Meta-analysis on effect of Grifola frondosa polysaccharide in regulating in vivo immunoregulatory function on animal disease models / 中国中药杂志

The study aimed to explore the in vivo immunoregulatory function of Grifola frondosa polysaccharide( GFP) on animal disease models. Databases of PubMed,Embase,Web of Scinece,CNKI,CBM and Wan Fang Data were searched from the date of their establishment to February 2018. Two reviewers independently screened included studies and evaluated their quality by using SYRCLE's risk of bias tool. R software was used to analyze the data. Finally,20 animal experiment studies were included. According to Metaanalysis. For cellular immunity,GFP could effectively enhance the proliferation of effect or T cells,natural killer cells and macrophages in mice. The percentage of CD4+T cells( MD = 1. 89,95% CI [0. 94,2. 83],P < 0. 000 1),CD8+T cells( MD = 8. 46,95% CI[5. 93,11. 00],P<0. 000 1),NK cells( MD= 2. 67,95% CI [0. 23,5. 11],P= 0. 03),and macrophages( MD= 14. 09,95% CI[0. 84,27. 34],P= 0. 04) were all higher than those in control group. For humoral immunity,GFP could increase the secretion of TNF-α and INF-γ． The secretion of TNF-α( SMD = 15. 92,95% CI [9. 07,22. 76],P<0. 000 1) and INF-γ( SMD = 5. 34,95% CI[3. 42,7. 26],P<0. 000 1) were all higher than those in control group. In conclusion,GFP could regulate immunologic function by enhancing the proliferation activity of immune cells( CD4+T cells,CD8+T cells,NK cells and macrophages) and the secretion of immune factors( TNF-α and INF-γ) ． However,it is necessary to further standardize the selection of specific surface markers of immune cells and the administration of GFP,in order to reduce the heterogeneity among the studies. At the same time,more attention shall be paid to experimental design,implementation and full report,especially to the establishment and implementation of animal experimental registration system,so as to improve the transparency and quality of the whole process of animal experimental research,enhance the value of basic research ultimately,and provide a reliable theoretical basis for the transformation of basic research into clinical research.

Aged Sanroque Mice Spontaneously Develop Sjögren's Syndrome-like Disease

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disorder that affects mainly salivary and lacrimal glands, but its cause remains largely unknown. Clinical data indicating that SS occurs in a substantial proportion of patients with lupus points to common pathogenic mechanisms underlying the two diseases. To address this idea, we asked whether SS develops in the lupus-prone mouse strain sanroque (SAN). Owing to hyper-activation of follicular helper T (Tfh) cells, female SAN mice developed lupus-like symptoms at approximately 20 wk of age but there were no signs of SS at that time. However, symptoms typical of SS were evident at approximately 40 wk of age, as judged by reduced saliva flow rate, sialadenitis, and IgG deposits in the salivary glands. Increases in serum titers of SS-related autoantibodies and numbers of autoantibody-secreting cells in cervical lymph nodes (LNs) preceded the pathologic manifestations of SS and were accompanied by expansion of Tfh cells and their downstream effector cells. Thus, our results suggest that chronic dysregulation of Tfh cells in salivary gland-draining LNs is sufficient to drive the development of SS in lupus-prone mice.

Establishment and evaluation of radiation-induced "inflammatory-fibrosis" heart damage model in rats / 第二军医大学学报

