Effectiveness of influenza vaccination in the elderly: a population-based case-crossover study.

BACKGROUND: There is limited information regarding the effectiveness of influenza vaccines for older adults. Particularly, controlling for healthy senior bias is challenging in observational studies. We aimed to assess the efficacy of influenza vaccination in the elderly while addressing potential healthy senior bias and whether it was related to virus-vaccine strains matching. METHOD: To control between-individual confounder, we used a case-crossover study design using Taiwan's National Health Insurance Research Dataset to analyse the association between influenza vaccination in older adults and the risk of hospitalisation for community-acquired pneumonia (CAP). Individuals were a 'case' in vaccinated years and a 'control' in unvaccinated years. The study periods were 2006/2007 and 2007/2008 seasons because virus-vaccine strains were matching in 2006/2007 season and unmatching in 2007/2008 season. Older adults were categorised into two groups: admitted for CAP during the pre-vaccination period (Admitted, n=311) and not hospital admitted for CAP (Non-admitted, n=572 432). The outcome was hospitalisation for CAP during the influenza period. Conditional logistic regression assessed influenza vaccine efficacy in reducing CAP. RESULTS: Influenza vaccination had no protective effects in Admitted group. However, because of the tiny numbers in Admitted group, we could draw very limited conclusions. Receiving an influenza vaccine significantly prevented CAP in Non-admitted group only during the vaccine-circulating strain-matched year (OR, 0.72; 95% CI, 0.64 to 0.83). In addition, there was no protective effect against CAP hospitalisation among individuals with a Charlson Comorbidity Index score over 2. CONCLUSION: Influenza vaccine efficacy was associated with vaccine-circulating strain-matched. When vaccine-circulating strains were all matching, receiving a shot reduced the probability of CAP hospitalisation by 28% in Non-admitted group. However, high comorbidity may reduce the vaccine efficacy. Therefore, it is necessary to educate older adults to receive annual influenza vaccination and in combination with non-pharmaceutical interventions to reduce the risk of CAP.

Adipose-Derived Neural Stem Cells Combined with Acellular Dermal Matrix as a Neural Conduit Enhances Peripheral Nerve Repair.

Reconstruction to close a peripheral nerve gap continues to be a challenge for clinical medicine, and much effort is being made to develop nerve conduits facilitate nerve gap closure. Acellular dermal matrix (ADM) is mainly used to aid wound healing, but its malleability and plasticity potentially enable it to be used in the treatment of nerve gaps. Adipose-derived stem cells (ADSCs) can be differentiated into three germ layer cells, including neurospheres. We tested the ability of ADSC-derived neural stem cells (NSCs) in combination with ADM or acellular sciatic nerve (ASN) to repair a transected sciatic nerve. We found that NSCs form neurospheres that express Nestin and Sox2, and could be co-cultured with ADM in vitro, where they express the survival marker Ki67. Following sciatic nerve transection in rats, treatment with ADM+NSC or ASN+NSC led to increases in relative gastrocnemius weight, cross-sectional muscle fiber area, and sciatic functional index as compared with untreated rats or rats treated with ADM or ASN alone. These findings suggest that ADM combined with NSCs can improve peripheral nerve gap repair after nerve transection and may also be useful for treating other types of neurological gaps.

Platelet-derived growth factor-AA is a substantial factor in the ability of adipose-derived stem cells and endothelial progenitor cells to enhance wound healing.

Nonhealing wounds with various forms of complications have been a major challenge for patients with different diseases, and few data are available regarding the clinical significance of platelet-derived growth factor-AA (PDGF-AA) in the enhanced wound healing with stem cells, and the precise molecular mechanism remains unclear. The study aims to investigate the role of PDGF-AA in adipose-derived stem cells (ASCs) and endothelial progenitor cells (EPCs) enhancing wound healing. In this study, ASCs and EPCs were applied to treat wounds in an animal wound model with a wound-healing assay. We knocked down PDGF-AA expression in ASCs using the PDGF-AA short hairpin RNA technique and investigated the related molecular mechanism. The wound model and wound-healing assay of the study showed that transplantation of ASCs could enhance wound healing. The results showed that the PDGF-AA knockdown ASC group had much less improvement of wound healing than other groups treated with wild-type ASCs in wound tissues. The regulation of PDGF-AA in ASCs may contribute to improve wound healing through the PI3K/Akt/eNOS signaling pathway. The data indicated that PDGF-AA might play a vital role in ASCs and EPCs enhancing wound healing, possibly by its effects on angiogenesis. It would be a potential approach using PDGF-AA for clinical treatment of chronic wounds.-Wu, L.-W., Chen, W.-L., Huang, S.-M., Chan, J. Y.-H. Platelet-derived growth factor AA is a substantial factor in the ability of adipose-derived stem cells and endothelial progenitor cells to enhance wound healing.

