Aberration of social behavior and gut microbiota induced by cross-fostering implicating the gut-brain axis.

The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites.

The association between financial support of adult children to their parents and informal care provision in China and its differences in household registration, residence arrangement and community-based care services: 2008 ~ 2018.

BACKGROUND: The changes in demographic and family structures have weakened the traditional norms of filial piety and intergenerational relationships dramatically. This study aims to examine the dynamic association between financial support of adult children to their parents and informal care provision in China and its differences in household registration, residence arrangement and community-based care services. METHODS: Data was derived from the 2008-2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), which is a longitudinal survey of a nationally representative sample of individuals aged 60 and over. Random effects model was used to assess the association between financial support and informal care provision of adult children to their parents. RESULTS: It was found that financial support showed an upward trend while informal care provision showed a download trend from 2008 to 2018. The result indicated a significant and negative association between financial support and informal care provision of adult children to their parents (B = -0.500, 95% confidence interval (CI) = -0.761 to -0.239). And the association was significant among elderly people who were from urban areas (B = -0.628, 95% CI = -0.970 to -0.287), co-resided with adult children (B = -0.596, 95% CI = -0.939 to -0.253), and had community-based services (B = -0.659, 95% CI = -1.004 to -0.315). CONCLUSION: Financial support was negatively associated with informal care provision of adult children to their parents in China, and the association has differences in household registration, residence arrangement and community-based care services. It is suggested that policymakers should prioritize planning interventions for elderly care services and establish a family caregiver support system.

Association between mild cognitive impairment and falls among Chinese older adults: the mediating roles of balance capacity and depressive symptoms.

BACKGROUND: This study aimed to examine the association between mild cognitive impairment (MCI) and the follow-up risk of falls among Chinese older adults, exploring the mediating roles of balance capacity and depressive symptoms in the association between MCI and falls. METHODS: A total of 5482 adults aged 60 years and above from waves 2015 and 2018 of the China Health and Retirement Longitudinal Study were included for analysis. Cognition was assessed by a global cognition score, which included three tests: episodic memory, figure drawing and Telephone Interview of Cognitive Status. Depressive symptoms were assessed with the Centre for Epidemiological Studies Depression Scale. Logistic regression models were used to estimate the association between MCI and falls. Mediation analysis was employed to explore the potential mediating roles of balance capacity and depressive symptoms in the association between MCI and falls. RESULTS: MCI was significantly associated with the risk of falls (OR 1.259, 95% CI 1.080 to 1.467). Balance capacity and depressive symptoms played parallel mediating roles in the association between MCI and falls, and the mediating effects were 0.004 (95% CI 0.003 to 0.024) and 0.010 (95% CI 0.004 to 0.016), respectively. CONCLUSIONS: It is necessary to screen for and recognise MCI in order to prevent falls among older adults. More efforts should be made to improve balance capacity and relieve depressive symptoms to reduce the risk of falls among older adults with MCI.

Optimism and survival: health behaviors as a mediator-a ten-year follow-up study of Chinese elderly people.

BACKGROUND: Optimism-the generalized expectation that good things will happen-is a promising health asset. Mounting evidence indicates that there are specific associations between optimism and survival rates. However, for public health purposes, it is critical to consider whether the relationship between optimism and survival holds for older adults as a whole and to explore the role of health behaviors as potential mediators. METHODS: Prospective data were obtained from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Optimism was measured in 2008, and survival was measured by survival time of the interviewees during the whole observation period from 2008 to 2018. Cox proportional hazard models were employed to evaluate the association between optimism and survival among the elderly. The mediating effect analysis method was used to explore the potential mediating role of health behaviors on the association between optimism and survival. RESULTS: Compared to less optimistic older adults, optimistic individuals were associated with lower odds of mortality (HR = 0.94, 95% CI = 0.89 - 0.99). Health behaviors are key elements that play a positive role in survival (HR = 0.95, 95% CI = 0.94 - 0.96). Health behaviors played an intermediary role in the relationship between optimism and mortality, and the mediating effect was -0.005. CONCLUSIONS: Optimism and health behaviors were broadly and robustly associated with a lower risk of mortality. Health behaviors mediate the relationship between optimism and mortality. Appropriate intervention should be carried out on optimism and health behaviors among elderly people to improve the likelihood of health in aging.

gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration.

