Pharmacological Effects of Guava (Psidium guajava L.) Seed Polysaccharides: GSF3 Inhibits PC-3 Prostate Cancer Cell Growth through Immunotherapy In Vitro.

The inhibitory effects of purified fractions isolated from guava seed polysaccharides (GSPS) including guava seed polysaccharide fraction 1 (GSF1), GSF2, and GSF3 on prostate cancer cells remain unclear. To clarify the anti-prostate cancer potential, GSPS, GSF1, GSF2, and GSF3 were isolated using Sepharose 6B gel filtration chromatography to assay their inhibitory effects on prostate PC-3 cell growth with direct action or indirect immunotherapy using either splenocyte conditioned media (SCM) or macrophage conditioned media (MCM). Correlations between cytokine profiles in the conditioned media and pro-apoptotic gene expression levels in the corresponding treated PC-3 cells were analyzed. Results showed that GSPS, GSF1, GSF2, and GSF3, particularly GSF3, through either direct action or indirect treatments using SCM or MCM, significantly (p < 0.05) inhibited PC-3 cell growth. GSF3 direct treatments increased pro-apoptotic Bax/anti-apoptotic Bcl-2 mRNA expression ratios in corresponding treated PC-3 cells. Either SCM or MCM cultured with GSF3 increased Fas mRNA expression levels in corresponding treated PC-3 cells. Both Th2-polarized and anti-inflammatory cytokine IL-10 either secreted in SCM or MCM were positively correlated with Fas mRNA expression levels in corresponding treated PC-3 cells. Our results suggest that GSF3 is a potent biological response modifier to decrease PC-3 cell growth through inducing apoptosis.

CRISPR/Cas9 Technology Targeting Fas Gene Protects Mice From Concanavalin-A Induced Fulminant Hepatic Failure.

Fulminant hepatic failure is a life-threatening disease which occurs in patients without preexisting liver disease. Nowadays, there is no ideal therapeutic tool in the treatment of fulminant hepatic failure. Recent studies suggested that a novel technology termed CRISPR/Cas9 may be a promising approach for the treatment of fulminant hepatic failure. In this project, we have designed single chimeric guide RNAs specifically targeting the genomic regions of mouse Fas gene. The in vitro and in vivo effects of sgRNAs on the production of Fas protein were examined in cultured mouse cells and in a hydrodynamic injection-based mouse model, respectively. The in vivo delivery of CRISPR/Cas9 could maintain liver homeostasis and protect hepatocytes from Fas-mediated cell apoptosis in the fulminant hepatic failure model. Our study indicates the clinical potential of developing the CRISPR/Cas9 system as a novel therapeutic strategy to rescue Concanavalin-A-induced fulminant hepatic failure in the mouse model. J. Cell. Biochem. 118: 530-536, 2017. © 2016 Wiley Periodicals, Inc.

Unusual Polyclonal IgM in an IgG Deficient Patient with Autoimmune Lymphoproliferative Syndrome: A Case Study and Literature Review.

Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disease caused germline mutation of FAS gene, gene encoding Fas ligand or Caspase 10 gene. However, in 20% of all ALPS patients, genetic defect is unknown. We presented a case of a 20-year-old male with a history of autoimmune lymphoproliferative syndrome (ALPS; confirmed by genetic study) who came to our medical center with a concern for malignancy. Although no malignancy was detected, his lack of IgA, very low level of IgG (requiring therapy with intravenous IgG) and highly elevated polyclonal IgM (hyperimmunoglobulin M syndrome) were unusual findings because ALPS patients with hypergammaglobulinemia usually demonstrate elevated IgA or IgG.

Therapeutic effect of targeted Fas-expressing adenoviruses method combining γδ T cells in a mouse model of human ovarian carcinoma.

