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Background: Ulcerative colitis is characterized by relapsing inflammation in the gastrointestinal tract with limited treatment options. The aim of the present study was to assess the anti-inflammatory effect of Suppressor of cytokine signaling (SOCS1) on lipopolysac- charide-stimulated RAW264.7 cells and to investigate its potential mechanisms., Methods: The in vitro ulcerative colitis model was established by using lipopolysaccharide-stimulated RAW264.7 cells. Western blot- ting was used to detect the protein expression levels of SOCS1, JAK2, STAT3, and VDR. Reverse transcription-quantitative polymerase chain reaction was used to measure the mRNA expression of SOCS1, miR-222-3p, and VDR. An enzyme-linked immunosorbent assay was performed to measure the levels of inflammatory cytokines. A luciferase assay assessed the binding of SOCS1 to miR-222-3p. A total of 15 patients with ulcerative colitis and 18 healthy controls were recruited. The expression levels of SOCS1 and miR-222-3p in the colonic mucosa tissues of patients with ulcerative colitis and healthy controls were determined by reverse transcription-quantitative polymerase chain reaction., Results: SOCS1 upregulation inhibited the lipopolysaccharide-induced inflammation in RAW264.7 cells. SOCS1 was confirmed to be tar- geted by miR-222-3p. Silencing SOCS1 significantly abolished the inhibitory effects of miR-222-3p downregulation on inflammation. MiR-222-3p activated STAT3 signaling and reduced VDR expression by targeting SOCS1 in lipopolysaccharide-treated RAW264.7 cells. Additionally, miR-222-3p expression was upregulated in ulcerative colitis patients (P = 5.16E-10), while SOCS1 (P = 2.75E-10) and VDR (P = 52.5E-9) expression was downregulated in ulcerative colitis patients. Endoscopic scores (UCEIS) revealed significant positive cor- relation with miR-222-3p and negative correlation with SOCS1 and VDR., Conclusion: MiR-222-3p targets SOCS1 to aggravate the inflammatory response by suppressing VDR and activating STAT3 signaling in ulcerative colitis.

Background: Coronavirus disease 2019 (COVID-19) vaccination is expected to end the pandemic; a high coverage rate is required to meet this end. This study aimed to investigate the prevalence of behavioral intention of free/self-paid COVID-19 vaccination and its associations with prosociality and social responsibility among university students in China., Methods: An anonymous online cross-sectional survey was conducted among 6922 university students in five provinces in China during November 1-28, 2020. With informed consent, participants filled out an online survey link distributed to them via WeChat study groups. The response rate was 72.3%., Results: The prevalence of behavioral intentions of free COVID-19 vaccination was 78.1%, but it dropped to 57.7% if the COVID-19 vaccination involved self-payment (400 RMB; around 42 USD). After adjusting for background factors, prosociality (free vaccination: adjusted odds ratio [ORa] = 1.10, 95% CI: 1.09-1.12; self-paid vaccination: ORa = 1.08, 95% CI: 1.07-1.09) and social responsibility (free vaccination: ORa = 1.17, 95% CI: 1.14-1.19; self-paid vaccination: ORa = 1.13, 95% CI: 1.11-1.14) were positively associated with the two variables of COVID-19 vaccination intention., Conclusion: The present study demonstrated the positive effects of prosociality and social responsibility on the intention of COVID-19 vaccination. Accordingly, modification of prosociality and social responsibility can potentially improve COVID-19 vaccination. Future longitudinal and intervention studies are warranted to confirm such associations across populations and countries., (© 2022 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: The prevalence of coronavirus disease 2019 (COVID-19) vaccination is very critical in controlling COVID-19. This study mainly aimed to (1) investigate behavioral intentions of COVID-19 vaccination under various specific scenarios, and (2) associated factors of the afore-mentioned vaccination intentions., Methods: A random anonymous telephone survey interviewed 450 Chinese adults from September 16-30, 2020 in Hong Kong, China. Nine scenarios of behavioral intentions of COVID-19 vaccinations were measured combining effectiveness (80% versus 50%), safety (rare versus common mild side effect), and cost (free versus HK$ 500)., Results: The prevalence of behavioral intentions of COVID-19 vaccination under the 9 specific scenarios was very low and varied greatly (4.2% to 38.0%). The prospective countries of manufacture also influenced vaccination intention (eg, Japan: 55.8% vs China: 31.1%). Only 13.1% intended to take up COVID-19 vaccination at the soonest