Therapeutic effects and mechanism of human amnion-derived mesenchymal stem cells on hypercoagulability in a uremic calciphylaxis patient.

Calciphylaxis is a rare cutaneous vascular disease that manifests with intolerable pains, non-healing skin wounds, histologically characterized by calcification, fibrointimal hyperplasia, and microvessel thrombosis. Currently, there are no standardized guidelines for this disease. Recent studies have recognized a high prevalence of thrombophilias and hypercoagulable conditions in calciphylaxis patients. Here, we report a case of uremic calciphylaxis patient whom was refractory to conventional treatments and then received a salvage strategy with intravenous and local hAMSC application. In order to investigate the therapeutic mechanism of hAMSCs from the novel perspective of hypercoagulability, coagulation-related indicators, wound status, quality of life and skin biopsy were followed up. Polymerase chain reaction (PCR) was performed to determine the distribution of hAMSCs in multiple tissues including lung, kidney and muscle after infusion of hAMSCs for 24 h, 1 week and 1 month in mice aiming to investigate whether hAMSCs retain locally active roles after intravenous administration. Improvement of hypercoagulable condition involving correction of platelet, D-dimer and plasminogen levels, skin regeneration and pain alleviation were revealed after hAMSC administration over one-year period. Skin biopsy pathology suggested regenerative tissues after 1 month hAMSC application and full epidermal regeneration after 20 months hAMSC treatment. PCR analysis indicated that hAMSCs were homing in lung, kidney and muscle tissues of mice even until tail vein injection of hAMSCs for 1 month. We propose that hypercoagulability is a promising therapeutic target of calciphylaxis patients, which can be effectively improved by hAMSC treatment.

Alcohol Consumption and Risk of Atrial Fibrillation: A Dose-Response Meta-Analysis of Prospective Studies.

Background: This study aimed to investigate the dose-response association between alcohol consumption and atrial fibrillation (AF) risk. Methods: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched using keywords related to alcohol and AF from the establishment of databases up to 1 March 2021. Prospective studies examining the impact of alcohol on the risk of AF with hazard ratios (HRs) were included. Restricted cubic spline regression was performed to quantify the dose-response relationship between alcohol consumption and AF risk. Results: Thirteen eligible studies were included in the meta-analysis, with a total of 645,826 participants and 23,079 cases of AF. When compared with non-/seldom-drinkers, the pooled adjusted HRs of AF were 1.30 (95% confidence interval [CI]: 1.20-1.41) and 1.00 (95% CI: 0.96-1.05) for high and low alcohol consumption, respectively. Moderate alcohol intake significantly increased the risk of AF in males (HR, 1.21; 95% CI: 1.10-1.33) but not in females (HR, 1.02; 95% CI: 0.91-1.14). The cubic spline regression analysis illustrated that the risk of AF significantly increased with daily alcohol intake in a Non-linear manner (R2 = 0.64, P = 5.785 × 10-12). Conclusion: This study revealed a Non-linearly positive association between alcohol intake and the risk of AF. Low alcohol intake was not associated with the development of AF, whereas moderate alcohol intake significantly increased the risk of AF in males but not in females. Our meta-analysis highlighted that alcohol consumption should be restricted to a low level to reduce the risk of AF.

Repression of the Antioxidant Pyrroloquinoline Quinone in Skin Aging Induced by Bmi-1 Deficiency.

It is uncertain whether Bmi-1 deficiency could lead to skin aging by redox imbalance and DNA damage. In this study, we first confirmed that Bmi-1 had a relatively high expression level in the skin and Bmi-1 expression levels gradually decreased with age. Then, we studied the role of Bmi-1 in the skin using a Bmi-1-/- mouse model. Bmi-1-/- mice were supplemented with or without pyrroloquinoline quinone (PQQ) for 5 weeks, and their skin phenotypes were compared with Bmi1-/- and wild-type littermates. Our results showed that Bmi-1-/- mice displayed decreased vertical thickness of skin, sparse hair follicles, and thinner and more irregular collagen bundles. Mechanistically, increased oxidative stress with reducing antioxidant capacity and induced DNA damage occurred in Bmi-1-/- mice. Subsequently, this would lead to reduced cell proliferation, increased cell senescence and matrix metalloproteinases (MMPs), and the degradation of fibroblast function and further reduce collagen synthesis. All pathological alterations in the skin of Bmi-1-/- mice were alleviated by PQQ supplementation. These results demonstrated that Bmi-1 might play a key role in protection from skin aging by maintaining redox balance and inhibiting DNA damage response and will be a novel and potential target for preventing skin aging.

Quantitative proteomics reveals the regulatory networks of circular RNA BTBD7_hsa_circ_0000563 in human coronary artery.

