Association between Vitamin D receptor (VDR) gene polymorphisms and hypertensive disorders of pregnancy: a systematic review and meta-analysis.

Background: Hypertensive disorders of pregnancy (HDP) are currently one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Recent studies provide evidence that maternal Vitamin D receptor (VDR) gene polymorphisms probably play a key role by affecting the biological function of vitamin D in some adverse pregnancy outcomes, while the relationship between the VDR gene polymorphisms and the risk of HDP remains controversial in current studies. This systematic review and meta-analysis aimed to comprehensively evaluate the association of the VDR gene polymorphisms with HDP susceptibility. Methods: This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and a protocol has been registered in the PROSPERO (ID: CRD42022344383) before commencing this review. PubMed, Web of Science, Embase, and the Cochrane Library databases were searched until January 21, 2023. Case-control and cohort studies that reported the association of the VDR gene polymorphisms with HDP were included. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for non-randomized studies. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) of the five models (allele model, dominant model, recessive model, homozygous model, heterozygous model) were pooled respectively, and subgroup analysis was performed based on ethnicity. Results: A total of ten studies were included. The VDR gene ApaI polymorphism was associated with HDP susceptibility in the dominant model (OR: 1.38; 95% CI [1.07-1.79]; P = 0.014) and the heterozygote model (OR: 1.48; 95% CI [1.12-1.95]; P = 0.006). In subgroup analysis, the heterozygote model (OR: 2.06; 95% CI [1.21-3.52]; P = 0.008) of the ApaI polymorphism was associated with HDP in Asians, but not in Caucasians. Conclusion: The VDR gene ApaI polymorphism may be associated with HDP susceptibility. Insufficient evidence to support the existence of ethnic differences in this association.

Characterization and microRNA Expression Analysis of Serum-Derived Extracellular Vesicles in Severe Liver Injury from Chronic HBV Infection.

BACKGROUND: Extracellular vesicle (EV) microRNAs have been documented in several studies to have significantly different expressions in hepatitis B virus (HBV)-related liver diseases, such as hepatocellular carcinoma (HCC). The current work aimed to observe the characteristics of EVs and EV miRNA expressions in patients with severe liver injury chronic hepatitis B (CHB) and patients with HBV-associated decompensated cirrhosis (DeCi). METHODS: The characterization of the EVs in the serum was carried out for three different groups, namely, patients with severe liver injury-CHB, patients with DeCi, and healthy controls. EV miRNAs were analyzed using miRNA-seq and RT-qPCR arrays. Additionally, we assessed the predictive and observational values of the miRNAs with significant differential expressions in serum EVs. RESULTS: Patients with severe liver injury-CHB had the highest EV concentrations when compared to the normal controls (NCs) and patients with DeCi (p < 0.001). The miRNA-seq of the NC and severe liver injury-CHB groups identified 268 differentially expressed miRNAs (|FC| > 2, p < 0.05). In this case, 15 miRNAs were verified using RT-qPCR, and it was found that novel-miR-172-5p and miR-1285-5p in the severe liver injury-CHB group showed marked downregulation in comparison to the NC group (p < 0.001). Furthermore, compared with the NC group, three EV miRNAs (novel-miR-172-5p, miR-1285-5p, and miR-335-5p) in the DeCi group showed various degrees of downregulated expression. However, when comparing the DeCi group with the severe liver injury-CHB group, only the expression of miR-335-5p in the DeCi group decreased significantly (p < 0.05). For the severe liver injury-CHB and DeCi groups, the addition of miR-335-5p improved the predictive accuracy of the serological levels, while miR-335-5p was significantly correlated with ALT, AST, AST/ALT, GGT, and AFP. Conclusions: The patients with severe liver injury-CHB had the highest number of EVs. The combination of novel-miR-172-5p and miR-1285-5p in serum EVs helped in predicting the progression of the NCs to severe liver injury-CHB, while the addition of EV miR-335-5p improved the serological accuracy of predicting the progression of severe liver injury-CHB to DeCi.

Application of mesenchymal stem cells in tumor therapy. / 间å 质干细胞在肿瘤治疗中的应用.

Mesenchymal stem cells (MSCs) are multipotent stem cells that exist widely in the human body, which can self-renewal and differentiate into different types of cell. Due to its advantages of tumor tissue tropism and easy to be engineered, it has been widely used in cancer treatment research recently. However, the tumor-promoting or anti-tumor effect of MSCs is controversial, especially for unmodified MSCs. Therefore, researchers are more inclined to use MSCs as carriers to engineer them. With the deepening in understanding of vesicles, it is found that the vesicles derived from MSCs seem to have greater advantages as carriers. Although the current research of MSCs in the treatment of tumors has been initiated in the clinic, there are still many problems to be solved in the pre-clinical application.

Global metabolomic and lipidomic analysis reveals the potential mechanisms of hemolysis effect of Ophiopogonin D and Ophiopogonin D' in vivo.

BACKGROUND: OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI. METHODS: Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids. RESULTS: Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism. CONCLUSIONS: This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.