BACKGROUND: A key cause of the high mortality of cardiovascular diseases is the cardiomyocyte inability to renew after cardiac injury. As a promising strategy to supplement functional myocytes for cardiac repair, there is a pressing need to understand the cellular and molecular mechanisms of heart regeneration. METHODS: Seven genetic mouse lines were used: global OSM (oncostatin M) knockout, monocyte-/macrophage-specific OSM deletion, cardiomyocyte-specific lines, including OSM receptor deletion, gp130 (glycoprotein 130) deletion, gp130 activation, and Yap (yes-associated protein) ablation with gp130 activation mice. A series of molecular signaling experiments, including RNA sequencing, immunostaining, coimmunoprecipitation, and imaging flow cytometry, were conducted. Two models of cardiac injury, apical resection and myocardial infarction operation, were performed in neonatal, juvenile, and adult mice. Heart regeneration and cardiac function were evaluated by Masson staining and echocardiography, respectively. Gene recombinant adenovirus-associated virus was constructed and infected myocardial-infarcted mice as a gene therapy. RESULTS: OSM was identified by RNA sequencing as a key upstream regulator of cardiomyocyte proliferation during neonatal heart regeneration in mice. Cardiomyocyte proliferation and heart regeneration were suspended in neonatal mice after cardiac injury when OSM was conditionally knockout in macrophages. The cardiomyocyte-specific deficiency of the OSM receptor heterodimers, OSM receptor and gp130, individually in cardiomyocytes reduced myocyte proliferation and neonatal heart regeneration. Conditional activation of gp130 in cardiomyocytes promoted cardiomyocyte proliferation and heart regeneration in juvenile and adult mice. Using RNA sequencing and functional screening, we found that Src mediated gp130-triggered cardiomyocyte proliferation by activating Yap (yes-associated protein) with Y357 phosphorylation independently of the Hippo pathway. Cardiomyocyte-specific deletion of Yap in Myh6-gp130ACT mice blocked the effect of gp130 activation-induced heart regeneration in juvenile mice. Gene therapy with adenovirus-associated virus encoding constitutively activated gp130 promoted cardiomyocyte proliferation and heart regeneration in adult mice after myocardial infarction. CONCLUSIONS: Macrophage recruitment is essential for heart regeneration through the secretion of OSM, which promotes cardiomyocyte proliferation. As the coreceptor of OSM, gp130 activation is sufficient to promote cardiomyocyte proliferation by activating Yap through Src during heart regeneration. gp130 is a potential therapeutic target to improve heart regeneration after cardiac injury.

The evolution trend of availability of China's community-based care services and its impact on the cognitive function of elderly people: 2008-2018.

BACKGROUND: To address the challenge of the aging population, community-based care services (CBCS) have been developed rapidly in China as a new way of satisfying the needs of elderly people. Few studies have described the evolution trend of availability of CBCS in rural and urban areas and evaluated their effectiveness. This study aims to show the availability of China's CBCS and further analyze the effect of the CBCS on the cognitive function of elderly people. METHODS: Longitudinal analysis was performed using data from the 2008 to 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 23937 observations from 8421 elderly people were included in the study. The Chinese version of the Mini-Mental State Examination (MMSE) was used to assess cognitive function. We aggregated similar CBCS to generate three binary variable categories (daily life support, emotional comfort and entertainment services, medical support and health services) indicating the availability of CBCS (1 = yes, 0 = no). Multilevel growth models were employed to estimate the association between CBCS and cognitive function while adjusting for many demographic and socioeconomic characteristics. RESULTS: The availability of CBCS increased a lot from 2008 to 2018 in China. Although the availability of CBCS in urban areas was higher than that in rural areas in 2008, by 2018 the gap narrowed significantly. Emotional comfort and entertainment services (B = 0.331, 95% CI = 0.090 to 0.572) and medical support and health services (B = 1.041, 95% CI = 0.854 to 1.228) were significantly and positively associated with cognitive function after adjusting for the covariates. CONCLUSION: There was a significant increase in the availability of CBCS from 2008 to 2018 in China. This study sheds light on the positive correlation between CBCS and cognitive function among Chinese elderly individuals. The results suggest that policymakers should pay more attention to the development of CBCS and the equity of the supply of CBCS in urban and rural areas.

