bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction Therapy With Mesenchymal Stem Cells in Kidney Transplantation: A Meta-Analysis
Authors: Zhao Lingfei , Hu Chenxia , Han Fei , Chen Dajin , Cheng Jun , Wu Jianyong , Peng Wenhan , Chen Jianghua
Published: June 2020

Objective The aim of this meta-analysis was to evaluate the therapeutic effects of mesenchymal stem cells (MSCs) versus other regimens as induction therapy in kidney transplantation patients.Methods PubMed, Embase, EBSCO, Ovid and the Cochrane Library were searched to identify prospective clinical trials which compared MSCs with other regimens as induction therapy in renal allograft.Results Four studies with five cohorts were contained, including a total of 301 patients. The pooled results revealed that the MSCs therapy had a lower 1-year infection rate (RR=0.73, 95% CI: 0.58–0.93, P=0.01), espeicially for 1-year opportunistic infection rate (RR=0.59, 95% CI: 0.37–0.93, P=0.02). There were no significant differences between the two protocols regarding 1-year acute rejection (AR) rate (RR=0.69, 95% CI: 0.42–1.14, P=0.15), 1-year graft survival rate (RR=0.99, 95% CI: 0.95–1.03, P=0.74), delayed graft function (DGF) rate (RR=0.72, 95% CI: 0.34–1.50, P=0.38) and renal graft function at 1 month (MD=2.4, 95% CI: -7.41– 12.22, p=0.63), 3 months (MD=0.91, 95% CI: -4.17– 5.98, p=0.73), 6 months (MD=-1.41, 95% CI: -5.69– 2.87, p=0.52), 12 months (MD=1.25, 95% CI: -3.89– 6.4, p=0.63) post surgery. Subgroup analysis demonstrated 1-year AR rate, DGF rate and renal graft function at 12 month post surgery did not reach to a significant difference between low-dose calcineurin inhibitors (CNIs) group with standard-dose CNIs group, indicating successful CNIs withdrawal in combination with MSCs treatment. Meanwhile, when applied MSCs as an alternative standard induction therapy regimen, all of those outcomes mentioned above were also comparable with those in MSCs plus standard induction therapy group.Conclusion Induction therapy of MSCs has similar inducing immune tolerance effects on the recipients in kidney transplantation compared with that of other regimens. However, regarding the long term effect, as represented by 1-year infection rate, 1-year opportunistic infection rate and CNIs withdrawl, MSCs therapy has a significant advantage.
Loss of PLK2 Induces Acquired Resistance to Temozolomide in GBM via Activation of Notch Signaling
Authors: Alafate Wahafu , Xu Dongze , Wu Wei , Xiang Jianyang , Ma Xudong , Xie Wanfu , Bai Xiaobin , Wang Maode , Wang Jia
Published: June 2020

BackgroundGlioblastoma (GBM) isa lethal type of primary brain tumor with a median survival less than 15 months.Despiting the recent improvements of comprehensive strategies,the outcomes for GBM patients remain dismal.Accumulating evidence indicates that rapid acquired chemoresistance is the major cause ofGBM recurrence thus leads to worse clinical outcomes. Therefore, developing novel biomarkers and therapeutic targets for chemoresistant GBM is crucial for long-term cures. MethodsTranscriptomic profiles of glioblastoma were downloaded from gene expression omnibus (GEO) and TCGA database. Differentially expressed genes were analyzed and candidate gene PLK2 was selected for subsequent validation. Clinical samples and corresponding data were collected from our center and measured using immunohistochemistry analysis. Lentiviral transduction and in vivo xenograft transplantation were used to validate the bioinformatic findings. GSEA analyses were conducted to identify potential signaling pathways related to PLK2 expression and further confirmed by in vitro mechanistic assays. ResultsIn this study, we identified PLK2 as an extremely suppressed kinase-encoding gene in GBM samples, particularly in therapy resistant GBM. Additionally, reduced PLK2 expression implied poor prognosis and TMZ resistance in GBM patients. Functionally, up-regulated PLK2 attenuated cell proliferation, immigration, invasion, and tumorigenesis of GBM cells. Besides, exogenous overexpression of PLK2 reduced acquired TMZ resistance of GBM cells. Furthermore, bioinformatics analysis indicated that PLK2 was negatively correlated with Notch signaling pathway in GBM. Mechanically, loss of PLK2 activated Notch pathway through negative transcriptional regulation of HES1 and degradation of Notch1.ConclusionLoss of PLK2 enhances aggressive biological behavior of GBM through activation of Notch signaling, indicating that PLK2 could be a prognostic biomarker and potential therapeutic target for chemoresistant GBM.
Alpha-Synuclein Pathology in the Submandibular Gland of LRRK2 p.G2019S Mutation Carriers.
Authors: Vilas Dolores , Tolosa Eduardo , Aldecoa Iban , Berenguer Joan , Vilaseca Isabel , Iranzo Alex , Marti Maria J. , Martí Carles , Lomeña Francisco , Alós Llucia , Gelpi Ellen
Published: June 2020

