Determination of the Combined Effects of Asian Herbal Medicine with Calcium and/or Vitamin D Supplements on Bone Mineral Density in Primary Osteoporosis: A Systematic Review and Meta-Analysis.

Our review of 52 RCTs from 5 databases suggests a tendency for notable improvement in BMD when combining herbal medicine with supplements (calcium and vitamin D variants) compared to supplement monotherapy in primary osteoporosis. However, caution is needed in interpreting results due to substantial heterogeneity among included studies. PURPOSE: To conduct a systematic review and meta-analysis to determine whether herbal medicine (HM) plus supplements such as calcium (Ca) or vitamin D (Vit.D) improves bone mineral density (BMD) compared to supplements alone in primary osteoporosis (OP) patients. METHODS: We searched 5 databases for randomized controlled trials (RCTs) using HMs with supplements (Ca or Vit.D variants) as interventions for primary OP patients published until August 31, 2022. Meta-analysis using BMD score as the primary outcome was performed using RevMan 5.4 version. Risk of bias in the included studies was assessed useing RoB 2.0 tool. RESULTS: In total, 52 RCTs involving 4,889 participants (1,408 men, 3,481 women) were included, with average BMD scores of 0.690 ± 0.095 g/cm2 (lumbar) and 0.625 ± 0.090 g/cm2 (femoral neck). As a result of performing meta-analysis using BMD scores for all 52 RCTs included in this review, combination of HMs with Ca and Vit.D variants improved the BMD score by 0.08 g/cm2 (lumbar, 38 RCTs, 95% CI: 0.06-0.10, p < 0.001, I2 = 97%) and 0.06 g/cm2 (femoral neck, 19 RCTs, 95% CI: 0.04-0.08, p < 0.001, I2 = 92%)compared to controls. However, statistical significance of the lumbar BMD improvement disappeared after adjusting for potential publication bias. CONCLUSION: Our data suggest that combining of HM and supplements tends to be more effective in improving BMD in primary OP than supplements alone. However, caution is needed in interpretation due to the reporting bias and high heterogeneity among studies, and well-designed RCTs are required in the future.

Exploring the relationship between work-family conflict and sleep disturbance: a study on stratification and interaction.

Introduction: Despite several studies on the association between work-family conflict (WFC) and sleep disturbances, a more comprehensive approach considering occupational factors is lacking. We aimed to analyze this association among Korean workers and the combined effects of WFC and job-related factors on sleep disturbance. Methods: Data on paid workers from the sixth Korean Working Conditions Survey were analyzed. Odds ratios (ORs) with 95% confidence intervals (CIs) for sleep disturbances with WFC were calculated using a multiple logistic regression model among Korean workers. Furthermore, stratification and interaction analyses were conducted between WFC and socioeconomic factors related to sleep disturbance. Results: Among the 24,923 workers (male: 11,752, female: 13,171) examined, 35.40% of males and 39.95% of females experienced sleep disturbances. In both sexes, the WFC group was significantly associated with sleep disturbance [adjusted OR (95% CI): male, 2.90 [2.67-3.16]; female, 2.54 [2.35-2.74]]. According to the stratification analysis, the association between sleep disturbance and WFC was prominent among younger and highly educated individuals, those engaged in quick returns, and larger companies in both sexes. In the interactions between WFC, quick return, occupation, and company size on sleep disturbance, there were significant additive associations, except between WFC and occupation among female workers. Conclusion: This study highlights the association between WFC and sleep disturbances in male and female workers and emphasizes the importance of maintaining work-life balance.

Socioeconomic Disparities in the Association Between All-Cause Mortality and Health Check-Up Participation Among Healthy Middle-Aged Workers: A Nationwide Study.

BACKGROUND: This study assessed the relationship between non-participation in health check-ups and all-cause mortality and morbidity, considering socioeconomic status. METHODS: Healthy, middle-aged (35-54 years) working individuals who maintained either self-employed or employee status from 2006-2010 were recruited in this retrospective cohort study from the National Health Insurance Service in Korea. Health check-up participation was calculated as the sum of the number of health check-ups in 2007-2008 and 2009-2010. Adjusted hazard ratio (HR) and 95% confidence interval (CI) of all-cause mortality were estimated for each gender using multivariable Cox proportional hazard models, adjusting for age, income, residential area, and employment status. Interaction of non-participation in health check-ups and employment status on the risk of all-cause mortality was further analyzed. RESULTS: Among 4,267,243 individuals with a median 12-year follow-up (median age, 44; men, 74.43%), 89,030 (2.09%) died. The proportion (number) of deaths of individuals with no, one-time, and two-time participation in health check-ups was 3.53% (n = 47,496), 1.66% (n = 13,835), and 1.33% (n = 27,699), respectively. The association between health check-up participation and all-cause mortality showed a reverse J-shaped curve with the highest adjusted HR (95% CI) of 1.575 (1.541-1.611) and 1.718 (1.628-1.813) for men and women who did not attend any health check-ups, respectively. According to the interaction analysis, both genders showed significant additive and multiplicative interaction, with more pronounced additive interaction among women who did not attend health check-ups (relative excess risk due to interaction, 1.014 [0.871-1.158]). CONCLUSION: Our study highlights the significant reverse J-shaped association between health check-up participation and all-cause mortality. A pronounced association was found among self-employed individuals, regardless of gender.

