Combining principal component analysis and logistic regression for multifactorial fall risk prediction among community-dwelling older adults.

Falls require comprehensive assessment in older adults due to their diverse risk factors. This study aimed to develop an effective fall risk prediction model for community-dwelling older adults by integrating principal component analysis (PCA) with machine learning. Data were collected for 45 fall-related variables from 1630 older adults in Taiwan, and models were developed using PCA and logistic regression. The optimal model, PCA with stepwise logistic regression, had an area under the receiver operating characteristic curve of 0.78, sensitivity of 74 %, specificity of 70 %, and accuracy of 71 %. While dimensionality reduction via PCA is not essential, it aids practicality. Our framework combines PCA and logistic regression, providing a reliable method for fall risk prediction to support consistent screening and targeted health promotion. The key innovation is using PCA prior to logistic regression, overcoming conventional limitations. This offers an effective community-based fall screening tool for older adults.

Effects of Taiwan's COVID-19 alert levels on the physical activity behaviors and psychological distress of community-dwelling older adults.

BACKGROUND: The Taiwanese government implemented stringent preventative health measures to curb the spread of COVID-19. However, these measures negatively affected the physical activity behaviors and psychological distress of individuals. In this study, we investigated the effects of Taiwan's COVID-19 alert-based restrictions on the physical activity behaviors and psychological distress of community-dwelling older adults. METHODS: In this longitudinal study, 500 community-dwelling older adults were randomly sampled from a health promotion center in Taiwan. Telephone interviews were conducted between May 11, 2021, and August 17, 2021, which coincided with the Level 3 alert period when group physical activities were prohibited. Telephone interviews were again conducted between June 20, 2022, and July 4, 2022, after the alert level was reduced to Level 2 but group physical activities were prohibited period. Through the telephone interviews, data regarding the participants' physical activity behaviors (type and amount) and 5-item Brief Symptom Rating Scale (BSRS-5) scores were collected. Moreover, data regarding physical activity behaviors were collected from the records of our previous health promotion programs, which were conducted before the national alert period. The obtained data were analyzed. RESULTS: The alert levels influenced physical activity behaviors. Because of strict regulations, physical activity amount decreased during the Level 3 alert period and did not recover rapidly during the Level 2 alert period. Instead of engaging in group exercises (e.g., calisthenics and qigong), the older adults chose to exercise alone (e.g., strolling, brisk walking, and biking). Our findings indicate that the COVID-19 alert level has a significant influence on the amount of physical activity for participants (p < 0.05, partial η2 = 0.256), with pairwise comparisons showing that the physical activity amount decreased significantly across the three time periods (p < 0.05). The psychological distress of the participants did not appear to change during the regulation period. Although the participants' overall BSRS-5 score was slightly lower during the Level 2 alert period compared to the Level 3 alert period, the difference was not statistically significant (p = 0.264, Cohen's d = 0.08) based on a paired t-test. However, the levels of anxiety (p = 0.003, Cohen's d = 0.23) and inferiority (p = 0.034, Cohen's d = 0.159) were considerably higher during the Level 2 alert period than during the Level 3 alert period. CONCLUSIONS: Our findings indicate that Taiwan's COVID-19 alert levels influenced the physical activity behaviors and psychological distress of community-dwelling older adults. Time is required for older adults to regain their prior status after their physical activity behaviors and psychological distress were affected by national regulations.

Physical fitness and its correlation with handgrip strength in active community-dwelling older adults.

In this cross-sectional study, we assessed the physical fitness levels of active community-dwelling older adults. Moreover, we investigated the correlation of their (stratified by age and sex) fitness levels with handgrip strength (HGS). Comprehensive physical fitness tests, including sarcopenia screening, were conducted with a total of 2,130 older adults residing in a rural area of Taiwan. The 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of age- and sex-specific physical fitness levels were determined. Furthermore, we identified the key parameters for assessing the physical fitness of older adults and performed stepwise multiple linear regression analysis. Both men and women exhibited age-related decreases in all aspects of functional fitness, a trend indicating that older adults in Taiwan may lose their independence in the future. Furthermore, the regression analysis revealed that HGS was positively correlated with sex, body mass index, and the results of 30-s arm curl and back scratch tests but negatively correlated with age and the result of 8-foot up-and-go test. Our reference values for physical fitness may help assess the fitness levels of active community-dwelling older adults and design community-based health programs to prevent the early loss of independence in community-dwelling older adults in Taiwan.