Background. The presence of intraneuronal aggregates of phosphorylated alpha-synuclein (pAS), the histological hallmark of Parkinson disease (PD), has been already demonstrated to be present in the autonomic nerve fibres that innervate the submandibular gland in approximately 75% of living PD patients. The presence of pAS in the peripheral autonomic nervous system in carriers of LRRK2 mutations has not been studied so far. The objective of the current study is to evaluate the presence of abnormal pAS aggregates in the submandibular gland tissue of LRRK2 p.G2019S mutations carriers.Methods. This is a prospective observational study conducted between 2014 and 2015 at Hospital Clínic de Barcelona, Spain. A random sample of nine asymptomatic LRRK2 (aLRRK2) and 11 LRRK2 associated PD (LRRK2-PD) patients were recruited among a cohort of LRRK2-PD patients and their relatives already identified at our centre. All the participants underwent transcutaneous needle core biopsy of the submandibular gland under ultrasound guidance. The presence of pAS was assessed in all the participants by immunohistochemistry using anti-Serine 129-phosphorylated AS antibody.Results. Submandibular biopsy material containing glandular parenchyma was obtained in 4 (44.44%) aLRRK2 and in 6 (54.55%) LRRK2-PD patients. Aggregates of pAS were detected in the glandular parenchyma in one of the four (25%) aLRRK2 subjects and in none (0%) of the LRRK2-PD patients. Conclusions. Our study shows that pAS aggregates obtained by needle core biopsy of the submandibular gland are infrequent in LRRK2 mutation carriers but may be detected in asymptomatic mutation carriers. The low rate of pAS positive biopsies suggests either a different physiopathology between LRRK2-related and idiopathic PD or that a one-time unilateral submandibular gland biopsy is not the optimal procedure for the study of synuclein aggregation in LRRK2 mutation carriers.
High viral load suggests increased COVID-19 severity in a longitudinal cohort
Authors: He Yuanlin , Xu Xin , Lu Qun , Hu Zhiliang , Jiang Yue , Song Ci , Chen Wei , Li Peipei , Wang Weixiao , Xu Chuanjun , Ma Yuting , Lin Yuan , Hu Zhibin , Yi Yongxiang , Shen Hongbing
Published: June 2020

Background: An outbreak caused by the 2019 novel coronavirus (2019-nCoV) has spread globally. However, the viral dynamics, co-infection and their associations with clinical severity, have not been well explored.Methods: We longitudinally enrolled 23 (Five severe-type, ten common-type and eight asymptomatic-type patients) hospitalized 2019-nCov-infected patients in Jiangsu between January 21 and February 11, 2020. Medical records and pharyngeal swab specimens, were collected to analyze the association between viral dynamic and disease severity.Results: Five severe-type, ten common-type and eight asymptomatic-type patients were enrolled. Linear mixed effects models revealed that the common and severe-type patients had a higher level of viral load (3.08 points, 95% CI, 0.51-5.65, P = 0.019; 6.07 points, 95% CI, 2.79-9.35, P < 0.001) and maintained a higher peak viral load ( P = 0.066 and 0.022, respectively), when compared with the asymptomatic group. Viral load shedding among older patients (aged ≥ 60) processed slower than that among younger patients ( P = 0.047). RNA virome sequencing identified two co-infected RNA viruses, Human endogenous retrovirus H (HERV) and Human picobirnavirus (HPBV). Of note, HPBV was detected in one severe-type and two common-type patients, while was not detected in all the asymptomatic cases.Conclusion: Higher viral load was positively associated with disease severity. This finding highlights the importance of monitoring the viral kinetics to identify patients at greater risk of progressing to severe pneumonia.
Recombinant Human Epidermal Growth Factor Combined with Vacuum Sealing Drainage for Wound Healing in Bama Pigs
Authors: Wei Shuai , Wang Wei , Li Li , Meng Haoye , Feng Chunzhen , Dong Yuying , Fang Xichi , Dong Qiqiang , Jiang Wen , Li Zhanzhen , Wang Xin
Published: June 2020

Background: Both vacuum sealing drainage (VSD) and epidermal growth factor (EGF) play important roles in the treatment of wounds. This study aims to explore the effect of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF.Methods: In this study, we tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations (0, 1, 5, 10, and 100 ng/ml) and different EGF action times (2, 10, and 30min). A full-thickness skin defect model was established using male, 30-week-old Bama pigs. The skin defects were randomly divided follows: routine dressing change after covering with sterile auxiliary material (Control), continuous negative pressure drainage of the wound (VSD), continuous negative pressure drainage of the wound and injection of epidermal growth factor 10 minutes followed by removal by continuous lavage (V+E 10 min), and continuous negative pressure drainage of the wound and injection of epidermal growth factor 30 minutes followed by removal by continuous lavage (V+E 30 min). The wound healing rate, histological repair effect and collagen deposition were compared among the four groups.Results: An EGF concentration of 10 ng/ml and an action time of 10 minutes had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells. The drug dispersion effect was better than drug infusion after bolus injection effect, and the contact surface was wider. Compared with other groups, the V+E 10min group promoted wound healing to the greatest extent and obtained the best histological score. Conclusions: A rhEGF concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro. VSD combined with rhEGF kept in place for 10 minutes and then washed, can promote wound healing better than the other treatments in vivo.
An R package for the integrative evaluation of statistical approaches for cancer incidence projections
Authors: Knoll Maximilian , Furkel Jennifer , Debus Jürgen , Abdollahi Amir , Karch André , Stock Christian
Published: June 2020

Background

Projection of future cancer incidence is of high importance for epidemiological and biomedical research. Age-Period-Cohort (APC) models are established for such projections, usually based on long-term cancer registry data (>20yrs). In many countries (including Germany), however, nationwide long-term data are not yet available. It is unclear which statistical approach should be recommended for projections using rather short-term data.

Methods

An R package (incAnalysis) for the comparative analysis of projection methods was developed, supporting in particular Bayesian models fitted by Integrated Nested Laplace Approximations (INLA). It was used to assess operating characteristics (bias, coverage, precision) of various statistical approaches to cancer incidence projection based on artificially shortened long-term data from three cancer registries (SEER-9, NORDCAN, Saarland). Additionally, a novel age-period INLA z-model with multivariate tensor product smoothers is described.

