The Relationship between Dynapenic Abdominal Obesity and Fall: A Systematic Review and Meta-Analysis of 15,506 Middle to Older Adults.

BACKGROUND: The main objective of this study was to investigate the risk of falls among middle-aged and older adults with dynapenic abdominal obesity. METHODS: A systematic literature search was conducted to review and analyze relevant studies. Dynapenia was measured by handgrip strength, and abdominal obesity was measured by waist circumference. The search keywords included "older people" OR "elderly" OR "middle age" AND "dynapenia" AND "abdominal obesity" AND "fall." The search was not limited by time and included articles published up until April 2023. The literature search process followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, involving extraction and examination of the retrieved relevant articles. Systematic literature searches were performed in databases such as Embase, PubMed, MEDLINE, CINAHL, and Cochrane Library. RESULTS: This study collected a total of eight articles with a combined sample size of 15,506 participants. The findings revealed that the average follow-up period for falls was 6.6 years (SD = 3.67). The overall results of the study showed that individuals with dynapenic abdominal obesity had a higher risk of falls compared to those without dynapenic abdominal obesity (RR = 6.91, 95% CI: 5.42-8.80). Subgroup analysis demonstrated that both prospective studies (HR = 6.61; 95% CI = 4.29-10.20) and retrospective studies (OR = 7.37; 95% CI = 5.13-10.59) consistently found a higher risk of falls among individuals with dynapenic abdominal obesity. However, there was no significant difference in fall risk between community-dwelling individuals with dynapenic abdominal obesity and hospitalized individuals with dynapenic abdominal obesity (Qbetweenx2 = 0.29, p = 0.58). Additionally, there was no difference in fall risk between individuals with dynapenic abdominal obesity residing in Europe and Latin America compared to those residing in Asia (Qbetweenx2 = 0.05, p = 0.81). It was worth noting that male individuals with dynapenic abdominal obesity had a higher risk of falls compared to females (Qbetweenx2 = 4.73, p = 0.03). CONCLUSIONS: Empirical studies have demonstrated that individuals with dynapenic abdominal obesity have a higher risk of falls. Therefore, healthcare professionals should conduct early fall risk assessments and develop effective preventive strategies specifically targeted at individuals with dynapenic abdominal obesity.

Isolinderalactone Induces Apoptosis, Autophagy, Cell Cycle Arrest and MAPK Activation through ROS-Mediated Signaling in Colorectal Cancer Cell Lines.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Isolinderalactone (ILL), a sesquiterpene isolated from the root extract of Lindera aggregata, has been reported to exhibit anti-proliferative and anti-metastatic activities in various cancer cell lines. However, the mechanisms associated with its antitumor effects on CRC cells remain unclear. ILL treatment significantly suppressed proliferation and induced cell cycle G2/M arrest in CRC cells by inhibiting the expression of cyclin B, p-cdc2, and p-cdc25c and up-regulating the expression of p21. In addition, ILL induced mitochondria-associated apoptosis through the up-regulation of cleaved -caspase-9 and -3 expression. ILL induced autophagy by increasing the levels of LC3B in CRC cells, which was partially rescued by treatment with an autophagy inhibitor (chloroquine). Furthermore, ILL increases the accumulation of reactive oxygen species (ROS) and activates the MAPK pathway. Application of the ROS scavenger, N-acetyl cysteine (NAC), effectively inhibited ILL toxicity and reversed ILL-induced apoptosis, cell cycle arrest, autophagy, and ERK activation. Taken together, these results suggest that ILL induces G2/M phase arrest, apoptosis, and autophagy and activates the MAPK pathway via ROS-mediated signaling in human CRC cells.

The relationships between physical function, nutrition, cognitive function, depression, and sleep quality for facility-dwelling older adults with dynapenia.