Different item characteristics of a mild cognitive impairment screening tool in the community-based Yilan Study: application of the item response theory.

BACKGROUND: This study aimed to use item response theory (IRT) to explore the item-by-item characteristics of a mild cognitive impairment (MCI) screening tool using community-based data. METHODS: The Yilan Study is a community-based study that has been conducted since 2012. Until March 2020, 2230 older adults were interviewed according to the household registration data. IRT was applied to determine the item-by-item distinctive characteristics of the Eight-item Interview to Differentiate Aging and Dementia (AD8). RESULTS: The MCI characteristics in the AD8 items have varying degrees of item response threshold. In all circumstances, item AD8-8, which is related to self-rated memory ability, had a low item response threshold. AD8-5 and AD8-7, which are related to the comparisons of time-oriented functional status, had slightly lower thresholds, especially for those aged 65-79 years or without activity limitations. Conversely, AD8-1, AD8-2, AD8-3, AD8-4, and AD8-6 had similar item response thresholds and discriminative power; these items have more detailed functional descriptions or examples for illustration. CONCLUSIONS: Concise and understandable elements are often expected in community-based screening tools. For community-based health screening and population empowerment in the early detection of MCI, assessment tool items with detailed functional descriptions and examples for illustration have similar validities in most of the population. Items related to self-rated memory ability might be less valid. More examples may be needed for items constructed for comparing time-oriented functional status, especially in extremely old adults and individuals with activity limitations.

Correlation analysis of physical fitness and its impact on falls in 2130 community- dwelling older adults: a retrospective cross-sectional study.

BACKGROUND: As the community-dwelling population ages in Taiwan, concerns regarding long-term care have grown more urgent. Physical fitness plays a key role in enabling community-dwelling older adults to independently complete daily tasks and avoid falling accidents. However, the effect of physical fitness on falls and other fitness-related factors remains poorly understood. METHODS: In this retrospective cross-sectional study, 2130 community-dwelling older adults were recruited from a rural region of Taiwan. Each of these participants completed a demographics interview and frailty questionnaire and reported their history of falls. We evaluated each participant's height and body weight measurements, calf circumference, bone mass density, and results on the grip strength, single-leg standing, chair sit-and-reach, 8-ft up-and-go, 30-second chair stand, 2-minute step, 30-second arm curl, 6-m walk, and back scratch tests to determine their overall physical fitness, which consisted of their body composition, muscular strength and endurance, flexibility, and cardiopulmonary fitness. RESULTS: The prevalence of falls in the preceding year among the older adults surveyed was 20.8%, and the resultant hospitalization rate was 10.9%. The older adults who were more physically active in the past week, had regular exercise habits, lived with family, and had no history of hospitalization due to falls, exhibited greater performance on the physical fitness tests. Three time fallers exhibited lower levels of overall physical fitness than did those who had not fallen. The nonfallers outperformed the fallers in grip strength (participants who had not fallen and those who had fallen once, twice, or three times in the preceding year: 24.66 ± 0.19 vs. 23.66 ± 0.35 vs. 20.62 ± 0.71 vs. 22.20 ± 0.90 kg) and single-leg standing duration (19.38 ± 0.39 vs. 16.33 ± 0.78 vs. 13.95 ± 1.67 vs. 12.34 ± 1.82 seconds). CONCLUSIONS: Exercise habits, living status, hospitalization due to falls, and amount of exercise were all associated with physical fitness in community-dwelling older adults. The results of all of the assessments indicated that the participants who had fallen three times exhibited lower levels of physical fitness than did those who had not fallen in the previous year. Physical measurements, including grip strength and single-leg standing duration, are associated with an individual's risk of falling, which indicates that they should be considered in the development of geriatric physical fitness and fall-prevention programs.

