Objective To explore the role of the base mismatch repair gene Mutyh in retinopathy of prematurity(ROP). Methods Mutyh(-/-)and wild-type(WT)mice were used for the modeling of oxygen-induced retinopathy.The retinal oxidative stress was examined,and the ultrastructures of photoreceptors and mitochondria were observed.The biomarkers of photoreceptors and mitochondria were tested.Furthermore,the photoreceptor cell line 661W was treated with hydrogen peroxide for the modeling of oxidative stress.In the cell model,and the oxidative stress and photoreceptor functions in the cells were measured. Results In both the mouse and cell models,the expression of Mutyh was up-regulated.Mutyh knockout in mice and knockdown in cells exerted negative effects on photoreceptors and mitochondria.Mutyh overexpression showed protective functions in the cell model,indicating that Mutyh played a role in repairing photoreceptors and mitochondria. Conclusions Mutyh showed the potential to become a biomarker of ROP.Increasing Mutyh expression might have therapeutic effects on ROP,which needs further validation.
Oxidative Stress ; Animals ; Mice ; DNA Glycosylases/metabolism* ; Retinopathy of Prematurity/etiology* ; Mice, Knockout ; Disease Models, Animal ; Humans ; Mitochondria/metabolism*

Daratumumab is the first CD38 monoclonal antibody drug approved for the treatment of patients with multiple myeloma. It can bind to CD38 expressed by tumor cells, inhibit tumor cell growth and induce myeloma cell apoptosis through a variety of immune-related mechanisms. Meanwhile, CD38 is also expressed in other cells, including regulatory T cells, regulatory B cells and myeloid-derived suppressor cells, which provides a theoretical basis for the treatment of hematological tumor diseases other than non-multiple myeloma diseases. This article reviews the research progress and application of this part.
Humans ; Multiple Myeloma/pathology* ; ADP-ribosyl Cyclase 1 ; Antibodies, Monoclonal/pharmacology* ; Hematologic Neoplasms/drug therapy*

OBJECTIVE: To investigate the predict significance of the high aldehyde dehydrogenase activity (ALDH METHODS: Bone marrow samples of 23 t(8;21) AML patients diagnosis and achieved complete remission in our hospital from April 2015 to June 2016 were collected, then flow cytometry method was used to detect the activity of ALDH, relationship between it and relapse was analyzed. RESULTS: All the patients were followed up for a median of 32 (2-52) months. The median percentage of CD34 CONCLUSION The percentage of CD34
ADP-ribosyl Cyclase 1 ; Antigens, CD34 ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; Neoplastic Stem Cells ; Prognosis ; Recurrence ; Remission Induction

Adenosine diphosphate (ADP)-ribosylation is a unique post-translational modification that regulates many biological processes, such as DNA damage repair. During DNA repair, ADP-ribosylation needs to be reversed by ADP-ribosylhydrolases. A group of ADP-ribosylhydrolases have a catalytic domain, namely the macrodomain, which is conserved in evolution from prokaryotes to humans. Not all macrodomains remove ADP-ribosylation. One set of macrodomains loses enzymatic activity and only binds to ADP-ribose (ADPR). Here, we summarize the biological functions of these macrodomains in DNA damage repair and compare the structure of enzymatically active and inactive macrodomains. Moreover, small molecular inhibitors have been developed that target macrodomains to suppress DNA damage repair and tumor growth. Macrodomain proteins are also expressed in pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, these domains may not be directly involved in DNA damage repair in the hosts or pathogens. Instead, they play key roles in pathogen replication. Thus, by targeting macrodomains it may be possible to treat pathogen-induced diseases, such as coronavirus disease 2019 (COVID-19).
ADP-Ribosylation ; COVID-19/metabolism* ; DNA Repair/physiology* ; Evolution, Molecular ; Humans ; Models, Biological ; Models, Molecular ; N-Glycosyl Hydrolases/metabolism* ; Poly(ADP-ribose) Polymerases/metabolism* ; Protein Domains ; SARS-CoV-2/pathogenicity*

Multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approaches, chimeric antigen receptor (CAR) T-cell therapy is the most promising star, based on the results of previous success in B-cell neoplasms. In this immunotherapy, autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure. Tisagenlecleucel and Axicabtagene, targeting the CD19 antigen, are the two pacesetters of CAR T-cell products. They were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Their development enabled unparalleled efficacy in combating hematopoietic neoplasms. In this review article, we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.
ADP-ribosyl Cyclase 1/immunology* ; B-Cell Maturation Antigen/immunology* ; Humans ; Immunotherapy, Adoptive/methods* ; Multiple Myeloma/therapy* ; Receptors, Chimeric Antigen/immunology* ; Receptors, G-Protein-Coupled/immunology* ; Signaling Lymphocytic Activation Molecule Family/immunology* ; Syndecan-1/immunology* ; T-Lymphocytes/immunology*