upon its availability. The attributes of effectiveness and side effect influenced vaccination intention most. Positively associated factors of behavioral intentions of COVID-19 vaccination included trust/satisfaction toward the government, exposure to positive social media information about COVID-19 vaccines, descriptive norms, perceived impact on the pandemic, perceived duration of protectiveness, and life satisfaction., Conclusion: Intention of COVID-19 vaccination was low in the Hong Kong general population, especially among younger people, females, and single people. Health promotion is warranted to enhance the intention. The significant factors identified in this study may be considered when designing such health promotion. Future research is required to confirm the findings in other countries. Such studies should pay attention to the specific context of cost, safety, and effectiveness, which would lead to different responses in the level of behavioral intention of COVID-19 vaccination (BICV)., (© 2022 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Uptake of social distancing behaviors may be determined by a combination of individual perceptions and social values. The study investigated (1) the associations between individual perception of perceived response efficacy and social distancing behaviors, (2) the association between social value of perceived freedom infringement and social distancing behaviors, and (3) whether perceived freedom infringement would moderate the association between perceived response efficacy and social distancing behaviors., Methods: A cross-sectional telephone survey interviewed 300 adults in the Hong Kong adult general population during April 21-28, 2020. The instruments of social distancing behaviors, perceived response efficacy, and perceived freedom infringement assessed the frequencies of practicing seven types of social distancing behaviors in the past week, perceived response efficacy of four types of governmental social distancing measures/instructions, and a 5-point Likert scale item on perceived infringement on personal freedom regarding a governmental social distancing measure of banning gatherings of >4 people in public areas. Linear regression adjusted for background factors was performed; the interaction term of perceived response efficacy × perceived freedom infringement was tested., Results: About 40.4%-83.0% of the respondents practiced various types of social distancing behaviors; 57.3%-75.0% perceived response efficacies of related governmental measures; about 20% showed perceived freedom infringement. Perceived response efficacy, but not perceived freedom infringement, was independently and positively associated with social distancing behaviors. Perceived freedom infringement significantly moderated the association between perceived response efficacy and social distancing behaviors; such a positive association was significant at higher (those scored "extremely agree"), but not lower (those scored "extremely disagree"), levels of perceived freedom infringement., Conclusion: Perceived response efficacy is a potential determinant of social distancing. However, the strength of such an association may be modified by opposing social values about personal freedom. Future studies are warranted to verify above findings and explore other potential determinants., (© 2022 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Adolescents encounter numerous challenges and need to restructure their social relationships when they enter secondary schools. Relationship adaptation is critical and failure in adaptation may be associated with Internet gaming disorder (IGD). This novel study investigated the association between relationship adaptation and IGD and related mediation mechanisms via social support and loneliness among first-year secondary school students in Shanghai and Xi'an, China in 2018. Of 2573 participants, the prevalence of IGD was 13.1%. Relationship adaptation, social support, and loneliness were all significantly associated with IGD. The association between relationship adaptation and IGD was fully mediated by three indirect paths, including relationship adaptation → social support → IGD (effect size = 35.5%), relationship adaptation → loneliness → IGD (effect size = 34.3%), and relationship adaptation → social support → loneliness → IGD (effect size = 6.1%). In conclusion, the observed high prevalence of IGD among first-year secondary school students in China was associated with poor relationship adaptation. The full mediation effects via social support and loneliness suggest that modification of these two psychosocial attributes may effectively reduce the harmful impacts of poor relationship