The present study aimed to investigate the therapeutic effect and safety of targeted use of Fas-expressing adenoviruses combined with γδ T cell-mediated killing to treat human ovarian cancer xenografts in BALB/c mice. Shuttle plasmids containing control elements of human telomerase reverse transcriptase promoter and two-step transcriptional amplification system were constructed and packaged into adenovirus-5 vectors to generate expression of an exogenous Fas gene. A mouse xenograft model of human ovarian carcinoma was constructed. A total of 35 BALB/c mice were randomly divided into five groups, which were injected with PBS, γδ T cells, Fas-expressing adenoviruses, taxol, or Fas-expressing adenovirus and γδ T cells. The weight and volume of tumors in mice in each group was monitored. Tissue sections of the various tissues of mice in the Fas-expressing adenovirus and γδ T cells group was compared with those in the PBS group to evaluate the safety of Fas-expressing adenovirus and γδ T cells in the treatment of human ovarian cancer xenograft tumors. The results of the present study indicated that mice in all treatment groups were alive at the end of the treatment course. Tumor weight and volume was the highest in the PBS group, followed successively by the adenovirus group, the γδ T cell group, the adenovirus and γδ T cell group, and the taxol group. The weight and volume inhibition rate in adenovirus and γδ T cell group were significantly higher compared with in the PBS group (P<0.05). Pathological observation of tissue samples revealed that none of vital organs in the adenovirus and γδ T cell group developed any evident morphological changes during treatment, when compared with healthy controls. In conclusion, the combined therapy with Fas-expressing adenoviruses and γδ T cells is efficient and safe for the treatment of mouse human ovarian carcinoma xenografts.

Autoimmune lymphoproliferative syndrome: analysis of 1 pedigree and review of literature / 白血病·淋巴瘤

Objective:To improve the understanding of autoimmune lymphoproliferative syndrome (ALPS).Methods:The clinical data of the proband and his family members in Children's Hospital Affiliated to Zhengzhou University in August 2018 were retrospectively analyzed, and the peripheral blood DNA of the proband, his parents and siblings was extracted. High-throughput next-generation sequencing was used to make gene analysis and validation. Phenotype and genotype of them were also analyzed. Relevant literature was reviewed.Results:The proband was a 1-year and 1-month old boy with hemolytic anemia, thrombocytopenia and splenomegaly as the main manifestations. The double negative T cells and the Vitamin B 12 of the proband were significantly increased and the autoantibodies were positive. The boy's father had a history of splenomegaly. His elder brother and sister had similar clinical manifestations. The results of next-generation sequencing showed that the FAS gene frameshift mutation (c.648delT) was detected in this boy and his father, elder brother and sister, which was a new mutation. After immunosuppressive treatment, the symptoms of the boy improved and the blood cells increased. Conclusions:The frameshift mutation of FAS gene may be the cause of the disease in this ALPS pedigree. Clinically, it is necessary to consider ALPS for children with unexplained hemocytopenia and hepatosplenomegaly. Double-negative T cells, autoantibodies, Vitamin B 12 should be tested, and high-throughput gene sequencing should be performed if necessary.

Family Aggregation of HTLV-1 Infection Associated with FAS -670A/G Polymorphism: A Case Report.

Human T-lymphotropic virus 1 (HTLV-1) infection has been associated with ATL and inflammatory diseases but remains a neglected health problem. HTLV-1 associated diseases were originally described as sporadic entities, but family aggregations have been reported. Viral, genetic, immunological and behavioral factors were used to explain family clusters, but until now a clear explanation remains uncertain. In the present study we report, for the first time, a family cluster of diseased persons presenting the infection across three generations associated with FAS -670A/G polymorphism.

Immunomodulatory Effect of H. Pylori CagA Genotype and Gastric Hormones On Gastric Versus Inflammatory Cells Fas Gene Expression in Iraqi Patients with Gastroduodenal Disorders.