Telocytes in Different Organs of Vertebrates: Potential Essence Cells of the Meridian in Chinese Traditional Medicine.

Telocytes (TCs) are very long, non-neuronal, somatic cells whose function is widely believed to be involved in providing connections between different cells within the body. The cellular characteristics of TCs in various organs have been studied by immunohistochemistry, double immunofluorescence and electron microscopy in different vertebrate species, and here we investigate the proposed properties of these cells in the context of the "meridian" in Chinese Traditional Medicine (CTM). The results show that TCs and their long extensions, telopodes (Tps) develop a complicated network by homo- and heterocellular junctions in the connective tissue throughout the body, which can connect the skin with distant organs. In concept, this is the analogue of ancient meridian maps connecting skin acupoints with the viscera. Various active cells and extracellular vesicles including exosomes move along Tps, which, along with developed mitochondria within the podoms of Tps, may account for the structural evidence for "Qi" (vital energy and signal communication) in CTM. Morphological associations of TCs with the nerve, vascular, endocrine, and immune systems are also compatible with previously proposed meridian theories in CTM. Close relationships exist between TCs and collagen fiber bundles and some structures in skin fascia provide the microanatomical support for acupuncture treatment based on the meridian principle. The dynamicity in the distribution and structure of TCs reflects the plasticity of the meridian at the cellular level. As the same attribute, both the meridian and the TC have been associated with various diseases. Here, we summarize structural analogues between the TC and the meridian, suggesting that TCs have the cytological characteristics of the CTM meridian. We, therefore, hypothesize that TCs are the "essence cells" of the CTM meridian, which can connect and integrate different cells and structures in the connective tissue.

Tissue Micro-channels Formed by Collagen Fibers and their Internal Components: Cellular Evidence of Proposed Meridian Conduits in Vertebrate Skin.

In order to clarify fine structures of the hypothetical meridian conduits of Chinese traditional medicine (CTM) in the skin, the present study used light and transmission electron microscopy to examine fasciae in different vertebrate species. Collagen fiber bundles and layers were arranged in a crisscross pattern, which developed into a special tissue micro-channel (TMC) network, in a manner that was analogs to the proposed skin meridian conduits. It was further revealed that tissue fluid in lateral TMC branches drained into wide longitudinal channels, which were distinctly different from lymphatic capillary. Mast cells, macrophages, and extracellular vesicles such as ectosomes and exosomes were distributed around telocytes (TCs) and their long processes (Telopodes, Tps) within the TMC. Cell junctions between TCs developed, which could enable the communication between contiguous but distant Tps. On the other hand, winding free Tps without cell junctions were also uncovered inside the TMC. Tissue fluid, cell junctions of TCs, mast cells, macrophages, and extracellular vesicles within the TMC corresponded to the circulating "" ("Qi-Xue", i.e., information, message, and energy) of meridian conduits at the cytological level. These results could provide morphological evidence for the hypothesis that "meridians are the conduit for Qi-Xue circulation" in CTM.

[Evaluation of the Acute Toxicity and Genotoxicity of the Rice Biofortified with ß-Glucan].

