Abstract: Objective The intestinal flora is closely related to nutritional obesity. Most of the previous research has focused on the fecal flora of the large intestine, with very few studies on the flora of the small intestine, which is the main site of absorption. We aimed to investigate the differences in bacterial flora between the colon and the ileum in a rat model of nutritional obesity using microbial diversity analysis. Methods Male Sprague-Dawley (SD) rats were fed with a high-fat diet (HFD) mixed with chow for 60 days to establish a nutritional obesity model, then fed with chow for another 60 days to eliminate the influence of the HFD. Total DNA was extracted from the contents of the ileum and colon and used as template for amplification of the V3 + V4 region of the 16S rRNA gene by PCR, then sequenced to establish operational taxonomic units (OTUs). Annotation and taxonomic analysis were performed against the Silva database. Results (1) Alpha analysis showed that the number of intestinal flora was higher than that of colon ( chao1, abundance-based coverage estimator), but the diversity was lower than that of the colon ( simpson’ s Index, shannon function) (P < 0. 05); (2) Beta analysis showed that the species similarity between the ileum and colon + ileum samples was low; (3) OTU annotation and cluster analysis showed that there were obvious differences in the types and species abundance distributions of dominant bacteria (top 10 in abundance) in the ileum and colon, with low overlap at the genus level; (4) The abundance of Rothia in the ileum of HFD-obesity resistant rats increased significantly, while that of Romboutsia decreased. Conclusions The ileum and colon had different levels of diversity in intestinal flora in rats with nutritional obesity. Rothia and Romboutsia may be the key ileum flora involved in obesity.

Abstract: Objective To investigate the clinical value of routine blood test indexes (WBC, PLT, MPV, NEUT, LYMPH, MONO, EO, BASO, NLR, MLR, and ELR) and blood biochemical indexes (TP, ALB, A/ G, GLOB, TG, CHO, HDL-C, LDL-C, and ALP) in cynomolgus monkeys with ankylosing spondylitis. Methods Forty cynomolgus monkeys with ankylosing spondylitis and 80 normal cynomolgus monkeys were selected and measured for routine blood test indicators and blood biochemical indicators. Comparisons between the two groups were performed using the rank sum test and t test method . In addition, the sensitivity, specificity, and area-und-the-curve (AUC) values of each index were calculated using receiver operator characteristic curve analysis. Results For routine blood indexes, with the exception of PLT, values of WBC, MPV, NEUT, LYMPH, MONO, EO, BASO, NLR, MLR, and ELR for the ankylosing spondylitis group were significantly higher than those of normal cynomolgus monkeys, and AUC values of the WBC ratio index were close to 0. 9. Moreover, blood biochemistry indexes (with the exception of TG, HDL-C, LDL-C, TP, and ALB) in the ankylosing spondylitis group were significantly lower than those in control group. In addition, GLOB, CHO, and white ALP of the ankylosing spondylitis group were significantly higher compared with the control group. Conclusions Routine blood and blood biochemical indexes screened in this study can be used as screening and drug evaluation indexes of cynomolgus monkeys with ankylosing spondylitis, and provide important reference for clinical diagnosis of ankylosing spondylitis.

Abstract: Objective To explore the function and mechanism of macrophage subsets in early immune responses to viral infection. Methods Fluorescence-assisted cell sorting was performed to acquire F4 / 80P>hiP> and F4 / 80P>loP> subsets of mouse peritoneal macrophages, which were stimulated with poly(I ∶C) for 8 h. qRT-PCR was performed to compare gene expression levels of pro-inflammatory factors and transcription factors. Furthermore, Western blot was performed to identify the potential activated signaling pathway. Finally, an inhibitor block experiment was conducted. Results The percentage of F4 / 80P>hiP> macrophages was significantly higher than the F4 / 80P>loP> subset (P < 0. 05). After stimulation with poly(I ∶C), gene expression of pro-inflammatory factors interleukin 6 ( IL-6), inducible nitic oxide synthase iNOS, interferon alpha (IFNα), and IFNγ was significantly higher in the F4 / 80P>hiP> subset compared with the F4 / 80P>loP> subset ( P < 0. 05), and expression of transcription factors IRF3 and IRF7 was significantly increased (P < 0. 05). Moreover, phosphorylation of the JNK pathway in the F4 / 80P>hiP> subset was significantly increased (P< 0. 05). Upregulated expression of IL-6 and IFNα were significantly attenuated by SP600125 (P < 0. 05), a phosphorylation inhibitor of the JNK signaling pathway. Conclusions The F4 / 80P>hiP> subset was more activated than the F4 / 80P>loP> subset during the early stage of viral infection, and may be modulated by IRF7 upregulation and JNK pathway activation.

