Abstract:Objective To observe the neurotoxic effects and mechanism of TCPP ( tris ( 2-chloroisopropyl)phosphate) exposure on mice. Methods Thirty adult KM mice were randomly divided into normal control (0 mg / ( kg·d)), low- (10 mg / (kg·d)) and high-dose TCPP groups (100 mg / (kg·d)), and were given oral gavage exposure once aday for consecutive 30 days. The body mass of mice was recorded. Morris water maze was used to examine the ability oflearning and memory ability in mice. The serum levels of total-triiodothyronine (TT3), total-tetraiodothyronine (TT4), freetetraimethionine ( FT4) and free triiodothyronine ( FT3) were detected with electro-chemiluminescence. The levels ofglutathione transferase (GST), superoxide dismutase ( SOD), catalase ( CAT), and malonaldehyde ( MDA) in braintissues were detected by chemical colorimetry. Results Compared with the control group, the water intake of the high-doseTCPP group was significantly reduced ( P < 0. 05), and the argan coefficients of the liver and spleen were significantlyincreased ( P < 0. 05). In addition, the escape latency of TCPP exposure mice was longer than that of control group in thewater maze test ( P < 0. 05). Furthermore, the total swimming course of the high-dose TCPP group was increased ( P <0. 05) and swimming time in the target quadrant was significantly reduced compared with the control group ( P < 0. 05). Inthe high-dose TCPP group, the serum levels of TT3 and FT3 were increased ( P < 0. 05), the activities of GST and SODwere decreased, and the content of MDA was increased ( P < 0. 05) compared with the control group. In the low-doseTCPP group, the activity of GST was decreased and the content of MDA was increased ( P < 0. 05) compared with thecontrol group. Conclusions TCPP exposure is neurotoxic by increasing thyroid hormones and inducing oxidative damage inmice.

Abstract:Objective To explore the molecular connotations of the TCM theory of refraction through theregulating of respiratory diseases and inflammatory bowel disease by Papaver nudicaule L., to analyze the changes of geneexpression in the animal models of the two diseases after treatment, and to reveal their molecular mechanisms in the lungand intestine. Methods The allergic asthma model was established by ovalbumin (OVA) atomization and compared withthe ulcerative colitis model established by the combined immunization. Normal rats were used as controls. After theadministration of Papaver nudicaule L., reverse-transcription polymerase chain reaction (RT-PCR) was used to detect theexpression levels of mRNA of the same differentially expressed genes in lung and intestinal tissues of the two groups of rats.Results Papaver nudicaule L. significantly improved the histological changes in the lung and colon tissues of rats. KEGGannotation analysis results for three key differentially expressed genes, C-C motif chemokine 11 ( Ccl11 ), carbonicanhydrase (Ca) 1, and nuclear receptor subfamily 1, group D, member 1 ( Nr1d1), and the RT-PCR results werebasically consistent with the RNA-sequencing results. Papaver nudicaule L. decreased the expression of C-C motifchemokine 11 mRNA ( P < 0. 05) and increased carbonic anhydrase (Ca) 1 and Nr1d1 mRNA expression in the lung andcolon tissues of both groups ( P < 0. 05, P < 0. 05). Conclusions The lung and intestinal tissues of the rats withrespiratory disease and inflammatory bowel disease have the same differentially expressed genes. Papaver nudicaule L. cansignificantly regulate the levels of differentially expressed genes in the lung and large intestine. This may be a molecularmechanism of Papaver nudicaule L.’s activity to locate the lung meridian and large intestine meridian.

Abstract:Objective Matrix metalloproteinase-12 (MMP12) also known as macrophage elastase, is capable ofdecomposing almost all extracellular matrix components and is required for monocyte recruitment. MMP12 has been found tobe involved in cancer invasion and metastasis. In addition, MMP12 is also closely related to adipose tissue. This studyinvestigated whether MMP12 regulates the macrophages in blood and white fat in MMP12 knockout (MMP12^{- / -}) mice.Methods MMP12^{- / -} mice were raised and genotyped, and littermate MMP12^{+ / +}male mice were used as controls. Theroutine blood indexes of the two groups of mice were analyzed, and the macrophage markers were detected by flowcytometry. Pathdogy using HE staining and immunohistochemistry was performed to determine the macrophages in adiposetissue after MMP12 deletion. Results (1) The genotype of MMP12^{- / -}mice and expansion was identified. (2) Comparedwith those of littermate MMP12^{+ / +}male mice, parameters including RBC count, HGB level, PLT count, and monocytecount and percentage were significantly reduced in MMP12^{- / -} male mice. However, the proportions of lymphocytes andeosinophils were significantly increased compared with those of control mice, but their absolute counts did not differsignificantly. ( 3) Further result suggested that the proportion of macrophage-specific marker CD11b and F4 / 80 doublepositive cells was significantly decreased in the blood, and their absolute count was also reduced. (4) The pathdogy usingHE staining and immunohistochemistry confirmed that macrophage (CD68+) expression was significantly increased in thewhite adipose tissue of MMP12^{- / -}male mice. Conclusions These results suggest that macrophage changes may be relatedto MMP12 knockout. The significance is that MMP12 may regulate the development of macrophages, the macrophages arereduced in the blood and increased in white fat.

