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Aim To research the neuroprotective effect of Haikun Shenxi (HKSX) medicated serum on N2a/ App695 cells and the underlying mechanism. Methods HKSX medicated serum was prepared and carbohydrate components in it was analyzed using high performance thin layer chromatography (HPTLC) . N2a/ App695 cells were intervened with HKSX medicated serum, the cytotoxicity of HKSX medicated serum was measured by MTT; AP[_
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Xenotransplantation holds the promise of being used to address the imbalance between organ supply and demand for clinical transplantation. Pigs have natural features that make them more suitable donors for transplant organs than non-human primates. A series of biological barriers that arise after pig organ transplantation have been overcome by genetic engineering and pharmacological suppression. Mean- while, the gradual maturity of the genetic engineering technology has been significantly optimized for suit- able pigs for xenotransplantation, and promoted the development of pig organ transplantation research. Although it will take time for pig organ xenotransplantation to enter the clinical trial stage, recent studies conducted in a few brain-dead or critically ill patients have exhibited the great potential of porcine xeno- transplantation in solving the imbalance between supply and demand of organs for clinical transplantation.
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Pancreatic cancer remains one of the deadliest cancer types with few effective treatment options. While the overexpression of ubiquitin-specific protease 14 (USP14) has been observed in many tumor cells, including pancreatic cancer cells, its precise role in pancreatic cancer is not well defined. Here, we investigated the biological function of USP14 in pancreatic cancer and its molecular mechanisms. Our analysis of the Cancer Genome Atlas database revealed that USP14 was highly expressed in pancreatic cancer tissues,and further investigation revealed that its expression level was negatively correlated with the prognosis of patients. In SW1990 and MIAPaCa2 pancreatic cancer cells,we established stable USP14-knockdown cell lines using the shRNA-USP14 lentivirus and found that USP14 knockdown inhibited the proliferation and migration ability of pancreatic cancer cells by CCK8, colony formation assay, wound-healing and Transwell assays. Western blotting analysis showed that downregulation of USP14 expression resulted in a decrease in CyclinD3 protein levels, while overexpression of USP14 increased the protein levels in SW1990 and MIAPaCa2 pancreatic cancer cells. Furthermore, co-immunoprecipitation demonstrated that USP14 interacts with CyclinD3 and ubiquitination assays show that overexpression of USP14 reduces the ubiquitination level of CyclinD3. Moreover, CRISPR / Cas9-mediated USP14 knockout in SW1990 pancreatic cancer cells resulted in decreased CyclinD3 protein levels. These findings suggest that USP14 promotes the proliferation and migration ability of pancreatic cancer cells by interacting with CyclinD3, highlighting USP14 as a potential therapeutic target for pancreatic cancer.
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Hrr25 is a member of the casein kinase 1 family in Saccharomyces cerevisiae and has serine / threonine protein kinase activity. It can function by phosphorylating a variety of proteins. The substrate proteins of Hrr25 include autophagy related proteins, COPII (coat protein complexes II) vesicle coat proteins Sec24 and Sec23, eukaryotic translation initiation factor 6, γ- Tubulin tub4, and extender complex protein 1, etc. In addition, Hrr25 can also interact with meiotic recombinant protein Rec8, Nucleoporin Nup53, transcription regulator Crz1, and transcription activator Haa1, etc. A variety of interacting proteins of Hrr25 enable it to play a role in autophagy, vesicular transport, microtubule assembly, meiosis, mitosis, DNA repair, ribosomal biogenesis, weak organic acid stress and other biological processes. In order to better understand the action mechanism of Hrr25 in various biological processes and the relationship between various biological processes, this paper summarizes the biological functions and action mechanism of Hrr25, and the potential significance of its research, so as to provide a theoretical basis for the further research of Hrr25.