Results

Coverage was high (mostly >90%) for Bayesian APC models (BAPC), whereas less complex models showed differences in coverage dependent on projection-period. Intercept-only models yielded values below 20% for coverage. Bias increased and precision decreased for longer projection periods for all except intercept-only models. Precision was lowest for BAPC, multivariate smoother and Age-Period GLMs with interaction effect.

Conclusion

The incAnalysis R package allows for straightforward comparison of (cancer incidence) rate projection approaches. Of the evaluated model classes, more complex models showed an increase in coverage at the cost of precision; bias increased for longer projection intervals, mostly irrespective of the level of complexity.
Family planning practices of women working in the Cambodian garment industry: a qualitative study
Authors: Masuda Chisato , Oreglia Elisa , Sokhey Ly , McLaren Megan , Free Caroline , Tijamo Camille , Amra Ou , Velthoven Michelle Helena van , Williamson Amy , Smith Chris
Published: June 2020

Background: Women working in Cambodian garment factories have unmet needs for contraception and safe abortion services, because of their background and living conditions. This study describes their experiences regarding abortion and contraception as part of a larger project to develop an intervention to support comprehensive post-abortion care.Methods: We conducted semi-structured interviews with women seeking abortion services at private health facilities. In addition, we interviewed the private providers of abortion and contraception services surrounding garment factories. Interviews lasted up to 60 minutes and were conducted in Khmer and later translated into English. A thematic analysis was undertaken, with medical abortion experiences coded according to the Cambodia comprehensive abortion care protocol.Results: We interviewed 16 women and 13 providers between August and November 2018. Most women were married and had at least one child. Among factory workers the major reported reasons for abortion were birth spacing and financial constraints. Family, friends, or co-workers were the major information resources regarding abortion and contraception, and their positive or negative experiences strongly influenced women’s attitude towards both. Medical abortion pills were not always provided with adequate instructions. Half of the participants had a manual vacuum aspiration procedure performed after medical abortion. While women knew the side effects of medical abortion, many did not know the adverse warning signs and the signs of abortion completion. Only three women started post abortion family planning, as most of the women expressed fear and hesitation due to side effects and misconceptions related to with modern contraception. Fear of infertility was particularly reported among young women without children.Conclusion: This research shows that in this setting not all women are receiving comprehensive abortion care and contraceptive counselling. Provision of accurate and adequate information about abortion methods and modern contraception was the dominant shortfall in abortion care. Future work needs to address this gap by developing appropriate and effective interventions and informative tools for women in the Cambodian garment industry.
Evaluation of Sida rhombifolia L roots extract on Immobilization stress induced male infertility in rats
Authors: Biradar Prakash R. , Karade Ashwini
Published: June 2020

Current study aimed to investigate protective effect of Sida rhombifolia L roots hydroalcoholic extract on immobilization stress induced male infertility in experimental rats. Male wistar rats (200-250g) were randomly divided into six groups (n=6). The male fertility enhancing activity was evaluated by sexual behavior, semen parameters, body weight, SGI, hematological parameters, vital and sexual accessory organ weight, histopathology by using standard procedure. GSH, SOD and LPO level were measured in testis tissues to evaluate antioxidant activity. The S. rhombifolia L. root hydroalcoholic extract indicated in vitro antioxidant activity on scavenging of hydroxy radicle, TAC and NO. Improvement in sperm quality i.e. count, motility, viability, Sexual behaviour, Body weight, sexual and vital organ weight, GSI, seminal fructose, Testicular cholesterol level, haematological parameters observed in treatment groups just like standard group. S. rhombifolia showed antioxidant capacity by lowering NO, MDA and elevated SOD in testis tissue. Investigations manifested that improved spermatogenesis in group treated with S. rhombifolia L in contrast with immobilization stress induced group resemblance to in silico finding study which revealed that SRR extract have adaptogenic and fertility enhancing effect.
Forecasting the Prevalence of COVID-19 in Maharashtra, Delhi, Kerala, and India using an ARIMA model
Authors: Marbaniang Strong P
Published: June 2020

Aims: As the whole world was preparing to welcome the year 2020, a new deadly virus, COVID-19, was reported in the Wuhan city of China in late December 2019. By May 18, 2020, approximately 4.7 million cases and 0.32 million deaths had been reported globally. There is an urgent need to predict the COVID-19 prevalence to control the spread of the virus.Methods: Time-series analyses can help understand the impact of the COVID-19 epidemic and take appropriate measures to curb the spread of the disease. In this study, an ARIMA model was developed to predict the trend of COVID-19 prevalence in the states of Maharashtra, Delhi and Kerala, and India as a whole.Results: The prevalence of COVID-19 from 16 March 2020 to 17 May 2020 was collected from the website of Covid19india. Several ARIMA models were generated along with the performance measures. ARIMA (2,3,1), ARIMA (2,2,0), ARIMA (2,2,0), and ARIMA (1,3,1) with the lowest MAPE (5.430, 10.440, 2.607, and 2.390) for Maharashtra, Delhi, Kerala, and India were selected as the best fit models respectively. The findings show that over the next 20 days, the total number of confirmed COVID-19 cases may increase to 2.45 lakhs in India, 93,709 in Maharashtra, 19,847 in Delhi, and 925 in Kerala.Conclusion: The results of this study can throw light on the intensity of the epidemic in the future and will help the government administrations in Maharashtra, Delhi, and Kerala to formulate effective measures and policy interventions to curb the virus in the coming days.
Tissue plasminogen activator worsens experimental autoimmune encephalomyelitis by complementary actions on lymphoid and myeloid cell responses
Authors: Hélie Pauline , Toledano Celia Camacho , Miralles Antonio J , Ortega Maria Cristina , Sol Virginia Vila del , Lesec Léonie , Vivien Denis , Mauff Brigitte Le , Clemente Diego , Docagne Fabian , Toutirais Olivier
Published: June 2020

