SPATS2L is a positive feedback regulator of the type I interferon signaling pathway and plays a vital role in lupus.

Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes ("eGenes", whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated.

Fibroblast expression of neurotransmitter receptor HTR2A associates with inflammation in rheumatoid arthritis joint.

The study of neuroimmune crosstalk and the involvement of neurotransmitters in inflammation and bone health has illustrated their significance in joint-related conditions. One important mode of cell-to-cell communication in the synovial fluid (SF) is through extracellular vesicles (EVs) carrying microRNAs (miRNAs). The role of neurotransmitter receptors in the pathogenesis of inflammatory joint diseases, and whether there are specific miRNAs regulating differentially expressed HTR2A, contributing to the inflammatory processes and bone metabolism is unclear.

Prevalence of Neutralizing Autoantibodies Against Type I Interferon in a Multicenter Cohort of Severe or Critical COVID-19 Cases in Shanghai.

Objective: We sought to explore the prevalence of type I interferon-neutralizing antibodies in a Chinese cohort and its clinical implications during the Omicron variant wave of SARS-CoV-2.

Methods: Type I interferon (IFN) autoantibodies possessing neutralizing capabilities were identified using luciferase assays. The capacity of the autoantibodies for in vitro interference with antiviral activity of IFN was assessed by using a SARS-CoV-2 replicon system.

Anti-Toxoplasma gondii antibodies as a risk factor for the prevalence and severity of systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the presence of numerous autoantibodies. The interaction of infectious agents (viruses, bacteria and parasites) and a genetically susceptible host may be a key mechanism for SLE. Toxoplasma gondii is a widespread intracellular parasite that has been implicated in the pathogenesis of autoimmune diseases.

Noncanonical functions of microRNAs in the nucleus.

MicroRNAs (miRNAs) are small noncoding RNAs (ncRNAs) that play their roles in the regulation of physiological and pathological processes. Originally, it was assumed that miRNAs only modulate gene expression posttranscriptionally in the cytoplasm by inducing target mRNA degradation. However, with further research, evidence shows that mature miRNAs also exist in the cell nucleus, where they can impact gene transcription and ncRNA maturation in several ways.

Serum Metabolic Fingerprints Characterize Systemic Lupus Erythematosus.

Metabolic fingerprints in serum characterize diverse diseases for diagnostics and biomarker discovery. The identification of systemic lupus erythematosus (SLE) by serum metabolic fingerprints (SMFs) will facilitate precision medicine in SLE in an early and designed manner. Here, a discovery cohort of 731 individuals including 357 SLE patients and 374 healthy controls (HCs), and a validation cohort of 184 individuals (SLE/HC, 91/93) are constructed.

Integration of risk variants from GWAS with SARS-CoV-2 RNA interactome prioritizes FUBP1 and RAB2A as risk genes for COVID-19.

The role of host genetic factors in COVID-19 outcomes remains unclear despite various genome-wide association studies (GWAS). We annotate all significant variants and those variants in high LD (R > 0.8) from the COVID-19 host genetics initiative (HGI) and identify risk genes by recognizing genes intolerant nonsynonymous mutations in coding regions and genes associated with cis-expression quantitative trait loci (cis-eQTL) in non-coding regions.

Enhanced synergy of pacritinib with temsirolimus and sunitinib in preclinical renal cell carcinoma model by targeting JAK2/STAT pathway.

Pacritinib is an oral medication that inhibits several kinases including JAK2, FLT3, IRAK and STAT3. It has been recently approved to treat patients with thrombocytopenia and myelofibrosis. Studies are currently exploring the potential use of pacritinib in treating other types of cancer such as leukaemia, breast cancer and prostate cancer.

Three-Dimensional Chromosomal Landscape Revealing miR-146a Dysfunctional Enhancer in Lupus and Establishing a CRISPR-Mediated Approach to Inhibit the Interferon Pathway.

Objective: The diminished expression of microRNA-146a (miR-146a) in systemic lupus erythematosus (SLE) contributes to the aberrant activation of the interferon pathway. Despite its significance, the underlying mechanism driving this reduced expression remains elusive. Considering the integral role of enhancers in steering gene expression, our study seeks to pinpoint the SLE-affected enhancers responsible for modulating miR-146a expression.

Venetoclax Synergizes Sunitinib in Renal Cell Carcincoma through Inhibition of Bcl-2.

Aims: More effective treatment options for patients with renal cell carcinoma (RCC) are needed, in particular advanced RCC.

Background: Sunitinib, a multitarget tyrosine kinase inhibitor, is a first-line treatment of metastatic RCC. However, the management of sunitinib-induced adverse events and resistance is complex.

EBV-encoded miRNAs BHRF1-1 and BART2-5p aggravate post- transplant lymphoproliferative disorder via LZTS2-PI3K-AKT axis.

Post-transplant lymphoproliferative disorder (PTLD) is one of the most serious complications after transplantation. Epstein-Barr virus (EBV) is a key pathogenic driver of PTLD. About 80% of PTLD patients are EBV positive.

