An examination of the status, contexts of anatomical body donation, and perspectives in China.

Body donation is a valuable resource in medical education, research, clinical diagnosis, and treatment. Consequently, donors are honored as "Silent Mentors" in Chinese medical schools. This article briefly reviews the history, current status, and strategies to promote body donation in China (excluding data from Hong Kong, Macao, and Taiwan regions) and discusses the problems encountered in body donation work in China. After establishing the People's Republic of China in 1949, the central government issued regulations on the use of dissected bodies. In 2001, the "Shanghai Regulations on Body Donation" were officially implemented and became China's first local legislative regulation on body donation. Subsequently, local legislative regulations and rules on body donation were issued in various regions to promote smooth and orderly body donation. There has been tremendous development in body donation in China for more than 40 years; however, the progress of this partial work has been uneven in various areas owing to the influence of traditional ethical concepts. It is, therefore, imperative to legislate body donations at a national level. Raising the public's scientific literacy and changing the traditional concept of funerals can create a positive social atmosphere for body donation, thus increasing the public's awareness and willingness to donate their bodies. Donating the body at the end of life contributes to life science and medical causes and is a noble act worthy of praise.

Clinical Analysis of Improved Particle Swarm Algorithm-Based Magnetic Resonance Imaging Diagnosis of Placenta Accreta.

The magnetic resonance imaging (MRI) image processing capabilities were investigated based on the improved particle swarm optimization (IPSO) algorithm, and the clinical application analysis of MRI images in the diagnosis of placenta accreta (PA) was evaluated in this study. The MRI uterine images were detected on the basis of IPSO. Besides, the clinical data of 89 patients with PA were selected and collected, who were diagnosed by clinical cesarean section surgery and pathological comprehensive diagnosis in hospital from January 2018 to July 2020. Then, all of them underwent the ultrasound (US) and MRI examinations, and the differences of sensitivity, specificity, and accuracy between MRI and US under IPSO in the diagnosis of PA were compared, as well as the differences in the diagnosis of adhesive, implantable, and penetrated PA. The results showed that the difference in detection between IPSO-based MRI images and US images was not statistically substantial (p > 0.05), but the number of initial detections was higher than the number of US examination. MRI examination had higher sensitivity and specificity in the diagnosis of PA during pregnancy, especially for implantable PA, compared with US examination (p < 0.05). In conclusion, MRI images based on the improved particle swarm optimization algorithm showed a good application effect in the diagnosis of placental implantation diseases, which was worthy of further promotion in clinical practice.

Down-regulated placental miR-21 contributes to preeclampsia through targeting RASA1.

Human placenta was obtained from early onset preeclampsia, late onset preeclampsia, and their gestational age-matched normal pregnancy. Using RT-qPCR, western blot, and immunohistochemistry, it was demonstrated that miR-21 expressions were significantly decreased in preeclampsia while RASA1 were increased. Suppression of miR-21 in placental HTR-8/SVneo cells, remarkably upregulated RASA1, decreased proliferation, inhibited invasion, and promoted apoptosis of trophoblast cells, while overexpression of miR-21 alleviated these effects. Dual-luciferase reporter assays revealed RASA1 to be a direct target of miR-21 in trophoblast cells. miR-21 may serve key roles in the development of preeclampsia by targeting RASA1.

AT1R Regulates Macrophage Polarization Through YAP and Regulates Aortic Dissection Incidence.

Aortic dissection (AD) is one of the most fatal cardiovascular emergency. At the anatomical level, AD occurs due to the formation of intimal tears. However, the molecular mechanism underlying this phenomenon remains unknown. Angiotensin II (Ang II) is a important effector in the development of cardiovascular disease that acts through binding to angiotensin type 1 receptor (AT1R). Yes-associated protein (YAP) was recently recognized as a key protein in macrophage activation. To determine whether AT1R and YAP are involved in macrophage-induced endothelial cell (EC) inflammation and AD incidence, we co-cultured THP-1 cells and HAECs in transwell chambers under different culture conditions and apply different conditions to the AD mice model. The results showed that Ang II promoted macrophage M1 polarization and adhesion, upregulated YAP phosphorylation, and induced EC injury that was related to increased levels of multiple pro-inflammatory chemokines. Blocking AT1R function pharmacologically or by transfection with AT1R siRNA can reduce the pro-inflammatory effect induced by Ang II. In addition, siRNA knock down of YAP expression further aggravated the pro-inflammatory effects of Ang II. Treatment with ARB effectively alleviated these pro-inflammatory effects. In the mice AD model, ARB effectively reduced the incidence of AD in mice, decreased M1 macrophages infiltration and AT1R content in the aortic wall and increased the tissue content of YAP. We found that AT1R induces YAP phosphorylation through binding to Ang II, and further promotes macrophage M1 polarization and adhesion to ECs. ARB reduces the incidence of AD in mice and affect macrophage polarization in mice aorta.