BACKGROUND: The growing population of older adults worldwide is associated with an extended life expectancy and an increasing proportion of older adults with dynapenia. Most research on dynapenia has involved only populations of older adults living in the community; little research has examined the effects of risk factors on sleep quality among older adults with dynapenia residing in assisted living facilities. AIM: This study examined the relationships among physical function, nutrition, cognitive function, depression, and sleep quality among older adults with dynapenia residing in assisted living facilities. METHODS: In this cross-sectional study, data on physical function, nutrition, cognitive function, depression, and sleep quality was collected from 178 older adults with dynapenia residing in assisted living facilities, who were selected using purposive sampling. Descriptive statistical analysis, independent-sample t tests, chi-squared tests, and logistic regression analysis were performed using SPSS 25.0. RESULTS: The statistical analyses revealed correlations between sleep quality and age (t = 2.37, p < 0.05), level of education (χ2 = 3.85, p < 0.05), grip strength (t = 3.40, p < 0.01), activities of daily living (t = 4.29, p < 0.001), instrumental activities of daily living (t = 2.23, p < 0.001), calf circumference (t = 2.89, p < 0.01), Mini Nutritional Assessment scores (t = 2.29, p < 0.05), Mini Mental State Exam (MMSE) scores (t = 4.50, p < 0.001), and Geriatric Depression Scale (GDS) scores (t = - 4.20, p < 0.001). Calf circumference (OR = 0.8, 95% CI = 0.650.97, p < 0.05), GDS score (OR = 1.42, 95% CI = 1.05-1.92, p < 0.05), and MMSE score (OR = 0.85, 95% CI = 0.73-0.97, p < 0.05) were related to sleep quality among the sample population. CONCLUSION: Physical function, nutrition, cognitive function, and depression affect the sleep quality of older adults with dynapenia residing in assisted living facilities. Facility nurses must regularly assess these aspects of their patients to ensure that facility-dwelling older adults can maintain their physical function and improve their health to improve the quality of their sleep.

Prediction of physiological state, cognition, sensory function, and biomarkers for frailty in patients aged 55 years or more with schizophrenia.

AIM: We explored the performance of demographic characteristics, physiological state, cognitive function, sensory function, and biomarkers when used as predictors of frailty for patients with schizophrenia. DESIGN: A cross-sectional study design was adopted. METHODS: Demographic data and data on physiological state, cognitive function, sensory function, biochemical indices, and frailty status of patients with schizophrenia were collected. The data were analysed using descriptive statistics, a chi-square test, one-factor analysis of variance, and logistic regression. RESULTS: The results revealed that frailty was prevalent among patients with lower educational attainment, longer hospital stay, higher skeletal muscle mass, higher basal metabolic rate, lower cognitive function, the use of tranquillisers and sleeping pills, and the use of assistive equipment as well as having fallen in the past year. In addition, cognitive function (p < 0.05), use of a wheelchair (p < 0.05), and use of an assistive walker (p < 0.001) were used as predictors of frailty condition of patients with schizophrenia. PATIENT CONTRIBUTION: Patients with schizophrenia have higher risk of having complications than patients with other chronic illnesses. Therefore, medical staff should regularly assess the levels of frailty risk to help patients with schizophrenia.

Muscle Strength, Physical Fitness, Balance, and Walking Ability at Risk of Fall for Prefrail Older People.

Aim: This study was to explore the relationship of older adults' demographic information, physiological indices, and stages of frailty with their risk of falling. Methods: In the cross-sectional study, a total of 221 older adults with the mean age 74.9 (SD = 6.8) years old were surveyed by senior fitness test. Results: Results were observed in terms of participants' physical fitness, with significant differences being observed in the correlations of left-hand grip strength (t = 5.05, p < .000), right-hand grip strength (t = 6.03, p < .000), and total grip strength (t = 5.70, p < .000), time up and go test (t = -6.25, p < .000), and 30-sec chair stand test (t = 7.19, p < .000) with the risk of falling. According to the logistic regression analysis results, long-term medication (OR = 0.12, 95% CI =0.02-0.62, p < .01) and right-hand grip strength (OR = 0.86, 95% CI =0.76-0.97, p < .01) are the main predictors of older adults' risk of falling. Conclusions: Older females with low education, history of falls, weaker grip strengths; taking longer to finish the TUG test; and standing fewer times during the 30-second chair stand test were at risk of fall. In prediction, older people using long-term medication were at lower risk of falling, and the greater the hand grip strength was, the lower the fall risk was. According to the research results, nursing personnel must develop care programs and improve older adults' risk of falls.

The Relationship between Sarcopenia and Injury Events: A Systematic Review and Meta-Analysis of 98,754 Older Adults.

