Abstract: Objective To investigate the effect of “ Jiangya Fang” acupuncture on internal carotid artery compliance and the mechanism of vascular protection in spontaneous hypertension rats (SHR). Methods Thirty 11-weekold male SHR rats were divided randomly into a model group (SHR) and an acupuncture group (SHR+Acu), with Wistar Kyoto Rats (WKR) as a control group (n= 15 rats per group). The model group and control group underwent the same handling procedures as the acupuncture group, while the acupuncture group also received “Jiangya Fang” acupuncture once a day for 4 weeks. The contractile and diastolic reactivities of the carotid artery in each group were then detected by in vitro thermostatic perfusion and biological function experiments, and the ultrastructure of the intima and middle membrane of the internal carotid artery were observed by electron microscopy. Serum levels of c-Jun N-terminal kinase (JNK) and monocyte chemoattractant protein-1 (MCP1) were detected by enzyme-linked immunosorbent assay, and the expression of phospho-JNK/ MCP1 in the internal carotid artery was observed by co-immunofluorescence staining. Protein expression of transcription activator protein 1 (AP1) and CC chemokine receptor 2 (CCR2) in the internal carotid artery were detected by Western blot. Results Acupuncture reduced the vasoconstriction sensitivity of the internal carotid artery to norepinephrine and enhanced its vasodilation response to sodium nitroprusside in SHR. Acupuncture also alleviated injury of the intima and middle membrane of the internal carotid artery in SHR, reduced serum levels of JNK and MCP1 (P<0. 05), and decreased p-JNK/ MCP1 fluorescence intensity and AP1 and CCR2 protein expression in the internal carotid artery (P< 0. 05). Conclusions Acupuncture can inhibit the JNK/ MCP1 pathway in the internal carotid artery and may play a benign role in regulating vasomotor reactivity of the carotid artery and alleviating injury of the internal carotid artery in SHR.

Abstract: Objective To investigate the effect of early pressure gradient (PG) after transverse aortic constriction(TAC) on the degree of aortic constriction and aortic pressure in mice, the relationship with myocardial hypertrophy and myocardial systolic function at the experimental endpoint, and to provide a basis for the early measurement of aortic constriction and selection of experimental mice. Methods Male C57BL/6 mice aged 14~16 weeks were selected for TAC surgery. Cardiac echocardiography was performed before and 1 week and 4 weeks after the operation, and hemodynamic testing and measurement of body weight and left ventricular weight/ tibial length (LV/ TL) were performed 4 weeks after surgery. Results Both flow velocity and PG were significantly higher 1 and 4 weeks after TAC compared with preoperative levels (P< 0. 05). PG at 4 weeks after TAC was significantly correlated with left ventricular systolic pressure (r=0. 773, P< 0. 001) and systolic blood pressure (r= 0. 658, P= 0. 002), indicating that hemodynamic testing by noninvasive ultrasound Doppler can replace the invasive hemodynamic detection of pressure caused by TAC. The PG 1 and 4 weeks after TAC was significantly and positively correlated with LV/ TL, left ventricular mass index, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular anterior wall thickness at diastole, and left ventricular posterior wall thickness at diastole. In addition, both 1 week and 4 weeks after TAC, the ejection fraction and fraction shortening were significantly negatively correlated with PG. Conclusions The PG 1 week after TAC predicted the degree of myocardial hypertrophy 4 weeks after TAC, and the larger the PG, the heavier the left ventricular weight, the more severe the ventricular wall thickness and ventricular dilation 4 weeks after TAC, and the more severe the impairment to myocardial systolic function.

