Potential plasma biomarkers: miRNA-29c, miRNA-21, and miRNA-155 in clinical progression of Hepatocellular Carcinoma patients.

This study evaluated differences in the clinical appearance of patients with hepatocellular carcinoma (HCC) based on plasma level and regulation of microRNAs (miRNA-29c, miRNA-21, and miRNA-155). The observational-analytical study with a cross-sectional design was conducted on 36 HCC patients and 36 healthy controls. The blood samples were collected from 2 Province Hospitals (Dr. Sardjito Hospital and Prof. Dr. Margono Soekarjo Hospital) for HCC and the Blood Bank Donor of the Indonesian Red Cross for 36 healthy controls. These blood samples were treated as follows: plasma isolation, RNA isolation, cDNA synthesis, quantification by qRT-PCR using a sequence-specific forward primer, and normalization of miRNA using housekeeping-stably miRNA-16. There were only 27 HCC patients with complete clinical variables (neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), platelet count, albumin, C-reactive protein (CRP), and cholinesterase (ChE)) that were able to analyses for regulation miRNAs based on its fold change expression miRNA target. All 27 HCC subjects were follow-up until 3-years of monitoring for their overall survival. The miRNA plasma expression was analyzed by Bio-Rad CFX 96 Manager software to determine the cycle of quantification, followed by the calculation of expression levels using Livak's methods. Data were analyzed using STATA 11.0, with a significant value of p<0.05. The miRNAs expression of HCC subjects were lower than that healthy control subjects in miRNA-29c (down-regulation 1.83-fold), higher than that healthy control subjects in miRNA 21 and miRNA-155 (up-regulation, 1.74-fold; 1.55-fold) respectively. NLR, CRP, ChE, and platelet count showed a significant difference in miRNA-29c regulation, though neutrophil count showed a significant difference in miRNA-21 and miRNA-155 regulation (p<0.05). Conclusion: Plasma biomarkers: miRNA-21 and miRNA-155 might be potential biomarkers as onco-miR in HCC subjects, while miRNA-29c might act as a tumor suppressor. Significant evidence was identified with clinical progression based on the regulation of miRNAs, which was consistent with miRNA -29c.

Clinical Application of Stem Cell Therapy for Liver Cirrhosis: Progress, Pitfalls, and Prospects.

Liver cirrhosis is the advanced stage of liver disease accounting for high morbidity and mortality rates worldwide. Liver transplantation for liver cirrhosis has several limitations, rendering stem cell transplantation as a potential therapy. Clinical trials of stem cell applications for liver cirrhosis are being established using various types of stem cells. This review will provide a current report of the achievements, limitations, and future directions of stem cell transplantation. Current progress of clinical trials is valuable in defining the best type of stem cells, mode of delivery, the number and frequency of cells to be injected, and determining potential candidates for cell therapy. Some of the encountered pitfalls are the limited homing and differentiation potential of stem cells, the use of non-xenofree culture system, and the risk for tumorigenesis in certain types of stem cells. The prospective developments of liver stem cell transplantation are the generation of genetically modified stem cells and the formation of liver organoids for treating liver cirrhosis.

The Effectiveness of Right- vs Left-lateral Starting Position in Unsedated Diagnostic Colonoscopy with Modified-water Immersion Method: A Randomized Controlled Trial Study.

OBJECTIVE: A colonoscopy study in sedated patients with air insufflation showed that right-lateral starting position (RLP) improved abdominal discomfort and reduced cecal intubation time. The aim of this study was to determine if RLP vs left-lateral starting position (LLP) may produce similar results in unsedated patients examined with a modified-water immersion (m-WI) method. METHODS: Consecutive patients for diagnostic colonoscopy meeting the inclusion criteria were randomized. Patients and colonoscopist were unblinded. The m-WI method entailed suction during insertion not only for fecal debris evacuation but also to facilitate passage through difficult or angulated colonic flexures. Water was infused as needed when any difficulty was encountered during insertion. A bowel visualization scale (BVS) (0=totally blurred visualization; 1=blurred lumen visualization; 2=small fecal debris with clear mucosa visualization; 3= clear visualization) was used to evaluate the interference of fecal debris with cecal intubation rate and time. RESULTS: A total of 142 patients (72 in RLP and 70 in LLP) were enrolled. The respective pain score, visual analog scale, (VAS) and cecal intubation rate were not significantly different. The cecal intubation time was nearly significantly different (13.4±4.5 min vs 11.7±5.4 min; p=0.054) and was significantly different in the constipation subgroup (16.0±3.5 min vs 8.6±3.8 min; p=0.001). The cecal intubation time based on BVS showed significant difference between RLP and LLP in Scale 2 (13.9±4.6 min vs 10.3±4.2 min; p=0.003) and Scale 2 and 3 combined (13.2±4.3 min vs 10.6±4.8 min; p=0.01), respectively. CONCLUSION: RLP did not improve the pain score, and LLP showed better performance in unsedated m-WI colonoscopy patients (ClinicalTrial.gov, NCT03489824).

Endoscope-connected water pump with high flow rates improves the unsedated colonoscopy performance by water immersion method.

