Abstract: Objective To elucidate the molecular mechanism of the negative regulation of inflammatory factors by menthol through transient receptor potential melastatin 8 (TRPM8). Methods In an in vivo experiment, we detected expression of the cold-sensitive receptor TRPM8, nuclear transcription factor NF-κB, and inflammatory factor TNF-α after intravenous injection of (-)-menthol. In an in vitro experiment, we examined the effect of menthol on TRPM8, NF-κB, and TNF-α expression in PC12 cells. Finally, we examined the negative relationship between TRPM8 and TNF-α in PC12 cells (TRPM8 knockdown). Results The three main findings of this study are as follows. First, after intravenous injection of menthol, expression of the cold-sensitive receptor TRPM8 in the hypothalamus of mice was activated, and expression of the nuclear transcription factor NF-κB and inflammatory factor TNF-α was inhibited. Second, in the neuron-like PC12 cells, menthol activated TRPM8 expression and inhibited NF-κB and TNF-α. Third, in PC12 cells with TRPM8 knockdown, menthol showed no significant effect on TRPM8 expression; in contrast, TNF-α expression was activated. Conclusions The negative regulation of inflammatory factors by menthol depends on the activation of TRPM8 expression.

Abstract: Objective To investigate the effect of rapamycin on primary sclerosing cholangitis in C57BL/ 6J mice induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and to explore its potential mechanism. Methods 6 ~ 8- week-old female C57BL/ 6J mice were randomly divided into a normal diet group ( healthy control group), a 0. 1% DDC diet model group (DDC group), and a DDC with rapamycin treatment group (RAPA group). Rapamycin (5 mg / kg body weight) was injected intraperitoneally every day for 1 week. Hematoxylin-eosin and Masson staining were used to semiquantitatively evaluate the degree of pathological changes and liver fibrosis in liver tissues, respectively. Immunohistochemistry was used to detect CK-19 and Ki-67 and to quantitatively analyze the degree of biliary duct proliferation in liver tissues. Real-time quantitative polymerase chain reaction was used to detect the expression of inflammatory cytokines (IL-6, TNF-α, IL-1β) and fibrosis-related molecules ( TIMP, TGF-β, and collagen I) at the mRNA level. Western blot was used to detect the expression of Akt / mTOR/ NF-κB signaling pathway proteins and their phosphorylation levels. Results Compared with the DDC group, the RAPA group showed a marked reduction in hepatic inflammation and biliary duct hyperplasia as well as amelioration of hepatic fibrosis. Inflammatory cytokines (IL-6, TNF-α, IL-1β) and fibrosis-related molecules ( TIMP, TGF-β, and collagen I) were significantly decreased; furthermore, the phosphorylation levels of Akt / mTOR/ NF-κB signaling pathway proteins were also remarkably decreased. After rapamycin treatment, bile duct injuries in the DDC group as indicated by expression of CK-19 and Ki-67 were also significantly improved. Conclusions Rapamycin can alleviate DDC-induced primary sclerosing cholangitis in mice by inhibiting the Akt / mTOR/ NF-κB signaling pathway.

Abstract: Objective To establish a high-efficiency and stable mouse model of liver orthotopic transplantation for hepatocellular carcinoma. Methods A 5 μL solution containing 5 × 10⁵ H22 cells was injected into the left liver lobe using a 10 μL micro-syringe. In the key step of sealing the pinholes on the liver surface, two method were used to prevent cell leakage: cotton-pressed and heat-sealed. The size, weight, and pathology of liver tumors were examined on the 19th day after inoculation in preparation for establishing a stable and uniform liver orthotopic transplantation model. Results The liver tumor formation rate of both method was 100%. Although there was no statistically significant difference in tumor size, weight, or pathological performance between the two groups, the size and weight of the transplanted liver tumors were more uniform and showed smaller fluctuation in the heat-sealed than cotton-pressed group. In particular, significantly high rates of ascites (36. 4%) and abdominal tumors (36. 4%) were found in the cotton-pressed group (P< 0. 05). However, these abnormalities did not develop in the heat-sealed group. This finding indicates that the tumor cells more easily leaked from the pinholes in the cotton-pressed group, which may have been the main cause of the larger fluctuations in the size and weight of orthotopic transplanted liver tumors. In addition, one mouse with multiple abdominal tumors in the cotton-pressed group also exhibited tumor nodules, which may have been the result of metastasis from abdominal or ascitic tumor cells through the vasculature. Conclusions In the present study, we established a method for preparing a uniform and stable mouse model of liver orthotopic transplantation for hepatocellular carcinoma and described the key implementation points. The merits of short time, an easy operation, and stability provide a good reference for liver cancer research.

