Background C57BL/6(B6) is a kind of routine mouse specie used in experimental autoimmune uveitis (EAU) research.Previous studies showed that the pathogenesis of uveitis related to inflammatory cytokines secreted by different helper T(Th) cells.However,the interaction of different Th cells in EAU is unclear.Objective This study was to investigate the dynamic changes of inflammatory factors in the spleen and serum after immunization in EAU mice.Methods Forty-four SPF B6 mice were immunized by injection of interphotoreceptor retinoid-binding protein (IRBP) and complete Freund adjuvant (CFA) emulsion via caudal vein and footpad.Indirect ophthalmoscope was used to examine the eyes 3 times per week and the inflammatory response was scored based on Thurau's criteria.In the thirty day after injection,20 model eyes were extracted and the sections of eye tissue were prepared for histopathological examination.The spleens of model mice were enucleated before injection and 2,5,10,15,20,25,30 days after injection,and reverse transcriptase PCR (RT-PCR) was used to detect the contents of interleukin-17 (IL-17) mRNA,interferon-γ (IFN-γ) mRNA,tumor necrosis factor-α (TNF-α) mRNA and IL-10 mRNA,and the contents of IL-17,IFN-γ,TNF-α and IL-10 in model serum were assayed by ELISA in 24 model mice.The experimental protocol and use of the animals were approved by Ethic Committee for Care and Use of Laboratory Animals of Shandong University of Traditional Chinese Medicine.Results Mild inflammatory response was seen in 12 days under the indirect ophthalmoscope with the scores of 0.5.The inflammatory scores peaked in 13-15 days with the scores of 1.0 and alleviated after that with the inflammatory scores of 0.5 in 30 days after injection.The histopathological score was consistent with the clinical score in the models on the 30 days.The serum IL-17 content of model mice was (0.98±0.05) ng/L before injection and increased to (51.85 ±2.42) ng/L on the fifth day,and decreased to (4.01±0.06)ng/L on the fifteen day.But,the serum IL-17 level increased to (25.00±0.94)ng/L again on the 25th day,and then lowed to (6.01 ±0.21)ng/L 30 days after injection,showing a significant elevation in comparison with that of before injection (P=0.000).The serum IFN-γ content of the model mice was (1.02±0.09)ng/L before injection and increased to (50.54±0.48) ng/L on the fifth day,and (73.21±0.12) ng/L on the tenth day,and then it declined gradually until (5.15±0.18)ng/L in the 30th day,which was still higher than that of before injection (P=0.000).After injection of IRBP+CFA,the serum TNF-α level upregulated from the second day to fifth day with the peak values (134.25±0.59)ng/L,and declined to valley on 15th day.A repeat elevation of serum TNF-α level was found on the 20th day with the values (60.54±0.62)ng/L and followed by decrease till the 30th day,which was higher than that of before injection (P=0.660).Serum IL-10 was detectable in the tenth day and peaked on the 15th day.Then a slight decrease was seen till the 30th day,compared with before injection(P =0.000).The contents of IL-10 mRNA,IL-17 mRNA,TNF-α mRNA,IFN-γmRNA in mice spleens followed the same pattern with serum levels of their proteins.Conclusions IL-17,IFN-γ,TNF-α and IL-10 are key inflammatory factors of Th1,Th2 and Th17,they present with specific changes during EAU,it confirming that IFN-γ probably play a pathogenic role in EAU,IL-17 and TNF-α levels probably associated with the chronic and recurrent procedure of uveitis,IL-10 plays an inhibit role in EAU.

Abstract: Due to the continued emergence of multiple variants of SARS-CoV-2, the ongoing pandemic has resulted in severe mortality over the past two years. After the Alpha, Beta, Gamma and Delta variants, the most recent new variant of concern (VOC) strain to emerge is Omicron (B.1.1.529), which evolved as a result of the accumulation of a large number of mutations. The Omicron variant, which has a much higher transmission rate than the Delta variant, soon replaced the Delta variant and others, is now the dominant variant worldwide. The emergence of Omicron poses new challenges for the prevention and control of COVID-19 and has raised a number of concerns worldwide. Recently, cases of Omicron infection have been reported in several parts of China, and therefore this paper provides a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant, including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going COVID-19 pandemic successfully.