Abstract:Objective To detect the effect of high fat diet and K / BxN serum on the distribution of immune cellsin ApoE gene knockout ( ApoE^{-/ -} ) mice. Methods ApoE^{-/ -} mice were fed with high fat diet (HFD) from 8 weeks of age,then the K / BxN serum whose anti-glucose-6-phosphate isomerase (GPI) antibodies were positive was injected intraperitoneallyonce a week, with each injection of 0. 2 mL, from 17 to 26 weeks of age. The control group was fed withordinary diet (CD) and injected the K / BxN serum in the same way. The level of blood lipid was analysed by ELISA, andthe ankle swelling was measured by vernier caliper before and after the K / BxN serum was injected intra-peritoneally. Thesplenocytes and bone marrow cells of ApoE^{-/ -} mice were isolated and stained by flow antibodies at 26 weeks of age, thendetected by flow cytometry. Results Serum LDL-C, TCHO and TG levels of ApoE^{-/ -} mice were significantly increasedbefore and after K / BxN serum was injected, and the areas of atherosclerotic plaques were significantly increased in aorticroots after K / BxN serum injected, suggested that whether K / BxN serum was injected, HFD could induce atherosclerosis of ApoE^{-/ -} mice, and the atherosclerotic symptom of ApoE^{-/ -} mice fed with HFD was more severe than the CD treated group.The ankle width and clinical scores showed that the ankle swelling of ApoE^{-/ -} mice was normal before K / BxN seruminjected. However, ApoE^{-/ -} mice fed with HFD had lower joint width and clinical score than ApoE^{-/ -} mice fed with CD after K / BxN serum injected. The flowcytometry analysis showed that HFD down-regulates CD3+ T cells and CD19+ B cells, upregulatesCD11b+ macrophages in splenocytes and bone marrow cells. Conclusions HFD down-regulates CD3+ T cells andCD19+ B cells, up-regulates CD11b+ macrophages in splenocytes and bone marrow cells, so aggravates the atherosclerosis and relieves arthritis of ApoE^{-/ -} mice.

Abstract:Objective To evaluate the method of detecting intestinal mucosal barrier damage, and investigatewhether propolis can lower glucose levels through repairing the intestinal mucosal barrier in diabetic rats. Methods A ratmodel of diabetes mellitus was established by administering a high-sugar and high-fat diet with a single intraperitonealinjection of 1% streptozotocin (STZ) at a dose of 40 mg/ kg. Then, the rats in the propolis treatment groups were orallysupplemented with 80 or 160 mg/ ( kg·d) propolis by gavage. The rats of control and model groups were orallysupplemented with soybean oil. After 4 weeks, a Roche glucometer was used to detect blood glucose concentration, highperformanceliquid chromatography was used to detect whole-blood hemoglobin A1c (HbA1c), ELISA was used to detectthe levels of plasma D-lactic acid (D-LA) and zonulin, western blotting was used to detect the expression levels of claudin-1, occludin, and ZO-1 in ileum and colon tissues, and the ultrastructure of ileum and colon tissues was examined bytransmission electron microscopy. Results The diabetic rat model was established successfully. After 4 weeks ofintervention, the blood glucose level in the 80 and 160 mg/ kg propolis treatment groups reached 17. 57 and 18. 24 mmol/L, and their HbA1c levels were 8. 94% and 8. 22%, respectively, which were significantly lower than that in the modelgroup ( P < 0. 05). Transmission electron microscopy showed that after propolis intervention, the tight junctions andadherens junctions of intestinal epithelium were improved. Western blotting showed that the expression levels of claudin-1,occludin, and ZO-1 in the ileum and the colon of the propolis intervention groups were significantly higher than in the modelgroup, in a dose-dependent manner ( P < 0. 05). ELISA data showed that the levels of plasma D-LA were 160. 03 and151. 18 ng/ mL in the 80 and 160 mg/ kg propolis intervention groups, respectively, and their plasma zonulin levels were650. 14 and 647. 60 μg/ mL, with no significant differences between them ( P > 0. 05). Conclusions Ultrastructuralobservation of the intestinal mucosal barrier and detection of the expression levels of proteins closely associated with theintestinal tissue have higher sensitivity than the serological determination of intestinal mucosal barrier function, so they canbe used as a reliable experimental method for studying the mechanism of the intestinal barrier repair associated with the hypoglycemic effect of propolis.