Abstract: Objective To investigate the adjuvant activity of polysaccharides from Ganoderma lucidum, Lycium barbaru, Versicolor, Astragalus and Lentinan on bone marrow-derived dendritic cells ( BMDCs) from C57BL/ 6 mice. Methods Bone marrow cells from C57BL/ 6 mice were cultured in the presence of granulocyte-macrophage colony- stimulating factor GM-CSF. After 6 days, immature BMDCs were collected and co-cultured with the polysaccharides of G. lucidum, L. barbaru, Versicolor, Astragalus or Lentinula. CpG oligodeoxynucleotides were used as a positive control. The cell surface expression of CD80, CD86 and MHCII were detected by fluorescence-activated cell sorting analysis. The release of cytokines interleukin (IL)-6, IL-12 and tumor necrosis factor TFN-α were measured by enzyme-linked immunosorbent assay. Results Versicolor polysaccharides significantly upregulated the surface expression of CD80, CD86 and MHCII on BMDCs, as well as the release of the cytokines IL-6, IL-12 and TFN-α compared with the control group. Conclusions Versicolor polysaccharides promoted the maturation of BMDCs in vitro and may have potential as an adjuvant for vaccine preparations.

Abstract: Objective This research aimed to: (1) investigate the effects of curcumin in phosphatase and tensin homolog (PTEN)-mediated DNA repair and in the sensitization of wild-type PTEN triple-negative breast cancer cells to Olaparib, a poly ADP ribose polymerase (PARP)1 inhibitor; and (2) provide a new therapeutic strategy for patients with wild-type PTEN triple-negative breast cancer in the clinical setting. Methods Wild-type PTEN and PTEN-deficient variants of the triple-negative breast cancer cell line BT549 were used. MTT was used to assay the cell survival rate. Western blot was performed to detect the expression of RAD51 (a key protein in homologous recombination repair) in wild- type PTEN cells. The comet assay was used to measure the DNA damage caused by curcumin and olaparib. Western blot was used to detect RAD51 after curcumin treatment. Results Wild-type PTEN cells were less sensitive to olaparib than PTEN-deficient BT549 cells. PTEN promoted DNA repair by increasing the expression of RAD51. Curcumin inhibited PTEN-mediated DNA repair by inhibiting RAD51 and enhanced the sensitivity of wild-type PTEN triple-negative breast cancer cells to olaparib. Conclusions Curcumin inhibited PTEN-mediated DNA repair and sensitized wild-type PTEN breast cancer cells to olaparib.

Abstract: Objective To study the protective effect of valeric acid combined with sodium valproate (VPA) on pentylenetetrazole-induced epilepsy mice and P-glycoprotein ( P-GP) expression. Methods Mice were divided into six groups: normal control group, model control group, VPA group, and valeric acid +VPA group ( low, medium, and high doses). The expression of P-GP and caspase-3 active fragments in brain tissue and the rate of neuronal apoptosis in the cerebral cortex were analyzed. Results Compared with the VPA group, the seizure duration in all dose valeric acid + VPA groups was shortened, and the seizure latency in the middle-dose valeric acid group was prolonged. The seizure level in the middle-dose and high-dose valeric acid groups was lower than that in the VPA group. P-GP in the cerebral cortex of the model control group was significantly higher than that of the normal control group. The expression of P-GP protein in the VPA group was not significantly different compared with the model control group. Levels of P-GP protein were decreased in all dose valeric acid + VPA groups compared with the VPA group. The expression of caspase-3 was decreased compared with the VPA group. The apoptosis rate in each dose valeric acid + VPA group was lower than that in the VPA group. Conclusions Valeric acid may reduce the severity of seizures in pentylenetetrazol ignition / VPA-treated mice through a mechanism related to reduced P-GP expression.