Abstract: Objective To investigate the effects of vitexin on the behavior, serum cystatin C ( CYS-C) and neuron-specific enolase ( NSE) levels, oxidative stress, and apoptosis of catecholamine neurons and substantia nigra dopaminergic neurons in a mouse model of Parkinson’s disease. Methods Thirty-two mice were randomly divided into a control group, model group, pramipexole group, and vitexin group. The mice in all groups except the control group were intraperitoneally injected with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine ( MPTP) for 7 consecutive days. Normal saline was administered to the mice in the control group and model group, and pramipexole tablets and vitexin were administered to the mice in the control group and model group, respectively. The intervention lasted for 30 days. The behavior of the mice was evaluated by a lever climbing experiment and swimming experiment. The levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), hypervanillic acid ( HVA), 5-hydroxytryptamine ( 5-HT), and serum CYS-C and NSE in the substantia nigra were detected by enzyme-linked immunosorbent assay. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in the brain tissues of mice were determined by spectrophotometry; the apoptosis rate of dopaminergic neurons was determined by TUNEL staining; and the protein expressions of Bax, Bcl-2, and cleaved caspase-3 in the substantia nigra were determined by Western blot. Results The swimming score; CYS-C, DA, DOPAC, HVA, 5-HT, SOD, and GSH-Px levels; and Bcl-2 protein expression of mice in the model group were all lower than those in the normal group, while the lever-climbing score; NSE and MDA levels; dopaminergic neuron apoptosis rate; and Bax and cleaved caspase-3 protein expression were all higher (P< 0. 01). The swimming score; CYS-C, DA, DOPAC, HVA, 5-HT, SOD, and GSH-Px levels; and Bcl-2 protein expression of mice in the vitexin group and pramipexole group were significantly higher than those in the model group, while the lever- climbing score; NSE and MDA levels; dopaminergic neuron apoptosis rate; and Bax and cleaved caspase-3 protein expression were significantly lower (P< 0. 01). Compared with the pramipexole group, The 5-HT, SOD, and GSH-Px levels and the Bcl-2 protein expression in the vitexin group were significantly higher than those in the pramipexole group, while the MDA level, dopaminergic neuron apoptosis rate, and Bcl-2 protein expression were significantly lower. Conclusions Vitexin has a protective effect on behavioral symptoms and nerve injury in mice with MPTP-induced Parkinson’s disease, and the mechanism may be related to the improvement of catecholamine neurotransmitters, inhibiting oxidative damage and cell apoptosis in the substantia nigra.

Abstract: Objective To investigate the effect of quercetin on cell proliferation, migration, and invasion and PI3K/ AKT pathway regulation in the oral cancer cell line Tca-8113. Methods Tca-8113 cells were cultured in vitro and divided into a control group and quercetin ( 50 μmol / L) treatment group. A CCK-8 assay was used to detect cell proliferation; a Transwell assay ( with Matrigel) was used to detect cell migration ( invasion); quantitative real-time polymerase chain reaction was used to detect the expression of PTEN, AKT, FOXO1, and BCL2L11 mRNA; and Western blot was used to detect FOXO1, p-FOXO1, AKT, p-AKT, PTEN, and BCL2L11 protein expression. Results Compared with the control group, the proliferation, migration, and invasion abilities of Tca-8113 cells in the quercetin treatment group were significantly reduced; the PTEN and BCL2L11 mRNA and protein expression levels were significantly up-regulated (P< 0. 05); and the phosphorylated FOXO1 and AKT levels were significantly down-regulated (P< 0. 01). However, there was no significant difference in the AKT and FOXO1 mRNA expression levels between the two groups. Conclusions Quercetin can inhibit the proliferation, migration, and invasion of Tca-8113 cells. In terms of the underlying mechanism, quercetin may promote the expression of PTEN and negatively regulate the PI3K/ AKT pathway to reduce the phosphorylation level of FOXO1, causing an increase in the expression of BCL2L11.

