Cucurbitacin IIb mitigates concanavalin A-induced acute liver injury by suppressing M1 macrophage polarization.

Cucurbitacins are a class of triterpenoid compounds extracted from plants and possess various pharmacological applications. Cucurbitacin IIb (CuIIb), extracted from the medicinal plant Hemsleya amabilis (Cucurbitaceae), has served as a traditional Chinese medicine for the treatment of bacterial dysentery and intestinal inflammation. CuIIb has been shown to exhibit anti-inflammatory activity; however, the protective effect of CuIIb against concanavalin A (Con A)-induced acute liver injury (ALI) and the fundamental mechanism remain unelucidated.

Clinical features of FOSMN syndrome in Korea: A comparative analysis with bulbar-onset amyotrophic lateral sclerosis.

Facial onset sensory and motor neuronopathy (FOSMN) syndrome is a rare neurodegenerative disorder initially characterized by facial sensory deficits, which later progress to motor deficits in a rostral-caudal distribution. This study investigated the prevalence, clinical features, and prognosis of FOSMN syndrome and compared these aspects with those of bulbar-onset amyotrophic lateral sclerosis (ALS) within a single institutional cohort of motor neuron diseases. We identified four patients with FOSMN syndrome who had been misclassified as having bulbar-onset ALS, representing approximately 2 % of such ALS cases.

FcγRI plays a pro-inflammatory role in the immune response to Chlamydia respiratory infection by upregulating dendritic cell-related genes.

Background: FcγRI, a pivotal cell surface receptor, is implicated in diverse immune responses and is ubiquitously expressed on numerous immune cells. However, its role in intracellular bacterial infections remains understudied.

Methods: Wild-type (WT) and FcγRI knockout (FcγRI-KO) mice were inoculated intranasally with a specific dose of C.

Targeting the Progression of Lupus-Like Disease in Humanized Mouse Model by Specific Dietary Components.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a number of immunological aberrations in the mechanisms of innate and adaptive immune responses. Spontaneous and induced mouse models of the disease have contributed significantly to the advancement in lupus treatments. The involvement of humanized models, engrafted with lupus patients' immune cells, represented the possibility to study the development of SLE.

Cerebellar Bergmann glia integrate noxious information and modulate nocifensive behaviors.

The cerebellum is activated by noxious stimuli and pathological pain but its role in noxious information processing remains unknown. Here, we show that in mice, cutaneous noxious electrical stimuli induced noradrenaline (NA) release from locus coeruleus (LC) terminals in the cerebellar cortex. Bergmann glia (BG) accumulated these LC-NA signals by increasing intracellular calcium in an integrative manner ('flares').

The D126G mutation contributes to the early-onset X-linked juvenile retinoschisis.

X-linked juvenile retinoschisis (XLRS) is an inherited retinal disease caused by mutations in the RS1 gene, resulting in splitting of the retinal layers and visual disturbances. To provide insights on this disease in our cohort, genetic examination, clinical presentation, and functional analysis were performed. We observed three main RS1 mutations in our cohort of six unrelated patients: RS1-D126G, RS1-R209H, and RS1-R213W.

TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen.

For the protozoan parasite Leishmania, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the L.

Targeting the EP2 receptor ameliorates inflammatory bowel disease in mice by enhancing the immunosuppressive activity of T cells.

Inflammatory bowel diseases (IBDs) are characterized by unrestrained innate and adaptive immune responses and compromised intestinal epithelial barrier integrity. Regulatory T (T) cells are crucial for maintaining self-tolerance and immune homeostasis in intestinal tissues. Prostaglandin E (PGE), a bioactive lipid compound derived from arachidonic acid, can modulate T cell functions in a receptor subtype-specific manner.

Developing a Serum-Free and Cytokine-Optimizing Induction Medium to Increase the Production of CD14CD16 and CD14CD16 Monocytes from Human CD133 Hematopoietic Stem and Progenitor Cells.

Immunotherapy utilizes immune cells to target cancer and improves treatment outcomes with few side effects. Despite the effectiveness of immunotherapy, the limited availability of monocytes, which are essential for the differentiation of antigen-presenting cells, remains a major challenge. In this study, we developed a technique for inducing monocytes from hematopoietic stem and progenitor cells by using a serum-free (SF) medium supplemented with optimal concentrations of serum substitutes and cytokines.

Inhibition of Bruton's tyrosine kinase restricts neuroinflammation following intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a devastating form of stroke with a lack of effective treatments. Following disease onset, ICH activates microglia and recruits peripheral leukocytes into the perihematomal region to amplify neural injury. Bruton's tyrosine kinase (BTK) controls the proliferation and survival of various myeloid cells and lymphocytes.

Use of a Personalized Clinical Decision Support System for Dosing in Psychopharmacotherapy in Patients with Alcoholic Hallucinosis Based on Pharmacogenomic Markers.

Introduction: Alcoholic hallucinosis (AH) is one of the severe complications of chronic alcoholism, characterized by psychotic symptoms such as auditory hallucinations and delusions. Haloperidol is widely used to treat AH; however, its therapy is often complicated by side effects. A personalized approach using pharmacogenetic testing (particularly the CYP2D6 polymorphism) allows individualization of haloperidol dosage, improving both safety and efficacy of therapy.

Sorafenib promotes Treg cell differentiation to compromise its efficacy via VEGFR/AKT/Foxo1 signaling in hepatocellular carcinoma.