Abstract: Objective To observe the effects of DIS3 overexpression or interference on expression of cell cycle and tumor-associated proteins in three types of human myeloma cells. Methods Human myeloma cell lines NCI-H929, RPMI 8226, and U266 were selected as study objects. A DIS3 gene overexpression vector and DIS3-siRNA were designed and constructed. Cell cycle was evaluated by propidium iodide single staining. qRT-PCR and western blotting were employed to detect expression of cyclin B1, P21, CDK2, and tumor-associated proteins MYC, RAS, TP53, and BRAF at mRNA and protein levels, respectively. In addition, activation of the ERK1 / 2 signaling pathway was detected by Western blot. Results Compared with the empty vector group, cells in the DIS3 overexpression group exhibited obvious G0 / G1 phase arrest and decreased expression levels of cycle-related proteins cyclin B1 and CDK2, as well as tumor-related proteins MYC, RAS, TP53, BRAF, and p-ERK1 / 2 (P < 0. 05, P < 0. 01). The expression of P21 was increased (P<0.01) in DIS3 overexpression group. In the siRNA group, trends for each index of mRNA expression or protein expression were opposite to those observed in the DIS3 overexpression group.Conclusions DIS3 overexpression can significantly block G0 / G1 phase in human myeloma cells and reduce expression of tumor-associated proteins, which may be closely related to the inhibition of ERK1 / 2 signaling pathway activation.

Abstract: Objective To investigate and explore the potential mechanism of the protective effects of artesunate on adriamycin-induced kidney injury in rats. Methods Thirty-two male Wistar rats were randomly divided into four groups of 8 rats each: negative control ( NC), kidney injury model ( ADR), low-dose artesunate ( ART-L), and high-dose artesunate (ART-H). The model group, ART-L and ART-H treatment groups received a single tail vein injection of adriamycin (7. 5 mg / kg body weight).After modeling, the rats in the treatment groups were given 25 mg / kg (ART-L) and 50 mg / kg (ART-H) artesunate, intragastrically for 3 consecutive weeks. The NC and ADR groups were injected with isotonic saline. Blood urea nitrogen ( BUN) and serum creatinine ( Scr) were measured by an automatic biochemical analyzer. Hematoxylin and eosin ( HE) staining was used to observed renal morphological changes. Kits were used to measure the levels of superoxide dismutase ( SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) in renal tissues of rats in each group. Results Serum levels of BUN and Scr, and the content of MDA in renal tissues were significantly higher in the ADR group than the NC group (P< 0. 01), while the serum levels of ALB and the activities of SOD and GSH-Px in renal tissues were significantly lower (P< 0. 01). Compared with the ADR group, serum levels of BUN and Scr, and the content of MDA in renal tissues were significantly lower in the ART-L and ART-H groups, while the serum levels of ALB and the activities of SOD and GSH-Px in renal tissues were significantly higher ( P< 0. 01). HE staining revealed that artesunate reduced renal injury induced by adriamycin. Conclusions Artesunate reduced urine protein in rats with adriamycin-induced kidney injury, improving renal function and pathological tissue damage. The underlying mechanism may be related to the inhibition of oxidative stress induced by adriamycin in renal tissue.

Abstract: Objective To study the neurotrophic and anti-inflammatory effects of senegenin on inflammatory factors in nerve cells to identify novel drugs that alleviate the toxic and side effects of anti-tumor drugs. Methods Microglial BV2 cells were cultured in vitro, and lipopolysaccharide (LPS) was used to prepare the cell inflammation model. The effects of different concentrations of senegenin (2, 2. 5, 3 μmol / L) on the LPS-induced cellular inflammatory factor nitric oxide (NO) were observed to determine the optimal dose of senegenin compared with the positive control group ( dexamethasone 10 μmol / L). The concentration of NO in inflammatory medium was detected by Griess Reagent. Results The effects of different concentrations of senegenin on the production of NO in LPS-induced BV2 cells were different. Compared with the LPS group, the anti-inflammatory effects of senegenin (5, 25, 50, 100 μmol / L) were not obvious. Moreover, the concentration of NO in the inflammatory medium was increased by 50 and 100, indicating a proinflammatory effect. In addition, in the senegenin 1, 2, 4, and 8 μmol / L dose range, 1, 2, and 2 kept up with each other and had significant anti-inflammatory effects (P < 0. 05 or P < 0. 01). The low doses of senegenin had anti-inflammatory effects. All doses of senegenin, especially 2 μmol / L (P < 0. 001), significantly reduced the concentration of NO. According to this result , senegenin was divided into low, medium and high dose groups in a follow-up test. CoX-2 mRNA expression in the senegenin 2 and 2. 5 μmol / L groups was significantly decreased (P < 0. 001) compared with the LPS group, but was slightly lower than that in the dexamethasone group. In addition, compared with the LPS group, 2, 2. 5, and 3 μmol / L senegenin reduced CoX-2 protein levels, with the most significant effect shown for 2 μmol / L senegenin ( P < 0. 05). Conclusions Senegenin reduces the release and expression of inflammatory factors in microglia induced by LPS, suggesting senegenin has neurotrophic effects that might protect nerve cells from inflammatory injury.

