Health state utility values in patients with Ankylosing Spondylitis: a systematic review and meta-analysis.

INTRODUCTION: Ankylosing spondylitis (AS) is a chronic condition that requires lifelong treatment and results in a serious disease burden. Health state utility values (HSUVs) are a valuable tool for quantifying this burden and conducting cost-utility analysis. OBJECTIVE: We conducted a systematic review and meta-analysis to obtain estimates of HSUVs in patients with AS, explored potential sources of heterogeneity, and compared pooled patient HSUVs with population norms. METHOD: We searched PubMed, Embase, Web of science, Cochrane database and Scopus until July, 2023 to obtain eligible studies. The methodological quality of the included studies was assessed using the ROBINS-I checklist. RESULTS: Forty-two publications involving 11,354 participants were included in this systematic review. The most commonly used instrument is the EQ-5D (38 studies). The estimated HSUVs for patients with AS from all available studies was pooled as 0.62 (95% CI 0.59 to 0.65). The pooled mean utility estimates from the random effects meta-analysis for SF-6D, EQ-5D-3L, EQ-5D-5L, and HUI3 were 0.65 (95% CI 0.62,0.68), 0.63 (95% CI 0.59,0.66), 0.60 (95% CI 0.42,0.79), and 0.48 (95% CI 0.43,0.53), respectively. For the EQ-5D-3L we conducted stratified meta-analyses and meta-regression based on key subgroups. The pooled estimates of EQ-5D-3L were lower for patients published before 2010, with high disease activity, long duration of disease, and in developed countries. CONCLUSION: Pooled estimates of HSUVs for people with AS were substantially lower than population norms. These estimates provide robust evidence that can inform the economic evaluation of new therapies for individuals with AS.

Isolated superior mesenteric artery dissection with concomitant vascular aberrancy: Extremely rare cases and clinical implications.

OBJECTIVE: Vascular aberrancy of superior mesenteric artery (SMA) may contribute to the occurrence of SMA dissection. However, there is no direct evidence to support this hypothesis. Etiology, natural history, classification, and treatment options of ISMAD are still in controversial at some degree. We also review the current understanding of ISMAD based on our results. METHODS: Out of 57 patients, 2 cases of isolated superior mesenteric artery dissection (ISMAD) which concomitant with replaced common hepatic artery with SMA origin, are first reported. RESULTS: Two patients have no any typical etiological factors, such as atherosclerosis, hypertension, long-term smoking, and connective tissue disease. The contrast-enhanced computed tomography and (or) angiography showed concomitant SMA aberrancy. They have 81.2°, 132.7° SMA angle, respectively. After conservative treatment of 4, 6 days, respectively, these 2 patients were discharged smoothly. CONCLUSION: Vascular aberrancy may be a new identified risk factor for ISMAD. Even in ISMAD cases with vascular aberrancy, conservative treatment still can be used as first line therapy.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Associations between family history of psoriatic disease and clinical characteristics on patients with psoriatic arthritis: a nationwide study from the Chinese Registry of Psoriatic Arthritis (CREPAR II).

OBJECTIVES: The study aimed to identify clinical characteristics in Chinese patients with psoriatic arthritis (PsA) with or without a family history of psoriasis and/or PsA. METHODS: Patients with PsA were recruited based on Chinese REgistry of Psoriatic ARthritis (CREPAR) between December 2018 and June 2021. The demographics, clinical information relating to PsA, laboratory variables and comorbidities were collected. The association between family history of psoriatic disease and clinical characteristics on PsA was analysed using logistic regression analysis. RESULTS: Among 1074 eligible patients with PsA, 313 (29.1%) had a family history of psoriasis and/or PsA. Compared with patients without a family history, notably, patients with a family history of psoriasis and/or PsA had an earlier age of onset of psoriasis and PsA, higher proportions of enthesitis and nail involvement, a higher prevalence of positive human leukocyte antigen-B27 (HLA-B27), lower disease activity score 28-erythrocyte sedimentation rate, higher proportions of hyperlipidaemia, lower proportions of hypertension and diabetes. Furthermore, after adjusting for confounding factors, logistic regression analysis demonstrated that a positive family history of psoriasis and/or PsA was associated with more females (OR 1.514, 95% CI 1.088-2.108, p=0.014), earlier age at psoriasis onset (OR 0.971, 95%CI 0.955-0.988, p=0.001), a higher prevalence of HLA-B27 (OR 1.625 95%CI 1.089-2.426, p=0.018), more presence of nail involvement (OR 1.424, 95%CI 1.007-2.013, p=0.046) and enthesitis (OR 1.393, 95%CI 1.005-1.930, p=0.046), a higher proportion of hyperlipidaemia (OR 2.550, 95%CI 1.506-4.317, p=0.001) in PsA patients. CONCLUSIONS: This was first nationwide study to characterize patients with and without a family history of psoriatic disease in China. The findings from the present study revealed that family history of psoriasis and/or PsA had greater effects on disease phenotypes of PsA, especially nail disease and enthesitis.

