Pleotropic

BACKGROUND: Large increases in glomerular protein filtration induce major changes in body homeostasis and increase risk of kidney functional decline and cardiovascular disease. We investigated how elevated protein exposure modifies the landscape of tubular function along the entire nephron, to understand the cellular changes that mediate these important clinical phenomena. METHODS: We conducted single nuclei RNA sequencing, functional intravital imaging, and antibody staining to spatially map transport processes along the mouse kidney tubule...

In atherosclerotic lesions, monocyte-derived macrophages are major source of interferon gamma (IFN-γ), a pleotropic cytokine known to regulate the expression of numerous genes, including the antiviral gene RSAD2. While RSAD2 was reported to be expressed in endothelial cells of human carotid lesions, its significance for the development of atherosclerosis remains utterly unknown. Here, we harnessed publicly available human carotid atherosclerotic data to explore RSAD2 in lesions and employed siRNA-mediated gene-knockdown to investigate its function in IFN-γ-stimulated human aortic smooth muscle cells (hAoSMCs)...

In recent years, the incidence of food-borne bacterial enteric diseases has increased worldwide causing significant health care and socioeconomic burdens. According to the World Health Organization, there are an estimated 600 million cases of foodborne illnesses worldwide each year, resulting in 420,000 deaths. Despite intensive efforts to tackle this problem, foodborne pathogenic microorganisms continue to be spread further. Therefore, there is an urgent need to find novel anti-microbial non-toxic compounds for food preservation...

Тhe poor prognosis of patients initially diagnosed at an advanced stage of colorectal cancer (CRC) and the heterogeneity within the same tumor stage define the need for additional predictive biomarkers. Tumor buds are proposed as a poor prognostic factor for CRC, however, they are still not implemented into routine pathology reporting. In turn, the chitinase-3-like protein 1 (CHI3L1) also known as YKL-40, is regarded as a candidate circulating biomarker and therapeutic target in CRC. The aim of our study was to investigate tissue YKL-40 localization and tumor budding in CRC...

The agricultural fumigant pesticide aluminum phosphide (AlP) is cardiotoxic. Water causes AlP to emit phosphine gas, a cardiac toxin that affects heart function and causes cardiogenic shock. AlP poisoning's high fatality rate is due to cardiotoxicity. This study examines how resveratrol reduces oxidative stress, mitochondrial activity, and apoptosis in human cardiac myocyte (HCM) cells. After determining the optimal doses of resveratrol using the MTT test, HCM cells were subjected to a 24-hour treatment of resveratrol following exposure to AlP (2...

INTRODUCTION: Despite aggressive standard-of-care therapy, including surgery, radiation, and chemotherapy, glioblastoma recurrence is almost inevitable and uniformly lethal. Activation of glioma-intrinsic Wnt/β-catenin signaling is associated with a poor prognosis and the proliferation of glioma stem-like cells, leading to malignant transformation and tumor progression. Impressive results in a subset of cancers have been obtained using immunotherapies including anti-CTLA4, anti-PD-1, and anti-PD-L1 or chimeric antigen receptor (CAR) T cell therapies...

Lipid handling in the intestine is important for maintaining energy homeostasis and overall health. Mishandling of lipids in the intestine contributes to dyslipidemia and atherosclerotic cardiovascular diseases. Despite advances in this field over the past few decades, significant gaps remain. The gut hormone glucagon-like peptide-2 (GLP-2) has been shown to play pleotropic roles in the regulation of lipid handling in the intestine. Of note, GLP-2 exhibits unique actions on post-prandial lipid absorption and post-absorptive release of intestinally stored lipids...

Grain hardness (Gh) is important for wheat processing and end-product quality. Puroindolines polymorphism explains over 60% of Gh variation and the novel genetic factors remain to be exploited. In this study, a total of 153 quantitative trait loci (QTLs), clustered into 12 genomic intervals (C1-C12), for 13 quality-related traits were identified using a recombinant inbred line population derived from the cross of Zhongkemai138 (ZKM138) and Chuanmai44 (CM44). Among them, C7 (harboring eight QTLs for different quality-related traits) and C8 (mainly harboring QGh...

Roots are the main sensing organ, initiating multiple signaling pathways in response to abiotic factors, including nutrients, drought, and salt stress. A focus on improving the root system architecture is a key strategy to mitigate these stresses in wheat crop. In the present study, a diversity panel comprising indigenous landraces and historical cultivars from Pakistan was characterized for the root system architecture (RSA) and important loci were identified using a genome-wide association study (GWAS). RSA of the diversity panel was characterized 30 days after sowing in brunch tubes, and root images were taken...

Cancer is a leading cause of mortality in humans, but the efficacy of current treatments for many cancers is limited, as they lack unique mechanistically defined targets. Here, we show that, upon malignant transformation, aggressive oncocells generate a second membrane exterior to their plasma membrane to form cytocapsulas (CCs) and cytocapsular tubes (CCTs), which all together constitute cytocapsular oncocells with pleotropic biological functions in cancer patient tissues in vivo. Proteomic and biochemical analyses revealed that the PMCA2 calcium pump is highly up-regulated in CCs and CCTs in malignant tumors but not in normal tissues, thus identifying a unique cancer biomarker and target for cancer therapy...

