CYP1B1 affects the integrity of the blood-brain barrier and oxidative stress in the striatum: An investigation of manganese-induced neurotoxicity.

Aims: Excessive influx of manganese (Mn) into the brain across the blood-brain barrier induces neurodegeneration. CYP1B1 is involved in the metabolism of arachidonic acid (AA) that affects vascular homeostasis. We aimed to investigate the effect of brain CYP1B1 on Mn-induced neurotoxicity.

Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson Syndrome and Toxic epidermal necrolysis.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is a rare but life-threatening cutaneous drug reaction mediated by human leukocyte antigen (HLA) class I-restricted CD8+ T-cells. To obtain an unbiased assessment of SJS/TEN cellular immunopathogenesis, we performed single-cell (sc) transcriptome, surface proteome, and TCR sequencing on unaffected skin, affected skin, and blister fluid from 17 SJS/TEN patients. From 119,784 total cells, we identified 16 scRNA-defined subsets, confirmed by subset-defining surface protein expression.

Emerging role of m6A modification in fibrotic diseases and its potential therapeutic effect.

Fibrosis can occur in a variety of organs such as the heart, lung, liver and kidney, and its pathological changes are mainly manifested by an increase in fibrous connective tissue and a decrease in parenchymal cells in organ tissues, and continuous progression can lead to structural damage and organ hypofunction, or even failure, seriously threatening human health and life. N6-methyladenosine (m6A) modification, as one of the most common types of internal modifications of RNA in eukaryotes, exerts a multifunctional role in physiological and pathological processes by regulating the metabolism of RNA. With the in-depth understanding and research of fibrosis, we found that m6A modification plays an important role in fibrosis, and m6A regulators can further participate in the pathophysiological process of fibrosis by regulating the function of specific cells.

TREM2: Potential therapeutic targeting of microglia for Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease, resulting in the loss of cognitive ability and memory. However, there is no specific treatment to mechanistically inhibit the progression of Alzheimer's disease, and most drugs only provide symptom relief and do not fundamentally reverse AD. Current studies show that triggering receptor expressed on myeloid cells 2 (TREM2) is predominantly expressed in microglia of the central nervous system (CNS) and is involved in microglia proliferation, survival, migration and phagocytosis.

The emerging importance role of m6A modification in liver disease.

N6-methyladenosine (m6A) modification, as one of the most common types of inner RNA modification in eukaryotes, plays a multifunctional role in normal and abnormal biological processes. This type of modification is modulated by m6A writer, eraser and reader, which in turn impact various processes of RNA metabolism, such as RNA processing, translation, nuclear export, localization and decay. The current academic view holds that m6A modification exerts a crucial role in the post-transcriptional modulation of gene expression, and is involved in multiple cellular functions, developmental and disease processes.

Positive regulators of T cell functions as predictors of prognosis and microenvironment characteristics of low-grade gliomas.

Background: Low-grade gliomas (LGG) are one of the most prevalent types of brain cancers. The efficacy of immunotherapy in LGG is limited compared to other cancers. Immunosuppression in the tumor microenvironment (TME) of LGG is one of the main reasons for the low efficacy of immunotherapy.

Candida albicans-induced activation of the TGF-β/Smad pathway and upregulation of IL-6 may contribute to intrauterine adhesion.

Iatrogenic injury to endometrial tissue is the main cause of intrauterine adhesions (IUA) and infection can also damage the endometrium. The microbiota plays an important role in the health of the female reproductive tract. However, the mechanism is still unclear.

Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the one of the most prevalent and fatal form of malignant tumors worldwide. Recently, immunotherapy is widely used in the treatment of patients with LUAD and has proved to be clinically effective in improve the prognosis of patients. But there still has been a tremendous thrust to further improve the efficacy of immunotherapy in individual patients with LUAD.

A low-cost, sensitive and specific PCR-based tool for rapid clinical detection of HLA-B*35 alleles associated with delayed drug hypersensitivity reactions.