Abstract: Objective To identify mRNA expression of 26S proteasome non-ATPase regulatory subunit 13(PSMD13) in Chinese hamsters with type Ⅱ diabetes mellitus (T2DM), analyze its physicochemical properties, signal peptides, subcellular localization, and functional domains, and provide a theoretical basis to study its function. Methods PSMD13 mRNA expression in the liver, skeletal muscle, fat and small intestinal tissues of Chinese hamsters with or without T2DM was determined by RT-qPCR. The amino acid sequence of PSMD13 was downloaded from the NCBI website and amino acid homology analysis was performed using DNAman software. Physicochemical properties of PSMD13 were analyzed by the Prot Param online tool. Hydrophobicity, signal peptides, and subcellular localization of PSMD13 were analyzed by Prot Scale software. The functional domain and secondary structure of PSMD13 were analyzed using the Conserved Domain database and SOPMA tool, respectively. The interacting proteins and functional networks of PSMD13 were analyzed using STRING databases. Results RT-qPCR showed that PSMD13 mRNA expression was decreased in adipose tissue of T2MD Chinese hamsters compared with that in normal Chinese hamsters. PSMD13 was located on chromosome 3, contained 13 exons, encoded a protein containing 378 amino acid residues, and its relative molecular mass was 42 942. 48. PSMD13 was an acidic protein and its theoretical isoelectric point was 6. 1. Amino acid sequence homology of PSMD13 with mice, rats, Drosophilae melanogaster, orangutans, and humans was as high as 97. 78%. PSMD13 protein had no signal peptide or transmembrane structure, and was mainly located in the cytoplasm. The carboxyl terminal of the PSMD13 protein contained a PCI domain that interacted with PSMD7, PSMD8, PSMA3, PSMC1, and USP14 to participate in ubiquitin-dependent protein catabolism. Conclusions The PSMD13 protein is highly conserved in evolution and its expression is low in adipose tissue of T2DM Chinese hamsters. PSMD13 is involved in the proteasome degradation pathway, and its downregulation in adipose tissue may be involved in the occurrence and development of T2MD.

Abstract: Objective To investigate the effect of long non-coding RNA Kinectin 1 antisense RNA 1 (lncRNA KTN1-AS1) on the proliferation, migration, and invasion of non-small cell lung cancer (NSCLC) cells and its mechanism of regulating the miR-153-3p/ activated T cell nuclear factor 5 (NFAT5) axis. Methods Real-time quantitative PCR(qRT-PCR) and Western blot were used to measure KTN1-AS1 and miR-153-3p expression and NFAT5 protein expression in NSCLC and adjacent tissues; human normal lung epithelial cells BEAS-2B; and NSCLC cell lines A549, HCC827, and H1299. A549 cells were divided into a Ct group, si-NC group, si-KTN1-AS1 group, mimic NC group, miR-153-3p mimic group, miR-153-3p mimic+pcDNA group, and miR-153-3p mimic+pcDNA-NFAT5 group. qRT-PCR was applied to detect the expressions of KTN1-AS1 and miR-153-3p in cells. CCK-8 assay was applied to detect cell proliferation, and a plate cloning assay was used to detect the ability of cells to form clones. A scratch-healing assay was applied to detect cell migration, and a Transwell assay was used to detect cell invasion. Western blot was applied to detect NFAT5, CyclinD1, matrix metalloproteinase (MMP)-2, and MMP-9 protein expression. Dual luciferase was applied to verify the relationships between KTN1-AS1 and miR-153-3p miR-153-3p, and NFAT5. Results In NSCLC tissues and cells, KTN1-AS1 and NFAT5 proteins were expressed at high levels, and miR-153-3p was expressed at low levels. In A549 cells, KTN1-AS1 and NFAT5 protein expression levels were the highest, and miR-153-3p levels were the lowest (P< 0. 05); therefore, A549 cells were selected as the research subject. Compared with the si-NC group, the si-KTN1-AS1 group showed decreased expression levels of KTN1-AS1 and NFAT5 protein and increased expression levels of miR-153-3p (P< 0. 05). Compared with the mimic NC group, the miR-153-3p mimic group showed statistically comparable KTN1-AS1 expression (P> 0. 05), decreased NFAT5 protein expression, and increased miR-153-3p expression (P< 0. 05). Compared with the miR-153-3p mimic and miR-153-3p mimic + pcDNA groups, the miR-153-3p mimic + pcDNA-NFAT5 group had statistically comparable expression of KTN1-AS1 and miR-153-3p in (P> 0. 05) and increased protein expression of NFAT5 (P< 0. 05). Down-regulation of KTN1-AS1 or up-regulation of miR-153-3p inhibited the proliferation, migration, invasion, and protein expression of CyclinD1, MMP-2, and MMP-9 in A549 cells. Overexpression of NFAT5 attenuated the inhibitory effect of upregulating miR-153-3p on the proliferation, migration, and invasion of A549 cells. KTN1-AS1 targeted the miR-153-3p/ NFAT5 axis. Conclusions Silencing KTN1-AS1 may inhibit the expression of NFAT5 by upregulating miR-153-3p, thereby inhibiting the proliferation, migration, and invasion of A549 cells.

