Application of mesenchymal stem cell-derived exosomes in kidney diseases.

Kidney injury (KI) has high morbidity and mortality; there has been no ideal practical treatment available in clinical practice until now. Exosomes are formed from fusing multisubunit body membranes and are secreted into the extracellular matrix, intercellular communication membracusses. As a cell-free treatment, it offers a new approach to the treatment of KI. Exosomes are spherical vesicles with or no separator cup that shapes proteins, and RNA acts on the target cells through various means to promote tissue damage and mitigate apoptosis, both inflammation and oxidative stress. Exosomes derived from mesenchymal stem cells (MSC) have a paracrine function in promoting tissue repair and immune regulation. The MSC-Exos provide specific benefits over the MSCs. The urinary exosomes closely follow the functions and diseases of the kidneys. Though much of the research in this field is only at the preliminary stages, previous research has demonstrated that MSC-Exos damaged tissues to offer proteins, mRNAs, and microRNAs as remedies for kidney injury. Although exosomes' role in tissue repair is currently is greatly debated, several key issues remain unaddressed. This is a summarization of the work done concerning MSC in the treatment of KI.

Cyanidin prevents cardiomyocyte apoptosis in mice after myocardial infarction.

Myocardial infarction is a worldwide disease with high morbidity and mortality and a major cause of chronic heart failure, seriously affecting patients' quality of life. Natural medicine has been used to cure or prevent cardiovascular disease for decades. As a natural flavonoid, anthocyanidin has been used to treat many diseases due to its antioxidative, anti-inflammatory, and other properties. A mouse model (C57BL/6) weighing 30-40 g was utilized to induce myocardial infarction by ligating the left anterior descending coronary artery. Cyanidin (30 mg/kg) was administered orally to mice for four weeks. A variety of assessments were used to evaluate cardiac function. The gene expression was measured using RNAseq and Western blot. Histological changes in myocardial tissue were assessed using staining techniques, including Masson, Hematoxylin Eosin (HE), and transmission electron microscopy. Tunnel staining was implemented as a method to detect cellular apoptosis. For the quantification of B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in the serum, an enzyme-linked immunosorbent assay (ELISA) was employed. Furthermore, autodock simulation was executed in order to assess the interaction between cyanidin and a subset of genes. Cyanidin treatment inhibited myocardial cell apoptosis, improved cardiac function, and reduced serum concentrations of BNP and atrial natriuretic peptide ANP, as well as mitigated histological cardiac tissue damage. Cyanidin also inhibited the activity of matrix metalloproteinases (MMP2/9) and Fibronectin 1 (Fn1). Cyanidin improves heart function and reduces myocardial damage in mice after MI. Furthermore, cyanidin can prevent cardiomyocyte apoptosis. These effects are most likely caused by suppression of MMP9/2 and control of the Akt signaling pathway, suggesting an appropriate therapeutic target.

Mesenchymal stem cell-derived exosome microRNA as therapy for cardiac ischemic injury.

Cardiovascular diseases (CVD) are a significant cause of human health harm. In the past, stem cell therapy was reported to have functional defects, such as immune rejection, tumorigenicity, and infusion toxicity. Exosomes are extracellular vesicles with lipid bilayer membrane structure, containing proteins, lipids, mRNA, miRNA, DNA, and other molecules, which can mediate various biological functions such as immune response, inflammatory response, cell migration, and differentiation intercellular communication. Exosomal miRNAs have outstanding advantages in disease diagnosis and curative effect prediction. Likewise, paracrine factors could also mediate the main therapeutic effect of mesenchymal stem cells. Research has shown that mesenchymal stem cell-derived micro-exosomes, which may come from stem cells, accumulate in the ischemic tissue and regulate cell proliferation, apoptosis, inflammation, and angiogenesis sites of myocardial injury after being transplanted. This review reviewed the molecular mechanisms of exosomes and internal microRNAs derived from mesenchymal stem cells in cardiac ischemic injury repair.

Expression characteristics of heparanase in colon carcinoma and its close relationship with cyclooxygenase-2 and angiogenesis.

