Dexamethasone potentiates chimeric antigen receptor T cell persistence and function by enhancing IL-7Rα expression.

Dexamethasone (dex) is a glucocorticoid that is a mainstay for the treatment of inflammatory pathologies, including immunotherapy-associated toxicities, yet the specific impact of dex on the activity of CAR T cells is not fully understood. We assessed whether dex treatment given ex vivo or as an adjuvant in vivo with CAR T cells impacted the phenotype or function of CAR T cells. We demonstrated that CAR T cell expansion and function were not inhibited by dex.

Systems biology approach reveals a link between mTORC1 and G2/M DNA damage checkpoint recovery.

Checkpoint recovery, the process that checkpoint-arrested cells with normal DNA repair capacity resume cell cycle progression, is essential for genome stability. However, the signaling network of the process has not been clearly defined. Here, we combine functional proteomics, mathematical modeling, and molecular biology to identify mTORC1, the nutrient signaling integrator, as the determinant for G2/M checkpoint recovery.

Identifying Cell Cycle Modulators That Selectively Target ARID1A Deficiency Using High-Throughput Image-Based Screening.

ARID1A, a component of the chromatin remodeling complex SWI/SNF, is an evolutionarily conserved complex that uses the energy of adenosine triphosphate hydrolysis to remodel chromatin structure and functions as a master regulator of gene transcription. Recent genomic studies have revealed that ARID1A is one of the most frequently mutated genes in human cancers. However, therapeutic approaches that selectively target ARID1A-mutant tumors are not yet clinically available.

Cellular responses to replication stress: Implications in cancer biology and therapy.

DNA replication is essential for cell proliferation. Any obstacles during replication cause replication stress, which may lead to genomic instability and cancer formation. In this review, we summarize the physiological DNA replication process and the normal cellular response to replication stress.

Phosphorylation of the BRCA1 C terminus (BRCT) repeat inhibitor of hTERT (BRIT1) protein coordinates TopBP1 protein recruitment and amplifies ataxia telangiectasia-mutated and Rad3-related (ATR) Signaling.

The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase functions as a central node in the DNA damage response signaling network. The mechanisms by which ATR activity is amplified and/or maintained are not understood. Here we demonstrate that BRIT1/microcephalin (MCPH1), a human disease-related protein, is dispensable for the initiation but essential for the amplification of ATR signaling.

Oral hygiene risk indicators among 6- to 9-year-old Taiwanese aboriginal children.

This study investigated the dental health status, dietary habits, oral hygiene levels, and caretaker risk indicators among Taiwanese children. This cross-sectional purposive sampling study included 256 aboriginal children, 6 to 9 years old, living in remote regions in southern Taiwan. Participants received dental examinations, and questionnaires were completed by caretakers.

Human nuclease/helicase DNA2 alleviates replication stress by promoting DNA end resection.

In precancerous and cancerous lesions, excessive growth signals resulting from activation of oncogenes or loss of tumor suppressor genes lead to intensive replication stress, which is recognized by a high level of replication-associated DNA double-strand breaks (DSB). However, the molecular mechanism by which cells alleviate excessive replication stress remains unclear. In this study, we report that the human nuclease/helicase DNA2 facilitates homologous recombination to repair replication-associated DNA DSBs, thereby providing cells with survival advantages under conditions of replication stress.

Toothbrushing habits and risk indicators of severe early childhood caries among aboriginal Taiwanese.

The purpose of this study was to investigate the toothbrushing habits and risk indicators among aboriginal children with severe early childhood caries (S-ECC). This was a cross-sectional purposive sampling study that included 281 aboriginal children aged 2 to 5 years living in remote regions in southern Taiwan. Participant received dental examinations and questionnaires that were completed by caretakers.

Chromodomain helicase DNA-binding protein 4 (CHD4) regulates homologous recombination DNA repair, and its deficiency sensitizes cells to poly(ADP-ribose) polymerase (PARP) inhibitor treatment.

To ensure genome stability, cells have evolved a robust defense mechanism to detect, signal, and repair damaged DNA that is generated by exogenous stressors such as ionizing radiation, endogenous stressors such as free radicals, or normal physiological processes such as DNA replication. Homologous recombination (HR) repair is a critical pathway of repairing DNA double strand breaks, and it plays an essential role in maintaining genomic integrity. Previous studies have shown that BRIT1, also known as MCPH1, is a key regulator of HR repair.

Correlation between air pollution and postneonatal mortality in a subtropical city: Taipei, Taiwan.

With growing evidence of the association between daily mortality and air pollution exposure in adults, it is important to investigate whether infants are also susceptible. The purpose of this study was to examine the relationship between air pollution exposure and postneonatal, defined as infant of more than 27 d and less than 1 yr old, mortality in Taipei, Taiwan's largest city, which has a subtropical climate, for the period 1994-2000, using a case-crossover analysis. This design is an alternative to Poisson time-series regression for studying the short-term adverse health effects of air pollution.

Air pollution and postneonatal mortality in a tropical city: Kaohsiung, Taiwan.

With growing evidence of the association between daily mortality and air pollution in adults, it is important to investigate whether infants are also susceptible to the adverse health effects of ambient air pollutants. The purpose of this study is to examine the relationship between air pollution and postneonatal mortality in Kaohsiung, Taiwan, a large industrial city with a tropical climate, during the period 1994-2000, using a case-crossover analysis. Case-crossover analysis provides an alternative to Poisson time-series regression for studying the short-term adverse health effects of air pollution.