AIM: To evaluate the Immunomodulatory effects of CagA expression; pepsinogen I, II & gastrin-17 on PMNs and lymphocytes Fas expression in inflammatory and gastric cells; demographic distribution of Fas molecule in gastric tissue and inflammatory cells. METHODS: Gastroduodenal biopsies were taken from 80 patients for histopathology and H. pylori diagnosis. Serum samples were used for evaluation of pepsinogen I (PGI); (PGII); gastrin-17 (G-17). RESULTS: Significant difference (p < 0.001) in lymphocytes & PMNs Fas expression; epithelial & lamina propria Fas localization among H. pylori associated gastric disorders. No correlation between grade of lymphocytes & PMNs Fas expression in gastric epithelia; lamina propria and types of gastric disorder. Significant difference (p < 0.001) in total gastric Fas expression, epithelial Fas; lamina propria and gastric gland Fas expression according to CagA, PGI; PGII; PGI/PGII; Gastrin-17. Total gastric Fas expression has significant correlation with CagA, PGII levels. Gastric epithelial and gastric lamina propria Fas expression have significant correlation with CagA, PGI; PGII levels. Significant difference (p < 0.001) was found in lymphocytes & PMNs Fas expression; epithelial & lamina propria localization of lymphocytes & PMNs Fas expression according to CagA, PGI; PGII; PGI/PGII; Gastrin-17. Lymphocytes Fas expression have correlation with PGI, PGII, PGI/PGII. PMNs Fas expression have correlation with PGI, PGII. CONCLUSION: Fas gene expression and localization on gastric and inflammatory cells affected directly by H. pylori CagA and indirectly by gastric hormones. This contributes to progression of various gastric disorders according to severity of CagA induced gastric pathology and gastric hormones disturbance throughout the course of infection and disease.

Single nucleotide polymorphisms of the Fas gene are associated with papillary thyroid cancer.

OBJECTIVES: Fas is the prototypic representative of the death receptor subgroup of the tumor necrosis factor (TNF) receptor family. Recently, single nucleotide polymorphisms (SNPs) of the Fas or Fas ligand (FasL) genes have been shown to be associated with an increased risk of several cancers and with the prognosis of several cancers. The objective of this study was to evaluate the association between the SNPs of the Fas and FasL genes and papillary thyroid cancer (PTC) and to assess the relationship between these SNPs and the clinicopathological characteristics of PTC. METHODS: Five SNPs located within the two genes of Fas and FasL were genotyped using direct sequencing in 94 patients with PTC and 364 healthy controls. Genetic data were analyzed using commercially available software. And, the statistical analyses were performed according to clinicopathologic characteristics of PTC. RESULTS: Genotyping analysis demonstrated that the intron SNP (rs1571013), promoter SNP (rs1800682) and 3'-UTR SNP (rs1468063) of Fas were significantly associated with the development of PTC. We also detected a significant difference between patients with PTC and healthy controls with respect to Fas gene allele frequencies. Furthermore, we found that the 3'-UTR SNP (rs1468063) of Fas was associated with the multifocality of cancer [dominant model, OR 0.28, p=0.028; log-additive model, OR 0.43, p=0.033]. CONCLUSION: We observed a significant association between SNPs of the Fas gene and the development of PTC. In addition, there was a significant association between a Fas SNP and the multifocality of PTC.

Autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma: what 18F-fluorodeoxyglucose positron emission tomography/computed tomography can do in the management of these patients? Suggestions from a case report.

A young patient with undefined autoimmune lymphoproliferative syndrome (ALPS-U) and low back pain underwent a CT and MRI study that showed enhancing vertebral lesions, some pulmonary nodules and diffuse latero-cervical lymphadenopathy. A (18)F-FDG-PET/CT scan showed many areas of intense (18)F-FDG uptake in multiple vertebrae, in some ribs, in the sacrum, in the liver, in both lungs, in multiple lymph nodes spread in the cervical, thoracic and abdominal chains. A bone marrow biopsy showed a "lymphomatoid granulomatosis", a rare variant of B-cell non-Hodgkin lymphoma (NHL). After the treatment, the (18)F-FDG-PET/CT scan showed a complete metabolic response.

Effect of Miao Nationality Herbs Spray for Serum SOD, MDA and Expression of Fas-mRNA and Caspase-3 mRNA in Lung Tissues of Silica-treated Rats / 世界科学技术-中医药现代化

