P-tau217 correlates with neurodegeneration in Alzheimer's disease, and targeting p-tau217 with immunotherapy ameliorates murine tauopathy.

Neuronal loss is the central issue in Alzheimer's disease (AD), yet no treatment developed so far can halt AD-associated neurodegeneration. Here, we developed a monoclonal antibody (mAb2A7) against 217 site-phosphorylated human tau (p-tau217) and observed that p-tau217 levels positively correlated with brain atrophy and cognitive impairment in AD patients. Intranasal administration efficiently delivered mAb2A7 into male PS19 tauopathic mouse brain with target engagement and reduced tau pathology/aggregation with little effect on total soluble tau.

Clinical translation for targeting DNA damage repair in non-small cell lung cancer: a review.

Despite significant advancements in screening, diagnosis, and treatment of non-small cell lung cancer (NSCLC), it remains the primary cause of cancer-related deaths globally. DNA damage is caused by the exposure to exogenous and endogenous factors and the correct functioning of DNA damage repair (DDR) is essential to maintain of normal cell circulation. The presence of genomic instability, which results from defective DDR, is a critical characteristic of cancer.

Immune-Ageing Evaluation of Peripheral T and NK Lymphocyte Subsets in Chinese Healthy Adults.

Unlabelled: Ageing is often accompanied with a decline in immune system function, resulting in immune ageing. Numerous studies have focussed on the changes in different lymphocyte subsets in diseases and immunosenescence. The change in immune phenotype is a key indication of the diseased or healthy status.

The combined effect of deoxynivalenol and Fumonisin B on small intestinal inflammation mediated by pyroptosis in vivo and in vitro.

Currently, due to the actual contamination levels of multiple mycotoxins, the limits for a single mycotoxin may be no longer applicable. Deoxynivalenol (DON) and Fumonisin B (FB) had high positive rate in grain and feed worldwide. The intestine is the first target of mycotoxins.

Taurine alleviates ochratoxin A-induced pyroptosis in PK-15 cells by inhibiting oxidative stress.

Ochratoxin A (OTA) is one of the most harmful mycotoxins, which can cause multiple toxicological effects, especially nephrotoxicity in animals and humans. Taurine is an essential amino acid with various biological functions such as anti-inflammatory and anti-oxidation. However, the protective effect of taurine on OTA-induced nephrotoxicity and pyroptosis had not been reported.

Nontoxic Concentration of Ochratoxin A Aggravates Renal Fibrosis Induced by Adriamycin/Cyclosporine A Nephropathy via TGF-β1/SMAD2/3.

Ochratoxin A (OTA) is the most common contaminant in food and feed, which causes nephrotoxicity. Studies revealed that a low level of OTA contamination could also cause physiological dysfunction. Chronic kidney disease (CKD) has become an important public health problem with increasing morbidity.

Crucial Function of Caveolin-1 in Deoxynivalenol-Induced Enterotoxicity by Activating ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis.

Deoxynivalenol (DON) is one of the most pervasive contaminating mycotoxins in grain, and exposure to DON is known to cause acute and chronic intestinal damage. As the gut is the most important target organ of DON, it is essential to identify the pivotal molecules involved in DON-induced enterotoxicity as well as the potential regulatory mechanisms. In the present study, we found that DON treatment dramatically decreased the jejunal villus height and increased the crypt depth in mice.

The therapeutic and preventive effects of a canine-origin VB -producing Lactobacillus on DSS-induced colitis in mice.

Vitamin B (VB ) plays vital roles as a cofactor in reactions related to biosynthesis and metabolic regulation. Animals with diarrhoea from intestinal inflammation are susceptible to VB deficiency due to dysfunctional absorption. No current medications for canine intestinal inflammation can simultaneously act as VB supplements.

B cell intrinsic and extrinsic factors impacting memory recall responses to SRBC challenge.

MBCs (MBCs) generated in T-dependent immune responses can persist for a lifetime and rapidly react upon secondary antigen exposure to differentiate into plasma cells (PCs) and/or to improve the affinity of their BCR through new rounds of hypermutation in germinal centers (GCs). The fate of a MBC in secondary immune reactions appears to depend upon multiple parameters, whose understanding is mandatory for the design of efficient vaccine strategies. We followed the behavior of MBCs in recall responses to SRBCs using an inducible AID fate mapping mouse model in which B cells engaged in a germinal center (GC) response are irreversibly labeled upon simultaneous tamoxifen ingestion and immunization.

mTOR-Mediated Autophagy Regulates Fumonisin B-Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro.

