Search

Helicobacter pylori is one of the most widespread infections involved in the pathogenesis of chronic gastritis, peptic ulcer, and gastric cancer. Hence, there is an urgent need to develop medications against H. pylori. This study aimed to evaluate synergistic effect of Rubus crataegifolius (RF) and Ulmus macrocarpa Hance (UL) against H. pylori. Antibacterial susceptibility of each extract either separately or in combination was studied against two H. pylori standard strains and 11 clinical isolates using agar dilution method. The effect of the extracts on H. pylori inoculated Balb/c mice model was also studied using single dosing (100 mg/kg each) approach. The MIC50 of RF and UL were more than 100 and 200 µg/ml, respectively, against the tested strains. However, simultaneous treatment with RF and UL at 75 and 50 µg/ml, respectively, showed decreased viable cell number, MIC70, and at 75 µg/ml each showed synergic effect with MIC90. On H. pylori inoculated Balb/c mice model, RF and UL separately (100 mg/kg each) showed moderate anti-H. pylori effect, while simultaneous treatment of RF and UL with same dose showed significant synergistic anti-gastric effects in stomach. The results showed a significant synergistic effect of plants extract against H. pylori infection and eventually gastric mucosal damage. Our finding could be considered a valuable support in the treatment of H. pylori induced gastritis and may contribute to the development of new and safe combined herbal product as anti-H. pylori regimens. more...

Background: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). Objective: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. Methods: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group’s liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. Results: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). Conclusions: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model. more...

Background: Preterm birth is a known leading cause of neonatal mortality and morbidity. The underlying causes of pregnancy-associated complications are numerous, but infection and inflammation are the essential high-risk factors. However, there are no safe and effective preventive drugs that can be applied to pregnant women. Objective: The objectives of the study were to investigate a natural product, Abeliophyllum distichum leaf (ADL) extract, to examine the possibility of preventing preterm birth caused by inflammation. Methods: We used a mouse preterm birth model by intraperitoneally injecting lipopolysaccharides (LPS). ELISA, Western blot, real-time PCR and immunofluorescence staining analyses were performed to confirm the anti-inflammatory efficacy and related mechanisms of the ADL extracts. Cytotoxicity and cell death were measured using Cell Counting Kit-8 (CCK-8) analysis and flow cytometer. Results: A daily administration of ADL extract significantly reduced preterm birth, fetal loss, and fetal growth restriction after an intraperitoneal injection of LPS in mice. The ADL extract prevented the LPS-induced expression of TNF-α in maternal serum and amniotic fluid and attenuated the LPS-induced upregulation of placental proinflammatory genes, including IL-1β, IL-6, IL-12p40, and TNF-α and the chemokine gene CXCL-1, CCL-2, CCL3, and CCL-4. LPS-treated THP-1 cell-conditioned medium accelerated trophoblast cell death, and TNF-α played an essential role in this effect. The ADL extract reduced LPS-treated THP-1 cell-conditioned medium-induced trophoblast cell death by inhibiting MAPKs and the NF-κB pathway in macrophages. ADL extract prevented exogenous TNF-α-induced increased trophoblast cell death and decreased cell viability. Conclusions: We have demonstrated that the inhibition of LPS-induced inflammation by ADL extract can prevent preterm birth, fetal loss, and fetal growth restriction. more...

We aimed to analyze the value of each criterion for clinically insignificant prostate cancer (PCa) in the selection of men for active surveillance (AS) of low-risk PCa. We identified 532 men who were treated with radical prostatectomy from 2006 to 2013 who met 4 or all 5 of the criteria for clinically insignificant PCa (clinical stage ≤ T1, prostate specific antigen [PSA] density ≤ 0.15, biopsy Gleason score ≤ 6, number of positive biopsy cores ≤ 2, and no core with > 50% involvement) and analyzed their pathologic and biochemical outcomes. Patients who met all 5 criteria for clinically insignificant PCa were designated as group A (n = 172), and those who met 4 of 5 criteria were designated as group B (n = 360). The association of each criterion with adverse pathologic features was assessed via logistic regression analyses. Comparison of group A and B and also logistic regression analyses showed that PSA density > 0.15 ng ml−1 and high (≥7) biopsy Gleason score were associated with adverse pathologic features. Higher (> T1c) clinical stage was not associated with any adverse pathologic features. Although ≤ 3 positive cores were not associated with any adverse pathology, ≥4 positive cores were associated with higher risk of extracapsular extension. Among potential candidates for AS, PSA density > 0.15 ng ml−1 and biopsy Gleason score > 6 pose significantly higher risks of harboring more aggressive disease. The eligibility criteria for AS may be expanded to include men with clinical stage T2 tumor and 3 positive cores. more...