OBJECTIVE: To investigate the apoptosis of CD34CD38-KG1a leukemia stem cells induced by Qinba selenium-mushroom extract(FA-2-b-β), and its related mechanism. METHODS: CD34CD38--KG1a cells were isolated from KG1a cell line by magnetic activated cell sorting. The proliferation ability of KG1a stem cells treatd by various concentration of FA-2-b-β(1.2-2.4 mg/ml) in vitro for 24 and 48 hours were tested by cell counting Kit-8(CCK8). Flow cytometry was used to detect the apoptosis rate of KG1a stem cells in each group after treated by FA-2-b-β in vitro. Expression of BAX,BCL-2,Casepase-3 and Cyclin D1 protein were detected by Western blot. RESULTS: The proportion of CD34CD38--KG1a stem cells was (95.35±2.63）% after immunomagnetic isolation. The proliferation of KG1a stem cells was inhibited significantly by FA-2-b-β, which shows a time- and dose-dependent manner (24 h,r=0.943; 48 h,r=0.976). Flow cytometry shows that with the increasing of drug concentration, the apoptosis was also increased, when KG1a stem cells was treated by FA-2-b-β for 24 h. Western blot indicated that the expression of apoptosis-related protein BAX and Casepase-3 were up-regulated, the expression of BCL-2 and Cyclin D1 were down-regulated. CONCLUSION FA-2-b-β can regulate proliferation and apoptosis KG1a stem cells, the involved mechanism may be related with the activation of mitochondrial-mediated apoptotic pathway.
ADP-ribosyl Cyclase 1 ; Antigens, CD34 ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Membrane Glycoproteins ; Neoplastic Stem Cells ; Selenium

BACKGROUND: Serum antinuclear antibodies (ANAs) are positive in some patients with chronic lymphocytic leukemia (CLL), but the prognostic value of ANAs remains unknown. The aim of this study was to evaluate the role of ANAs as a prognostic factor in CLL. METHODS: This study retrospectively analyzed clinical data from 216 newly diagnosed CLL subjects with ANAs test from 2007 to 2017. Multivariate Cox regression analyses were used to screen the independent prognostic factors related to time to first treatment (TTFT), progression free survival (PFS) and overall survival (OS). Receiver operator characteristic curves and area under the curve (AUC) were utilized to assess the predictive accuracy of ANAs together with other independent factors for OS. RESULTS: The incidence of ANAs abnormality at diagnosis was 13.9%. ANAs positivity and TP53 disruption were independent prognostic indicators for OS. The AUC of positive ANAs together with TP53 disruption was 0.766 (95% confidence interval [CI]: 0.697-0.826), which was significantly larger than that of either TP53 disruption (AUC: 0.706, 95% CI: 0.634-0.772, P = 0.034) or positive ANAs (AUC: 0.595, 95% CI: 0.520-0.668, P < 0.001) in OS prediction. Besides, serum positive ANAs as one additional parameter to CLL-international prognostic index (IPI) obtained superior AUCs in predicting CLL OS than CLL-IPI alone. CONCLUSION This study identified ANAs as an independent prognostic factor for CLL, and further investigations are needed to validate this finding.
ADP-ribosyl Cyclase 1 ; blood ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Antinuclear ; blood ; Autoimmunity ; physiology ; Female ; Humans ; Kaplan-Meier Estimate ; Leukemia, Lymphocytic, Chronic, B-Cell ; blood ; mortality ; Male ; Middle Aged ; Multivariate Analysis ; Mutation ; genetics ; Proportional Hazards Models ; Retrospective Studies ; Survival Analysis ; Tumor Suppressor Protein p53 ; blood ; Young Adult ; ZAP-70 Protein-Tyrosine Kinase ; blood

Sequence type (ST) 33 of Shiga toxin-producing Escherichia coli (STEC) strain O91:H14 has been proposed as a potential domestic clone of STEC in Korea because of its high prevalence among human patients with mild diarrhea or asymptomatic carriers. Herein, the clonal diversity of 17 STEC O91:H14 isolates of ST33 during 2003 to 2014 was analyzed by pulsed-field gel electrophoresis, including 14 isolates from human patients and 3 from retail meats. Their virulence characteristics, acid resistance, and antimicrobial susceptibility were also determined. Our results showed that all isolates were clustered mainly into three different pulsotypes and were likely low pathogenic without antimicrobial resistance.
Clone Cells ; Diarrhea ; Electrophoresis, Gel, Pulsed-Field ; Escherichia coli ; Humans ; Korea ; Meat ; Molecular Epidemiology ; Prevalence ; Shiga Toxin ; Shiga-Toxigenic Escherichia coli ; Virulence

