CircRBM23 regulates the switch between osteogenesis and adipogenesis of mesenchymal stem cells via sponging miR-338-3p.

BACKGROUND: The disruption of the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in bone marrow contributes to the adipocytes accumulation and bone loss, which leads to the development of osteoporosis (OP). The circular RNA (circRNA), circRBM23, was generated from the RNA binding motif protein 23 (RBM23) gene. It was reported that circRBM23 was down-regulated in OP patients, but it remains unknown whether its down-regulation is involved in the lineage switch of MSCs. OBJECTIVE: We aimed to explore the role and mechanism of circRBM23 in regulating the switch between osteogenic and adipogenic differentiation of MSCs. METHODS: The expression and function of circRBM23 in vitro were detected by qRT-PCR, alizarin red staining, and oil Red O staining. The interactions between circRBM23 and microRNA-338-3p (miR-338-3p) were analyzed by RNA pull-down assay, FISH, and dual-luciferase reporter assay. MSCs treated with lentivirus overexpression of circRBM23 was applied for both in vitro and in vivo experiments. RESULTS: CircRBM23 was expressed at lower levels in OP patients. Besides, circRBM23 was up-regulated during osteogenesis and down-regulated during adipogenesis of MSCs. CircRBM23 could promote the osteogenic differentiation but inhibit the adipogenic differentiation of MSCs. Mechanistically, circRBM23 acted as a sponge for microRNA-338-3p (miR-338-3p) to enhance the expression of RUNX family transcription factor 2 (RUNX2). CONCLUSIONS: Our research indicates that circRBM23 could promote the switch from adipogenic to osteogenic differentiation of MSCs via sponging miR-338-3p. It might improve the understanding of the lineage switch of MSCs and provide a potential target for diagnosing and treating OP.

The association between vision impairment and cognitive outcomes in older adults: a systematic review and meta-analysis.

OBJECTIVES: To provide a quantitative synthesis of studies on the relationship between vision impairment (VI) and cognitive outcomes in older adults. METHOD: A systematic search was undertaken of relevant databases for original articles published before April 2020. Random effect models were used to obtain pooled estimates of the associations between VI and cognitive outcomes (cognitive impairment and dementia) with subgroup analyses of VI measures, cross-sectional associations of VI with cognitive impairment, and longitudinal associations of baseline VI with incident cognitive impairment and dementia. Potential sources of heterogeneity were explored by meta-regression. Publication bias was evaluated with Egger's test. RESULTS: Sixteen studies including 76,373 participants were included in this meta-analysis, with five cross-sectional studies and eleven longitudinal studies. There was a significantly increased risk of cognitive outcomes with VI identified by subjective measures (odds ratio (OR)=1.63; 95% confidence interval (CI): 1.26-1.99) and objective measures (OR = 1.59; 95% CI: 1.40-1.78). The odds of baseline cognitive impairment were 137% higher in older adults with VI compared with those without VI (OR = 2.37, 95% CI: 1.84-3.03) at baseline. Compared with older adults without VI at baseline, those with baseline VI had a higher relative risk (RR) of incident cognitive impairment (RR = 1.41; 95% CI: 1.31-1.51) and dementia (RR = 1.44, 95% CI: 1.19-1.75). CONCLUSIONS: VI was associated with increased risks of cognitive impairment and dementia across cross-sectional and longitudinal studies. Additional research and randomized clinical trials are warranted to examine the implications of treatment for VI, such as wearing glasses and cataract surgery, to avoid cognitive impairment and dementia.

Multimorbidity measures differentially predicted mortality among older Chinese adults.