Fumonisin B (FB) is a fungal metabolite, which has an incremental detection rate in grains and feed worldwide. The nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) inflammasome is a critical element in pyroptosis activation, which participates in regulating enteritis. Meanwhile, autophagy is also engaged in intestinal inflammation.

Infection Induces IL-17 Production by Promoting STAT3 Phosphorylation in CD4 T Cells.

infection in the central nervous system is a severe infectious disease with poor outcomes and high mortality. It has been estimated that there are 220,000 new cases each year. Over 90% of meningitis cases were diagnosed in AIDS patients with CD4 T cell count <100 cells/μl; however, the mechanism of cryptococcal meningitis in patients with normal immune functions remains unclear.

Melatonin mitigates aflatoxin B1-induced liver injury via modulation of gut microbiota/intestinal FXR/liver TLR4 signaling axis in mice.

Aflatoxin B1 (AFB1) is a widespread contaminant in foods and feedstuffs, and its target organ is the liver. Melatonin (MT) has been shown to alleviate inflammation in organs and remodel gut microbiota in animals and humans. However, the underlying mechanism by which MT alleviates AFB1-induced liver injury remains unclear.

Screening for malignant tumor cells in serous effusions with an automatic hematology analyzer using a novel diagnostic algorithm.

Background: Due to the high false-positive rate of the high-fluorescence body fluid (HF-BF) cell parameter of the hematology analyzer in BF mode, a novel algorithm based on the Mindray BC-6800 Plus hematology analyzer (BC-6800Plus), with higher diagnostic accuracy compared to that of the traditional HF-BF algorithm, was used to screen for malignant tumor cells in clinical BF samples. In this study, the body fluid mode of BC-6800Plus was applied to investigate the ability of its available parameters and characteristic regional particles in tumor cells screening.

Methods: A total of 220 BF samples (including pleural effusion and ascites) were randomly classified into a training cohort (154 samples) and a validation cohort (66 samples), and detected on the BC-6800Plus in BF mode.

Low dose of arsenic exacerbates toxicity to mice and IPEC-J2 cells exposed with deoxynivalenol: Aryl hydrocarbon receptor and autophagy might be novel therapeutic targets.

Deoxynivalenol (DON) and arsenic (As) are widespread environmental contaminants, which are frequently found in human and animal food products. The intestine is a common target of As and DON when they are digested. Numerous studies mainly evaluate the individual effects whereas their combined toxicity has rarely been elucidated.

Low Dose of Deoxynivalenol Aggravates Intestinal Inflammation and Barrier Dysfunction Induced by Enterotoxigenic Infection through Activating Macroautophagy/NLRP3 Inflammasomes.

The toxicity of deoxynivalenol (DON) in healthy humans and animals has been extensively studied. However, whether the natural-low-dose DON is scatheless under unhealthy conditions, especially intestinal injury, is unknown. Infection of enterotoxigenic (ETEC) is a classical intestinal injury model.

Phenethyl isothiocyanate as an anti-nutritional factor attenuates deoxynivalenol-induced IPEC-J2 cell injury through inhibiting ROS-mediated autophagy.

Deoxynivalenol (DON) is considered to be the most harmful mycotoxin that affects the intestinal health of animals and humans. Phenethyl isothiocyanate (PEITC) in feedstuff is an anti-nutritional factor and impairs nutrient digestion and absorption in the animal intestinal. In the current study, we aimed to explore the effects of PEITC on DON-induced apoptosis, intestinal tight junction disorder, and its potential molecular mechanism in the porcine jejunum epithelial cell line (IPEC-J2).

Selenomethionine alleviated Ochratoxin A induced pyroptosis and renal fibrotic factors expressions in MDCK cells.