BACKGROUND: BTBD7_hsa_circ_0000563, which is located on chromosome 14, contains conserved binding sites with miR-155/130a and RNA-binding proteins according to bioinformatic prediction. We investigated the association of BTBD7_hsa_circ_0000563 expression in coronary artery segments with atherosclerotic stenosis and identified the proteome-wide BTBD7_hsa_circ_0000563-regulated proteins in human coronary artery. METHODS: The atherosclerotic grade and extent in coronary artery segments were determined by hematoxylin and eosin staining. BTBD7_hsa_circ_0000563 expression in eight coronary artery segments from one patient was quantified by RT-qPCR assay. A proteomic approach was adopted to reveal significant differences in protein expression between among four groups differing in their BTBD7_hsa_circ_0000563 expression levels. RESULTS: The RT-qPCR assay revealed that coronary artery segments with severe atherosclerotic stenosis had significantly low BTBD7_hsa_circ_0000563 levels. The proteomic analysis identified 49 differentially expressed proteins among the segment groups with different BTBD7_hsa_circ_0000563 expression levels, of which 10 were downregulated and 39 were upregulated with increases in the BTBD7_hsa_circ_0000563 level. The 10 downregulated proteins were P61626 (LYSC_HUMAN), P02760 (AMBP_HUMAN), Q02985 (FHR3_HUMAN), P01701 (LV151_HUMAN), P06312(KV401_HUMAN), P01624 (KV315_HUMAN), P13671 (CO6_HUMAN), P01700(LV147_HUMAN), Q9Y287(ITM2B_HUMAN), and A0A075B6I0 (LV861_HUMAN). The top 10 upregulated proteins were Q92552 (RT27_HUMAN), Q9UJY1(HSPB8_HUMAN), Q9Y235(ABEC2_HUMAN), P19022 (CADH2_HUMAN), O43837(IDH3B_HUMAN), Q9H479(FN3K_HUMAN), Q9UM22(EPDR1_HUMAN), P48681(NEST_HUMAN), Q9NRP0(OSTC_HUMAN), and Q15628(TRADD_HUMAN). CONCLUSION: BTBD7_hsa_circ_0000563 is involved in the atherosclerotic changes in human coronary artery segments. Verification, mechanistic, and function studies are needed to confirm whether patients with coronary artery disease would benefit from such personalized medicine in the future.

Proteomic landscape of human coronary artery atherosclerosis.

In order to investigate novel biomarkers for the detection of coronary artery disease for effective therapeutic targets, a comprehensive understanding of the protein networks and protein expression abundance in coronary artery samples is required. This was established by means of liquid chromatography (LC)­mass spectrometry (MS)/MS analysis in the present study. A total of 20 human coronary artery specimens from 2 autopsied adults were employed in the present study. The natural history and histological classification of the atherosclerotic lesions of the coronary artery samples were analyzed by hematoxylin and eosin (H&E) staining, and the human coronary arterial proteome and proteomics features were characterized by MS analysis. The present study identified 2,135 proteins in the 20 coronary artery segments samples from the 2 cases. Combined with the results of H&E staining of the coronary artery samples, a total of 174 proteins, including 4 upregulated proteins and 164 downregulated proteins (excluding 6 proteins with inconsistent expression tendencies), were shown to be associated with coronary artery disease. In addition, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment of the differentially expressed proteins revealed that the mitochondrial energy metabolism may be responsible for the occurrence and development of coronary artery atherosclerosis. The human coronary arterial proteome can be considered as a complex network whose architectural characteristics vary considerably as a function of the presence or absence, and histological classification of coronary artery atherosclerosis. These data thus suggest that the prevention of mitochondrial dysfunction via the retrieval of the mitochondrial associated proteins expression may be a promising target in coronary artery disease.

Circular RNA profile in coronary artery disease.

Circular RNAs (circRNAs) are potential biomarkers and therapeutic targets of coronary artery disease due to their high stability, covalently closed structure. And implied roles in gene regulation. The aim of this study was to identify and characterize circRNAs from human coronary arteries. Epicardial coronary arteries were removed during the autopsy of an 81-year-old man who died from heart attack. The natural history and histological classification of atherosclerotic lesions in coronary artery segments were analyzed by hematoxylin and eosin staining, and their circRNA expression profiles were characterized by RNA sequencing. RNA sequencing identified 1259 annotated and 381 novel circRNAs. Combined with the results of histologic examination, intersection analysis identified 54 upregulated and 12 downregulated circRNAs, representing 4.0% of the total number. Coronary artery segments with or without severe atherosclerosis showed distinctly different circRNA profiles on the basis of hierarchical clustering. Our results suggest that these 66 circRNAs contribute to the pathology underlying coronary artery atherosclerosis and may serve as diagnostic or therapeutic targets in coronary artery disease.

An overview of the roles and responsibilities of Chinese medical colleges in body donation programs.

The use of human tissue is critical for gross anatomy education in the health professions. Chinese medical colleges have faced a shortage of anatomical specimens over the past decade. While body donation plays an important role in overcoming this gap, this practice has only recently been introduced in China, and the donation rate is relatively low and fraught with a number of difficulties. In the past, traditional Chinese culture focused on preserving the human body intact, which often limited body donation. In recent years, the public has become more open toward body donation. At Nanjing Medical University, only 20 bodies were donated in 2001. After the university became involved in an organized body donation program, this number increased to 70 donated bodies per year (2007 to 2012). This article describes and reviews Chinese medical colleges as a special case study among body donation programs, particularly in terms of the multiple responsibilities and roles that such institutions must assume in the course of adopting these programs. Medical colleges in China must serve as advocates, coordinators, builders, managers, educators, and beneficiaries in undertaking body donation programs. It is important for medical colleges to recognize these pluripotent roles and educate the public in order to promote body donation programs. This case study may also effectively guide and encourage Chinese medical colleges in refining their own body donation programs in the future.