Abstract: Objective Establish a reasonable and stable rat model of uric acid nephropathy to provide a pathological model for screening, research, and treatment of uric acid nephropathy. Methods Experimental rats were randomly divided into three model groups and a control group. Model mice were administrated orally with 750 mg / kg oteracil potassium combined with 150 mg / kg low dose uric acid (M-A), 750 mg / kg oteracil potassium combined with 300 mg / kg medium dose uric acid (M-B), or 750 mg / kg oteracil potassium combined with 600 mg / kg high dose uric acid (M- B). After continuous intragastric administration for 4 weeks, changes in blood uric acid, blood creatinine, urea nitrogen, triglycerides, cholesterol and other indicators as well as pathological changes of the kidneys were observed for 4 weeks. Results Compared with the control group, the serum uric acid of the three model groups was significantly higher (P< 0.01, P<0.05, P<0.05), serum creatinine of the M-B and M-C groups was increased significantly (P<0.05, P<0. 01), triglycerides of the M-B group were significantly lower (P<0.05). Renal pathology scores of M-B and M-C groups were significantly higher those of the control group (P<0.01). Masson staining of morphology showed that, in comparison with the control group, kidney damage was more obvious in the three model groups ( P< 0.05, P< 0.01, P< 0.01 ). Immunohistochemical staining of inflammation marker CD68 showed that, compared with the control group, its expression was increased of in three model groups (P<0. 05, P<0. 01, P<0. 01). Expression of epithelial cell marker E-Cadherin was significantly reduced in M-B and M-C groups in comparison with to the control group ( P< 0.01 ). Expression of myofibroblast marker protein α-SMA was increased the three model groups compared with the control group (P<0.05, P< 0.01, P<0.01). Conclusions Oteracil potassium (750 mg / kg) combined with the middle dose of uric acid (300 mg / kg) is ideal to establish a rat model of uric acid nephropathy.

Abstract: Objective To investigate whether the Isodon ternifolius ( D. Don ) Kudo attenuates carbon tetrachloride (CCl₄ )-induced liver fibrosis in rats by downregulating the nuclear transcription factor-κB (NF-κB) signaling pathway through interference with IκB-α phosphorylation. Methods Hepatic fibrosis was induced in rats with CCl₄ . Biochemical analysis was used to detect alanine aminotransferase (ALT) and hydroxyproline ( HYP), and the enzyme- linked immunosorbent assay was used to detect transforming growth factor (TGF-β1), α-smooth muscle actin (α-SMA), interleukin-6 (IL-6) and tumor necrosis factor-α ( TNF-α) levels in sera. Fluorescence quantitative PCR was used to detect Toll-like receptor 4 (TLR4), NF-κB p65, IκB-α mRNA expression, and Western blot were used to analyze TLR4, NF-κB p65, and phosphorylated (p)-IκB-α protein expression in rat liver tissues. Hematoxylin-eosin staining was used to evaluate histopathological damage in the rat livers. Results Compared with that in the model group, the pathological damage to the livers of rats treated with Isodon ternifolius (D. Don) Kudo extracts was ameliorated; the levels of ALT, HYP, TGF-β1, α-SMA, IL-6 and TNF-α in the serum of rats with liver fibrosis treated with Isodon ternifolius (D. Don) Kudo extracts were significantly reduced; the expression of TLR4 and NF-κB p65 mRNA were significantly inhibited; IκB- α mRNA was significantly upregulated; and the expression of TLR4, NF-κB p65 and p-IκB-α protein was downregulated. Conclusions Isodon ternifolius (D. Don) Kudon alleviated liver fibrosis by downregulating IκB-α phosphorylation and inhibiting activation of the NF-κB signaling pathway.

