Subset of DN Memory B Cells Expressing Low Levels of Inhibitory Receptor BTLA Is Enriched in SLE Patients.

The dialogue between T and B cells can be regulated by different mechanisms, such as co-inhibitory receptors, which therefore play a crucial role in preventing autoimmune diseases such as systemic lupus erythematosus (SLE). B and T lymphocyte attenuator (BTLA) is a co-inhibitory receptor expressed on many myeloid and lymphoid cells. Although peripheral B cells express a very high amount of BTLA, previous works in the context of autoimmunity mainly focused on T cells, and whether BTLA expression on B cells plays a role in the lupus pathogenesis is still unclear.

The Chemokine System as a Key Regulator of Pulmonary Fibrosis: Converging Pathways in Human Idiopathic Pulmonary Fibrosis (IPF) and the Bleomycin-Induced Lung Fibrosis Model in Mice.

Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal interstitial lung disease (ILD) of unknown origin, characterized by limited treatment efficacy and a fibroproliferative nature. It is marked by excessive extracellular matrix deposition in the pulmonary parenchyma, leading to progressive lung volume decline and impaired gas exchange. The chemokine system, a network of proteins involved in cellular communication with diverse biological functions, plays a crucial role in various respiratory diseases.

Mutant p53-Mediated Tumor Secretome: Bridging Tumor Cells and Stromal Cells.

The tumor secretome comprises the totality of protein factors secreted by various cell components within the tumor microenvironment, serving as the primary medium for signal transduction between tumor cells and between tumor cells and stromal cells. The deletion or mutation of the gene leads to alterations in cellular secretion characteristics, contributing to the construction of the tumor microenvironment in a cell non-autonomous manner. This review discusses the critical roles of mutant p53 in regulating the tumor secretome to remodel the tumor microenvironment, drive tumor progression, and influence the plasticity of cancer-associated fibroblasts (CAFs) as well as the dynamics of tumor immunity by focusing on both secreted protein expression and secretion pathways.

Decoding the Nexus: Cellular and Molecular Mechanisms Linking Stroke and Neurotoxic Microenvironments in Brain Cancer Patients.

Stroke is an often underrecognized albeit significant complication in patients with brain cancer, arising from the intricate interplay between cancer biology and cerebrovascular health. This review delves into the multifactorial pathophysiological framework linking brain cancer to elevated stroke risk, with particular emphasis on the crucial role of the neurotoxic microenvironment (NTME). The NTME, characterized by oxidative stress, neuroinflammation, and blood-brain barrier (BBB) disruption, creates a milieu that promotes and sustains vascular and neuronal injury.

Identification of Transcriptional Regulators of Immune Evasion Across Cancers: An Alternative Immunotherapeutic Strategy for Cholangiocarcinoma.

Background: Cancer immune evasion is a multifaceted process that synchronizes pro-tumoral immune infiltration, immunosuppressive inflammation, and inhibitory immune checkpoint expression (IC). Current immunotherapies combat this issue by reinstating immunosurveillance of tumors; however, it benefits a limited patient population. Thus, a more effective immunotherapeutic strategy is warranted to cater to specific patient populations.

Viral infection, APOBEC3 dysregulation, and cancer.

Viral infection plays a significant role in the development and progression of many cancers. Certain viruses, such as Human Papillomavirus (HPV), Epstein-Barr Virus (EBV), and Hepatitis B and C viruses (HBV, HCV), are well-known for their oncogenic potential. These viruses can dysregulate specific molecular and cellular processes through complex interactions with host cellular mechanisms.

Inhibitory Effect of Human Anti-CA I Autoantibodies and Development of Monoclonal Antibody mAb 2B8 Targeting Carbonic Anhydrase I.

Spontaneous tumor regression is a recognized phenomenon across various cancer types. Recent research emphasizes the alterations in autoantibodies against carbonic anhydrase I (CA I) (anti-CA I) levels as potential prognostic markers for various malignancies. Particularly, autoantibodies targeting CA I and II appear to induce cellular damage by inhibiting their respective protein's catalytic functions.

The IBEX Imaging Knowledge-Base: A Community Resource Enabling Adoption and Development of Immunofluoresence Imaging Methods.

