Molecular Hydrogen as a Potential Adjunctive Therapy to Improve Renal Function and Reduce Fatigue in an Elderly Patient With Chronic Comorbidities: A Case Report.

Background/aim: Hydrogen therapy has demonstrated potential as an antioxidant and anti-inflammatory intervention, particularly in the management of chronic diseases such as chronic kidney disease (CKD) and autoimmune conditions. This case report presents the possible therapeutic benefits of molecular hydrogen capsule treatment in enhancing renal function and alleviating chronic fatigue in an elderly female with coronary artery disease (CAD), type 2 diabetes mellitus (DM) complicated by nephropathy, and systemic lupus erythematosus (SLE). The aim of this study was to investigate the efficacy of adjunctive hydrogen therapy in an elderly patient with multiple chronic comorbidities.

Precision Assessment of Anti-NMDA Receptor Encephalitis: A Case Report on Integrating Clinical Course, Immunophenotyping, and Comprehensive Symptomatology in a Pediatric Patient With Adjunctive Hydrogen Therapy.

Background/aim: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, though rare, is the most common form of autoimmune encephalitis, predominantly affecting young individuals, particularly females. Standard treatments include corticosteroids, intravenous immunoglobulins (IVIG), and plasmapheresis, with rituximab recommended for those unresponsive to first-line therapies. However, reliable biomarkers for clinical assessment remain elusive.

Ganglioside GD2 Contributes to a Stem-Like Phenotype in Intrahepatic Cholangiocarcinoma.

Background & Aims: GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.

Methods: The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON).

Humoral response 24 months after the first COVID-19 vaccination in people with HIV with and without diabetes.

People with HIV (PWH) and people with diabetes mellitus have increased risk of severe COVID-19, but little is known about humoral response to COVID-19 vaccines in PWH with DM. We investigated SARS-CoV-2 antireceptor-binding domain (anti-RBD) immunoglobulin G (IgG) geometrical concentrations and neutralizing antibody capacity (nAB) in PWH with and without diabetes mellitus. Anti-RBD IgG and nAB in COVID-19-vaccinated PWH were not associated with diabetes mellitus-status or HbA1c 24 months after the initial COVID-19 vaccination.

Pushing the boundaries of radiotherapy-immunotherapy combinations: highlights from the 7 immunorad conference.

Over the last decade, the annual Immunorad Conference, held under the joint auspicies of Gustave Roussy (Villejuif, France) and the Weill Cornell Medical College (New-York, USA) has aimed at exploring the latest advancements in the fields of tumor immunology and radiotherapy-immunotherapy combinations for the treatment of cancer. Gathering medical oncologists, radiation oncologists, physicians and researchers with esteemed expertise in these fields, the Immunorad Conference bridges the gap between preclinical outcomes and clinical opportunities. Thus, it paves a promising way toward optimizing radiotherapy-immunotherapy combinations and, from a broader perspective, improving therapeutic strategies for patients with cancer.

The antitumor activity of TGFβ-specific T cells is dependent on IL-6 signaling.

Although interleukin (IL)-6 is considered immunosuppressive and tumor-promoting, emerging evidence suggests that it may support antitumor immunity. While combining immune checkpoint inhibitors (ICIs) and radiotherapy in patients with pancreatic cancer (PC) has yielded promising clinical results, the addition of an anti-IL-6 receptor (IL-6R) antibody has failed to elicit clinical benefits. Notably, a robust TGFβ-specific immune response at baseline in PC patients treated solely with ICIs and radiotherapy correlated with improved survival.

Dual specific STAT3/5 degraders effectively block acute myeloid leukemia and natural killer/T cell lymphoma.

The transcription factors STAT3, STAT5A, and STAT5B steer hematopoiesis and immunity, but their enhanced expression and activation promote acute myeloid leukemia (AML) or natural killer/T cell lymphoma (NKCL). Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, but these kinase blockers are not selective against STAT3/5 activation and frequent resistance causes relapse, emphasizing the need for targeted drugs. We evaluated the efficacy of JPX-0700 and JPX-0750 as dual STAT3/5 binding inhibitors promoting protein degradation.

Integrating Prior Knowledge Using Transformer for Gene Regulatory Network Inference.

Gene regulatory network (GRN) inference, a process of reconstructing gene regulatory rules from experimental data, has the potential to discover new regulatory rules. However, existing methods often struggle to generalize across diverse cell types and account for unseen regulators. Here, this work presents GRNPT, a novel Transformer-based framework that integrates large language model (LLM) embeddings from publicly accessible biological data and a temporal convolutional network (TCN) autoencoder to capture regulatory patterns from single-cell RNA sequencing (scRNA-seq) trajectories.

Polyol pathway-generated fructose is indispensable for growth and survival of non-small cell lung cancer.

Despite recent treatment advances, non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related deaths worldwide, and therefore it necessitates the exploration of new therapy options. One commonly shared feature of malignant cells is their ability to hijack metabolic pathways to confer survival or proliferation. In this study, we highlight the importance of the polyol pathway (PP) in NSCLC metabolism.

Cultivating the next generation of leaders : How postdocs, principal investigators and institutes can nurture and select for leadership competencies.