DNA damage and NF-κB inactivation implicate glycyrrhizic acid-induced G1 phase arrest in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is the most frequently occurring liver malignancy in Asia. Glycyrrhizic acid is known to reduce the risk of HCC formation in patients with chronic hepatitis C. To identify whether glycyrrhizic acid may play a role in anti-HCC therapy as an adjuvant is important. However, the inhibitory effect of glycyrrhizic acid on cell cycle progression in HCC cells and the mechanism of such have not been fully elucidated. This study used the comet assay, cell cycle analysis, immunofluorescence staining, the TUNEL assay, and Western blotting to identify the anti-HCC role of glycyrrhizic acid. Glycyrrhizic acid may induce DNA damage, apoptosis, activation of ATM, and expression of p21, and p27 in HCC cells. In addition, glycyrrhizic acid may also induce G1 phase arrest and suppress NF-κB-mediated Cyclin D1 expression. DNA damage and NF-κB inactivation may be associated with glycyrrhizic acid-induced G1 phase arrest in HCC cells.

Identification of early response to hypertonic dextrose prolotherapy markers in knee osteoarthritis patients by an inflammation-related cytokine array.

BACKGROUND: Osteoarthritis (OA) is one of the most common forms of arthritis, and hypertonic dextrose prolotherapy has long been used clinically to treat knee OA. The aim of this study was to investigate the inflammation-related protein-expression profile characterizing the efficacy of the hypertonic dextrose prolotherapy in knee OA as prognostic markers. METHODS: OA patients over the age of 65 were recruited for Western Ontario McMaster University Osteoarthritis (WOMAC) index, knee X-ray evaluation and knee joint synovial fluid analysis before and after hypertonic dextrose prolotherapy. The expressions of inflammation-related factors were measured using a novel cytokine antibody array methodology. The cytokine levels were quantified by quantitative protein expression and analyzed by ELISA using the patients' knee-joint synovial fluid. RESULTS: The WOMAC Index and minimum joint space width before receiving the intra-articular injection and at 2-week intervals were compared. Twelve patients who received OA intervention were enrolled and finally a clinical evaluation of 12 knee joints and knee synovial fluid samples were analyzed. In this study, after receiving hypertonic dextrose prolotherapy, the OA patients clearly demonstrated a significant improvement in WOMAC index and increasing tendency in the medial minimum joint space width after intervention. Meanwhile, we observed a significantly associated tendency between hypertonic dextrose treatment of knee OA and the upregulation of MMP2, TIMP-1, EGF, CXCL9 and IL-22. CONCLUSION: The findings provide knee OA patients receiving hypertonic dextrose prolotherapy, which is accompained by the improvemeny of knee symptoms and associated tendency of upregulation of MMP2, EGF, CXCL 9 and IL-22.

Effect of a Comprehensive Rehabilitation Program for Community Women with Urinary Incontinence: A Retrospect Cohort Study.

Urinary incontinence (UI) is a common problem affecting older adult women globally, but studies regarding combined treatments for all types of UI are still lacking. Here we evaluate the efficacy of a comprehensive rehabilitation program for women with UI. A comprehensive rehabilitation program was introduced that combines pelvic floor muscle (PFM) exercises, functional electrical stimulation, and timely biofeedback during the training process. Data of patients with stress (SUI), urgency (UUI), or mixed (MUI) urinary incontinence who participated in this program between 2016 and 2019 were reviewed retrospectively. Seventy-three subjects (mean age 59.2 ± 12.7 years) were enrolled. After 12 weeks of rehabilitation, vaginal pressure and control accuracy increased in all groups. PFM maximum recruitment increased significantly at week 12 in SUI and UUI, but not in MUI. At week 6, only the SUI group had achieved significant improvements in vaginal pressure, PFM maximum recruitment and control accuracy. The Short-form Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7) scores declined dramatically after the program started, and significant improvements were maintained to week 48. The comprehensive rehabilitation program is effective and decreases urinary leakage episodes and improves quality of life in women with UI, especially SUI.

The Development of a Rapid Classification Scale for Sleep Quality in Community-Dwelling Older Adults - The Yilan Study, Taiwan.