Abstract: Objective To investigate the effect of theca cells on granulosa cells injured by chemotherapy and the intervention effect of serum containing Zuogui pill ( ZGW). Methods Serum containing Zuogui pill components was prepared. Granulosa and theca cells were cultured and divided into 8 groups, including blank control group, coculture group, ZGW serum group, ZGW serum+coculture group, model group, model+coculture group, model+ZGW serum group and model+ZGW serum+coculture group. The expression levels of Bax, Caspase-3, Beclin 1, p62 and LC3B were detected by qRT-PCR and Western blot. Results Beclin-1, LC3B, Bax and Caspase-3 were highly expressed in the model group at the transcriptional and translational levels, which were downregulated after adding 10% serum containing Zuogui pill components or co-culturing with theca cells. The gene expression of p62 was lower in the model group than that in the control group, and was upregulated by adding 10% serum containing Zuogui pill components or co-culturing with theca cells. When the experimental group was co-cultured with theca cells, the expression of these genes changed more substantially after the addition of 10% serum containing Zuogui pill components. Conclusions Theca cells alleviated the chemotherapy-induced injury of granulosa cells in vitro and demonstrated a synergistic effect with serum containing Zuogui pill components. These effects were related to the inhibition of autophagy and reduction in apoptosis of granulosa cells.

Abstract: Objective To determine the effects of Yinxing Mihuan (YM) oral solution on the proliferation, migration, tubule formation and protein expression of vascular endothelial growth factor (VEGF) and CD31 in rat cardiac microvascular endothelial cells (CMECs) and whether YM promotes angiogenesis in vitro. Methods CMECs were cultured and divided into a control group and YM high dose (2. 6 mg / mL), YM medium dose (1. 3 mg / mL) and low dose (0. 6 mg / mL) YM groups. The cell counting CCK-8 assay was used to measure proliferation, and the scratch test was used to detect the migration of CMECs. A Matrigel-based angiogenesis assay was used to detect tube formation by CMECs, and Western blot were used to detect the expression of VEGF and CD31. Results Compared with that in the control group, the high, medium and low YM doses significantly promoted the proliferation of CMECs, and the proliferation rate in YM high dose YM group was significantly higher than that in YM medium and low dose YM groups. Six hours after scratching the CMEC monolayer, the migration rate of CMECs in YM high dose YM group was significantly higher than that in the control group; the migration rates of CMECs in YM medium and low dose YM groups were increased, but there was no significant difference compared with the control group. Twenty-four hours after scratching the monolayer, the migration rates of CMECs in YM high, medium and low dose groups were significantly increased compared with that in the control group. The Matrigel matrix number, area and cross points for CMECs in YM high dose group were significantly improved compared with those in YM medium and low dose YM groups. Compared with that in the control group, the expression of VEGF and CD31 in YM high and medium dose YM groups was significantly increased. Conclusions YM can promote proliferation, migration, angiogenesis and expression of VEGF and CD31 proteins in CMECs in vitro. These effects were dose-dependent, suggesting that YM has a significant ability to promote angiogenesis.

Abstract: Objective To compare and analyze the differences between two commonly used modeling method for rabbit knee osteoarthritis (KOA) and provide references for the selection and establishment of different types of animal models for knee osteoarthritis. Methods Nine healthy New Zealand white rabbits were randomly divided into 3 groups: blank group, modified Hulth group and collagenase group. The model groups were treated with a modified Hulth method or intra-articular injection of collagenase. After 1 week, the rabbits were encouraged to move daily. After 6 weeks, they were evaluated using Lequesne MG scores, X-rays, micro-computed tomography, Pelletier scores, Mankin scores and enzyme- linked immunosorbent assays, and then the gross and pathological changes in the knee were observed. Results Compared with that in the blank group, the cartilage surface of the rabbit knee joints in the two model groups displayed defects. The pathological result showed that the cartilage layer appeared to be cracked, safranin O staining was decreased, the tide line was distorted, and the blood vessels passed. The concentrations of TNF-α in serum from the blank group, modified Hulth group, and collagenase group were (624. 99 ± 17. 82), (1140. 56 ± 129. 81) and (1480. 69 ± 492. 08) pg / mL, and the IL-1β concentrations in serum were (30. 23 ± 0. 25), (46. 67 ± 0. 71) and (46. 82 ± 1. 04) pg / mL, respectively. The modified Hulth and collagenase groups showed statistically significant differences compared with that in the blank group (all P<0. 05). In addition, the modified Hulth group was accompanied by osteophyte formation in the knee joint and more serious damage in the medial femoral condyle cartilage, while the medial tibial condyle was the main injury in the collagenase group. Conclusions Both modeling method can be used to construct an ideal KOA model. The degree of damage using the modified Hulth method was more serious, while the collagenase-induced model was closer to the process and pathogenesis of human KOA.