Accurate Prediction of Soil Heavy Metal Pollution Using an Improved Machine Learning Method: A Case Study in the Pearl River Delta, China.

In traditional soil heavy metal (HM) pollution assessment, spatial interpolation analysis is often carried out on the limited sampling points in the study area to get the overall status of heavy metal pollution. Unfortunately, in many machine learning spatial information enhancement algorithms, the additional spatial information introduced fails to reflect the hierarchical heterogeneity of the study area. Therefore, we designed hierarchical regionalization labels based on three interpolation techniques (inverse distance weight, ordinary kriging, and trend surface interpolation) as new spatial covariates for a machine learning (ML) model. It was demonstrated that regional spatial information improved the prediction performance of the model (R2 > 0.7). On the basis of the prediction results, the status of HM pollution in the Pearl River Delta (PRD) region was evaluated: cadmium (Cd) and copper (Cu) were the most serious pollutants in the PRD (the point overstandard rates are 18.77% and 12.95%, respectively). The analysis of index importance and bivariate local indicators of spatial association (LISA) shows that the key factors affecting the spatial distribution of heavy metals are geographical and climatic conditions [namely, altitude, humidity index, and normalized vegetation difference index (NDVI)] and some industrial activities (such as metal processing, printing and dyeing, and electronics industry). This study develops a novel approach to improve existing spatial interpolation techniques, which will enable more precise and scientific soil environmental management.

Income-related equity in inpatient care utilization and unmet needs between 2013 and 2018 in Tibet, China.

BACKGROUND: Providing equitable access to health care for all populations is an important sustainable development goal. China has made significant progress in achieving equity in healthcare utilization. However, research on equity in healthcare utilization in Tibet is sparse. This study aims to evaluate changes in income-related inequity in inpatient care utilization and unmet needs between 2013 and 2018 among the Tibetan population and identify the inequity source. METHODS: Data for this cross-sectional study were obtained from the fifth and sixth waves of the National Health Services Survey in 2013 and 2018. After excluding observations with missing values for key variables, 11,092 and 10,397 respondents were included in this study, respectively. The outcome variables of interest were inpatient service utilization and unmet hospitalization needs. The concentration index and horizontal inequity index (HI) were used to assess income-related inequity. Non-linear decompositions were performed to identify the main contributors to inequity. In the decomposition method, need variables included sex, age, chronic diseases, and the EuroQol-Visual Analog Scale; non-need variables consisted of income, education, employment status, marital status, and health insurance schemes. RESULTS: The probability of inpatient care utilization increased from 6.40% in 2013 to 8.50% in 2018. The HI for inpatient care utilization was 0.19 (P < 0.001) in 2013, whereas it decreased to 0.07 (P < 0.001) in 2018. The contribution of income to inequity in inpatient care utilization decreased from 87.09% in 2013 to 59.79% in 2018. As for unmet inpatient care needs, although its probability increased from 0.76 to 1.48%, the percentage of reasons for financial hardship decreased from 47.62 to 28.57%. The HI for unmet hospitalization need was - 0.07 in 2013 and - 0.05 in 2018, and neither was statistically significant. The New Rural Cooperative Medical Scheme made majority contributions to promote equity in unmet hospitalization need. Moreover, the female respondents reporting low EuroQol-Visual Analog Scale scores and patients with chronic disease were not only more likely to seek for inpatient care, but also have more unmet need than the reference groups. CONCLUSIONS: The inequity in inpatient care utilization in Tibet narrowed from 2013 to 2018, and there was no inequity in unmet hospitalization needs in 2013 and 2018. Income and the New Rural Cooperative Medical Scheme are the main drivers of equity promotion. To promote access to inpatient care utilization and decrease the probability of unmet hospitalization need in future, policymakers should target high-need residents in Tibet to improve accessibility, availability, and acceptability.