OBJECTIVE: Poor sleep quality is prevailing, deleterious, but heterogeneous in older adults. This study aimed to develop a simplified instrument to screen and classify poor sleep quality in community-dwelling older adults, by which stepped care with needs-based interventions could be implemented. METHODS: Cohorts of adults aged 65 years and older were used to develop the Rapid Classification Scale for Sleep Quality (RCSSQ). Poor sleep quality was defined with the Pittsburgh Sleep Quality Index (PSQI). Established subgroups of poor sleep quality in the development dataset (n = 2622) were used as the criterion standard. Two independent validation datasets (n = 964 and 193, respectively) were used to examine the external validity. Questions in the PSQI were examined by the stepwise multinomial logistic regressions to determine the optimal numbers of items in the RCSSQ. On the premise of item parsimony and instrument validity, the optimal combination of reduced items was determined. RESULTS: In the development dataset, the 4-item RCSSQ (RCSSQ-4) was the optimal predictive model. In terms of internal validity, the accuracy rates to identify PSQI-defined poor sleep quality and its subgroups in the developmental dataset by the RCSSQ-4 were 89.0% and 79.9%, respectively. Meanwhile, the RCSSQ-4 also had good external validity in the validation datasets to detect PSQI-defined poor sleep quality (accuracy rates: 89.1-90.7%). Furthermore, the profiles of PSQI component scores and comorbid conditions for the predicted subgroups in the validation dataset were comparable with the criterion standard. CONCLUSION: The RCSSQ-4 is a valid instrument for screening and subgrouping poor sleep quality in community-dwelling older adults. The RCSSQ-4 may help guide tailored interventions under the context of stepped care in the community.

A Rehabilitation-Based Multidisciplinary Care Model Reduces Hip Fracture Mortality in Older Adults.

PURPOSE: In older adults, the one-year mortality rate after experiencing a hip fracture ranges between 8% and 36%. The purpose of this study was to look at the efficacy of rehabilitation-based multidisciplinary care for older individuals who had hip fractures. PATIENTS AND METHODS: The study included 185 people (aged 65 and over) with a history of hip fracture surgery between February 2014 and March 2017. A survey was conducted one month and six months following the operation to assess the recovery of 93 individuals who were part of a rehabilitation-based multidisciplinary care program and 92 patients who were getting standard therapy with surgery and unsupervised physical therapy. RESULTS: Physical activity, gait, balance evaluation, and depression scale ratings all had statistical significance (P < 0.05) after participants received rehabilitation-based care services from multidisciplinary medical professionals. Furthermore, the refracture and one-year mortality rates in this rehabilitation-based multidisciplinary care model were lower than in the groups getting standard therapy. CONCLUSION: The research indicates the efficacy of a multidisciplinary rehabilitation strategy provided by a collaborative medical team to older individuals with hip fractures.

Sorafenib Induces Apoptosis and Inhibits NF-κB-mediated Anti-apoptotic and Metastatic Potential in Osteosarcoma Cells.

BACKGROUND/AIM: Sorafenib, an oral multi-kinase inhibitor, has been shown to improve the outcome of patients with osteosarcoma (OS). However, the anti-OS effect and mechanism of sorafenib has not yet been fully understood. The main purpose of this study was to investigate the effect of sorafenib on apoptotic signaling and Nuclear Factor-κB (NF-κB)-mediated anti-apoptotic and metastatic potential in OS in vitro. MATERIALS AND METHODS: The effect of sorafenib on apoptotic signaling transduction, anti-apoptotic, and metastatic potential of OS U-2 cells was verified with flow cytometry, trans-well invasion/migration, and western blotting assay. RESULTS: Sorafenib induced the extrinsic and intrinsic apoptotic pathways. In addition, sorafenib reduced the invasion and migration ability of OS cells, induced NF-κB activation, and the expression of anti-apoptotic proteins and metastasis-associated proteins encoded by NF-κB target genes. CONCLUSION: Sorafenib led to stimulation of extrinsic/intrinsic apoptotic pathways and NF-κB inactivation in U-2 OS cells.

Normative data and associated factors of hand grip strength among elderly individuals: The Yilan Study, Taiwan.