Cytochrome P450s (CYP450s) are a versatile superfamily of enzymes known to undergo rapid evolution. They have important roles across growth and development pathways in crustaceans, although it is difficult to characterise orthologs between species due to their sequence diversity. Conserved CYP450s enzymes in crustaceans are those associated with ecdysteroidogenesis: synthesising and breaking down the active moult hormone, 20-hydroxyecdysone. The complex life cycle of the ornate spiny lobster, Panulirus ornatus , relies on moulting in order to grow and develop...

Gene expression in Escherichia coli is controlled by well-established mechanisms that activate or repress transcription. Here, we identify CedA as an unconventional transcription factor specifically associated with the RNA polymerase (RNAP) σ70 holoenzyme. Structural and biochemical analysis of CedA bound to RNAP reveal that it bridges distant domains of β and σ70 subunits to stabilize an open-promoter complex. CedA does so without contacting DNA. We further show that cedA is strongly induced in response to amino acid starvation, oxidative stress and aminoglycosides...

Lipocalin-2 (LCN2), a neutrophil gelatinase-associated lipocalin (NGAL), is a 25 kDa secreted protein implicated in a broad range of inflammatory diseases affecting the brain and periphery. It is a pleotropic protein expressed by various immune and non-immune cells throughout the body. Importantly, the surge in LCN2 levels in disease states has been associated with a myriad of undesirable effects, further exacerbating the ongoing pathological processes. In the brain, glial cells are the principal source of LCN2, which plays a definitive role in determining their functional phenotypes...

BACKGROUND: Ketone bodies are pleotropic metabolites that play important roles in multiple biological processes ranging from bioenergetics to inflammation regulation via suppression of the NLRP3 inflammasome, and epigenetic modifications. Ketone bodies are elevated in left ventricular failure (LVF) and multiple approaches that increase ketone concentrations exert advantageous cardiac effects in rodents and humans. However, the relationships between ketone bodies and right ventricular failure (RVF) are relatively unexplored...

A locus, dt3, modulating semideterminancy in soybean, was discovered by a combination of genome-wide association studies and linkage mapping with multiple distinct biparental populations. Stem growth habit is a key architectural trait in many plants that contributes to plant productivity and environmental adaptation. In soybean, stem growth habit is classified as indeterminate, semideterminate, or determinate, of which semideterminacy is often considered as a counterpart of the "Green Revolution" trait in cereals that significantly increased grain yields...

Pancreatic cancer is currently one of the least curable types of human cancer and remains a key health problem. One of the most important characteristics of pancreatic cancer is its ability to grow under hypoxic conditions. Hypoxia is associated with resistance of cancer cells to radiotherapy and chemotherapy. It is a major contributor to pancreatic cancer genetic instability, which local and systemic resistance that may result in poor clinical outcome. Accordingly, identifying gene expression changes in cancer resistance genes that occur under hypoxic conditions may identify a new therapeutic target...

DHTKD1 is a nuclear gene that encodes "dehydrogenase E1 and transketolase domain-containing 1", essential in mitochondrial metabolism. First identified in the patients of 2-amino-apidic and 2 oxoapidic aciduria, mutation in this gene has recently been implicated in CMT2Q and ALS. Here we report the case of a septuagenarian who presented with a 2 years progressive history of respiratory and neck muscle weakness without significant bulbar and limb involvement. Clinical and electrophysiological examination revealed lower motor neuron involvement with widespread chronic denervation and reinnervation...

Connective tissue growth factor (CTGF) is a distinct signaling molecule modulating many physiological and pathophysiological processes. This protein is upregulated in numerous fibrotic diseases that involve extracellular matrix (ECM) remodeling. It mediates the downstream effects of transforming growth factor beta (TGF-β) and is regulated via TGF-β SMAD-dependent and SMAD-independent signaling routes. Targeting CTGF instead of its upstream regulator TGF-β avoids the consequences of interfering with the pleotropic effects of TGF-β...

Background: Eicosapentaenoic acid (EPA) is an omega-3 fatty acid that protects against cardiovascular diseases in patients with hypertriglyceridemia and may have pleotropic effects beyond lowering triglycerides. Many degenerative diseases, such as atherosclerosis and diabetes, are related to cellular senescence as a pathophysiological mechanism. We aimed to examine whether EPA could protect vascular endothelial cells under stress conditions against stress-induced accelerated senescence (SIAS). Methods: Cultured human umbilical vein endothelial cells (HUVECs) were exposed to H2 O2 as oxidative stress and a high glucose concentration with palmitate as a glucolipotoxic condition...

PURPOSE/OBJECTIVE(S): Treating Glioblastoma remains a major challenge. Radiotherapy has a long-standing role in extending survival, but almost all tumors are expected to recur and be fatal. Historic dose-escalation studies do not yield additional benefit beyond the current 60 Gy dose. Further therapeutic improvement can be gained with radiosensitizers. An undiscovered potential radiosensitization approach may exist in inhibiting the N-myristoylation pathways upregulated in malignant cells...