OBJECTIVES: The aim of this study was to determine if different water pump flow rates influence the insertion time of water immersion method in unsedated patients. We tested the hypothesis that high flow rate (HFR) is more effective than low flow rate (LFR) in facilitating insertion. Clinical registration number: NCT01869296. METHODS: Consecutive symptomatic patients without prior abdominal surgery were consented and enrolled. They were randomized to an HFR (10.4 mL/s) or LFR (1.7 mL/s) group. The patients were not informed about the flow rate of the water pump (single blinded). Patients underwent unsedated colonoscopy examination with standard colonoscope. Demographic and procedural parameters were recorded. Data were analyzed with Student's t-test or Chi-square test as appropriate. RESULTS: A total of 132 patients (66 in HFR and 66 in LFR group) were recruited. The HFR group showed significantly shorter cecal intubation time (12.5±6.2 min in HFR vs 16.3±7.3 min in LFR, p=0.004), shorter time to pass rectosigmoid (3.6±2.2 min in HFR vs 6.2±4.6 min in LFR, p<0.001), and lower pain score (4.2±2.8 in HFR vs 5.3±2.6 in LFR, p=0.024). The cecal intubation rate was not significantly different (87.9% in HFR vs 80.3% in LFR, p=0.34), and 29 (14 in HFR and 15 in LFR) patients with signs of colon redundancy were successfully intubated to the cecum after repeated loop reduction and position changes. CONCLUSION: Compared to LFR, HFR of the water infusion pump significantly reduced colonoscopy insertion time and pain score in unsedated patients. Significantly shorter time to pass the rectosigmoid appeared to play a contributory role.

Are Mucosa CD4+/CD8+ T-Cells Expressions Correlated with the Endoscopic Appearance of Chronic Gastritis Related with Helicobacter pylori Infection?

Local inflammatory processes in the gastric mucosa are followed by extensive immune cell infiltration, resulting in chronic active gastritis characterized by a marked infiltration of T(h)1 cytokine-producing CD4+ and CD8+T-cells Objective. To investigate the correlation between CD4+/CD8+ T-cells in gastric mucosa with endoscopic appearance in chronic gastritis with or without H.pylori infection. Prospective, cross sectional study is performed in a chronic dyspepsia population in July-November 2009 at Dr. Sardjito General Hospital Yogyakarta, Indonesia. The update Sydney system was used to analyze the gastroscopy appearance. Biopsy specimens were stained with HE-stain and IHC-stain. Data were analyzed by t-test, Mann-Whitney and Spearman correlation test. Number of 88 consecutive subjects are enrolled the study (50% male; 50% female), age 46±15 years; 25% H.pylori positive. The expression of CD4+ and CD8+ were higher in H.pylori negative subjects, but only the CD4+ was significant (P=0.011). A significant correlation was found between CD4+ and CD8+ in both subjects (r(Hp+)=0.62 and r(Hp-)=0.68; P<0.05). The expression of CD4+ and CD8+ in H.pylori positive showed a significant correlation with gastric lesions (r(CD4+)=-0.60; r(CD8+)=-0.42 ; P<0.05), only erosion showed a significant difference in both subjects. A positive correlation was found between CD4+ and CD8+ infiltration in both subjects with or without H.pylori infection, and a negative correlation was only found between gastric lesion with CD4+ and CD8+ infiltration in H.pylori subject.

Protective effects of HLA-DPA1/DPB1 variants against Hepatitis B virus infection in an Indonesian population.

Human leukocyte antigen (HLA) DPA1/DPB1 variants have been reported to influence Hepatitis B virus (HBV) infection. HLA-DPA1/DPB1 plays a pivotal role in antigen presentation to CD4(+) helper T cells and influences the outcome of HBV infection. To investigate the influence of HLA-DP variants on the outcome of HBV infection in an Indonesian population where it has the third-highest prevalence of HBV infection worldwide, we performed a case-control study of 686 participants, including patients with HBV-related advanced or nonadvanced liver disease, patients with spontaneously resolved HBV, and healthy controls. Single-nucleotide polymorphisms in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs228388) were genotyped using real-time TaqMan® genotyping assays. Because rs2281388 deviated from Hardy-Weinberg equilibrium, it was excluded from subsequent analyses. The results of logistic regression analyses showed that the HLA-DPB1 rs9277535 variants were associated with a reduced risk of persistent HBV infection (odds ratio [OR] 0.70, 95% confidence interval [95% CI] 0.52-0.96, P=0.026, additive genetic model; OR 0.60, 95% CI 0.38-0.96, P=0.033, dominant genetic model). The HLA-DPA1 rs3077 variant was associated with a protective effect increasing the spontaneously resolved HBV infection (OR 0.64, 95% CI 0.41-0.98, P=0.039, dominant genetic model). By contrast, the HLA-DPB1 rs3135021 variant was not associated with the outcome of HBV infection, including susceptibility, spontaneously resolved, or disease progression. Combinations of haplotype markers were also associated with HBV susceptibility (CA for rs3077-rs9277535, OR 0.57, 95% CI 0.36-0.92, P=0.021; GA for rs3135021-rs9277535, OR 0.56, 95% CI 0.36-0.86, P=0.0087). In conclusion, these findings confirm that HLA-DPA1/DPB1 variants were associated with the outcomes of HBV infection in an Indonesian population.