Abstract: Objective To explore whether sphingosine 1-phosphate ( S1P) is involved in pancreatic fibrosis in KkAy type 2 diabetic mice, and whether this process is related to transforming growth factor-β1 (TGF-β1). Methods Real-time (RT)-PCR was used to detect the level of sphingosine kinase 1 (SphK1), TGF-β1 and smooth muscle actin α (α-SMA), which were measured as an index that reflects the activation of pancreatic stellate cells in the pancreas in KkAy type 2 diabetic mice and C57 mice. The main components of the extracellular matrix, collagen α1( I) [Col α1( I)] and collagen α1(III) [Col α1(III)], were also measured by Real-time RT-PCR. Results SphK1, TGF-β1, α-SMA, Col α1 (I) and Col α1( III) were overexpressed in the pancreas in KkAy type 2 diabetic mice. There was a significant positive correlation between SphK1 and TGF-β1 in pancreatic tissue of KkAy type 2 diabetic mice. Conclusions S1P may be involved in the development of pancreatic fibrosis in KkAy type 2 diabetic mice, and this process may be related to TGF-β1.

Abstract: Objective To observe the effects of treadmill exercise on learning, memory, and expression levels of inflammatory cytokine interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and nerve growth factor (NGF) in the hippocampus of type 1 diabetic rats. Methods Forty-four adult male Sprague – Dawley rats were randomly divided into control, exercise, STZ, and STZ exercise (STZ+E) groups ( n = 11). A rat model of type 1 diabetes was established by STZ intraperitoneal injection. Exercise and STZ+E groups were subjected to 8 weeks of treadmill exercise. Subsequently, learning and memory were evaluated by Y maze test, IL-6 and TNF-α levels were measured by enzyme-linked immunosorbent assay, and NGF expression was detected by immunohistochemical staining. Results Compared with the control group, STZ group rats exhibited significantly increased standard training times and error times in 30 trials ( P<0. 01), IL-6 and TNF-α were levels significantly increased and the number and area of NGF expression in hippocampal CA1, CA3, and dentate gyrus was decreased (P< 0. 01). Treatment of STZ-induced diabetic rats with exercise improved STZ-induced declines in learning and memory and significantly decreased TNF-α expression ( P< 0. 05). However, hippocampal IL-6 expression in STZ+E group rats was not significantly different (P> 0. 05), and NGF expression in the hippocampus CA1, CA3, and dentate gyrus was significantly upregulated (P< 0. 05). Conclusions Treadmill exercise can improve the learning and memory ability of type I diabetic rats by enhancing NGF expression and anti-inflammatory abilities in the hippocampus.

Abstract: Objective To explore the effects of high-intensity focused ultrasound (HIFU) on immune function and survival time in rats with cervical cancer. Methods Sixty female Wistar rats were randomly divided into control, model, and HIFU groups, with 20 rats per group. In the model and HIFU groups, human cervical cancer HeLa cells were subcutaneously injected into the left axilla to establish cervical cancer xenograft models. After modeling, the HIFU group underwent local HIFU treatment. The single-point and single treatment time was 10 s for 250 s. After treatment, 10 rats were randomly selected from each group to observe changes in survival time and weight within 9 weeks after model induction. The remaining 10 rats in each group were sacrificed 14 d after treatment. The volume and weight of xenografts in each group were calculated. MTT was applied to detect the vitality of spleen lymphocytes. The apoptosis of peripheral blood T lymphocyte subsets and T lymphocytes was analyzed by flow cytometry. The histopathological changes of xenografts tissues were observed by HE staining. Results Compared with the control group, at 3, 5, and 7 weeks after modeling, rat body weight was significantly decreased in the model and HIFU groups (P<0. 05); the vitality of spleen lymphocytes, peripheral blood CD4⁺ T cells and CD8⁺ T cells, and CD4⁺ / CD8⁺ T cells was significantly decreased (P<0. 05); and the apoptosis rate of T lymphocytes was significantly increased (P<0. 05). Compared with the model group, the median survival time in the HIFU group was significantly prolonged [(54. 51±3. 16) vs (48. 03±1. 05), log rank (χ² )= 7. 504, P = 0. 006]. At 3, 5, and 7 weeks after model induction, the weight of rats was significantly increased (P<0. 05); tumor volume and mass were significantly decreased (P<0. 05); vitality of spleen lymphocytes, peripheral blood CD4⁺ T cells and CD8⁺ T cells, and CD4⁺ / CD8⁺ T cells were significantly increased (P<0. 05); and the apoptosis rate of T lymphocyte was significantly reduced compared with (P<0. 05). Conclusions HIFU can improve the immune function of rats and prolong the survival time of rats with cervical cancer.

