Factors Associated with HIV-1 Proviral DNA Loads in Patients with Undetectable Plasma RNA Load

To evaluate factors associated with human immunodeficiency virus type 1 (HIV-1) proviral DNA load, we conducted a cross-sectional study of 36 chronically HIV-1-infected individuals with undetectable plasma viral RNA. We used real-time polymerase chain reaction to determine the number of HIV-1 proviral DNA copies per 106 peripheral blood mononuclear cells. The mean level of plasma viral RNA when the CD4+ T cell count was above 500 cells/µL without highly active antiretroviral therapy (HAART) was significantly associated with proviral DNA load at the time of undetectable plasma HIV RNA with HAART. Strategies to reduce the level of plasma viral RNA when patients' CD4+ T cell counts are above 500 cells/µL without HAART could help reduce HIV-1 proviral DNA load

Apoptotic Effects of Genistein, Biochanin-A and Apigenin on LNCaP and PC-3 Cells by p21 through Transcriptional Inhibition of Polo-like Kinase-1

Natural isoflavones and flavones are important dietary factors for prostate cancer prevention. We investigated the molecular mechanism of these compounds (genistein, biochanin-A and apigenin) in PC-3 (hormone-independent/p53 mutant type) and LNCaP (hormone-dependent/p53 wild type) prostate cancer cells. A cell growth rate and apoptotic activities were analyzed in different concentrations and exposure time to evaluate the antitumor activities of genistein, biochanin-A and apigenin. The real time PCR and Western blot analysis were performed to investigate whether the molecular mechanism of these compounds are involving the p21 and PLK-1 pathway. Apoptosis of prostate cancer cells was associated with p21 up-regulation and PLK-1 suppression. Exposure of genistein, biochanin-A and apigenin on LNCaP and PC-3 prostate cancer cells resulted in same pattern of cell cycle arrest and apoptosis. The inhibition effect for cell proliferation was slightly greater in LNCaP than PC-3 cells. In conclusion, flavonoids treatment induces up-regulation of p21 expression, and p21 inhibits transcription of PLK-1, which promotes apoptosis of cancer cells

Metabolic effects of aloe vera gel complex in obese prediabetes and early non-treated diabetic patients: Randomized controlled trial

a b s t r a c t Objective: The metabolic effects of an aloe vera gel complex (Aloe QDM complex) on people with prediabetes or early diabetes mellitus (DM) are unknown. The goal of this study was to determine the effects of Aloe QDM complex on body weight, body fat mass (BFM), fasting blood glucose (FBG), fasting serum insulin, and Homeostasis Model of Assessment -Insulin Resistance (HOMA-IR) in obese individuals with prediabetes or early DM who were not on diabetes medications. Methods: Participants (n ¼ 136) were randomly assigned to an intervention or a control group and evaluated at baseline and at 4 and 8 wk. Results: The study lost six participants in the control group and eight in the intervention group. At 8 wk, body weight (P ¼ 0.02) and BFM (P ¼ 0.03) were significantly lower in the intervention group. At 4 wk, serum insulin level (P ¼ 0.04) and HOMA-IR (P ¼ 0.047) were lower in the intervention group; they also were lower at 8 wk but with borderline significance (P ¼ 0.09; P ¼ 0.08, respectively). At 8 wk, FBG tended to decrease in the intervention group (P ¼ 0.02), but the between-group difference was not significant (P ¼ 0.16). Conclusion: In obese individuals with prediabetes or early untreated DM, Aloe QDM complex reduced body weight, BFM, and insulin resistance

