Menstrual blood-derived mesenchymal stem cells combined with collagen I gel as a regenerative therapeutic strategy for degenerated disc after discectomy in rats.

BACKGROUND: Annulus fibrosis (AF) defects have been identified as the primary cause of disc herniation relapse and subsequent disc degeneration following discectomy. Stem cell-based tissue engineering offers a promising approach for structural repair. Menstrual blood-derived mesenchymal stem cells (MenSCs), a type of adult stem cell, have gained attention as an appealing source for clinical applications due to their potential for structure regeneration, with ease of acquisition and regardless of ethical issues. METHODS: The differential potential of MenSCs cocultured with AF cells was examined by the expression of collagen I, SCX, and CD146 using immunofluorescence. Western blot and ELISA were used to examine the expression of TGF-ß and IGF-I in coculture system. An AF defect animal model was established in tail disc of Sprague-Dawley rats (males, 8 weeks old). An injectable gel containing MenSCs (about 1*106/ml) was fabricated and transplanted into the AF defects immediately after the animal model establishment, to evaluate its repairment properties. Disc degeneration was assessed via magnetic resonance (MR) imaging and histological staining. Immunohistochemical analysis was performed to assess the expression of aggrecan, MMP13, TGF-ß and IGF-I in discs with different treatments. Apoptosis in the discs was evaluated using TUNEL, caspase3, and caspase 8 immunofluorescence staining. RESULTS: Coculturing MenSCs with AF cells demonstrated ability to express collagen I and biomarkers of AF cells. Moreover, the coculture system presented upregulation of the growth factors TGF-ß and IGF-I. After 12 weeks, discs treated with MenSCs gel exhibited significantly lower Pffirrmann scores (2.29 ± 0.18), compared to discs treated with MenSCs (3.43 ± 0.37, p < 0.05) or gel (3.71 ± 0.29, p < 0.01) alone. There is significant higher MR index in disc treated with MenSCs gel than that treated with MenSCs (0.51 ± 0.05 vs. 0.24 ± 0.04, p < 0.01) or gel (0.51 ± 0.05 vs. 0.26 ± 0.06, p < 0.01) alone. Additionally, MenSCs gel demonstrated preservation of the structure of degenerated discs, as indicated by histological scoring (5.43 ± 0.43 vs. 9.71 ± 1.04 in MenSCs group and 10.86 ± 0.63 in gel group, both p < 0.01), increased aggrecan expression, and decreased MMP13 expression in vivo. Furthermore, the percentage of TUNEL and caspase 3-positive cells in the disc treated with MenSCs Gel was significantly lower than those treated with gel alone and MenSCs alone. The expression of TGF-ß and IGF-I was higher in discs treated with MenSCs gel or MenSCs alone than in those treated with gel alone. CONCLUSION: MenSCs embedded in collagen I gel has the potential to preserve the disc structure and prevent disc degeneration after discectomy, which was probably attributed to the paracrine of growth factors of MenSCs.

Low Level of Vitamin D is a Risk Factor for the Occurrence of Early and Late Onset Pre-Eclampsia in Pregnant Women.

BACKGROUND: This study was aimed to investigate the relationship between 25-hydroxy vitamin D (25(OH)D) level and the occurrence of pre-eclampsia (PE) and also the risk factors of developing early and late onset PE. METHODS: A total of 370 pregnant women were included between January 2015 and December 2016 at our hospital. PE was defined as the presence of maternal blood pressure > 140/90 mmHg and 24-hour proteinuria levels > 300 mg or 2 + in a random sample of urine after the 20th week of pregnancy. Controls were pregnant women without hypertension and proteinuria. Assessment of 25(OH)D was performed at 16 - 20 weeks of gestation. Univariate and multivariate analyses were used to evaluate the association of vitamin D with PE. RESULTS: There were 201 patients with PE while 169 pregnant women were controls. Patients with PE had older maternal age (p < 0.001), earlier gestation age (p < 0.001), and higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p < 0.001). The level of 25(OH)D in the PE group (17.26 ± 13.95 µg/L) was significantly lower than that in controls (22.15 ± 12.65 µg/L, p = 0.019). Moreover, the proportion of 25(OH)D deficiency in patients with PE was significantly higher than that of controls (27.6% vs. 0.9%, p < 0.001). Older age, high SBP, and low level of 25(OH)D were independent risk factors of both early and late onset PE during pregnancy. CONCLUSIONS: Low 25(OH)D level was more likely presented in PE patients and was an independent risk factor of both early and late onset PE.