Abstract: Objective To construct a simvastatin nano drug delivery system and explore its effect on atherosclerosis model rats. Methods Laser confocal microscopy was used to detect the cell uptake capacity of simvastatin nanoparticles. Rats were randomly divided into a model group (Model), simvastatin group (Sim), simvastatin nanoparticle group (Sim-LPNs), and control group (Control, normal rats), with 10 animals per group. A biochemical analyzer was used to detect TG, TC, LDL-C, and HDL-C levels. HE staining was used to detect pathological changes in arteries and vessels. Western blot was used to detect changes in p-AMPK and p-ACC protein levels. Results Sim-LPNs had a uniform spherical appearance with a mean dynamic diameter of 180 ± 23 nm. Compared with COU-6 treatment, the green fluorescence intensity of Caco-2 cells treated with COU-6-LPNs was significantly enhanced (P<0. 01). Compared with the Control group, the TC, TG and LDL-C levels in the Model group were significantly increased, and HDL-C was significantly decreased (P<0. 01). Compared with the Model group, the Sim group had significantly lower TC and LDL-C levels (P< 0. 01 or P<0. 05). Compared with the Model group, the Sim-LPNs group had significantly reduced TC, TG, and LDL-C levels, as well as significantly increased HDL-C levels (P<0. 01). Compared with the Sim group, TC and LDL-C levels in Sim-LPNs rats were significantly reduced ( P< 0. 01). In the Model group, mucosal degeneration, edema, and typical atherosclerotic plaques with a thick lipid core and foam cells were observed in the arterial blood vessel walls. The Sim group showed some improvement, but the Sim-LPNs group had a more obvious improvement. Compared with the Control group, the relative plaque area and relative plaque area / total surface of the arterial blood vessel wall of the Model group were significantly increased (P<0. 01). Compared with the Model group, the relative plaque area and the relative plaque area / total surface of the arterial wall of the Sim-LPNs groups were significantly reduced (P<0. 01). Compared with the Control group, the expressions of p-AMPK and p-ACC proteins in the liver tissues of the Model group were significantly downregulated ( P < 0. 01). Compared with the model group, the expression of p-AMPK protein in the Sim group was significantly increased (P< 0. 05), and the expressions of p-AMPK and p-ACC proteins in the Sim-LPNs groups were significantly increased (P<0. 05 or P<0. 01). Compared with the Sim group, p-AMPK protein expression in the Sim-LPNs groups was significantly upregulated (P<0. 01). Conclusions Simvastatin nanoparticles have a good anti-atherosclerotic effect, which may be related to the enhanced absorption of small intestinal cells and activation of the liver cell AMPK-ACC signaling pathway to regulate blood lipid levels.

