METHODS: Fifty-two patients with colorectal cancer were randomized at four weeks after surgery to receive either a placebo (n = 25) or 30 billion colony-forming unit (CFU) of a mixture of six viable strains including 107 mg of Lactobacillus acidophilus BCMC® 12,130, Lactobacillus lactis BCMC® 12,451, Lactobacillus casei subsp BCMC® 12,313, Bifidobacterium longum BCMC® 02120, Bifidobacterium bifidum BCMC® 02290 and Bifidobacterium infantis BCMC® 02129 (n = 27). Patients were instructed to take the product orally twice daily for six months. Infection status, diarrhea or hospital admission were recorded throughout the study. Blood was taken pre- and post-intervention to measure TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 using ELISA multiplex kit.
RESULTS: The majority of cases (~ 70%) were in Duke's C colorectal cancer for both groups. No surgical infection occurred and no antibiotics were required. Chemotherapy induced diarrhea was observed in both groups. Significant reduction in the level of pro-inflammatory cytokine, TNF-α, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 were observed in CRC patients who received probiotics as compared to pre-treatment level (P
MATERIALS AND METHODS: A literature search was performed to identify potential miRNAs involved in the pathogenesis of HCC. Unpaired serum and ascitic fluid were obtained from 52 patients with NASH related liver cirrhosis (n=26 for each group of with and without HCC). Exosomal miRNA was isolated from all samples. Expression levels of miR-182, miR-301a and miR- 373 were determined using quantitative real-time PCR.
RESULTS: Serum-derived exosomal mir-182, miR-301a and miR-373 were significantly up-regulated with fold change of 1.77, 2.52, and 1.67 (p< 0.05) respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC. We identified the expression levels of ascitic fluid-derived exosomal mir-182, miR-301a, and miR-373 were significantly up-regulated with fold change of 1.6, 1.94 and 2.13 respectively in NASH-induced liver cirrhosis with HCC as compared to NASH-induced liver cirrhosis without HCC (p <0.05). There was poor correlation expression of all the selected exosomal miRNA between serum- and ascitic fluid-derived in HCC group.
CONCLUSIONS: This preliminary data showed significant increase in the expression levels of exosomal miR-182, miR-301a and miR- 373 in both serum and ascetic fluid suggesting the possible roles of these miRNAs as circulating biomarkers for NASH-induced liver cirrhosis with hepatocellular carcinoma.
METHODS: This is a prospective cross-sectional study of IUS performed on IBD patients in a tertiary centre. IUS parameters including intestinal wall thickness, loss of wall stratification, mesenteric fibrofatty proliferation, and increased vascularity were compared with endoscopic and clinical activity indices.
RESULTS: Among the 51 patients, 58.8% were male, with a mean age of 41 years. Fifty-seven percent had underlying ulcerative colitis with mean disease duration of 8.4 years. Against ileocolonoscopy, IUS had a sensitivity of 67% (95% confidence interval (CI): 41-86) for detecting endoscopically active disease. It had high specificity of 97% (95% CI: 82-99) with positive and negative predictive values of 92% and 84%, respectively. Against clinical activity index, IUS had a sensitivity of 70% (95% CI: 35-92) and specificity of 85% (95% CI: 70-94) for detecting moderate to severe disease. Among individual IUS parameters, presence of bowel wall thickening (>3 mm) had the highest sensitivity (72%) for detecting endoscopically active disease. For per-bowel segment analysis, IUS (bowel wall thickening) was able to achieve 100% sensitivity and 95% specificity when examining the transverse colon.
CONCLUSIONS: IUS has moderate sensitivity with excellent specificity in detecting active disease in IBD. IUS is most sensitive in detecting a disease at transverse colon. IUS can be employed as an adjunct in the assessment of IBD.
AIM: To investigate the regulation of rs10889677 and the role of buparlisib in the PI3K signaling pathway in CAC pathogenesis.
METHODS: Genomic DNA from 32 colonic samples, including CAC (n = 7), UC (n = 10) and CRC (n = 15), was sequenced for the rs10889677 mutation. The mutant and wildtype fragments were amplified and cloned in the pmirGLO vector. The luciferase activity of cloned vectors was assessed after transfection into the HT29 cell line. CAC mice were induced by a mixture of a single azoxymethane injection and three cycles of dextran sulphate sodium, then buparlisib was administered after 14 d. The excised colon was subjected to immunohistochemistry for Ki67 and Cleaved-caspase-3 markers and quantitative real-time polymerase chain reaction analysis for Pdk1 and Sgk2.
RESULTS: Luciferase activity decreased by 2.07-fold in the rs10889677 mutant, confirming the hypothesis that the variant disrupted miRNA binding sites, which led to an increase in IL23R expression and the activation of the PI3K signaling pathway. Furthermore, CAC-induced mice had a significantly higher disease activity index (P < 0.05). Buparlisib treatment significantly decreased mean weight loss in CAC-induced mice (P < 0.05), reduced the percentage of proliferating cells by 5%, and increased the number of apoptotic cells. The treatment also caused a downward trend of Pdk1 expression and significantly decreased Sgk2 expression.
CONCLUSION: Our findings suggested that the rs10889677 variant as a critical initiator of the PI3K signaling pathway, and buparlisib had the ability to prevent PI3K-non-AKT activation in the pathophysiology of CAC.
Methods: A retrospective analysis was performed on 946 patients with CRC diagnosed from 1997 to 2017 at Universiti Kebangsaan Malaysia Medical Centre. The time trend was assessed by dividing the two decades into four 5-year periods. The mean age-standardized and age-specific incidence rates were calculated by using the 5-year cumulative population of Kuala Lumpur and World Health Organization standard population. The mean incidence was expressed per 100,000 person-years.
Results: After a stable (all age groups) CRC incidence rate during the first decade (3.00 per 100,000 and 3.85 per 100,000), it sharply increased to 6.12 per 100,000 in the 2008-2012 period before decreasing to 4.54 per 100,000 in the 2013-2017 period. The CRC incidence trend in later-onset CRC showed a decrease in the 2013-2017 period. Contrariwise, for age groups of 40-44 and 45-49 years, the trends showed an increase in the latter 15 years of the study period (40-44 years: 1.44 to 1.92 to 2.3 per 100,000; 45-49 years: 2.87 to 2.94 to 4.01 per 100,000). Malays' EOCRC incidence rate increased from 2008-2012 to 2013-2017 for both the age groups 40-44 years (1.46 to 2.89 per 100,000) and 45-49 years (2.73 to 6.51 per 100,000). Nearly one-fifth of EOCRC cases were diagnosed at an advanced stage (Dukes D: 19.9%), and the majority of them had rectal cancer (72.8%).
Conclusion: The incidence of EOCRC increased over the period 1997-2017; the patients were predominantly Malays, diagnosed at a later stage, and with cancer commonly localized in the rectal region. All the relevant stakeholders need to work on the management and prevention of CRC in Malaysia.
METHODS: A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored.
RESULTS: APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045).
CONCLUSION: The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children.
TRIAL REGISTRATION: The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).