Weak grip strength is associated with subsequent mortality in elderly populations. The normative data and associated factors of HGS in community-dwelling elderly Taiwanese populations require further evaluation. From February 2012 until the end of 2016, all residents of Yilan City, Taiwan aged 65 years or older were randomly selected for a population-based community health survey. A total of 2,470 older adults were enrolled in this study. The relationships between HGS and various anthropometric and sociodemographic correlates were examined. The results showed that HGS was higher in men than in women. The mean HGS exhibited a decreasing trend with advanced age in both men and women. HGS was significantly associated with height, weight, and exercise habits. The physical as well as the mental component summary measures of health-related quality of life (HRQoL) were positively associated with HGS. After HRQoL was integrated into the regression model, female sex, age, waist circumference, and diabetes mellitus were significantly negatively associated with HGS. In conclusion, HGS significantly decreased with advanced age. among community-dwelling Taiwanese elderly people, Various factors had different effects on HGS.

Effectiveness of a machine-assisted healthy physical fitness promotion program for community elderly.

BACKGROUND: Maintaining physical fitness is important for health of the elderly. How to implement an effective and efficient model is a practical issue. A healthy physical fitness promotion program with machine-assisted exercises was designed for elderly and executed in a community in 2015 and 2016. The program was implemented for 10 to 12 weeks with two (group 1) or three (group 2) sessions per week, and functional fitness tests were conducted before, at the end, and 3 months after the training. This study is to investigate the effectiveness of machine-assisted physical fitness promotion program for the community elderly. METHODS: A retrospective analysis was conducted on the participants' data, including sex, age, height, weight, waist-hip ratio, grip strength, back stretch, chair sit-and-reach, 30-second chair stand, 30-second arm curl, 2-minute step, single-leg standing, 8-ft up-and-go, and body composition. The differences in test results before, at the end, and 3 months after the training and the percentage change at different time intervals between the two groups were compared. RESULTS: After training, body mass index in group 2 and the test completion time for 8-ft up-and-go in group 1 decline significantly; furthermore, significant increase was noted in the height and number of times of 2-minute step in both groups, and grip strength, number of times of their 30-second arm curl, and 30-second chair stand in group 2. The training effect sustained 3 months after the training in height and number of times of 2-minute step in both groups, and grip strength, number of times of their 30-second arm curl, and 30-second chair stand in group 2. CONCLUSION: This study discovered that 10 to 12 weeks of machine-assisted exercise training can improve the elderly community members' body composition, muscle strength, muscle endurance, agility, dynamic balance, and cardiorespiratory endurance. Moreover, with three sessions per week, its effects were even maintained for 3 months after the training.

Glycyrrhizic Acid Modulates Apoptosis through Extrinsic/Intrinsic Pathways and Inhibits Protein Kinase B- and Extracellular Signal-Regulated Kinase-Mediated Metastatic Potential in Hepatocellular Carcinoma In Vitro and In Vivo.

A previous study presented that glycyrrhizic acid as the hepatoprotective agent inhibits total parenteral nutrition-associated acute liver injury in rats. However, the anticancer effect and mechanism of glycyrrhizic acid in human hepatocellular carcinoma (HCC) is ambiguous. The purpose of the present study was to investigate the effect of glycyrrhizic acid on apoptosis dysregulation and metastatic potential in HCC in vitro and in vivo. Both SK-Hep1 and Hep3B cells were treated with different concentrations of glycyrrhizic acid for 24 or 48h. SK-Hep1/luc2 tumor-bearing mice were treated with vehicle or glycyrrhizic acid (50mg/kg/day by intraperitoneal injection) for 7 days. Tumor cells growth, apoptotic, and metastatic signaling transduction were evaluated by using MTT assay, digital caliper, bioluminescence imaging (BLI), flow cytometry, western blotting assay, and immunohistochemistry (IHC) staining. The results demonstrated glycyrrhizic acid significantly inhibits tumor cell growth, cell invasion, and expression of AKT (Ser473), extracellular-signal-regulated kinase (ERK), epidermal growth factor receptor (EGFR) phosphorylation, anti-apoptotic and metastatic proteins in HCC in vitro and in vivo. Glycyrrhizic acid also significantly triggered apoptosis and extrinsic/intrinsic apoptotic signaling transduction. In addition, PD98059 (ERK inhibitor) and LY294002 (AKT inhibitor) obviously reduced cell invasion and expression of metastasis-associated proteins. Taken together, these results indicated that glycyrrhizic acid induces apoptosis through extrinsic/intrinsic apoptotic signaling pathways and diminishes EGFR/AKT/ERK-modulated metastatic potential in HCC in vitro and in vivo.