Objective: To screen and optimize the modeling condition for radiation-induced heart damage (RIHD) models characterized by inflammatory-fibrosis pathological injury. Methods: The rats were irradiated with single whole-body X-ray to screen the maximal tolerated dose. Based on the screened whole-body dose, single local heart irradiation doses were used to screen the minimal X-ray dose which could induce the significant cardiac damage. And the RIHD rat model was established by exposure to the screened dose of X-ray. Tissue samples were harvested 1 day, 1 week, 2 weeks, 4 weeks and 6 weeks after irradiation. The cardiac pathological injury score, collagen volume fraction (CVF) in myocardial tissues by Masson staining, plasma myocardial enzyme level, and the expression of inflammatory and fibrosis factors in myocardial tissues were examined for evaluating the animal model. Results: The tolerance dose of whole-body irradiation was lower than 16 Gy for rats. Local irradiation dose at least 25 Gy could induce RIHD in rats. The pathological injury score of myocardial tissues, CVF in myocardial tissues and creatine kinase isoenzyme MB (CK-MB) and cardiac troponin (cTn) in plasma were increased in the RIHD model rats. Inflammatory factors including nuclear factor (NF)-κB p65, NF-κB p50 and tumor necrosis factor α (TNF-α) in myocardial tissues were increased 1 day after irradiation in the RIHD rats and maintained high to the fourth week. The expression levels of fibrotic molecules transforming growth factor β1 (TGF-β1), collagen type I (Col I) and Col III in myocardial tissues were increased gradually, and reached the peaks at week 4 after irradiation. Conclusion: Stable RIHD rat model can be established by irradiating the precardiac region with 25 Gy X-ray. Pathological observation and CVF can dynamically reflect the early inflammatory changes and the progression of fibrosis in RIHD rats. The sustained high expression of NF-κB p65, NF-κB p50 and TNF-α at early stage and the progressive increases of TGF-β1, Col I and Col III can be used to evaluate the acute inflammatory injury and delayed fibrosis in the RIHD inflammatory-fibrosis model.

Research progress of producing genetically modified pigs by CRISPR/Cas9 in the medical field / 生物医学工程学杂志

As pigs are similar to humans in anatomy, physiology and pathology, nutrition metabolism and disease characteristics, genetically modified pigs are already used for the studies of disease mechanism, pathology and toxicology and the evaluation of drugs. But the production of large modified animals is difficult, cumbersome, time-consuming and costly. With the breakthrough of gene editing technology, clustered regularly interspersed short palindromic repeat (CRISPR)/CRISPR-associated 9( Cas9)(CRISPR/Cas9) technology has greatly improved the mutation efficiency, reduced the cost and simplified the steps, and promoted the widespread application of genetically modified pigs. In this paper, the production methods of genetically modified pigs and the research progress of genetically modified pigs by CRISPR/Cas9 in the medical field were reviewed.

Application of CRISPR/Cas9 genome editing technology in the research of eye diseases / 中华实验眼科杂志

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) is an adaptive immune system against invasive viruses and exogenous DNA,which is developed by bacteria and archaer during long-term evolution.With advances in technology,researchers have found that CRISPR/ Cas9 system can precisely edit the genomes of eukaryotic cells through insertion,replacement or deletion of target genes.Using CRISPR/Cas9 genome editing technology,researchers found that overexpression of paired box gene 6 (PAX6) in cornea can cause congenital corneal epithelial damage;this technology promoted the research on the pathogenic mechanism of keratin 12 (KRT12) mutation in Meesmann corneal epithelial dystrophy;it has also built congenital cataract animal models by knocking out the G JA8 gene and αA lens gene,which is beneficial to the application of the diagnosis and pathological analysis of congenital cataract.In addition,the researchers have used CRISPR/Cas9 genome editing technology to confirm the correlation of RHOS334 mutated RHO allele,P23H mutated RHO gene,Y347X mutated Pde6b gene,and mutant RP9 allele with retinitis pigmentosa.The application of this technology has provided evidence to support the association of KCNJ13 gene and mutant CEP290 gene with Leber congenital amaurosis.CRISPR/Cas9 can provide target spot of intraocular neovascular diseases the targeted therapy by editing of VEGFR2 gene and TXNIP gene,and it also playse an important role in the study of pathogenic genes and establishment of animal models for proliferative vitreoretinopathy and retinoblastoma.In this review,we introduced the evolutionary history,the molecular characteristics and the mechanism of CRISPR/Cas9,and summarized its current research advances in eye diseases.

Study of Different Doses of Letrozole and Medroxyprogesterone Acetate Co-treating Endometriotic Rats / 实用妇产科杂志