Background
Tissue plasminogen activator (tPA) is a serine protease involved in fibrinolysis. It is released by endothelial cells, but also expressed by neurons and glial cells in the central nervous system (CNS). Interestingly, this enzyme also contributes to pathological processes in the CNS such as neuroinflammation by activating microglia and increasing blood-brain-barrier permeability. Nevertheless, its role in the control of adaptive and innate immune response remains poorly understood.
Methods
tPA effects on myeloid and lymphoid cell response were studied in vivo in the mouse model of multiple sclerosis experimental autoimmune encephalomyelitis and in vitro in splenocytes.
Results
tPA−/− animals exhibited less severe experimental autoimmune encephalomyelitis than their wild type counterparts. This was accompanied by a reduction in both lymphoid and myeloid cell populations in the spinal cord parenchyma. In parallel, tPA increased T cell activation and proliferation, as well as cytokine production by a protease-dependent mechanism and via plasmin generation. In addition, tPA raised the expression of MHC-II and the co-stimulatory molecule CD80 and CD86 at the surface of dendritic cells and macrophages by an effect dependent of the proteolytic activity of tPA and of the activation of epidermal growth factor receptor.
Conclusions
Our study provides new insights into the mechanisms responsible for the harmful functions of tPA in multiple sclerosis and its animal models: tPA promotes the proliferation and activation of both lymphoid and myeloid populations by distinct, though complementary, mechanisms.
Real-world effectiveness, treatment pattern, and safety of ranibizumab in Korean patients with neovascular age-related macular degeneration: Subgroup analyses from the LUMINOUS study
Authors: Sagong Min , Woo Se Joon , Lee Youkyung
Published: June 2020

Background
To evaluate the real-world effectiveness, treatment patterns, and safety of ranibizumab in Korean patients with neovascular age-related macular degeneration (nAMD).
Methods
LUMINOUS™ is a 5-year, global, prospective, observational, open-label study. Adults aged ≥18 years who were either treatment-naïve or prior-treated were enrolled and treated with ranibizumab 0.5 mg per the local label. Outcome measures included mean (±standard deviation) changes from baseline in visual acuity (VA) and central retinal thickness (CRT), and rate of ocular and non-ocular adverse events (AEs).
Results
Overall, 367 Korean patients with nAMD (152 treatment-naïve and 215 prior-treated) were enrolled. The mean VA changes from baseline at 1-year were +10.1 (±21.77; P = 0.0005) and +1.4 (±15.17; P = 0.2142) Early Treatment Diabetic Retinopathy Study letters, with mean number of injections of 5.2 and 3.4 in the treatment-naïve and prior-treated groups, respectively. VA gains were greater in patients with worse baseline VA, who received a loading dose, and with polypoidal choroidal vasculopathy (PCV). Multivariate logistic regression analyses demonstrated younger age, worse baseline VA, and those who received loading dose being associated with higher odds of any gain in VA at 1 year ( P < 0.05). Mean CRT changes from baseline were –126.7 (±174.90) µm ( P < 0.0001) and +10.8 (±89.52) µm ( P = 0.5833) in the treatment-naïve and prior-treated groups, respectively, with greater reductions observed in patients with PCV. Ocular and non-ocular AEs were reported in 8.4% (n=31) and 10.1% (n=37) of patients, respectively.
Conclusion
The LUMINOUS study confirms real-world effectiveness and safety of ranibizumab in Korean patients with nAMD; factors including age, baseline VA, and loading-dose were associated with VA gain at one-year post-treatment.
A Systematic and Meta-Analysis Review on the Diagnostic Accuracy of Antibodies in the Serological Diagnosis of COVID-19.
Authors: Vengesai Arthur , Midzi Herald , Kasambala Maritha , Mutandadzi Hamlet , Mduluza-Jok Tariro L. , Rusakaniko Simbarashe , Mutapi Francisca , Naicker Thajasvarie , Mdul Takafira
Published: June 2020