Protein Kinase B and Extracellular Signal-Regulated Kinase Inactivation is Associated with Regorafenib-Induced Inhibition of Osteosarcoma Progression In Vitro and In Vivo.

Osteosarcoma is the most common type of bone cancer. Multimodality treatment involving chemotherapy, radiotherapy and surgery is not effective enough to control osteosarcoma. Regorafenib, the oral multi-kinase inhibitor, has been shown to have positive efficacy on disease progression delay in chemotherapy resistant osteosarcoma patients. However anti-cancer effect and mechanism of regorafenib in osteosarcoma is ambiguous. Thus, the aim of this study is to investigate the efficacy and molecular mechanism of regorafenib on osteosarcoma in vitro and in vivo. Human osteosarcomas U-2 OS or MG-63 were treated with regorafenib, miltefosine (protein kinase B (AKT) inhibitor), or PD98059 (mitogen-activated protein/extracellular signal-regulated kinase (MEK) pathway inhibitor) for 24 or 48 h. Cell viability, apoptotic signaling transduction, tumor invasion, expression of tumor progression-associated proteins and tumor growth after regorafenib treatment were assayed by MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, transwell assay, Western blotting assay and in vivo animal experiment, respectively. In these studies, we also indicated that regorafenib suppressed cell growth by prompting apoptosis of osteosarcoma cells, which is mediated through inactivation of ERK and AKT signaling pathways. After regorafenib treatment, downregulation of related genes in invasion (vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9)), proliferation (CyclinD1) and anti-apoptosis (X-linked inhibitor of apoptosis protein (XIAP), myeloid cell leukemia-1 (MCL-1), and cellular FLICE (FADD-like IL-1ß-converting enzyme)-inhibitory protein (C-FLIP)) were found. Moreover, upregulation of caspase-3 and caspase-8 cleavage were also observed. In sum, we suggest that regorafenib has potential to suppress osteosarcoma progression via inactivation of AKT and ERK mediated signaling pathway.

Comparisons of mortality and rehospitalization between hip-fractured elderly with outpatient rehabilitation and those without: A STROBE-compliant article.

Geriatric patients with hip fractures have high mortality. This study aimed to compare the mortality and rehospitalization of recipient and nonrecipient of outpatient rehabilitation in hip-fractured elderly.This retrospective cohort study used nationwide claims data in Taiwan and included 3585 senior citizen patients admitted for hip fractures between January 1, 2005, and December 31, 2012. Patients were divided into the recipient (717) and nonrecipient (2868) of outpatient rehabilitation during the first 3 months after hospital discharge. Each patient was followed up for 1 year. Mortality rates of hip-fractured elderly after discharge during the first 3-month period in different groups were analyzed with Chi-square test. Cox proportional hazards regression model was employed for both death and rehospitalization risk analyses.The mortality rate of the rehabilitation group was lower than that of the nonrehabilitation group (12.69% vs 16.70%, P < .05). A more beneficial effect was observed for patients receiving continuous rehabilitation. The rehabilitation group had a lower adjusted risk of death [hazard ratio (HR) = 0.74; 95% confidence interval (95% CI): 0.59-0.94] than that of the nonrehabilitation group. However, the rehabilitation group was at a higher risk of rehospitalization (HR = 1.37; 95% CI: 1.22-1.55).Hip-fractured elderly receiving outpatient rehabilitation have a lower risk of death but a higher risk of rehospitalization than those not receiving rehabilitation within 1 year after fracture.

Amentoflavone Enhances the Therapeutic Efficacy of Sorafenib by Inhibiting Anti-apoptotic Potential and Potentiating Apoptosis in Hepatocellular Carcinoma In Vivo.