Abstract: Objective To investigate the effect of calorie restriction (CR) cardiomyocyte hypertrophy induced by angiotensin Ⅱ (AngⅡ) and the possible mechanisms involved. Methods H9c2 cells were divided into six groups: Control, AngⅡ (1 μmol/ L), CR, CR+AngⅡ, CR+AngⅡ+Ss and CR+AngⅡ+Bet groups. The cell viability of each group was detected using the CCK-8 method after corresponding drug treatments. The surface area of cardiomyocytes was detected by TRITC-phalloidin staining. The concentrations of lactic dehydrogenase (LDH), myeloperoxidase (MPO), Reactive oxygen species(ROS), Superoxide dismutase(SOD), and Malondialdehyde(MDA) in cell culture supernatants were detected with kits. The mRNA expression of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP),myosin heavy chain-β ( β-MHC), NOD-like receptor protein 3 ( NLRP3), apoptosis-associated speck-like protein ( ASC), the protein levels of NLRP3, ASC, GSDMD, caspase1 and Nuclear factor-κB(NF-κB) in cardiomyocytes were detected by Western blot. Results The surface area of H9c2 cardiomyocytes and the mRNA expression levels of hypertrophy markers(ANP, BNP, β-MHC) were significantly increased in Ang Ⅱ-induced H9c2 cardiomyocytes compared with the controls, and these changes were attenuated by CR intervention. CR reversed the AngⅡ-induced increase in LDH and MPO in myocardium mast cells. The mRNA expression levels of NLRP3, ASC, GSDMD, caspase1, IL-18, and IL-1β and the protein levels of NLRP3, ASC, GSDMD, caspase1, and NF-κB were significantly decreased in Ang Ⅱ-induced hypertrophied cardiomyocytes under CR intervention compared with Ang Ⅱ only. An NF-κB inhibitor further reduced the mRNA expression of NLRP3 and GSDMD compared with expression in the CR+Ang Ⅱ group, while an NF-κB agonist blocked the effect of CR on the mRNA expression of coke-death related genes. Conclusions CR reduced the cardiomyocyte hyperplasia induced by Ang Ⅱ in rats, and it may protect cardiomyocytes by inhibiting pyroptosis through the regulation of NF-κB.

Abstract: Objective To investigate behavioral, blood, and skin histopathological indexes in psoriasis mice. Methods BALB/ c mice were randomly divided into a control group, imiquimod-induced psoriasis model group (IMQ), and emotional stress complex imiquimod-induced psoriasis model group (ES+IMQ) and observed in an open field test (OFT) and Y maze test, and tested for serum substance P (SP) and skin histopathological indexes. Results In the OFT, Compared with the control group, both the IMQ group and ES+IMQ group covered shorter total distances, with decreased average velocity and extended residence time in the total areas and they had a shorter residence time and distance in the central area and extended distance and residence time in the edge area. In the Y maze test, the percentage of entries and percentage of residence time in the new arm decreased in both IMQ and ES+IMQ groups compared with control group. The serum SP concentration was increased in the IMQ group and decreased in the ES+IMQ group compared with the control group, and there was a statistical difference between the two model groups. Psoriasis-like skin histopathological changes were observed in both IMQ and ES+IMQ groups. The Baker score of changes were statistically different, but there were no statistical differences between the IMQ and ES+IMQ groups. Conclusions Under the experimental conditions, both IMQ and ES+IMQ group s showed decreased spontaneous activity, anxiety-like behavior, and impaired cognitive ability, which had an effect on serum SP levels, and they showed psoriasis-like skin histopathological changes. The ES+IMQ group showed more anxiety than the IMQ group, which was inversely proportional to the difference in serum SP levels, and the other indicators showed no significant differences.