The Association between New-Onset Depressive Symptoms and Participating in Medical Check-Ups among Elderly Individuals.

The association between adherence to medical check-ups and new-onset depressive symptoms, after adjusting for comprehensive risk factors such as social characteristics, remains unclear. This study aimed to assess the association between mental health and participating in medical check-ups. The survey data of participants aged 60 to 89 were recruited from the seventh Korean Longitudinal Study on Aging. The primary outcome was new-onset depressive symptoms within 2 years measured using the Center for Epidemiologic Studies Depression Scale. Participating in medical check-ups was defined as undergoing biennial medical check-ups. Multivariable logistic regression was performed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with consideration of a 2-year time lag. Among 4255 participants, the prevalence of new-onset depressive symptoms was 7.36% (n = 313). The prevalence of non-participation in medical check-ups was 11.96% (n = 509). The adjusted OR of new-onset depressive symptoms by non-participation in medical check-ups was 1.65 [95% CI 1.22-2.24; p = 0.001] after adjusting for various demographic, behavioral, occupational, and social participation characteristics. Our findings demonstrated a significant inverse relationship between participation in medical check-ups and new-onset depressive symptoms. It is necessary to monitor and manage depressive symptoms in vulnerable elderly individuals who do not participate in medical check-ups.

The Association between Replacement Drivers and Depressive Symptoms.

A replacement driver is a type of gig worker who provides driving services to the target point with the drunk driver's own car. This study aimed to examine the association of replacement drivers (ref: paid workers) with depressive symptoms. Information on replacement drivers was collected through online/offline surveys. Data from the 8th Korea National Health and Nutrition Examination Survey were applied to construct the control group. The Patient Health Questionnaire-9; ≥5 points was defined as depressive symptoms. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated by performing multivariable logistic regression analysis. The mean age of replacement drivers was 56.11. The prevalence of depressive symptoms in replacement drivers and controls were 49.63% and 12.64%, respectively. Replacement drivers showed a higher association with depressive symptoms than paid workers (aOR 7.89, 95% CI [5.53-11.26]). This relationship was prominent in the older, low-education, and low-income groups. Linear discriminant analysis was the most effective in predicting depressive symptoms among the machine learning models. Using the replacement driver feature increased the AUC values of the models. Given the strong association between depressive symptoms and replacement drivers, in-depth studies to establish guidelines to prevent mental diseases among replacement drivers are required.

Proton beam therapy reduces the risk of severe radiation-induced lymphopenia during chemoradiotherapy for locally advanced non-small cell lung cancer: A comparative analysis of proton versus photon therapy.

HYPOTHESIS: We investigated differences in severe radiation-induced lymphopenia (SRL) after pencil beam scanning proton therapy (PBSPT) or intensity-modulated (photon) radiotherapy (IMRT) for patients with locally advanced non-small cell lung cancer. METHODS: We retrospectively reviewed 223 patients who received definitive concurrent chemoradiotherapy with PBSPT (n = 29) or IMRT (n = 194). SRL was defined when ≥2 events of absolute lymphocyte counts (ALCs) of <200 cells/µL were observed in weekly laboratory tests conducted during treatment. Stepwise multivariate logistic regression with 10-fold cross-validation was performed to identify predictive values of SRL. Furthermore, 1:2 propensity score matching (PSM) analysis was performed between the PBSPT and IMRT groups. RESULTS: Baseline ALC was comparable between the PBSPT and IMRT groups (median, 2130 vs. 2040 cells/µL; p = 0.983). Lung volumes receiving ≥ 5-20 GyE and the mean dose were significantly lower in patients receiving PBSPT than those receiving IMRT (p < 0.001). Among 72 (32.3%) patients with SRL; 69 (95.8%) and 3 (4.2%) patients were treated with IMRT and PBSPT, respectively. After multivariable analysis, PBSPT reduced SRL compared to IMRT (odds ratio [OR] 0.13, p = 0.003). Specifically, lung V5Gy were identified as the strongest predictor of SRL before (OR 1.11) and after PSM (OR, 1.07) (p < 0.05). With a median follow-up of 23.0 months, the 2-year overall survival in patients with SRL was worse than that those without SRL (63.4% vs. 79.9%; p = 0.003). CONCLUSIONS: Reduced irradiated lung volumes of PBSPT consequently reduced SRL. In addition, lung V5Gy contributed to the SRL. Reduction of SRL through the optimized RT might be essential to improve the outcomes.