Background: Serological testing based on different antibody types are an alternative method being used to diagnose SARS-CoV-2 and has the potential of having higher diagnostic accuracy compared to the current gold standard RT-PCR. Therefore, the objective of this review was to evaluate the diagnostic accuracy of IgG and IgM based Point-of-care (POC) lateral flow immunoassays (LFIA), chemiluminescence enzyme immunoassay (CLIA), fluorescence enzyme-linked immunoassay (FIA) and ELISA systems that detect SARS-CoV-2 antigens.Method: A systematic literature search was carried out in PubMed, Medline complete and MedRxiv. Studies evaluating the diagnostic accuracy of serological assays for SARS-CoV-2 were eligible. Study selection and data-extraction were done by two authors independently. QUADAS-2 checklist tool was used to assess the quality of the studies. The bivariate model and the hierarchical summary receiver operating characteristic curve model were performed to evaluate the diagnostic accuracy of the serological tests. Subgroup meta-analysis analyses was performed to explore the heterogeneity. Results: The pooled sensitivity for IgG, IgM and IgG-IgM based LFIA tests were 0.5856, 0.4637 and 0.6886 respectively compared to RT-PCR method. The pooled sensitivity for IgG and IgM based CLIA tests were 0.9311 and 0.8516 respectively compared to RT-PCR. The pooled sensitivity the IgG, IgM and IgG-IgM based ELISA tests were 0.8292, 0.8388 and 0.8531 respectively compared to RT-PCR. All tests displayed high specificities ranging from 0.9693 to 0.9991. Among the evaluated tests, IgG based CLIA expressed the highest sensitivity signifying its accurate detection of the largest proportion of infections identified by RT-PCR. ELISA and CLIA tests performed better in terms of sensitivity compared to LFIA. IgG based tests performed better compared to IgM ones expect for the ELISA. Conclusions: We report that IgG-IgM based ELISA tests have the best overall diagnostic test accuracy. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type independently. Given the poor performances of the current LFIA devices there is need for more research on the development of highly sensitivity and specific POC LFIA that are adequate for most individual patient applications and attractive for large sero-prevalence studies.Systematic review registration: PROSPERO Registration Number is: CRD42020179112
Niaoduqing Granules Inhibits TGF-β1-induced Epithelial-Mesenchymal Transition in Human Renal Tubular Epithelial HK-2 Cells
Authors: Huo Chu-Ying , Yang Hua-Yi , Ning Wei-Min , Yu Lin-Zhong , Fan Chun-Lin , Quan Jing-Yu , Deng Li-Er , Yu Zhi-Ling , Liu Jun-Shan , Cao Hui-Hui
Published: June 2020

Background: Chronic renal failure (CRF) is a worldwide public health burden. Niaoduqing granules (NDQ) is widely used for CRF treatment in China. However, the underlying mechanism of NDQ is not fully studied. This study is aimed to investigate whether NDQ ameliorate CRF by inhibiting TGF-β1-induced EMT in human renal tubular epithelial HK-2 cells.Methods: MTT assay and colony formation assay were used to investigate the cytotoxicity of NDQ in HK-2 cells. Morphological changes of HK-2 cells after TGF-β1 or/and NDQ treatment were observed under a microscope. Wound-healing, migration and invasion assays were performed to determine the cell movement, migratory and invasive abilities, respectively. Western blot analysis was carried out to examine the protein levels of TGF-β type I receptor (TβRI) and EMT-associated factors. Fluorescence confocal microscopy was applied to observe the organization of F-actin.Results: NDQ suppressed TβRI expression dose-dependently. NDQ inhibited TGF-β1-stimulated EMT in HK-2 cells, supported by the evidences that NDQ prevented morphology change, attenuated cell migration and invasion, downregulated EMT factors and reorganized F-actin distribution in TGF-β1-stimulated HK-2 cells.Conclusions: NDQ attenuates chronic renal failure which may be associated with inhibition of TβRI expression and EMT process.
Dentin-derived Inorganic Minerals Promote the Osteogenesis of Bone Marrow-derived Mesenchymal Stem Cells: Potential Applications for Bone Regeneration
Authors: Lei Gang , Wang Yanqiu , Yu Yan , Li Zehan , Lu Jiamin , Ge Xingyun , Li Na , Yu Jinhua
Published: June 2020

Background Oral and maxillofacial bone loss is highly prevalent among populations and nowadays increased attention has been focused on dentin derivatives as desirable graft materials for bone regeneration. In this study, dentin-derived inorganic minerals (DIM) were fabricated with a high-temperature calcination technique and the effects of DIM on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMMSCs) and the bone formation were elucidated.Methods The effects of DIM on BMMSCs proliferation, apoptosis capacity were evaluated by CCK-8, flow cytometry and EdU assays. Alkaline phosphatase (ALP) activity detection, ALP staining, alizarin red staining and osteogenic markers expression analysis were performed to investigate the influence of DIM on the osteogenic differentiation of BMMSCs, as well as the relevant signal mechanisms. The model of critical-sized defects in calvarium of rats was constructed for exploring the in vivo efficiency of DIM on bone regeneration.Results Cell viability assays indicated that DIM had no cytotoxicity. BMMSCs cultured with DIM presented a higher level of osteogenic differentiation ability than those in the control group. The activation in ERK and p38 signals was detected in DIM-treated BMMSCs, and both pathways and osteogenic process were suppressed while using ERK inhibitor U0126 and p38 inhibitor SB203580, respectively. Furthermore, the animal experiments revealed that DIM could dramatically enhance new bone formation compared to the control group.Conclusion All these results demonstrated that DIM could promote BMMSCs osteogenic differentiation via triggering ERK and p38 MAPK signaling pathways and be a novel predictable material for facilitating bone formation.
Regeneration of a Full-Thickness Defect of Rotator Cuff Tendon with Freshly Thawed Umbilical Cord-Derived Mesenchymal Stem Cells in a Rat Model
Authors: Yea Ji-Hye , Park Jin-Kyung , Kim InJa , Sym Gayoung , Bae Tae Soo , Jo Chris Hyunchul
Published: June 2020