The main purpose of this study was to investigate the relationship between sarcopenia and injury events (falls, fractures, hospitalization, disability, and death). This study systemically searched the literature from Embase, PubMed, MEDLINE, CINAHL, and Cochrane Library and analyzed the collected literature using the random effects model to demonstrate the relationship between sarcopenia and injury events. This study followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and collected a total of 38 prospective studies, and the results showed that, when compared to robust individuals, the risk of injury events for older individuals with sarcopenia was significantly higher for fractures (HR = 9.66, CI: 5.07-18.38), hospital admissions (HR = 11.80, CI: 4.86-28.65), and death (HR = 9.57, CI: 3.17-28.94). In consideration of the negative impact of sarcopenia on the subsequent health of older adults, professional nursing personnel should assess older adults for sarcopenia as early as possible and propose relevant care policies to further reduce negative health impacts.

Incidence of low-level viremia and its impact on virologic failure among people living with HIV-1 who switched to elvitegravir-based antiretroviral therapy.

OBJECTIVES: We aimed to investigate the incidence of low-level viremia (LLV) and its impact on virologic failure (VF) in people living with HIV (PLWH) on stable antiretroviral therapy (ART) who switched to co-formulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide (EVG/c/FTC/TAF). METHODS: PLWH aged 18 years or older who had received ART with plasma HIV RNA load (PVL) <50 copies/mL for 6 months or longer and switched to EVG/c/FTC/TAF between March and October 2018 were retrospectively included. The incidence of LLV (defined as PVL of 50-999 copies/mL) and VF (PVL ≥1000 copies/mL) was calculated and represented by Kaplan-Meier plots. The generalised estimating equation model was constructed to identify factors associated with LLV and VF. Resistance-associated mutations were determined using population sequencing. RESULTS: A total of 1078 PLWH were included. The incidence rates of LLV and VF after the switch to EVG/c/FTC/TAF were 3.5 and 0.8 events per 100 person-years of follow-up, respectively, whereas the respective cumulative incidence of LLV and VF reached 11.7% and 2.9% within 3 years of follow-up. LLV was associated with any LLV episode before or after the switch and prior exposure to integrase strand transfer inhibitor-based ART. VF was associated with any LLV before or after the switch and prior exposure to raltegravir, but not the level or frequency of LLV. CONCLUSION: The risks of LLV and VF were low in PLWH who had achieved virologic suppression and switched to EVG/c/FTC/TAF, and the presence of LLV and prior exposure to raltegravir increased the risk of VF.

Hispolon Induces Apoptosis, Suppresses Migration and Invasion of Glioblastoma Cells and Inhibits GBM Xenograft Tumor Growth In Vivo.

Hispolon, a polyphenol compound isolated from Phellinus linteus, has been reported to exhibit antioxidant, antiproliferative, and antitumor activities. This study aimed to explore the antitumor effects of hispolon on glioblastoma multiforme (GBM) cells in vitro and in vivo. The results revealed that hispolon significantly inhibited GBM cell proliferation and induced apoptosis through caspase-9 and caspase-3 activation and PARP cleavage. Hispolon also induced cell cycle G2/M phase arrest in GBM cells, as supported by flow cytometry analysis and confirmed by a decrease in cyclin B1, cdc2, and cdc25c protein expressions in a dose- and time-dependent manner. Furthermore, hispolon suppressed the migration and invasion of GBM cells by modulating epithelial-mesenchymal transition (EMT) markers via wound healing, transwell assays, and real-time PCR. Moreover, hispolon significantly reduced tumor growth in DBTRG xenograft mice and activated caspase-3 in hispolon-treated tumors. Thus, our findings revealed that hispolon is a potential candidate for the treatment of GBM.

Adverse Health Effects of Frailty: Systematic Review and Meta-Analysis of Middle-Aged and Older Adults With Implications for Evidence-Based Practice.