OBJECTIVE: To provide a scientific evaluation of the food safety of the rice biofortified with ß-glucan. METHODS: The acute toxicity and genotoxicity of the rice were evaluated by 14-day feeding experiment, Ames experiment, erythrocyte micronucleus test and mouse lymphoma thymidine kinase gene ( TK) mutation assay respectively. RESULTS: In the acute toxicity test, there was no obvious toxicity of rice biofortified with ß-glucan, and no abnormality was found in anatomical observation. The median lethal dose (LD 50) to rats and mice wereall greater than 15 mg/kg, which belonged to the actual non-toxic level. Whether with S 9 activation or not, no genotoxicity was found to the tested strains TA97a, TA98, TA100, TA102 and TA1535. No induction of polychromatic erythrocytes and inhibition of bone marrow were found in erythrocyte micronucleus test. The results of TK gene mutation assay did not show the mutagenicity of ß-glucan bioaugmentation rice. All results of the three genotoxicity tests were negative. CONCLUSION: Under the current experimental conditions, ß-glucan biofortified rice showed no obvious acute toxicity and genotoxicity.

[Research progress on chemical structures and pharmacological activities of Poria cocos polysaccharide and its derivatives].

Poria cocos is a both medicinal and edible Chinese herb variety, with the effects of diuretic, spleen-enhancing and tranquilizing. P. cocos polysaccharide(PCP) is one of the most important active substances of P. cocos. Pharmacological research shows that PCP has a variety of pharmacological activities such as regulating immunity, anti-inflammatory, anti-oxidation, antitumor, and liver protection, with a huge development and utilization value. By consulting the relevant literature, we systematically summarized the chemical structures and the research progress on pharmacological activities of PCP and its derivatives in recent years to explore the chemical compositions and activities of PCP thoroughly. In addition, the current problems were discussed in this article to provide reference for further exploration of the structure-activity relationship of PCP and its further development and utilization.

[Textual research on Sojae Semen Nigrum].

In this paper, the name, origin and producing area of Sojae Semen Nigrum were studied to provide the basis for the selection of medicinal varieties of Sojae Semen Nigrum. The textual research of this herbal was carried out through the textual research of ancient and modern literature and the comparative study of botany, combined with agricultural archaeology and the investigation of adulterant products. Before Qin Dynasty, the Sojae Semen Nigrums had not been selected, and the edible beans should only be Glycine soja. From Qin to the Northern and Southern dynasties, the Sojae Semen Nigrums G. max were selected,but the medicinal Sojae Semen Nigrum was G. soja. After Tang Dynasty, Sojae Semen Nigrums were recorded more, the medicinal Sojae Semen Nigrums referred to G. soja,G. max and G. gracilis. In modern times, G. soja was hardly to use as the medicine. The harvest time is August or September, and there are many processing methods, such as frying, making tofu, making Semen Sojae Praeparatum, boiling, boiling with auxiliary materials, germination, etc. The quality evaluation of Sojae Semen Nigrum was consistent in past dynasties, and it was considered that "it is better for those who are tight and small". Before Tang Dynasty, the better should only be G. soja. After the Qing Dynasty, the better should be green cotyledon varieties of G. max,which are recommended. In addition, there are many varieties of Sojae Semen Nigrum. It is hoped that that the scientific researchers of traditional Chinese medicine can use modern technology to distinguish the efficacy of Sojae Semen Nigrum with green and yellow cotyledon, and make a comparison between large and small Sojae Semen Nigrum. The results provide scientific basis for the selection of medicinal varieties of Sojae Semen Nigrum.

A long noncoding RNA NR_045363 controls cardiomyocyte proliferation and cardiac repair.

Long noncoding RNAs (lncRNAs) play important roles in the regulation of genes involved in cell proliferation. We have previously sought to more globally understand the differences of lncRNA expression between human fetal heart and adult heart to identify some functional lncRNAs which involve in the process of heart repair. We found that a highly conserved long noncoding RNA NR_045363 was mainly expressed in cardiomyocytes and rarely in non-cardiomyocytes. NR_045363 overexpression in 7-day-old mice heart could improve cardiac function and stimulate cardiomyocyte proliferation after myocardial infarction. Furthermore, NR_045363 knockdown inhibited proliferation of primary embryonic cardiomyocytes, while NR_045363 overexpression enhanced DNA synthesis and cytokinesis in neonatal cardiomyocytes in vitro. Mechanistic analysis revealed that NR_045363 promoted cardiomyocyte proliferation through interaction with miR-216a, which regulated the JAK2-STAT3 pathway. Our results showed that NR_045363 is a potent lncRNA modulator essential for cardiomyocyte proliferation.