Abstract:Objective To investigate the protective effect and mechanism of action of Coptis chinensispolysaccharide (CCPW) on the kidney in a streptozotocin (STZ)-induced rat model of diabetes. Methods A Sprague-Dawley (SD) rat model of diabetes was established by intraperitoneal injection of STZ (60 mg/ kg). The diabetic rats wererandomly divided into disease model, high-dose CCPW (300 mg/ kg/ d), low-dose CCPW (100 mg/ kg/ d) and losartan(30 mg/ kg/ d) groups, containing 10 rats each. A group of 10 non-diabetic SD rats was included as the normal controlgroup. The rats were intragastrically administered the drugs once a day continuously for 8 weeks. At the end of the 8-weekadministration period, the effects of CCPW on body weight, kidney-to-body weight ratio, serum BUN and SCr levels, 24-hour urine protein levels, pathological changes in renal tissue, changes in the activity of the antioxidant enzymes SOD,CAT and GSH-Px, MDA content, and changes in the expression of IL-6, hs-CRP and TNF-α were observed in the diabeticrats. Results Compared with the disease model group, the CCPW-treated diabetic rats demonstrated a significant increasein body mass and a significant decrease in the kidney-to-body weight ratio. Significant decreases in serum BUN and SCrlevels as well as the 24-hour urine protein level were also observed. Pathological changes in the renal tissues of CCPW ratswere also less apparent, when compared with the untreated disease model animals. SOD, CAT and GSH-Px activity in renaltissues was significantly elevated, while MDA content and IL-6, hs-CRP and TNF-α expression in the serum weresignificantly reduced in the CCPW-treated groups. Conclusions CCPW may have a protective effect on the renal tissue of diabetic rats, possibly through its inhibition of oxidative stress and inflammation.

Abstract:Objective To observe the effects of treatment with Guizhi Fuling decoction on human endometrialcarcinoma HEC-1-B cancer in unde mouse models. Methods HEC-1-B cancer model nude mice were divided into threegroups. The model group received intragastric gavage of deionized water, the Guizhi Fuling decoction group receivedintragastric gavage of 2. 4 g/ kg Guizhi Fuling decoction, and the carboplatin injection group received a single intraperitonealinjection of 20 mg/ kg carboplatin. Results Both Guizhi Fuling decoction and carboplatin injection significantly reducedthe HEC-1-B tumor volume ( P <0. 05). Guizhi Fuling decoction promoted the expression of caspase-3 and reduced the expression of Bcl-2 protein. Conclusions Guizhi Fuling decoction has inhibitory effects on endometrial cancer.

Abstract:Objective To explore the effect of intervention of downregulating miR-192 on post-injury renalinterstitial fibrosis in rats with unilateral ureteral obstruction (UUO), and the mechanism involved. Methods Forty-fivehealthy male SD rats were randomly divided into a sham group, model group, and antagomir-192 group. The rat model ofrenal interstitial fibrosis was constructed in all rats (except the sham group) through left ureter ligation. Rats in theantagomir-192 group were given tail vein injection of antagomir-192 on days 1, 7, and 14 after surgery, while rats in thesham group and model group were given tail vein injection of an equivalent amount of normal saline. All rats were sacrificedon day 21 after surgery. Changes in miR-192 expression in the obstruction-side renal tissues were detected through real-timefluorescence quantitative PCR (qRT-PCR). Blood was collected from the heart to determine the serum levels of blood ureanitrogen (BUN) and creatinine (Cr) in rats, and the pathological changes in the obstruction-side renal tissues wereobserved using HE staining. Moreover, the obstruction-side renal interstitial collagen fiber deposition rate was calculatedusing Masson staining, and western blotting was performed to detect the changes in expression of epithelial-mesenchymaltransition (EMT)-related markers, E-cadherin, α-smooth muscle actin (a-SMA), vimentin, and collagen I, in theobstruction-side renal tissues. Results Compared with the sham group, the miR-192 expression level in renal tissues,serum BUN and Cr levels, renal interstitial injury score, and renal interstitial collagen fiber deposition rate in the modelgroup were markedly upregulated ( P <0. 01); E-cadherin protein expression in renal tissues was notably downregulated ( P <0. 01); while α-SMA, vimentin, and collagen I protein expression was dramatically elevated ( P <0. 01). Compared withthose in the model group, the miR-192 expression level in renal tissues, serum BUN and Cr levels, renal interstitial injuryscore, and renal interstitial collagen fiber deposition rate in the antagomir-192 group were remarkably reduced ( P <0. 01); E-cadherin protein expression in renal tissues was evidently increased ( P < 0. 01); while α-SMA, vimentin, andcollagen I protein expression was dramatically decreased ( P < 0. 01). Conclusions miR-192 expression is elevated inrenal tissues of rats with renal interstitial fibrosis, and downregulating miR-192 can suppress renal interstitial fibrosis in UUO rats, thus exerting a protective effect.