Psychometric properties and comparison of four health utility approaches among myopia patients in China.

BACKGROUND: The increased prevalence of myopia creates and earlier age of onset has created public health concerns for the long-term eye health, vision impairment and carries with it a significant economic burden. The quality of the economic evaluation is dependent on the sensitivity and validity of the approaches. Nowadays, there are many approaches to measure patients' health state utility (HSU). However, little is known regarding the performance of direct approach and indirect approach in people with myopia. This study is aimed to compare the psychometric properties of four HSU approaches among patients with myopia in mainland China, including two direct approaches (TTO and SG), the generic preference-based measures (PBM) (AQoL-7D) and the disease-specific PBM (VFQ-UI). METHODS: A convenience sampling framework was used to recruit patients with myopia who attended a large ophthalmic hospital in Jinan, China. Spearman's rank correlations coefficient was used to assess concurrent validity. Known-group validity was analyzed by: (1) whether the patients wear corrective devices; (2) severity of myopia as low or moderate to high of the better eye; (3) duration of myopia as ≤ 10 years or > 10 years. Effect size (ES), relative efficiency (RE) statistic and the largest area under the receiver operating characteristic curve (AUC) were used to assess sensitivity. The intra-class correlation coefficient (ICC) and Bland-Altman plots were used to assess agreement. RESULTS: A valid sample size of 477 myopia patients was analyzed (median duration: 10 years). The mean HSU scores between TTO and SG were similar (0.95) and higher than AQoL-7D (0.89) and VFQ-UI (0.83). Overall, the VFQ-UI had the best performance based on the psychometric analysis. The agreement indicated that there was no pair of approaches that could be used interchangeably. CONCLUSIONS: The VFQ-UI showed better psychometric properties than other three approaches for providing health state utility in Chinese myopia patients. Given the widespread use and its generic nature of the AQoL-7D, it could be used alongside with VFQ-UI to provide complementary health state utility from a generic and disease-specific perspective for economic evaluation. More evidence on the responsiveness of four health utility approaches in myopia patients is required.

Mapping the Seattle Angina Questionnaire to EQ-5D-5L in patients with coronary heart disease.

BACKGROUND: Health economic evaluation is critical in supporting novel cardiovascular disease therapies. However, most clinical studies do not include preference-based questionnaires to calculate utilities for health economic evaluations. Thus, this study aimed to develop mapping algorithms that convert the Seattle Angina Questionnaire (SAQ) to EQ-5D-5L health utility scores for patients with coronary health disease (CHD) in China. METHODS: Data were obtained from a longitudinal study of patients with CHD conducted at the Tianjin Medical University General Hospital in China. Convenience sampling was used to recruit patients with CHD. The inclusion criteria were having been diagnosed with CHD through a medical examination and being aged 18 years or older. The exclusion criteria were a lack of comprehension ability, serious comorbidities, mental illness, and hearing or vision impairment. All eligible patients were invited to participate, and 305 and 75 patients participated at baseline and in the follow-up, respectively. Seven regression models were developed using a direct approach. Furthermore, we predicted the five EQ-5D items using ordered logit model and derived the utility score from predicted responses using an indirect approach. Model performances were evaluated using mean absolute error (MAE), root mean squared error (RMSE), correlation coefficient (ρ), and Lin's concordance correlation coefficient (CCC). A five-fold cross-validation method was used to evaluate internal validation. RESULTS: The average age was 63.04 years, and 53.72% of the included patients were male. Most (70.05%) patients had unstable angina pectoris, and the mean illness duration was 2.50 years. The EQ-5D scores were highly correlated with five subscales of the SAQ, with Spearman's rank correlation coefficients ranging from 0.6184 to 0.7093. The mixture beta model outperformed the other regression models in the direct approach, with the lowest MAE and RMSE and highest ρ and CCC. The ordered logit model in the indirect approach performed the same as the mixture beta regression with equal MAE, lower RMSE, and higher ρ and CCC. CONCLUSION: Mapping algorithms developed using mixture beta and ordered logit models accurately converted SAQ scores to EQ-5D-5L health utility values, which could support health economic evaluations related to coronary heart disease.

Immunomodulatory effect and molecular mechanism of deoxyribonucleic acid receptor toll-like receptor 9 signaling pathway on newborn babies with acute lung injury.