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The harm of plant virus disease is serious, which significantly restricts the sustainable development of agriculture and can cause huge economic losses. Monitoring plant health and early detection of viral pathogens are essential to reduce the spread of disease. Therefore, in order to realize the early detection of plant viral diseases in the field, a sensitive, specific and efficient colorimetric visual technique for plant viral RNA was designed by combining the colorimetric method based on gold nanoparticles (AuNPs) and hybrid chain reaction (HCR). In this study, tobacco mosaic virus (TMV) was used as a model to design two hairpin structures H1/ H2 with single-stranded tails based on TMV-specific conserved fragments. TMV could open the hairpin structure to alternately form long double-straight DNA. The binding difference between AuNPs and two nucleic acid states before and after HCR reaction resulted in colorimetric signal generation, thus realizing visual detection of TMV. After optimizing the concentration of Tris-HAc, the concentration of hairpin structure and the reaction time of HCR, the best detection conditions were obtained. The sensitivity and specificity of the technique were analyzed and real samples were tested under optimal conditions. The results showed that the absorbance ratio of AuNPs (A
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Gas molecules including hydrogen sulfide, nitric oxide, carbon monoxide, ethylene, hydrogen gas, ammonia, methane, hydrogen cyanide, and sulfur dioxide were the main components of primitive atmosphere on the earth four billion years ago. Nowadays, these gases are viewed as gasotransmitters (GTs) in organisms, namely endogenously gaseous molecules. GTs not only regulate many physiological and pathological processes, such as breathing, blood pressure, learning, memory, and the inflammatory response in animals, but also play a key role in the stomatal movement, seed germination, plant growth, development, and response to environmental stress. In this review, we cover the current progress on the metabolism of GTs, their response to temperature stress in plants, and their general characteristics, anabolism, catabolism. In addition, we highlight the key role of the antioxidant system, the osmoregulation system, the ion balance system, the water balance system, heat shock proteins, post-translational modifications, and re-establishment and repair of biomembranes in the mitigation of oxidative stress, osmotic stress, ion stress, water stress, protein denaturation, and biomembrane injury induced by temperature stress. The alleviation of these injuries could increase the resistance of plants to high temperature and low temperature stresses. Furthermore, we summarize the interactions among GTs by initiating chemical reaction, regulating metabolic enzymes, competing target molecules, and triggering new signaling to modulate temperature stress tolerance in plants. The aim of this review is to drive the rapid progress on GTs in the field of plant biology in the future.
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Atherosclerosis involving peripheral arteries can cause skeletal muscle lesions, in which oxidative damage is an important manifestation, and atherosclerosis also reduces the production and secretion of beneficial myokines. Irisin, musclin and β-aminoisobutyric acid (BAIBA) are thought to be involved in improving atherosclerosis. However, the molecular mechanism of atherosclerosis-induced skeletal muscle lesions and the effects of aerobic exercise training on the oxidative damage of skeletal muscle and myokine production remain unclear. In this study, apolipoprotein E knockout (ApoE
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The most common type of intracranial malignancy is glioma. Although the current treatments are surgery, radiation and chemotherapy, the prognosis for patients with glioma is not promising. Therefore, it becomes critical to find an effective management. The literature shows that microRNA (miRNA) plays an important role in tumorigenesis and progression. Based on this, this study aimed to investigate the molecular mechanism of miR-525-5p in regulating the migration, invasion and proliferation of glioma cells. The TCGA database was used to identify perilipin 3 (PLIN3) differentially expressed in normal tissues and glioma tissues, and the CGGA and GEPIA databases were used to query that high expression of PLIN3 was associated with poor prognosis in glioma patients and Western blot experiments revealed that PLIN3 was highly expressed in glioma cells (P<0. 05) . The results of wound healing assay and Transwell invasion assay showed that knockdown or overexpression of PLIN3 respectively inhibited or promoted the migration and invasion of glioma cells (P < 0. 05) . Dual luciferase assays confirmed that PLIN3 could bind to miR-525-5p target. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) showed that miR-525-5p expression was lower in LN229 and U251 glioma cells than in human astrocyte (HA) (P < 0. 05) . Transwell assay and 5-ethynyl-2-deoxyuridine (EdU) cell proliferation assay verified that down- or up-regulation of miR-525-5p could reverse the effects of overexpression or knockdown of PLIN3 on LN229 glioma cells (P<0. 05) . Taken together, miR-525-5p was able to regulate the migration, invasion and proliferation of glioma cells by targeting PLIN3.
