Bioengineering chitosan-antibody/fluorescent quantum dot nanoconjugates for targeted immunotheranostics of non-hodgkin B-cell lymphomas.

B-cell non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy, capable of invading the brain, meninges, and nerve roots of the brain and spine, leading to high lethality. Herein, we designed and developed novel nanostructures for the first time by biofunctionalizing chitosan with two specific antibodies (i.e.

Bioengineering stimuli-responsive organic-inorganic nanoarchitetures based on carboxymethylcellulose-poly-l-lysine nanoplexes: Unlocking the potential for bioimaging and multimodal chemodynamic-magnetothermal therapy of brain cancer cells.

Regrettably, glioblastoma multiforme (GBM) remains the deadliest form of brain cancer, where the early diagnosis plays a pivotal role in the patient's therapy and prognosis. Hence, we report for the first time the design, synthesis, and characterization of new hybrid organic-inorganic stimuli-responsive nanoplexes (NPX) for bioimaging and killing brain cancer cells (GBM, U-87). These nanoplexes were built through coupling two nanoconjugates, produced using a facile, sustainable, green aqueous colloidal process ("bottom-up").

Neutrophils insert elastase into hepatocytes to regulate calcium signaling in alcohol-associated hepatitis.

Neutrophil infiltration occurs in a variety of liver diseases, but it is unclear how neutrophils and hepatocytes interact. Neutrophils generally use granule proteases to digest phagocytosed bacteria and foreign substances or neutralize them in neutrophil extracellular traps. In certain pathological states, granule proteases play a destructive role against the host as well.

Burden of liver disease in Brazil, 1996-2022: a retrospective descriptive study of the epidemiology and impact on public healthcare.

Background: Liver disease is a major cause of mortality and morbidity worldwide and its epidemiology depends on the genetic background, exposure to risk factors, access to healthcare and other sociodemographic characteristics. Brazil is a large country with diverse multicultural and ethnic heritages and important socioeconomic inequalities. The burden of liver disease in Brazil, its regions and population is unknown.

Adaptation to volumetric compression drives hepatoblastoma cells to an apoptosis-resistant and invasive phenotype.

Unlabelled: Liver cancer involves tumor cells rapidly growing within a packed tissue environment. Patient tumor tissues reveal densely packed and deformed cells, especially at tumor boundaries, indicative of physical crowding and compression. It is not well understood how these physical signals modulate tumor evolution and therapeutic susceptibility.

Nanozymes with Peroxidase-like Activity for Ferroptosis-Driven Biocatalytic Nanotherapeutics of Glioblastoma Cancer: 2D and 3D Spheroids Models.

Glioblastoma (GBM) is the most common primary brain cancer in adults. Despite the remarkable advancements in recent years in the realm of cancer diagnosis and therapy, regrettably, GBM remains the most lethal form of brain cancer. In this view, the fascinating area of nanotechnology has emerged as an innovative strategy for developing novel nanomaterials for cancer nanomedicine, such as artificial enzymes, termed nanozymes, with intrinsic enzyme-like activities.

Calcium signaling in chemotherapy-induced neuropathy.

Alterations in calcium (Ca) signaling is a major mechanism in the development of chemotherapy-induced peripheral neuropathy (CIPN), a side effect caused by multiple chemotherapy regimens. CIPN is associated with numbness and incessant tingling in hands and feet which diminishes quality of life during treatment. In up to 50% of survivors, CIPN is essentially irreversible.

The des-Arg-bradykinin/B1R axis: Hepatic damage in COVID-19.

Patients infected by the SARS-CoV-2 virus are commonly diagnosed with threatening liver conditions associated with drug-induced therapies and systemic viral action. RNA-Seq data from cells in bronchoalveolar lavage fluid from COVID-19 patients have pointed out dysregulation of kallikrein-kinin and renin-angiotensin systems as a possible mechanism that triggers multi-organ damage away from the leading site of virus infection. Therefore, we measured the plasma concentration of biologically active peptides from the kallikrein-kinin system, bradykinin and des-Arg-bradykinin, and liver expression of its proinflammatory axis, bradykinin 1 receptor (B1R).

Inositol 1,4,5-trisphosphate receptor type 3 is involved in resistance to apoptosis and maintenance of human hepatocellular carcinoma.

The expression of the inositol 1,4,5-trisphosphate receptor type 3 (ITRP3) in hepatocytes is a common event in the pathogenesis of hepatocellular carcinoma (HCC), regardless of the type of underlying liver disease. However, it is not known whether ITPR3 expression in hepatocytes is involved in tumor maintenance. The aim of the present study was to determine whether there is an association between ITPR3 expression and clinical and morphological parameters using HCC samples obtained from liver explants from patients (n=53) with different etiologies of underlying chronic liver disease (CLD).

Correlation Between Clinical and Pathological Findings of Liver Injury in 27 Patients With Lethal COVID-19 Infections in Brazil.

Liver test abnormalities are frequently observed in patients with coronavirus disease 2019 (COVID-19) and are associated with worse prognosis. However, information is limited about pathological changes in the liver in this infection, so the mechanism of liver injury is unclear. Here we describe liver histopathology and clinical correlates of 27 patients who died of COVID-19 in Manaus, Brazil.

