Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective To establish a PCR-based capillary electrophoresis(PCR/CE)to detect Survival Motor Neuron 1(SMN1)and Survival Motor Neuron 2(SMN2)genes and to evaluate its performance.Methods PCR/CE and Multiplex Ligation-dependent Probe Amplification(MLPA)for SMA gene diagnosis were used to blindly test the samples in sync.The performance of PCR/CE was assessed using MLPA results as the standard.Results A total of 336 samples were included in this study,consisting of 50 homozygous deletion types(14.9%),65 heterozygous deletion types(19.3%),and 221 non-deletion types(65.8%).The results of PCR/CE for detect-ing SMN1 and SMN2 copy numbers(0,1,2,3,≥4)were in complete agreement with the results of the MLPA.Conclusions PCR/CE for gene testing related to SMA could accurately detect copy numbers of exon 7 and exon 8 of the SMN1 and SMN2 genes(0,1,2,3,≥4).

Objective:To evaluate the effect and possible mechanism of B-cell-specific moloney murine leukemia virus insertion site 1(BMI-1) on the radiosensitivity of pancreatic cancer SW1990 cell line.Methods:According to our previous study results, 4 Gy X-ray and down-regulation of BMI-1 expression were adopted as intervention conditions. The effect on the proliferation of SW1990 cells was assessed by clony formation assay. The effect on cell apoptosis and cell cycle was evaluated by flow cytometry. The effect upon the epithelial-mesenchymal transition (EMT) was determined by Western blot.Results:Clony formation assay and flow cytometry found that the lowest cell proliferation ability and the highest apoptotic rate were obtained after BMI-1 down-regulation and 4 Gy X-ray compared with other groups (all P<0.05). Flow cytometry revealed that the proportion of G 0/G 1 phase was significantly decreased, whereas the G 2/M phase was remarkably increased in pancreatic cancer stem cells treated with 4 Gy X-ray compared with the control group (both P<0.05). Nevertheless, opposite results were obtained after down-regulation of BMI-1 expression. Western blot showed that the expression of E-cadherin was up-regulated, whereas that of Vimentin was down-regulated following 4 Gy X-ray (both P<0.05). Conclusion:Downregulation of BMI-1 expression can enhance the radiosensitivity of pancreatic cancer SW1990 cells, and its mechanism may be related to cell cycle and EMT.

Objective To screen the active components of Bushen Huoxue Decoction ( BSHXD) involved in promoting the proliferation of bone marrow mesenchymal stem cells ( MSCs). Methods BSHXD and its subdivisions were extracted with petroleum ether, ethyl acetate, water-free ethanol and water respectively. MSCs were isolated and cultured by the bone marrow adherent method. At the third passage, MSCs were identified by the specific surface markers with immunofluorescence, and their osteogenic and adipogenic differentiation were tested by alizarin red staining and oil red “O” staining. After treated with the extracts of BSHXD and its subdivisions at gradient concentrations for 24 hours, cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay for the screening of active components and optimal concentration. MTT assay was used to describe the growth curve of MSCs treated with the most effective components, and cell cycle was analyzed by flow cytometry. Results Compared with the blank control group, the extracts of BSHXD and its subdivisions could protect MSCs from death to various degrees. Of all the extracts, the ethyl acetate extract of Bushen Division ( BSD) , ethyl acetate extract of BSHXD, ethyl acetate extract of Huoxue Division ( HXD) had the strongest effect, and the effect was dose-dependent, 100 μg/mL being the optimal active concentration while having no any cytotoxic reaction. The results of MTT assay revealed that BSD extracts promoted the proliferation of MSCs significantly and was the most effective component, and then came BSHXD. The results of flow cytometry indicated that BSD extract had the most strongest effect on increasing the amount of MSCs at proliferative phase, and then came BSHXD. Conclusion BSD ethyl acetate extract is the active component of BSHXD for promoting the proliferation of MSCs, showing an effect on increasing the proportion of MSCs at proliferative phase.

OBJECTIVETo observe the effects of three traditional Chinese medicine (TCM) such as Amomi Fructus Rotundus, Perillae Folium and Angelicae Dahuricae Radix on lung-yang deficiency rats induced by compound factors.

METHODLung-yang deficiency rats were established with three-factor combination, such as smoking (exogenous evil effect on lung), swimming in common and ice water (cold body and exhaustoin) and drinking ice water (inhale cold). Meanwhile, rats were given water extracts of the three TCM by intragastric administration for 24 days everyday. Indexes such as general behavior, weight, rectal temperature, back temperature and grip strength were observed. Blood was collected to determine NO, IgG in blood serum. Lung and heart were dissected to measure organs index.

RESULTThe water extracts of Amomi Fructrs Rotundus, Perillae Folium and Angelicae Dahuricae Radix could markedly heighten weight, back temperature, grip strength, content of IgG in blood serum, reduce content of NO in blood serum, lung index and heart index. The water extracts of Amomi Fructrs Rotundus and Perillae Folium could heighten rectal temperature.

CONCLUSIONAmomi Fructrs Rotundus, Perillae Folium and Angelicae Dahuricae Radix were TCM with pungent-flavor, warm-nature and meridian tropism in lung, which could improve the symptoms of physique emaciation, aversion to cold of the back, weary and acratia and so on. It provides an important reference for the regularity of the properties theories about pungent-flavor, warm-nature and meridian tropism in lung.

Amomum ; chemistry ; Angelica ; chemistry ; Animals ; Body Temperature ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Enteral Nutrition ; Female ; Heart ; drug effects ; Immunoglobulin G ; blood ; Lung ; drug effects ; pathology ; Male ; Meridians ; Nitric Oxide ; blood ; Perilla ; chemistry ; Plant Extracts ; administration & dosage ; Rats ; Yang Deficiency ; drug therapy ; pathology