A cross-sectional study of SARS-CoV-2 antibodies among healthcare workers in a tertiary care hospital in Taiwan: implications for protection against the Omicron variants.

BACKGROUND: Taiwan, deeply impacted by the 2003 SARS outbreak, promptly implemented rigorous infection control and prevention (ICP) measures in January 2020 to combat the global COVID-19 pandemic. This cross-sectional serologic study was conducted among healthcare workers (HCWs) in a tertiary care hospital in Taiwan from August 1, 2022, to February 28, 2023. The study aimed to assess HCWs' antibody responses to COVID-19 vaccination against Omicron subvariants BA.1, BA.4, and BA.5, considering variations in prior infection. Additionally, it evaluated the effectiveness of ICP and vaccination policies within the hospital setting in Taiwan. METHODS: A cross-sectional serology study was conducted in Taiwan to investigate the seroprevalence rates of Omicron subvariants BA.1, BA.4, and BA.5 among HCWs. A total of 777 HCWs participated in this study. A structured questionnaire was collected to obtain the epidemiological characteristics and risk factors for potential exposure. Enzyme-linked immunosorbent assay was used to detect antibody responses. Serum samples were selected for protection against Omicron subvariants BA.1, BA.4, and BA.5 by using a pseudotyped-based neutralization assay. RESULTS: More than 99% of the participants had received SARS-CoV-2 vaccination. Overall, 57.7% had been infected with SARS-CoV-2, with some being asymptomatic. The SARS-CoV-2 Anti-Spike S1 protein IgG (Anti-S) distribution was 40,000 AU/mL for 20.2% (157/777) of participants, with a mean ± standard deviation of 23,442 ± 22,086. The decay curve for Anti-S was less than 20,000 AU/ml after 120 days. The probability curve of 50% neutralization showed an Anti-S of 55,000 AU/ml. The optimum Anti-S was 41,328 AU/mL (equal to 5,869 WHO's standard BAU/mL), with 86.1% sensitivity and 63.5% specificity. CONCLUSIONS: In this significant study, 20.2% of HCWs achieved seroprotection against Omicron subvariants BA.1, BA.4, and BA.5. Their immunity against Omicron subvariants was further reinforced through recommended vaccinations and the development of natural immunity from SARS-CoV-2 exposure, collectively enhancing their protection against Omicron.

Develop and Validate a Prognostic Index With Laboratory Tests to Predict Mortality in Middle-Aged and Older Adults Using Machine Learning Models: A Prospective Cohort Study.

BACKGROUND: Prognostic indices can enhance personalized predictions of health burdens. However, a simple, practical, and reproducible tool is lacking for clinical use. This study aimed to develop a machine learning-based prognostic index for predicting all-cause mortality in community-dwelling older individuals. METHODS: We utilized the Healthy Aging Longitudinal Study in Taiwan (HALST) cohort, encompassing data from 5 663 participants. Over the 5-year follow-up, 447 deaths were confirmed. A machine learning-based routine blood examination prognostic index (MARBE-PI) was developed using common laboratory tests based on machine learning techniques. Participants were grouped into multiple risk categories by stratum-specific likelihood ratio analysis based on their MARBE-PI scores. The MARBE-PI was subsequently externally validated with an independent population-based cohort from Japan. RESULTS: Beyond age, sex, education level, and BMI, 6 laboratory tests (low-density lipoprotein, albumin, aspartate aminotransferase, lymphocyte count, high-sensitivity C-reactive protein, and creatinine) emerged as pivotal predictors via stepwise logistic regression (LR) for 5-year mortality. The area under curves of MARBE-PI constructed by LR were 0.799 (95% confidence interval [95% CI]: 0.778-0.819) and 0.756 (95% CI: 0.694-0.814) for the internal and external validation data sets, and were 0.801 (95% CI: 0.790-0.811) and 0.809 (95% CI: 0.774-0.845) for the extended 10-year mortality in both data sets, respectively. Risk categories stratified by MARBE-PI showed a consistent dose-response association with mortality. The MARBE-PI also performed comparably with indices constructed with clinical health deficits and/or laboratory results. CONCLUSIONS: The MARBE-PI is considered the most applicable measure for risk stratification in busy clinical settings. It holds potential to pinpoint older individuals at elevated mortality risk, thereby aiding clinical decision-making.