adaptation on adolescent IGD. Future longitudinal studies are warranted to confirm the findings., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Metal exposures are ubiquitous around the world, while it is lack of prospective studies to evaluate the associations of exposure to multiple metal/metalloids with incident dyslipidemia. A total of 2947 participants without dyslipidemia at baseline were included in the analyses. We utilized inductively coupled plasma mass spectrometry to measure the baseline plasma metal concentrations. Unconditional logistic regression models were applied to estimate the relations between plasma metals and risk of incident dyslipidemia, and principal component analysis was performed to extract principal components of metals. During 5.01 ± 0.31 years of follow-up, 521 subjects were diagnosed with incident dyslipidemia. After multivariable adjustment, the odds ratios (ORs) of dyslipidemia comparing the highest quartiles to the lowest were 1.58 (95% CI: 1.20, 2.08; P trend  = 0.001) for aluminum, 1.34 (95% CI: 1.03, 1.75; P trend  = 0.03) for arsenic, 1.44 (1.09, 1.91; P trend  = 0.03) for strontium, and 1.47 (95% CI: 1.09, 2.00; P trend  = 0.005) for vanadium. The four metals also showed significant associations with the subtypes of dyslipidemia, including low HDL-C and high LDL-C. The first principal component, which mainly represented aluminum, arsenic, barium, lead, vanadium, and zinc, was associated with increased risk of incident dyslipidemia, and the adjusted OR was 1.40 (95% CI: 1.07, 1.84; P trend  = 0.02) comparing extreme quartiles. The study indicated that elevated plasma aluminum, arsenic, strontium, and vanadium concentrations were associated with a higher incidence of dyslipidemia. These findings highlight the importance of controlling metal exposures for dyslipidemia prevention., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The urban drainage system (UDS) with the integration of new and old, green and gray infrastructures has become an underlying trend, but its sewage dispatch is getting more and more difficult owing to complex network topology, much uncertainty introduced by the lack of empirical data or monitoring system, and consideration of multiple objectives. We propose a novel framework for deriving dispatching rules that allocate the wastewater inflow according to the comprehensive capacity of treatment facilities. The main innovative point of the framework is using the Prophet algorithm to handle sewage volume uncertainty introduced by rainfall. Moreover, we construct a multi-objective optimization model of operating costs and surface water quality and apply it in multiple scenarios. Lastly, we build a decision tree to mine dispatching rules and threshold identification. Taking the Pingshan River Basin, we plot dispatching diagrams and discover the threshold of creating the risk to surface water quality. When the sewage volume reached 18.0 × 10 5  m³ in winter, water quality exceeded limits. Other than that, the wastewater spatiotemporal allocation placed receiving water quality and operating cost in a competitive relationship. An application of dispatching rules shows that they fill a gap in the scientific and reasonable dispatch of the UDS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Drug discovery focused on target proteins has been a successful strategy, but many diseases and biological processes lack obvious targets to enable such approaches. Here, to overcome this challenge, we describe a deep learning-based efficacy prediction system (DLEPS) that identifies drug candidates using a change in the gene expression profile in the diseased state as input. DLEPS was trained using chemically induced changes in transcriptional profiles from the L1000 project. We found that the changes in transcriptional profiles for previously unexamined molecules were predicted with a Pearson correlation coefficient of 0.74. We examined three disorders and experimentally tested the top drug candidates in mouse disease models. Validation showed that perillen, chikusetsusaponin IV and trametinib confer disease-relevant impacts against obesity, hyperuricemia and nonalcoholic steatohepatitis, respectively. DLEPS can generate insights into pathogenic mechanisms, and we demonstrate that the MEK-ERK signaling pathway is a target for developing agents against nonalcoholic steatohepatitis. Our findings suggest that DLEPS is an effective tool for drug repurposing and discovery., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The outbreak of COVID-19 in China occurred around the Chinese New Year (January 25, 2020), and infections decreased continuously afterward. General adoption of preventive measures during the Chinese