Background: It is difficult to immediately use mesenchymal stem cells (MSCs) for the patient with rotator cuff disease because isolation and culture time are required. Thus, the MSCs would be prepared in advanced in cryopreserved condition for an “off-the-shelf” usage in clinic. This study investigated the efficacy of freshly thawed MSCs on the regeneration of a full-thickness tendon defect (FTD) of rotator cuff tendon in a rat model. Methods: We evaluated morphology, viability and proliferation of cultured umbilical cord-derived MSCs (C-UC MSCs) and freshly thawed umbilical cord-derived MSCs (T-UC MSCs) at passage 10 in vitro. In animal experiments, we created a FTD in the supraspinatus tendon of rats and injected the injured tendon with saline, cryopreserved agent (CPA; control), C-UC MSCs, and T-UC MSCs respectively. Two to four weeks later, macroscopic, histological and biomechanical changes were evaluated. T-test and ANOVA were used with SPSS. Differences with p < .05 were considered statistically significant.Results: T-UC MSCs had fibroblast-like morphology and showed greater than 97% viability and stable proliferation comparable to the C-UC MSCs at passage 10. In animal experiments, compared with the control group, the macroscopic appearance of the T-UC MSCs was further recovered at two and four weeks such as inflammation, defect size, neighboring tendon, swelling/redness and the connecting surrounding tissue and slidability. Histologically, compared to the control group the nuclear aspect ratio, orientation angle of fibroblasts, collagen organization and fiber coherence were improved by 33.33%, 42.75%, 1.86- and 1.99-fold and GAG-rich area was suppressed by 81.05% at four weeks. Further, the T-UC MSCs showed enhanced ultimate failure load by 1.55- and 1.25-fold compared with the control group at both two and four weeks. All the improved values of T-UC MSCs were comparable to those of C-UC MSCs. Conclusions: The morphology, viability and proliferation of T-UC MSCs are comparable to those of C-UC MSCs. Treatment with T-UC MSCs induces tendon regeneration of FTD at the macroscopic, histological and biomechanical levels comparable to treatment with C-UC MSCs.
Mitigative Efficacy of the Clinical Dosage Administration of Granulocyte Colony-stimulating Factor and Romiplostim in Mice With Severe Acute Radiation Syndrome
Authors: Yamaguchi Masaru , Suzuki Marino , Funaba Moeri , Chiba Akane , Kashiwakura Ikuo
Published: June 2020

Background:It has been reported that the high-dosage administration of domestically approved pharmaceutical drugs, especially granulocyte colony-stimulating factor (G-CSF) and romiplostim (RP), is a rapid and appropriate medical treatment for preventing severe acute radiation syndrome (ARS) of victims exposed to lethal total-body irradiation (TBI). However, it remains unclear whether or not the clinical dosage administration of these drugs can ameliorate TBI-induced ARS and related high mortality in order to find various drug treatment options and less toxic optimum protocol depending on the situation surrounding the radiological accidents.Methods:We assessed the clinical dosageadministration in combination with G-CSF and RP as intraperitoneal injection in C57BL/6J mice exposed to more than 7-Gy lethal dose of X-ray TBI for the survival studyevaluated by the log-rank test. Bone marrow and splenic cellswere collected on the 21st day, when1 week have passed from last administration, to detect the level of cell apoptosis, intracellular reactive oxygen species (ROS), and nuclear factor erythroid 2-related factor 2 (Nrf2)-related anti-oxidative gene expressions, and enzyme-linked immune sorbent assayusing serawas performed for cell senescence and inflammationstatusanalyzed with one-way ANOVA and Tukey-Kramer or Bonferroni/Dunn multiple comparison tests.Results: The combined once-daily administration of 10 μg/kg G-CSF for 4 times and 10 μg/kgRP once a week for 3 times improve the 30-day survival rate of lethal TBI mice compared with untreated TBI mice, accompanied by a gradual increase in the body weight and hematopoietic cell numbers. The radio-mitigative effect is probably attributed to the scavenging of ROS and the reduction in cell apoptosis. These changes were associated with the upregulation of Nrf2 and its downstream anti-oxidative targets in TBI mice. Furthermore, this combination modulated TBI-induced cell senescence and inflammation markers. Conclusions:This study suggested that the clinical dosage administration in combination with G-CSF and RP may also have radio-mitigative effects on mice exposed to lethal TBI and may be a potent therapeutic agent for mitigating radiation-induced severe ARS.
Severity distribution of Alzheimer’s disease dementia and mild cognitive impairment in the Framingham Heart Study
Authors: Yuan Jing , Maserejian Nancy , Liu Yulin , Devine Sherral , Gillis Cai , Massaro Joseph , Au Rhoda
Published: June 2020

Background: Studies providing Alzheimer’s disease (AD) prevalence data have largely neglected to characterize the proportion of AD that is mild, moderate or severe. Estimates of the severity distribution along the AD continuum, including the mild cognitive impairment (MCI) stage, are important to plan research and allocate future resources, particularly resources targeted at particular stages of disease. Methods: Participants (aged 50-94) with prevalent MCI or AD dementia clinical syndrome were cross-sectionally selected from three time-windows of the population-based Framingham Heart Study in 2004-2005 (n=381), 2006-2007 (n=422), and 2008-2009 (n=389). Summary estimates of the severity distribution were achieved by pooling results across time-windows. Diagnosis and severity were assessed by consensus dementia review. MCI-progressive was determined if the participant had documented progression to AD dementia clinical syndrome using longitudinal data.Results: Among AD dementia participants, the pooled percentages were 50.4% for mild, 30.3% for moderate, and 19.3% for severe. Among all MCI and AD participants, the pooled percentages were 29.5%, 19.6%, 25.7%, and 45.2% for MCI-not-progressive, MCI-progressive, mild AD dementia, and the combined group of MCI-progressive & mild AD dementia, respectively. Distributions by age and sex were presented.Conclusions: Heterogeneity in severity of the AD population exists. That half of prevalent cases have mild disease underscores the need for research and interventions to slow decline of this burdensome disease.Limitations: First, the FHS cohort participants were almost homogenously Caucasians and residents of a single city in MA, that limits the generalization of the results. Second, although FHS is a longitudinal study, the study population over the three time-windows would not be expected to be as dynamic as that of sampling participants from different geographic areas. Lastly, the study lacked AD biomarker confirmation (e.g., amyloid, tau, neurodegeneration), which would have increased the accuracy of case ascertainment.
Impact of the COVID-19 epidemic on outpatient visits of common respiratory diseases
Authors: Wang Weiyi , Zheng Yulu , Jiang Libin
Published: June 2020

Background/Purpose

The outbreak of corona virus disease 2019 (COVID-19) has become a worldwide threat to public health. The purpose of this study is to analyze the impact of COVID-19 epidemic on outpatient visits of common respiratory diseases.