BACKGROUND/AIMS: Heparanase (HPA) influences tumourigenesis and tumour progression by various mechanisms, including angiogenesis. Cyclooxygenase-2 (COX-2) was strongly correlated with microvessel density, and that COX-2 expression is up-regulated by HPA in esophageal cancer. In this study, we examined the relationship between HPA expression and that of COX-2 in colon carcinoma. The aim of this study was to determine whether the expression of HPA is related to the angiogenesis in colorectal cancer and whether it could be involved in clinical behaviour of colon carcinoma. METHODOLOGY: HPA and COX-2 was analyzed with Immunohistochemistry and Western blot. Microvessels in colon carcinoma were examined by using anti-CD34 antibody. Statistical analysis was applied to test for the prognostic and diagnostic associations. RESULTS: Immunohistochemistry revealed that HPA was expressed at low level in normal colonic mucosa (4/78, 5.1%), but at higher level in tumor tissues (63/78, 80.7%) and closely correlated with tumor lymph node metastasis (p < 0.05). This result was further confirmed by Western blot analysis. Furthermore, carcinomas with high HPA expression demonstrated high COX-2 expression and high MVD (microvesseldensity) labelled with CD34. In addition, mortality was higher in patients with HPA+ phenotype and HPA was an independent predictor of overall survival (p < 0.05). CONCLUSIONS: Our findings indicated that HPA might be an important biomarker for malignant transformation and be involved in promoting colon carcinoma metastasis by increasing angiogenesis.

Protein Changes in Response to Lead Stress of Lead-Tolerant and Lead-Sensitive Industrial Hemp Using SWATH Technology.

Hemp is a Pb-tolerant and Pb-accumulating plant and the study of its tolerance mechanisms could facilitate the breeding of hemp with enhanced Pb tolerance and accumulation. In the present study, we took advantage of sequential window acquisition of all theoretical mass spectra (SWATH) technology to study the difference in proteomics between the leaves of Pb-tolerant seed-type hemp variety Bamahuoma (BM) and the Pb-sensitive fiber-type hemp variety Yunma 1 (Y1) under Pb stress (3 g/kg soil). A total of 63 and 372 proteins differentially expressed under Pb stress relative to control conditions were identified with liquid chromatography electro spray ionization tandem mass spectrometry in BM and Y1, respectively; with each of these proteins being classified into 14 categories. Hemp adapted to Pb stress by: accelerating adenosine triphosphate (ATP) metabolism; enhancing respiration, light absorption and light energy transfer; promoting assimilation of intercellular nitrogen (N) and carbon (C); eliminating reactive oxygen species; regulating stomatal development and closure; improving exchange of water and CO2 in leaves; promoting intercellular transport; preventing aggregation of unfolded proteins; degrading misfolded proteins; and increasing the transmembrane transport of ATP in chloroplasts. Our results provide an important reference protein and gene information for future molecular studies into the resistance and accumulation of Pb in hemp.

Effects of tire rubber ash and zinc sulfate on crop productivity and cadmium accumulation in five rice cultivars under field conditions.

Cadmium (Cd) is among the most widespread and toxic heavy metals becoming a severe threat to humans. A field study was conducted to examine the role of various zinc (Zn) fertilization treatments and cultivars on crop productivity and Zn and Cd concentrations in brown rice and rice straw. The Zn fertilization treatments included an unfertilized control, foliar applied Zn sulfate (ZnSO4) at panicle initiation stage, foliar applied ZnSO4 at milky stage, soil application of rubber ash, and soil-applied ZnSO4, while five rice cultivars were Swat-1, Shadab, Shua-92, Swat-2, and Sada Hayat. All the Zn fertilization treatments resulted in significantly higher number of panicles, number of spikelets per panicles, spikelet fertility, 1,000-grain weight, grain yield, brown rice and rice straw Zn concentrations, and significantly lower Cd concentrations. Soil application of rubber ash remained the best among all Zn fertilization treatments as it resulted in 73% higher grain yield and reduced Cd concentration by 51% as compared with control. Variations were also apparent among cultivars, and Shua-92 and Swat-2 performed better in terms of all studied attributes as compared with other cultivars. Conclusively, cultivar selection and Zn application are effective strategies to improve rice grain yield as well as quality. Rubber ash appeared a viable source of Zn having the ability to increase yield along with reducing Cd accumulation.

A proteomics sample preparation method for mature, recalcitrant leaves of perennial plants.

Sample preparation is key to the success of proteomics studies. In the present study, two sample preparation methods were tested for their suitability on the mature, recalcitrant leaves of six representative perennial plants (grape, plum, pear, peach, orange, and ramie). An improved sample preparation method was obtained: Tris and Triton X-100 were added together instead of CHAPS to the lysis buffer, and a 20% TCA-water solution and 100% precooled acetone were added after the protein extraction for the further purification of protein. This method effectively eliminates nonprotein impurities and obtains a clear two-dimensional gel electrophoresis array. The method facilitates the separation of high-molecular-weight proteins and increases the resolution of low-abundance proteins. This method provides a widely applicable and economically feasible technology for the proteomic study of the mature, recalcitrant leaves of perennial plants.