New Year period was crucial in driving the decline. It is imperative to investigate preventive behaviors among Chinese university students, who could have spread COVID-19 when travelling home during the Chinese New Year break., Objective: In this study, we investigated levels of COVID-19-related personal measures undertaken during the 7-day Chinese New Year holidays by university students in China, and associated COVID-19-related cognitive factors., Methods: A cross-sectional anonymous web-based survey was conducted during the period from February 1 to 10, 2020. Data from 23,863 students (from 26 universities, 16 cities, 13 provincial-level regions) about personal measures (frequent face-mask wearing, frequent handwashing, frequent home staying, and an indicator that combined the 3 behaviors) were analyzed (overall response rate 70%). Multilevel multiple logistic regression analysis was performed., Results: Only 28.0% of respondents (6684/23,863) had left home for >4 hours, and 49.3% (11,757/23,863) had never left home during the 7-day Chinese New Year period; 79.7% (19,026/23,863) always used face-masks in public areas. The frequency of handwashing with soap was relatively low (6424/23,863, 26.9% for >5 times/day); 72.4% (17,282/23,863) had frequently undertaken ≥2 of these 3 measures. COVID-19-related cognitive factors (perceptions on modes of transmission, permanent bodily damage, efficacy of personal or governmental preventive measures, nonavailability of vaccines and treatments) were significantly associated with preventive measures. Associations with frequent face-mask wearing were stronger than those with frequent home staying., Conclusions: University students had strong behavioral responses during the very early phase of the COVID-19 outbreak. Levels of personal prevention, especially frequent home staying and face-mask wearing, were high. Health promotion may modify cognitive factors. Some structural factors (eg, social distancing policy) might explain why the frequency of home staying was higher than that of handwashing. Other populations might have behaved similarly; however, such data were not available to us., (©Joseph Lau, Yanqiu Yu, Meiqi Xin, Rui She, Sitong Luo, Lijuan Li, Suhua Wang, Le Ma, Fangbiao Tao, Jianxin Zhang, Junfeng Zhao, Dongsheng Hu, Liping Li, Guohua Zhang, Jing Gu, Danhua Lin, Hongmei Wang, Yong Cai, Zhaofen Wang, Hua You, Guoqing Hu, COVID-19 University Student Research Group. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 07.10.2021.)

Background: The COVID-19 epidemic may elevate mental distress and depressive symptoms in various populations in China., Objective: This study investigates the levels of depression and mental distress due to COVID-19, and the associations between cognitive, behavioral, and psychosocial factors, and depression and mental distress due to COVID-19 among university students in China., Methods: A large-scale online cross-sectional study (16 cities in 13 provinces) was conducted among university students from February 1 to 10, 2020, in China; 23,863 valid questionnaires were returned. The Patient Health Questionnaire-9 was used to assess depression. Structural equation modeling was performed to test mediation and suppression effects., Results: Of the 23,863 participants, 47.1% (n=11,235) reported high or very high levels of one or more types of mental distress due to COVID-19; 39.1% (n=9326) showed mild to severe depression. Mental distress due to COVID-19 was positively associated with depression. All but one factor (perceived infection risks, perceived chance of controlling the epidemic, staying at home, contacted people from Wuhan, and perceived discrimination) were significantly associated with mental distress due to COVID-19 and depression. Mental distress due to COVID-19 partially mediated and suppressed the associations between some of the studied factors and depression (effect size of 6.0%-79.5%)., Conclusions: Both mental distress due to COVID-19 and depression were prevalent among university students in China; the former may have increased the prevalence of the latter. The studied cognitive, behavioral, and psychosocial factors related to COVID-19 may directly or indirectly (via mental distress due to COVID-19) affect depression. Interventions to modify such factors may reduce mental distress and depressive symptoms during the COVID-19 epidemic., (©Yanqiu Yu, Rui She, Sitong Luo, Meiqi Xin, Lijuan Li, Suhua Wang, Le Ma, Fangbiao Tao, Jianxin Zhang, Junfeng Zhao, Liping Li, Dongsheng Hu, Guohua Zhang, Jing Gu, Danhua Lin, Hongmei Wang, Yong Cai, Zhaofen Wang, Hua You, Guoqing Hu, Joseph Tak-Fai Lau. Originally published in JMIR Mental Health (http://mental.jmir.org), 22.02.2021.)