Unlabelled: Our study revealed that sorafenib (Sora) induced the formation of an immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) by promoting the differentiation of regulatory T (Treg) cells through VEGFR/AKT/Foxo1 signaling, leading to compromised Sora efficacy. Importantly, combination treatment with an anti-CD25 antibody or the Foxo1 inhibitor AS1842856 inhibited Treg cell differentiation and increased the therapeutic efficacy of Sora in HCC.

Background & Aims: Sora is the first-line drug for advanced HCC.

NRP1 instructs IL-17-producing ILC3s to drive colitis progression.

Group 3 innate lymphoid cells (ILC3s) control tissue homeostasis and orchestrate mucosal inflammation; however, the precise mechanisms governing ILC3 activity are fully understood. Here, we identified the transmembrane protein neuropilin-1 (NRP1) as a positive regulator of interleukin (IL)-17-producing ILC3s in the intestine. NRP1 was markedly upregulated in intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) compared with healthy controls.

Roles of blood monocytes carrying TREM2 mutation in pathogenesis of Alzheimer's disease and its therapeutic potential in APP/PS1 mice.

Introduction: The triggering receptor expressed on myeloid cells 2 (TREM2) arginine-47-histidine (R47H) mutation is a significant risk for Alzheimer's disease (AD) with unclear mechanisms. Previous studies focused on microglial amyloid-β (Aβ) phagocytosis with less attention on the impact of TREM2 mutation on blood monocytes.

Methods: Bone marrow transplantation (BMT) models were used to assess the contribution of blood monocytes carrying TREM2 mutation to AD.

Effects of Probiotics on Liver Diseases: Current In Vitro and In Vivo Studies.

Various types of liver or hepatic diseases cause the death of about 2 million people worldwide every year, of which 1 million die from the complications of cirrhosis and another million from hepatocellular carcinoma and viral hepatitis. Currently, the second most common solid organ transplant is the liver, and the current rate represents less than 10% of global transplant requests. Hence, finding new approaches to treat and prevent liver diseases is essential.

Phosphorylation of the prokaryotic histone-like protein H-NS modulates bacterial virulence in Salmonella Typhimurium.

H-NS is a prokaryotic histone-like protein that binds to bacterial chromosomal DNA with important regulatory roles in gene expression. Unlike histone proteins, hitherto post-translational modifications of H-NS are still largely uncharacterized, especially in bacterial pathogens. Salmonella Typhimurium is a primary enteric pathogen and its virulence is mainly dependent on specialized type III secretion systems (T3SSs), which were evolutionarily acquired via horizontal gene transfer.

Insights into genetic aberrations and signalling pathway interactions in chronic lymphocytic leukemia: from pathogenesis to treatment strategies.

Chronic lymphocytic leukemia (CLL) is prevalent in adults and is characterized by the accumulation of mature B cells in the blood, bone marrow, lymph nodes, and spleens. Recent progress in therapy and the introduction of targeted treatments [inhibitors of Bruton's tyrosine kinase (BTKi) or inhibitor of anti-apoptotic B-cell lymphoma-2 (Bcl-2i) protein (venetoclax)] in place of chemoimmunotherapy have significantly improved the outcomes of patients with CLL. These advancements have shifted the importance of traditional predictive markers, leading to a greater focus on resistance genes and reducing the significance of mutations, such as TP53 and del(17p).

[Issues of treatment and prevention of recurrent inflammatory diseases of the upper respiratory tract: An immunologist's view. A review].

Often ill people are, first of all, patients with recurrent infectious and inflammatory diseases of the upper respiratory tract (URT). They put a significant financial burden on the healthcare system. The leading etiological factors of recurrent inflammatory diseases of URT, in addition to pathogenic bacterial microflora, are viral agents (viruses of the viral respiratory infections group, herpes viruses).

Genetic Association of Juvenile Idiopathic Arthritis With Adult Rheumatic Disease.

Importance: Patients with juvenile idiopathic arthritis (JIA) may develop adult rheumatic diseases later in life, and prolonged or recurrent disease activity is often associated with substantial disability; therefore, it is important to identify patients with JIA at high risk of developing adult rheumatic diseases and provide specialized attention and preventive care to them.

Objective: To elucidate the full extent of the genetic association of JIA with adult rheumatic diseases, to improve treatment strategies and patient outcomes for patients at high risk of developing long-term rheumatic diseases.

Design, Setting, And Participants: In this genetic association study of 4 disease genome-wide association study (GWAS) cohorts from 2013 to 2024 (JIA, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], and systemic sclerosis [SSc]), patients in the JIA cohort were recruited from the US, Australia, and Norway (with a UK cohort included in the meta-analyzed cohort), while patients in the other 3 cohorts were recruited from US and Western European countries.

Rat Models in Post-Traumatic Stress Disorder Research: Strengths, Limitations, and Implications for Translational Studies.

Post-Traumatic Stress Disorder (PTSD) is a multifaceted psychiatric disorder triggered by traumatic events, leading to prolonged psychological distress and varied symptoms. Rat models have been extensively used to explore the biological, behavioral, and neurochemical underpinnings of PTSD. This review critically examines the strengths and limitations of commonly used rat models, such as single prolonged stress (SPS), stress-re-stress (S-R), and predator-based paradigms, in replicating human PTSD pathology.