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N6, 2′ -O-dimethyladenosine (m
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With the ongoing epidemic of the Coronavirus disease in China and the widespread development of radiotherapy, radiation-induced lung injury has gradually become a clinical problem that has attracted much attention. The pathogenesis of radiation-induced lung injury is complex, involving an imbalance in the polarization state of alveolar macrophages and an upregulation of alveolar epithelial cell apoptosis. Previous studies have shown that vitamin C is an important antioxidant substance, and preventive use of vitamin C can effectively treat acute lung injury. However, whether prophylactic use of vitamin C can effectively prevent or treat lung injury caused by radioactive substances, and its specific molecular mechanism remains to be studied. The purpose of this study is to investigate whether the prophylactic use of vitamin C to treat the alveolar macrophage cell line RAW 264. 7 and human lung epithelial cells BEAS-2B can effectively control the abnormal polarization of macrophages and the abnormal apoptosis of lung epithelial cells. This study found that after 4 weeks and 8 weeks of radioactive X-ray irradiation, the expression of macrophage M1 polarization state markers such as iNOS was significantly up-regulated (P< 0. 05), and preventive use of vitamin C to treat macrophages and lung epithelial cells can alleviate the polarization state disorder of macrophages and the apoptosis of alveolar epithelial cells caused by external radiation exposure, which is manifested in the down-regulation of the expression of Cleaved Caspase3. In addition, the preventive application of vitamin C treatment can inhibit the MAPK signaling pathway activated by external radiation exposure. Further experimental results showed that the inhibition of the MAPK pathway is the key to inhibiting the M1 polarization of macrophages and the apoptosis of lung epithelial cells. In summary, our findings suggest that vitamin C may play a protective role in acute radiation-induced lung injury by inhibiting macrophage M1 polarization/ promoting macrophage M2 polarization and alleviating alveolar epithelial cell apoptosis. This study will help to better understand the process and mechanism of the preventive effect of vitamin C, a common vitamin, on radiation-induced lung injury.
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microRNA-21(miR-21) is an endogenous non-coding RNA and plays a key regulatory role in the process of cell proliferation and differentiation. In recent years, miR-21, as a widely studied miRNA, has attracted much attention for its role in skin- related diseases and wound healing. The study shows that miR-21, as a " broad factor", affects the proliferation, apoptosis, migration and invasion of different cells (keratinocytes, T cells, fibroblasts, etc.) by inhibiting the transcription and translation of different target genes (PTEN, TIMP, PDCD4, etc.) . At the same time, it plays a crucial role in skin tumors, skin immune diseases, skin inflammatory diseases, skin wounds and scar tissue formation by promoting inflammation through different signaling pathways. In this study, we reviewed the regulatory roles of miR-21 in different skin diseases (melanoma, cutaneous squamous cell carcinoma, T-cell lymphoma, psoriasis, scleroderma, etc.) and wound healing, aiming at deepening the understanding of miR-21 molecule in skin-related diseases and wound healing. The potential of miR-21 as a biomarker for skin disease diagnosis and its ability to evaluate the efficacy of drugs were also discussed. miR-21 is expected to become a new target of skin disease and wound healing, which may provide a new direction for clinical research.
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Betulinic acid (BA) exerts protective effects on organs in septic animals. However, whether BA can improve cardiac function in sepsis and the underlying mechanism remain unclear. Here, male Sprague-Dawley rats were pretreated with BA (25 mg/ kg/ d, i. g.) for 5 days and then intraperitoneally injected with lipopolysaccharide (LPS, 10 mg/ kg). The rats were anesthetized to determine transthoracic echocardiography using a high-resolution imaging system for small animals after they were treated with LPS for 6 h. Histopathologic alterations were examined by HE staining. Myocardial injury markers (cTnI and CK-MB) and inflammatory factors (TNF-α, IL-1β and IL-6) in the serum were measured by the enzyme-linked immunosorbent assay. Autophagy-related proteins (p62 and LC3 Ⅱ) and AKT-modulated autophagy pathways in the myocardium were determined by Western blotting. Pretreatment with BA markedly improved left ventricular ejection fraction (EF) and fraction shortening (FS) (P<0. 05), improved myocardial histomorphology, and significantly inhibited cTnI, CK-MB, TNF-α, IL-1β and IL-6 (P<0. 05) in the septic rat serum. BA markedly decreased p62 (P<0. 01), increased LC3 Ⅱ (P< 0. 001), and significantly down-regulated p-AKT (Thr308), p-AMPKα (Ser485/ 491), p-mTOR (Ser2448) and p-S6K (Thr389) (P<0. 05), while markedly up-regulated p-AMPKα (Thr172) and pULK1 (Ser317) (P<0. 01) in septic rat hearts. The findings indicate that BA can attenuate sepsis-induced myocardial dysfunctions associated with down-regulating autophagy inhibiting pathways mediated by AKT/ mTOR and AKT/ AMPK pathways.