OBJECTIVES: This study aimed to examine and compare the associations between different multimorbidity measures and mortality among older Chinese adults. STUDY DESIGN AND SETTING: Using the Chinese Longitudinal Healthy Longevity Survey 2002-2018, data on fourteen chronic conditions from 13,144 participants aged ≥65 years were collected. Multimorbidity measures included condition counts, multimorbidity patterns (examined by exploratory factor analysis), and multimorbidity trajectories (examined by a group-based trajectory model). Mortality risk associated with different multimorbidity measures was each analyzed using Cox regression. C-statistic, the Integrated Discrimination Improvement (IDI), and the Net Reclassification Index (NRI) were used to compare the performance of different multimorbidity measures. RESULTS: Participants with multimorbidity, regardless of measurements, had a higher risk of death compared with people without multimorbidity. Compared with the mortality prediction model using age and sex, C-statistics showed added discrimination (over 0.77, all P < .05) for models with multimorbidity measures. Multimorbidity trajectory showed integrated discrimination and net reclassification improvement for mortality prediction compared to condition count (IDI = 0.042, NRI = 0.033) and multimorbidity pattern (IDI = 0.041, NRI = 0.069). CONCLUSION: Adding multimorbidity measures significantly improved the performance of a mortality prediction model using age and sex as predictors. Trajectory-based measures of multimorbidity performed better than count- and pattern-based measures for mortality prediction.

Patterns of cardiometabolic multimorbidity and the risk of depressive symptoms in a longitudinal cohort of middle-aged and older Chinese.

BACKGROUND: Cardiometabolic diseases (CMDs) are associated with depression. However, it is unclear whether coexisting CMDs may increase the risk of depression. We examined associations between cardiometabolic multimorbidity and depressive symptoms among middle-aged and older Chinese. METHODS: Participants aged ≥45 years were enrolled from the China Health and Retirement Longitudinal Study 2011-2018 (N = 18,002). Cardiometabolic multimorbidity was defined as the coexistence of ≥2 CMDs, including stroke, heart disease, diabetes, hypertension, and dyslipidemia. Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. We used generalized estimating equation models to examine associations between cardiometabolic multimorbidity and depressive symptoms, including the dose effect of disease count and prevalent disease combinations, as well as individual and additive effects of specific CMDs. RESULTS: The prevalence of cardiometabolic multimorbidity was 24.5%. A higher number of CMDs had an additive dose effect on depressive symptoms that persisted consistently in specific CMDs. Stroke only, heart disease only, and diabetes only were each associated with a higher risk of depressive symptoms compared with no CMDs. CMD combinations involving stroke, heart disease, or diabetes were each associated with an increased risk of depressive symptoms compared with the absence of stroke, heart disease, or diabetes. LIMITATION: Self-reported chronic conditions. CONCLUSION: Stroke, heart disease, and diabetes showed individual and additive effects on CMD combinations, whereas hypertension and dyslipidemia only showed associations with depressive symptoms in combinations with other CMDs. These results suggest person-centered healthcare of mental health prevention and treatment for middle-aged and older adults with individual or multiple CMDs.

Self-reported vision impairment, vision correction, and depressive symptoms among middle-aged and older Chinese: Findings from the China health and retirement longitudinal study.

OBJECTIVE: To investigate associations between vision impairment (VI), vision correction (VC) and depressive symptoms among middle-aged and older Chinese. METHODS: 22 203 participants aged ≥45 years from China Health and Retirement Longitudinal Study 2011 to 2015 were divided into four self-reported VI categories: no VI, distance VI (DVI) only, near VI (NVI) only, and both distance and near VI (DNVI); and four self-reported VI/VC subgroups: VI(+)/VC(-), VI(+)/VC(+), VI(-)/VC(-) and VI(-)/VC(+). Depressive symptoms were evaluated by 10-item Center for Epidemiological Studies Depression Scale (CESD-10). RESULTS: Compared with no VI, DVI only (OR = 2.12, 95% CI: 1.95, 2.31), NVI only (OR = 1.51, 95% CI: 1.39, 1.63) and DNVI (OR = 2.75, 95% CI: 2.47, 3.07) were associated with higher odds of depressive symptoms. Compared with VI(+)/VC(-), VI(+)/VC(+) (OR = 0.91, 95% CI: 0.83, 0.98), VI (-)/VC(-) (OR = 0.50, 95% CI: 0.48, 0.53) and VI(-)/VC(+) (OR = 0.49, 95% CI: 0.47, 0.54) were associated with lower odds of depressive symptoms. Compared with no VI at baseline, baseline DNVI was significantly associated with higher odds of depressive symptoms after two (OR = 1.48, 95% CI: 1.16, 1.88) and four (OR = 1.32, 95% CI: 1.04, 1.68) years. Baseline depressive symptoms were significantly associated with higher odds of VI after two (OR = 1.53, 95% CI: 1.34, 1.74) and four (OR = 1.54, 95% CI: 1.34, 1.76) years. CONCLUSION: Adults with DNVI were more likely to report depressive symptoms in the future and those with depressive symptoms were more likely to report VI in the future. VC might be a protective factor for preventing depressive symptoms among adults with VI.

Vision impairment, vision correction, and cognitive decline among middle-aged and older Chinese: results from the China health and retirement longitudinal study.

OBJECTIVES: To investigate the associations between vision impairment (VI), vision correction (VC), and cognitive function. METHOD: We included 20,677 participants aged ≥45 years from the China Health and Retirement Longitudinal Study (2011-2015). Participants were grouped into no VI, distance VI (DVI) only, near VI (NVI) only, or both distance and near VI (DNVI), and VI(+)/VC(-), VI(+)/VC(+), VI(-)/VC(-), or VI(-)/VC(+) further at baseline. Cognitive function at baseline and subsequently every two years was applied as a dependent variable in a generalized estimating equation model. RESULTS: DVI only, NVI only, and DNVI had significantly worse cognitive function over time than no VI (all p < .05). DNVI had significantly worse cognitive function over time than DVI only and NVI only (all p < .001). VI(+)/VC(+), VI(-)/VC(-), and VI(-)/VC(+) had significantly better cognitive function over time than VI(+)/VC(-) (all p < .05). VI(-)/VC(+) had significantly better cognitive function over time than VI(+)/VC(+) and VI(-)/VC(-) (all p < .05). CONCLUSION: Cognitive function was worse in middle-aged and older Chinese with VI, especially in those with DNVI. VC was associated with better cognitive function over time regardless of the status of vision.

Blood exosomal micro ribonucleic acid profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers for differential diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a shortage of effective biomarkers for its diagnosis. AIM: To explore blood exosomal micro ribonucleic acids (miRNAs) as potential biomarkers for HCC diagnosis. RESULTS: The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p. The miRNA profiles also revealed the tumor stages of HCC patients. High expression of miR-455-5p and miR-30c-5p, which significantly correlated with better overall survival in tumor tissues, could also be detected in blood exosomes. Two pairs of miRNAs (miR-584-5p/miR-106-3p and miR-628-3p/miR-941) showed a 94.1% sensitivity and 68.4% specificity to differentiate HCC patients from non-HCC patients. The specificity of the combination was substantially influenced by alcohol consumption habits. CONCLUSION: This study suggested that blood exosomal miRNAs can be used as new non-invasive diagnostic tools for HCC. However, their accuracy could be affected by tumor stage and alcohol consumption habits.

Associations between Multimorbidity and Physical Performance in Older Chinese Adults.

Background: Evidence on the association between physical performance and multimorbidity is scarce in Asia. This study aimed to identify multimorbidity patterns and their association with physical performance among older Chinese adults. Methods: Individuals aged ≥60 years from the China Health and Retirement Longitudinal Study 2011-2015 (N = 10,112) were included. Physical performance was measured by maximum grip strength (kg) and average gait speed (m/s) categorized as fast (>0.8 m/s), median (>0.6-0.8 m/s), and slow (≤0.6 m/s). Multimorbidity patterns were explored using exploratory factor analysis. Generalized estimating equation was conducted. Results: Four multimorbidity patterns were identified: cardio-metabolic, respiratory, mental-sensory, and visceral-arthritic. An increased number of chronic conditions was associated with decreased normalized grip strength (NGS). Additionally, the highest quartile of factor scores for cardio-metabolic (ß = -0.06; 95% Confidence interval (CI) = -0.07, -0.05), respiratory (ß = -0.03; 95% CI = -0.05, -0.02), mental-sensory (ß = -0.04; 95% CI = -0.05, -0.03), and visceral-arthritic (ß = -0.04; 95% CI = -0.05, -0.02) patterns were associated with lower NGS compared with the lowest quartile. Participants with ≥4 chronic conditions were 2.06 times more likely to have a slow gait speed. Furthermore, the odds ratios for the highest quartile of factor scores of four patterns with slow gait speed compared with the lowest quartile ranged from 1.26-2.01. Conclusion: Multimorbidity was related to worse physical performance, and multimorbidity patterns were differentially associated with physical performance. A shift of focus from single conditions to the requirements of a complex multimorbid population was needed for research, clinical guidelines, and health-care services. Grip strength and gait speed could be targeted to routinely measure clinical performance among older adults with multimorbidity, especially mental-sensory disorders, in clinical settings.

Associations Between Somatic Multimorbidity Patterns and Depression in a Longitudinal Cohort of Middle-Aged and Older Chinese.

OBJECTIVES: Depressive symptoms are commonly seen among patients with multiple chronic somatic conditions, or somatic multimorbidity (SMM); however, little is known about the relationships between depressive symptoms and different SMM combinations. Our study aimed to delineate the patterns of SMM and their longitudinal associations with depressive symptoms among a nationally representative sample of middle-aged and older Chinese adults. DESIGN: We employed a longitudinal design. SETTING AND PARTICIPANTS: Older adults (N = 10,084) aged ≥45 years from the China Health and Retirement Longitudinal Study 2011-2015 participated (mean age = 57.7 years at baseline; 53.3% men). METHODS: Sixteen chronic somatic conditions were ascertained at baseline via questionnaires. Depression was assessed with the Center for Epidemiological Studies Depression Scale at baseline and during follow-up. Patterns of SMM were identified via exploratory factor analyses. Generalized estimating equations were used to evaluate the longitudinal associations between patterns of SMM and the presence of depressive symptoms at follow-up. RESULTS: Compared with participants with no somatic condition, those with 1, 2, and 3 or more somatic conditions had a 21%, 66%, and 111% greater risk, respectively, for the presence of depressive symptoms. Increased factor scores for 4 patterns identified, cardio-metabolic pattern [adjusted odds ratio (AOR) 1.12, 95% confidence interval (CI) 1.06, 1.20], respiratory pattern (AOR 1.25, 95% CI 1.17, 1.33), arthritic-digestive-visual pattern (AOR 1.29, 95% CI 1.22, 1.37), and hepatic-renal-skeletal pattern (AOR 1.09, 95% CI 1.02, 1.16), were all associated with a higher risk of having depressive symptoms. CONCLUSIONS AND IMPLICATIONS: All SMM patterns were independently associated with depression among middle-aged and older Chinese adults, with greater odds for people with comorbid arthritic-digestive-visual conditions and respiratory conditions. Clinical practitioners should treat the middle-aged and older population under a multiple-condition framework combining SMM and mental disorders.

Prevalence and Patterns of Multimorbidity in a Nationally Representative Sample of Older Chinese: Results From the China Health and Retirement Longitudinal Study.

BACKGROUND: Multimorbidity has become a prominent problem worldwide; however, few population-based studies have been conducted among older Chinese with multimorbidity. This study aimed to examine the prevalence of multimorbidity and explore its common patterns among a nationally representative sample of older Chinese. METHODS: This study used data from the China Health and Retirement Longitudinal Study and included 19,841 participants aged at least 50 years. The prevalence of individual chronic diseases and multimorbidity during 2011-2015 were evaluated among the entire cohort and according to residential regions and gender. The relationships between participants' demographic characteristics and multimorbidity were examined using logistic regression model. Patterns of multimorbidity were explored using hierarchical cluster analysis and association rule mining. RESULTS: Multimorbidity occurred in 42.4% of the participants. The prevalence of multimorbidity was higher among women (odds ratio [OR] = 1.31, 95% confidence interval [CI]: 1.13-1.51) and urban residents (OR = 1.14, 95% CI: 1.02-1.27) than their respective counterparts after accounting for potential confounders of age, education, smoking, and alcohol consumption. Hierarchical cluster analysis revealed four common multimorbidity patterns: the vascular-metabolic cluster, the stomach-arthritis cluster, the cognitive-emotional cluster, and the hepatorenal cluster. Regional differences were found in the distributions of stroke and memory-related disease. Most combinations of conditions and urban-rural difference in multimorbidity patterns from hierarchical cluster analysis were also observed in association rule mining. CONCLUSION: The prevalence and patterns of multimorbidity vary by gender and residential regions among older Chinese. Women and urban residents are more vulnerable to multimorbidity. Future studies are needed to understand the mechanisms underlying the identified multimorbidity patterns and their policy and interventional implications.

Exosomal microRNAs as potential biomarkers for cancer cell migration and prognosis in hepatocellular carcinoma patient-derived cell models.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and current treatments exhibit limited efficacy against advanced HCC. The majority of cancer-related deaths are caused by metastasis from the primary tumor, which indicates the importance of identifying clinical biomarkers for predicting metastasis and indicating prognosis. Patient-derived cells (PDCs) may be effective models for biomarker identification. In the present study, a wound healing assay was used to obtain 10 fast-migrated and 10 slow-migrated PDC cultures from 36 HCC samples. MicroRNA (miRNA) signatures in PDCs and PDC-derived exosomes were profiled by microRNA-sequencing. Differentially expressed miRNAs between the low- and fast-migrated groups were identified and further validated in 372 HCC profiles from The Cancer Genome Atlas (TCGA). Six exosomal miRNAs were identified to be differentially expressed between the two groups. In the fast-migrated group, five miRNAs (miR-140-3p, miR-30d-5p, miR-29b-3p, miR-130b-3p and miR-330-5p) were downregulated, and one miRNA (miR-296-3p) was upregulated compared with the slow-migrated group. Pathway analysis demonstrated that the target genes of the differentially expressed miRNAs were significantly enriched in the 'focal adhesion' pathway, which is consistent with the roles of these miRNAs in tumor metastasis. Three miRNAs, miR-30d, miR-140 and miR-29b, were significantly associated with patient survival. These findings indicated that these exosomal miRNAs may be candidate biomarkers for predicting HCC cell migration and prognosis and may guide the treatment of advanced HCC.

Impact of osmoregulation on the differences in Cd accumulation between two contrasting edible amaranth cultivars grown on Cd-polluted saline soils.

This study aimed to investigate the difference of osmoregulation between two edible amaranth cultivars, Liuye (high Cd accumulator) and Quanhong (low Cd accumulator), under salinity stress and determine the effects of such difference on Cd accumulation. A pot experiment was conducted to expose the plants to sewage-irrigated garden soil (mean 2.28 mg kg-1 Cd) pretreated at three salinity levels. Under salinity stress, the concentrations of Cd in the two cultivars were significantly elevated compared with those in the controls, and the Cd concentration in Liuye was statistically higher than that in Quanhong (p < 0.05). Salinity-induced osmoregulation triggered different biogeochemical processes involved in Cd mobilization in the rhizosphere soil, Cd absorption, and translocation by the two cultivars. Rhizosphere acidification induced by an imbalance of cation over anion uptake was more serious in Liuye than in Quanhong, which obviously increased soil Cd bioavailability. Salinity-induced injuries in the cell wall pectin and membrane structure were worse in Liuye than in Quanhong, increasing the risk of Cd entering the protoplasts. The chelation of more cytoplasmic Cd2+ with Cl- ions in the roots of Liuye promoted Cd translocation into the shoots. Furthermore, the less organic solutes in the root sap of Liuye than in that of Quanhong also favored Cd translocation into the shoots. Hence, osmoregulation processes can be regarded as important factors in reducing Cd accumulation in crop cultivars grown on saline soils.