Abstract: Objective To analyze the expression, protein-protein interaction network, and clinical significance of histamine receptor H3 (HRH3) in hepatocellular carcinoma (HCC) using a public database. Methods The ULACAN database was used to analyze the expression of HRH3 in HCC and normal liver tissues. The STRING database was used to study the protein-protein interaction network, GO, and KEGG pathway of HRH3. The Kaplan-Meier Plotter database was used to study the relationship between the expression of HRH3 and the prognosis of HCC. Results The expression of HRH3 was significantly higher in HCC than in normal liver tissues ( P< 0. 05). Moreover, the expression of HRH3 was not associated with sex, tumor stage, tumor differentiation, lymph node metastasis, or TP53 mutation in HCC. Furthermore, HRH3 interacted closely with 5-hydroxytryptamine receptor family members and metabotropic glutamate receptor family members, functioning as a G protein-coupled receptor to transmit signals in cells. High expression of HRH3 was associated with a good prognosis in the early stage of HCC and with a poor prognosis in the advanced stage of HCC. Conclusions The expression of HRH3 was increased in HCC. HRH3 functioned as a G protein-coupled receptor in HCC cells. HRH3 might function as a tumor suppressor gene in the early stage of HCC and as an oncogene in the advanced stage of HCC.

Abstract: Objective To investigate the protective effect of puerarin on radiation-induced acute intestinal mucosal injury in rats and elucidate the underlying molecular mechanism. Methods Sprague-Dawley rats were randomly divided into three groups of eight rats each: a control group, radiation alone group, and radiation + puerarin group. The rats in the radiation alone group and radiation + puerarin group received a single dose of 12-Gy radiation, and the rats in the radiation + puerarin group were injected with 15 mg( kg·d) of puerarin via the tail vein for 7 consecutive days. Jejunal tissues were collected, and pathomorphologic changes in the intestine were observed by hematoxylin-eosin staining. The expression and distribution of Ki-67 antigen and platelet endothelial cell adhesion molecule 1 in jejunal tissues were detected by immunohistochemical staining. The protein expressions of claudin-1 and zonula occludens protein-1 (ZO-1) in jejunal tissues were detected by Western blot. The malonyldialdehyde level and superoxide dismutase activity in jejunal tissues were detected with the corresponding kits. Results Pathological examination showed that puerarin increased the villus length, maintained the villus epithelial structure, reduced the loss of villus epithelial cells, reduced the loss of crypts, promoted the regeneration of crypt cells, and reduced the density of goblet cells within crypts. Puerarin also significantly restored the reduced expression of claudin-1 and ZO-1 proteins and reduced the oxidative stress injury in jejunal tissues induced by radiation. Conclusions Puerarin protects rats from radiation-induced intestinal injury by promoting the expression of tight junction proteins, reducing oxidative stress injury, promoting the regeneration of crypt cells, and maintaining the integrity of the intestinal villus epithelial structure.

Abstract: Objective To explore the effects of electroacupuncture on synaptic plasticity and microglial polarization and detect the expression of miR-21 / signal transducer and activator of transcription 3 (STAT3) pathway in rats with cerebral ischemia. Methods The distal end of the external carotid artery was double-ligated with a thin wire for 60 minutes to establish a rat model of focal cerebral ischemia. The neurological deficit score was used to evaluate the model preparation. The successful model rats were divided into a model group, electroacupuncture group, and nimodipine group.The control group comprised rats treated by a sham operation. After 3 weeks of treatment, the cerebral infarction volume was measured by 2,3,5-triphenyltetrazolium chloride staining, the synapse ultrastructure was observed by electron microscopy and analyzed by morphometry, and the microglial polarization was assessed by immunofluorescence staining. Additionally, the level of miR-21 in the cerebral cortex of rats in each group was measured by real-time fluorescence quantitative polymerase chain reaction, and western blotting was used to detect the levels of Janus kinase 2 (JAK2), p-JAK2, STAT3, and p-STAT3 in the cerebral cortex of rats in each group. Results The neurological deficit score, cerebral infarction volume, number of M1 microglia, and levels of miR-21, p-STAT3, and p-JAK2 were significantly higher and the number of M2 microglia, numerical density of synapsis (N_v ), volume density of synapsis (V_v ), surface density of synapsis ( S_v ), postsynaptic density (PSD), synaptic curvature, and width of the synaptic cleft were significantly lower in the model group than in the control group (P< 0. 05). The neurological deficit score, cerebral infarction volume, number of M1 microglia, and levels of miR-21, p-STAT3, and p-JAK2 were significantly lower and the number of M2 microglia, N_v, V_v, S_v, PSD, synaptic curvature, and width of the synaptic cleft were significantly higher in the electroacupuncture group and nimodipine group than in the model group (P<0. 05). Conclusions Electroacupuncture can promote synaptic remodeling and induce microglial polarization from M1 to M2 in rats with focal cerebral ischemia.

Abstract: Objective To explore the establishment of a rat model of interstitial cystitis based on intraperitoneal injection of cyclophosphamide. Methods Saline or gradient concentrations of cyclophosphamide were intraperitoneally injected in rats to establish an animal model of interstitial cystitis. The grade of bladder inflammation was then estimated at the histological and molecular levels based on hematoxylin-eosin staining and real-time polymerase chain reaction. The rats’ pain sensation was tested by both behavior recording and Von Frey examination. Mortality during the study was also recorded. Results The bladder inflammatory indices and pain sensitivity of the rats in the 150-, 200-, 250-, and 300- mg cyclophosphamide groups were significantly higher than those of the control rats. Urodynamic examination revealed impaired contraction capacity of the rats’bladders in the 250- and 300-mg cyclophosphamide groups. Rats in the 100-mg cyclophosphamide group showed observable inflammatory changes in their bladders without a significant increase in sensitivity to spontaneous visceral pain or somatic nociception. The rats in the 50-mg cyclophosphamide group showed no alteration of bladder inflammatory indices or pain sensitivity. Some rats died within 48 hours after cyclophosphamide injection in the 200-, 250-, and 300-mg groups. Conclusions Intraperitoneal injection of cyclophosphamide is a feasible and reliable method for the establishment of a rat model of interstitial cystitis, showing the two critical features of this disease: bladder inflammation and pain sensation. Based on our data, we recommend 150 mg / kg as a suitable dose for the establishment of a rat model of interstitial cystitis.

Abstract: Objective To observe the protective effect of salidroside on the mouse model of hyperoxic lung injury and to explore its mechanism of action. Methods Fifty C57BL/ 6 mice were randomly divided into normal control group, model group, positive control group (10 mg / kg dexamethasone), high-dose salidroside group (50 mg / kg) and low-dose salidroside group (25 mg / kg). All mice except those in the normal control group were exposed to hyperoxia for 3 days to establish a model of hyperoxic lung injury. The wet / dry weight (W/ D) ratio and partial pressure of arterial oxygen (PaO₂) of the lung tissues were measured in each group of mice. Hematoxylin-eosin staining was used to observe the pathological changes in the lung tissues of the mice. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the content of TNF-α, IL-1β, IL-6, MDA and SOD activity of lung tissues. Western blot and real-time quantitative polymerase chain reaction were used to detect Notch1, HERP, and HES1 protein and mRNA expression levels. Results Compared with the normal control group, the W/ D value of lung tissues in the model group increased, PaO₂ level decreased, lung tissue structure was disordered, alveolar wall thickened, inflammation infiltration and collagen deposition were obvious, TNF-α, IL-1β, IL-6 content of the lung tissues increased, SOD activity decreased, MDA content increased, Notch1, HERP, HES1 mRNA and protein expression decreased (P<0.05). Compared with the model group, the W/ D value of the lung tissues of the mice in salidroside high-dose group and the low-dose group was significantly reduced, and the PaO₂ level was significantly increased. The lung tissue alveolar structure of the mice in the high-dose salidroside group was basically normal and inflammation cells and collagen deposits were less, the inflammatory factors TNF-α, IL-1β, IL-6 content of the lung tissues decreased, SOD activity increased, MDA content decreased, and the expression levels of Notch1, HERP, HES1 protein and mRNA in lung tissues increased (P<0.05). Compared with the positive control group, the effect of high-dose salidroside was not statistically different (P>0.05). Conclusions Salidroside has a protective effect against hyperoxia- induced lung injury in mice, and its mechanism of action may be related to changes in the expression of the Notch signaling pathway.

Abstract: Objective To investigate the neuroprotective effect of tongxinluo capsule on cognitive impairment of rats exposed to acute hypobaric hypoxia and its related mechanism. Methods Sixty-four male Sprague-Dawley rats were randomly divided into four groups: the control group, tongxinluo group ( TXL group), hypobaric hypoxia group ( HH group), and tongxinluo + hypobaric hypoxia group ( TXL + HH group). All rats were trained in a Morris water maze (MWM) for 5 days prior to hypobaric hypoxia exposure. They were then exposed to hypobaric hypoxia for 7 days. After 7 days, the rats’ cognitive function was evaluated by open field and MWM tests. The hippocampi were then extracted for molecular biological examination. Morphological changes were observed by pathological staining. The expressions of TLR-4, MyD88, IκBα, NF-κB p65, and AQP4 in the hippocampus were detected by Western blot. Results In the behavioral experiment, no significant difference in the open field test was observed among the four groups (P > 0. 05). Likewise, in the training part of the MWM tests, no significant difference in the escape latency was found among the four groups (P> 0. 05). However, in the probe trials, the residence time in the targeted quadrant and the crossing time to the original platform were significantly shorter in the rats exposed to hypobaric hypoxia than in the control group ( P< 0. 05). Tongxinluo treatment significantly attenuated hypobaric hypoxia-induced cognitive impairment ( P< 0. 05 ). Next, measurement of inflammatory markers showed that the serum and hippocampal IL-1β, TNF-α, and IL-6 levels as well as the hippocampal TLR-4, MyD88, and NF-κB p65 protein levels were all significantly higher in the HH group than in the control group (P< 0. 05). The levels of these inflammatory proteins decreased after TXL intervention ( P< 0. 05). Finally, examination of hippocampal tissue damage revealed that hypobaric hypoxia increased the brain water content, with increased AQP4 and MMP-9 expression in the hippocampus (P< 0. 05). The cells in the hippocampus were disordered with obvious swelling and blurred boundaries. However, after TXL intervention, the brain water content and AQP4 and MMP-9 expression were significantly reduced (P< 0. 05). Conclusion Acute hypobaric hypoxia exposure can lead to cognitive impairment and brain edema by activating the TLR-4/ MyD88 / NF-κB pathway. Tongxinluo intervention may improve cognitive impairment and brain edema by inhibiting the TLR-4/ MyD88 / NF-κB signaling pathway.

Abstract: Objective To investigate the effect of resveratrol (RSV) on the lymphotoxin analog ( LIGHT) / herpesvirus entry mediator (HVEM) pathway in rats with preeclampsia ( PE) and its protective effect on kidney injury. Methods Fifty pregnant Sprague-Dawley rats were randomly divided into 5 groups of 10 rats each: the normal group, PE model group, RSV low dose group (50 mg / kg), RSV high dose group (200 mg / kg), and LIGHT/ HVEM pathway blocker group (lymphotoxin beta receptor-immunoglobulin fusion protein [LTβR-Ig], 1600 μg / kg). All rats except those in the normal group were intraperitoneally injected with nitroso-L-arginine methyl ester ( 300 mg / kg, once daily for 5 days) to establish a rat model of PE. After successful establishment of the model, RSV solution was given by gavage to the rats in the RSV low and high dose groups, LTβR-Ig solution was injected via the tail vein to the rats in the LIGHT/ HVEM pathway blocker group, and the same amount of normal saline was given by gavage and tail vein injection to the rats in the Normal and PE groups. Each group was treated once a day for 5 consecutive days. After the last administration, 24-hour urine was collected and blood samples were obtained, and the serum creatinine ( Scr), blood urea nitrogen (BUN), and 24-hour urinary protein were measured as renal function indices using enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the pathological changes of renal tissue. Real-time fluorescent quantitative polymerase chain reaction was used to detect the relative levels of LIGHT and HVEM mRNA in renal tissue. Western blot was used to detect the relative expression levels of LIGHT, HVEM, nuclear factor kappa B (NF-κB), interleukin-6 ( IL-6) in renal tissue. Results Compared with the rats in the Normal group, those in the PE group exhibited pathological damage such as diffuse proliferation of glomerular endothelial cells and higher levels of Scr, BUN, 24-hour urine protein, renal tissue LIGHT mRNA and protein, HVEM mRNA and protein, and NF-κB and IL-6 protein expressions (P< 0. 05). Compared with the PE group, the pathological damage of renal tissue was alleviated in the RSV low dose group, RSV high dose group, and LIGHT / HVEM pathway blocker group; additionally, the Scr, BUN, 24-hour urine protein, renal tissue LIGHT mRNA and protein, HVEM mRNA and protein, and NF-κB and IL-6 protein expressions were lower (P< 0. 05). The changes in these indicators in the RSV high dose group were better than those in the RSV low dose group. No significant difference was observed between the LIGHT/ HVEM pathway blocker group and RSV high dose group (P> 0. 05). Conclusions RSV can inhibit the protein expression of the LIGHT/ HVEM pathway in renal tissue of rats with PE and improve PE-induced renal injury.

Abstract: Objective To explore the effects and mechanism of Shenqu Xiaoshi oral liquid ( SXOL) on gastrointestinal motility in mice with functional dyspepsia (FD). Methods This study involved 50 KM mice. Ten mice were randomly assigned to the normal group, and the remaining 40 mice were used to establish animal models of FD by the irregular eating and L-arginine method . They were then randomly divided into a model group, low-dose SXOL group, medium-dose SXOL group, and high-dose SXOL group. Routine blood and liver/ kidney function indexes were measured. Their body weight was recorded, gastric residual rate and intestinal propulsion rate were calculated, and pathological changes in gastric tissues were observed. Real-time quantitative polymerase chain reaction and Western blot were used to detect expression of inositol-requiring enzyme 1 (IREl) and tumor necrosis factor receptor-associated factor 2 (TRAF2) in gastric tissues. Results There were no significant differences in the white blood cell count, red blood cell count, hemoglobin concentration, platelet count, lymphocyte count, monocyte count, neutrophil count, aspartate aminotransferase concentration, alanine aminotransferase concentration, total bile acid concentration, blood urea nitrogen concentration, or creatinine concentration among all groups ( P> 0. 05). The structure of the gastric mucosal layer, submucosal layer, muscle layer, and serosal layer in each group was clear, and there were no obvious pathological changes. Compared with the model group, the gastric emptying rate and small intestinal propulsion rate were significantly higher in the low-dose, medium-dose, and high-dose SXOL groups, while expression of IREl and TRAF2 mRNA and protein was significantly decreased in gastric tissues (P< 0. 05). Conclusions SXOL has no significant effects on routine blood and liver/ kidney function indices in normal mice. However, SXOL can significantly improve gastrointestinal motility function in mice with FD, which may be related to down-regulation of the expression of the endoplasmic reticulum factors IR11 and TRAF2.