OBJECTIVEHirschsprung's Disease (HD) and allied Hirschsprung's disorder (HAD) have very similar clinical manifestations, but there are many different theories about the two diseases. The present study was designed to understand the expression of Ret protein in HD and HAD, and to explore the role of Ret protein in the pathogenesis of HD and HAD.

METHODSColon specimens from patients with confirmed HD and HAD, including 15 cases of HD (male 12, female 3) and 11 cases of HAD (male 8, female 3) were collected for this study. At the same time normal colon specimens from 10 individuals with other diseases were used as control. The expression of Ret protein in the intestinal tissue was detected by using immunohistochemical SABC technique with mouse anti-Ret monoclonal antibody.

RESULTSIn the colon specimens from normal controls and the dilated segments of colon from HD and HAD patients, moderate to large number of Ret-positive cells were observed among the ganglion cells of myenteric plexuses and submucosal plexuses (P > 0.05). On the contrary, Ret-positive cells were not seen in the stenotic segment of colon from HD patients. But there was positive staining in the stenotic segment of the colon from HAD. Moreover, giant ganglion cells showing strongly positive staining could be seen. There were also displastic cells, small cells, and cells with irregular shape. Statistical analysis showed significant differences in Ret cells positivity between the stenotic segment of colon of HD and the normal control (P < 0.001) as well as between HD and HAD (P < 0.001).

CONCLUSIONRet protein may play an important role in the pathogenesis of HD and could not have definite relationship with HAD.

Case-Control Studies ; Child ; Child, Preschool ; Colon ; pathology ; Female ; Hirschsprung Disease ; genetics ; metabolism ; Humans ; Infant ; Male ; Neurons ; pathology ; Proto-Oncogene Proteins c-ret ; genetics ; metabolism

Adult ; Amyloidosis ; diagnosis ; pathology ; Female ; Humans ; Liver Diseases ; diagnosis ; pathology

OBJECTIVETo investigate the correlation between uncoupling protein 2 (UCP2) expression and myocardial mitochondria injury in rats with sepsis induced by lipopolysaccharide (LPS).

METHODSThe rat model of sepsis was established through an intraperitoneal injection of LPS. Forty male Sprague-Dawley rats were randomly and equally divided into control group (an intraperitoneal injection of normal saline), sepsis 6 h group (LPS-6 h group), sepsis 12 h group (LPS-12 h group), sepsis 24 h group (LPS-24 h group), and sepsis 48 h group (LPS-48 h group). The serum and heart tissues were harvested at corresponding time points and myocardial mitochondria was extracted. The microplate reader was applied to measure creatine kinase (CK), creatine kinase-MB (CK-MB), and reactive oxygen species (ROS). Flow cytometry was applied to measure the degree of mitochondrial swelling and mitochondrial membrane potential (MMP). Western blot was used to measure the expression level of UCP2. Electron microscopy was applied to observe the morphological changes in heart tissues and myocardial mitochondria.

RESULTSCompared with the control group, the LPS groups had significantly increased serum levels of CK, CK-MB, and myocardial ROS, as well as a significantly increased degree of mitochondrial swelling (P<0.05), and these values reached their peaks at 24 hours after LPS injection. The LPS groups had a significant decrease in MMP (P<0.05), which reached the lowest level at 24 hours after LPS injection. Western blot showed that the LPS groups had a significant increase in the expression level of myocardial UCP2 compared with the control group (P<0.05), which reached its peak at 24 hours after LPS injection. The results of electron microscopy showed mitochondrial swelling, partial rupture of the mitochondrial membrane, and cavity formation in rats in the LPS groups. The most severe lesions occurred in the LPS-24 h group. In rats with LPS, the ROS level in the myocardial mitochondria and the degree of mitochondrial swelling were positively correlated with the expression level of UCP2 (r=0.796 and 0.893, respectively; P<0.05), while MMP was negatively correlated with the expression level of UCP2 (r=-0.903, P<0.05).

CONCLUSIONSIn the rat model of sepsis, the myocardium and myocardial mitochondria have obvious injuries, and the expression level of UCP2 is closely correlated with mitochondrial injury. Therefore, UCP2 might play an important role in myocardial mitochondrial injury in sepsis.