The iterative bleaching extends multiplexity (IBEX) Knowledge-Base is a central portal for researchers adopting IBEX and related 2D and 3D immunofluorescence imaging methods. The design of the Knowledge-Base is modeled after efforts in the open-source software community and includes three facets: a development platform (GitHub), static website, and service for data archiving. The Knowledge-Base facilitates the practice of open science throughout the research life cycle by providing validation data for recommended and non-recommended reagents, e.

Tax1bp1 enhances bacterial virulence and promotes inflammatory responses during infection of alveolar macrophages.

Crosstalk between autophagy, host cell death, and inflammatory host responses to bacterial pathogens enables effective innate immune responses that limit bacterial growth while minimizing coincidental host damage. () thwarts innate immune defense mechanisms in alveolar macrophages (AMs) during the initial stages of infection and in recruited bone marrow-derived cells during later stages of infection. However, how protective inflammatory responses are achieved during infection and the variation of the response in different macrophage subtypes remain obscure.

Asynchronous Transitions from Hepatoblastoma to Carcinoma in High-Risk Pediatric Tumors.

Most malignant hepatocellular tumors in children are classified as either hepatoblastoma (HB) or hepatocellular carcinoma (HCC), but some tumors demonstrate features of both HB and HCC. These tumors have been recognized under a provisional diagnostic category by the World Health Organization and are distinguished from HB and HCC by a combination of histological, immunohistochemical, and molecular features. Their outcomes and cellular composition remain an open question.

Efficacy of natural NF-κB inhibitors in the treatment of fibrosarcoma: an in vitro model study.

Introduction: NF-κB plays a pivotal role in the progression of cancers, including myosarcomas such as fibrosarcoma. Plants possess considerable potential for the provision of chemotherapeutic effects against cancer. The present study assessed, among others, the cytotoxicity, migration capacity and DNA damage induced by several natural compounds (berberine, curcumin, biochanin A, cucurbitacin E (CurE) and phenethyl caffeic acid (CAPE)) in cancer cells (WEHI-164) and normal muscle cells (L6).

A multiplex method for rapidly identifying viral protease inhibitors.

With current treatments addressing only a fraction of pathogens and new viral threats constantly evolving, there is a critical need to expand our existing therapeutic arsenal. To speed the rate of discovery and better prepare against future threats, we establish a high-throughput platform capable of screening compounds against 40 diverse viral proteases simultaneously. This multiplex approach is enabled by using cellular biosensors of viral protease activity combined with DNA-barcoding technology, as well as several design innovations that increase assay sensitivity and correct for plate-to-plate variation.

Endogenous thymic regeneration: restoring T cell production following injury.

Despite its importance for generating and maintaining a healthy and broad T cell repertoire, the thymus is exquisitely sensitive to acute damage. Marked thymic involution occurs in response to stimuli as diverse as infection, stress, pregnancy, malnutrition, drug use and cytoreductive chemotherapy. However, the thymus also has a remarkable capacity for repair, although this regenerative capacity declines with age.

Targeting mutant p53: Evaluation of novel anti-p53 monoclonal antibodies as diagnostic tools.

About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The p53 missense mutation p53 (p53 in mice) is a hotspot mutation in various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like p53 could prove immensely value.

Core-genome guided novel therapeutic targets identification and chimeric vaccine designing against Rickettsia rickettsii.

Rocky Mountain Spotted Fever, caused by the gram-negative intracellular bacteria Rickettsia rickettsii, is a serious tick-borne infection with a fatality rate of 20-30%, if not treated. Since it is the most serious rickettsial disease in North America, modified prevention and treatment strategies are of critical importance. In order to find new therapeutic targets and create multiepitope vaccines, this study integrated subtractive proteomics with reverse vaccinology.

The modulation of immune cell death in connection to microRNAs and natural products.

Immunogenic cell death (ICD) spatiotemporally regulates damage-associated molecular patterns (DAMPs) derived from dying cancer cells to signal the immune response. Intriguingly, these DAMPs and cytokines also induce cellular responses in non-immune cells, particularly cancer cells. Several ICD-modulating natural products and miRNAs have been reported to regulate the DAMP, cytokine, and cell death responses, but they lack systemic organization and connection.