Abstract: Objective To explore the role of the long non-coding RNA ( lncRNA) taurine up-regulated gene 1 (TUG1) in the regulation of microRNA (miR)-137 and nerve injury in rats with focal cerebral ischemia. Methods The dual luciferase assay was used to identify the target sites of miR-137 and TUG1. A rat model of focal cerebral ischemia was established using the Longa thread bolt method. Ischemic rats were randomly divided into the following groups (n= 12): model group, small interfering RNA ( si)-negative control ( NC) group ( 10 μL si-NC), si-TUG1 group ( 10 μL si- TUG1), si-TUG1 + anti-miR-NC group (10 μL si-TUG1 and 10 μL anti-miR-NC), si-TUG1 + anti-miR-137 group (10 μL si-TUG1 and 10 μL anti-miR-137). Another group of 12 rats were used in the sham surgery group. Once every 5 days, three injections and detection on the 16th day. The levels of TUG1 and miR-137 in the hippocampus were detected by real- time fluorescence quantitative PCR (RT-qPCR). Cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride staining. The morphology of hippocampal neurons was observed by hematoxylin-eosin and Nissl staining, and the protein levels of JAK1, STAT1, B-cell lymphoma-2 (BCL-2), BCL-2-associated X protein (BAX) and cysteinyl aspartate-specific proteinase-3 (caspase3) were detected by Western blot. Results Starbase analysis showed that there were complementary binding sites between miR-137 and TUG1, which were verified by the double luciferase assay. In the model group, neurons in the hippocampus were disordered, the number of neurons was decreased, neuronal gaps were larger, some neurons underwent nuclear pyknosis or dissolution, nucleoli disappeared, and the number of Nissl bodies decreased. In the si-TUG1 group, the number of neurons increased, the morphology of neurons recovered, and the number of Nissl bodies increased. Compared with that in the si-TUG1 group, damage to the neurons in the si-TUG1 + anti-miR-137 group was more serious, neuronal gaps were larger, and the number of neurons decreased. Compared with those in the sham surgery group, the cerebral infarction volume; TUG1 RNA; and JAK1, STAT1, BAX, and caspase3 protein levels in the hippocampus were higher in the model and si-NC groups (P<0. 05), and the levels of miR-137 and BCL-2 protein were lower (P<0. 05). Compared with that in the model and si-NC groups, the levels of TUG1, JAK1, STAT1, BAX, and caspase3 in the hippocampus and cerebral infarction volume in the model and si-NC groups were lower (P<0. 05), and the miR-137 and BCL-2 levels in the hippocampus were higher (P<0. 05). Compared with that in the si-TUG1 and si-TUG1 + anti-miR-NC groups, TUG1 RNA and JAK1, STAT1, BAX, and caspase3 protein in the hippocampus and cerebral infarction volume were higher in the model and si-NC groups (P<0. 05), and the level of miR-137 and BCL-2 protein in the hippocampus were lower ( P< 0. 05). Conclusions Interfering with TUG1 lncRNA upregulated miR-137 and alleviated neuronal ischemic morphology and apoptosis in rats with focal cerebral ischemia, thus protecting against nerve injury.