Animals ; Cardiomyopathies ; genetics ; metabolism ; Disease Models, Animal ; Humans ; Ion Channels ; genetics ; metabolism ; Lipopolysaccharides ; adverse effects ; Male ; Mitochondria, Heart ; metabolism ; Mitochondrial Proteins ; genetics ; metabolism ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sepsis ; genetics ; metabolism ; Uncoupling Protein 2

OBJECTIVETo investigate the role of D-galactose, especially in the structural and functional changes of the immune system in aging.

METHODSSerum levels of advanced glycation end-products (AGE) were determined by ELISA method. Ultra-structures of thymus and spleen were detected by transmission electron microscopy. MTT method was used to determine the lymphocyte proliferation. IL-2 activity was determined by bioassay. Northern blot was used to detect the IL-2 mRNA levels.

RESULTSSerum AGE levels of D-galactose- (P < 0.01) and AGE-treated (P < 0.05) mice (n = 8) were increased significantly. The ultra-structures of thymus and spleen in D-galactose- and AGE-treated mice showed regressive changes similar to those in the aged control group. The lymphocyte mitogenesis and IL-2 activity of spleen were also decreased significantly (P < 0.01, n = 8). The change of IL-2 activity shown by Northern blot resulted from the change of mRNA expression. The AGE plus aminoguanidine group, however, showed no significant change in these parameters in comparison with the young control group (P < 0.01 or P < 0.05, n = 8).

CONCLUSIOND-galactose and AGE lead to a mimic regression change of aging in the immune system in vivo.

Aging ; drug effects ; immunology ; Animals ; Cell Proliferation ; drug effects ; Galactose ; pharmacology ; Glycation End Products, Advanced ; blood ; Interleukin-2 ; metabolism ; Lymphocytes ; drug effects ; immunology ; Mice ; Microscopy, Electron, Transmission ; RNA, Messenger ; metabolism ; Spleen ; drug effects ; immunology ; ultrastructure ; Thymus Gland ; drug effects ; immunology ; ultrastructure

OBJECTIVEX-linked inhibitor of apoptosis protein (XIAP) To gastrointestinal (GI) investigate the expression of XAF1 and heat-shock transcription factors 1 èHSF1éand their relationship in human gastrointestinal cancers.

METHODSImmunoblotting was used to analyze the expression of HSF1 and XAF1 in either gastric or colon cancer tissue and GI cancer cell line. Transient expression of the HSF1-containing vector in GI cell lines and RNA interference were used to up/down-regulae the expression of the HSF1, and the subsequent expression of XAF1 was measured.

RESULTSThe expression of HSF1 was higher in GI cancers than in normal tissues. The expression of XAF1 and HSF1 was negatively correlated in GI cancer cell lines. Stress stimuli up-regulated the expression of HSF1 while the alteration of XAF1 expression was negatively correlated with HSF1 expression.

CONCLUSIONThe high expression of HSF1 in GI cancers is associated with suppressed expression of XAF1, which can be one of the mechanisms for low-expression of XAF1 and insufficient apoptosis in GI cancers.

Animals ; Base Sequence ; Cell Line, Tumor ; DNA-Binding Proteins ; genetics ; Gastrointestinal Neoplasms ; genetics ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Heat Shock Transcription Factors ; Humans ; Intracellular Signaling Peptides and Proteins ; Neoplasm Proteins ; genetics ; Oxidative Stress ; genetics ; Temperature ; Transcription Factors ; genetics

OBJECTIVETo investigate the expressions of X-linked inhibitor of apoptosis protein (XIAP)-associated factor-1 (XAFI) and heat-shock transcription factor 1 (HSF1) and their relationship in human gastrointestinal cancers.

METHODSImmunoblotting was used to analyze the expressions of HSF1 and XAF1 in gastric and colon cancer tissues and in gastrointestinal cancer cells. The gastrointestinal cancer cells were tranfected with a eukaryotic expression vector containing HSF1 gene fragment or subjected to RNA interference to induce up- or down-regulation of HSF1 expression, and the consequence changes in XAF1 expression in the cells was measured. XAF1 expression was also assayed in the cells after stress stimulation for HSF1 expression.

RESULTSThe expression of HSF1 was higher in gastrointestinal cancer tissues than in normal tissues. The expression of XAF1 and HSF1 was inversely correlated in the cancer cell lines, and stress stimuli of the cells up-regulated the expression of HSF1 but down-regulated XAF1 expression.