Abstract: Objective To explore the protective effect of curcumin ( Cur) on acute renal injury caused by pregnancy-induced hypertension ( PIH) and to explore the mechanism of any effect. Methods Thirty-two pregnant Sprague-Dawley female rats were divided into four groups: normal, curcumin, PIH, and PIH + curcumin groups. Rats in the PIH and PIH + curcumin groups were injected with 26 mol / L NG-nitro-L-arginine methyl ester every day for 4 days to induce PIH. The rats in the curcumin and PIH + curcumin groups were fed curcumin 204. 8 mol / L ( suspended in 2% carboxymethyl cellulose solution) from day 18 for 7 days. Hematoxylin-eosin staining, enzyme-linked immunosorbent assays and spectrophotometry were used to detect a series of indicators to evaluate the pathological morphology of kidney tissue, renal function, oxidative stress and inflammation. Immunohistochemistry and Western blot were used to detect the expression levels and distribution of TGF-β1 and p-SMAD3. Results Compared with the PIH group, the renal function of rats in the PIH + curcumin group was significantly improved (P<0. 01), and renal tissue damage and oxidative stress were also significantly reduced (P<0. 01). The renal tissue score decreased from 191. 23±18. 82 to 108. 35±11. 24 (P<0. 01). Levels of TGF-β1 and p-SMAD3 in the kidneys of PIH group rats were significantly increased, but decreased significantly after the application of curcumin. The expression of TGF-β1 decreased from (356. 25±40. 13)% to (178. 40±18. 45)% (P<0. 01). p-SMAD3 / SMAD3 decreased from (312. 82±30. 26)% to (143. 05±15. 31)% (P<0. 01). Conclusions Curcumin can protect against acute kidney injury in pregnant hypertensive rats by regulating the TGF-β1 pathway.

Abstract:Autoimmune diseases (AIDs) are disorders in which the body reacts to autoantigens, leading to tissue damage. The exact pathogenesis of AIDs is still unknown. Many studies have shown that genetic factors play an important role in the occurrence and development of AIDs. In recent years, the development and application of whole-exon sequencing technology has identified several genetic variants associated with AIDs and has confirmed that these variants are involved in various disease processes through different mechanisms, including breaking immune tolerance and affecting disease severity and prognosis. This has promoted a greater understanding of AIDs. Therefore, this article reviews the application and research progress of whole-exon sequencing in patients with systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, psoriasis, Sjogren’s syndrome, and Beh?et’s disease in an effort to more clearly understand the pathogenesis of AIDs and provide new ideas for diagnosis and treatment.

Abstract:Testicular orphan nuclear receptor 4 (TR4)plays an important regulatory role in many key physiological processes, and the signal dysregulation it controls are related to many diseases. In recent years, the role of TR4 in prostate cancer has received increasing attention. Systematic analysis and understanding of the role of TR4 in the initiation, development, and treatment of prostate cancer are of great significance to improving the precise treatment strategy for prostate cancer.

Abstract:Alcoholic liver disease (ALD) is a chronic progressive disease with no effective drug therapy. The characteristics of multi-target and multi-pathway treatment using traditional Chinese medicine (TCM) are highly consistent with the overall regulation effect of the gut microbiota. TCM can be used to treat ALD by improving the gut microbiota structure, restoring the gut barrier function, and relieving gut inflammation. This report focuses on the progress in research of the use of TCM to regulate ALD, summarizes the relationship between the gut microbiota and ALD, and discusses the role of TCM in ALD in terms of its regulation of the gut microbiota, improvement of the gut microbiota structure, restoration of the gut barrier function, and relief of gut inflammation. The overall aim of this report is to provide a reference for the study of the mechanism of TCM in the treatment of ALD.