Abstract: Objective To investigate the effect of naringenin (NAR) on microglial activation in oxygen-induced retinopathy (OIR) based on the microRNA (miR)-223 / nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) axis. Methods Seven-day-old (P7) C57BL/ 6J mice ( n= 150) were divided into normoxia, OIR, NAR, NAR + negative RNA control and NAR + miR-223 antagomir groups with 30 mice per group. Except for mice in the normoxic group, the young mice and their mothers were moved to a closed oxygen box with an oxygen volume fraction of (75 ± 2)% for 5 consecutive days from P7~ P12 and subsequently returned to a normoxic environment; the normoxic group was raised in a normoxic environment. The 12-day-old mice in the NAR groups were injected intraperitoneally with 100 mg / (kg ·d) NAR. The mice in the NAR + negative RNA control group were also injected with 2. 5 mg / kg miR-223 negative control RNA via the tail vein, and mice in the NAR + miR-223 antagomir group were injected with 2. 5 mg / kg miR-223 antagomir via the tail vein. Mice in the normoxic and OIR groups were intraperitoneally injected with an equal volume of carboxymethyl cellulose and tail vein-injected with an equal volume of normal saline each day. For evaluation of retinas in the young mice, real time quantitative PCR (RT-qPCR) was used to detect the level of miR-223; fundus fluorescein angiography was performed; hematoxylin eosin staining was used to observe morphology; immunofluorescence was used to detect the expression of the microglia marker calcium binding protein-1 (Iba-1); and Western blot were used to detect the expression NLRP3, cysteinyl aspartate-specific proteinase-1 ( Caspase-1), interleukin ( IL)-1β and IL-18. Results In the OIR group, blood vessels were ruptured, fluorescence leaked in the retina, the retinas were white, blood vessels were contracted, the retinas were thickened, cell arrangement was loose, and some cells were missing and angiogenesis occurred. In the NAR and NAR + negative RNA control groups, vascular rupture and retinal whitening were alleviated, but retinal cells were still loosely arranged. In the NAR + miR-223 antagomir group, vessels were ruptured, fluorescence leaked in the retina, retinal whitening was obvious, and retinal cells were severely loosened and missing. Compared with that in the normoxic group, miR-223 levels in retinas of the OIR mice decreased (P<0. 05), and the retinal levels of Iba-1, NLRP3, Caspase-1, IL-1β, IL-18 increased (P<0. 05). Compared with that in the OIR group, miR-223 levels in the retinas from the NAR and NAR + negative RNA control groups increased (P<0. 05), and retinal levels of Iba-1, NLRP3, Caspase-1, IL-1β and IL-18 decreased (P<0. 05). Compared with that in the NAR and NAR + negative control groups, retinal levels of miR-223 in the NAR + miR-223 antagomir group decreased (P<0. 05), and the levels of Iba-1, NLRP3, Caspase-1, IL-1β and IL-18 increased (P<0. 05). Conclusions NAR increased the expression of miR-223 and inhibited components of the NLRP3 inflammasome, thus alleviating the over-activation of microglia and reducing OIR.

Abstract: Objective The mouse ear blue staining test was used to evaluate anaphylactoid reactions to different injected doses of osteopeptide. Methods The positive model was selected by using histamine phosphate, histamine hydrochloride and histamine as the positive drugs. Mouse ear blue staining tests were performed by injecting different doses of osteopeptide. The rate of blue staining and the rising rate of evans blue were used as the indices for evaluating the anaphylactoid reactions. Results The positive model established by histamine phosphate as the positive drug exhibited obvious anaphylactoid reactions. The osteopeptide injections showed positive reactions to various degrees at high and medium doses and negative reactions at low doses. Conclusions Based on the result of the mouse ear staining test, the anaphylactoid reactions to osteopeptide injections at different doses were intuitively evaluated. These data may be used as a reference for the evaluation of anaphylactoid reactions of other complex matrix preparations.

Abstract: Objective To investigate the method of using isoproterenol ( ISO) to induce myocardial injury in rhesus monkeys. Methods Eleven rhesus monkeys were selected and divided into a high-dose, low-dose and control group. The injections of ISO in the model groups were 4. 6 mg / kg (high-dose) and 3. 2 mg / kg (low-dose) and conducted twice per day. The control animals were injected with 1 mL of normal saline once per day. Color Doppler ultrasound imaging examinations were performed on days 1, 3, 5, 7 and weeks 2, 3, 4, and 5 after the injections and included: IVSTd, IVSTs, LVPWTd, LVPWTs, LVEDD, LVESD, EF, FS, LVM. Electrocardiography was used to measure the changes in cardiac electrical activity. AST, ALT, LDH, CK, CK-MB, PLR, NLR and other physiological and biochemical indicators in the blood were measured. Results In the high-dose group, AST, ALT, LDH, CK, CK-MB, PLR and NLR increased significantly within one week of ISO administration. Furthermore, IVSTd, IVSTs, LVPWTd, LVPWTs, LVEDD and LVESD increased, EF and FS decreased. Compared with that in the high-dose group, these values in the low-dose group were similar to the control group. The electrocardiography result showed that the T wave and ST segments changed to varying degrees by the fifth week after ISO administration. Conclusions Subcutaneous injection of ISO can induce myocardial injury in rhesus monkeys. These comprehensive indices of echocardiography, electrocardiography, and hematology can be used as the basis for evaluating non-invasive heart injury in rhesus monkeys.