Hyperuricemia is an independent risk factor for renal pathological damage and poor prognosis in lupus nephritis patients.

OBJECTIVE: To explore the correlation between hyperuricemia and renal damage in patients with lupus nephritis (LN).
 Methods: The data for clinical features, laboratory and renal pathological examination were collected from 177 renal biopsy-proven LN patients with or without hyperuricemia and were retrospectively analyzed to determine the correlation between serum uric acid and renal damage.
 Results: LN patients with hyperuricemia group had higher rate of hypertension and higher level of blood urea nitrogen and serum creatinine while lower estimated glomerular filtration rate (eGFR) and lower positive rate of anti-U1RNP antibody (P<0.05). In the LN patients with hyperuricemia group, renal pathological scores, including acitive index, chronic index and tubulointerstitial lesions, were higher than those in the LN patients without hyperuricemia group (P<0.05). The level of serum uric acid was positively correlated with serum creatinine, renal pathological classification and renal pathological scores while negatively correlated with eGFR (P<0.05).
 Conclusion: LN patients with hyperuricemia are associated with more serious renal damage. Hyperuricemia is an important predictor for poor prognosis in patients with LN.

Cardioprotection of Shenfu preparata on cardiac myocytes through cytochrome P450 2J3.

OBJECTIVE: To evaluate whether Shenfu injection (SFI) protects against cardiac myocyte injury induced by Fupian injection (FPI) in vitro. METHODS: H9c2 cells were separately treated with FPI, Renshen injection (RSI) and SFI. Cell viability, lactate dehydrogenase (LDH) release, spontaneous beating rate of primative cardical cells, caspase-3/7 activity, cell apoptosis, and cytochrome P450 2J3 (CYP2J3) mRNA expression were analyzed. RESULTS: The viability of H9c2 cells treated with SFI (37 and 75 mg/mL) was significantly higher than that of H9c2 cells treated with FPI (25 and 50 mg/mL) (P<0.05, P<0.01, respectively). LDH activity of H9c2 cells treated with SFI (75 mg/mL) was significantly decreased (P<0.01) compared with that of H9c2 cells treated with FPI (50 mg/mL). SFI (150 mg/mL) significantly attenuated FPI (100 mg/mL)-induced spontaneous beating rate decrease in primary myocardial cells after 4-hour treatment. Compared with FPI (12 and 25 mg/mL), SFI (18 and 37 mg/mL) treatment could effectively reverse the change of caspase-3/7 activity (P<0.01 and P<0.01, respectively). Compared with FPI (6 and 25 mg/mL), apoptotic cells decreased significantly (P<0.05, P<0.01, respectively) when H9c2 cells were incubated with SFI (9 and 37 mg/mL). The expression of CYP2J3 mRNA was down-regulated by FPI, while RSI and SFI could up-regulate the expression of CYP2J3 (P<0.01), which suggested the potential mechanism of protection of RSI against cardiac myocyte damage induced by FPI treatment. CONCLUSION: These observations indicate that SFI has the potential to exert cardioprotective effects against FPI toxicity. The effect was possibly correlated with the activation of CYP2J3.

Association between elevated visfatin and carotid atherosclerosis in patients with chronic kidney disease.

OBJECTIVE: To determine the levels of visfatin in patients with chronic kidney disease (CKD) and to explore the relationship between visfatin levels and caroid atherosclerosis in CKD patients. METHODS: A total of 180 CKD patients (102 non-dialyzed patients and 78 dialysis patients) and 42 healthy subjects enrolled in this study. The serum levels of visfatin, IL-6, and high sensitive C-reactive protein (hsCRP) were measured by ELISA. Common carotid arteries intima-media thickness (CCA-IMT), cross-sectional calculated intima-media thickness (c IMT) area and atherosclerotic plaque were detected by non-invasive high-resolution B-mode ultrasonography. RESULTS: The serum levels of visfatin, IL-6 and hsCRP were significantly increased in CKD patients compared with age matched healthy subjects (P<0.01). The serum levels of visfatin, IL-6 and hsCRP in the dialyzed patients were significantly higher than those in non-dialyzed patients (P<0.05). Visfatin levels increased with the progression of renal dysfunction and inversely related to creatinine clearance (Ccr) in non-dialyzed patients (r=-0.415, P<0.05). Patients with carotid artery plaques showed significantly higher levels of visfatin[(34.22±7.96) ng/mL)] compared with those without plaques [(28.24±6.18) ng/mL, P<0.05]. The serum levels of visfatin were closely correlated with IL-6 (r=0.548, P<0.001), hsCRP (r=0.430, P<0.001), CCA-IMT (r=0.462, P<0.05), and c IMT area (r=0.411, P<0.05). After adjusting for GFR, age, gender, and other risk factors associated with atherosclerosis, multiple stepwise regression analysis showed that serum visfatin is a independent risk factor for CCA-IMT (ß=0.433, P<0.01) and c IMT area (ß=0.412, P<0.01). CONCLUSION: The serum level of visfatin increase with the progression of CKD and should be considered to be a new risk factor for atherosclerosis in CKD.