BACKGROUND: Scholars have noted that frailty easily leads to functional deterioration and proneness to complications. Little literature addresses the stages of frailty in middle-aged and older adults and the effects of frailty on overall health. AIMS: This study explores the effect of different stages of frailty on the prospective health (falls, bone fractures, disability, dementia, hospitalization, and death) of middle-aged and older adults. In addition, different frailty indicators were compared to determine their usefulness in predicting future adverse health outcomes. METHODS: The authors of this study separately reviewed and extracted data from the literature obtained while searching the following keywords: "frailty" OR "frail" and "fall" OR "disability" OR "fracture" OR "hospitalization" OR "mortality" OR "cognitive function" "dementia" OR "Alzheimer's disease" and "middle-aged people" OR "older people" OR "elderly" OR "geriatric" OR "senior." The literature search was performed from January 2001 to November 2019 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Specifically, we performed a systematic literature search in multiple databases-Embase, PubMed, MEDLINE, CINAHL, and Cochrane Library-and analyzed all obtained literature results using a random-effects model. RESULTS: We collected a total of 29 prospective studies for the systematic literature review and meta-analysis. The main results indicated that the frail groups had significantly higher risks of adverse health effects (falls, bone fractures, disability, dementia, hospitalization, and death) than the robust or prefrail groups. LINKING EVIDENCE TO ACTION: Frailty is a crucial healthcare topic among geriatric syndromes. Considering that older adults with frailty are most likely to develop severe adverse health outcomes, professional nursing personnel should assess frailty among middle-aged and older adults and offer relevant care strategies to reduce the adverse effects of frailty in this population.

The Relations Among Physical Indicators, Cognitive Status, Community Participation, and Depression of the Frail Male Elderly in Taiwan.

This study explored the basic attributes, physiological indices, cognitive states, and community participation of older male outpatients with frailty for predicting depression. Questionnaires were collected using purposive sampling from a medical clinic in a teaching hospital in northern Taiwan. One hundred and ninety frail men enrolled as participants. The results revealed that older male adults with frailty, the age, residence, income, self-reported health status, alcohol consumption, total instrumental activities of daily living (IADL) scores in physiological indices, IADL grouping, cognitive state score, each Mini-Mental State Examination category, and involvement and dedication scores exhibited statistical differences from depression scores. Depression determinants, such as an excellent and normal self-reported health status and IADL total score, could predict the depression status of male older adults with frailty. Nursing personnel should assess the self-reported health status and self-care ability of male older adults with frailty early to prevent or delay geriatric depression.

The Synergistic Anti-Cancer Effects of NVP-BEZ235 and Regorafenib in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Regorafenib is a multi-kinase inhibitor and the second-line treatment for HCC. Since the PI3K/Akt/mTOR signaling pathway is dysregulated in HCC, we evaluated the therapeutic effects of regorafenib combined with a dual PI3K/mTOR inhibitor BEZ235 in the human HCC cell lines (n = 3). The combined treatment with BEZ235 and regorafenib enhanced the inhibition of cell proliferation and increased the expression of cleaved caspase-3 and cleaved PARP in HCC cells. Moreover, the combined treatment suppressed HCC cell migration and invasion in the transwell assay. Further, the Western blot analyses confirmed the involvement of epithelial-mesenchymal transition (EMT)-related genes such as slug, vimentin, and matrix metalloproteinase (MMP)-9/-2. Additionally, the proteinase activity of MMP-9/-2 was analyzed using gelatin zymography. Furthermore, the inhibition of phosphorylation of the Akt, mTOR, p70S6K, and 4EBP1 after combined treatment was validated using Western blot analysis. Therefore, these results suggest that the combined treatment with BEZ235 and regorafenib benefits patients with HCC.

Effect of resistance training on quality of life in older people with sarcopenic obesity living in long-term care institutions: A quasi-experimental study.