The Potential of Acellular Dermal Matrix Combined With Neural Stem Cells Induced From Human Adipose-Derived Stem Cells in Nerve Tissue Engineering.

INTRODUCTION: Reconstruction of segmental peripheral nerve gap is still challenging when the autografts are unavailable owing to limited availability of donor site and functional recovery. The creation of artificial conduits composed of biological or synthetic materials is still developing. Acellular dermal matrix (ADM) has been widely studied and its extension and plasticity properties may become suitable nerve conduits under different forms of nerve gaps. Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell types of different germ layers including neural stem cells (NSCs). The purpose of this experiment is to use ADM as a scaffold combined with NSCs induced by ADSCs to establish neural tissue engineering. METHODS: The ADSCs were isolated from syringe-liposuction adipose tissue harvested from abdominal fat and then cultured in keratinocyte serum free media to trigger into neural stem cells. Stem cells were confirmed by the expression of surface markers nestin and SOX2 in NSCs with Western blot and immunofluorescent staining. Matrix enzyme treatment was used to obtain ADM to remove immunogenic cells while maintaining the integrity of the basement membrane complex and the extracellular matrix structure of the dermis. The NSCs were cocultured with ADM for 3 days, and survival markers Ki67 and neural stem cell markers nestin were detected. RESULTS: These NSCs can form neurospheres and express nestin and SOX2. The NSC can further coculture with ADM, and it will continue to express survivor markers and neural stem cell markers on ADM. CONCLUSIONS: These findings provide evidence that the combination of ADM and NSC has the same potential as neural tissue engineering as other acellular sciatic nerve.

Exploring the association between thyroid- stimulating hormone and metabolic syndrome: A large population-based study.

A growing amount of evidence suggests that thyroid-stimulating hormone (TSH) is associated with cardiometabolic risk. However, there have been few longitudinal studies. The aim of this study was to explore the causal relationship between TSH and metabolic syndrome (MetS) in a large population-based longitudinal study. From 2010 to 2016 at the Health Management Center at Tri-Service General Hospital, 25,121 eligible patients were enrolled in our cross-sectional analyses. Cox proportional hazard models were used to investigate the longitudinal association among hypertension (HTN), prediabetes (pre-DM), MetS, diabetes (DM) and TSH levels (N = 12,463). The average follow-up time was 7.2 years. In the cross-sectional analysis, the OR for MetS was 1.06 (95% CI = 1.03-1.09; P< 0.05), while the ORs for DM, pre-DM or HTN were not statistically significant (all P> 0.05). After dividing TSH levels into four quartiles, the ORs for the presence of MetS determined by comparing the highest TSH quartile with the lowest TSH quartile were 1.37 (95% CI = 1.18-1.60), 1.42 (95% CI = 1.20-1.67), and 1.44 (95% CI = 1.22-1.69) (all, P<0.05) in model 1, model 2 and model 3 respectively. The HR for the incidence of MetS was 1.33 (95% CI = 1.17-1.51; P < 0.05). Our study revealed that TSH levels had a strong association with incident MetS.

Overexpression of CD164 in oral cavity squamous cell carcinoma predicts a favourable prognosis.

The aim of the present study was to investigate the association between cluster of differentiation (CD) 164 expression with clinicopathological parameters and prognosis among patients with oral cavity squamous cell carcinoma (OSCC). The present study retrospectively reviewed 70 patients with OSCC who underwent curative primary surgery. A number of patients subsequently received postoperative chemoradiotherapy although the specimens were not exposed to radiation or chemotherapy prior to anti-CD164 antibody immunohistochemical staining. CD164 overexpression was arbitrarily defined as exhibiting an H-score of ≥120. Univariate and multivariate analyses were performed for sex, age, American Joint Committee on Cancer stage, tumour location, histological grade, surgical margin and H-score. The 5-year overall survival rate was 54.4% and the median follow-up time was 46 months for surviving patients. Univariate analyses revealed that a low overall survival rate was associated with advanced-stage disease (P<0.001), buccogingival tumour location (P=0.038) and a CD164 H-score of <120 (P=0.016). Multivariate Cox's regression analyses revealed that poor overall survival rate was associated with advanced-stage disease (P=0.001) and a CD164 H-score of <120 (P=0.04). CD164 overexpression in OSCC was associated with favourable survival rate. Thus, CD164 expression may be a clinically useful predictor of prognosis in patients with OSCC.

CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling.

CD164 is a cell adhesion molecule that increases hematopoietic stem cell proliferation, adhesion, and migration via C-X-C chemokine receptor type 4 (CXCR4) signaling. Emerging evidence indicates that elevated CD164 expression is associated with aggressive metastasis, advanced stages, and shorter overall survival in lung cancer. However, no data are available regarding the clinical significance of CD164 expression in lung cancer. This study explores whether CD164 promotes tumor-initiation and drug resistance through the stem cell property. Using tissue microarrays, we determine that CD164 expression is correlated with clinicopathological characteristics in human lung cancer. The CD164 overexpression in normal lung epithelial cells (BEAS2B cells) leads to malignant transformation in vitro, tumorigenicity in xenografted mice, stem cell-like property, and drug resistance through ATP-binding cassette transporters. The CD164 overexpression increases CXCR4 expression and activates Akt/mTOR signaling. Rapamycin, an mTOR inhibitor, hinders cell proliferation along with sphere formation in vitro and impedes tumor growth in vivo. In conclusion, we have provided evidence that CD164 promotes the growth of lung tumor-initiating cells with stem cell properties and induces tumor growth and drug resistance through Akt/mTOR signaling. Therefore, identification of CD164 as a cancer stem cell therapeutic marker may develop an effective therapy in patients with chemoresistant lung cancer.

Associations among integrated psychoneuroimmunological factors and metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) has been reported to cause considerable psychoneuroimmunology (PNI) disturbances such as, psychological distress, autonomic nervous imbalance, and impaired immune function. Associations among these psychoneuroimmunology (PNI) factors and their integrated effects with MetS and risk components of MetS necessitate further exploration. OBJECTIVE: This study investigated associations among psychoneuroimmunological factors, their integrated effects with MetS and risk components of MetS. METHODS: This was a cross-sectional study. Participants were recruited from two health management centers at a medical center in Northern Taiwan. Demographics and data on psychological distress (e.g., perceived stress and depression) were collected using self-reported questionnaires. Heart rate variability (HRV) and C-reactive protein values (CRP) were measured to evaluate participants' autonomic nervous function and immune reaction. The risk components of MetS (e.g., elevated blood pressure, impaired fasting glucose, dyslipidemia, and abdominal obesity) were identified according to the Taiwan-specific definition of MetS and were determined based on participants' health examination profiles. RESULTS: A total of 345 participants with complete data were included for data analysis. Compared with healthy controls, participants with MetS exhibited higher depression scores (11.2±8.5 vs. 8.7±7.0), higher CRP values (2.1±2.5 vs. 0.7±1.0), and lower HRV (total power: 758.7±774.9 vs. 1064.4±1075.0). However, perceived stress in participants with MetS did not significantly differ from that of their healthy counterparts (p>0.05). Univariate analyses indicated that associations among psychoneuroimmunological factors and MetS risk components were statistically heterogeneous: a) perceived stress and depression were significantly associated only with high blood glucose (p<0.05); b) CRP was significantly associated with all MetS risk components (p<0.05); and c) HRV was significantly associated with high triglycerides and high fasting blood glucose (p<0.05). Multivariate analysis indicated that the integrated effects of depression, CRP, and HRV were significantly associated with MetS (p<0.01) after controlling for age and education level. CONCLUSIONS: Higher depression scores, higher CRP values, and lower HRV are independently and additively associated with MetS and risk components of MetS. Accordingly, a multidisciplinary approach to alleviating psychological distress, immune dysfunction, and autonomic nervous imbalance is recommended for promoting well-being in people with subclinical metabolic abnormalities or MetS to minimize downstream health consequences.

All-cause mortality risk in elderly individuals with disabilities: a retrospective observational study.