Integrative Functional Genomics Identifies Systemic Lupus Erythematosus Causal Genetic Variant in the IRF5 Risk Locus.

Objective: IRF5 plays a crucial role in the development of lupus. Genome-wide association studies have identified several systemic lupus erythematosus (SLE) risk single-nucleotide polymorphisms (SNPs) enriched in the IRF5 locus. However, no comprehensive genome editing-based functional analysis exists to establish a direct link between these variants and altered IRF5 expression, particularly for enhancer variants.

Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study.

Objective: Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis.

Methods: We built gene expression predictive models in blood B cells, CD4 and CD8 T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals.

Lupus enhancer risk variant causes dysregulation of IRF8 through cooperative lncRNA and DNA methylation machinery.

Despite strong evidence that human genetic variants affect the expression of many key transcription factors involved in autoimmune diseases, establishing biological links between non-coding risk variants and the gene targets they regulate remains a considerable challenge. Here, we combine genetic, epigenomic, and CRISPR activation approaches to screen for functional variants that regulate IRF8 expression. We demonstrate that the locus containing rs2280381 is a cell-type-specific enhancer for IRF8 that spatially interacts with the IRF8 promoter.

SARS-CoV-2-Encoded MiRNAs Inhibit Host Type I Interferon Pathway and Mediate Allelic Differential Expression of Susceptible Gene.

Infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing the rapid spread of coronavirus disease 2019 (COVID-19), has generated a public health crisis worldwide. The molecular mechanisms of SARS-CoV-2 infection and virus-host interactions are still unclear. In this study, we identified four unique microRNA-like small RNAs encoded by SARS-CoV-2.

Protective Role of microRNA-31 in Acetaminophen-Induced Liver Injury: A Negative Regulator of c-Jun N-Terminal Kinase (JNK) Signaling Pathway.

Background & Aims: Sustained c-Jun N-terminal kinase (JNK) activation plays a major role in drug-induced liver injury (DILI). Stress-responsive microRNA-31 (miR-31) has been implicated in regulating different cellular damage, and JNK activation could induce miR-31 expression. However, the regulatory role of miR-31 in DILI has not been studied previously.

Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups.

Systemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated.

SLE non-coding genetic risk variant determines the epigenetic dysfunction of an immune cell specific enhancer that controls disease-critical microRNA expression.

Since most variants that impact polygenic disease phenotypes localize to non-coding genomic regions, understanding the consequences of regulatory element variants will advance understanding of human disease mechanisms. Here, we report that the systemic lupus erythematosus (SLE) risk variant rs2431697 as likely causal for SLE through disruption of a regulatory element, modulating miR-146a expression. Using epigenomic analysis, genome-editing and 3D chromatin structure analysis, we show that rs2431697 tags a cell-type dependent distal enhancer specific for miR-146a that physically interacts with the miR-146a promoter.

Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.

Zirconia Hybrid Nanoshells for Nutrient and Toxin Detection.

Monitoring milk quality is of fundamental importance in food industry, because of the nutritional value and resulting position of milk in daily diet. The detection of small nutrients and toxins in milk is challenging, considering high sample complexity and low analyte abundance. In addition, the slow analysis and tedious sample preparation hinder the large-scale application of conventional detection techniques.

The MicroRNA Represses Th17 Cell Pathogenicity by Targeting PTEN-Regulated Pathways.

Multiple sclerosis is a chronic autoimmune disease driven by pathogenic Th17 cells. In this study, we dissected the role of - in pathogenic Th17 cells by autoantigen-specific disease models. We first showed that was upregulated in peripheral lymphoid organs and spinal cords of mice developed autoimmune encephalomyelitis.

MicroRNA-125a-Loaded Polymeric Nanoparticles Alleviate Systemic Lupus Erythematosus by Restoring Effector/Regulatory T Cells Balance.

Systemic lupus erythematosus (SLE), a common lethal autoimmune disease, is characterized by effector/regulatory T cells imbalance. Current therapies are either inefficient or have severe side effects. MicroRNA-125a (miR-125a) can stabilize Treg-mediated self-tolerance by targeting effector programs, but it is significantly downregulated in peripheral T cells of patients with SLE.

Interferon-α exacerbates neuropsychiatric phenotypes in lupus-prone mice.

Background: Neuropsychiatric systemic lupus erythaematosus (NP-SLE) is one of the major manifestations of lupus. However, the mechanisms involved in NP-SLE are still largely unknown. The abnormal activation of the type I IFN signalling pathway is involved in SLE pathogenesis and is linked to NP-SLE, but the effect of IFN-α on NP-SLE encephalopathy has not been systematically studied.

Identification of Serum Biomarkers for Systemic Lupus Erythematosus Using a Library of Phage Displayed Random Peptides and Deep Sequencing.

Systemic lupus erythematosus (SLE) is one of the most serious autoimmune diseases, characterized by highly diverse clinical manifestations. A biomarker is still needed for accurate diagnostics. SLE serum autoantibodies were discovered and validated using serum samples from independent sample cohorts encompassing 306 participants divided into three groups, healthy, SLE patients, and other autoimmune-related diseases.