Methods

Through statistics and comparing the data with the same period last year,we present the changes of outpatient visits of 14 common respiratory diseases in an upper first-class hospital in China from January to May,2020.

Results

From January to May,2020, the number of outpatient visits of most common respiratory diseases fell below the previous year,and total number of outpatient visits of 14 common respiratory diseases decreased by 58.07% year-on-year. Bronchitis, pneumonia, cough, acute upper respiratory infection and bronchiectasis infection are in our top 5 drop list,decreased by 76.79%,71.03%,66.51%56.87% and 56.31% respectively.

Conclusion

COVID-19 epidemic had a strong influence on the outpatient visits of common respiratory diseases, particularly for infectious diseases.
The Reasons for not Utilization of Intrauterine Device among Short Term Modern Contraceptive User Women in Hossana Town Public Health Facilities: Qualitative Study
Authors: Handiso Demelash Woldeyohannes
Published: June 2020

Background

Intrauterine device (IUD) is a safe, long-acting, and effective method of contraception. However, is under-utilized in many countries, including Ethiopia. The several studies presented to address the problem, nearly all are quantitative. These have primarily generated a list of associated factors and reasons that did not seem to help health systems to design effective strategies to address the problem. This study looked at the problem with a different approach to explore the issue in detail and help to develop locally appropriate strategies to increase the utilization of IUD in the study area. To this end, qualitative method focused entirely on understanding why short term contraceptive user women are not using IUD from the maternal health service programs.

Objective

To explore the reasons for not utilization of IUD among short term modern contraceptive users in Hossana town public health facilities, southern Ethiopia.

Method

A Phenomenological qualitative study was conducted in Hossana town public health facilities, Southern Ethiopia from November 1-30, 2019. A total of 13 in-depth interviews were conducted: eleven short term contraceptive users, one health centre head and one health extension worker/community health worker/ were included in the study. Semi-structured interviewer guided questions and tape recorder were used to collect data. The collected data were expanded, labelled and ordered chronologically. Data were organized after subsequent detailed reading and analysis. Thematic analysis was used to analyze the collected data.

Result

In this study, the reasons for not utilization of IUD was poor knowledge about the benefits of IUD, insufficient counseling and not providing informed choices, and the absence of trained health personals and shortage of necessary supplies.

Conclusion

The main reasons for not utilization of IUD was poor counseling of mothers, unsupportive provider-client relationships, and poor counseling by service providers. Efforts to rise IUD users need to focus on improving counseling of mothers and strengthening the health systems.
Low high-density lipoprotein level is correlated with the severity of COVID-19 patients
Authors: Wang Guyi , Zhang Quan , Dong Haiyun , Wu Chenfang , Wu Fang , Yu Bo , Lv Jianlei , Zhang Siye , Wu Ying , Wu Guobao , Wu Shangjie , Zhong yanjun
Published: June 2020

Background
The aim of the present study was to describe the clinical characteristics of patients with different levels of high-density lipoproteins (HDLs) and analyze the correlation between HDL levels and prognosis of coronavirus disease 2019 (COVID-19) patients.
Methods
In the clinical retrospective analysis, a total of 228 adult COVID-19 patients admitted to Public Health Treatment Center of Changsha, China from January 17 to March 14, 2020 were enrolled. Median with interquartile range and Mann-Whitney test were used to depict and analyze the clinical characteristics of patients. The Kaplan-Meier (KM) curve and cox regression were adopted to analyze the association between HDLs and severe events of COVID-19 patients.
Results
Median levels of high-density lipoprotein cholesterol (HDL-C) in adult COVID-19 patients were below normal range. Compared with patients with high HDL-C, patients with low HDL-C showed higher proportion of male (69.6% vs 45.6%, P = 0.004), higher levels of C-reactive protein (CRP) (median, 27.83 vs 12.56 mg/L, P = 0.000) and alanine aminotransferase (ALT) (median, 21.49 vs 18.81 U/L, P = 0.044), as well as higher proportion of severe events (37.0% vs 14.8%, P = 0.001). Moreover, they presented a higher risk of developing severe events compared with those with high HDL-C (Log Rank P < 0.001, Fig. 1). After adjusting for age, gender and underlying diseases, patients with low HDL-C still had elevated possibility of developing to severe cases than those with high HDL-C (HR 2.852, 95% CI 1.505–5.407, P = 0.001).
Conclusions
HDL-C level decreased in COVID-19 adult patients, and low HDL-C in COVID-19 patients was correlated with a higher risk of developing severe events.
Imaging the rapid yet transient accumulation of regulatory lipids, lipid kinases, and protein kinases during membrane fusion, at sites of exocytosis of MMP-9 in cancer cells
Authors: Stephens Dominique , Powell Tyrel , Taraska Justin , Harris Dinari
Published: June 2020