Abstract: Objective To investigate the effects of sevoflurane on hypoxia-induced inflammatory responses of microglia and regulation of the nuclear factor erythroid 2-related factor 2 (NRF2) / heme oxygenase 1 (HO-1) / high mobility group protein B1 (HMGB1) pathway. Methods BV-2 mouse microglia were activated by inducing hypoxia for 0, 2, 4, 6, 8 and 12 h to establish an inflammation model. The activated cells were observed by inverted microscope, and the proportion of activated cells was calculated. Western blot were used to detect the expression levels of NRF2, HO-1, HMGB1 and interleukin (IL)-1β proteins in microglia. The optimal hypoxia time was 8 h. BV-2 microglia were activated under hypoxic conditions for 8 h; treated with different concentrations of sevoflurane (0%, 2%, 4% and 6%) for 30 min; and NRF2, HO-1, HMGB1, IL-1β protein expression was observed. BV-2 cells were divided into a control group, hypoxia- induction group, 6% sevoflurane group, SnPP group ( NRF2 / HO-1 pathway inhibitor stannous porphyrin), and 6% sevoflurane + SnPP group. The ratio of activated cells was calculated, and the protein expression levels of NRF2, HO-1, HMGB1, nuclear factor-κB p65 (NF-κB p65), phosphorylated NF-κB p65 (p-NF-κB p65) and IL-1β were determined. Results With prolonged hypoxia time, the proportion of activated cells and expression of HMGB1 and IL-1β gradually increased, and NRF2 and HO-1 proteins decreased to the lowest level at 8 ~ 12 h ( P< 0. 05). Therefore, the hypoxia- induction time of 8 h was chosen. With the increase in sevoflurane concentration, the proportion of activated cells and expression of HMGB1 and IL-1β gradually decreased, and NRF2 and HO-1 expression gradually increased (P< 0. 05). These effects were dose-dependent, and 6% sevoflurane was selected as the treatment concentration. Compared with that in the control group, the expression of NRF2 and HO-1 in the hypoxia-induced group decreased, and the proportion of activated cells and expression of HMGB1, IL-1β and p-NF-κB p65 / NF-κB p65 expression increased ( P< 0. 05). The changes in the above indices in the 6% sevoflurane group were opposite to those in the hypoxia-induced group (P<0. 05). The changes in the SnPP group were consistent with those in hypoxia-induced group and were more serious than those in hypoxia-induced group (P<0. 05). The changes in the above parameters in the 6% sevoflurane + SnPP group were opposite to those in 6% sevoflurane group ( P< 0. 05). Conclusions Sevoflurane treatment reduced hypoxia-induced microglial activation and inflammatory processes by promoting NRF2 / HO-1 activation and inhibiting HMGB1 expression.

Abstract: Objective To investigate the effects of the long non-coding RNA ( LncRNA) SNHG1 on the proliferation and metastasis of skin squamous cell carcinoma induced by interleukin ( IL)-6. Methods The relative expression of SNHG1 was detected by qRT-PCR, and cell viability was detected using the cell counting kiT-8 assay. The migration and invasion ability of the cells was detected using the Transwell system, and protein expression of the proliferation marker Ki67, matrix metalloproteinase-2 (MMP-2), E-cadherin, N-cadherin and vimentin was detected by Western blot. Results Compared with that in the normal skin cell line HaCaT, the expression of SNHG1 was significantly increased in the skin squamous cell carcinoma lines A431, SCC13 and SCL-1. After A431 cells were treated with different concentrations of IL-6, the relative expression of SNHG1, cell viability, and number of migrating and invading cells increased significantly compared with that in untreated cells. Furthermore, the expression of Ki67, MMP-2, N-cadherin and vimentin protein was upregulated, whereas E-cadherin protein was downregulated after IL-6 treatment and the expression was dose-dependent. The relative expression of SNHG1, cell viability, number of migrating and invasive cells, and expression of Ki-67, MMP-2, N-cadherin, and vimentin proteins in the IL-6+si-SNHG1 group were significantly lower than those in the IL-6+si-NC group and the expression of E-cadherin protein was significantly higher than that in the IL-6+si- SNHG1 group. Conclusions Interference with SNHG1 expression inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition of skin squamous cell carcinoma cells induced by IL-6.