How cells respond to environmental cues - insights from bio-functionalized substrates.

Biomimetic materials have long been the (he)art of bioengineering. They usually aim at mimicking in vivo conditions to allow in vitro culture, differentiation and expansion of cells. The past decade has witnessed a considerable amount of progress in soft lithography, bio-inspired micro-fabrication and biochemistry, allowing the design of sophisticated and physiologically relevant micro- and nano-environments. These systems now provide an exquisite toolbox with which we can control a large set of physicochemical environmental parameters that determine cell behavior. Bio-functionalized surfaces have evolved from simple protein-coated solid surfaces or cellular extracts into nano-textured 3D surfaces with controlled rheological and topographical properties. The mechanobiological molecular processes by which cells interact and sense their environment can now be unambiguously understood down to the single-molecule level. This Commentary highlights recent successful examples where bio-functionalized substrates have contributed in raising and answering new questions in the area of extracellular matrix sensing by cells, cell-cell adhesion and cell migration. The use, the availability, the impact and the challenges of such approaches in the field of biology are discussed.

MicroRNA-21 Knockout Exacerbates Angiotensin II-Induced Thoracic Aortic Aneurysm and Dissection in Mice With Abnormal Transforming Growth Factor-ß-SMAD3 Signaling.

OBJECTIVE: Thoracic aortic aneurysm and dissection (TAAD) are severe vascular conditions. Dysfunctional transforming growth factor-ß (TGF-ß) signaling in vascular smooth muscle cells and elevated angiotensin II (AngII) levels are implicated in the development of TAAD. In this study, we investigated whether these 2 factors lead to TAAD in a mouse model and explored the possibility of using microRNA-21 (miR-21) for the treatment of TAAD. APPROACH AND RESULTS: TAAD was developed in Smad3 (mothers against decapentaplegic homolog 3) heterozygous (S3+/-) mice infused with AngII. We found that p-ERK (phosphorylated extracellular regulated protein kinases)- and p-JNK (phosphorylated c-Jun N-terminal kinase)-associated miR-21 was higher in TAAD lesions. We hypothesize that downregulation of miR-21 mitigate TAAD formation. However, Smad3+/-:miR-21-/- (S3+/-21-/-) mice exhibited conspicuous TAAD formation after AngII infusion. The vascular wall was dilated, and aortic rupture occurred within 23 days during AngII infusion. We then examined canonical and noncanonical TGF-ß signaling and found that miR-21 knockout in S3+/- mice increased SMAD7 and suppressed canonical TGF-ß signaling. Vascular smooth muscle cells lacking TGF-ß signals tended to switch from a contractile to a synthetic phenotype. The silencing of Smad7 with lentivirus prevented AngII-induced TAAD formation in S3+/-21-/- mice. CONCLUSIONS: Our study demonstrated that miR-21 knockout exacerbated AngII-induced TAAD formation in mice, which was associated with TGF-ß signaling dysfunction. Therapeutic strategies targeting TAAD should consider unexpected side effects associated with alterations in TGF-ß signaling.

In Vivo Multivesicular Body and Exosome Secretion in the Intestinal Epithelial Cells of Turtles During Hibernation.

The present study was designed to investigate the in vivo biological processes of multivesicular bodies (MVBs) and exosomes in mitochondria-rich cells (MRCs), goblet cells (GCs), and absorptive cells (ACs) in turtle intestines during hibernation. The exosome markers, cluster of differentiation 63 (CD63) and tumor susceptibility gene 101 (TSG101), were positively expressed in intestinal villi during turtle hibernation. The distribution and formation processes of MVBs and exosomes in turtle MRCs, GCs, and ACs were further confirmed by transmission electron microscopy. During hibernation, abundantly secreted early endosomes (ees) were localized in the luminal and basal cytoplasm of the MRCs and ACs, and late endosomes (les) were dispersed with the supranuclear parts of the MRCs and ACs. Many "heterogeneous" MVBs were identified throughout the cytoplasm of the MRCs and ACs. Interestingly, the ees, les, and MVBs were detected in the cytoplasm of the GCs during hibernation; however, they were absent during nonhibernation. Furthermore, the exocytosis pathways of exosomes and autophagic vacuoles were observed in the MRCs, GCs, and ACs during hibernation. In addition, the number of different MVBs with intraluminal vesicles (ILVs) and heterogeneous endosome-MVB-exosome complexes was significantly increased in the MRCs, GCs, and ACs during hibernation. All these findings indicate that intestinal epithelial cells potentially perform a role in the secretion of MVBs and exosomes, which are essential for mucosal immunity, during hibernation.