This work was to demonstrate the immunomodulatory effect of toll-like receptor 9 (TLR9) signaling on newborn babies with acute lung injury (ALI) and the mechanism of TLR9 in vivo, so as to provide experimental basis for clinical treatment of newborn babies with ALI. Firstly, the expression of TLR9 in peripheral blood mononuclear cell (PBMC) was compared among ALI and healthy newborn babies. Then, PBMCs of newborn babies with ALI were extracted and divided into three groups. They were added with non-methylated cytosine purine-guanine dinucleotide sequence oligodeoxyribonucleotide (CpG ODN), ODN without non-methylated CpG, and blank nutrient solution, respectively, so as to determine the proliferation changes of PBMC. The immunohistochemistry (IHC) method was applied to detect the protein expression of TLR9-myeloid differentiation factor 88 (MyD88) signaling in lung tissue, and the number of T cell subsets (CD3+, CD4+, and CD8+) was detected by flow cytometry. Besides, enzyme-linked immunosorbent assay (ELISA) was employed to determine the concentration of interferon-α (INF-α) and INF-γ. The results revealed a neglectable difference in TLR9 expression in PBMCs among ALI and healthy newborn babies (P>0.05). Additionally, the proliferation number of PBMC cultured in CpG ODN group was greatly superior to the number of ODN and blank groups (P<0.05), and the INF-α and INF-γ of CpG ODN group increased obviously versus those of blank and ODN groups (P<0.05). In conclusion, TLR9 in PBMCs was present in both ALI and healthy newborn babies. CpG ODN could specifically recognize the TLR9 signaling, so as to activate the immune function of T lymphocyte subsets in newborn babies with ALI and promote the release of inflammatory factors from the neonatal patient's immune cells, thereby mediating the immune response of neonatal patients.

Identification of genetic susceptibility in preterm newborns with bronchopulmonary dysplasia by whole-exome sequencing: BIVM gene may play a role.

Bronchopulmonary dysplasia (BPD) is a common chronic respiratory disease in preterm infants caused by multifactorial etiology. Genetic factors are involved in the occurrence of BPD, but studies have found that candidate genes have poor reproducibility and are influenced by ethnic heterogeneity; therefore, more exploration is still needed. We performed whole-exon sequencing in 34 preterm infants with BPD and 32 non-BPD control neonates. The data were analyzed and interpreted by Fisher difference comparison, PLINK and eQTL association analysis, KEGG and GO enrichment analysis, STRING tool, Cytoscape software, ProtParam tool, HOPE online software, and GEOR2 analysis on NCBI GEO dataset. BPD has a highly heterogeneity in different populations, and we found 35 genes overlapped with previous whole-exon sequencing studies, such as APOB gene. Arterial and epithelial cell development and energy metabolism pathways affect BPD. In this study, 24 key genes were identified, and BIVM rs3825519 mutation leads to prolonged assisted ventilation in patients with BPD. A novel DDAH1 mutation site (NM_012137: exon1: c.89 T > G: p.L30R) was found in 9 BPD patients. CONCLUSION: BIVM gene rs3825519 mutation may play a role in the pathogenesis of BPD by affecting cilia movement, and the DDAH1 and APOB genes mutations may have a pathogenic role in BPD. WHAT IS KNOWN: • Genetic factors are involved in the occurrence of bronchopulmonary dysplasia. • The candidate genes have poor reproducibility and are influenced by ethnic heterogeneity, therefore, more exploration is still needed. WHAT IS NEW: • We identified the role of susceptible SNPs in BPD in Shenzhen, China, and identified 24 key genes that influence the pathogenesis of BPD, and also found 35 genes overlapped with previous whole exon sequencing studies, such as APOB gene. • We found that BIVM and DDAH1 genes may play a pathogenic role in the pathogenesis of BPD.

Cryopreservation of human dental roots using vitrification for autologous human tooth tissue banking.