AIMS AND OBJECTIVES: To measure the effect of chair resistance training (RT) on the quality of life (QoL) of older long-term care residents with sarcopenic obesity (SO). BACKGROUND: Sarcopenia combined with obesity, commonly called SO, is considered to be related to health-related QoL. Despite concerns regarding SO-related long-term healthcare issues, intervention studies on SO residents in nursing homes are scant in Taiwan. DESIGN: This research was a quasi-experiment conducted according to the TREND Checklist. A total of 123 older persons were enrolled from six nursing facilities. The RT was implemented between October 2015-March 2016. METHOD: The intervention group received progressive RT with sandbags/dumbbells twice a week for 3 months, whereas the comparison group received the usual care. QoL was the major outcome variable. Data were analysed using chi-square test, Student's t test and generalised estimating equation (GEE). RESULTS: The various definition criteria for SO can influence the results of QoL in the older persons. From the body composition perspective, in the GEE analysis, the SO cut-off points for neither skeletal muscle mass percentage (SMMp) nor appendicular skeletal muscle mass index demonstrated significant between-group differences in the QoL variable after the 3-month RT intervention. Between-group analysis revealed a significant effect of time on anxiety/depression [Exp(B): 0.41, 95% confidence interval: 0.18-0.93, p-value < .05] in participants who met all three criteria of the definition of SO (low SMMp, low handgrip strength, and obesity). RT was one of the protective factors. CONCLUSION: In the SO group, the effect of muscle strength on QoL is greater than the effect of changes in body composition after RT. RELEVANCE TO CLINICAL PRACTICE: This study analysed the influence of RT on QoL in subjects with different categories of SO. RT is one of the ways to promote QoL among the SO population. ClinicalTrials.gov Identifier: NCT02912338.

The Protective Effect of Hispidin against Hydrogen Peroxide-Induced Oxidative Stress in ARPE-19 Cells via Nrf2 Signaling Pathway.

Hispidin, a polyphenol compound isolated from Phellinuslinteus, has been reported to possess antioxidant activities. In this study, we aimed to investigate the mechanisms underlying the protective effect of hispidin against hydrogen peroxide (H2O2)-induced oxidative stress on Adult Retinal Pigment Epithelial cell line-19 (ARPE-19) cells. Hispidin was not cytotoxic to ARPE-19 cells at concentrations of less than 50 µM. The levels of intracellular reactive oxygen species (ROS) were analyzed by dichlorofluorescin diacetate (DCFDA) staining. Hispidin significantly restored H2O2-induced cell death and reduced the levels of intracellular ROS. The expression levels of antioxidant enzymes, such as NAD(P)H:Quinine oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) were examined using real-time PCR and Western blotting. Our results showed that hispidin markedly enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1, NQO-1, GCLM, and GCLC in a dose-dependent manner. Furthermore, knockdown experiments revealed that transfection with Nrf2 siRNA successfully suppresses the hispidin activated Nrf2 signaling in ARPE-19 cells. Moreover, activation of the c-Jun N-terminal kinase (JNK) pathway is involved in mediating the protective effects of hispidin on the ARPE-19 cells. Thus, the present study demonstrated that hispidin provides protection against H2O2-induced damage in ARPE-19 cells via activation of Nrf2 signaling and up-regulation of its downstream targets, including Phase II enzymes, which might be associated with the activation of the JNK pathway.

The Relationship Between Depression and Frailty in Community-Dwelling Older People: A Systematic Review and Meta-Analysis of 84,351 Older Adults.

OBJECTIVES: In this study we investigated the correlation between depression and frailty in older adults. Additionally, correlations among study designs (prospective vs. cross-sectional), regions, depression indices, frailty indices, covariance corrections, and sexes were explored to support the analysis. METHODS: A systematic literature review and meta-analysis were conducted. A total of 84,351 older adults, all 65 years of age or older, were analyzed. Both authors independently extracted and examined retrieved articles. Searched keywords included "depression" or "depressive"; "frailty" or "frail"; and "older people," "elderly," "geriatric," or "senior." Articles published between January 2000 and December 2016 were searched. A literature quality assessment was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic REVIEWS AND META-ANALYSES: Systematic literature searches were conducted on the Embase, PubMed, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases, and collected studies were analyzed using a random effects model. RESULTS: Fourteen studies on people 65 years of age or older were collected, and a correlation analysis was conducted for depression and frailty. According to the meta-analysis, the risk for frailty due to depression was nonsignificant among the subgroups for study design (p for heterogeneity = .149), region (p = .429), depression criteria (p = .934), covariate adjustment (p = .702), and frailty criteria (p = .661). Notably, the risk for frailty due to depression was significantly higher in men than in women (pooled odds ratios for men and women: 4.76 and 2.25, respectively; Qbetween χ2 = 9.93, p = .002). CONCLUSION: Older adults with depression are more prone to frailty than are those without depression. Regardless of study design, region, depression index, frailty index, and covariance corrections, no significant differences were observed in the results of studies on depression and frailty in older adults. The only factor that had a significant influence was sex; older men with depression were at a higher risk for frailty than were older women with depression. CLINICAL RELEVANCE: Depression and frailty are pertinent health concerns related to geriatric syndromes. Because older adults with depression have a high risk for frailty, nursing personnel should use a depression index as early as possible to screen for depression and further reduce the occurrence of frailty in older adults. Furthermore, based on the aforementioned differences between the sexes, special attention should be paid to older men with depression to reduce their risk for frailty.