This study was aimed to prepare the spraying agent of prescriptions of Miao nationality herb and investigate the effect of Miao nationality herbs spray for serum SOD, MDA, and expression of Fas and Caspase-3 mRNA in lung tissues of silica-treated rats. The healthy SD rats were divided into 5 groups. Silica dust suspension was used in the model establishment of 4 groups. After the model was successfully established, 3 groups were randomly selected and given glucocorticoids atomization inhalation, Miao nationality herbs spray, Miao nationality herbs spray combined with intragastric administration of herbal medicine, respectively. After 40-day treatment, water-solubletetrazolium salt (WST-1) was used in the detection of serum superoxide dismutase (SOD). Thiobarbituric acid (TBA) was used in the detection of malondialdehyde (MDA). The mRNA expression variance of the Fas and Caspase-3 were detected by RT-PCR. The results showed that compared with the silica dust suspension group, the SOD activity of serum in the Miao nationality herbs spray group was significantly increased (P< 0.05). MDA content and the mRNA of Fas and Caspase-3 were significantly lower in the Miao nationality herbs spray group (P< 0.05). It was concluded that Miao nationality herbs spray group was able to increase the SOD activity of serum, decrease MDA content, and obviously decrease the expression of Fas and Caspase-3 of lung tissues among silica dust suspension rats.

Progress of autoimmune lymphoproliferactive syndrome / 国际儿科学杂志

Autoimmune lymphoproliferactive syndrome is a rare group disorders associated with self stability and immune tolerance of lymphocyte due to genetic mutation which affects the lymphocyte apoptosis .The clinical manifestations comprise lymphoproliferation, development of autoimmunity and malignancies.The pathogenesis and clinical features are complex ALPS were easily missed and no case had been reported until now in China.

Association of Fas gene polymorphisms with bone mineral density in postmenopausal Korean women / 대한산부인과학회지

OBJECTIVE: To examine the relationship between Fas gene polymorphisms, and bone mineral density (BMD). METHODS: Restriction fragment length polymorphisms at the Fas A670G, G1377A gene site, and BMD at the lumbar spine and proximal femur were analyzed in 229 postmenopausal Korean women (81 normal, 111 osteopenic and 37 osteoporotic patients). BMDs were measured by DEXA. RESULTS: The distribution of A670G and G1377C polymorphisms in all postmenopausal women was as follows: AA 18.3%, AG 46.3%, GG 35.4%; GG 38.0%, GA 39.7%, AA 22.3%, respectively. After adjusting for potential confounding factors such as age, BMI, and menopause duration, A670G polymorphism was significantly associated with BMD at the lumbar spine, the femur neck and trochanter in osteopenic and osteoporotic patients, and G1377A polymorphism was significantly associated with BMD at lumbar spine and the femur neck in osteopenic patients. CONCLUSION: These findings suggest that Fas gene polymorphisms may be an important contributor to the variation of BMD among postmenopausal Korean women.

Role of Fas Mediated Cells Apoptosis in Pathogenesis of Human Colonic Cancer Tissue / 中国医师杂志

Objective To explore the role of Fas gene expression in pathogenesis of human colonic cancer tissue.Method Expression of Fas gene protein in benign and malignant colonic tissue was detected by using flow cytometry in forty patients.Results Expression rate of Fas in normal control mucosas was(12 17?3 68)%.The expression rate in colonic cancer tissue was lower than both normal control group and benign tissue.The expression rate in inflammatory tissue was higher than the normal mucosal tissue,and the expression rate was correlated with the tumor differentiation.Conclusions Fas-mediated apoptosis may play an important role in carcinogenesis of colonic tissue.

Association of a Polymorphism in the Promoter Region of Apo-1/Fas Gene with Bipolar Disorder

OBJECTIVE: Recently, many experimental evidences have been reported that psychiatric diseases are closely related with neurodevelopmental abnormalities and this can be properly explained by apoptosis. It is known that Apo-1/Fas is one of the genes in charge of apoptosis related with neurodevelopmental abnormalities. In this study, the association between bipolar disorder and functional polymorphism in Apo-1/Fas promoter gene has been investigated. METHOD: For 81 bipolar disorder patients and 217 healthy control subjects, MvaI restriction fragment length polymorphism(RFLP) of Apo-1/Fas promoter gene was analyzed after polymerase chain reaction(PCR) amplification. RESULT: There was a statistical significant difference in genotypic distribution(chi2=16.656, df=2, p=0.0002) and allelic frequencies(chi2=14.225, df=1, p=0.0002) between bipolar disorder patients and healthy control subjects. CONCLUSION: Our results suggest an association between functional polymorphism in Apo-1/Fas promoter gene and bipolar disorder and provide the important genetic information related with the pathogenesis of the disease. Further studies employing larger samples are required to clarify the present results.