Abstract:Objective To investigate the role of cyclooxygenase-2 (COX-2) gene expression in TGF-β1-indcuedcollagen synthesis, transformation and Notch signaling in human fetal lung fibroblasts. Methods Human fetal lungfibroblasts MRC-5 cells transfected with non-targeting control or COX-2-specific siRNAs were treated with or without TGF-β1 for 48 h. Western blotting was used to detect COX-2 protein expression, alterations in the synthesis of COX-I and COXIII,and the EMT marker α-SMA, and changes in the expression of the Notch signal pathway receptor Notch1 and itscognate ligand Jagged1. Cell viability was assessed by CCK8 assay. Results COX-2 expression was significantly higher inthe TGF-β1 group than the control group. Transfection of cells with COX-2-specific siRNAs significantly attenuated TGF-β1-dependent induction of COX-2 expression ( P <0. 05), while transfection of cells with control siRNAs had no effect. Cellviability and the expression of COX-I, COX-III, α-SMA, Notch1 and Jagged1 proteins were significantly increased in theTGF-β1 group ( P <0. 05), when compared with the TGF-β1 group, but were suppressed following the transfection of cellswith COX-2 siRNA ( P <0. 05). Conclusions Inhibition of COX-2 gene expression may play a protective role in pulmonaryfibrosis by reducing lung fibroblast viability and suppressing the ability of these cells to synthesize collagen and activate Notch pathway signaling.

Abstract:Determination of the quality of laboratory animals is essential for managing them, and the formulationand revision of standards are the main approaches for promoting the quality of laboratory animals in our contry. In recentyears, new pathogens of laboratory animals have emerged and novel detection techniques are constantly being updated. Theestablishment and renewal of national standards do not meet the quality management requirements of laboratory animals inour country. In this project, taking advantage of social organization standards for innovation, a number of laboratory animalsocial organization standards on PCR for pathogen detection were developed, combined with the practical needs of laboratoryanimals. These standards are useful supplements to national standards and should play an important role in improving the quality of laboratory animals in our country.

Abstract:Tree shrews are similar to human beings in terms of their metabolism, physiological function, generalanatomy, and genome. They have thus been widely used in medical and biological research. For this new experimentalanimal resource of great value in scientific research, standardized quality control has become a technical bottleneck and aninevitable trend of research and development in the use of tree shrews. This paper analyzes and summarizes the qualitycontrol group standards of laboratory animal tree shrew, strengthens the promulgation and implementation of thesestandards, and provides a reference for the establishment of standardized tree shrew populations and national standards.Finally, this paper promotes the application and industrial development of tree shrews.

Abstract:Specific-pathogen-free (SPF) chicken is the only recognized laboratory terrain poultry animal, and SPFchicken embryos are a major production and verification material for almost all poultry and some human and livestockvaccines. A series of quality standards on the microbiology, genetics, and formula feed as well as breeding and managementof SPF chicken have been established and implemented recently. This paper introduces SPF chicken quality-relatedstandards on microbiology, genetics, formula feed, breeding, care, and transport, including several sets of nationalstandards, group standards, and local standards. We hope that this paper provides a useful reference for SPF chicken producers and users.

Abstract:With the increasing need for high-quality lab animals, the continuous improvement of lab animalstandards has become particularly important. Murine norovirus (MNV) has a high infection rate in lab mice. MNV infectionnot only harms the animals themselves, but also has a great impact on the experimental results. The national standards forlaboratory animals in China do not yet include murine norovirus in the list of routine examination items. We have compiledgroup standards for murine norovirus by referring to the latest research results on murine norovirus at home and abroad,along with relevant foreign standards. This paper introduces the background, and legal and regulatory basis for thepreparation of murine norovirus group standards and explains the sets for the standard content. The establishment of suchstandards should improve the quality of lab animals. They can provide technical support for promoting improved quality of lab animals and adapting to the needs of the international development of lab animals.