CONCLUSIONHSF1 expression is increased in gastrointestinal cancer tissues to result in suppressed expression of XAF1, which may be one of the reasons for the low expression of XAF1 in association with the defect of the apoptosis mechanisms in the cancer cells

Cell Line, Tumor ; Colonic Neoplasms ; genetics ; metabolism ; pathology ; DNA-Binding Proteins ; biosynthesis ; genetics ; Heat Shock Transcription Factors ; Humans ; Immunoblotting ; Intracellular Signaling Peptides and Proteins ; Neoplasm Proteins ; biosynthesis ; genetics ; RNA Interference ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Transcription Factors ; biosynthesis ; genetics ; Transfection

OBJECTIVETo evaluate the efficacy of nimotuzumab combined with palitaxel liposome and carboplatin (LP) regimen for treatment of advanced non-small cell lung cancer (NSCLC), and to observe the changes of tumor markers and toxicities in the treatment. METHODS Forty-one patients with advanced NSCLC were randomly divided into 2 groups: 21 patients in the observation group were treated with nimotuzumab (200 mg per week for 6 weeks), palitaxel liposome 160 mg/m2 and carboplatin (AUC = 6). 20 patients in the control group were given LP regimen. Each group completed two cycles of chemotherapy. The level of tumor markers (CEA, CYFR21-1 and NSE) and toxicities were checked at one week before and after the treatment. Thoracic CT examinations were taken before treatment and at the fourth week and eighth week after treatment.

RESULTSIn the observation group, there were 2 cases of CR, 7 cases of PR, 9 cases of SD and 3 cases of PD. The objective response rate (RR) was 42. 9% in the observation group. In the control group, there were 1 case of CR, 6 cases of PR, 8 cases of SD and 5 cases of PD, with a RR of 35.0% in this group. There was no significant difference in the RR between the two groups (P = 0.751). The time to progression (TIP) was 6. 9 months in the observation group and 5. 7 months in the control group, with a significant difference (P = 0.027). The levels of NSE decreased significantly in both groups and showed a significant difference (P = 0.039). The levels of CEA and CYFRA21 in both groups were decreased after treatment, but did not show a significant difference before and after treatment, respectively. Except 3 cases had I-II skin toxicities on the faces in the observation group, there was no significant difference in toxicities between the two groups.

CONCLUSIONNimotuzmab combined with LP regimen shows a synergistic effect, can increase the efficacy and prolong TFP in advanced NSCLC patients. The toxicities are mild and tolerable.

Adult ; Aged ; Antibodies, Monoclonal, Humanized ; adverse effects ; therapeutic use ; Antigens, Neoplasm ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoembryonic Antigen ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; therapy ; Combined Modality Therapy ; Exanthema ; chemically induced ; Female ; Humans ; Keratin-19 ; metabolism ; Liposomes ; administration & dosage ; Lung Neoplasms ; metabolism ; pathology ; therapy ; Male ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Phosphopyruvate Hydratase ; metabolism ; Remission Induction

OBJECTIVESTo find possible factors correlated with combined loss of heterozygosity (LOH) of 1p and 19q.

METHODSThe status of 1p and 19q of 138 glioma specimen from January 2009 to December 2009 was evaluated by Fluorescence in situ hybridization (FISH) method, and the frequencies of combining LOH of 1p/19q were compared between different pathologies, brain sub-regions, genders and ages.

RESULTSThe frequencies of combined LOH of 1p and 19q of oligodendroglial (81.3%) and oligo astrocytic tumors (55.8%) were significantly higher than that of astrocytic tumor (22.2%) (P < 0.01), and the frequency of oligodendroglial tumor was significantly higher than that of oligo astrocytic tumor (P < 0.05). The frequency of combining LOH of 1p and 19q in frontal lobe (61.8%) was higher than that in temporal (31.8%) and insular lobes (34.6%) (P < 0.05).

CONCLUSIONCombining LOH of 1p and 19q has significant correlation with the pathologies and brain sub-regions.

Adolescent ; Adult ; Aged ; Brain Neoplasms ; genetics ; Chromosomes, Human, Pair 1 ; genetics ; Chromosomes, Human, Pair 19 ; genetics ; Female ; Glioma ; genetics ; Humans ; Loss of Heterozygosity ; Male ; Middle Aged ; Young Adult