Differences in the health behaviors of elderly individuals and influencing factors: Evidence from the Chinese Longitudinal Healthy Longevity Survey.

INTRODUCTION: Health behaviors play an important role in determining individual health status; thus, understanding differences in the health behaviors of elderly individuals and their influencing factors is a prerequisite for the formulation and implementation of health behavior promotion policies for elderly individuals. The objectives of this study were to explore differences in health behaviors among Chinese elderly people and their influencing factors. METHODS: Based on data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2014, this paper applied latent class analysis (LCA) to explore differences in the health behaviors of elderly individuals in China and employed a multinomial logit model to identify the influencing factors that cause these differences. RESULTS: Results showed that there are five classes of health behaviors among elderly individuals in China: passive, relatively passive, general, relatively positive, and positive, the proportions of which were 31.07%, 15.86%, 24.06%, 17.24%, and 11.76%, respectively. Community medical and health services, pension, living arrangements, and family income were the primary factors explaining differences in the health behaviors of elderly individuals. In addition, there were significant demographic differences in the health behaviors of elderly individuals in China, including gender, age, education, marital status, census register, region, and others. CONCLUSION: There are significant differences in the behaviors of elderly individuals in China, and the behaviors of the majority of elderly people are not healthy. China is expected to invest more medical and health resources to tackle health prevention and management and to provide targeted education, guidance, and intervention in elderly health behaviors, urging them to control and correct risky health behaviors with a focus on elderly individuals that are the oldest, are females, have low education levels, and live in the countryside and in towns.

NR4A1 is Involved in Fibrogenesis in Ovarian Endometriosis.

BACKGROUND/AIMS: Excess fibrosis may lead to chronic pain, scarring, and infertility as endometriosis develops and progresses. The pathogenesis of endometriosis has been linked to transforming growth factor-ß (TGF-ß), the most potent promoter of fibrosis. METHODS: Levels of NR4A1 and P-NR4A1 protein in human endometrial and endometriotic tissue were assessed by western blotting and immunohistochemistry. The expression levels of fibrotic markers in stromal cells were evaluated by real-time PCR. The degree of fibrosis in mouse endometriotic lesions was detected by Masson trichrome and Sirius red staining. RESULTS: The level of phosphorylated-NR4A1 was higher in ovarian endometriotic tissue than in normal endometrium, and long-term TGF-ß1 stimulation phosphorylated NR4A1 in an AKT-dependent manner and then promoted the expression of fibrotic markers. Furthermore, inhibition of NR4A1 in stromal cells increased the TGF-ß1-dependent elevated expression of fibrotic markers, and loss of NR4A1 stimulated fibrogenesis in mice with endometriosis. Additionally, Cytosporone B (Csn-B), an NR4A1 agonist, effectively decreased the TGF-ß1-dependent elevated expression of fibrotic markers in vitro and significantly inhibited fibrogenesis in vivo. CONCLUSION: NR4A1 can regulate fibrosis in endometriosis and may serve as a new target for the treatment of endometriosis.

MicroRNA-155 promotes neointimal hyperplasia through smooth muscle-like cell-derived RANTES in arteriovenous fistulas.