Effects of intra-bile duct radiation on the Fas gene expression and prevention of bile duct stricture in dogs / 中华消化杂志

Objective To study ?-radiation-induced expression of Fas gene and its significance in the apoptosis of proliferative muscle cells of bile duct wall in dog model. Methods The ~ ~103 Palladium (Pd) radioactive stent or general stent was inserted into dog extrahepatic bile duct, and bile duct specimens were ~obtained after 30 days. Expression of Fas and apoptosis of bile duct muscle cells in the control and ?-radiation-~induced groups were determined by immunohistochemical technique. The square of bile duct cavities of two groups were measured by computer ~imaging detecting system. Results The ~expre- ~ssion of Fas was much higher in the bile duct wall of dogs with ~ ~103 Pd radioactive stent than that in dogs with the general stent, and apoptotic muscle cells were more common in Fas highly expreessed than that in the Fas lowly ~experssed subgroup, and no stricture of extrahepatic bile duct was seen in former subgroup. No obvious ~apoptotic muscle cells were observed in the Fas lowly expressed subgroup, however, the dog in this ~subgroup had the obvious stricture of extrahepatic bile duct. Conclusions The level of Fas gene expression was associated with the rate of cell apoptosis in dog bile duct wall, and the ~ ~103 Pd radioactive stent may increase the expression of Fas gene, enhance the apoptosis of proliferative muscle cells of bile duct, and therefore prevent the stricture of extrahepatic bile duct.

APOPTOSIS AND CHANGES IN APOTOSIS REGULATING GENES IN LUNG TISSUE CELLS AFTER SMOKE INHALATION INJURY IN RATS / 解放军医学杂志

To explore the role of apoptosis, apoptosis regulating genes in the pathogenesis and development of smoke inhalation injury. With smoke inhalation injury rat model, the changes int the expression of Bcl 2, Bax, Fas, FasL genes mRNA and protein contents and their relationship with apoptosis of lung tissue cells at different time points after the injury were observed with TUNEL, immunohistochemistry and RT PCR techniques. The results showed that: ①apoptosis indet of lung colls after smoke inhalation injury increased, ②expressions of Bcl 2, Bax, Fas, FasL genes were obviously up regulated in injury group, peaking at the 12th hour, whereas the peak of protein expression was at the 24th hour. Furthermore, a significant correlation was found between the expression of Fas, Fasl, Bax gene and apoptosis indices in lung cells. The results suggested that apoptosis participated in the early pathological process of smoke inhalation injury, and apoptosis regulating genes foot part in the regulation of apoptosis in smoke inhalation injury.

In vitro Observation on the Apoptosis Induced by H_2O_2 in Protoscolex of Echinococcus granulosus / 中国寄生虫学与寄生虫病杂志

Objective To explore the apoptosis induced by hydrogen peroxide ( H2O2) in protoscolex of Echinococcus granulosus. Methods Protoscoleces were cultured in vitro, and used for the experiment in 2 groups: RPMI 1640 medium and RPMI 1640 medium added with glutamine. They were then treated with different concentrations of H2O2 to induce apoptosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay (TUNEL) was employed to observe the apoptosis. Protein expression of caspase-1, caspase-3 and Fas was detected by SP immunohistochemical technique, stained with DAB restained with hematoxylin. A yellow or brown color nucleus revealed positive apoptosis cells in protoscolex, a brown reaction product in cytoplasm showed positive cells of caspase-1 and caspase-3, and brown cell membrane and cytoplasm revealed Fas product; otherwise it was judged as negative. According to the percentage of positive cells in a protoscolex, the expression level was divided as 4 grades. The percentage of less than 5% was regarded as "-", 5%-25% as "+", 26%-50% as "++", more than 50% as "+++". The experiments were repeated 2 times with controls. Results In RPMI 1640 group, positive TUNEL was found in the protoscolex induced by 1 mmol/L H2O2 inducing for 12 hours. Induced by 1 mmol/L H2O2 for 4 h, the "+ -++" expression rate of caspase-1 and caspase-3 in the protoscoleces was 86.6% and 77.8% , and for 8 h, 86.6% and 80.0% respectively, a significant increase in comparison to the control (P