Abstract:AbstractArrhythmia is one of the most common abnormalities of the circulatory system and can affect the functions of many important organs, including the heart, brain, and kidneys. Severe arrhythmia can be life-threatening; sudden cardiac death caused by arrhythmia accounts for approximately 25% of all deaths. The underlying pathophysiological mechanism of arrhythmia remains incompletely understood. In-depth research on the pathogenesis of arrhythmia is helpful to the development of new clinical prevention and treatment strategies, and the establishment of precision animal models is an important basis for the study of pathogenesis. Such models are not only effective research tools but can also be used for the study of pathogenesis and drug intervention measures. Therefore, this article summarizes and compares the progress in research using animal models of arrhythmia in China and abroad, including the species characteristics of the model application, the preparation principle, and the model application. The overall aim is to provide a basis for the selection of models for arrhythmia-related research.

Abstract:Alzheimer’ s disease (AD) is a neurodegenerative disorder characterized by impairment of cognitive memory. The clinical treatment of AD is currently dominated by a few drugs; however, these drugs can only be applied to relieve symptoms without slowing or stopping the progression of AD. Moreover, these drugs have weaker effects in patients with advanced AD. Stem cell therapy is recognized as a promising approach for AD therapy because of the self-renewal and multi-directional differentiation ability of stem cells. As the first described mesenchymal stem cells, bone marrow mesenchymal stem cells ( BM-MSCs) are reported to easily expand in the in vitro condition, readily differentiate into neuron-like cells, and contribute to immunomodulation and microenvironment remodeling by producing abundant immunomodulatory molecules. All of these properties endow BM-MSCs a potentially significant role in the clinical treatmen of AD. This paper summarizes the current information about the application of BM-MSCs in AD treatment, including direct transplantation of BM-MSCs, transplantation of genetically modified BM-MSCs, and injection of BM-MSC-derived exosomes. The therapeutic effects and underlying mechanisms as well as the advantages and disadvantages of BM-MSCs in AD treatment are also discussed to provide fundamental support for the future clinical application of BM-MSCs.

Abstract:Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disease caused by irreversible damage to pancreatic β cells. No effective cure for T1DM has been established. Daily injection of exogenous insulin is the primary way to maintain quality of life in patients with T1DM. Although islet transplantation is an effective therapy for T1DM, it is limited by the severe shortage of donors and permanent immunosuppression. The replacement of pancreatic β cells by stem cells is an innovative biomedical therapy that aims to restore the function of the islets and replace exogenous insulin in patients with T1DM. This review summarizes the progress in the research of stem cell-differentiated pancreatic β cell treatment in recent years and provides references for the clinical application of stem cell therapy in the treatment of T1DM.

Abstract:Alzheimer’ s disease ( AD) is a widespread neurodegenerative disease caused by complicated pathogenic factors. Its pathological features include β-amyloid precipitation in the brain, neurofibrillary tangles, and brain atrophy, and its clinical manifestations are brain cognitive dysfunction and memory loss. Astrocytes are widely distributed and abundant in the central nervous system. These cells can have protective or harmful effects in different periods of the disease course of AD through a variety of mechanisms. In recent years, astrocytes have received increasingly more attention with respect to their role in the pathophysiological mechanism of AD. This article focuses on the current status of the field of astrocyte research, especially their functional characteristics and the latest research progress in the pathological characteristics of AD. The overall aim of this report is to provide a theoretical basis for the treatment of AD and other neurodegenerative diseases.

Abstract:Alzheimer’ s disease ( AD) is a chronic progressive neurodegenerative disease characterized by dementia as the main symptom. The main neuropathologic features include senile plaques, neurofibrillary tangles, neuroinflammation, and neuron loss. Deposition of amyloid β-protein and misfolded tau protein in patients with AD induces the activation of microglia; this leads to the secretion of cytokines and chemokines, which jointly induce a neuroinflammatory response and affect the progression of AD. This review briefly summarizes the role of microglial activation and chemokine release in the neuroinflammation of AD and provides new insight into the treatment of AD.