Aqueous Extracts of Ocimum gratissimum Sensitize Hepatocellular Carcinoma Cells to Cisplatin through BRCA1 Inhibition.

Ocimum gratissimum (O. gratissimum), a medicinal herb with antifungal and antiviral activities, has been found to prevent liver injury and liver fibrosis and induce apoptosis in hepatocellular carcinoma (HCC) cells. In this study, we evaluated the effect of aqueous extracts of O. gratissimum (OGE) on improving the efficacy of chemotherapeutic drugs in HCC cells. Proteomic identification and functional assays were used to uncover the critical molecules responsible for OGE-induced sensitization mechanisms. The antitumor activity of OGE in combination with a chemotherapeutic drug was evaluated in a mouse orthotopic tumor model, and serum biochemical tests were further utilized to validate liver function. OGE sensitized HCC cells to the chemotherapeutic drug cisplatin. Proteomic analysis and Western blotting validation revealed the sensitization effect of OGE, likely achieved through the inhibition of breast cancer type 1 susceptibility protein (BRCA1). Mechanically, OGE treatment resulted in BRCA1 protein instability and increased proteasomal degradation, thereby synergistically increasing cisplatin-induced DNA damage. Moreover, OGE effectively inhibited cell migration and invasion, modulated epithelial-to-mesenchymal transition (EMT), and impaired stemness properties in HCC cells. The combinatorial use of OGE enhanced the efficacy of cisplatin and potentially restored liver function in a mouse orthotopic tumor model. Our findings may provide an alternate approach to improving chemotherapy efficacy in HCC.

Conventional Western Treatment Combined With Chinese Herbal Medicine Alleviates the Progressive Risk of Lung Cancer in Patients With Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study.

Background and purpose: Lung cancer has high global incidence and mortality rates. Chronic obstructive pulmonary disease (COPD) is strongly associated with lung cancer and is an independent risk factor for lung cancer with or without smoking. Chinese herbal medicines (CHMs) are used to treat COPD. This study sought to determine whether CHM treatment effectively decreases the incidence of lung cancer in COPD patients receiving conventional Western medical treatment. Methods: Records obtained from the National Health Insurance Research Database (NHIRD) were used to identify 81,780 adults aged ≥18 years newly diagnosed with COPD in Taiwan between 2000 and 2010. Among them, 11,180 received CHMs after COPD diagnosis and 23,319 did not (non-CHM). After excluding patients with missing basic demographic information, each group consisted of 2,682 patients. Statistical methods analyzed the baseline characteristics for both groups and we performed a Cox proportional hazard regression analysis to examine the incidence of lung cancer. The cumulative incidence of lung cancer in COPD patients with or without CHM treatment was calculated by the Kaplan-Meier method. The association between herbs and formulas was examined by NodeXL to perform a network analysis of CHM. Results: COPD patients using CHM had a lower risk for lung cancer (adjusted hazards ratio [aHR] = 0.36, 95% confidence interval [CI] = 0.24-0.53, p < 0.001). Older age was associated with a higher risk of lung cancer: patients aged 40-59 years (aHR = 5.32, 95% CI = 2.19-12.94, p < 0.001) and those aged ≥60 years (aHR = 16.75, 95% CI = 7.54-37.23, p < 0.001) were at significantly greater risk compared with patients aged 18-39 years. CHM use was associated with a trend for a lower cumulative incidence of lung cancer compared with non-CHM use (p < 0.001). Among the 10 most commonly used single herbs and formulas used to decrease the risk of lung cancer in COPD patients, Fritillariae thunbergii was the most commonly used single herb and Xiao Qing Long Tang the most commonly used formula. Conclusion: The findings from this nationwide retrospective cohort study indicate that CHM as adjunctive therapy in COPD treatment regimens may reduce the risk of lung cancer in this vulnerable patient population.

Waist-to-height ratio is a useful index for nonalcoholic fatty liver disease in children and adolescents: a secondary data analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a global problem and pediatric obesity has risen dramatically. Early NAFLD might progress to nonalcoholic steatohepatitis (NASH) or liver cirrhosis and significantly increase liver disease-related mortality. We looked for NAFLD predictors in children and adolescents. METHODS: This community-based, cross-sectional study ran from December 2012 to September 2013 in southwestern Taiwan. Children <10 and >19 years old, with detected hepatic diseases, or who drank alcohol were excluded. The diagnosis of NAFLD was based on ultrasound: age, sex, anthropometric measurements, and laboratory data were evaluated for associated risks by using logistic regression analysis. Receiver operating characteristic (ROC) curves were used to determine cutoff values. RESULTS: We enrolled one thousand, two hundred and ten children (594 males; 616 females; mean age: 15.5 ± 2.8 years). Age, anthropometric measurements, and laboratory data were significantly higher in children with NAFLD. The association between NAFLD and the waist-to-height ratio (WHtR) was significant (adjusted odds ratio: 2.6; 95% confidence interval: 1.909-3.549; P < 0.001). It indicated highly suspicion of NAFLD (sensitivity: 70.1%; specificity 76.9%) when the WHtR for children and adolescents is above the cutoff value of 0.469. CONCLUSIONS: The WHtR might be a powerful index of the severity of pediatric NAFLD.

The use of Chinese herbal medicine as an adjuvant therapy to reduce incidence of chronic hepatitis in colon cancer patients: A Taiwanese population-based cohort study.

ETHNOPHARMACOLOGICAL RELEVANCE: There is a decided lack of in-depth studies to evaluate the effectiveness of Chinese Herbal Medicine (CHM) as an adjuvant therapy on the incidence of chronic hepatitis in patients with colon cancer. AIM OF THE STUDY: The aim of this study is to assess whether CHM treatment decreased the incidence of chronic hepatitis in colon cancer patients who received conventional Western medical treatment. MATERIALS AND METHODS: A Taiwanese nationwide population-based study of colon cancer patients receiving Western medicine treatment in conjunction with CHM treatment, using data provided by the National Health Insurance (NHI) Research Database, was conducted. A total of 61676 patients were diagnosed with colon cancer in Taiwan within the defined study period, from 1997 to 2010. After randomly equal matching for age, sex, excluding patients younger than 18 years of age, chronic hepatitis before colon cancer diagnosis date, receiving acupuncture and/or moxibustion and taking CHM for less than 30 days, data from 155 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence of CHM and the therapeutic potential of herbal products in treating patients with colon cancer. RESULTS: CHM used for patients with colon cancer exhibited significantly decreased incidence rates of chronic hepatitis [hazard ratio (HR)=0.53; 95% confidence interval (CI):0.38-0.74], with multivariate adjustment, compared to those without CHM use. The protective effect of CHM treatment with statistical significance across the stratification of age, gender, co-morbidity and treatment modality was noted. The cumulative incidence of chronic hepatitis was also reduced in patients with colon cancer receiving CHM treatment during a five-year period. In this study, we provide the ten most used single herbs and herbal formulas that were prescribed for patients with colon cancer; moreover, we identify the eight single herbs and five formulas used in CHM treatment which significantly decreased incidence of chronic hepatitis among colon cancer patients. CONCLUSIONS: This nationwide retrospective cohort study determined that therapy using CHM as an adjuvant modality may have a significant impact on liver protection in patients with colon cancer.

Impact of Apolipoprotein B on Hepatosteatosis in a Population Infected with Hepatitis C Virus: A Cross-Sectional Observational Study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an established risk factor for diabetes, cardiovascular disease, antiviral treatment resistance, and progression of chronic hepatitis C virus (HCV) infection to fibrosis. Apolipoprotein-B 100 (ApoB-100) is a dyslipidemia marker and steatosis predictor. We assess the correlation between ApoB-100 and hepatosteatosis. METHODS: This cross-sectional study enrolled 1,218 HCV-seropositive participants from a 2012-2013 health checkup in Taiwan. NAFLD was detected using ultrasound. All anthropometric and laboratory studies that included ApoB-100 were evaluated whether or not ApoB-100 predicts NAFLD. Logistic regression was also used to examine the association between ApoB-100 and NAFLD. RESULTS: Participants were 47.16 ± 16.08 years old (mean age). The overall prevalence of NAFLD was 35.8% (n = 436; 32.8% men, 38.1% women). Participants with ApoB-100 ≥ 8 had a significantly higher incidence of NAFLD (39.4 vs. 29.4%; 95% CI 0.044-0.156; p < 0.001). After confounding factors had been adjusted for, ApoB-100 was significantly associated with NAFLD (OR 5.45; 95% CI 1.64-18.06; p = 0.006) and high-grade hepatosteatosis (OR 7.73; 95% CI 1.74-34.35; p = 0.007). CONCLUSION: ApoB-100 is strongly associated with NAFLD in people with non-genotype 3 HCV; greater ApoB-100 content is significantly correlated with higher-grade hepatosteatosis.

Pharmacological effects of Salvia miltiorrhiza (Danshen) on cerebral infarction.

Danshen, the dried root of Salvia miltiorrhiza, is a Chinese medicine used to promote blood flow and treat vascular disease. The present article reviews the pharmacological effects of Danshen on cerebral infarction and possible interactions between Danshen and Western drugs. Danshen may reduce or prolong the development of atherosclerosis and may have anti-hypertensive and anti-platelet aggregation effects, which prevent cerebral infarction. Danshen may enhance endogenous anti-oxidative enzyme activities such as the expression of endothelial nitric oxide synthase and may scavenge oxygen free radicals. Prevention and treatment of cerebral infarction by Danshen involves multiple pathways, including anti-atherosclerosis, anti-hypertension, anti-platelet aggregation, anti-inflammatory and anti-oxidative effects.

Influence of menstrual cycle on pulse pressure waveforms measured from the radial artery in biphasic healthy women.

OBJECTIVES: The aim of this study was to investigate the effects of the menstrual cycle on the pulse pressure waveforms in women with regular biphasic cycles. METHODS: We recruited 36 biphasic healthy eumenorrheic volunteers. Pulse pressure waveforms from the radial artery were recorded by sphygmography in both hands, each with three measurement positions and three different preload pressures, in a total of 18 measured points. The experimental design was single blinded and the technician who measured the waveforms did not know the menstrual time point of the subjects. The parameters included the pulse rate (PR), the height of the main wave (h(1)), the height of the dicrotic wave (h(3)), the rapid ejection time, the single systolic area (sSA), and the 1-minute systolic area (tSA). RESULTS: Our results showed that PR was significantly greater during the luteal phase (81.5 +/- 1.5/minutes versus 78.3 +/- 1.5/minutes, p < 0.05) with an accompanying greater h(1), h(3), sSA, and tSA (p < 0.05). We also demonstrated that h(1), h(3), sSA, and tSA increased with preload pressures and decreased when the detector was moved proximally, possibly a resultant of differences in the diameter and depth of radial artery. Furthermore, we found that h(3) taken from the right hand was larger than that taken from the left hand and may reflect a shorter and simpler route of the right radial artery. CONCLUSIONS: We conclude that pulse waveforms taken from the radial artery may assist in the identification of greater plasma volume, ventricular ejection volume, and vasodilatation increase in the luteal compared to the follicular phase.