The role of bFGF in preventing the shrinkage of cardiac progenitor cell-engineered conduction tissue by downregulating α-SMA expression.

AIMS: Engineered conduction tissues (ECTs) fabricated from cardiac progenitor cells (CPCs) and collagen sponges were precisely targeted for the treatment of atrioventricular conduction block in our previous studies. However, obvious shrinkage and deformation of ECTs was observed during in vitro culture. According to the literature, it can be speculated that basic fibroblast growth factor (bFGF) may downregulate alpha-smooth muscle actin (α-SMA) produced by CPCs to prevent the shrinkage of CPC-engineered conduction tissues. MAIN METHODS: In this study, culture media with or without bFGF were used for both cell culture and 3D tissue construction. The expression of α-SMA and the size change of engineered tissue were analyzed to evaluate the feasibility of adding bFGF to regulate α-SMA expression and shrinkage of constructs. In addition, cardiac-specific examinations were performed to evaluate the effect of bFGF on cardiac tissue formation. KEY FINDINGS: Supplementation with bFGF efficiently relieved shrinkage of engineered tissue by downregulating the expression of α-SMA at both the cellular and 3D tissue levels. Moreover, bFGF had a positive influence on cardiac tissue formation in terms of cell viability, tissue organization and electrical conduction velocity. SIGNIFICANCE: This study provides a guide for both shape control and quality improvement of CPC-engineered cardiac tissues.

Identification of Diagnostic CpG Signatures in Patients with Gestational Diabetes Mellitus via Epigenome-Wide Association Study Integrated with Machine Learning.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most prevalent metabolic disease during pregnancy, but the diagnosis is controversial and lagging partly due to the lack of useful biomarkers. CpG methylation is involved in the development of GDM. However, the specific CpG methylation sites serving as diagnostic biomarkers of GDM remain unclear. Here, we aimed to explore CpG signatures and establish the predicting model for the GDM diagnosis. METHODS: DNA methylation data of GSE88929 and GSE102177 were obtained from the GEO database, followed by the epigenome-wide association study (EWAS). GO and KEGG pathway analyses were performed by using the clusterProfiler package of R. The PPI network was constructed in the STRING database and Cytoscape software. The SVM model was established, in which the ß-values of selected CpG sites were the predictor variable and the occurrence of GDM was the outcome variable. RESULTS: We identified 62 significant CpG methylation sites in the GDM samples compared with the control samples. GO and KEGG analyses based on the 62 CpG sites demonstrated that several essential cellular processes and signaling pathways were enriched in the system. A total of 12 hub genes related to the identified CpG sites were found in the PPI network. The SVM model based on the selected CpGs within the promoter region, including cg00922748, cg05216211, cg05376185, cg06617468, cg17097119, and cg22385669, was established, and the AUC values of the training set and testing set in the model were 0.8138 and 0.7576. The AUC value of the independent validation set of GSE102177 was 0.6667. CONCLUSION: We identified potential diagnostic CpG signatures by EWAS integrated with the SVM model. The SVM model based on the identified 6 CpG sites reliably predicted the GDM occurrence, contributing to the diagnosis of GDM. Our finding provides new insights into the cross-application of EWAS and machine learning in GDM investigation.

Naringenin prevents pregnancy-induced hypertension via suppression of JAK/STAT3 signalling pathway in mice.

BACKGROUND: Pregnancy-induced hypertension (PIH) is characterized by high blood pressure during pregnancy, which causes perinatal and maternal mortality. Inflammation, oxidative stress and the JAK2/STAT3 signalling pathway have been reported to play critical roles in the pathogenies of PIH. Due to the safety and side effects of current treatments for PIH, searching for new therapeutic agents is urgently needed. Naringenin is a flavonoid with anti-inflammation and anti-oxidation activities. In the current study, the effects of naringenin on PIH were investigated. METHODS: We established the PIH mouse model and administrated naringenin to these mice. The blood pressure, total urine protein, plasma levels of vasodilation converting enzyme (VCE), α-1A adrenergic receptor (α-ADR) and angiotensin, inflammatory cytokines, oxidative stress markers were measured. The protein levels of reactive oxygen species proto-oncogene 1 (ROS1), superoxide dismutase 2 (SOD2), signal transducer and activator of transcription 3 (STAT3), phospho-STAT3, Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), Janus kinase 2 (JAK2) and phospho-JAK2, in vascular endothelium cells were detected by western blot. RESULTS: Administration of naringenin significantly decreased blood pressure, total urine protein level, plasma levels of VCE, α-ADR and angiotensin in PIH mice. Naringenin decreased serum levels of pro-inflammatory cytokines interleukin (IL)-2, IL-6 and tumour necrosis factor alpha (TNF-α), while increased IL-10. Naringenin decreased serum levels of ROS, endothelin while increased SOD and nitric oxide levels. Western blot analysis showed that naringenin inhibited ROS expression, while increased SOD expression in vascular endothelial cells of mice. In addition, western blot also showed that naringenin inhibited JAK2/STAT3 signalling by suppressing SHP-1 expression in vascular endothelial cells of mice. CONCLUSION: Naringenin suppressed the activation of JAK2/STAT3 signalling pathway and promoted SHP-1 expression, leading to ameliorated hypertension in pregnancy.

