Advancements in rheumatoid arthritis therapy: a journey from conventional therapy to precision medicine nanoparticles targeting immune cells.

Rheumatoid arthritis (RA) is a progressive autoimmune disease that mainly affects the inner lining of the synovial joints and leads to chronic inflammation. While RA is not known as lethal, recent research indicates that it may be a silent killer because of its strong association with an increased risk of chronic lung and heart diseases. Patients develop these systemic consequences due to the regular uptake of heavy drugs such as disease-modifying antirheumatic medications (DMARDs), glucocorticoids (GCs), nonsteroidal anti-inflammatory medicines (NSAIDs), .

Single-cell atlas of healthy human blood unveils age-related loss of NKG2CGZMBCD8 memory T cells and accumulation of type 2 memory T cells.

Extensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for the systematic understanding of human aging. Here, using single-cell RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 healthy individuals aged 25-85 years old. From this, we generated a dataset from ∼2 million cells that described 55 subpopulations of blood immune cells.

Cellular and plasma proteomic determinants of COVID-19 and non-COVID-19 pulmonary diseases relative to healthy aging.

We examine the cellular and soluble determinants of coronavirus disease 2019 (COVID-19) relative to aging by performing mass cytometry in parallel with clinical blood testing and plasma proteomic profiling of ~4,700 proteins from 71 individuals with pulmonary disease and 148 healthy donors (25-80 years old). Distinct cell populations were associated with age (GZMKCD8 T cells and CD25 CD4 T cells) and with COVID-19 (TBETEOMES CD4 T cells, HLA-DRCD38 CD8 T cells and CD27CD38 B cells). A unique population of TBETEOMES CD4 T cells was associated with individuals with COVID-19 who experienced moderate, rather than severe or lethal, disease.

Itaconate confers tolerance to late NLRP3 inflammasome activation.

Itaconate is a unique regulatory metabolite that is induced upon Toll-like receptor (TLR) stimulation in myeloid cells. Here, we demonstrate major inflammatory tolerance and cell death phenotypes associated with itaconate production in activated macrophages. We show that endogenous itaconate is a key regulator of the signal 2 of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation after long lipopolysaccharide (LPS) priming, which establishes tolerance to late NLRP3 inflammasome activation.

Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK CD8 T Cells as Conserved Hallmark of Inflammaging.

Systematic understanding of immune aging on a whole-body scale is currently lacking. We characterized age-associated alterations in immune cells across multiple mouse organs using single-cell RNA and antigen receptor sequencing and flow cytometry-based validation. We defined organ-specific and common immune alterations and identified a subpopulation of age-associated granzyme K (GZMK)-expressing CD8 T (Taa) cells that are distinct from T effector memory (Tem) cells.

Dysregulation of 1-carbon metabolism and muscle atrophy: potential roles of forkhead box O proteins and PPARγ co-activator-1α.

Homocysteine, a non-proteinogenic amino acid but an important metabolic intermediate is generated as an integral component for the "1-carbon metabolism" during normal physiology. It is catabolized to cysteine via the transulfuration pathway resulting in the generation of hydrogen sulfide, a naturally endogenous byproduct. Genetics or metabolic derangement can alter homocysteine concentration leading to hyperhomocysteinemia (HHcy), a physiologically unfavorable condition that causes serious medical conditions including muscle wasting.

Hydrogen sulfide intervention in cystathionine-β-synthase mutant mouse helps restore ocular homeostasis.

Aim: To investigate the applications of hydrogen sulfide (HS) in eye-specific ailments in mice.

Methods: Heterozygous cystathionine-β-synthase (CBS) and wild-type C57BL/6J (WT) mice fed with or without high methionine diet (HMD) were administered either phosphate buffered saline (PBS) or the slow-release HS donor: GYY4137. Several analyses were performed to study GYY4137 effects by examining retinal lysates for key protein expressions along with plasma glutamate and glutathione estimations.

Circular RNAs constitute an inherent gene regulatory axis in the mammalian eye and brain .

Circular RNAs (circRNAs) are being hailed as a newly rediscovered class of covalently closed transcripts that are produced via alternative, noncanonical pre-mRNA back-splicing events. These single-stranded RNA molecules have been identified in organisms ranging from the worm (Cortés-López et al. 2018.

Expression Analysis of the Circular RNA Molecules in the Human Retinal Cells Treated with Homocysteine.

Purpose: To characterize the global profile of circular RNAs (circRNAs) and their differential expression levels in homocysteine (Hcy)-treated ARPE-19 cells, a line of human retinal pigment epithelial (RPE) cells.

Materials And Methods: We treated ARPE-19 cells with and without Hcy to investigate the influence of Hcy on circRNA expression levels using dedicated human circRNA microarrays.

Results: A total of 12,233 circRNAs were identified out of them 54 were differentially expressed (17 were down-regulated, and 37 were up-regulated) with a fold change >2.

Remote ischemic conditioning as a cytoprotective strategy in vasculopathies during hyperhomocysteinemia: An emerging research perspective.

Higher levels of nonprotein amino acid homocysteine (Hcy), that is, hyperhomocysteinemia (HHcy) (~5% of general population) has been associated with severe vasculopathies in different organs; however, precise molecular mechanism(s) as to how HHcy plays havoc with body's vascular networks are largely unknown. Interventional modalities have not proven beneficial to counter multifactorial HHcy's effects on the vascular system. An ancient Indian form of exercise called 'yoga' causes transient ischemia as a result of various body postures however the cellular mechanisms are not clear.

Connecting homocysteine and obesity through pyroptosis, gut microbiome, epigenetics, peroxisome proliferator-activated receptor γ, and zinc finger protein 407.

Although homocysteine (Hcy), a part of the epigenome, contributes to cell death by pyroptosis and decreases peroxisome proliferator-activated receptor γ (PPARγ) levels, the mechanisms are unclear. Hcy is found in high concentrations in the sera of obese individuals, which can elicit an immune response as well by hypermethylating CpG islands of specific gene promoters, a marker of epigenetics. Hcy has also been established to chelate divalent metal ions like Cu and Zn, but this role of Hcy has not been established in relationship with obesity.

Circular RNAs profiling in the cystathionine-β-synthase mutant mouse reveals novel gene targets for hyperhomocysteinemia induced ocular disorders.

Cystathionine-β-synthase (CBS) gene encodes L-serine hydrolyase which catalyzes β-reaction to condense serine with homocysteine (Hcy) by pyridoxal-5'-phosphate helps to form cystathionine which in turn is converted to cysteine. CBS resides at the intersection of transmethylation, transsulfuration, and remethylation pathways, thus lack of CBS fundamentally blocks Hcy degradation; an essential step in glutathione synthesis. Redox homeostasis, free-radical detoxification and one-carbon metabolism (Methionine-Hcy-Folate cycle) require CBS and its deficiency leads to hyperhomocysteinemia (HHcy) causing retinovascular thromboembolism and eye-lens dislocation along with vascular cognitive impairment and dementia.