Drug Development.

Background: Tau proteins aggregate in a number of neurodegenerative disorders known as tauopathies. Various studies have highlighted the role of microtubule-binding domains in the intracellular aggregation of Tau protein.

Method: Using a library of synthetic VHHs humanized in collaboration with Hybrigenics, we have developed a number of anti-tau VHHs.

Drug Development.

Background: Cardiometabolic diseases, such as type 2 diabetes, hypertension, dyslipidemia or obesity, constitute major causes of mortality and morbidity worldwide, especially among middle-aged individuals. The increasing incidence and association with aging and lifestyle, render the cardiometabolic diseases a societal concern. This is further reinforced by their association with an increased risk of cognitive impairment and neurodegenerative diseases (namely dementia and Alzheimer's disease (AD)).

Thymidine Phosphodiester Chemiluminescent Probe for Sensitive and Selective Detection of Ectonucleotide Pyrophosphatase 1.

ENPP-1 is a transmembrane enzyme involved in nucleotide metabolism, and its overexpression is associated with various cancers, making it a potential therapeutic target and biomarker for early tumor diagnosis. Current detection methods for ENPP-1 utilize a colorimetric probe, , which has significant limitations in sensitivity. Here, we present probe , the first nucleic acid-based chemiluminescent probe designed for rapid and highly sensitive detection of ENPP-1 activity.

Cardiovascular Disease and Cancer: A Dangerous Liaison.

The field of cardio-oncology has traditionally focused on the impact of cancer and its therapies on cardiovascular health. Mounting clinical and preclinical evidence, however, indicates that the reverse may also be true: cardiovascular disease can itself influence tumor growth and metastasis. Numerous epidemiological studies have reported that individuals with prevalent cardiovascular disease have an increased incidence of cancer.

The Effects of Moderate to High Static Magnetic Fields on Pancreatic Damage.

Background: Pancreatic damage is a common digestive system disease with no specific drugs. Static magnetic field (SMF), the key component of magnetic resonance imaging (MRI), has demonstrated prominent effects in various disease models.

Purpose: To study the effects of 0.

Relapsed childhood T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma.

While outcomes for pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) have improved dramatically in recent decades, relapsed and refractory disease remain a significant therapeutic challenge. This is particularly true for patients with T-cell ALL and LBL, where survival for patients with relapsed/refractory disease remains dismal. Recent efforts to comprehensively profile the genomics of T-ALL/LBL to improve understanding of disease biology have enhanced our ability to identify high-risk patients at diagnosis who are more likely to relapse and have also identified novel targets for precision medicines.

Purine metabolites regulate leukemic cell sensitivity toward cytarabine.

Not available.

Dendritic cell immunometabolism - a potential therapeutic target for allergic diseases.

Allergic diseases are a group of chronic inflammatory disorders driven by abnormal immune responses. Dendritic cells (DCs) play a pivotal role in the initiation and progression of allergic diseases by modulating T cell responses. Extensive progress has been made in characterizing crucial roles of metabolic reprogramming in the regulation of immune cell functions.

TNF-α Expression and Plasma Cell and Macrophage Numbers in Traumatic Ulcers in a Rat Model Treated by Topical or Systemic Probiotic .

: Live microorganisms, named probiotics, can improve overall physical well-being, particularly the oral cavity's health. , a popular probiotic, can influence the immune response by increasing the number of macrophages and plasma cells that play a role in traumatic ulcer healing. : To determine the expression of tumor necrosis factor-alpha (TNF-α) and the varied number of plasma cells and macrophages on a traumatic ulcer animal model treated with topical or systemic administration of a probiotic : Thirty-six healthy, 2-3-month-old male weighing 175-250 gram, were designed into control and topical and systemic administration probiotic groups.

S6K1 is a Targetable Vulnerability in Tumors Exhibiting Plasticity and Therapy Resistance.

Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms associated with cancer cell plasticity and heterogeneity. We used a chemical biology approach to identify protein targets in cancer cells exhibiting diverse driver mutations and representing models of tumor lineage plasticity and therapy resistance. An unbiased screen of a drug library was performed against cancer cells followed by synthesis of chemical analogs of the most effective drug.

TEAD1 Prevents Necroptosis and Inflammation in Cisplatin-Induced Acute Kidney Injury Through Maintaining Mitochondrial Function.

Cisplatin is widely used for the treatment of solid tumors and its antitumor effects are well established. However, a known complication of cisplatin administration is acute kidney injury (AKI). In this study, we examined the role of TEA domain family member 1 (TEAD1) in the pathogenesis of cisplatin-induced AKI.

Toll-like receptor adaptor protein TIRAP has specialized roles in signaling, metabolic control and leukocyte migration upon wounding in zebrafish larvae.

The TIRAP protein is an adaptor protein in TLR signaling which links TLR2 and TLR4 to the adaptor protein Myd88. The transcriptomic profiles of zebrafish larvae from a , and mutant and the corresponding wild type controls under unchallenged developmental conditions revealed a specific involvement of in calcium homeostasis and myosin regulation. Metabolomic profiling showed that the mutation results in lower glucose levels, whereas a mutation leads to higher glucose levels.

The development and maintenance of immunity against visceral leishmaniasis.

Understanding the development and maintenance of immunological memory is important for efforts to eliminate parasitic diseases like leishmaniasis. Leishmaniasis encompasses a range of pathologies, resulting from infection with protozoan parasites belonging to the subgenera and of the genus A striking feature of these infections is that natural or drug-mediated cure of infection generally confers life-long protection against disease. The generation of protective T cell responses are necessary to control infections.

Sensitivity of renal cell carcinoma to cuproptosis: a bioinformatics analysis and experimental verification.

Targeting cuproptosis is considered as a promising therapeutic strategy for the prevention of tumors. However, the potential role of cuproptosis and its related genes in clear cell renal cell carcinoma (ccRCC) remains elusive. The present study aims to explore the sensitivity of ccRCC to cuproptosis and its underlying mechanism.

Unlocking the Hidden Potential of Cancer Therapy Targeting Lysine Succinylation.

Lysine succinylation is an emerging post-translational modification of proteins. It involves the addition of the succinyl group to lysine residues of target proteins through both enzymatic and non-enzymatic pathways. This modification can alter the structure of the target protein, which, in turn, impacts protein activity and function and is involved in a wide range of diseases.

PRMT5-Mediated ALKBH5 Methylation Promotes Colorectal Cancer Immune Evasion via Increasing CD276 Expression.

Numerous diseases have been connected to protein arginine methylations mediated by protein arginine methyltransferase 5 (PRMT5). Clinical investigations of the PRMT5-specific inhibitor GSK3326595 are currently being conducted, and the results are promising for preventing cancers. However, the detailed mechanism of PRMT5 promoting colorectal cancer (CRC) malignant progression remains unclear.

Navigating the landscape of neoadjuvant immunotherapy for NSCLC: progress and controversies.

Recently, attention has increasingly centered on non-small-cell lung cancer (NSCLC) with immune checkpoint inhibitors application. Numerous clinical studies have underscored the potential of immunotherapy in treating resectable NSCLC, highlighting its role in improving patient outcomes. However, despite these promising results, there is ongoing debate regarding the efficacy of immunological combination therapy strategies, the prevalence of treatment-related side effects, the identification of predictive biomarkers, and various other challenges within the neoadjuvant context.

Prior thermal acclimation gives White Sturgeon a fin up dealing with low oxygen.