Hsa-microRNA-181a is a regulator of a number of cancer genes and a biomarker for endometrial carcinoma in patients: a bioinformatic and clinical study and the therapeutic implication.

The aberrant expression of human microRNA-181a-1 (hsa-miR-181a) has been implicated in the pathogenesis of various cancers, serving as an oncogene or a tumor suppressor. However, the role of hsa-miR-181a in the pathogenesis of endometrial carcinoma (EC) and its clinical significance are unclear. This study aimed to search for the molecular targets of hsa-miR-181a using bioinformatic tools and then determine the expression levels of hsa-miR-181a in normal, hyperplasia, and EC samples from humans. To predict the targets of hsa-miR-181a, ten different algorithms were used, including miRanda-mirSVR, DIANA microT v5.0, miRDB, RNA22 v2, TargetMiner, TargetScan 6.2, PicTar, MicroCosm Targets v5, and miRWALK. Two algorithms, TarBase 6.0 and miRTarBase, were used to identify the validated targets of hsa-miR-181a-5p (a mature product of hsa-miR-181a), and the web-based Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.7 was used to provide biological functional interpretation of the validated targets of hsa-miR-181a-5p. A total of 78 formalin-fixed, paraffin-embedded tissue specimens from 65 patients and 13 healthy subjects were collected and examined, including normal endometrium (n=13), endometrial hyperplasia (n=18), and EC (37 type I and 10 type II EC cases). Our bioinformatic studies have showed that hsa-miR-181a might regulate a large number of target genes that are important in the regulation of critical cell processes, such as cell fate, cell survival, metabolism, and cell death. To date, 313 targets of hsa-miR-181a have been validated, and 22 of these targets are cancer genes. The precision of predictions by all the algorithms for hsa-miR-181a-1's targets was low. Many of these genes are involved in tumorigenesis of various cancers, including EC, based on the DAVID and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In comparison with normal endometrial tissue, the expression level of hsa-miR-181a was significantly increased in type I and type II EC (P<0.05), and type II EC exhibited a significant higher expression level of hsa-miR-181a than that in type I EC (P<0.05). In addition, there was a significant increase in the expression level of hsa-miR-181a in type II EC compared with endometrial hyperplasia (P<0.05). Taken together, these results suggest that hsa-miR-181a may serve as an oncogene in endometrial tumorigenesis and that hsa-miR-181a might be used as a new biomarker in the prediction of prognosis of EC in clinical practice. More functional and mechanistic studies are needed to validate the role of hsa-miR-181a in the development, progression, and metastasis of EC.

Bisphosphonates for the prevention and treatment of osteoporosis in patients with rheumatic diseases: a systematic review and meta-analysis.

BACKGROUND: While bisphosphonates (BPs) are commonly used in clinical treatment for osteoporosis, their roles on osteoporosis treatment for rheumatic patients remain unclear. We performed a meta-analysis to evaluate the efficacy of BPs on fractures prevention and bone mass preserving in rheumatic patients. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed, EmBase, and the Cochrane Central Register of Controlled Trials for relevant literatures with a time limit of Jan. 6, 2012. All randomized clinical trials of BPs for adult rheumatic patients with a follow-up of 6 months or more were included. We calculated relative risks (RRs) for fractures and weighted mean difference (WMD) for percent change of bone mineral density (BMD). Twenty trials were included for analysis. The RR in rheumatic patients treated with BPs was 0.61 (95%CI [0.44, 0.83], P = 0.002) for vertebral fractures, and 0.49 (95%CI [0.23, 1.02], P = 0.06) for non-vertebral fractures. The WMD of BMD change in the lumbar spine was 3.72% (95%CI [2.72, 4.72], P<0.001) at 6 months, 3.67% (95%CI [2.84, 4.50], P<0.001) at 12 months, 3.64% (95%CI [2.59, 4.69], P<0.001) at 24 months, and 5.87% (95%CI [4.59, 7.15], P<0.001) at 36 months in patients using BPs, as compared with those treated with calcium, vitamin D or calcitonin. In subgroup analyses, rheumatic patients using BPs for osteoporosis prevention had greater WMD than those using BPs for treating osteoporosis at 6 months (4.53% vs. 2.73%, P = 0.05) and 12 months (4.93% vs. 2.91%, P = 0.01). CONCLUSIONS/SIGNIFICANCE: In both short-term and middle-term, BPs can preserve bone mass and reduce the incidence of vertebral fractures in rheumatic patients, mainly for those who have GC consumption. The efficacy of BPs is better when using BPs to prevent rather than to treat osteoporosis in rheumatic patients.