Abstract: Objective To examine the level of mitochondrial autophagy in nerve cells after cerebral ischemiareperfusion and to explore the relationship between cerebral ischemia-reperfusion injury and mitochondrial autophagy in mice. Methods Seventy C57BL/6J mice were divided randomly into a blank group, sham operation group, and ischemiareperfusion group. Body weight and Zea Longa score were recorded daily. After rapid head decapitation, infarcted side brain tissue was taken for detection. 2,3,5-triphenyte-trazolium chloride detection, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling, transmission electron microscopy, Western blot and quantitative polymerase chain reaction detection at the 1st, 3rd, and 7th day. Results After modeling, the Zea Longa score decreased continuously, the relative cerebral infarction area increased, and the pathological changes of cerebral ischemia and the proportion of neuronal apoptosis were all aggravated on day 3 and alleviated on day 7. Structural changes in the mitochondria and the presence of autophagy lysosomes were observed by electron microscopy at all three time points. Protein expression of P62 decreased continuously (P< 0. 05), the LC3Ⅱ/ LC3Ⅰ ratio increased continuously(P<0. 05), expression levels of Caspase3 and cytC protein increased (P<0. 05), and mRNA expression levels of all factors increased (P<0. 05). Conclusions Mitochondrial autophagy was continuously activated after ischemia-reperfusion, but reperfusion injury was not alleviated until 3 days after reperfusion.

Abstract: Objective To investigate the effect of long non-coding RNA (LncRNA) small nucleolar RNA host gene 16 (SNHG16) on the proliferation, apoptosis, migration, and invasion of colorectal cancer (CRC) cells via the miR-106b-5p/ PHD family finger protein 1 (PHF1) axis. Methods The expression of SNHG16, miR-106b-5p, and PHF1 in CRC tissues, adjacent normal tissues, CRC cell lines (LoVo, Caco-2, HCT116 and SW480), and normal human colon epithelial cells (CCD 841 CON) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). SW480 cells were randomly divided into Control group, si-NC group, si-SNHG16 group, si-SNHG16+inhibitor-NC group, si-SNHG16+ miR-106b-5p inhibitor group, si-PHF1 group, miR-NC group, miR-106b-5p group, miR-106b-5p + pcDNA group, and miR-106b-5p+pcDNA-PHF1 group. The expression levels of SNHG16, miR-106b-5p, and PHF1 in SW480 cells were detected by qRT-PCR. The proliferation, apoptosis, migration, and invasion abilities of SW480 cells were detected by MTT method, flow cytometry and Transwell method, respectively. The interactions between SNHG16, miR-106b-5p, and PHF1 were verified by dual luciferase reporter gene experiments. The protein level of PHF1 was measured by Western blot. Results SNHG16 and PHF1 were expressed at high levels, while miR-106b-5p was expressed at low levels(P<0. 05), in CRC tissues and cells. SW480 cells with the highest expression of SNHG16 were selected for a transfection experiment. The down-regulation of SNHG16 reduced the proliferation, migration, and invasion and promoted the apoptosis of SW480 cells (P<0. 05). MiR-106b-5p was able to interact with SNHG16, and its inhibitor restored the inhibitory effect of silencing SNHG16 on SW480 cell progression (P<0. 05). PHF1 was a target of miR-106b-5p, and silencing PHF1 inhibited the progression of SW480 cells (P<0. 05). PHF1 overexpression restored the inhibitory effect of miR-106b-5p on CRC cell progression (P<0. 05). SNHG16 promoted the expression of PHF1 in SW480 cells by downregulating miR-106b-5p (P<0. 05). Conclusions LncRNA SNHG16 regulates miR-106b-5p/ PHF1 axis by targeting to promote the proliferation, migration, and invasion of CRC cells and inhibits apoptosis.