OBJECTIVES: Disability is considered an important issue that affects the elderly population. This study aimed to explore the relationship between disability and all-cause mortality in US elderly individuals. DESIGN: Retrospective and longitudinal designs. SETTING: Data from the National Health and Nutrition Examination Survey (NHANES 1999-2002) conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. PARTICIPANTS: A total of 1834 participants in the age range 60-84 years from NHANES 1999-2002. MAIN OUTCOME MEASURES: We acquired five major domains of disability (activities of daily living (ADL), general physical activities (GPA), instrumental ADL (IADL), lower extremity mobility (LEM) and leisure and social activities (LSA)) through self-reporting. We applied an extended-model approach with Cox (proportional hazards) regression analysis to investigate the relationship between different features of disability and all-cause mortality risk in the study population. RESULTS: During a mean follow-up of 5.7 years, 77 deaths occurred. An increased risk of all-cause mortality was identified in elderly individuals with disability after adjustment for potential confounders (HR 2.23; 95% CI 1.29 to 3.85; p=0.004). Participants with more than one domain of disability were associated with a higher risk of mortality (ptrend=0.047). Adjusted HRs and 95% CIs for each domain of disability were 2.53 (1.49 to 4.31), 1.99 (0.93 to 4.29), 1.74 (0.72 to 4.16), 1.57 (0.76 to 3.27) and 1.52 (0.93 to 2.48) for LEM, LSA, ADL, IADL and GPA, respectively. CONCLUSIONS: The results of this study support an increased association between disability and all-cause mortality in the elderly in the USA. Disability in LEM may be a good predictor of high risk of all-cause mortality in elderly subjects.

Selective Criteria and Markers in Adipose-Derived Stromal Cells Collection Quality and Expansion Potency.

BACKGROUND: Adipose tissue-derived stromal cells (ADSCs) have been extensively used in clinical trials for various therapeutic applications. However, there is a paucity of selective criteria regarding collection and expansion procedures. The purpose of this study was to investigate the effect of liposuction and donor age on ADSCs and to assess the criteria and markers for ADSC long-term expansion potential. METHODS: Adipose tissues were collected using syringe liposuction, water-jet, or ultrasonic techniques. Tissue/cell viability was evaluated using the XTT assay. CD34 and SSEA-4 expression were examined using flow cytometry. SOX2 gene expression was estimated using quantitative polymerase chain reaction, and Nile-red staining was performed to evaluate the adipogenesis potency during ADSC expansion. RESULTS: The lipoaspirates obtained from syringe and ultrasonic liposuction methods were superior to those of the water-jet method in stromal vascular fraction yield and durability during temporary storage. SSEA-4, SOX2 expression, and adipogenesis potency of early-passage ADSCs were significantly correlated with the P15 cumulative population doublings data. CD34 expression was strongly correlated with P0 ADSC yield and doubling time. Tissue viability, P0 ADSC CD34⁺ percentage, and P15 cumulative population doublings were decreased along with donor age. CONCLUSIONS: This study established criteria and markers to determine whether lipoaspirate tissue and cultured ADSCs are suitable for further large-scale expansion and allogenic universal cell banking.

The regulatory mechanisms of myogenin expression in doxorubicin-treated rat cardiomyocytes.

Doxorubicin, an anthracycline antibiotic, has been used as an anti-neoplastic drug for almost 60 years. However, the mechanism(s) by which anthracyclines cause irreversible myocardial injury remains unclear. In order to delineate possible molecular signals involved in the myocardial toxicity, we assessed candidate genes using mRNA expression profiling in the doxorubicin-treated rat cardiomyocyte H9c2 cell line. In the study, it was confirmed that myogenin, an important transcriptional factor for muscle terminal differentiation, was significantly reduced by doxorubicin in a dose-dependent manner using both RT-PCR and western blot analyses. Also, it was identified that the doxorubicin-reduced myogenin gene level could not be rescued by most cardio-protectants. Furthermore, it was demonstrated how the signaling of the decreased myogenin expression by doxorubicin was altered at the transcriptional, post-transcriptional and translational levels. Based on these findings, a working model was proposed for relieving doxorubicin-associated myocardial toxicity by down-regulating miR-328 expression and increasing voltage-gated calcium channel ß1 expression, which is a repressor of myogenin gene regulation. In summary, this study provides several lines of evidence indicating that myogenin is the target for doxorubicin-induced cardio-toxicity and a novel therapeutic strategy for doxorubicin clinical applications based on the regulatory mechanisms of myogenin expression.

Relationship between hyperuricemia and lipid profiles in US adults.