A1, an innovative fluorinated CXCR4 inhibitor, redefines the therapeutic landscape in colorectal cancer.

Background: Colorectal cancer (CRC) is a globally prevalent malignancy, primarily affecting the colon and rectum, characterized by uncontrolled cellular changes in the intestinal wall lining. Recent evidence underlines the significant role of the CXCL12/CXCR4 axis in the development of CRC, suggesting that inhibiting this pathway could be a promising therapeutic approach. This study focuses on investigating the potential of N, N''-thiocarbonylbis (N'-(3,4-dimethyl phenyl)-2,2,2-trifluoroacetimidamide) (A1), a novel fluorinated CXCR4 inhibitor, through a comprehensive analysis encompassing in silico, in vitro, and in vivo studies.

A Similar Mutation in the AAUU-Rich Elements of the Mouse TNF Gene Results in a Distinct Ileocolitic Phenotype: A New Strain of TNF-Overexpressing Mice.

Background: Tumor necrosis factor (TNF) is a pleiotropic cytokine that plays a critical role in the pathogenesis of immune-mediated diseases including inflammatory bowel disease (IBD). The stability of its mRNA transcript, determined in part by destabilizing sequences in its AAUU repeats (ARE) gene region, is an important regulator of its tissue and systemic levels. A deletion in the ARE region of the gene resulted in IBD and arthritis in mice and pigs, supporting a critical role for the cytokine in human IBD and several human arthritides.

A 3D Computational Study on the Formation and Progression of Tumor Cells in Diffuse Gastric Cancer.

Hereditary diffuse gastric cancer is characterized by an increased risk of diffuse gastric cancer and lobular breast cancer, and is caused by pathogenic germline variants of E-cadherin and -E-catenin, which are key regulators of cell-cell adhesion. However, how the loss of cell-cell adhesion promotes cell dissemination remains to be fully understood. Therefore, a three-dimensional computer model was developed to describe the initial steps of diffuse gastric cancer development.

Phosphorylation of a nuclear condensate regulates cohesion and mRNA retention.

Nuclear speckles are membraneless organelles that associate with active transcription sites and participate in post-transcriptional mRNA processing. During the cell cycle, nuclear speckles dissolve following phosphorylation of their protein components. Here, we identify the PP1 family as the phosphatases that counteract kinase-mediated dissolution.

Spatial and single-cell transcriptomics reveal cellular heterogeneity and a novel cancer-promoting Treg cell subset in human clear-cell renal cell carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common histologic type of RCC. However, the spatial and functional heterogeneity of immunosuppressive cells and the mechanisms by which their interactions promote immunosuppression in the ccRCC have not been thoroughly investigated.

Methods: To further investigate the cellular and regional heterogeneity of ccRCC, we analyzed single-cell and spatial transcriptome RNA sequencing data from four patients, which were obtained from samples from multiple regions, including the tumor core, tumor-normal interface, and distal normal tissue.

Blood-based diagnosis of pediatric tuberculosis: A prospective cohort study in South Africa and Dominican Republic.

Objectives: Pediatric tuberculosis (TB) diagnosis is complicated by challenges in obtaining invasive respiratory specimens that frequently contain few Mycobacterium tuberculosis (Mtb) bacilli. We report the diagnostic performance of an Mtb antigen-derived peptide (MAP-TB) assay and its ability to monitor TB treatment response.

Methods: Study cohorts enrolled children who presented with presumptive TB at two hospitals in South Africa from 2012 to 2017 (157 children aged <13 years) and at community-based clinics in the Dominican Republic from 2019 to 2023 (101 children aged <18 years).

Leptin, NK cells, and the weight of immunity: Insights into obesity.

Obesity is a chronic inflammatory disease that affects more than 1 billion people worldwide and is associated with various metabolic and physiological dysfunctions, directly impacting the dynamics of the immune response, partly due to elevated leptin levels. Leptin is an important peptide hormone that regulates neuroendocrine function and energy homeostasis, with its blood levels reflecting energy reserves, fat mass, or energy deprivation. This hormone also plays a fundamental role in regulating immune function, including the activity of NK cells, which are essential components in antiviral and antitumor activity.