Abstract: Objective To explore the proliferation-inhibition and inducement of apoptosis efficacy of decoction of Euphorbia fischeriana Steud. and jujuba (DEFSJ) on the human breast cancer cell line MCF-7 and reveal the underlying molecular mechanisms. Methods DEFSJ-containing serum (CS) was prepared via a serum pharmacology method . Cell morphology was observed by optical microscope and transmission electron microscope (TEM). After MCF-7 cells were treated with DEFSJ-CS and LY294002 ( PI3k signaling pathway inhibitor), the CCK-8 method was used to detect proliferation, the apoptosis rate was detected with a flow cytometer, and the expression of PI3k/ Akt signaling pathway and Bcl-2 family-related proteins were detected by immunostaining. Results Morphological changes and typical features of apoptosis were observed by optical microscope and TEM. DEFSJ-CS had a significant inhibitory effect on the proliferation of MCF-7 cells (P< 0. 01), and the inhibitory effect was more significant when combined with LY294002 (P< 0. 05,P<0. 01). Annexin V-FITC/ PI staining result showed that, compared with the negative control group, the apoptosis rate significantly increased with the increase of DEFSJ-CS, and the apoptosis rate was more significant when combined with LY294002. Immunostaining result showed that the protein expression levels of PI3k, p-Akt, p-FoxO3a, and Bcl-2 were down-regulated and the levels of Bax and Bim were up-regulated (P<0. 05, P<0. 01), and p-Akt and p-FoxO3a were down-regulated more significantly after combined treatment with LY294002. Conclusions The PI3k/ Akt signaling pathway is involved in the effect of DEFSJ-CS on proliferation inhibition and inducing apoptosis in MCF-7 cells.

Abstract: Objective To prepare an acute myocardial infarction (AMI) model in Bama mini-pigs by minimally invasive intracoronary balloon occlusion and comprehensively evaluate establishment of the model by hematological, functional, and pathological method. Methods After collecting baseline data and performing a femoral artery puncture under general anesthesia, the left anterior descending branch (2~5 mm below the first diagonal branch) of 12 Bama minipigs was blocked by percutaneous intracoronary balloon occlusion for 90 min. During the operation, Holter monitoring was performed, and intravenous blood was collected regularly after the operation to analyze myocardial injury markers. Echocardiography was also performed after the operation to assess cardiac functions, and the area and severity of myocardial infarction were evaluated by gross observation, and Masson and Sirius red staining. Results Among the 12 mini-pigs, 10 completed the process of balloon occlusion, and the other two did not reach the blocking time because of frequent malignant arrhythmias during the operation. Seven of the animals that completed occlusion survived to 28 days, and the remaining three died unexpectedly before the end point of the experiment. In successfully established models, the ST-T segment of the electrocardiogram showed dynamic changes after occlusion, and myocardial injury markers had increased most obviously at 4 h after the operation compared with before surgery with statistically significant differences (P< 0. 01). Echocardiography on day 7 after the operation showed significant changes in the left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic volume, and left ventricular end-systolic volume compared with preoperative values (P< 0. 05). Gross observation of the heart indicated that the infarcted myocardium was gray-white and mainly located in the left anterior wall. Pathological staining showed that the infarct area involved the full thickness of the ventricular wall. Conclusions We established an AMI model in Bama mini-pigs successfully and subsequently conducted comprehensive evaluation of the model validity.