Objective:To explore the treatment effect on EMT in rats using different doses of letrozole and Medroxyprogesterone acetate (MPA) and their effects on liver,renal,skeletal and reproductive system.To provide lab evidence for treatment of EMT before menopause using letrozole.Methods:Endometriotic rat model was set up by surgical transplantation of autologous uterine tissues to ectopic site outside the uterus.70 EM model rats were randomly divided into 7 groups,each with 10:A ～C:LE 1 mg/(kg · d-1) and MPA [8、4、2 mg/(kg · d-1) respectively];D ～ F:LE 0.5mg/(kg · d-1) and MPA[8、4、2 mg/(kg · d-1) respectively];G:0.9％ saline (control group).The volume of ectopic lesion in each group was compared before and after the treatment.The expression of P450arom and Ki-67 and cell apoptosis in the endometriotic tissues of the rat models were detected.The serum levels of FSH,LH and E2 were determined and liver and renal functions were detected.Bone mineral density(BMD) was measured in the right femur.Results:①Except for group F,the volume of the endometriotic tissues of the five groups reduced significantly compared with the G group(P ＜ 0.05),and the greatest decrease in the volume were in group A and B (P＜0.01);②Compared with the G group,the expression of P450arom and Ki-67 protein decreased while the apoptotic rate increased in tissues of endometriosis (EM) on rat models among group A to group E (P＜0.05),in which group A and B were the most notable (P＜0.01);(③Compared with the G group,the level of FSH,LH and E2 reduced in group A、B and D (P＜0.05),moreover,the E2 level of group A and B was lower than that in group D (P＜0.05);④Compared with the G group,the ovarian weight in group C increased greatly,and the ovaries showed polycystic.The uterine weights decreased among group A to group E,and the endometrium presented atrophy or inhibition of proliferation;⑤There was no change on the bone density among each group(P ＞ 0.05);⑥Abnormal liver function was only detected in group A after treatment,and no ab normal renal function detected in any group(P＞0.05).Conclusions:LE 1 mg/(kg · d-1) associated with MPA 4mg/(kg · d-1) had the most effect on EM rat models.Moreover,it had no influence on liver or renal function.The mechanism may be decreasing the serum level of E2,reducing local estrogen along with increasing the apoptosis while decreasing the proliferation of the ectopic tissues.

Molecular genetic decoding of malformations of cortical development

Malformations of cortical development (MCD) cover a broad spectrum of developmental disorders which cause the various clinical manifestations including epilepsy, developmental delay, and intellectual disability. MCD have been clinically classified based on the disruption of developmental processes such as proliferation, migration, and organization. Molecular genetic studies of MCD have improved our understanding of these disorders at a molecular level beyond the clinical classification. These recent advances are resulted from the development of massive parallel sequencing technology, also known as next-generation sequencing (NGS), which has allowed researchers to uncover novel molecular genetic pathways associated with inherited or de novo mutations. Although an increasing number of disease-related genes or genetic variations have been identified, genotype-phenotype correlation is hampered when the biological or pathological functions of identified genetic variations are not fully understood. To elucidate the causality of genetic variations, in vivo disease models that reflect these variations are required. In the current review, we review the use of NGS technology to identify genes involved in MCD, and discuss how the functions of these identified genes can be validated through in vivo disease modeling.

Metabolomics in the fight against malaria

Metabolomics uses high-resolution mass spectrometry to provide a chemical fingerprint of thousands of metabolites present in cells, tissues or body fluids. Such metabolic phenotyping has been successfully used to study various biologic processes and disease states. High-resolution metabolomics can shed new light on the intricacies of host-parasite interactions in each stage of the Plasmodium life cycle and the downstream ramifications on the host’s metabolism, pathogenesis and disease. Such data can become integrated with other large datasets generated using top-down systems biology approaches and be utilised by computational biologists to develop and enhance models of malaria pathogenesis relevant for identifying new drug targets or intervention strategies. Here, we focus on the promise of metabolomics to complement systems biology approaches in the quest for novel interventions in the fight against malaria. We introduce the Malaria Host-Pathogen Interaction Center (MaHPIC), a new systems biology research coalition. A primary goal of the MaHPIC is to generate systems biology datasets relating to human and non-human primate (NHP) malaria parasites and their hosts making these openly available from an online relational database. Metabolomic data from NHP infections and clinical malaria infections from around the world will comprise a unique global resource.

Investigate the application of animal disease models in non-clinical safety evaluation / 中国药理学通报

The current drug non-clinical safety evalua-tion has been highly systematized and standardized, but the standard toxicology model is still some inade-quacies, need to consider other animal models of safety evaluation. This paper will expound the need of animal disease models using in safety evaluation from the as-pect of scientific theories, data requirements and the need of clinical. Then recognizing on the perspective of drug regulatory agencies to explore the feasibility of u-sing animal disease models for safety evaluation and the deficiencies, in order to predict as accurately as possi-ble of the adverse drug reactions in clinical, applied to reduce the risk of clinical patients ( patients benefit ) , and reduce the risk of drug development failures ( pharmaceutical companies benefit ) . All in all we should attach great importance to the applications of animal disease models in non-clinical safety evalua-tion.