The transition from postdoc to PI is the most challenging career step. Peer groups, PIs and research institution can help postdocs to acquire the necessary skills and experience. [Image: see text]

RhoA regulates oligodendrocyte differentiation and myelination by orchestrating cortical and membrane tension.

Timely differentiation and myelin formation by oligodendrocytes are essential for the physiological functioning of the central nervous system (CNS). While the Rho GTPase RhoA has been hinted as a negative regulator of myelin sheath formation, the precise in vivo mechanisms have remained elusive. Here we show that RhoA controls the timing and progression of myelination by oligodendrocytes through a fine-tuned balance between cortical tension, membrane tension and cell shape.

The role of mesenchymal cells in cholangiocarcinoma.

The tumour microenvironment (TME) significantly influences tumour formation and progression through dynamic interactions. Cholangiocarcinoma (CCA), a highly desmoplastic tumour, lacks early diagnostic biomarkers and has limited effective treatments owing to incomplete understanding of its molecular pathogenesis. Investigating the role of the TME in CCA progression could lead to better therapies.

Molecular Hydrogen Therapy in Sjögren's Syndrome With Pulmonary Arterial Hypertension and Right-sided Heart Failure: A Case Report of Improved Immune Markers Including Treg, B Cells and Plasma Cell.

Background/aim: Connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) is a severe complication characterized by elevated pulmonary artery pressure, which can lead to right heart failure and death, if untreated. Standard treatments often fail to adequately manage symptoms, highlighting the need for novel therapeutic approaches. This study investigated the efficacy of molecular hydrogen (H) therapy in a patient with CTD-PAH.

Distinct strategies for intravascular triglyceride metabolism in hearts of mammals and lower vertebrate species.

Lipoprotein lipase (LPL) and multiple regulators of LPL activity (e.g., APOC2 and ANGPTL4) are present in all vertebrates, but GPIHBP1-the endothelial cell (EC) protein that captures LPL within the subendothelial spaces and transports it to its site of action in the capillary lumen-is present in mammals but in not chickens or other lower vertebrates.

A proinflammatory stem cell niche drives myelofibrosis through a targetable galectin-1 axis.

Myeloproliferative neoplasms are stem cell-driven cancers associated with a large burden of morbidity and mortality. Most patients present with early-stage disease, but a substantial proportion progress to myelofibrosis or secondary leukemia, advanced cancers with a poor prognosis and high symptom burden. Currently, it remains difficult to predict progression, and therapies that reliably prevent or reverse fibrosis are lacking.

Mimicking and analyzing the tumor microenvironment.

The tumor microenvironment (TME) is increasingly appreciated to play a decisive role in cancer development and response to therapy in all solid tumors. Hypoxia, acidosis, high interstitial pressure, nutrient-poor conditions, and high cellular heterogeneity of the TME arise from interactions between cancer cells and their environment. These properties, in turn, play key roles in the aggressiveness and therapy resistance of the disease, through complex reciprocal interactions between the cancer cell genotype and phenotype, and the physicochemical and cellular environment.

Catalytic and noncatalytic functions of DNA polymerase κ in translesion DNA synthesis.

Translesion DNA synthesis (TLS) is a cellular process that enables the bypass of DNA lesions encountered during DNA replication and is emerging as a primary target of chemotherapy. Among vertebrate DNA polymerases, polymerase κ (Polκ) has the distinctive ability to bypass minor groove DNA adducts in vitro. However, Polκ is also required for cells to overcome major groove DNA adducts but the basis of this requirement is unclear.

Age-Related Decline in Pancreas Regeneration Is Associated With an Increased Proinflammatory Response to Injury.

Background And Aims: The regenerative capacity of the pancreas diminishes with age. Understanding acinar cell responses to injury and the resolution of regenerative processes is crucial for tissue homeostasis. However, knowledge about the impact of aging on these processes remains limited.

Data enhancement in the age of spatial biology.

Unveiling the intricate interplay of cells in their native environment lies at the heart of understanding fundamental biological processes and unraveling disease mechanisms, particularly in complex diseases like cancer. Spatial transcriptomics (ST) offers a revolutionary lens into the spatial organization of gene expression within tissues, empowering researchers to study both cell heterogeneity and microenvironments in health and disease. However, current ST technologies often face limitations in either resolution or the number of genes profiled simultaneously.

Glioblastoma cells increase expression of notch signaling and synaptic genes within infiltrated brain tissue.

Glioblastoma remains one of the deadliest brain malignancies. First-line therapy consists of maximal surgical tumor resection, accompanied by chemotherapy and radiotherapy. Malignant cells escape surgical resection by migrating into the surrounding healthy brain tissue, where they give rise to the recurrent tumor.

Mosaic chromosomal alterations in hematopoietic cells and clinical outcomes in patients with multiple myeloma.

Mosaic chromosomal alterations (mCAs) in hematopoietic cells increase mortality and risk of hematological cancers and infections. We investigated the landscape of mCAs and their clinical consequences in 976 patients with multiple myeloma undergoing high-dose chemotherapy and autologous stem cell support (ASCT) with median 6.4 years of follow-up.