Background: The control of exocytosis is physiologically essential. In vitro SNARE proteins are sufficient to drive membrane fusion, but in cells there are additional proteins and lipids that work together to drive efficient, fast, and timely release of secretory vesicle cargo. Growing evidence suggests that regulatory lipids act as important lipid signals and regulate various biological processes including exocytosis. Though functional roles of many of these regulatory lipids has been linked to exocytosis, the dynamic behavior of these lipids during membrane fusion at sites of exocytosis in cell culture remains unknown. Methods: We used total internal reflection fluorescence microscopy (TIRF) to observe the spatial organization and temporal dynamics of several lipids, and accessory proteins, like lipid kinases and protein kinases, in the form of protein kinase C (PRKC) relative to single sites of exocytosis of MMP-9 in living MCF-7 cancer cells. Results: After stimulating exocytosis with PMA, we observed a transient accumulation of the regulatory lipids (e.g. PIP, PIP2, and DAG), lipid kinases (e.g. PI4K2B, PI4K3A, and PIP5KA), and protein kinases (e.g. PRKCA and PRKCE) at exocytic sites centered on the time of membrane fusion, before rapidly diffusing away from the fusion sites. Additionally, the synthesis of these regulatory lipids, degradation of these lipids, and the downstream effectors activated by these lipids, are also achieved by the recruitment and accumulation of key enzymes at exocytic sites (during the moment of cargo release), including lipid kinases, protein kinases, and phospholipases that facilitate membrane fusion and exocytosis of MMP-9. Conclusions: This work suggests that these regulatory lipids and associated effector proteins are locally synthesized and/or recruited to exocytic sites, during the time of membrane fusion and cargo release, and their enrichment at fusion sites serves as an important spatial and temporal organizing “element” defining individual exocytic sites.
Bomb Blast: Imaging Findings, Treatment and Clinical Course of Extremity Traumas
Authors: Tahtabasi Mehmet , Er Sadettin , Karasu Recep , Ucaroglu Erhan Renan
Published: June 2020

Background: To determine the severity and types of blast-related extremity injuries and the presence of accompanying vascular injuries (VI) and amputation, and to identify the predictive factors affecting the treatment management and clinical course.
Methods: The study included 101 patients with extremity injuries caused by a bomb explosion. The radiographs and computed tomography angiographies of the patients were evaluated in terms of injury patterns, presence of shrapnel fragments and fractures, and localization (upper or lower extremity) and type (open or closed) of injury. The Gustilo-Anderson classification was used for open fractures. According to their severity, open fractures classified as types 1, 2 and 3A were included in Group 1 and those classified as type 3B and 3C in Group 2.
Results: As a result of the explosion, 101 (57.7%) patients had extremity injuries, of which 76 (75.2%) presented with at least one fracture. Of the total of 103 fractures, nine (8.8%) were closed and 94 (91.2%) were open. Thirty-eight (40.4%) of the open fractures were located in the upper extremities, and 56 (59.6%) in the lower extremities and pelvis. Open fractures were most frequently localized in the femur (n=20; 21.2%), followed by the tibia (n=18; 19.1%). The majority of patients with open fractures were in Group 1 (74.2%). The duration of hospital stay was longer in Group 2 (11.7±5.8 vs. 6.8±6.7 days, p <0.0001). Mortality among patients in Group 2 (44.4%) was significantly higher than in Group 1 (6.1%) ( p <0.0001). Similarly, the injury severity score (ISS) was higher in Group 2 (median 20 vs. 9, p<0.0001). Similarly, the rate of VI was higher in Group 2 (66.1%) than in Group 1 (2.4%) ( p <0.0001). VI was present in 13 (12.9%) of all patients, and amputation in seven (7.9%).
Conclusion: The presence of severe open fractures, VI, and high ISS score can be considered as important factors that increase morbidity and mortality. In extremity traumas, through the secondary blast mechanism, contaminated-fragmented tissue injuries occur. Therefore, we believe that it will be beneficial to apply damage control surgery in places with low socioeconomic level and poor hygienic conditions.
A Unique Role Of TRPV1 Ion Channels In The Suppression Of Gastric Cancer Development
Authors: Gao Nannan , Yang Feng , Chen Siyuan , Wan Hanxing , Zhao Xiaoyan , Dong Hui
Published: June 2020

Background: Although the aberrant expression and function of most Ca2+-permeable channels are known to promote gastrointestinal tumors, the association of transient receptor potential vanilloid receptor 1(TRPV1) channels and gastric cancer (GC) has not been explored so far. We sought to determine their role in the development of GC and to elucidate the underlying molecular mechanisms. Methods: The expression of TRPV1 in GC cells and tissues was detected by qPCR, immunohistochemistry, western blot analysis and immunofluorescence. CCK8 and flow cytometry were used to detect the proliferation and cell cycle, while transwell assay was used to detect migration and invasion. The role of TRPV1 in GC development in vivo was tested using tumor xenograft and peritoneal dissemination assays in nude mice. Results: The decreased expression of TRPV1 protein in primary human GC tissues was closely correlated with poor prognosis of GC patients. TRPV1 protein was predominately expressed on the plasma membrane of several GC cell lines. TRPV1 overexpression attenuated proliferation, migration and invasion of GC cells in vitro, but TRPV1 knockdown increased them. Moreover, TRPV1 significantly reduced gastric tumor sizes, numbers and peritoneal dissemination in vivo. Mechanistically, TRPV1 overexpression increased [Ca2+]i, activated CaMKKβ and AMPK phosphorylation, and decreased expression of cyclin D1 and MMP2, but TRPV1 knockdown caused the opposite effects.Conclusions: TRPV1 uniquely suppresses GC through a novel Ca2+/CaMKKβ/AMPK pathway and its downregulation is correlated with poor survival in human GC. TRPV1 upregulation and its downstream signaling may be a promising strategy for GC prevention and therapy.