OBJECTIVE: Arteriovenous fistula (AVF) suffers from a high number of failures caused by insufficient outward remodeling and venous neointimal hyperplasia formation. The aim was to investigate the exact mechanism by which microRNA-155 (miR-155) in the outflow vein of AVF is regulated. METHODS: AVFs between the branch of the jugular vein and carotid artery in an end-to-end manner were created in C57BL/6 and miR-155-/- mice with a C57BL/6 background. The venous segments were harvested at day 7, 14, 21, and 28, and the AVFs were analyzed histologically and at a messenger RNA level using real-time quantitative polymerase chain reactions. The outflow vein of AVF and the normal great saphenous vein, collected from patients with chronic kidney disease and coronary artery bypass surgery, were analyzed by histologic and molecular biologic approaches. RESULTS: Venous neointimal hyperplasia is significantly alleviated in miR-155-/- mice, and the expression of several chemokines and cytokines in the vessel wall, including regulated on activation, normal T-cell expressed and secreted factor (RANTES), monocyte chemoattractant protein 1, and vascular endothelial growth factor, was inhibited. miR-155 promoted the RANTES expression of smooth muscle-like cells, which in turn facilitated cell proliferation and extracellular matrix production. CONCLUSIONS: miR-155 enhances venous neointima formation through the autocrine and paracrine effects of smooth muscle-like cell-derived RANTES in a nuclear factor κB-dependent manner during the entire AVF process, especially at the advanced stage.

Predictive Value of Head-Neck CTA Combined with ABCD2 Scale Score for Patients with Cerebral Infarction of Vertebrobasilar Transient Ischemic Attack (TIA).

BACKGROUND The present study was designed to evaluate the predictive value of head-neck computed tomography angiography (CTA) combined with ABCD2 score scale for patients with cerebral infarction of vertebrobasilar transient ischemic attack (TIA). MATERIAL AND METHODS A total of 92 patients with TIA who were admitted to our hospital from January 2014 to June 2015 were enrolled in this study. ABCD2 score and CTA combined with ABCD2 score were assessed. RESULTS The incidence of cerebral infarction was highest in the high-risk group, followed by the middle-risk group and low-risk group. The incidence of cerebral infarction was related to the degree of stenosis in head-neck CTA, which was highest in the severe stenosis group, followed by the moderate stenosis group and mild stenosis/normal group, with significant differences. The incidence of cerebral infarction in patients with cerebral artery stenosis was correlated with the incidence of cerebral infarction in the head and neck CTA, which was severe > medium > normal/low (P<0.05). CONCLUSIONS The ABCD2 score can accurately predict the early development from TIA to cerebral infarction. If it is used in combination with head-neck CTA; CTA combined ABCD2 score can further improve the accuracy of prediction, which makes it feasible for use in prediction of the development of vertebrobasilar TIA to cerebral infarction.

MicroRNA-155 Promotes the Directional Migration of Resident Smooth Muscle Progenitor Cells by Regulating Monocyte Chemoattractant Protein 1 in Transplant Arteriosclerosis.

OBJECTIVE: Smooth muscle-like cells are major cell components of transplant arteriosclerosis lesions. This study investigated the origin of the smooth muscle-like cells, the mechanisms responsible for their accumulation in the neointima, and the factors that drive these processes. APPROACH AND RESULTS: A murine aortic transplantation model was established by transplanting miR-155(-/-) bone marrow cells into miR-155(+/+) mice. MicroRNA-155 was found to play a functional role in the transplant arteriosclerosis. Moreover, we found that the nonbone marrow-derived progenitor cells with markers of both early differentiated smooth muscles and stem cells in the allograft adventitia were smooth muscle progenitor cells. Purified smooth muscle progenitor cells expressed a mature smooth muscle cell marker when induced by platelet-derived growth factor-BB in vitro. In vivo, these cells could migrate into the intima from the adventitia and could contribute to the neointimal hyperplasia. The loss of microRNA-155 in bone marrow-derived cells decreased the concentration gradient of monocyte chemoattractant protein 1 between the intima and the adventitia of the allografts, which reduced the migration of smooth muscle progenitor cells from the adventitia into the neointima. CONCLUSIONS: This study demonstrated that microRNA-155 promoted the directional migration of smooth muscle progenitor cells from the adventitia by regulating the monocyte chemoattractant protein 1 concentration gradient, which aggravated transplant arteriosclerosis.