HLA (HLA) alleles are risk factors for CD8+ T-cell-mediated drug hypersensitivity reactions. However, as most HLA associations are incompletely predictive and/or involve risk alleles at low frequency, costly sequence-based typing can elude an economically productive cost: benefit ratio for clinical validation studies and diagnostic and/or preventative screening. Hence rapid and low-cost detection assays are now required, both for single alleles but also across risk loci associated with broader multi-disease risk; exemplified by associations with diverse alleles in HLA-B*35, including HLA-B*35:01 and green tea- or co-trimoxazole-induced liver injury.

Practical Implementation of Genetics: New Concepts in Immunogenomics to Predict, Prevent, and Diagnose Drug Hypersensitivity.

Delayed drug hypersensitivities are CD8 T cell-mediated reactions associated with up to 50% mortality. Human leukocyte antigen (HLA) alleles are known to predispose disease and are specific to drug, reaction, and patient ethnicity. Pretreatment screening is recommended for a handful of the strongest associations to identify and prevent drug use in high-risk patients.

Emerging Importance of Chemokine Receptor CXCR4 and Its Ligand in Liver Disease.

Chemokine receptors are members of the G protein-coupled receptor superfamily, which together with chemokine ligands form chemokine networks to regulate various cellular functions, immune and physiological processes. These receptors are closely related to cell movement and thus play a vital role in several physiological and pathological processes that require regulation of cell migration. CXCR4, one of the most intensively studied chemokine receptors, is involved in many functions in addition to immune cells recruitment and plays a pivotal role in the pathogenesis of liver disease.

Visual Genomics Analysis Studio as a Tool to Analyze Multiomic Data.

Type B adverse drug reactions (ADRs) are iatrogenic immune-mediated syndromes with mechanistic etiologies that remain incompletely understood. Some of the most severe ADRs, including delayed drug hypersensitivity reactions, are T-cell mediated, restricted by specific human leukocyte antigen risk alleles and sometimes by public or oligoclonal T-cell receptors (TCRs), central to the immunopathogenesis of tissue-damaging response. However, the specific cellular signatures of effector, regulatory, and accessory immune populations that mediate disease, define reaction phenotype, and determine severity have not been defined.

Genomic Risk Factors Driving Immune-Mediated Delayed Drug Hypersensitivity Reactions.

Adverse drug reactions (ADRs) remain associated with significant mortality. Delayed hypersensitivity reactions (DHRs) that occur greater than 6 h following drug administration are T-cell mediated with many severe DHRs now associated with human leukocyte antigen (HLA) risk alleles, opening pathways for clinical prediction and prevention. However, incomplete negative predictive value (NPV), low positive predictive value (PPV), and a large number needed to test (NNT) to prevent one case have practically prevented large-scale and cost-effective screening implementation.

An Updated Review of the Diagnostic Methods in Delayed Drug Hypersensitivity.

Delayed drug hypersensitivity reactions are clinically diverse reactions that vary from isolated benign skin conditions that remit quickly with no or symptomatic treatment, drug discontinuation or even continued drug treatment, to the other extreme of severe cutaneous adverse reactions (SCARs) that are associated with presumed life-long memory T-cell responses, significant acute and long-term morbidity and mortality. Diagnostic "in clinic" approaches to delayed hypersensitivity reactions have included patch testing (PT), delayed intradermal testing (IDT) and drug challenges for milder reactions. Patch and IDT are, in general, performed no sooner than 4-6 weeks after resolution of the acute reaction at the maximum non-irritating concentrations.

The density of endometrial glandular openings: a novel variable to predict the live birth rate in patients with intrauterine adhesions following hysteroscopic adhesiolysis.

Study Question: Can the density of endometrial glandular openings (DEGO) be a reliable and simple new variable in the prediction of live birth after hysteroscopic adhesiolysis?

Summary Answer: The DEGO grade at follow-up hysteroscopy outperforms American Fertility Society (AFS) score in predicting the live birth rate after hysteroscopic adhesiolysis for patients with intrauterine adhesions (IUAs).

What Is Known Already: Several methods, such as endometrial thickness and AFS score, have been proposed for predicting the live birth rate in patients with IUAs who undergo hysteroscopic adhesiolysis.

Study Design, Size, Duration: A test cohort of 457 patients with IUAs who underwent hysteroscopic adhesiolysis and had satisfactory follow-up hysteroscopy videos were retrospectively enrolled between January 2016 and January 2017.