Ochratoxin A (OTA) is universally known to induce nephrotoxicity via inducing oxidative stress and apoptosis, inhibiting protein synthesis and activating autophagy. Our previous studies have proved that OTA induces nephrotoxicity in vitro and in vivo by adjusting the NOD-like receptor protein 3 (NLRP3) inflammasome activation and caspase-1-dependent pyroptosis. Based on these findings, we further investigated the protective role of selenomethionine (SeMet) on OTA-caused nephrotoxicity using the Madin-Darby canine kidney (MDCK) epithelial cells as an in vitro model, proposing to offer a new way for remedying OTA-induced nephrotoxicity by nutritional manipulation.

Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors.

Clinical evidence has established that concomitant traumatic brain injury (TBI) accelerates bone healing, but the underlying mechanism is unclear. This study shows that after TBI, injured neurons, mainly those in the hippocampus, release osteogenic microRNA (miRNA)-enriched small extracellular vesicles (sEVs), which targeted osteoprogenitors in bone to stimulate bone formation. We show that miR-328a-3p and miR-150-5p, enriched in the sEVs after TBI, promote osteogenesis by directly targeting the 3'UTR of FOXO4 or CBL, respectively, and hydrogel carrying miR-328a-3p-containing sEVs efficiently repaires bone defects in rats.

Liquid biopsy in extranodal NK/T-cell lymphoma: a prospective analysis of cell-free DNA genotyping and monitoring.

Satisfactory tumor material is often hard to obtain for molecular analysis in extranodal natural killer (NK)/T-cell lymphoma (NKTCL) at present. However, the accuracy and utility of circulating cell-free DNA (cfDNA) genotyping have not been adequately assessed in NKTCL. We therefore performed targeted next-generation sequencing on tumor tissues and a series of longitudinal plasma samples prospectively collected from a cohort of high-risk NKTCL patients.

TIM-3 regulates the NETs-mediated dendritic cell activation in myeloperoxidase-ANCA-associated vasculitis.

Objectives: T cell immunoglobulin and mucin domain 3 (TIM-3) has been reported as an important regulatory molecule on T cells and plays a pivotal role in autoimmune diseases, but the impact on dendritic cells (DCs) is poorly explored. The formation of neutrophil extracellular traps (NETs) is considered as strongly implicated in the pathogenesis of autoimmune diseases, such as in myeloperoxidase-antineutrophil cytoplasmic autoantibody associated vasculitis (MPO-AAV). This study thus aimed to investigate the potential regulation roles of TIM-3 in the regulation of NETs-mediated DC activation in MPO-AAV.

Nontoxic dose of Phenethyl isothiocyanate ameliorates deoxynivalenol-induced cytotoxicity and inflammation in IPEC-J2 cells.

The intestinal tract is a target for the deoxynivalenol (DON), which has adverse effects in animals and humans' health by affecting intestinal functions. Phenethyl isothiocyanate (PEITC) is an important degradation product of glucosinolates (GSLs), belonging to an anti-nutritional factor that affects the digestion and absorption of nutrients in the animals' intestinal. However, little attention has been paid to the interaction and its mechanism between DON and PEITC.

The prognostic value of longitudinal circulating tumor DNA profiling during osimertinib treatment.

Background: Serial profiling of circulating tumor DNA (ctDNA) could reflect dynamic molecular changes in response to treatment and potentially predict impending disease progression (PD). Herein, we investigated the molecular factors and dynamic changes in ctDNA that can serve as predictors of survival outcomes of patients with epidermal growth factor receptor ()-mutated advanced non-small cell lung cancer (NSCLC) who received osimertinib therapy after progression from prior EGFR inhibitor regimen.

Methods: Capture-based targeted sequencing was performed on the baseline and longitudinal plasma samples collected from 72 and 57 patients, respectively, using a 168-gene panel.

Anlotinib combined with PD-1 blockade for the treatment of lung cancer: a real-world retrospective study in China.

Background: This study evaluated the efficacy and safety of anlotinib combined with programmed cell death protein 1 (PD-1) blockade for the treatment of small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC).

Patients And Methods: SCLC (n = 28) and NSCLC (n = 177) patients who received treatment at Hunan Cancer Hospital between June 1, 2019, and July 1, 2020, were retrospectively analyzed. Progression-free survival (PFS) and treatment responses were compared among patients who received combination therapy of anlotinib plus PD-1 inhibitor, or monotherapy of either chemotherapy or PD-1 inhibitor.