Abstract: Objective To investigate the effect of hippocampal autophagy on sevoflurane-induced cognitive impairment in aged rats and its possible mechanism. Methods Seventy-two Sprague-Dawley rats were randomly divided into 6 groups: CON, RAP, CQ, SEV, SEV+RAP, and SEV+CQ. The following method were used to collect data from each group: blood gas indexes; learning and memory ability testing by Morris water maze; ultrastructural changes of hippocampal neurons under transmission electron microscopy; apoptosis of hippocampal CA1 neurons observed by terminal deoxynucleotidyl transferase dUTP nick end labeling; quantification of LC3 mRNA expression by reverse transcription- quantitative PCR; and protein expression of p62, LC3, Caspase3, Bax and Bcl-2 in the hippocampus detected by Western blot. Results There were no significant differences in arterial blood gas result in the 6 groups of rats ( P> 0. 05). Compared with the CON group, in the SEV group the escape latency was prolonged (P < 0. 01), the percentage of target quadrant time was shortened (P < 0. 05), and the number of crossing platforms was reduced ( P < 0. 01), while the expression of p62, cleaved caspase-3 and Bax protein increased in the hippocampus (P< 0. 05), Bcl-2 decreased (P< 0. 01), and the number of autophagic vesicles and the rate of apoptosis were increased in the hippocampus (P< 0. 01). Compared with the SEV group, the escape latency of the SEV+RAP group was decreased (P< 0. 01). Additionally, the expression of p62, p-mTOR, p-s6k1, cl-caspase-3 and Bax protein were all decreased in the hippocampus (P< 0. 05), while the expression of LC3 mRNA and bcl-2 protein increased (P< 0. 01), and the number of autophagic vesicles and the rate of apoptosis increased (P< 0. 01) in the hippocampus. Conclusions Cognitive dysfunction caused by sevoflurane anesthesia in elderly rats may be related to impaired autophagy in hippocampal neurons.

Abstract: Objective To investigate the effects and molecular mechanisms of midazolam (MID) on myocardial cell injury induced by hypoxia. Methods To determine the optimal MID concentration, H9C2 cells were pretreated with different concentrations of MID for 24 h, induced with hypoxia, and the survival rate was assayed using the cell counting kit (CCK-8). H9C2 cells were divided into seven groups: normal control ( NC); hypoxia; MID + hypoxia; microRNA (miRNA) negative control (NC) + hypoxia; miR-290-5p + hypoxia; anti-miR-NC + MID + hypoxia; and anti-miR-290- 5p + MID + hypoxia. Flow cytometry was used to detect apoptosis. Real-time quantitative PCR (RT-qPCR) was used to detect miR-290-5p expression. Western blot was used to detect phosphatidylinositol-3-kinase / protein kinase B ( PI3K/ AKT) signaling pathway-related protein expression. Results The cell survival rate of H9C2 cells pretreated with MID at 8, 16 and 32 μmol / L was significantly increased after hypoxia (P < 0. 05); 16 μmol / L was the optimal concentration. Compared with the NC group, the apoptosis rate of H9C2 cells in the hypoxia group was significantly increased, while the expression of miR-290-5p and the PI3K pathway activity were significantly reduced ( P< 0. 05). Compared with the hypoxia group, the apoptosis rate of H9C2 cells in the MID + hypoxia group was significantly reduced, and the expression of miR-290-5p and the activity of the PI3K pathway were significantly increased (P< 0. 05). Compared with the MID + hypoxia group, the survival rate of H9C2 cells in the miR-290-5p + hypoxia group was significantly increased, and the apoptosis rate was significantly reduced (P< 0. 05). Compared with the anti-miR-NC + MID + hypoxia group, the survival rate of H9C2 cells in the anti-miR-290-5p + MID + hypoxia group was significantly reduced, the apoptosis rate was significantly increased, and PI3K pathway activity was significantly reduced (P<0.05). Conclusions Midazolam protected hypoxia-induced cardiomyocyte damage by upregulating miR-290-5p to activate PI3K/ AKT signaling pathway.

Abstract:Asthma is a common chronic respiratory inflammatory disease. Additional asthma-related pathophysiology research and new drug trials are needed. This would be greatly expedited using corresponding animal asthma models. However, to date, there is no ideal model that can represent all the characteristics of the complex disease of human asthma. Therefore, this review provides the characteristics of commonly used animals currently used to make asthma models, different modeling method , different selected reagents, and the time required for modeling, which should help researchers in choosing appropriate animals, Methods and allergens.

Abstract:Heterogeneity is the main clinical feature of prostate cancer and is manifest in the tumor histological characteristics between different patients as well as tumor cell growth and metastasis speed in the same patient. Thus, it is very important to establish corresponding individualized animal models to develop clinical treatments for prostate cancer. Patient-derived organoid (PDO) models accurately display the tissue structure, function, and genetic characteristics of prostate cancer in vivo, which reflect the heterogeneity of clinical tissues. PDO models have unique advantages when applied to prostate cancer research. We summarize the culture conditions of prostate cancer PDO models, and review the application of these in vitro models for research related to the pathogenesis, drug screening, individualized treatment, and drug resistance mechanisms of prostate cancer to provide a perfect model for heterogeneity research in prostate cancer.

Abstract:Rheumatoid arthritis (RA), an autoimmune disease, affects the joints and eventually leads to joint deformity. Without intervention, the disability rate can exceed 60% over 10 years, which seriously affects the quality of life of patients. Animal models of RA have played an important role in the study of the pathogenesis, treatment, and identification of therapeutic targets of RA. In this review, the construction method , pathogenesis, and applications of several common animal models of RA are introduced to aid researchers in selecting appropriate animal models for future disease research.

Abstract:Ferroptosis, a type of non-apoptotic cell death discovered in recent years, plays an important role in the development of tumors. Many studies have shown that hematological malignant tumors, such as leukemia and lymphoma, are sensitive to ferroptosis. Moreover, regulation of the ferroptosis pathway can accelerate or inhibit the disease progression of tumors. Herein, the mechanism of ferroptosis and current research examining its involvement in hematological malignant tumors are reviewed to provide a reference for future research and treatment of ferroptosis in hematological tumors.

Abstract:Lysosomes are not only the degradation center for substances in cells, but also an important metabolic sensor for many substances, metabolic processes, and cell growth. Similarly, mitochondria are the main metabolic centers that determine the fate of cells. Together, these two organelles jointly regulate cell metabolism through interactions with each other, and their dysfunction is closely related to metabolic diseases, neurodegenerative diseases, and lysosomal storage diseases. At present, we recognize that mitochondria interact with lysosomes through mitophagy, mitochondrial-derived vesicles, and mitochondrial-lysosomal membrane contact sites. However, the mechanisms regulating these pathways remains unclear. In recent years, Rab7 protein has been implicated in processes of mitochondria-lysosome crosstalk, including the formation of mitochondrial autophagosomes, fusion of mitochondrial autophagosomes with lysosomes, and mitochondrial- lysosome contact and dissociation. In this article, we review the role of Rab7 in crosstalk between mitochondria and lysosomes, which provides a new theoretical basis for disease involving mitochondrial and lysosomal dysfunction.

Abstract:Cardiovascular disease currently accounts for more than 30% of all deaths. In patients with cardiovascular disease, acute myocardial infarction is usually the first manifestation and may progress to heart failure. In addition, the human heart has low regeneration ability, which causes the irreversible loss of myocardial cells and persistent tissue scars. This inevitably causes serious pathological sequelae. New treatments for myocardial regeneration are urgently required. This article summarizes recent research, including the role of inflammatory responses, in myocardial regeneration and provides direction towards the realization of human myocardial regeneration.

Abstract:Calcific aortic valve disease is an active progressive disease characterized by inflammation, fibrosis and calcification, but the exact pathologic mechanism is unclear. At present, research is mainly conducted in animal models. Those animal models that best simulate the disease process help to clarify the mechanisms of the occurrence and development of the disease, and may lead to the identification of effective clinical treatments. In this paper, we reviewed and evaluated the mouse model of calcific aortic stenosis to provide a reference for the selection of other animal models of calcified valvular disease.

Abstract:Mesenchymal stem cells (MSCs) possess the ability to self-renew and give rise to highly differentiated cell types, and can be isolated from a wide range of sources, making them the first choice for cell therapy. MSCs are widely used in tissue repair, autoimmune diseases and degenerative diseases, and have high value. Currently, biosafety is one of the most challenging problems in the clinical translation of MSCs. Previous research on the biosafety of MSCs has been largely unclear. Therefore, we reviewed the research progress on several aspects of MSC biosafety, including genetic stability, tumorigenicity and immunogenicity. This review may provide a reference for the safety evaluation and clinical transformation of MSCs.

Abstract:Coagulation disorders are a key link in the process of endotoxic shock-induced microcirculation dysfunction and sepsis, which is closely related to organ injury and mortality of patients. Based on the three aspects of “reducing blood hypercoagulability, supplementing coagulation factors, and inhibiting fibrinolytic hyperactivity”, this paper reviews the beneficial effects of preventive and therapeutic measures to restore coagulation homeostasis and improve the prognosis and reduce the mortality of endotoxin shock or sepsis.