Abstract: Objective To simulate the detection of plankton-aerosols generated by the rearing and flushing of rhesus monkeys using standard operating procedure ( SOP ) for microbes in an animal biosafety level 3 ( ABSL-3) laboratory. Methods The ground excreta and filter basket at the outlets of the monkey cages were measured during the stationary or feeding state. The SOP for feeding the monkeys and cleaning the cages was either not strictly followed or was strictly followed. A bacillus bacterium was used as the indicator microorganism and aerosols were collected using the Sedolis Airport MD 8 portable plankton sampler. The detection method included live cell cultures and PCR detection. Results (1) In the stationary state, there were < 5 bacteria. (2) In the feeding state, the bacterial culture count from the floor of the monkey cage was approximately 30 / dish. The yeast growth number was 1 / dish, and the bacterial count in the filter basket at the drain outlet was > 300 / dish accompanied by the growth of > 10 / dish. ( 3) The comparative test result demonstrated that the growth of bacteria and yeast was significantly reduced when strict SOP was followed for cleaning compared with not following the SOP. No bacterial DNA was detected on the absorbent mat. Conclusions The risk of microbiological contamination can be effectively controlled by strict implementation of SOPs for feeding and cleaning cages of rhesus monkeys in the ABSL-3 laboratory.

Abstract:Thyroid disease is a common endocrine system disease, and its etiology is complex and diverse. At present, research on thyroid diseases is mainly limited to the evaluation of clinical efficacy of drugs with few studies on the pathogenesis of this disease. Therefore, it is important to establish animal models of thyroid diseases for analyzing pathological mechanisms and improving the clinical efficacy of disease treatment. A successful experimental animal model can not only increase disease samples in a short period of time with low cost but also avoid harm to the human body. Furthermore, animal models have the advantage of stability. This review summarizes the method used to establish animal models of thyroid diseases in recent years, such as those for hypothyroidism, hyperthyroidism, hashimoto’s thyroiditis, and thyroid cancer, and analyzes the advantages and disadvantages of various models to provide a theoretical basis for the development of related experiments.

Abstract:Cardiovascular diseases constitute a substantial health and economic burden worldwide. Kruppel like factor 2 is a key cardiovascular-protective transcription factor and is involved in the pathophysiological processes of cardiovascular diseases, such as atherosclerosis, stroke, myocardial infarction and heart failure. This paper reviews the biological functions and mechanisms of Kruppel like factor 2 and research progress in cardiovascular diseases.

Abstract:TRIM46, a relatively novel tripartite motif (TRIM) family protein, consists of two RING fingers, a B- box motif, a coiled-coil region, C-terminal COS, FN3 and B30. 2 / SPRY domains. TRIM46 controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays. TRIM46 plays a role in tumor proliferation and migration and is also involved in innate immune regulation. The data from Genecards suggested that TRIM46 was highly expressed in the brain, although it was broadly expressed in other human organs. This review focuses on recent studies of TRIM46 protein structure and function. Future research directions and method for gene-edited animals regarding TRIM46 are also predicted and discussed.

Abstract:Liver fibrosis is an important topic in the field of liver disease research, and the establishment of animal models for liver fibrosis is key to exploring the pathogenesis of this disease. This article summarizes the ten commonly used types of mice models of liver fibrosis and discusses their respective mechanisms, Methods of establishment, effects, and advantages and disadvantages of establishing a particular mice model. The differences and similarities between the models are compared to provide a reference for the selection of an appropriate model for liver fibrosis research.