Background: As a large capillary network, the human placenta plays an important role throughout pregnancy. Placental vascular development is complex and delicate and involves many types of placental cells, such as trophoblasts, and mesenchymal stem cells. There has been no systematic, comparative study on the roles of these two groups of placental cells and the whole placental tissue in the placental angiogenesis. In this study, primary cytotrophoblasts (CTBs) from early pregnancy and primary human placenta-derived mesenchymal stem cells (hPDMSCs) from different stages of pregnancy were selected as the cell research objects, and full-term placental tissue was selected as the tissue research object to detect the effects of their conditioned medium (CM) on human umbilical vein endothelial cell (HUVEC) angiogenesis., Methods: We successfully isolated primary hPDMSCs and CTBs, collected CM from these placental cells and sub-cultured placental tissue, and then evaluated the effects of the CM on a series of angiogenic processes in HUVECs in vitro. Furthermore, we measured the levels of angiogenic factors in the CM of placental cells or tissue by an angiogenesis antibody array., Results: The results showed that not only placental cells but also sub-cultured placental tissue, to some extent, promoted HUVEC angiogenesis in vitro by promoting proliferation, adhesion, migration, invasion, and tube formation. We also found that primary placental cells in early pregnancy, whether CTBs or hPDMSCs, played more significant roles than those in full-term pregnancy. Placental cell-derived CM collected at 24 h or 48 h had the best effect, and sub-cultured placental tissue-derived CM collected at 7 days had the best effect among all the different time points. The semiquantitative angiogenesis antibody array showed that 18 of the 43 angiogenic factors had obvious spots in placental cell-derived CM or sub-cultured placental tissue-derived CM, and the levels of 5 factors (including CXCL-5, GRO, IL-6, IL-8, and MCP-1) were the highest in sub-cultured placental tissue-derived CM., Conclusions: CM obtained from placental cells (primary CTBs or hPDMSCs) or sub-cultured placental tissue contained proangiogenic factors and promoted HUVEC angiogenesis in vitro. Therefore, our research is helpful to better understand placental angiogenesis regulation and provides theoretical support for the clinical application of placental components, especially sub-cultured placental tissue-derived CM, in vascular tissue engineering and clinical treatments.

Background: Adolescent males were consistently reported to have a higher prevalence of Internet gaming disorder (IGD) than females. The mechanisms underlying the sex difference were potentially important for designing sex-specific interventions but were under-researched. Maladaptive cognitions were potential mediators between sex and adolescent IGD, as they were positively associated with both sex and adolescent IGD., Methods: A total of 3,075 students participated in a cross-sectional survey that was conducted in Guangzhou and Chengdu, China. IGD was measured by using the DSM-5 checklist and maladaptive cognitions were measured by the validated Chinese version of Revised Internet Gaming Cognition Scale (C-RIGCS). Structural equation modeling was used to test the mediation hypotheses., Results: Adolescent males showed a significantly higher prevalence of IGD than females (19.2% versus 7.8%, p < .05). Significant positive associations were found between sex and both maladaptive cognitions and IGD. The sex difference in IGD prevalence was partially mediated by the overall scale of C-RIGCS and its three subscales (i.e., perceived overvaluation of rewards of Internet gaming, perceived urges for playing Internet games, and perceived unwillingness to stop playing without completion of gaming tasks), with large mediation effect sizes ranging from 35.0% to 60.0% (Sobel test, p < ,01)., Conclusions: The higher levels of maladaptive cognitions among adolescent males explained a relatively large part of the substantially higher prevalence of IGD among adolescent males than females. Interventions targeting adolescent males may consider modifying such cognitions to reduce their IGD., (Copyright © 2020. Published by Elsevier Ltd.)

The extracellular matrix component collagen is widely expressed in human tissues and participates in various cellular biological processes. The collagen amount generally remains stable due to intricate regulatory networks, but abnormalities can lead to several diseases. During the development of renal fibrosis and vascular calcification, the expression of collagen is significantly increased, which promotes phenotypic changes in intrinsic renal cells and vascular smooth muscle cells, thereby exacerbating disease progression. Reversing the overexpression of collagen substantially prevents or slows renal fibrosis and vascular calcification in a wide range of animal models, suggesting a novel target for treating patients with these diseases. Stem cell therapy seems to be an effective strategy to alleviate these two conditions. However, recent findings indicate that the natural pore structure of collagen fibers is sufficient to induce the inappropriate differentiation of stem cells and thereby exacerbate renal fibrosis and vascular calcification. A comprehensive understanding of the role of collagen in these diseases and its effect on stem cell biology will assist in improving the unmet requirements for treating patients with kidney disease.