Comparison of the infectivity of Trypanosoma cruzi insect-derived metacyclic trypomastigotes after mucosal and cutaneous contaminative challenges

Trypanosoma cruzi infects humans when infected triatomine vector excreta contaminate breaks in skin or mucosal surfaces. T. cruzi insect-derived metacyclic trypomastigotes (IMT) invade through gastric mucosa after oral challenges without any visible inflammatory changes, while cutaneous and conjunctival infections result in obvious local physical signs. In this study we compared the infectivity of T. cruzi IMT in mice after cutaneous and oral contaminative challenges simulating natural infections. The 50% infective dose (ID50) for oral challenge was 100 fold lower than the ID50for cutaneous challenge, indicating that oral mucosal transmission is more efficient than cutaneous transmission.

O uso da talidomida como terapia adjuvante na leptospirose experimental / The use of thalidomide as adjuvant therapy in experimental leptospirosis

A leptospirose é uma zoonose de importância global, causada por leptospiras patogênicas. Seu tratamento é limitado quando iniciado após quatro dias do surgimento de sintomas, portanto, novas terapias adjuvantes são necessárias. Objetivo. Testar a droga imunomoduladora talidomida como terapia adjuvante à ampicilina no modelo de tratamento tardio da leptospirose experimental em hamsters. Métodos. 60 hamsters foram infectados via intraperitoneal por Leptospirainterrogans cepa L1-130, e foram separados em grupos: nenhum tratamento (NONE), talidomida (TAL), ampicilina (AMP) e ambos (AMP-TAL)...

Leptospirosis is a zoonosis of global importance, caused by pathogenic leptospira. His treatment is limited when started after four days of onset of symptoms, increasing the risk of morbidity and mortality, so new adjuvant therapies are needed.Objectives.To test the immunomodulatory drug, thalidomide, as an adjuvant therapy to antibiotics in experimental leptospirosis. Methods. Hamsters were infected by Leptospirainterrogans strain L1-130, and groups were assigned based on no treatment (NONE), thalidomide only (TAL), ampicillin only (AMP) or both (AMP-TAL). Thalidomide was administered via a gastric tube: 50 mg/kg in linseed oil and 2 ml/kg for three days. Ampicillin was administered intramuscularly at the rate of 100 mg/kg/bid for six days. Treatment was started two days after the onset of symptoms (experiment 1) and immediately after detection of the first death (experiment 2). Results. Experiment 1: all hamsters from the groups AMP and AMP-TAL...

INFLUENCE OF ZHAOLIAN ON LIVER PRECANCEROUS LESION INDUCED BY DIETHYLNITROSA MINE IN RATS / 中国癌症杂志

PURPOSE AND METHODS In order to investigate the effects of Zhaolian on anti tumor promotion,we studied its influence on liver precancerous lesion in rats induced by DEN.RESULTS (1)Liver function of rats was protected ( P

RELATIONSHIP BETWEEN DEGREE OF INVASION AND TUMOR METASTASIS / 中国癌症杂志

PURPOSE To provide evidence for the relationship between degree of invasion and tumor metastasis. The tumor cells of transplantable mouse histiocytic sarcoma (L1) were inoculated at the right hind footpads of inbred 615-strain mice. METHODS Once bearing the tumor, all the mice were sacrificed respectively on the 1st. 3th, 5th. 10th, 20th, 30th, and 40th day as to observe the degree of tumor invasion and the process of tumor metastasis. RESULTS When the degree of tumor invasion was grade Ⅲ or Ⅳ , the metastasis of tumor cells was found earliest in draining lymph nodes. However, the tumor metastasis in lung appeared later than in lymph nodes. CONCLUSION According to the time of tumor growth and degree of invasion and metastasis, the authors suggest a new classification for cancer staging, namely, latent, invasive and metastatic stages. During the stage of tumor invasion, it is redivided into early, middle and late invasive phases. During the stage of tumor metastasis, it is redivided into early, middle and late metastatic phases.