Frail Phenotype and Disability Prediction in Community-Dwelling Older People: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

BACKGROUND: The World Health Organization has identified frailty as a crucial factor affecting successful aging. Systematic literature reviews have yet to focus on the relationship between stages of frailty and disability in community-dwelling older adults. PURPOSE: The purpose of this study was to investigate the relationships between various frailty types and disability in community-dwelling older adults and to explore how various frailty criteria have been used to assess disability in this population. METHODS: A systematic literature review and meta-analysis were conducted on articles from the following databases: Cochrane Library, CINAHL, PubMed, and Ovid. Database search criteria included articles that were published between January 2001 and July 2017 and study samples that included community-dwelling adults aged 60 years and older. We excluded studies that were conducted in institutions or hospitals and experimental studies on frailty. Two reviewers independently assessed eligibility and extracted data. A random-effects model was used to analyze the literature and to calculate the pooled disability of frailty. RESULTS: In total, nine studies with a total sample of 32,998 participants that recorded 8,666 disabilities and a mean follow-up time of 30.4 months (SD = 29.26) were pooled for the meta-analysis. Using various indicators to predict the risk of disability compared with robust older adults, those with frailty faced a higher risk of disability, followed by older adults at risk of frailty. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Frailty is a crucial health consideration among older adults. Those who are frail have the highest relative risk of disability, followed by those at risk of frailty. Early assessment of frailty may effectively prevent the occurrence of frailty-induced disability in older adults.

Outcome assessment of apical surgery: A study of 234 teeth.

BACKGROUND/PURPOSE: Apical surgery is an option for management of endodontically-treated tooth with persistent periapical lesions or symptom and sign. The objective of this study was to investigate the correlation between the demography, preoperative, postoperative factors and healed rate of apical surgery. METHODS: Subjects were retrospectively collected from patients who received apical surgery/apicoectomy at the Endodontic Department, National Taiwan University Hospital from January 2013 to June 2015. The standard apical surgery procedures were performed. The demography, preoperative clinical and radiographic examination data as well as postoperative variables were collected. The outcome assessment was carried out after surgery. Statistical analysis was performed by chi square test to evaluate the potential outcome predictors. RESULTS: Total 187 patients and 234 teeth receiving apical surgery were included. 53 male and 134 female patients were collected. The age was ranged between 17 and 89 years old and the mean age was 43.64 years old. Better healed rate with significant differences were observed in female patient (p < 0.05), age ≤60 years old (p < 0.01), preoperative root canal filling material >2 mm short of apex (p < 0.01), lesion size from ≤2 mm to ≤12 mm (p < 0.05) and follow-up period â‰§12 months (p < 0.01) groups. CONCLUSION: Gender, age, preoperative root canal filling material extent, lesion size and follow-up period may affect the outcome of apical surgery. Tooth type, post, prosthesis, and lesion area showed no marked effect on apical healing. These results provide more detailed information for the clinical practitioners to make treatment plans and are important for clinical endodontic practices.

Anti-Cancer Effects of Radix Angelica Sinensis (Danggui) and N-Butylidenephthalide on Gastric Cancer: Implications for REDD1 Activation and mTOR Inhibition.

BACKGROUND/AIMS: Radix Angelica Sinensis (danggui in Chinese) is widely used in traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive compound in danggui, is a potential antitumor agent for various cancer types. However, its clinical effect and mechanism in the treatment of gastric cancer remain undetermined. METHODS: The in vivo protective effect of danggui in patients with gastric cancer were validated using data from Taiwan's National Health Insurance Research Database (NHIRD). The genes induced by BP-treatment were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell migration and invasion was evaluated in transwell assays. The antitumor effects of BP were evaluated in vivo in an AGS xenograft animal model. RESULTS: Danggui users were found to have an increased survival rate when compared with danggui nonusers (log-rank test p = 0.002) . The use of danggui highly associated with decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95 % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited gastric cancer cell proliferation, and triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we found that REDD1 was the highest transcript induced by BP in gastric cancer cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling, thus inhibiting gastric cancer growth. We used RNA interference to demonstrate that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo. CONCLUSION: Danggui can prolong the survival rate of gastric cancer patients in Taiwan. BP caused gastric cancer cell death through the activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo growth of AGS xenograft tumors. These results may provide the basis for a new therapeutic approach toward the treatment of gastric cancer progression.

Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study.

BACKGROUND: Increasing trends of resistance-associated mutations (RAMs) to non-nucleoside reverse-transcriptase inhibitors (nNRTIs) have raised concerns about the effectiveness of the regimens in the national HIV treatment programs in resource-limited countries. We aimed to retrospectively investigate the incidence and patterns of emergent RAMs of HIV-1 in HIV-positive adults experiencing virological failure to first-line nNRTI-containing combination antiretroviral therapy (cART) in Taiwan. PATIENTS AND METHODS: Between June 2012 and March 2016, 1138 antiretroviral-naïve HIV-positive adults without baseline RAMs who initiated nNRTI-containing regimens were included for analysis. Virological failure was defined as plasma viral load (PVL) ≥200 copies/mL after 6 months of cART or confirmed PVL ≥200 copies/mL after achieving PVL <50 copies/mL. Population sequencing was retrospectively performed to detect baseline and emergent RAMs. RAMs were interpreted using the International AIDS Society-USA 2016 mutations list. RESULTS: Seventy-one patients (6.2%) developed virological failure, which occurred in 14.8% (43/291), 3.9% (26/675), and 1.2% (2/172) of patients receiving 2 nucleoside reverse-transcriptase inhibitors (NRTIs) plus nevirapine, efavirenz, and rilpivirine, respectively. Among those, 53 (74.6%) had emergent RAMs identified, which included 43 (81.1%), 53 (100.0%), and 1 (1.9%) with RAMs to NRTIs, nNRTIs, and protease inhibitors, respectively; and 43 (81.1%) had multi-drug resistance. The most common emergent RAMs to NRTIs were M184V/I (42.3%) and K65R (28.2%), and those to nNRTIs were Y181C (42.3%), K103N (15.5%), G190A/E/Q (12.7%), V179D/E (12.7%), and V108I (9.9%). CONCLUSION: While the rates of virological failure varied with the nNRTI used, the rate of emergent RAMs of HIV-1 to NRTIs and nNRTIs among the antiretroviral-naïve patients who failed nNRTI-containing cART remained low.

The Relationship of Frailty and Hospitalization Among Older People: Evidence From a Meta-Analysis.

OBJECTIVES: This research explored the relationship between the stages of frailty and risk for hospitalization in older adults and evaluated the risk for hospitalization among the elderly in relation to various frailty assessment indexes. METHODS: A systematic literature review and meta-analysis were carried out. A total of 32,998 older people, 8,666 of whom were hospitalized, were included in this study. Two of the researchers independently collected and reviewed the literature. The key search terms used were "frailty" or "frail," "hospitalization," and "older people" or "older" or "geriatric" or "senior." Data were recorded from January 2001 to July 2016. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adopted for quality assessment. A systematic search was carried out using Embase and Scopus to analyze the collected literature. FINDINGS: A meta-analysis was conducted on eight studies that discussed the relationship between frailty and hospitalization risk in older adults 65 years of age or older. The results showed that frail older people exhibited the highest risk for hospitalization, following by prefrail and robust older people. Next, different frailty assessment indicators were used to predict the risk for hospitalization among older people. All of these indexes also showed that older persons with frailty had the highest risk for hospitalization, followed by prefrail older people. CONCLUSIONS: Frailty is a vital issue in geriatric care and is a crucial factor in the hospitalization of older people. Frail older people were at the highest risk for hospitalization, following by prefrail and robust older people. Assessing frailty as early as possible can reduce the hospitalization risk among older people. CLINICAL RELEVANCE: Professional nursing staff should use frailty indicators in a timely fashion to assess the status of frailty in older people and should effectively develop frailty prevention strategies to decrease the risk for hospitalization and to enhance quality of life for older adults.