This study aims to preliminarily evaluate the feasibility of autologous transplantation of tooth tissues cryopreserved with vitrification, by investigating the influence of cryopreservation with vitrification on human dental root, regarding the morphology, microhardness, cell apoptosis, proliferation and differentiation. Freshly extracted human permanent premolars were collected with crown removed. Dental roots were cryopreserved using a commercial vitrification medium (Kitazatousa). After six-month storage in liquid nitrogen, cryopreserved roots were thawed, and then evaluated using histological and immunohistochemical methods. Microhardness of dentine was measured with a Vickers indenter. Cells in periodontal ligament and dental pulp tissues were isolated and characterized. The proliferation, immunophenotype, apoptosis and differentiation ability of cells isolated from cryopreserved roots were evaluated. The data was analyzed using one-way analysis of variance (ANOVA) and Student's t-test. The gross and histological morphology of dental roots was not significantly changed after vitrification and thawing. A few tiny cracks were found in 3 of all 10 cryopreserved samples. No obvious changes were found in microstructure of dentine under SEM observation. Dental pulp cells and periodontal ligament cells were successfully isolated from tissues of cryopreserved human dental roots. There were also no significant differences of those periodontal ligament cells in the two groups regarding morphology, immunophenotype, viability, proliferation and apoptosis. The osteogenic and adipogenic differentiation capability of periodontal ligament cells was maintained by cryopreservation with vitrification. In the conditions of this study, cryopreservation with vitrification preserves cell survival, hardness and structural integrity of dental roots. Vitrification can be a potential way to preserve tooth tissue for future auto-transplantation and autologous cell therapy.

Human three-dimensional dental pulp organoid model for toxicity screening of dental materials on dental pulp cells and tissue.

AIM: To establish a 3D model for screening the biocompatibility of dental materials/drugs on dental pulp cells and tissue. METHODOLOGY: Human dental pulp cells (hDPC) and endothelial cells (EC) were mixed with or without human dental pulp derived extracellular matrix (hDP-ECM) according to several protocols and cultured in 3D plates to fabricate 3D organoids. Cell viability and proliferation in organoids were evaluated using Live/Dead cell viability assay and ATPase assay. Organoids were fixed, cut and stained with a H&E staining kit. The expressions of DSPP, DMP-1, CD31, vWF and COL1A in 3D organoids were evaluated using immunofluorescence. To assess the feasibility of 3D organoids on drug/material toxicity screening, the organoids were treated with lipopolysaccharides (LPS) or iRoot BP. Then, cell viability and apoptosis were assessed. The expressions of IL-6, TNF-α, and IL-1ß were compared in LPS-treated and non-treated organoids. Alizarin Red S staining was used to evaluate calcium deposit formation in organoids. Data were analysed using one-way anova followed by Tukey's post hoc comparison. RESULTS: The 3D spheres/organoids were formed at day 1 or day 2. Cells in 3D organoids maintained a high viability rate and low proliferation activity. The level of CD31 increased significantly (p < .05) when EC were added to coculture with hDPC. The expressions of odontogenesis-associated proteins (DSPP, COL1A) upregulated (p < .05) with the addition of hDP-ECM. Level of IL-6 expression and rates of dead and apoptotic cells in 3D organoids were increased significantly (p < .05) in response to LPS. Calcium deposit formation was observed in iRoot BP-treated organoids. CONCLUSIONS: Coculture of hDPC and EC in the presence of hDP-ECM formed functional dental pulp organoids. The experimental model provides an alternative tool for toxicity screening of dental pulp capping agents and dental pulp regeneration research.

Osthole enhances the immunosuppressive effects of bone marrow-derived mesenchymal stem cells by promoting the Fas/FasL system.

Thanks to the advantages of easy harvesting and escape from immune rejection, autologous bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for immunosuppressive therapy against inflammation and autoimmune diseases. However, the therapy is still challenging because the immunomodulatory properties of BMSCs are always impaired by immunopathogenesis in patients. Because of its reliable and extensive biological activities, osthole has received increased clinical attention. In this study, we found that BMSCs derived from osteoporosis donors were ineffective in cell therapy for experimental inflammatory colitis and osteoporosis. In vivo and in vitro tests showed that because of the down-regulation of Fas and FasL expression, the ability of osteoporotic BMSCs to induce T-cell apoptosis decreased. Through the application of osthole, we successfully restored the immunosuppressive ability of osteoporotic BMSCs and improved their treatment efficacy in experimental inflammatory colitis and osteoporosis. In addition, we found the immunomodulatory properties of BMSCs were enhanced after osthole pre-treatment. In this study, our data highlight a new approach of pharmacological modification (ie osthole) to improve the immune regulatory performance of BMSCs from a healthy or inflammatory microenvironment. The development of targeted strategies to enhance immunosuppressive therapy using BMSCs may be significantly improved by these findings.