Abstract:Biliary atresia (BA) is an important indication for liver transplantation during the neonatal period. With the improvement in diagnostic techniques in recent years, the diagnosis rate for BA is increasing continuously. However, the specific etiology and pathogenesis of BA remains unclear. Related knowledge and research models for BA are still relatively limited in China. At present, the BA models are divided mainly into three categories: drug or poison- induced, mechanical biliary tract ligation and rotavirus-induced. Among them, the drug-poison-induced BA model is selective to the bile duct, and there are still many unsolved problems. Although the method of biliary ligation causes bile duct atresia, it is inconsistent with the onset age of BA in the real world. The rotavirus-induced bile duct atresia model is widely accepted and is the main research model at present; however, all of the animals die before the formation of liver fibrosis, and this model does not fully reflect the disease progression process of BA. The rotavirus gene recombination method may result in liver fibrosis and is a promising model because the survival time of the animals is relatively long, and the model more closely relates to the actual pathological process. In general, BA still lacks an ideal animal model that fully conforms to clinical practice and reflects the development of clinical disease.

Abstract:Currently, many countries have rapidly stepped into the aging society and the elderly population is growing sharply. The aging process is accompanied by a series of changes in the immune system, which is known as “immunosenescence” and leads to an increase in the incidence of various infections and mortality from geriatric diseases, increasing the demand for healthcare in all counties. Periodontitis is chronic inflammation of periodontal tissue caused by an interaction between pathogenic bacteria and host immune system, which has shown a rising trend in vulnerability and periodontal destruction in the elderly population. It seriously affects both physical and mental health of the elderly and increases the medical burden. This article reviews the effects of senescence and immunosenescence on periodontitis, especially the effects of aging on immune cells, which include innate immune cells and adaptive immune cells, on periodontitis.

Abstract:Demyelination and autoimmune chronic inflammation in the central nervous system are the typical pathological features of multiple sclerosis (MS). A range of immune and nerve cells participate in the disease process of MS. The regulation of inflammation and remyelination is mainly performed by microglia ( MG) and oligodendrocyte precursor cells (OPCs), respectively. In non-repairing lesions of MS patients, an imbalance of MG polarization and a failure of OPC differentiation are likely to contribute to inefficient remyelination. Previous researchers have emphasized that these are independent functions. However, it has recently been reported that MG polarization is closely connected with OPC differentiation, an imbalance of MG polarization can inhibit OPC differentiation. Conversely, OPCs can also interfere with the inflammatory response of MG. Taken together, interactions between MG and OPCs form a holistic entity and function as a crucial mechanism of remyelination. Currently approved treatments for MS mainly target the aberrant immune response, and are able to improve the disease-related symptoms but do not cure MS, particularly intractable secondary progressive multiple sclerosis ( SPMS ). Therapeutic strategies or agents that promote remyelination remain under extensive investigation. This review summarizes the interactions between MG polarization and OPC differentiation, and provides strategies to overcome the failure of OPC differentiation by attempting to rebalance MG polarization, which will be beneficial for the development of demyelinating diseases including SPMS.

Abstract:Skeletal muscle dysfunction (SMD) is a common complication of chronic obstructive pulmonary disease (COPD), which usually causes a decline in exercise activity and quality of life. Mitochondrial injury is one of the main mechanisms by which SMD coexists with COPD, and injury is mainly caused by oxidative stress, energy metabolism disorders, and abnormal autophagy. An increase in mitochondrial reactive oxygen species production leads to oxidative stress and decreased mitochondrial biosynthesis, volume density, and mitochondrial respiratory function (respiratory control ratio evaluation). Decreased mitochondrial membrane potential and ATP synthase activity and excessive opening of the mitochondrial membrane permeability transition pore may result in mitochondrial-mediated metabolic disorders. Severe oxidative stress and systemic inflammation can trigger abnormal mitochondrial autophagy and accelerate degradation and clearance of mitochondria. Traditional Chinese medicine ( TCM) has obvious benefits in improving exercise ability and quality of life in patients with COPD. With the in-depth study of TCM in recent years, TCM has been shown to improve mitochondrial injury after treatment of COPD-induced SMD. In this study, we reviewed the relevant literature and summarized the relationship between mitochondrial injury and COPD combined with SMD and treatment with TCM. This review may provide a basis for further research.

Abstract:Chronic kidney disease (CKD) is prevalent worldwide and represents a serious threat to human life and health with a high morbidity and mortality. Currently, there are no effective curative therapeutics for CKD except hemodialysis and renal transplantation. Stem cells, which are able to self-renew and differentiate into multiple lineages, have been explored as a potentially viable treatment for CKD in recent years. In this review, the potential applications of three types of stem cells for treatment of CKD are briefly summarized, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells.