Pericytes are mesenchymal cells that surround the endothelial cells of small vessels in various organs. These cells express several markers, such as NG2, CD146, and PDGFRβ, and play an important role in the stabilization and maturation of blood vessels. It was also recently revealed that like mesenchymal stem cells (MSCs), pericytes possess multilineage differentiation capacity, especially myogenic, adipogenic, and fibrogenic differentiation capacities. Although some previous studies have reported that pericytes also have osteogenic potential, the osteogenesis of pericytes can still be further elucidated. In the present study, we established novel methods for isolating and culturing primary murine pericytes. An immortalized pericyte line was also established. Multilineage induction of the pericyte line induced osteogenesis, adipogenesis, and chondrogenesis of the cells in vitro. In addition, pericytes that were injected into the fracture site of a bone fracture mouse model contributed to callus formation. Furthermore, in vivo pericyte-lineage-tracing studies demonstrated that endogenous pericytes also differentiate into osteoblasts and osteocytes and contribute to bone fracture healing as a cellular source of osteogenic cells. Pericytes can be a promising therapeutic candidate for treating bone fractures with a delayed union or nonunion as well as bone diseases causing bone defects.

Background: Non-communicable diseases (NCDs) are emerging as a serious problem for many low-and middle-income countries, especially in societies with rapidly growing economies. During such economic growth, rapid urbanization may affect population health as much as other economic factors. However, there have been few studies comparing the urban-rural difference in NCDs prevalence in low-and middle-income countries. This study aimed to compare differences in major NCDs prevalence between urban and rural residency after controlling for socioeconomic and behavioral risk factors in Vietnam. Methods: Residents aged ≥15 years from an urban (the district-level town of Thuận An, n=2,126) and rural (Quốc Oai, n=2,970) district in Vietnam participated in a communitybased survey in 2016. Information on NCD history, socioeconomic status, and lifestyle factors was collected on an individual or household basis. Associations between residential area, other risk factors, and NCD prevalence was investigated using multiple logistic regression analysis. Results: Urban residency was significantly associated with cardiovascular diseases (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.01-1.68) and diabetes (OR, 1.86; 95% CI, 1.01-3.41) for those aged 15-59 years after controlling for other socioeconomic characteristics, and inversely associated with respiratory diseases (OR, 0.66; 95% CI, 0.48-0.90) (rural residency showed more significant prevalence to respiratory diseases). For aged individuals ≥60 years old, urban living was similarly positively associated with diabetes (OR, 2.26; 95% CI, 1.25-4.10), and inversely associated with other NCDs (OR, 0.49; 95% CI, 0.36-0.67) (rural residency showed more significant prevalence to other NCDs), in contrast to younger adults. Conclusions: The study disclosed different prevalence patterns of NCDs for differently aged urban residents in Vietnam. The Vietnamese government is encouraged to develop health care policies that strategically targeted to the different patterns of disease prevalence.

Alzheimer’s disease (AD) is an aging-dependent neurodegenerative disease that impairs cognitive function. Although the main pathologies of AD are the aggregation of amyloid-beta (Aβ) and phosphorylated Tau protein, the mechanisms that lead to these pathologies and their effects are believed to be heterogeneous among patients. Many epidemiological studies have suggested that sex is involved in disease prevalence and progression. The reduction of sex hormones contributes to the pathogenesis of AD, especially in females, suggesting that the supplementation of sex hormones could be a therapeutic intervention for AD. However, interventional studies have revealed that hormone therapy is beneficial under limited conditions in certain populations with specific administration methods. Thus, this suggests the importance of identifying crucial factors that determine hormonal effects in patients with AD. Based on these factors, it is necessary to decide which patients will receive the intervention before starting it. However, the long observational period and many uncontrollable environmental factors in clinical trials made it difficult to identify such factors, except for the APOE ε4 allele. Induced pluripotent stem cells (iPSCs) derived from patients can differentiate into neurons and recapitulate some aspects of AD pathogenesis. This in vitro model allows us to control non-cell autonomous factors, including the amount of Aβ aggregates and sex hormones. Hence, iPSCs provide opportunities to investigate sex-dependent pathogenesis and predict a suitable population for clinical trials of hormone treatment.

Cortical excitatory neurons (Cx neurons) are the most dominant neuronal cell type in the cerebral cortex and play a central role in cognition, perception, intellectual behavior, and emotional processing. Robust in vitro induction of Cx neurons may facilitate as a tool for the elucidation of brain development and the pathomechanism of the intractable neurodevelopmental and neurodegenerative disorders, including Alzheimers disease, and thus potentially contribute to drug development. Here, we report a defined method for the efficient induction of Cx neurons from the feeder-free-conditioned human embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells). Using this method, human ES/iPS cells could be differentiated into ~99% MAP2-positive neurons by three weeks, and these induced neurons displayed several characteristics of mature excitatory neurons within 5 weeks, such as strong expression of glutamatergic neuron-specific markers (subunits of AMPA and NDMA receptors and CAMKIIα), highly synchronized spontaneous firing and excitatory postsynaptic current (EPSC). In addition, the Cx neurons showed susceptibility to Aβ oligomer toxicity and excessive glutamate excitotoxicity, which is another advantage for toxicity testing and searching for therapeutic agent discovery. Taken together, this study provides a novel research platform for studying neural development and degeneration based on the feeder-free human ES/iPS cell system.

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Sole measurement of plasma vitamin B12 is no longer enough to identify vitamin B12 (B12) deficiency. When plasma vitamin B12 is in the low-normal range, especially between 201 and 350 ng/L, B12 deficiency should be assessed by measurements of plasma homocysteine and/or plasma methylmalonic acid (MMA). However, these biomarkers also accumulate during renal impairment, leading to a decreased specificity for B12 deficiency. In such cases, urinary methylmalonic acid/creatinine ratio (uMMA/C) could be of interest, due to the stable urinary excretion of MMA. The objectives were to evaluate the influence of renal impairment on uMMA/C compared to plasma homocysteine and plasma methylmalonic acid, and to determine the diagnostic performances of uMMA/C in the diagnosis of B12 deficiency. We prospectively studied 127 patients with a plasma B12 between 201 and 350 ng/L. We noticed that uMMA/C was not dependent on renal function (p = 0.34), contrary to plasma homocysteine and plasma methylmalonic acid. uMMA/C showed a perspective diagnostic performance (AUC 0.71 [95% CI: 0.62–0.80]) and the threshold of 1.45 umol/mmol presented a high degree of specificity (87.9% [95% CI: 72.0–98.9]). In conclusion, uMMA/C is a promising biomarker to assess vitamin B12 status in doubtful cases, notably during renal impairment.

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