Mycobacterium abscessus (Mab), a nontuberculous mycobacterium, is increasing in prevalence worldwide and causes treatment-refractory pulmonary diseases. However, how Mab rewires macrophage energy metabolism to facilitate its survival is poorly understood. We compared the metabolic profiles of murine bone marrow-derived macrophages (BMDMs) infected with smooth (S)- and rough (R)-type Mab using extracellular flux technology. Mab infection shifted BMDMs towards a more energetic phenotype, marked by increased oxidative phosphorylation (OXPHOS) and glycolysis, with a significantly greater enhancement in OXPHOS. This metabolic adaptation was characterized by enhanced ATP production rates, particularly in cells infected with S-type Mab, highlighting OXPHOS as a key energy source. Notably, Mab infection also modulated mitochondrial substrate preferences, increasing fatty acid oxidation capabilities while revealing significant changes in glutamine dependency and flexibility. R-type Mab infections exhibited a marked decrease in glutamine reliance but enhanced metabolic flexibility and capacity. Furthermore, targeting metabolic pathways related to glutamine and fatty acid oxidation exacerbated Mab growth within macrophages, suggesting these pathways play a protective role against infection. These insights advance our understanding of Mab’s impact on host cell metabolism and propose a novel avenue for therapeutic intervention. By manipulating host mitochondrial metabolism, we identify a potential host-directed therapeutic strategy against Mab, offering a promising alternative to conventional treatments beleaguered by drug resistance. This study underscores the importance of exploring metabolic interventions to combat Mab infection, paving the way for innovative approaches in the fight against this formidable pathogen. more...

BACKGROUND:Our hypothesis is that the location of the seminal vesicles near the base of the prostate, the more positive cores are detected in the base, the greater the risk of seminal vesicle invasion. Therefore we investigate the clinical outcomes of base dominant prostate cancer (BDPC) in transrectal ultrasound (TRUS) -guided biopsies compared with anteromiddle dominant prostate cancer (AMPC). METHODS:From November 2003 to June 2014, a total of 990 intermediate and high risk prostate cancer (PCa) patients who underwent radical prostatectomy (RP) were enrolled and stratified into two groups according to proportion of positive cores-BDPC group had ≥ 33.3% ratio of positive cores from the prostate base among all positive cores and AMPC group < 33.3% in systemic biopsy. Between two groups, we compared the rate of pathologic outcomes and biochemical recurrence (BCR). We performed multivariate logistic regression model to confirm the significance of BDPC to seminal vesicle invasion (SVI) and Cox proportional hazard analysis to BCR. RESULTS:Among these 990 PCa patients, the 487 patients in BDPC group had more advanced clinical stage (p more...

A significant proportion of patients undergoing salvage radiotherapy (RT) for biochemical recurrence (BCR) following radical prostatectomy (RP) may again experience BCR after salvage RT. Thus, we evaluated the clinical significances of different parameters on the biochemical outcome of RT in salvage setting.We reviewed the records of 212 patients who underwent salvage RT between November 2003 and December 2012 for BCR following primary RP. BCR-free survivals after salvage RT were estimated using the Kaplan-Meier method. Cox proportional hazard regression models were used to evaluate the impacts of clinicopathologic parameters on BCR following salvage RT.The overall median follow-up duration was 63.5 months. The BCR-free survival rate after salvage RT was 58.2% at 5 years. Multivariate analysis showed that a pre-RT prostate-specific antigen (PSA) level of ≤0.5 ng/mL, a pre-RT PSA doubling time (PSADT) of >4.5 months, concomitant androgen deprivation therapy (ADT) with salvage RT, and a positive surgical margin were independent predictors of favorable biochemical outcomes after salvage RT (hazard ratios [HR] = 3.012, 1.132, 2.000, and 1.805, respectively, p = less than 0.001, 0.013, 0.005, and 0.036, respectively). In the early (pre-RT PSA ≤0.5 ng/mL) salvage RT setting, concomitant ADT administration was also shown to be significantly associated with higher risk of BCR-free survival following salvage RT (HR = 2.611, p = 0.038).Lower pre-RT PSA value, longer PSADT before salvage RT, concomitant ADT administration, and a positive surgical margin were significant predictors of favorable biochemical outcomes following salvage RT performed for BCR after primary RP. more...