Objective: To investigate the characteristic and prognostic significance of leukemia stem cells associated antigens expressions including CD34, CD38, CD123, CD96 and TIM-3 in t (8;21) AML. Methods: Bone marrow samples of 47 t (8;21) AML patients were collected at diagnosis from October 2015 to April 2018 in Peking University Peoples' Hospital, then flow cytometry method was performed to detect the expression frequencies of CD34, CD38, CD123, CD96 and TIM-3 to analyze the relationship between leukemia stem cells associated antigens expressions and relapse. Results: Of 47 t (8;21) AML patients tested, the median percentages of CD34(+)CD38(-), CD34(+) CD38(-)CD123(+), CD34(+)CD38(-) CD96(+) and CD34(+) CD38(-) TIM-3(+) cells among nucleated cells were 2.37%, 0.24%, 0.27% and 0.06%, respectively. All the frequencies of CD34(+)CD38(-), CD34(+)CD38(-)CD123(+), CD34(+)CD38(-)CD96(+) and CD34(+) CD38(-)TIM-3(+) cells had no impact on the achievement of CR after the first course of induction. All higher frequencies of CD34(+)CD38(-), CD34(+)CD38(-)CD123(+), CD34(+)CD38(-)CD96(+) cells were related to higher 2-year CIR rate. Whereas, the frequency of CD34(+) CD38(-) TIM-3(+) cells had no impact on CIR rate. Both high frequency of CD34(+) CD38(-) cells and the high level of minimal residual diseases (patients with <3-log reduction in the RUNX1-RUNX1T1 transcript level after the second consolidation therapy) were independent poor prognostic factors of CIR[P=0.025, HR=6.9 (95%CI 1.3-37.4) ; P=0.031, HR=11.1 (95%CI 1.2-99.2) ]. Conclusion: Different leukemia stem cells associated antigens had distinct prognostic significance in t (8;21) AML. High frequencies of CD34(+) CD38(-), CD34(+) CD38(-) CD123(+) and CD34(+)CD38(-)CD96(+) cells at diagnosis predicted relapse in patients with t (8;21) AML.
ADP-ribosyl Cyclase 1 ; Antigens, CD ; Flow Cytometry ; Humans ; Interleukin-3 Receptor alpha Subunit ; Leukemia, Myeloid, Acute ; Neoplastic Stem Cells ; Prognosis ; Stem Cells

PURPOSE: To investigate the efficacy, and identify predictors of success of selective laser trabeculoplasty (SLT) in open-angle glaucoma (OAG) patients after adjusting for intraocular pressure (IOP) changes in the untreated fellow eye. METHODS: This retrospective chart review included 52 eyes of 52 OAG patients who underwent SLT in one eye and were followed-up for at least 1 year after the procedure. The IOP was measured before the treatment, at 1, 2, and 3 months posttreatment, and every 3 months thereafter. To account for the possible influence of IOP fluctuations on laser outcomes, post-laser IOP values of the treated eye of each patient were also analyzed, after adjusting for IOP changes in the untreated fellow eye. Success was defined as an IOP decrease ≥20% of the pretreatment IOP. The success rate was determined based on Kaplan-Meier survival analysis and factors predictive of success were analyzed using the Cox proportional hazard model. RESULTS: The mean pretreatment IOP was 23.17 ± 6.96 mmHg. The mean IOP reduction was 5.59 ± 4.78 mmHg (29.7%) and the success rate was 65.4% at 1 year. The adjusted mean IOP reduction was 4.70 ± 4.67 mmHg (23.9%) and the adjusted success rate was 53.9%. Pretreatment IOP was associated with SLT success; the higher the pretreatment IOP, the greater the post-laser IOP reduction (p = 0.025). Age and mean deviation index did not show a significant association with SLT success (p = 0.066 and p = 0.464, respectively). CONCLUSIONS: SLT is a safe and effective alternative method of IOP reduction in OAG patients. Herein, pretreatment IOP was the only factor significantly associated with SLT success. IOP fluctuations of the untreated eye should be considered for a better understanding of the impact of treatment.
Glaucoma, Open-Angle ; Humans ; Intraocular Pressure ; Methods ; Proportional Hazards Models ; Retrospective Studies ; Shiga Toxin 1 ; Trabeculectomy