Diagnosis and treatment of cervical incompetence combined with intrauterine adhesions.

Background: Cervical insufficiency (CI) with concomitant intrauterine adhesions (IUAs) is a common clinical phenomenon among CI patients. But there are neither published reports regarding the difference in diagnosis and treatment of such patients compared to those with CI only, nor any report about their prognosis. This study aimed to preliminary the alteration in diagnostic and curative aspects of these patients, so as to provide a certain reference for the clinical management of such conditions.

New genetic predictors for abacavir tolerance in HLA-B*57:01 positive individuals.

Abacavir hypersensitivity syndrome (ABC HSS) is strongly associated with carriage of human leukocyte antigen (HLA)-B*57:01, which has a 100% negative predictive value for the development of ABC HSS. However, 45% of individuals who carry HLA-B*57:01 can tolerate ABC. We investigated immune and non-immune related genes in ABC HSS (n = 95) and ABC tolerant (n = 43) HLA-B*57:01 + patients to determine other factors required for the development of ABC HSS.

Controllably Enriched Oxygen Vacancies through Polymer Assistance in Titanium Pyrophosphate as a Super Anode for Na/K-Ion Batteries.

Although sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs) are promising prospects for next-generation energy storage devices, their low capacities and inferior kinetics hinder their further application. Among various phosphate-based polyanion materials, titanium pyrophosphate (TiPO) possesses outstanding ion transferability and electrochemical stability. However, it has rarely been adopted as an anode for SIBs/PIBs due to its poor electronic conductivity and nonreversible phase transitions.

MiR-34c/SOX9 axis regulates the chemoresistance of ovarian cancer cell to cisplatin-based chemotherapy.

Cisplatin (DDP)-based chemotherapy is a standard strategy for ovarian cancer (OC), while chemoresistance remains a major therapeutic challenge. Transcription factor SOX9 has been reported to be associated with tumor cell proliferation, metastasis, and chemoresistance. In the current study, we observed a higher SOX9 expression in OC cell lines; SOX9 overexpression might aggravate the chemoresistance of the OC cell to DDP, whereas its knockdown enhanced the chemoresistance.

The Protective Role of Brain CYP2J in Parkinson's Disease Models.

CYP2J proteins are present in the neural cells of human and rodent brain regions. The aim of this study was to investigate the role of brain CYP2J in Parkinson's disease. Rats received right unilateral injection with lipopolysaccharide (LPS) or 6-hydroxydopamine (6-OHDA) in the substantia nigra following transfection with or without the CYP2J3 expression vector.

MircroRNA-139 sensitizes ovarian cancer cell to cisplatin-based chemotherapy through regulation of ATP7A/B.

Purpose: Ovarian cancer remains a most malignant female cancer nowadays. The acquisition of chemoresistance to common-used cisplatin-based chemotherapy results in a decreased overall patient survival. The present study is aimed to investigate the role and mechanism by which miR-139/ ATPases7A/B axis modulates the chemoresistance of ovarian cancer to cisplatin-based chemotherapy.

The Protein Encoded by the CCDC170 Breast Cancer Gene Functions to Organize the Golgi-Microtubule Network.

Genome-Wide Association Studies (GWAS) and subsequent fine-mapping studies (>50) have implicated single nucleotide polymorphisms (SNPs) located at the CCDC170/C6ORF97-ESR1 locus (6q25.1) as being associated with the risk of breast cancer. Surprisingly, our analysis using genome-wide differential allele-specific expression (DASE), an indicator for breast cancer susceptibility, suggested that the genetic alterations of CCDC170, but not ESR1, account for GWAS-associated breast cancer risk at this locus.

LincIN, a novel NF90-binding long non-coding RNA, is overexpressed in advanced breast tumors and involved in metastasis.

Background: Recent genome-wide profiling by sequencing and distinctive chromatin signatures has identified thousands of long non-coding RNA (lncRNA) species (>200 nt). LncRNAs have emerged as important regulators of gene expression, involving in both developmental and pathological processes. While altered expression of lncRNAs has been observed in breast cancer development, their roles in breast cancer progression and metastasis are still poorly understood.