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Autophagy and inflammation are the important physiological reactions, especially in innate immunity. Autophagy, as a conservative metabolic process, can degrade its own disorder components through lysosomes to maintain cell homeostasis. Autophagy plays a pivotal role in degrading damaged organelles, resisting pathogenic infection and regulating inflammatory response. In the past decades, the study of autophagy in yeast and mammals has greatly increased our understanding for autophagy and its relationship with the diseases. In human, the regulation on autophagy levels can be used to prevent or treat neurodegenerative diseases, inflammatory diseases, tumors and various pathogenic microbial infections. However, in fish, the researches on autophagy and application are limited. Inflammation is a highly complex biological process, which is a natural defense response under the stimulation of ultraviolet, pathogen infection, oxidative stress and mechanical damage. Fish, as a lower vertebrate, has an incomplete acquired immune system. Innate immunity plays an important role in defensing against pathogen infection. Compared with higher vertebrate animals, although the researches on autophagy in fish cells were carried out lately, the great progress has been made in recent years on autophagy phenomenon, expression regulation of autophagy-related genes, and mechanism caused by pathogenic infection. As an important part of innate immunity, autophagy is involved in a variety of fish pathogenic infections, and fish diseases are usually accompanied by inflammatory reaction. In this review, we summarized the update findings in recent references on the autophagy and inflammatory response caused by pathogenic infection in fish, and the correlation between them, in order to deeply understand the correlation relationship between autophagy and inflammatory response in fish. This review could provide the guidance for understanding the immune mechanism of fish, and supply the foundation for developing new strategy to prevent and control fish disease.
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In recent years, the prevalence of hyperglycemia has been increasing, and patients’ bodies have been seriously damaged. Compared with conventional Western drugs, natural products have fewer adverse reactions and delay the complications of hyperglycemia. As a valuable natural product resource, Small-leaf Kuding (SLK) contains various beneficial components for the human body. The aim of this study was to study the regulation effect of SLK extract at different doses on blood glucose metabolism in hyperglycemic mice. Lipopolysaccharide and streptozotocin were used to induce hyperglycemia in mice. Extract of SLK were administered intragastrically at low, medium, and high doses (5 g·kg
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Chimeric RNA is a fusion transcript composed of exons from two or more different genes and generated by chromosome rearrangement or RNA splicing. Chimeric RNAs have the potential to encode novel proteins or function as non-coding RNAs. Chimeric RNAs were ubiquitously expressed across different cancers and normal tissues. To date, mechanistic and functional studies of chimeric RNAs still remain unclear. Precise definition and terminology in the research field of chimeric RNA will be discussed in this review. The formation, classification and clinical significance of chimeric RNAs in cancer progression will be summarized. Previous studies showed that products of chimeric RNAs may play important roles in regulating cell proliferation, motility, invasion and apoptosis through encoded fusion proteins or long non-coding chimeric RNAs. In cancer, chimeric RNA and its encoded specific protein or non-coding RNA can regulate tumorigenesis by changing cell phenotypes or directly affecting gene expression or regulatory pathways, which have the potential to be important diagnostic biomarkers and therapeutic targets. In recent years, more and more cancer-specific chimeric RNAs have been discovered from multiple types of cancers and used as therapeutic targets due to their vital roles in disease prognosis. Therefore, this review will focus on the functions and applications of chimeric RNAs in different tumors, which can shed a light on cancer diagnosis and therapeutics from the new perspective.
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N6-adenosine methylation, a form of methylation of the adenosine N6 site, is often found in eukaryotic mRNA and is one of the most common forms of internal RNA modification. Studies have shown that m6A affects cellular biological processes by regulating gene expression; also the regulators of m6A play a key role in the occurrence and development of various cancers. Prostate Cancer (PCa) is a common malignant tumor in men, and the risk of the disease in men over 60 years of age is increasing year by year. With the aging population, the number of PCa can be expected to continue to rise. In recent years, the role of m6A in tumorigenesis has received widespread attention, but studies on m6A methylation modification in PCa are still limited; therefore, it is particularly important to further explore the relationship between m6A methylation and PCa. In this paper, we review the recent research progress on the role, mechanism, and application of m6A methylation modification in PCa, especially the detailed review of the mechanism of METTL3, FTO, YTHDF2, three classical m6A-related regulatory proteins in PCa; and the potential application of m6A in advanced PCa (e. g., destructive resistant prostate cancer, bone metastatic prostate cancer). From the perspective of methylation modification, this paper may provide some clues to find effective therapeutic strategies for early diagnosis, treatment, and prognosis of PCa, and more theoretical references to achieve individualized treatment.
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The vascular system constitutes the largest surface of the human body. Vascular endothelial cells are a layer of flat epithelial cells covering the inner wall of blood vessels and have a variety of biolog-