The present study was performed to investigate the potential effects of the unripened dried fruit of Rubus coreanus Miq., Rubi Fructus (RF), on hepatic steatosis and lipid metabolism in mice fed with a high-fat diet (HFD) known to induce obesity and hyperlipidaemia. Rubi Fructus extract (RFex) fed mice demonstrated a reduced body weight and adipose tissue weight. RFex fed mice also demonstrated decreased aminotransferase levels, lipid contents [triglyceride (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C)], leptin content and increased high-density lipoprotein-cholesterol (HDL-C) contents in the plasma. These effects were accompanied by a decreased expression of lipogenic genes, including sterol regulatory element binding protein-1c, liver X receptor, fatty acid synthase (FAS), acetyl-CoA carboxylase, cluster of differentiation 36, lipoprotein lipase and decreased lipogenic enzyme FAS and 3-hydroxy-3 methylglutamyl coenzyme reductase enzyme activities, while elevating carnitine palmitoyltrasferase-1 activity. Based on these results, the present study hypothesized that the inhibitory effect on hepatic steatosis of RFex is the result of the suppression of lipid synthesis in mice fed with HFD, suggesting that RFex may be beneficial in preventing hepatic steatosis and liver lipotoxicity. [ABSTRACT FROM AUTHOR] more...

Purpose: To evaluate the association of a specific type of lower urinary tract symptom (LUTS) and the depression in community-dwelling elderly Korean men. Materials and Methods: A total of 392 men aged 65 years or older, who completed urological and psychiatric evaluations as a participant of the Korean Longitudinal Study on Health and Aging, were included. From each subject, an interview on the demographic characteristics and medical history, IPSS, and psychiatric questionnaire were taken. Subjects were divided into two groups; depression and euthymic. Subjects with IPSS subscore more than 3 points was considered 'high' subscore. IPSS subscores were compared between the two groups, and the relationship between depression and LUTS severity was assessed. Results: The mean age of the subjects was 75, and 6.4% of the subjects were diagnosed to have major depressive disorders. The depression group showed higher IPSS scores than the euthymic group (16.1±9.9 vs. 11.6±8.6, p=0.01). IPSS subscores of question 1 (incomplete empty), question 3 (intermittency), question 4 (urgency) and question 6 (straining to void) were higher in the depression group compared with the euthymic group. Chi-square test revealed subjects with high IPSS 1, 3, 4, and 6 score were associated with depression, but multivariate analysis identified only high IPSS question 4 as a significant prognostic factor for depression. Conclusions: Elderly population with depression is more likely to have more severe LUTS than population without depression. Among the urinary symptoms, urgency was strongly associated with depression. Patients with moderate to severe LUTS and especially urgency may need their mental health status evaluation. [ABSTRACT FROM AUTHOR] more...

The hepatitis B virus-X protein (HBx) regulates fundamental aspects of mitochondrial physiology. We show that HBx down-regulates mitochondrial enzymes in. volved in electron transport in oxidative phosphorylation (complexes I, III, IV, and V) and sensitizes the mitochondrial membrane potential in a hepatoma cell line. HBx also increases the level of mitochondrial reactive oxygen species and lipid peroxide production. HBx does not activate apoptotic signaling, although it sensitizes hepatoma cells to apoptotic signaling, which is dependent on reactive oxygen species. Increased intrahepatic lipid peroxidation in HBx transgenic mice demonstrated that oxidative injury occurs as a direct result of HBx expression. Therefore, we conclude that mitochondrial dysfunction is a crucial pathophysiological factor in HBx-expressing hepatoma cells and provides an experimental rationale in the investigation of mitochondrial function in rapidly renewed tissues, as in hepatocellular carcinomas. [ABSTRACT FROM AUTHOR] more...