Background and Purpose- Circulating metals synchronously reflect multiple metal exposures from both natural and anthropogenic sources, which may be linked with the risk of stroke. However, there is a lack of prospective studies investigating the associations of multiple metal exposures with incident stroke. Methods- We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008. A total of 1304 incident stroke cases (1035 ischemic strokes and 269 hemorrhagic strokes) were prospectively identified by December 31, 2016, and matched to incident identity sampled controls according to age (within 1 year), sex, and blood sampling date (within 1 month). We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model. Results- The average follow-up was 6.1 years. After adjusting for established risk confounders, copper, molybdenum, and titanium were significantly associated with higher risk of ischemic stroke (odds ratios according to per interquartile range increase, 1.29 [95% CI, 1.13-1.46], 1.19 [95% CI, 1.05-1.35], and 1.30 [95% CI, 1.07-1.59]), whereas rubidium and selenium were associated with lower risk of hemorrhagic stroke (odds ratios according to per interquartile range increase, 0.66 [95% CI, 0.50-0.87] and 0.68 [95% CI, 0.51-0.91]). The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke (adjusted odds ratios according to per interquartile range increase, 1.37 [95% CI, 1.20-1.56] and 1.53 [95% CI, 1.16-2.01]). Conclusions- Plasma copper, molybdenum, and titanium were associated with higher risk of ischemic stroke, whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke. These findings may have important public health implications given the ever-increasing burden of stroke worldwide.

Prospective studies on the relations between platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and incident cardiovascular disease (CVD) were still limited. This study aimed to investigate the above-mentioned prospective relations in the middle-aged and older Chinese populations based on the Dongfeng-Tongji cohort. We included 31,751 participants who were free of coronary heart disease (CHD), stroke, cancer, or severely abnormal electrocardiogram at baseline. During a median follow-up of 5.9 years, we identified 5,683 incident CVD cases, including 4,423 CHD and 1,260 stroke cases. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confident intervals (CIs) for the relation analyses. Compared with participants with 146 ≤ PLT ≤ 233 10E9/L, the adjusted HR (95% CI) of those with PLT < 146 10E9/L was 0.80 (0.68 to 0.95) for incident stroke. Compared with participants with 7.3 ≤ MPV ≤ 10.3 fl, the adjusted HRs (95% CIs) of those with MPV < 7.3 fl were 0.81 (0.75 to 0.88), 0.80 (0.73 to 0.88) and 0.84 (0.71 to 1.00) for incident CVD, CHD and stroke, respectively. Compared with participants with 13.2 ≤ PDW ≤ 18.1 %, the adjusted HRs (95% CIs) of those with PDW < 13.2 % were 0.80 (0.73 to 0.87) and 0.78 (0.70 to 0.86) for incident CVD and CHD, respectively. In conclusion, lower levels of PLT and MPV were significantly related to lower risk of stroke, while lower levels of MPV and PDW were significantly related to lower risks of CVD and CHD., (Copyright © 2018. Published by Elsevier Inc.)

Stem cells are one kind of cells that have the potential of proliferation and differentiation. The human beings are originated from a totipotential stem cell-fertilized egg. After birth, the proliferation and differentiation of stem cells contribute to the development and maturation of individual tissues and organs. After maturation, aging is a phases of the life process, the stem cells within the individual's tissues ensure the metabolism of different cells and tissues, such as the hematopoietic stem cells in the bone marrow, which ensure there are still enough red blood cells (RBCs) being responsible for the mission of transporting oxygen after a single RBC has completed its 120-day physiological life cycle. After pathological damage and necrosis occurring on the intestinal epithelial cells or tubular epithelial cells, there will be regenerative epithelial cells continuing to maintain the integrity of the structure and function of the intestine and renal tubules. The role of stem cells in the regeneration and repair of tissues and organs is not only because of the ability of proliferation and differentiation of stem cells but also of the secretion function of stem cells, which secrete various growth factors and cytokines to regulate the tissue microenvironment. For example, mesenchymal stem cells derived from bone marrow are important regulators in bone marrow hematopoietic stem cell niche. Mesenchymal stem cells maintain the "stemness" of hematopoietic stem cells by secreting various cytokines.Aging is a phases of the life process, and all creatures obey this rule of nature. Different organs of the body have different time of entering into aging. Aging is reflected in structural changes and reduced function. Among them, the reduction of regeneration and repair capacity is the main feature of aging. As we age, the aging of stem cells in human tissues is a major cause of the decline in tissue regeneration capacity. Therefore, the elderly's ability of regenerate and repair can be improved by application of advance stem cell technology. It can delay the aging process and treat aged diseases (showed in Fig. 16.1).