Regulative effect of maternal serum fatty acid-binding protein 4 on insulin resistance and the development of gestational diabetes mellitus.

Fatty acid binding protein 4 (FABP4) was found to be closely correlated with gestational diabetes mellitus (GDM), a severe pregnancy syndrome. However, safe and efficient treatment for GDM is limited. We aimed to investigate whether inhibition of FABP4 could ameliorate GDM and the underlying mechanism. An evaluation of blood samples from a total of 109 patients showed significantly positive correlations between serum FABP4 and biochemical parameters known to associate with GDM. This correlation was subsequently explored in vitro. FABP4 inhibition was achieved using BMS309403 in GDM mice. GDM related symptoms, including insulin resistance and macrophage infiltration in the adipose tissues, were measured. Lipid metabolism in 3T3-L1 adipocytes was tested. We firstly confirmed the positive correlations between serum FABP4, insulin resistance and inflammation cytokines, including tumor necrosis factor-α (TNF) and interleukin-6 (IL-6), in GDM patients. Surprisingly, inhibition of FABP4 by BMS309403 resulted in significant alleviation of GDM symptoms in GDM mouse model. BMS309403 improved glucose and insulin tolerance and transcriptionally repressed the levels of TNF-α and IL-6, suggesting a role of FABP4 in inflammation. Furthermore, macrophage infiltration into the adipose tissues was dramatically decreased in the BMS309403-treated GDM mice compared to untreated GDM mice. Interestingly, incubation of 3T3-L1 adipocytes with FABP4 protein decreased the mRNA and protein levels of peroxisome proliferator-activated receptor γ (PPARγ), which was absent when BMS309403 was used. However, lipid accumulation was promoted in FABP4-treated 3T3-L1 adipocytes which showed no change in the presence of BMS309403. In conclusion, inhibition of FABP4 by BMS309403 could be an effective treatment to alleviate GDM.

The Role of Macrophages in Aortic Dissection.

Aortic dissection (AD) is a fatal disease that accounts for a large proportion of aortic-related deaths and has an incidence of about 3-4 per 100,000 individuals every year. Recent studies have found that inflammation plays an important role in the development of AD, and that macrophages are the hub of inflammation in the aortic wall. Aortic samples from AD patients reveal a large amount of macrophage infiltration. The sites of macrophage infiltration and activity vary throughout the different stages of AD, with involvement even in the tissue repair phase of AD. Angiotensin II has been shown to be an important factor in the stimulation of macrophage activity. Stimulated macrophages can secrete metalloproteinases, inflammatory factors and other substances to cause matrix destruction, smooth muscle cell apoptosis, neovascularization and more, all of which destroy the aortic wall structure. At the same time, there are a number of factors that regulate macrophages to reduce the formation of AD and induce the repair of torn aortic tissues. The aim of this review is to take a close look at the roles of macrophages throughout the course of AD disease.

Conserved peptides enhance immune efficiency of inactive vaccines against emerging avian influenza viruses in chicken.

Avian influenza viruses (AIVs) such as H5N1 and H7N9 are a great threat to poultry economics and public health. Vaccination can effectively inhibit the spread of AIV in poultry, which is also a viable strategy for controlling virus transmission from poultry to human. Adjuvants that are commonly used in current inactivated vaccines to provide stronger anti-AIV immune responses are often limited in their capacity to quantitatively induce both humoral and cellular immune responses. Herein, we assessed the levels of immune responses generated by a vaccine formulation comprising inactivated H5N1 antigen and synthetic peptides covering conserved CD4+, CD8+ T cell, and B cell epitopes. We found that the synthetic peptides enhanced the antibody responses against conserved influenza virus antigen M2e. Notably, the hemagglutination inhibition test results indicated that the peptides significantly augmented the antibody responses of inactivated H5N1 antigen even in the 1/10 or 1/5 dose group, in the identical antibody level as antigen alone used at the full dose. This indicates that the peptide can significantly reduce the use of inactivated virus, lowering the cost of the vaccine. Moreover, the peptides increased the transcript levels of interleukin-4 and interferon-γ cytokines in chicken peripheral blood mononuclear cells, which may facilitate both humoral and cellular immune responses. Our data suggest that this peptide combined with inactivated H5N1 antigen enhances both the humoral and cellular immune responses, which may benefit the prediction and design of synthetic peptide-based adjuvants for vaccines in chicken.