Abstract: Objective For tissues that require continuous diastole and systole in vivo, such as the heart, there are many problems with traditional tissue fixation method. This study verified and evaluated selection of a potassium chloride termination concentration and procedure from the animal heart sampling process and compared it with traditional and active perfusion fixation method to optimize sampling and fixation method of heart tissue in small experimental animals such as rats. Methods Intracardiac injection of a KCl solution in situ and transposition of a KCl solution after heart extraction were compared and analyzed. Then, the reduction degree of heart morphology in vivo, the consistency of diastolic termination, the success rate of modeling, the morphology of the myocardium, and the application of specialized staining were analyzed. The traditional fixation method, active perfusion fixation method, and KCl arrest were systematically compared. Results In the traditional passive fixation method, the overall shape of the heart was irregular, and some samples showed ventricular collapse, obvious contraction of the epicardium, and obvious thrombus in the ventricular lumen and myocardial vessels. Because of the inconsistency in the arrest period, heart morphology varied greatly among individuals. In the active perfusion method, the overall size of the heart was significantly increased, the double ventricle was severely dilated, muscle fibers were broken, and the microstructure was damaged. In KCl arrest, the overall heart shape was intact, there was no obvious contraction of the epicardium, the arrest period was relatively consistent, and there was little difference between individuals. Conclusions Modified KCl arrest is superior to traditional passive fixation method and active perfusion method in terms of the in vivo shape reduction of the heart and subsequent analysis by histopathological staining. This method provides a reference for pathological and histological studies of cardiac tissue fixation method ology. Furthermore, the difference between individual heart tissue morphological analysis of the consistency and in vivo shape reduction, the animal model of the heart internal fine structure, such as left and right ventricles, left and right atria, and the ventricular septum, papillary muscle, valves, such as analysis of observation, is of great significance.

Abstract: Objective To improve user experience and the management efficiency of laboratory animals in medical universities, it’ s critical to develop an intelligent, scientific, and process-oriented comprehensive management system for laboratory animals. Methods We developed a comprehensive and scientific management system for laboratory animal production, sales, animal experiments, data statistics, and analysis using computer clusters, the Internet of Things(IoT) cloud platform, and mobile communication terminal technology. Results The comprehensive management system for laboratory animals achieved stable operation over its main technological processes and steps after undergoing testing and trialing. Conclusions The system performs stable and reliably, and achieving intelligent management, reducing operation costs, and meeting the expectation of system design.

Abstract:Before beginning human clinical drug trials, researchers need to conduct extensive preclinical studies involving animal experiments to preliminarily clarify each drug’s effects, toxicity, and pharmacokinetics. In addition to general considerations related to study design, the calculations for determining the appropriate sample sizes are a core element of experimental studies. Currently, there is a great deal of randomness in the selection of animal sample sizes, which not only leads to a reduction in the reproducibility and representativeness of experimental result but also causes funds to be wasted. Therefore, in this paper, we divide medical experimental research into exploratory and confirmatory studies and provide examples of sample size determination method based on the literature and our experience. Precision analysis, two-sample mean, resource equation, and KISS approach determination method are described with the aim of providing a calculation scheme for the selection of sample sizes and, therefore, reduce unnecessary harm to animals and improving the accuracy of the experiments. With the development and dissemination of combinations of medical statistics and medical experiments, research on the determination of animal experimental sample sizes will become increasingly perfected, providing firm theoretical and experimental bases for a rigorous research process and reliable conclusion.

Abstract:Lactoferrin is a natural multifunctional protein found in animal colostrum. It is involved in iron transport and has powerful biological functions involved in regulating the immune system and fighting broad-spectrum bacteria, oxidation and cancer. Recent studies have found that lactoferrin can pass the blood-brain barrier through receptormediated cytocytosis and activate microglia/ macrophage coupling to induce pro-inflammatory responses. Thus, lactoferrin plays an important role in regulating iron homeostasis, inflammatory responses, oxidative stress, apoptosis, and angiogenesis. Therefore, this article reviews the biological characteristics and functions of lactoferrin and its related mechanisms and the progress of research into early neural development and cognitive functions, neurodegenerative diseases of the central nervous system, intracerebral hemorrhage, acute ischemic stroke, and tumors of central nervous system to provide a reference for related research.