Assessing how at-risk species respond to co-occurring stressors is critical for predicting climate change vulnerability. In this study, we characterized how young-of-the-year White Sturgeon () cope with warming and low oxygen (hypoxia) and investigated whether prior exposure to one stressor may improve the tolerance to a subsequent stressor through "cross-tolerance". Fish were acclimated to five temperatures within their natural range (14-22°C) for one month prior to assessment of thermal tolerance (critical thermal maxima, CTmax) and hypoxia tolerance (incipient lethal oxygen saturation, ILOS; tested at 20°C).

Drought induced metabolic shifts and water loss mechanisms in canola: role of cysteine, phenylalanine and aspartic acid.

Drought conditions severely curtail the ability of plants to accumulate biomass due to the closure of stomata and the decrease of photosynthetic assimilation rate. Additionally, there is a shift in the plant's metabolic processes toward the production of metabolites that offer protection and aid in osmoadaptation, as opposed to those required for development and growth. To limit water loss via non-stomatal transpiration, plants adjust the load and composition of cuticle waxes, which act as an additional barrier.

Oral cell lysates reduce osteoclastogenesis in murine bone marrow cultures.

Mechanical and thermal cell damage can occur due to invasive procedures related to drilling, the insertion of dental implants, and periodontal treatments. Necrotic cells release the content of their cytoplasm and membrane fragments, thereby signaling the need for repair, which includes bone resorption by osteoclasts and inflammation. Here we screened lysates from human gingival fibroblasts, HSC2 and TR146 oral squamous carcinoma cell lines, as well as murine IDG-SW3 osteocytic and RAW264.

Physiologic and structural characterization of desisobutyryl-ciclesonide, a selective glucocorticoid receptor modulator in newborn rats.

Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC).

PAXIP1 is regulated by NRF1 and is a prognosis‑related biomarker in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is characterized by a poor prognosis globally. PAX-interacting protein 1 (PAXIP1) serves a key role in the development of numerous human cancer types. Nevertheless, its specific involvement in HCC remains poorly understood.

TLE1 corepressor promotes gefitinib resistance in lung cancer A549 cells via E‑cadherin silencing.

As a putative lung specific oncogene, the transducin-like enhancer of split 1 (TLE1) corepressor drives an anti-apoptotic and pro-epithelial-mesenchymal transition (EMT) gene transcriptional programs in human lung adenocarcinoma (LUAD) cells, thereby promoting anoikis resistance and tumor aggressiveness. Through its survival- and EMT-promoting gene regulatory programs, TLE1 may impact drug sensitivity and resistance in lung cancer cells. In the present study, a novel function of TLE1 was uncovered as an inhibitor of the antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib in the human LUAD cell line A549, which exhibits moderate sensitivity to EGFR-TKI.

A biofuel cell of (methyl violet/AuNPs)/FTO photoanode and bilirubin oxidase/CuCoO bio-photocathode inspired by the photoelectrochemistry activities of fluorescent materials/molecules.

Herein, we discuss the idea that fluorescent materials/molecules should logically show potential photoelectrochemistry (PEC) activity, and, in particular, the PEC of fluorescent small molecules (previously usually acting only as dye sensitizers for conventional semiconductors) is explored. After examining the PEC activities of some typical inorganic or organic fluorescent materials/molecules and by adopting methyl violet (MV) with the highest PEC activity among the examined fluorescent small molecules, a new and efficient (MV/Au nanoparticles (AuNPs))/fluorine-doped tin oxide (FTO) photoanode without conventional semiconductor(s) is prepared by layer-by-layer alternating the electrodeposition of AuNPs and the adsorption of MV. A bilirubin oxidase (BOD)/CuCoO/FTO bio-photocathode is prepared by electrodeposition, calcination and cast-coating.

Intratumoral Injection of Engineered Induces Antitumor Immunity and Inhibits Tumor Growth.

Conventional type 1 dendritic cells are essential for antigen presentation and successful initiation of antitumor CD8 T cells. However, their abundance and function within tumors tend to be limited. , a fast-growing, nonpathogenic mycobacterium, proves to be easily modified with synthetic biology.