Efficient biogenesis of Cu2O nanoparticles using extract of Camellia sinensis leaf: Evaluation of catalytic, cytotoxicity, antioxidant, and anti-human ovarian cancer properties.

At the moment, metallic nanoparticles especially copper nanoparticles are administrated for the cure of different disorders, such as tumor and cancer. In recent years, many chemotherapeutic supplements have been formulated by copper nanoparticles. In the present study, copper nanoparticles were prepared and synthesized in aqueous medium using Camellia sinensis leaf extract. The as-prepared Cu2O nanoparticles was thoroughly characterized using XRD, FT-IR, FESEM, EDX, TEM and X-ray elemental mapping techniques. The as-synthesized Cu2O/C. sinensis NPs applied as novel nanocatalyst for the synthesis of annulated fused pyrano[2,3-d]pyrimidinones via a one-pot, three-component condensation of a barbituric acid, aromatic aldehydes, and malonitrile or ethylcyanoacetate under mild condition at 25 °C. Main properties of this facile method are the involves an easy work-up procedure, avoidance of hazardous or polluting chemicals, significant yields under mild conditions, and one-pot reaction. We assessed the anti-human ovarian cancer potentials of these nanoparticles against Caov-3, SW-626, and SK-OV-3 cell lines. For investigating the antioxidant activities of CuCl2⋅2H2O, C. sinensis, and copper nanoparticles, the DPPH free radical test was used. For the determining of anti-human ovarian cancer properties of CuCl2⋅2H2O, Camellia sinensis leaf aqueous extract, copper nanoparticles, and Carboplatin (Standard positive control), MTT assay was used on normal (HUVECs) and human ovarian cancer (Caov-3, SW-626, and SK-OV-3) cell lines. Copper nanoparticles had high cell death and anti-human ovarian cancer properties against Caov-3, SW-626, and SK-OV-3 cell lines. Among the above cell lines, the best result was gained in the cell line of SW-626. According to the above findings, it looks copper nanoparticles green-synthesized by Camellia sinensis leaf aqueous extract have the potential to be used as a chemotherapeutic material for human ovarian cancers.

Pharmacokinetics, bioavailability and metabolism of neferine in rat by LC-MS/MS and LC-HRMS.

In this study, a simple and sensitive analytical method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of neferine in rat plasma. After acetonitrile-mediated protein precipitation, the samples were separated on an Acquity BEH C18 column (2.1 × 50 mm, 1.7 µm) maintained at 40°C. The mobile phase comprising 0.1% formic acid in water and acetonitrile was delivered at a flow rate of 0.4 ml/min. The mass detection was conducted using multiple reaction monitoring mode with ion transitions at 625.4 > 206.3 and m/z 622.9 > 380.9 for neferine and internal standard, respectively. The assay was demonstrated to be linear over the concentration range of 0.5-1,000 ng/ml, with correlation coefficient >0.999 (r > 0.999). The validated method was further applied to the pharmacokinetic study of neferine in rat plasma. In addition, the metabolism of neferine was investigated using high-resolution mass spectrometry. A total of six metabolites from rat liver microsomes and plasma were detected and their structures were identified according to their fragment ions. The proposed metabolic pathways of neferine were demethylation, dealkylation, dehydrogenation and glucuronidation.

Cancer Cell Membrane Vesicle for Multiplex MicroRNA Imaging in Living Cells.

Highly efficient cellular transfection and intracellular signal amplification is a prerequisite for low-abundant microRNA (miRNA) imaging and biomedical application. Herein, we report a functional cancer cell membrane (CM) vesicle, Au-P/DSN@CM (DSN, double-specific nucleases), which consists of Au nanoparticles modified with three types of fluorescent miRNA detection probes (Au-P) and DSN that simultaneously encapsulate in cancer CM. We find that the Au-P/DSN@CM could specifically target the cancer cell and transfect the cell with higher efficiency than Au nanoparticles. The internalized Au-P/DSN@CM could further specifically recognize the target miRNA and induce DSN-assisted target recycle signal amplification, leading to multiple miRNA simultaneous detection with high sensitivity. It successfully detects oncogenic miRNAs in MCF-7 cells with high sensitivity and is amenable to monitor the dynamic expression change of oncogenic miRNAs in cancer cells. Our study represents a promising gene delivery vector for cancer diagnosis and potential therapy.