Objective: Pathological myopia (PM) is a hereditary ocular disease leading to severe loss of visual acuity and blindness. Lumican gene (LUM) is one of those candidate genes of PM. The purpose of this study was to establish a mutant Lumican transgenic mouse model, and to prepare for the further study of the pathogenesis of PM., Methods: Experimental study. Mutation of LUM gene was created by site-directed mutagenesis. Recombinant DNA techniques were used for the construction of the pRP. EX3d-EF1A>LUM/flag>IRES/hrGFP transgene. The gene fragments were microinjected into the zygote male pronuclei of BDF1 mice, and then the zygote cells alive were transplanted into the oviduct of acceptor pregnant female ICR mice. The F0 generation transgenic mice obtained were named C57-TgN (LUM)CCMU. Genome DNA from mice tail was detected by PCR and Western blotting., Results: Six of 31 F0 generation mice were positive transgenic mice. The western blotting study showed that the flag-tag was expressed in the mouse tail tissue. Sixty-eight of 128 mice (F1 to F3 generation) were positive transgenic mice, the positive rate is 53.13%., Conclusions: The mutant Lumican (cDNA 596T>C) transgenic mouse model has been established. This model will provide fundamental conditions for studies of the pathogenesis of PM. Also it will be the basis of further studies about the effect of Lumican mutation on the development of PM and structure and function of the extra cellular matrix.

Two integrins, alpha3beta1 and alpha6beta4, are high-affinity receptors for laminin 332, the major laminin isoform of the dermal-epidermal junction, although they are thought to have different functions. Biological and genetic studies have firmly established that the alpha6beta4 integrin is indispensable for the stable anchorage of the epidermis to the underlying dermis. In contrast, the alpha3beta1 integrin is thought to be important for cell migration, although the issue is controversial, and both positive and negative effects have been reported. To address the function of alpha3beta1 integrin, we used small interfering RNA to down-regulate the alpha3 subunit in human keratinocytes. The resulting phenotype indicates that lack of alpha3beta1 integrin compromises intercellular adhesion and collective migration, while it enhances single cell migration with a concomitant increase of both focal adhesion kinase and extracellular signal-regulated kinase. In addition, down-regulation of integrin alpha3 subunit results in an increased expression of fibronectin and precursor laminin 332, two extracellular matrix proteins known to be up-regulated during wound healing. Thus, down-regulation of alpha3beta1 integrin recapitulates crucial events governing keratinocyte migration associated with wound healing and tissue repair.

Samples of healthy and full-term human umbilical cord blood samples were obtained asceptically. Mesenchymal stem cells (MSCs) were isolated by lymphocyte separation medium, and were characterized morphologically by fluorescence-activated cell sorting analysis. Differentiation of chondroblast and osteoblast was induced by 10 ng/ml TGF-beta, 100 ng/ml insulin and 10(-7) mol/L decaesadril, 6.25 microg/ml siderophilin, 10 mmol/L beta-sodium glycerophosphate, 50 microg/ml antiscorbic acid, respectirely; the aim was to investigate the potentiality of differentiation. Umbilical cord blood-derived MSCs were stained positive for MSCs marker CD13, CD90, CD166, CD73, CD44 and HLA-AB, but were negative for hematopoietic stem cell marker CD45, CD34 and HLA-DR. After 21 days induction, Toluidine Blue staining and von-Kossa staining were positive. Immunocytochemistry showed that Collagen II expressed in the induced cells. The results demonstrated that mesenchymal stem cells can be isolated from human umbilical cord blood and differentiated into chondroblasts and osteoblasts in vitro.