BACKGROUND: Although the link between hyperuricemia and metabolic syndrome had been recognized, the association of the dyslipidemia among individuals with hyperuricemia remains not comprehensively assessed. METHODS: Using NHANES III study, we examined the relation between serum lipid profiles and different serum uric acid levels, including serum total cholesterol, LDL cholesterol, triglycerides, HDL cholesterol, apolipoprotein-B, lipoprotein (a), apolipoprotein AI, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein-B to AI. RESULTS: After adjusting for potential confounders, average differences (95% confidence interval) comparing the top to the bottom (reference) serum uric acid were 0.29 (0.19, 0.39) mmol/L for total cholesterol, 0.33 (0.26, 0.41) mmol/L for triglycerides, 0.14 (0.01, 0.27) mmol/L for LDL cholesterol, -0.08 (-0.11, -0.05) mmol/L for HDL, and 0.09 (0.05, 0.12) g/L for serum apolipoprotein-B. Notably, ratios of triglycerides to HDL cholesterol and apolipoprotein-B to AI were also linearly associated with uric acid levels (P for trend < 0.001). CONCLUSIONS: This study suggested that serum LDL cholesterol, triglycerides, total cholesterol, apolipoprotein-B levels, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein-B to AI are strongly associated with serum uric acid levels, whereas serum HDL cholesterol levels are significantly inversely associated. In the clinical practice, the more comprehensive strategic management to deal with dyslipidemia and hyperuricemia deserves further investigation.

The effect of gender on health-related quality of life and related factors in post-lobectomy lung-cancer patients.

PURPOSE: While studies have documented gender differences by histologic type among lung cancer patients, the effect of these differences on the health-related quality of life (HRQoL) of post-lobectomy lungcancer patients and related factors remain uncertain. This study examines gender-specific HRQoL and related factors in post-lobectomy lung-cancer patients. METHODS: A cross-sectional study design was applied. A convenience sample of 231 post-lobectomy lungcancer patients was recruited from the thoracic surgery outpatient departments of two teaching hospitals in Taipei, Taiwan from March to December 2012. Patients performed a spirometry test and completed instruments that included a Beck Depression Inventory-II, an Interpersonal Support Evaluation List, and the symptom and function scales of the Quality of Life Questionnaire. Data analysis used descriptive statistics, including mean and standard deviations, frequency, and percentage values. Independent-sample Student's t-tests and multivariate analyses were used for comparative purposes. RESULTS: This study confirmed a significant gender effect on HRQoL and HRQoL-related factors such as marital status, religious affiliation, smoking status, histologic type, symptoms, pulmonary function, depression, and family support. Moreover, multivariate analysis found gender to be a significant determinant of the HRQoL aspects of physical functioning, emotional functioning, and cognitive functioning. Finally, results indicated that factors other than gender were also significant determinants of HRQoL. CONCLUSION: Gender impacts the HRQoL and related factors of postoperative lung-cancer patients. Therefore, gender should be considered in assessing and addressing the individual care needs of these patients in order to attain optimal treatment outcomes.

Relationship between lung function and metabolic syndrome.

Although the link between impaired lung function and cardiovascular events and type 2 diabetes mellitus has been recognized, the association between impaired lung function and metabolic syndrome has not been comprehensively assessed in the United States (U.S.) population. The aim of our study was to explore the association between impaired lung function and metabolic syndrome in a nationally representative sample of men and women. This cross-sectional population-based study included 8602 participants aged 20-65 years in the Third National Health and Nutrition Examination Survey (NHANES III). We examined the relationship between the different features of metabolic syndrome and lung function, including forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1). After adjusting for potential confounders such as age, body mass index, inflammatory factors, medical condition, and smoking status, participants with more components of metabolic syndrome had lower predicted values of FVC and FEV1 (p for trend <0.001 for both). Impaired pulmonary function was also associated with individual components of metabolic syndrome, such as abdominal obesity, high blood pressure, high triglycerides, and low high density lipoprotein (HDL) cholesterol (p<0.05 for all parameters). These results from a nationally representative sample of US adults suggest that a greater number of features of metabolic syndrome is strongly associated with poorer FVC and FEV1. In clinical practice, more comprehensive management strategies to address subjects with metabolic syndrome and impaired lung function need to be developed and investigated.

Characterization of a new mouse p53 variant: loss-of-function and gain-of-function.