BACKGROUND/AIM: In a previous study, we showed that amentoflavone promotes sorafenib-induced apoptosis in hepatocellular carcinoma (HCC) cells in vitro. However, whether amentoflavone augments anticancer efficacy of sorafenib in HCC in vivo is unknown. The aim of the present study was to verify the anticancer effect of amentoflavone combined with sorafenib in HCC in vivo. MATERIALS AND METHODS: HCC SK-Hep1 tumor-bearing mice were treated with vehicle, sorafenib, amentoflavone, or combination for 14 days, respectively. Effect of sorafenib, amentoflavone, or their combination on tumor growth, anti-apoptotic potential, apoptotic signaling and general toxicity were evaluated with digital caliper, immunohistochemistry staining and body weight. RESULTS: Our results demonstrated that amentoflavone significantly enhanced sorafenib-inhibited tumor growth and expression of ERK/AKT phosphorylation and anti-apoptotic proteins compared to single-agent treatment. Additionally, amentoflavone also triggered sorafenib-induced apoptosis through extrinsic and intrinsic apoptotic pathways. CONCLUSION: Amentoflavone boosts therapeutic efficacy of sorafenib through blockage of anti-apoptotic potential and induction of apoptosis in HCC in vivo.

Amentoflavone Inhibits Metastatic Potential Through Suppression of ERK/NF-κB Activation in Osteosarcoma U2OS Cells.

AIM: The study goal was to investigate effect of amentoflavone on nuclear factor-κB (NF-κB)-modulated metastatic mechanism in osteosarcoma U2OS cells. U2OS cells were treated with amentoflavone, NF-κB inhibitor, protein kinase B (PKB or AKT) inhibitor or mitogen-activated protein kinase (MAPK) inhibitor. Change of cell viability, NF-κB activation, expression of metastasis-associated proteins, signal transduction, and cell migration and invasion were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, NF-κB reporter gene assay, western blotting, and cell migration and invasion assays. The results demonstrated that inhibition of activation of extracellular signal-regulated kinases (ERK) was a key point for suppression of NF-κB-modulated metastatic mechanism. Amentoflavone significantly inhibited NF-κB activation, ERK phosphorylation, expression of metastasis-associated proteins, and cell migration and invasion. Our findings indicate that amentoflavone reduces metastatic potential through suppression of ERK and NF-κB activation in osteosarcoma U2OS cells.

Regorafenib induces extrinsic and intrinsic apoptosis through inhibition of ERK/NF-κB activation in hepatocellular carcinoma cells.

The aim of the present study was to investigate the role of NF-κB inactivation in regorafenib-induced apoptosis in human hepatocellular carcinoma SK-HEP-1 cells. SK-HEP-1 cells were treated with different concentrations of the NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine (QNZ) or regorafenib for different periods. The effects of QNZ and regorafenib on cell viability, expression of NF-κB-modulated anti-apoptotic proteins and apoptotic pathways were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blotting, DNA gel electrophoresis, flow cytometry and NF-κB reporter gene assay. Inhibitors of various kinases including AKT, c-Jun N-terminal kinase (JNK), P38 and extracellular signal-regulated kinase (ERK) were used to evaluate the mechanism of regorafenib-induced NF-κB inactivation. The results demonstrated that both QNZ and regorafenib significantly inhibited the expression of anti-apoptotic proteins and triggered extrinsic and intrinsic apoptosis. We also demonstrated that regorafenib inhibited NF-κB activation through ERK dephosphorylation. Taken all together, our findings indicate that regorafenib triggers extrinsic and intrinsic apoptosis through suppression of ERK/NF-κB activation in SK-HEP-1 cells.

Mammography and the risk of thyroid and hematological cancers: a nationwide population-based study.

To investigate the association between thyroid cancer as well as the most radiosensitive hematological cancers and radiation exposure from mammography. This study used information from a random sample of two million persons enrolled in the nationally representative Taiwan National Health Insurance (NHI) Research Database. The exposed group was composed of women aged 18-65 who had undergone diagnostic mammography between 2000 and 2007. The nonexposed control group was composed of women in the NHI database who had never undergone diagnostic mammography. There were 25,362 women in the exposed group and 203,317 women in the nonexposed group. After adjusting for age and comorbidities, the patients who had been exposed to radiation from mammography did not have a significantly higher risk of developing thyroid cancer and hematological cancers (adjusted HR, 1.201; 95% CI, 0.813-1.774 for thyroid cancer and adjusted HR, 1.228; 95% CI, 0.838-1.800 for hematological cancers). The scattered radiation dose delivered by mammography should be cautiously handled, but no additional concerns about the risk of thyroid cancer developing malignancy should be emphasized.