Abstract:Chemotherapy is the main cornerstone of hematological tumor therapy. However, foot therapy and highdose chemotherapeutic drugs often inhibit bone marrow hematopoiesis, which commonly causes thrombocytopenia and can increase the risk of bleeding, delay follow-up treatment, increase treatment costs, and even endanger life. In recent years, accumulating studies have found that anti-tumor drugs mediate thrombocytopenia through cell aging, apoptosis, autophagy, and ferroptosis. This article reviews the mechanism of chemotherapy-induced thrombocytopenia in hematological malignant tumors.

Abstract:Narcolepsy type 1, which is caused by loss of hypothalamic orexin-producing neurons, is a rare sleep disorder characterized by excessive daytime sleepiness, cataplexy, and sleep disorders. Genetic and environmental factors play a major role in the pathogenesis of narcolepsy, especially in people with HLA-DQB1?06:02 alleles. Substantial genetic and epidemiological evidence points to the immune system, for instance, a significantly increased incidence of narcolepsy was seen after the pandemic H1N1 influenza and vaccination, suggests that H1N1 may contribute to the development of NT1, but the exact mechanism of hypothalamic neuron injury by the immune system is not well understood. Autoreactive T cells against orexin neurons have been detected in samples of patients with NT1, in which helper CD4⁺ T cells and cytotoxic CD8⁺ T cells may be pathological, indicating that NT1 pathogenesis is related to T cell-mediated autoimmunity. This article reviews the recent research progress in the pathogenesis of narcolepsy type 1 induced by T cells.

Abstract:Organoids have become the preferred model for new drug development, pathological and toxicological research, and mechanistic exploration in recent years because of their ability to maximally simulate the structure and function of human tissues and organs in vitro. With the development of regenerative medicine technology and the gradual advancement of organoid research, organoids lacking a vascularized microenvironment suffer from apoptosis and even tissue necrosis in the later stage of culture because of the lack of oxygen and nutrients, making it difficult to maintain the structure and function of the organoid in the long term. This has become a major obstacle for further application in the clinic. By focusing on the above issues, this review summarizes the formation of blood vessels and the current construction system of vascularized organoids in vitro, and condenses the core problems in the culture of vascularized organoids to provide new perspectives for future research and applications.

Abstract:Radiotherapy is an important treatment for malignant tumors. However, tumor radioresistance remains the main factor limiting the efficacy of radiotherapy, which leads to tumor recurrence and metastasis. The intracellular DNA damage response pathway is activated in the presence of damage DNA. Studies have shown that the DNA damage response affects tumorigenesis and is closely associated with sensitivity to tumor radiotherapy, making it an extremely promising therapeutic target for clinical cancer treatment. Phase I clinical trials of small-molecule DNA damage response inhibitors are underway. In this article, the role of the DNA damage response in tumors, as well as the potential applications of key DNA damage response genes and repair pathways as biomarkers and therapeutic targets for radiosensitization therapy, were reviewed.

Abstract:Cerebrovascular disease, which has high prevalence; high disability, mortality, and recurrence rates and is associated with high costs, is a major disease affecting human health. Ischemic stroke occurs in approximately 80% of cases. Animal model studies are essential if we want an in-depth understanding of the pathophysiology of the disease, therapeutic response mechanisms, and how to develop neuroprotective drugs. Animal models of ischemic stroke can be divided into global and focal ischemic stroke models, and there have been deeper explorations of focal ischemia models. Given the diversity of models, researchers can also choose an animal model of cerebral ischemia according to the research aims and other needs. The advances made in the production of animal models of focal ischemic stroke, the selection of animal models of focal ischemic stroke, the advantages and disadvantages of various models, and matters needing attention in the making of focal ischemic stroke rat model by intraluminal suture middle cerebral artery occlusion are briefly described. This review provides a reference for the production of and research using subsequent cerebral ischemia models.