Inositol 1,4,5-trisphosphate receptor type 3 plays a protective role in hepatocytes during hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion injury is seen in a variety of clinical conditions, including hepatic thrombosis, systemic hypotension, and liver transplantation. Calcium (Ca) signaling mediates several pathophysiological processes in the liver, but it is not known whether and how intracellular Ca channels are involved in the hepatocellular events secondary to ischemia-reperfusion. Using an animal model of hepatic ischemia-reperfusion injury, we observed a progressive increase in expression of the type 3 isoform of the inositol trisphosphate receptor (ITPR3), an intracellular Ca channel that is not normally expressed in healthy hepatocytes.

Correction to: A role for mast cells and mast cell tryptase in driving neutrophil recruitment in LPS-induced lung inflammation via protease-activated receptor 2 in mice.

The original article can be found online.

A role for mast cells and mast cell tryptase in driving neutrophil recruitment in LPS-induced lung inflammation via protease-activated receptor 2 in mice.

Objective: This study aims to investigate the role of protease-activated receptor (PAR) 2 and mast cell (MC) tryptase in LPS-induced lung inflammation and neutrophil recruitment in the lungs of C57BL/6 mice.

Methods: C57BL/6 mice were pretreated with the PAR2 antagonist ENMD-1068, compound 48/80 or aprotinin prior to intranasal instillation of MC tryptase or LPS. Blood leukocytes, C-X-C motif chemokine ligand (CXCL) 1 production leukocytes recovered from bronchoalveolar lavage fluid (BALF), and histopathological analysis of the lung were evaluated 4 h later.

Molecular Mechanism for Protection Against Liver Failure in Human Yellow Fever Infection.

Yellow fever (YF) is a viral hemorrhagic fever that typically involves the liver. Brazil recently experienced its largest recorded YF outbreak, and the disease was fatal in more than a third of affected individuals, mostly because of acute liver failure. Affected individuals are generally treated only supportively, but during the recent Brazilian outbreak, selected patients were treated with liver transplant.

Inositol 1,4,5-trisphosphate receptor in the liver: Expression and function.

The liver is a complex organ that performs several functions to maintain homeostasis. These functions are modulated by calcium, a second messenger that regulates several intracellular events. In hepatocytes and cholangiocytes, which are the epithelial cell types in the liver, inositol 1,4,5-trisphosphate (InsP) receptors (ITPR) are the only intracellular calcium release channels.

Polymorphism in the Promoter Region of NFE2L2 Gene Is a Genetic Marker of Susceptibility to Cirrhosis Associated with Alcohol Abuse.

Alcoholic liver disease (ALD) is a highly prevalent spectrum of pathologies caused by alcohol overconsumption. Morbidity and mortality related to ALD are increasing worldwide, thereby demanding strategies for early diagnosis and detection of ALD predisposition. A potential candidate as a marker for ALD susceptibility is the transcription factor nuclear factor erythroid-related factor 2 (Nrf2), codified by the nuclear factor erythroid 2-related factor 2 gene (NFE2L2).

Effects of Endotoxin on Type 3 Inositol 1,4,5-Trisphosphate Receptor in Human Cholangiocytes.

Clinical conditions that result in endotoxemia, such as sepsis and alcoholic hepatitis (AH), often are accompanied by cholestasis. Although hepatocellular changes in response to lipopolysaccharide (LPS) have been well characterized, less is known about whether and how cholangiocytes contribute to this form of cholestasis. We examined effects of endotoxin on expression and function of the type 3 inositol trisphosphate receptor (ITPR3), because this is the main intracellular Ca release channel in cholangiocytes, and loss of it impairs ductular bicarbonate secretion.

Efficacy of Meglumine Antimoniate in a Low Polymerization State Orally Administered in a Murine Model of Visceral Leishmaniasis.

Progress toward the improvement of meglumine antimoniate (MA), commercially known as Glucantime, a highly effective but also toxic antileishmanial drug, has been hindered by the lack of knowledge and control of its chemical composition. Here, MA was manipulated chemically with the aim of achieving an orally effective drug. MA compounds were synthesized from either antimony pentachloride (MA-SbCl) or potassium hexahydroxyantimonate [MA-KSb(OH)] and prepared under a low polymerization state.

Relationship between quality of life and work ability among judicial employees.

Background: As is known, occupational diseases hamper productivity by impairing not only the work ability, but also all the aspects related with the quality of life of employees. Maintenance of work ability is associated with the state of health needed to perform work activities, which when are properly done lead to satisfactory results for both organizations and workers.

Objective: To investigate the relationship between quality of life and work ability among judicial employees.

Cholesterol-enriched membrane microdomains are needed for insulin signaling and proliferation in hepatic cells.

Hepatocyte proliferation during liver regeneration is a well-coordinated process regulated by the activation of several growth factor receptors, including the insulin receptor (IR). The IR can be localized in part to cholesterol-enriched membrane microdomains, but the role of such domains in insulin-mediated events in hepatocytes is not known. We investigated whether partitioning of IRs into cholesterol-enriched membrane rafts is important for the mitogenic effects of insulin in the hepatic cells.

Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer.

Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade.

GPR91: expanding the frontiers of Krebs cycle intermediates.

Since it was discovered, the citric acid cycle has been known to be central to cell metabolism and energy homeostasis. Mainly found in the mitochondrial matrix, some of the intermediates of the Krebs cycle are also present in the blood stream. Currently, there are several reports that indicate functional roles for Krebs intermediates out of its cycle.

Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation.

Background: Succinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models.

Results: We found that succinate causes cardiac hypertrophy in a GPR91 dependent manner.