampling unit was conducted from February to May 2019. The pro forma checklist, interview-guided Skala Kepuasan Interaksi Perubatan-11, and Patient Assessment of Chronic Illness Care (Malay version; PACIC-M) questionnaire were used for data collection. Univariate analysis and linear regression were used to determine the status of perceived quality of care and the factors associated with the perceived quality of care, respectively., Results: Overall, data from 772 participants were analyzed. The majority was from the Malay ethnic group (95.6%) with a mean (standard deviation [SD]) glycated hemoglobin A1c (HbA1c) level of 8.91% (2.30). The median (interquartile range [IQR]) of the number of medical officers available at each clinic was 6 (7), with Family Doctor Concept (FDC) clinics having a higher number of medical officers than non-FDC clinics (p = 0.001). The overall mean (SD) PACIC-M score was 2.65 (0.54) with no significant difference between scores of patients treated in the two clinic types (p = 0.806). Higher perceived quality of care was associated with lower number of medical officers (adjusted regression coefficient [Adj.β], - 0.021; p-value [p], 0.001), and greater doctor-patient interaction in all domains: distress relief (Adj.β, 0.033; p, < 0.001), rapport (Adj.β, 0.056; p, < 0.001), and interaction outcome (Adj.β, 0.022; p, 0.003)., Conclusion: Although there was no significant difference found between clinic type, this study reflects that patients are comfortable when managed by the same doctor, which may support a better doctor-patient interaction. A larger specialized primary care workforce could improve diabetes care in Malaysia.

Background: Cosmos caudatus is an annual plant known for its medicinal value in treating several health conditions, such as high blood pressure, arthritis, and diabetes mellitus. The α-glucosidase inhibitory activity and total phenolic content of the leaf aqueous ethanolic extracts of the plant at different growth stages (6, 8. 10, 12 and 14 weeks) were determined in an effort to ascertain the best time to harvest the plant for maximum medicinal quality with respect to its glucose-lowering effects., Methods: The aqueous ethanolic leaf extracts of C. caudatus were characterized by NMR and LC-MS/MS. The total phenolic content and α-glucosidase inhibitory activity were evaluated by the Folin-Ciocalteu method and α-glucosidase inhibitory assay, respectively. The statistical significance of the results was evaluated using one-way ANOVA with Duncan's post hoc test, and correlation among the different activities was performed by Pearson's correlation test. NMR spectroscopy along with multivariate data analysis was used to identify the metabolites correlated with total phenolic content and α-glucosidase inhibitory activity of the C. caudatus leaf extracts., Results: It was found that the α-glucosidase inhibitory activity and total phenolic content of the optimized ethanol:water (80:20) leaf extract of the plant increased significantly as the plant matured, reaching a maximum at the 10th week. The IC 50 value for α-glucosidase inhibitory activity (39.18 μg mL - 1 ) at the 10th week showed greater potency than the positive standard, quercetin (110.50 μg mL - 1 ). Through an 1 H NMR-based metabolomics approach, the 10-week-old samples were shown to be correlated with a high total phenolic content and α-glucosidase inhibitory activity. From the partial least squares biplot, rutin and flavonoid glycosides, consisting of quercetin 3-O-arabinofuranoside, quercetin 3-O-rhamnoside, quercetin 3-O-glucoside, and quercetin 3-O-xyloside, were identified as the major bioactive metabolites. The metabolites were identified by NMR spectroscopy (J-resolve, HSQC and HMBC experiments) and further supported by dereplication via LC-MS/MS., Conclusion: For high phytomedicinal quality, the 10th week is recommended as the best time to harvest C. caudatus leaves with respect to its glucose lowering potential.

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by continuous hyperglycemia associated with insulin resistance and /or reduced insulin secretion. There is an emerging trend regarding the use of medicinal plants for the treatment of diabetes mellitus. Melicope lunu-ankenda (ML) is one of the Melicope species belonging to the family Rutaceae. In traditional medicines, its leaves and flowers are known to exhibit prodigious health benefits. The present study aimed at investigating anti-diabetic effect of Melicope lunu-ankenda (ML) leaves extract., 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 1 H 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 1 H 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.

Background: Obesity is a major health concern both in developed and developing countries. The use of herbal medicines became the subject of interest for the management of obesity due to its natural origin, cost effectiveness and minimal side effects. The present study aimed at investigating anti-obesity potential of ethanolic extract from Cosmos caudatus Kunth leaf (EECCL)., Methods: In this study, the rats were randomly divided into six groups i.e., (1) Normal Diet (ND); (2) Normal Diet and 175 mg/kgBW of EECCL (ND + 175 mg/kgBW); (3) Normal Diet and 350 mg/kgBW of EECCL (ND + 350 mg/kgBW); (4) High Fat Diet (HFD); (5) High Fat Diet and 175 mg/kgBW of EECCL (HFD + 175 mg/kgBW); (6) High Fat Diet and 350 mg/kgBW of EECCL (HFD + 350 mg/kgBW). The anti-obesity potential was evaluated through analyses of changes in body weight, visceral fat weight, and blood biochemicals including total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), leptin, insulin, adiponectin, ghrelin and fecal fat content. In addition, metabolite profiling of EECCL was carried out using NMR spectroscopy., Results: Rats receiving EECCL together with HFD showed significant (p < 0.05) reduction in body weight gain compared to rats receiving HFD only. At the end of study, the body weight gain of EECCL treated rats was not significantly (p > 0.05) different with those of ND rats. Other related obesity biomarkers including plasma lipid profiles, insulin, leptin, ghrelin and adiponectin levels also showed significant improvement (p < 0.05). Administration of EECCL caused significant (p < 0.05) increase in fecal fat excretion, which validates the hypothesis of lipase inhibition, an anti-obesity mechanism similar to standard drug of Orlistat. The 1 H-NMR spectra of EECCL ascertained the presence of catechin, quercetin, rutin, kaempherol and chlorogenic acid in the extract., Conclusion: Conclusively, EECCL showed anti-obesity properties by inhibition of intestinal lipid absorption and modulation of adipocytes markers.

Background: Type 2 diabetes mellitus is a major health threat worldwide. Cosmos caudatus is one of the medicinal plants used to treat type 2 diabetes. Therefore, this study aims to determine the effectiveness and safety of C. caudatus in patients with type 2 diabetes. Metabolomic approach will be carried out to compare the metabolite profiles between C. Caudatus treated diabetic patients and diabetic controls., Methods and Design: This is a single-center, randomized, controlled, two-arm parallel design clinical trial that will be carried out in a tertiary hospital in Malaysia. In this study, 100 patients diagnosed with type 2 diabetes will be enrolled. Diabetic patients who meet the eligibility criteria will be randomly allocated to two groups, which are diabetic C. caudatus treated(U) group and diabetic control (C) group. Primary and secondary outcomes will be measured at baseline, 4, 8, and 12 weeks. The serum and urine metabolome of both groups will be examined using proton NMR spectroscopy., Discussion: The study will be the first randomized controlled trial to assess whether C. caudatus can confer beneficial effect in patients with type 2 diabetes. The results of this trial will provide clinical evidence on the effectiveness and safety of C. caudatus in patients with type 2 diabetes., Trial Registration: ClinicalTrials.gov identifier: NCT02322268.