BACKGROUND: p53 is a major tumor suppressor that is inactivated in over 50% of human cancer types through either mutation or inactivating interactions with viral or cellular proteins. The uncertainties around the link between p53 status, therapeutic response, and outcome in cancer suggest that additional factors may be involved. p53 isoforms that are generated via the alternative splicing pathway may be promising candidates for further investigation. RESULT: In this study, we report one new p53 protein with two internally deleted regions, resulting in one deleted amino acid fragment (from amino acid residues 42 to 89) and one reading frame-shift region (from amino acid residues 90-120) compared to wild-type p53. The functional status of the new p53 protein, which has a defect in its proline-rich and N-terminal DNA-binding domains, was characterized as possessing an intact conformation, exhibiting no transactivation activity, exerting a dominant-negative effect and an interacting with a coactivator with an arginine methyltransferase activity. CONCLUSION: Taken together, our findings provide valuable information about the structure and function of p53 for the regulation of transactivation activity and cellular protein-protein interactions. Furthermore, natural p53 isoforms will help us understand the functional roles of the p53 family and potential therapeutics for p53-dependent cancers.

Effects of an early postoperative walking exercise programme on health status in lung cancer patients recovering from lung lobectomy.

AIMS AND OBJECTIVES: To examine the effects of an early postoperative walking exercise programme on postlobectomy lung cancer patients. BACKGROUND: Few interventional studies on the postoperative health status of lung cancer patients have considered the efficacy of programmes designed to improve critical health variables. DESIGN: A two-group quasi-experimental, longitudinal approach repeated four times examined participant data collected 12-18 hours prior to surgery and again at one, three and six months after surgery. METHODS: We assigned the first 33 enrolled participants to the intervention group and the second 33 to the control group. The intervention was a daily supervised walking exercise programme consisting of 12 weeks of brisk walking exercise that began on the day following transfer to the regular ward along with weekly telephone calls until 12 weeks after discharge. Health status was measured using a structured questionnaire (World Health Organization Quality of Life, brief version) and clinical tests (pulmonary function test and 6-minute walk test). We analysed data using general estimating equations, with p < 0·05 considered significant. RESULTS: Intervention group pulmonary and physical functions were increasingly better over time than those of the control group, with no significant difference in quality of life between the two groups. Compared to the control group, the intervention group earned significantly better values for FVC% at postoperative month 3 and for FEV1 % at postoperative months 3 and 6. Intervention group 6MWT scores were significantly better than those of the control group at postoperative months 1, 3 and 6. CONCLUSION: This study demonstrated the benefits of an early postoperative walking exercise intervention for pulmonary and physical function in postlobectomy lung cancer patients. RELEVANCE TO CLINICAL PRACTICE: The results may guide the design of appropriate interventions in the future. Clinical trials in other populations are needed to confirm the results of this study.

CD164 regulates the tumorigenesis of ovarian surface epithelial cells through the SDF-1α/CXCR4 axis.

BACKGROUND: CD164 (endolyn), a sialomucin, has been reported to play a role in the proliferation, adhesion, and differentiation of hematopoietic stem cells. The potential association of CD164 with tumorigenicity remains unclear. METHODS: The clinicopathological correlation of ovarian cancer with CD164 was assessed in a 97-patient tumor tissue microarray. Overexpression or silence CD164 was to analyze the effect of CD164 on the proliferation, colony formation and apoptosis via a mouse xenograft and western blotting analysis. The subcellular localization of CD164 was collected in the immunohistochemical and confocal analysis. RESULTS: Our data demonstrated that higher expression levels of CD164 were identified in malignant ovarian cancer cell lines, such as SKOV3 and HeyA8. The clinicopathological correlation analysis showed that the upregulation of CD164 protein was significantly associated with tumor grade and metastasis. The overexpression of CD164 in human ovarian epithelial surface cells promoted cellular proliferation and colony formation and suppressed apoptosis. These tumorigenicity effects of CD164 were reconfirmed in a mouse xenograft model. We also found that the overexpression of CD164 proteins increased the amounts of CXCR4 and SDF-1α and activated the SDF-1α/CXCR4 axis, inducing colony and sphere formation. Finally, we identified the subcellular localization of CD164 in the nucleus and cytosol and found that nuclear CD164 might be involved in the regulation of the activity of the CXCR4 promoter. CONCLUSIONS: Our findings suggest that the increased expression of CD164 is involved in ovarian cancer progression via the SDF-1α/CXCR4 axis, which promotes tumorigenicity. Thus, targeting CD164 may serve as a potential ovarian cancer biomarker, and targeting CD164 may serve as a therapeutic modality in the management of high-grade ovarian tumors.