CBFA2T2 promotes adipogenic differentiation of mesenchymal stem cells by regulating CEBPA.

The unique metabolic characteristics and diverse functions of marrow adipose tissue (MAT) have drawn more attention recently. Previously, we have reported that CBFA2T2 is required for BMP2-induced osteogenic differentiation of mesenchymal stem/stromal cells (MSCs). In the present study, we further investigated the role of CBFA2T2 in regulation of adipogenic differentiation in mouse bone marrow-derived MSCs (mBMSCs) and human dental pulp stem cells (hDPSCs). We found CBFA2T2 expression was dramatically upregulated during adipogenesis of mBMSCs and hDPSCs. More importantly, knockdown of CBFA2T2 in mBMSCs and hDPSCs significantly inhibited the process of adipogenic differentiation, as revealed by the expression of adipogenic markers and Oil Red O staining. Mechanistically, we found knockdown of CBFA2T2 led to an increase in H3K9me2 and H3K9me3 levels at promoter of CEBPA, an essential transcription factor of adipogenesis. Taken together, these findings suggest CBFA2T2 is key regulator of adipogenic differentiation of MSCs, and it may represent a therapeutic target for conditions with excessive MAT.

OIP5-AS1 contributes to tumorigenesis in hepatocellular carcinoma by miR-300/YY1-activated WNT pathway.

BACKGROUND: It has reported that long non-coding RNAs (lncRNAs) exerted regulatory functions by targeting specific genes through a competing endogenous RNA (ceRNA) pathway. LncRNA OIP5-AS1 has been identified as a tumor-enhancer in several tumor types. Nonetheless, its molecular mechanism in HCC remains to be masked. AIM OF THE STUDY: This study was aimed at exploring whether and how OIP5-AS1 exert functions in HCC. METHODS: qRT-PCR and western blot were employed for detecting gene expression. CCK-8, colony formation and EdU assays were implemented to evaluate the proliferative ability of HCC cells. Caspase-3 activity and flow cytometry analyses were implemented to determine cell apoptosis and cell cycle distribution. RNA pull down, ChIP, RIP and luciferase reporter assays explored the interplays between molecules. RESULTS: YY1 was upregulated in HCC cells, and silenced YY1 restrained HCC cell proliferation in vitro and hampered tumor growth in vivo. Later, we discovered that miR-300 could regulate WNT pathway via targeting YY1. Furthermore, OIP5-AS1 was identified as the sponge of miR-300 and promoted cell growth in HCC. Importantly, YY1 transcriptionally activate OIP5-AS1 in turn. Rescue experiments indicated that miR-300 inhibition or YY1 overexpression abrogated the inhibitive effect of OIP5-AS1 silencing on the malignant growth of HCC cells. CONCLUSIONS: OIP5-AS1/miR-300/YY1 feedback loop facilitates cell growth in HCC by activating WNT pathway.

iTRAQ-Based Proteomic Analysis Exploring the Influence of Hypoxia on the Proteome of Dental Pulp Stem Cells under 3D Culture.

Hypoxic preconditioning is commonly applied to enhance mesenchymal stem cells (MSCs) therapeutic effect before transplantation. Elucidating the effect of hypoxic preconditioning would be beneficial for improved application. However, the influence of hypoxia on dental tissue derived MSCs cultured in 3D was unknown. Thus, the present study is to investigate gene expression and proteome of dental pulp stem cells (DPSCs) after hypoxic preconditioning. DPSCs were isolated, cultured in a 3D system under the normoxic and hypoxic conditions. The gene expression was examined with reverse transcription polymerase chain reaction, and the proteome was analyzed using iTRAQ-based mass spectrometry. The expressions of HIF-1α, VEGFA, KDR at mRNA level was upregulated while BMP-2 was downregulated. Two thousand one hundred and fifteen proteins were identified and 57 proteins exhibited significant differences after hypoxic preconditioning (30 up-regulated, 27 down-regulated). Bioinformatic analysis revealed the majority of up-regulated proteins are involved in cellular process, angiogenesis, protein binding and transport, regulation of response to stimulus, metabolic processes, and immune response. Increased IL-6 and decreased TGF-1ß protein expression under hypoxic condition were verified by ELISA. Hypoxic preconditioning partly affected the gene and protein expression in DPSCs under 3D culture and may enhance the efficacy of MSCs transplantation.