Abstract:The good quality of laboratory animals is the foundation of laboratory animal science as a support for lifescience research. The monitoring of animal quality relies on well-established and scientific examination standards.Corynebacterium bovis is an important pathogen causing infection in nude mice, but no relevant examination standards haveyet been developed for it. The development of such standards can provide and normalize the method for detecting C. bovis,which is helpful for timely monitoring and control of this bacterium.

Abstract:Brucella can cause acute and chronic infectious diseases in humans and animals, so it is one of themicroorganisms that must be excluded from experimental animals. With the passage of time, changes in conditions andadvances in technology, the original testing method and standards are no longer applicable for current Brucella detection,thus new method and standards for the detection of Brucella in laboratory animals need to be developed. This articleintroduces the background, legal basis, content compilation, and future prospects of the PCR test standards for Brucella inlaboratory animals, so that relevant personnel can better understand the standards and better carry out the detection ofBrucella in laboratory animals. This paper provides technical support for promoting the improved quality of laboratory animals and adapting to the needs of the international development of laboratory animals.

Abstract:Heart failure is one of the leading causes of death for patients at the end stage of chronic cardiovasculardisease. The adverse remodeling of the myocardium plays a critical role in the occurrence of heart failure, and myocardialfibrosis is an important manifestation of adverse cardiac remodeling. Increasing evidence indicates that the epigeneticregulatory mechanisms play important roles in the occurrence and development of myocardial fibrosis. This review focuses onthe progress of research on epigenetic regulation, including DNA methylation, histone modification, and microRNA, in myocardial fibrosis.

Abstract:Diabetic macrovascular disease is a low-grade inflammatory state, and its pathological basis is sustainedvascular injury caused by immune inflammatory reaction. An imbalance of immune cells leading to immune inflammatorymicroenvironmental disorder in the large blood vessels is the central immune inflammatory reaction in this condition, but itsexact pathological mechanism is unclear. Therefore, this paper presents a review of the presence and rde macrophages,lymphocytes, dendritic cells, and mast cells, among others, in this condition. The immune cell development pathway isbriefly analyzed here with respect to the possible mechanisms of involvement of immune cells in the development of diabetic macroangiopathy.

Abstract:Patient-derived organoids (PDOs) and patient-derived xenografts (PDXs) are new models for cancerresearch. They can accurately simulate the physiological structures and characteristics of in situ tissues, help to formulateappropriate medication regimens for patients, and achieve individualized treatment. Thus, they are necessary for the rapidtransformation of basic scientific research to clinical applications. In addition, PDO and PDX models can be used to carryout basic research on tumor clonal evolution and tumor pathogenesis. This review focuses on the application of PDO and PDX models in cancer preclinical and basic research.

Abstract:Drugs for the effective treatment of rheumatoid arthritis (RA) are currently lacking. While there is growing interest in the potential application of mesenchymal stem cells (MSCs) in the treatment of RA, there are potential risks associated with cell-based therapies. MSCs secrete functional exosomes (MSC-Exos) that can mediate many of the functions of MSCs and, consequently, these extracellular vesicles provide an attractrive alternative that may circumvent many of the risks associated with cell-based strategies. With current advances in exosomal technology, including on-going studies in animal models and findings from large-scale clinical trials, there is great expectation that MSC-Exos will provide a new and exciting strategy for the treatment of RA.

Abstract:Depression represents one of the most common comorbidities in patients with epilepsy, influencing patients’ quality of life and prognosis. However, the mechanisms of depression in epilepsy patients are poorly understood.The establishment of animal models of epilepsy-associated depression is critical for understanding the mechanisms involved.In this paper we reviewed the progress in research on animal models of epilepsy-associated depression.

Abstract:Alkaloids are a class of nitrogen-containing alkaloids, which have many physiological activities, such asanti-tumor, and hypoglycemic effects. At present, the main alkaloids that can alleviate or delay the process of diabeticnephropathy in experimental animals include pyridine derivatives, pyrrolidine derivatives, scopolamine derivatives,isoquinoline derivatives, pyridine derivatives, isoquinoline derivatives, pyrazine derivatives, organic amines, and terpenealkaloids. Common alkaloids are berberine, ligustrazine, anisodamine, betaine, matrine, and colchicine, among others.Alkaloids have a variety of mechanisms for renal protection, including regulating oxidative stress, improving insulin resistance, reducing the infiltration of inflammatory factors, and downregulating or increasing the expression of related factors.