Lower HbA1C of glycemic control is associated with higher risk of depressive symptoms in elderly with type 2 diabetes mellitus-A Nationwide Community-based study.

OBJECTIVE: We investigated the correlation between glycemic control status and depressive symptoms in type 2 diabetes elderly. METHODS: A total of 1527 participants with type 2 diabetes aged 55 years and older from the Healthy Aging Longitudinal Study in Taiwan study were included in this cross-sectional study. The Center for Epidemiologic Studies Depression Scale (CESD) (20 items) score of ≥16 was indicative of depressive symptoms. The participants were divided into HbA1c ≥ 6.5% and < 6.5% representing the glycemic control. Multiple logistic regression (MLR) and Generalized linear model (GLM) were used. RESULTS: The MLR analysis showed that the low HbA1c group had significant two-fold increased odds of depressive symptoms compared to the high HbA1c group (OR 1.89, 95% CI 1.17-3.05). The risk of depressive symptoms was lower among males (OR 0.49, 95% CI 0.30-0.80) and those with higher BMI (OR 0.93, 95% CI 0.86-1.00); whereas the risk was higher among those who lived alone (OR 2.37, 95% CI 1.31-4.27) and with ADL disability (OR 3.01, 95% CI 1.85-4.89). The GLM showed that the dimension of depressive affect reached statistical significance with lower HbA1c. CONCLUSION: This nationwide community-based study shows that depressive symptoms are associated with lower HbA1C, reminding us that more attention should be paid to the presence of depressive symptoms in those with lower HbA1C. Further research is needed to clarify the causal relationship.

Association of 25(OH)-Vitamin D and metabolic factors with colorectal polyps.

BACKGROUND: Studies have revealed the association of vitamin D with specific types of cancer development, however, its correlation with colorectal polyps (CRPs) remains unverified. Our study aimed to investigate the relationship between vitamin D levels, metabolic factors, and CRPs. METHODS: A cross-sectional study from 2017 to 2019 involving 1306 participants was conducted to investigate the association among vitamin D levels, metabolic factors, uric acid and CRPs in Taiwan. CRPs diagnoses were determined via colonoscopies conducted by experienced gastrointestinal physicians, and biopsied polyps were inspected under a microscope by experienced pathologists. We employed both simple and multiple logistic regression analyses to identify significant factors associated with CRPs and adenomatous polyps, respectively. RESULTS: Our result showed that the prevalence of 25(OH)-vitamin D deficiency (≦ 20 ng/mL) and CRPs was 21.21% and 40.89%, respectively. Multiple logistic regression revealed that the risk of CRPs increased with old age, male sex, hyperglycemia, high triglyceride levels, and low 25(OH)D levels after adjustment for other factors. Besides, low 25(OH)D levels were significantly associated with CRPs risk in women, whereas elevated blood pressure was associated with CRPs risk in men. 25(OH)D Deficiency was revealed to be significantly associated with risk of CRPs in adults over 50 years old. Compared to nonadenomatous polyps, older age, higher 25(OH) vitamin D and higher uric acid levels were at increased risk for adenomatous polyps. CONCLUSIONS: Our study revealed that vitamin D deficiency was significantly associated with the risk of CRPs, especially in adults over 50 years old and women. We should therefore be concerned about the CRP risk of vitamin D deficiency and metabolic syndrome (especially hyperglycemia, elevated blood pressure in men, and high triglyceride levels) in this population.

miR-146a participates in the regulation of cancer stemness of oral carcinoma cells.

Background/purpose: Increasing evidence regarded the existence of cancer stem cells (CSCs) as a leading cause of therapy failure and tumor relapse due to their self-renewal and differentiation abilities. Although ectopic overexpression of micro-RNAs (miRNAs) can modulate the cancer stemness and tumor development in oral cancer, their molecular mechanism is still unclear. Therefore, in the present study, we attempt to uncover the role of miR-146a in the maintenance of oral CSCs. Materials and methods: The expression of miR-146a was determined using qRT-PCR analysis. Aldehyde dehydrogenase (ALDH) enzymic activity and sphere formation assays were used to evaluate the cancer stemness and self-renewal, respectively. Functional assays, including migration/invasion Transwell and colony formation assay, were used to evaluate the aggressive abilities. Luciferase reporter assay was performed to validate the relationship between miR-146a and Numb. Results: In the present study, we reported an increased expression of miR-146a in the oral squamous cell carcinoma (OSCC) specimen, primary OSCC cells sphere, and high ALDH1 activity population within OSCC cells. Inhibition of miR-146a significantly suppressed the ALDH1 activity, self-renewal capacity, and aggressive abilities, including migration, invasion, and colony formation. Moreover, we demonstrated that Numb is a functional target of miR-146a in OSCC-CSCs. Notably, silencing of Numb could retrieve the self-renewal and migration impaired by knockdown of miR-146a. Conclusion: Our results indicate that miR-146a can regulate the cancer stemness in OSCC by modulating Numb, and hence miR-146a/Numb axis can serve as a potential target for oral cancer therapy.

The electronic medical record management systems may improve monitoring and control of disease activity in patients with ankylosing spondylitis.

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (6.4 (8.5, 11.2) vs. 6.3 (8.3, 10.8) min, p = 0.073), especially among patients whose with an inactive disease activity was < 1.3 (ASDAS C-reactive protein (CRP) 6.7 (8.8, 11.1) vs. 6.1 (8.0, 10.3) min, p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.

Investigation of changes in ankylosing spondylitis disease activity through 2021 COVID-19 wave in Taiwan by using electronic medical record management system.

We aim to investigate the alteration in disease activity of ankylosing spondylitis (AS) individuals before, during, and after the COVID-19 wave in Taiwan by using electronic medical-record management system (EMRMS). We identified 126 AS individuals from the single center, and gathered data of the three disease activities (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score with erythrocyte sedimentation rate [ASDAS-ESR], and Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein [ASDAS-CRP]) by using EMRMS before (7 February to 1 May, 2021), during (2 May to 24 July, 2021), and after the COVID-19 wave (25 July to 16 October, 2021). We compared the disease activity measures of the three phases through a paired t test. Among the 126 individuals, CRP was significantly higher during the COVID-19 wave (0.2 (0.1, 0.5) mg/dl, p = 0.001) than before the wave (0.2 (0.1, 0.4) mg/dl), ESR (8.0 (4.0, 15.0) mm/h, p = 0.003) and ASDAS-ESR (1.4 (1.0, 1.9), p = 0.032) were significantly higher after the wave than during the wave (6.0 (3.0, 12.0) mm/h and 1.2 (0.9, 1.8) mm/h) e. ESR, CRP, ASDAS-ESR and ASDAS-CRP were all significant higher after COVID-19 wave than before. The disease activities of AS individuals in Taiwan worsened after 2021 COVID-19 wave in Taiwan.

Relationship between Preoperative Nutritional Status and Clinical Outcomes in Patients with Head and Neck Cancer.

The nutritional status in cancer patients is related to cancer survival and surgical outcome. The objective of this study was to examine the relationship between preoperative prognostic nutritional index (PNI) and post-operative clinical outcomes in head and neck cancer (HNC) patients. A total of 1282 head and neck cancer patients receiving surgical resection in Changhua Christian Hospital between 1 January 2010 and 30 August 2021 were recruited in the final analysis after undergoing propensity score matching analysis. The logistic regression model was used to assess the association of the PNI group with overall and various complications. The patients in the high PNI group had a significant lower incidence of overall complications, medical complications, and pulmonary complications; but not significant surgical complications. The high PNI group had lower mortality risk. The results in this study revealed that PNI score was a significant independent predictor of postoperative complications in HNC patients undergoing surgical resection. We recommend preoperative testing and evaluation of HNC patients to identify low PNI and high-risk groups for postoperative surveillance.

Shuterin Enhances the Cytotoxicity of the Natural Killer Leukemia Cell Line KHYG-1 by Increasing the Expression Levels of Granzyme B and IFN-γ through the MAPK and Ras/Raf Signaling Pathways.

Natural killer (NK) cell therapy is an emerging tool for cancer immunotherapy. NK cells are isolated from peripheral blood, and their number and activity are limited. Therefore, primary NK cells should be expanded substantially, and their proliferation and cytotoxicity must be enhanced. Shuterin is a phytochemical isolated from Ficus thonningii. In this study, we explored the possible capacity of shuterin to enhance the proliferation and activity of KHYG-1 cells (an NK leukemia cell line). Shuterin enhanced the proliferation of KHYG-1 cells and their cytotoxicity to K562 cells. Moreover, this phytochemical induced the expression of granzyme B by promoting the phosphorylated cyclic adenosine monophosphate response element-binding protein (CREB) and mitogen-activated protein kinase (MAPK) signaling pathways. Furthermore, the secretion of interferon (IFN)-γ increased with increasing levels of shuterin in KHYG-1 cells and NK cells obtained from adults with head and neck squamous cell carcinoma. Shuterin appeared to induce IFN-γ secretion by increasing the expression of lectin-like transcript 1 and the phosphorylation of proteins involved in the Ras/Raf pathway. Thus, shuterin represents a promising agent for promoting the proliferation and cytotoxicity of NK cells.

Association between a History of herpes zoster and the risk of Sjögren's syndrome: a nationwide, population-based, case-control study.

OBJECTIVE: Viral infection is an exogenous factor for Sjögren's syndrome (SS). The relationship between herpes zoster infection and the ensuring risk of SS has remained unclear. This study investigated the association between a history of herpes zoster infection and the risk of SS through a nationwide population-based case-control study. DESIGN: Retrospective case-control study. SETTING: General population of Taiwan. DATA SOURCE: 2003-2013 National Health Insurance Research Database of Taiwan. PARTICIPANTS: We identified all patients with newly diagnosed SS between 1 January 2007 and 31 December 2012 without a history of rheumatoid arthritis or systemic lupus erythematosus as the SS group. CONTROLS: We randomly selected patients without SS between 1 January 2003 and 31 December 2012 and matched 1:5 with controls based on index year, age and sex. MAIN OUTCOME MEASURE: Conditional logistic regression analysis to examine the association between a history of herpes zoster and the risk of SS. RESULTS: The study included 5751 patients with SS and 28 755 matched controls. The risk of SS was significantly associated with a history of herpes zoster (model A (adjusted for Charlson Comorbidity Index (CCI) (excluding connective tissue disease, CTD)): OR 1.89; 95% CI 1.71 to 2.08; model B (adjusted for comorbidities used to calculate CCI (excluding CTD)): OR 1.90; 95% CI 1.72 to 2.10), in particular if the interval from the last visit for herpes zoster infection to the index date was <3 months (model A: OR 3.09; 95% CI 2.20 to 4.34; model B: OR 3.13; 95% CI 2.20 to 4.45). Such associations remained robust using various definitions of herpes zoster. CONCLUSION: This nationwide, population-based, case-control study revealed a significant association between a history of herpes zoster and the risk of SS.

The effects of modest drinking on life expectancy and mortality risks: a population-based cohort study.

Modest drinking has been repeatedly discussed in scientific papers as protective against certain diseases, such as cardiovascular diseases, but in most cases, alcohol worsens health conditions, especially when consumed at high risk levels. The complexity of the risk relationship between alcohol and health conditions has confused clinicians as to whether it should be recommended. The study aims to balance the risks and benefits of modest drinking. This retrospective cohort study of 430,016 adults recruited from a standard health-screening program since 1994, with 11,031 deaths identified as of 2008. Drinking distinguished "modest drinker" (no more than one drink a day) from "regular drinker". Mortality risks including all-cause mortality and diseases-specific mortality with hazard ratio (HR) were calculated by adjusting for 15 confounders. Life table was used for life expectancy. Risk predictors were subjected to Cox proportional hazards regression analysis to identify significant predictors in multivariate models and life expectancy analysis. Nearly one out of 4 males (23%) was a modest drinker, who gained 0.94 year (95% CI 0.65-1.23 year) in life over non-drinker and had 8% reduction in adjusted all-cause mortality (HR 0.92, 95% CI 0.86-0.97). In contrast, regular drinkers had 43% increase in overall mortality (HR 1.43, CI 1.35-1.52) and shortened life by 6.9 years (95% CI 6.6-7.1 years). As most drinkers also smoked, 59% in modest and 75% in regular, the combined effect shortened life by 2.0 years (95% CI 1.6-2.4 years) in modest drinker and 10.3 years (95% CI 9.8-10.7 years) in regular drinker. Cancer were increased in modest drinkers for oral (HR 2.35, CI 1.38-4.01) and esophageal (HR 3.83, CI 1.90-7.73) cancer. The gain of one year by modest drinkers was erased by a two to fourfold increase in oral and esophageal cancer and that drinking beyond modest amount led to a large loss of life expectancy. Given that drinkers are prone to cross the line of drinking, clinicians should balance the risks and benefits of drinking, as well as the understanding of whether the patient is at risk for addiction.

Association between α-glucosidase inhibitor use and psoriatic disease risk in patients with type 2 diabetes mellitus: A population-based cohort study.

AIMS: To investigate the association between the use of alpha-glucosidase inhibitors (AGIs) and the risk of psoriatic disease (ie, psoriasis and psoriatic arthritis) in patients with type 2 diabetes mellitus (T2DM) treated with metformin. METHODS: Using the 1999-2013 Taiwanese Longitudinal Cohort of Diabetes Patients Database, we identified patients with T2DM who initiated hypoglycaemic treatment between 2003 and 2012. After excluding patients with a history of psoriatic disease (International Classification of Disease, Ninth Revision, Clinical Modification codes 696.0-1) before T2DM diagnosis, patients who received antidiabetic treatment for <90 days, and patients aged <20 or >100 years, we identified 1390 patients who received metformin+AGIs (AGI exposure group) and 47 514 patients who received metformin only (comparison group). We matched the two groups at a 1:10 ratio by age, sex, and index date of T2DM drug use. The association between AGI use and psoriatic disease risk was analysed using a Cox proportional hazard mode; time-dependent covariates for factors were reported in terms of hazard ratios (HRs) with 95% confidence intervals (CIs) after age, sex, T2DM duration, and comorbidities were controlled for. RESULTS: After adjusting the AGI exposure and comparison groups for potential confounders, we found that psoriatic disease risk was associated with metformin+AGI use when AGI was discontinued for 30 days (HR, 8.77; 95% CI, 1.58-48.5) and when a high AGI dose was administered; furthermore, the risk declined during AGI discontinuation. CONCLUSIONS: This population-based study reports that AGI use and interruption of AGI use may be associated with increased psoriatic disease risk in treated patients with T2DM.

The Efficacy and Adverse Events in Patients with Head and Neck Cancer Following Radiotherapy Combined with S-1 Therapy: A Meta-Analysis.

This meta-analysis was conducted to assess the efficacy and adverse events associated with S-1 chemotherapy combined with radiotherapy for patients with head and neck cancer. The PubMed, Embase, and Cochrane Library databases were searched up to 10 February 2021. Eligible studies included clinical trials using S-1 chemotherapy combined with radiotherapy for head and neck cancer patients that measured tumor response, local control rate, overall survival, and grade 3/4 adverse events. A meta-analysis was performed using a random effects model. Twelve trials involving 378 patients met the selection criteria. The objective response and clinical benefit rate (complete/partial response and stable disease) of S-1 chemotherapy with radiotherapy were 86.3% (95% confidence interval (CI), 60.3-96.3) and 88.3% (95% CI, 70.1-96.1), respectively. The median 3-year local control rate, 3-year overall survival rate, and grade 3/4 adverse event rate were 84.0% (95% CI, 71.4-91.7), 69.6% (95% CI, 54.9-81.1), and 42.0% (95% CI, 36.2-48.0), respectively. S-1 combined with radiotherapy for patients with head and neck squamous cell carcinoma results in a good tumor response, favorable survival rate, and low toxicity. A prospective randomized, double-blind trial is required to assess the efficacy and safety of S-1 combined with radiotherapy to treat HNSCC.

Longitudinal changes in physical and mental health of older adults with chronic hepatitis B infection: Trajectories and predictors.

Despite the increasing health burden of chronic hepatitis B (CHB) in aging populations, little is known about the course of health-related quality of life (HRQoL) changes. We aimed to assess individual-level longitudinal HRQoL changes in elderly patients with CHB and to examine their correlates. A prospective 5.1 years-cohort study was conducted in community-dwelling adults aged 55 years with hepatitis B surface antigen-positive. Participants underwent serial measurement of HRQoL using the short-form (12) health survey version 2. Of 503 participants, 82.7% remained in good physical health throughout the study period, whereas 9.1% had declining physical health and 8.2% were in poor physical health. We likewise identified three trajectories of mental health changes ("good mental health" [86.9%], "declining mental health" [6.8%], and "poor mental health" [6.4%]). Three baseline characteristics were independently associated with a lower likelihood of remaining physically or mentally healthy: sarcopenic obesity (odds ratio [OR] with 95% confidence interval [95% CI] of 7.5 [2.8-20.5] for poor physical health, 3.1 [1.1-8.4] for declining physical health, 4.3 [1.4-13.0] for poor mental health), a higher number of metabolic abnormalities (OR [95% CI] of 3.6 [1.6-8.0] for poor physical health) and depressed mood (OR [95% CI] of 21.7 [5.8-81.0] for poor physical health, 5.3 [1.4-19.9] for declining physical health, 83.1 [19.7-350.2] for poor mental health, 13.6 [2.9-64.8] for declining mental health). In conclusion, in a cohort of elderly patients with CHB, we demonstrated the heterogeneity and nonlinearity of HRQoL changes and their associations with variations in specific extrahepatic organs/systems.

Differential relationship of uric acid to mortality and clinical biomarkers of aging according to grip strength in older adults: a cohort study.

Uric acid is both a pro-oxidant and antioxidant. We investigated serum uric acid's association with mortality and aging biomarkers in older adults with varying levels of grip strength. A total of 5329 community-dwelling adults aged ≥55 years underwent assessments of serum uric acid levels, grip strength, and biomarkers of diverse physiological systems. The primary outcome was all-cause mortality. We observed a significant (P < .001) interaction between uric acid levels and grip strength on all-cause mortality risk. Among participants with low grip strength, a nonlinear association (P for nonlinearity = .006) was observed between serum uric acid levels and mortality risk after multivariate adjustment. Compared with participants with neither extreme uric acid levels nor low grip strength, those with a combination of high serum uric acid and low grip strength exhibited greater risks of mortality (adjusted hazard ratio [aHR], 1.52; 95% confidence interval [CI], 1.15-2.02) and deviations in biomarkers of specific systems, so did those with a combination of low serum uric acid and low grip strength (aHR, 1.52; 95% CI, 1.13-2.05). In conclusion, there was a J-shaped association between serum uric acid and the risk of all-cause mortality in older adults. This was primarily true for those with low grip strength.

Platyphyllenone Induces Autophagy and Apoptosis by Modulating the AKT and JNK Mitogen-Activated Protein Kinase Pathways in Oral Cancer Cells.

Platyphyllenone is a type of diarylheptanoid that exhibits anti-inflammatory and chemoprotective effects. However, its effect on oral cancer remains unclear. In this study, we investigated whether platyphyllenone can promote apoptosis and autophagy in SCC-9 and SCC-47 cells. We found that it dose-dependently promoted the cleavage of PARP; caspase-3, -8, and -9 protein expression; and also led to cell cycle arrest at the G2/M phase. Platyphyllenone up-regulated LC3-II and p62 protein expression in both SCC-9 and SCC-47 cell lines, implying that it can induce autophagy. Furthermore, the results demonstrated that platyphyllenone significantly decreased p-AKT and increased p-JNK1/2 mitogen-activated protein kinase (MAPK) signaling pathway in a dose-dependent manner. The specific inhibitors of p-JNK1/2 also reduced platyphyllenone-induced cleavage of PARP, caspase-3, and caspase -8, LC3-II and p62 protein expression. These findings are the first to demonstrate that platyphyllenone can induce both autophagy and apoptosis in oral cancers, and it is expected to provide a therapeutic option as a chemopreventive agent against oral cancer proliferation.

Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells.

Nasopharyngeal carcinoma (NPC) is an important issue in Asia because of its unique geographical and ethnic distribution. Cisplatin-based regimens are commonly the first-line used chemotherapy, but resistance and toxicities remain a problem. Therefore, the use of anticancer agents derived from natural products may be a solution. Asiatic acid (AA), extracted from Centella asiatica, was found to have anticancer activity in various cancers. The aim of this study is to examine the cytotoxic effect and mediated mechanism of AA in cisplatin-resistant NPC cells. The results shows that AA significantly reduce the cell viability of cisplatin-resistant NPC cell lines (cis NPC-039 and cis NPC-BM) in dose and time dependent manners caused by apoptosis through the both intrinsic and extrinsic apoptotic pathways, including altered mitochondrial membrane potential, activated death receptors, increased Bax expression, and upregulated caspase 3, 8, and 9. The Western blot analysis of AA-treated cell lines reveals that the phosphorylation of MAPK pathway proteins is involved. Further, the results of adding inhibitors of these proteins indicates that the phosphorylation of p38 are the key mediators in AA-induced apoptosis in cisplatin-resistant human NPC cells. This is the first study to demonstrate the AA-induced apoptotic pathway through the phosphorylation p38 in human cisplatin-resistant nasopharyngeal carcinoma. AA is expected to be another therapeutic option for cisplatin-resistant NPC because of the promising anti-cancer effect and fewer toxic properties.

Lotus Seedpod Extracts Reduced Lipid Accumulation and Lipotoxicity in Hepatocytes.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders, including hepatic lipid accumulation and lipotoxicity. Plant-derived polyphenols have attracted considerable attention in the prevention of NAFLD. Lotus seedpod, rich in polyphenols, is a traditional Chinese herbal medicine. Previous studies have showed that lotus seedpod possess radioprotective, antioxidant, anti-cancer, and anti-inflammatory activities. In this study, the in vitro hepatoprotective effect of lotus seedpod extract (LSE) and its main component epigallocatechin (EGC) was examined. Firstly, oleic acid (OA), an unsaturated fatty acid, was used to induce the phenotype of NAFLD in human hepatocytes, HepG2 cells. LSE dose-dependently improved the OA-induced viability loss of HepG2 cells. Non-cytotoxic concentrations of LSE or EGC abolished intracellular lipid accumulation and oxidative stress in the OA-treated cells. In addition, LSE and EGC showed a minor effect on autophagy, and potential in reducing OA-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the formation of apoptotic bodies, the exposure of phosphatidylserine, and activation of caspases. Molecular data showed the anti-apoptotic effect of LSE might be mediated via downregulation of the mitochondrial pathway. Our data imply that EGC-enriched LSE potentially could be developed as an anti-NAFLD agent.

Pinostilbene Hydrate Inhibits the Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Downregulating MMP-2 Expression and Suppressing Epithelial-Mesenchymal Transition Through the Mitogen-Activated Protein Kinase Signaling Pathways.

Background: Nasopharyngeal carcinoma (NPC) is one of the most common head and neck cancers in East and Southeast Asia. During the past decades, advances in radiotherapy and chemotherapy had shown the improvement in tumor control with fewer side effects. Nevertheless, metastasis of NPC causes treatment failure and is often associated with poor clinical outcome and cancer mortality. Hypothesis/Purpose: Pinostilbene hydrate (PSH) was recently demonstrated to have anti-metastatic properties on human oral cancers. However, the effects of PSH on NPC cells remain unknown. Methods and Results: This study aims to investigate the anti-cancer ability of PSH on human NPC by wound healing, transwell assays, zymography assay, and Western blot assay to explore the possible underlying mechanisms. PSH significantly reduced the migrated distance of NPC cells in a dose-dependent manner and the abilities of cancer cell migration and invasion were markedly inhibited. The activity and the expression of MMP-2 were also significantly decreased after treatment with PSH. Furthermore, combined treatment of PSH with ERK1/2 inhibitor (U0126) caused significant elevation of the activity and the expression of MMP-2. Additionally, PSH upregulated the expression levels of E-cadherin and Claudin-1 while downregulating that of N-cadherin and vimentin on both NPC cell lines. Conclusion: Our research illustrates that PSH inhibits the migration and invasion of human NPC cells. After exposure to PSH on NPC, the expression of MMP-2 is downregulated and EMT is suppressed through MAPK signaling pathways. These observations suggest that PSH could be a potential anti-metastatic agent for patients with NPC.