Promotion of wound healing using adipose-derived stem cells in radiation ulcer of a rat model.

BACKGROUND: Wound healing is a complex biologic process that involves the integration of inflammation, mitosis, angiogenesis, synthesis, and remodeling of the extracellular matrix. However, some wounds fail to heal properly and become chronic. Although some simulated chronic wound models have been established, an efficient approach to treat chronic wounds in animal models has not been determined. The aim of this study was to develop a modified rat model simulating the chronic wounds caused by clinical radiation ulcers and examine the treatment of chronic wounds with adipose-derived stem cells. RESULTS: Sprague-Dawley rats were irradiated with an electron beam, and wounds were created. The rats received treatment with adipose-derived stem cells (ASCs), and a wound-healing assay was performed. The wound sizes after ASC treatment for 3 weeks were significantly smaller compared with the control condition (p < 0.01). Histological observations of the wound edge and immunoblot analysis of the re-epithelialization region both indicated that the treatment with ASCs was associated with the development of new blood vessels. Cell-tracking experiments showed that ASCs were colocalized with endothelial cell markers in ulcerated tissues. CONCLUSIONS: We established a modified rat model of radiation-induced wounds and demonstrated that ASCs accelerate wound-healing.

Adipose-derived stem cells seeded on acellular dermal matrix grafts enhance wound healing in a murine model of a full-thickness defect.

INTRODUCTION: The promotion of wound healing using dermal substitutes has become increasingly widespread, but the outcomes of substitute-assisted healing remain functionally deficient. Adipose-derived stem cells (ASCs) have been investigated widely in regenerative medicine and tissue engineering, and they have the potential to enhance wound healing. In this study, we focused on investigating the effects and mechanism of ASCs combined with an acellular dermal matrix (ADM) to treat full-thickness cutaneous wounds in a murine model. METHODS: The ADM was prepared from the dorsal skin of nude mice by decellularization by treatment with trypsin followed by Triton X-100. The human ASCs were isolated and cultured from abdominal lipoaspirate. We created a rounded, 8-mm, full-thickness cutaneous wound in nude mice and divided the mice into the following 4 groups: silicon sheet cover only, silicon sheet with spreading ASCs, ADM only, and ASCs seeded on ADM. The granulation thickness was evaluated by histology after 7 days. Further comparisons between the ADM only and ASC-seeded ADM groups were undertaken by assessing the reepithelialization ratio and blood vessel density at postoperative days 9 and 14. Statistical analyses were conducted using Student 2-tailed t test. Immunofluorescent histology and ASC labeling were also performed to identify possible mechanisms. RESULTS: The ADM was successfully prepared, and the cytometry analysis and differentiation assay provided the characterization of the human ASCs. A marked improvement in granulation thickness was detected in the ADM-ASC group in comparison with other 3 groups. A significantly increased rate of reepithelialization in the ADM-ASC group (80 ± 6%) compared to the ADM only group (60 ± 7%) was noted on postoperative day 9. The blood vessel density was evidently increased in the ADM-ASC group (7.79 ± 0.40 vessels per field) compared to the ADM only group (5.66 ± 0.23 vessels) on day 14. Cell tracking experiments demonstrated that labeled ASCs were colocalized with staining for VEGF or endothelial cell maker vWF after the transplantation of ADM-ASCs on postoperative day 14. CONCLUSIONS: Adipose-derived stem cells seeded on an ADM can enhance wound healing, promote angiogenesis, and contribute to newly formed vasculature, and VEGF-expressing ASCs can be detected after transplantation. This model could be used to improve the other clinical applications of ASCs and to decipher the detailed mechanism by which ASCs interact with wound tissue.

Physical and functional interactions between hnRNP K and PRMT family proteins.

The mechanism underlying the protein-protein interaction of hnRNP K and PRMT family proteins is unclear. We examined and confirmed the arginine methylation of hnRNP K protein by PRMT1, not CARM1, via their direct binding. We also studied hnRNP K protein complexes containing CARM1, as well as PRMT1, using co-immunoprecipitation analysis. PRMT family proteins might be involved in the regulation of hnRNP K functions in nuclear receptor coactivator, transactivation, and p21 gene and protein expressions. We believe these observations will help provide insights into the regulation of hnRNP K protein functions via the recruitment of its associated proteins, including its arginine methylation-modifying proteins.