Geographic differences in the epidemiological features of HCV infection in Korea

Background/AimsThe prevalence of hepatitis C virus (HCV) infection in Korea exhibits significant geographic variation, with it being higher in Busan and Jeonam than in other areas. The reason for this intranational geographic difference was investigated in this study by conducting a comparative analysis of the risk factors related to HCV infection among three geographic areas: the capital (Seoul), Busan, and the province of Jeolla.MethodsIn total, 990 patients with chronic HCV infection were prospectively enrolled at 5 university hospitals located in Seoul (n=374), Busan (n=264), and Jeolla (n=352). A standardized questionnaire survey on the risk factors for HCV infection was administered to these three groups of patients, and a comparative analysis of the findings was performed.ResultsThe analysis revealed significant regional differences in exposure to the risk factors of HCV infection. By comparison with patients in Seoul as a control group in the multivariate analysis, patients in Busan had significantly more experience of invasive medical procedures, acupuncture, cosmetic procedures, and multiple sex partners. In contrast, patients in Jeolla were significantly older, and they had a higher prevalence of hepatocellular carcinoma, a lower prevalence of multiple sex partners, and had experienced fewer invasive procedures.ConclusionsThere was a significant geographic difference in the exposure to potential risk factors of HCV infection between patients from the three studied regions. This may explain the regional variation of the prevalence of HCV infection in Korea, and should be taken into account when planning strategies for the prevention and management of HCV infection

Urinary adiponectin and albuminuria in non-diabetic hypertensive patients: an analysis of the ESPECIAL trial

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background Although adiponectin levels have been reported to be correlated with albuminuria, this issue remains unresolved in non-diabetic hypertensive subjects, particularly when urinary adiponectin is considered. Methods Urinary adiponectin levels were examined using an enzyme-linked immunosorbent assay in 229 participants. who used olmesartan as a hypertensive agent. Their albuminuria levels were measured for 16 weeks after randomization and initiation of conventional or intensive diet education. Linear or logistic regression models were applied, as appropriate, to explore the relationship with albuminuria itself or its response after the intervention. Results Urinary adiponectin levels were positively related to baseline albuminuria level (r = 0.529). After adjusting for several covariates, the adiponectin level was associated with the albuminuria level (β = 0.446). Among the 159 subjects with baseline macroalbuminuria, the risk of consistent macroalbuminuria (> 300 mg/day) at 16 weeks was higher in the 3rd tertile of adiponectin than in the 1st tertile (odds ratio = 6.9), despite diet education. In contrast, among all subjects, the frequency of the normoalbuminuria achievement (< 30 mg/day) at 16 weeks was higher in the 1st tertile than in the 3rd tertile (odds ratio = 13.0). Conclusions Urinary adiponectin may be a useful biomarker for albuminuria or its response after treatment in non-diabetic hypertensive patients

Prevalence of Anti-Ganglioside Antibodies and Their Clinical Correlates with Guillain-Barre Syndrome in Korea: A Nationwide Multicenter Study

Background and Purpose No previous studies have investigated the relationship between various anti-ganglioside antibodies and the clinical characteristics of Guillain-Barre syndrome (GBS) in Korea. The aim of this study was to determine the prevalence and types of anti-ganglioside antibodies in Korean GBS patients, and to identify their clinical significance. Methods Serum was collected from patients during the acute phase of GBS at 20 university-based hospitals in Korea. The clinical and laboratory findings were reviewed and compared with the detected types of anti-ganglioside antibody. Results Among 119 patients, 60 were positive for immunoglobulin G (IgG) or immunoglobulin M antibodies against any type of ganglioside (50%). The most frequent type was IgG anti-GM1 antibody (47%), followed by IgG anti-GT1a (38%), IgG anti-GD1a (25%), and IgG anti-GQ1b (8%) antibodies. Anti-GM1-antibody positivity was strongly correlated with the presence of preceding gastrointestinal infection, absence of sensory symptoms or signs, and absence of cranial nerve involvement. Patients with anti-GD1a antibody were younger, predominantly male, and had more facial nerve involvement than the antibody-negative group. Anti-GT1a-antibody positivity was more frequently associated with bulbar weakness and was highly associated with ophthalmoplegia when coupled with the coexisting anti-GQ1b antibody. Despite the presence of clinical features of acute motor axonal neuropathy (AMAN), 68% of anti-GM1- or anti-GD1a-antibody-positive cases of GBS were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (AMP) by a single electrophysiological study. Conclusions Anti-ganglioside antibodies were frequently found in the serum of Korean GBS patients, and each antibody was correlated strongly with the various clinical manifestations. Nevertheless, without an anti-ganglioside antibody assay, in Korea AMAN is frequently misdiagnosed as AIDP by single electrophysiological studies.OAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000004487/14SEQ:14PERF_CD:SNU2014-01EVAL_ITEM_CD:102USER_ID:0000004487ADJUST_YN:YEMP_ID:A075641DEPT_CD:801CITE_RATE:1.807FILENAME:kimjk-anti ganlioside ab-gbs-j clin neurol-2014-10(2)94.pdfDEPT_NM:의학과SCOPUS_YN:YCONFIRM:

YH29407 with anti-PD-1 ameliorates anti-tumor effects via increased T cell functionality and antigen presenting machinery in the tumor microenvironment

Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8+ T and natural killer (NK) cells. In this study, we compared the anti-tumor effects of YH29407, the best-in-class IDO1 inhibitor with improved pharmacodynamics and pharmacokinetics, with first and second-generation IDO1 inhibitors (epacadostat and BMS-986205, respectively). YH29407 treatment alone and anti-PD-1 (aPD-1) combination treatment induced significant tumor suppression compared with competing drugs. In particular, combination treatment showed the best anti-tumor effects, with most tumors reduced and complete responses. Our observations suggest that improved anti-tumor effects were caused by an increase in T cell infiltration and activity after YH29407 treatment. Notably, an immune depletion assay confirmed that YH29407 is closely related to CD8+ T cells. RNA-seq results showed that treatment with YH29407 increased the expression of genes involved in T cell function and antigen presentation in tumors expressing ZAP70, LCK, NFATC2, B2M, and MYD88 genes. Our results suggest that an IDO1 inhibitor, YH29407, has enhanced PK/PD compared to previous IDO1 inhibitors by causing a change in the population of CD8+ T cells including infiltrating T cells into the tumor. Ultimately, YH29407 overcame the limitations of the competing drugs and displayed potential as an immunotherapy strategy in combination with aPD-1

Fimasartan versus perindopril with and without diuretics in the treatment of elderly patients with essential hypertension (Fimasartan in the Senior Subjects (FITNESS)): study protocol for a randomized controlled trial

Background Hypertension is an important risk factor for cardiovascular disease, even in the elderly. Fimasartan is a new non-peptide angiotensin II receptor blocker with a selective type I receptor blocking effect. The objective of this study is to confirm the safety and the non-inferiority of the blood pressure–lowering effect of fimasartan compared with those of perindopril, which has been proven safe and effective in elderly patients with hypertension. Methods This is a randomized, double-blind, active-controlled, two-parallel group, optional-titration, multicenter, phase 3 study comparing the efficacy and safety of fimasartan and perindopril arginine. The study population consists of individuals 70 years old or older with essential hypertension. The primary outcome will be a change in sitting systolic blood pressure from baseline after the administration of the investigational product for 8 weeks. The secondary outcomes will be a change in sitting diastolic blood pressure from baseline and changes in sitting systolic blood pressure and diastolic blood pressure from baseline after the administration of the investigational product for 4, 16, and 24 weeks. The sample size will be 119 subjects for each group to confer enough power to test for the primary outcome. Discussion Research to confirm the efficacy and safety of a new medicine compared with those of previously proven anti-hypertensive drugs is beneficial to guide physicians in the selection of therapeutic agents. If it is confirmed that the new drug is not inferior to the existing drug, the drug will be considered as an option in the treatment of hypertension in elderly patients. Trial registration ClinicalTrials.gov Identifier: NCT03246555, registered on July 25, 2017.The study is funded by Boryung Pharmaceutical Co., Ltd. The company was involved in all stages of the study conduct and design. Boryung also took responsibility for all costs associated with the development and publishing of the manuscript