Functional Test Scales for Evaluating Cell-Based Therapies in Animal Models of Spinal Cord Injury.

Recently, spinal cord researchers have focused on multifaceted approaches for the treatment of spinal cord injury (SCI). However, as there is no cure for the deficits produced by SCI, various therapeutic strategies have been examined using animal models. Due to the lack of standardized functional assessment tools for use in such models, it is important to choose a suitable animal model and precise behavioral test when evaluating the efficacy of potential SCI treatments. In the present review, we discuss recent evidence regarding functional recovery in various animal models of SCI, summarize the representative models currently used, evaluate recent cell-based therapeutic approaches, and aim to identify the most precise and appropriate scales for functional assessment in such research.

Selective Targeting of Cancer Stem Cells by 2-Aminodihydroquinoline Analogs.

Many aminodihydroquinoline compounds have been studied to determine their cytotoxicity to cancer cells. However, anti-cancer stem cells (CSCs) activity of aminodihydroquinoline has not been tested in spite that CSC is believed to do an important roles in chemotherapy resistance and recurrence. The CSC selective targeting activities of 10 recently synthesized 2-aminodihydroquinoline analogs were examined on CSCs and bulk culture of a glioblastoma cell line. A diethylaminopropyl substituted aminodihydroquinoline, 5h, showed a strong anti-CSC effect and general cytotoxicity. However, a benzyl substituted aminodihydroquinoline, 5i, displayed the most effective anti-CSC effect, with no or small significant cytotoxic effect in bulk culture conditions. While 5h temporarily enhanced CSC marker-positive cells and eventually suppressed the CSC population, which is similar to other cytotoxic anticancer reagents reported, 5i selectively eliminated CSC marker-positive cells based on fluorescence activated cell sorter (FACS) analysis. 5h also temporarily activated some genes associated with signaling required for CSC, while 5i selectively suppressed these genes supporting that the differential effects are resulted from different molecular responses. In addition, the selective CSC effect is also found against a colon cancer cell line. Collectively, we suggest that these two novel aminodihydroquinoline compounds possess novel anti-CSC effects in colon and brain tumor derived cell lines probably through independent pathways.

Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses.

Bipolar disorder (BD), characterized by recurrent mood swings between depression and mania, is a highly heritable and devastating mental illness with poorly defined pathophysiology. Recent genome-wide molecular genetic studies have identified several protein-coding genes and microRNAs (miRNAs) significantly associated with BD. Notably, some of the proteins expressed from BD-associated genes function in neuronal synapses, suggesting that abnormalities in synaptic function could be one of the key pathogenic mechanisms of BD. In contrast, however, the role of BD-associated miRNAs in disease pathogenesis remains largely unknown, mainly because of a lack of understanding about their target mRNAs and pathways in neurons. To address this problem, in this study, we focused on a recently identified BD-associated but uncharacterized miRNA, miR-1908-5p. We identified and validated its novel target genes including DLGAP4, GRIN1, STX1A, CLSTN1 and GRM4, which all function in neuronal glutamatergic synapses. Moreover, bioinformatic analyses of human brain expression profiles revealed that the expression levels of miR-1908-5p and its synaptic target genes show an inverse-correlation in many brain regions. In our preliminary experiments, the expression of miR-1908-5p was increased after chronic treatment with valproate but not lithium in control human neural progenitor cells. In contrast, it was decreased by valproate in neural progenitor cells derived from dermal fibroblasts of a BD subject. Together, our results provide new insights into the potential role of miR-1908-5p in the pathogenesis of BD and also propose a hypothesis that neuronal synapses could be a key converging pathway of some BD-associated protein-coding genes and miRNAs.

Systemic approaches identify a garlic-derived chemical, Z-ajoene, as a glioblastoma multiforme cancer stem cell-specific targeting agent.

Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and TGFß signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.