Effect of Purified Resveratrol Butyrate Ester Monomers against Hypertension after Maternal High-Fructose Intake in Adult Offspring.

Background: Offspring hypertension arising from adverse maternal conditions can be mitigated through dietary nutritional supplementation, including resveratrol. Previously, we identified derivatives of resveratrol butyrate ester (RBE), specifically 3,4'-di-O-butanoylresveratrol (ED2) and 3-O-butanoylresveratrol (ED4), demonstrating their superior antioxidant capabilities compared to RBE itself. This study sought to assess the protective impact of maternal supplementation with ED2 or ED4 on offspring hypertension in a rat model subjected to a high-fructose (HF) diet during pregnancy and lactation.

Promising Experimental Treatment in Animal Models and Human Studies of Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain Syndrome (IC/BPS) remains a mysterious and intricate urological disorder, presenting significant challenges to healthcare providers. Traditional guidelines for IC/BPS follow a hierarchical model based on symptom severity, advocating for conservative interventions as the initial step, followed by oral pharmacotherapy, intravesical treatments, and, in refractory cases, invasive surgical procedures. This approach embraces a multi-tiered strategy.

Impact of Transgenerational Nutrition on Nonalcoholic Fatty Liver Disease Development: Interplay between Gut Microbiota, Epigenetics and Immunity.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent pediatric liver disorder, primarily attributed to dietary shifts in recent years. NAFLD is characterized by the accumulation of lipid species in hepatocytes, leading to liver inflammation that can progress to steatohepatitis, fibrosis, and cirrhosis. Risk factors contributing to NAFLD encompass genetic variations and metabolic disorders such as obesity, diabetes, and insulin resistance.

Carbohydrate-Mediated Pregnancy Gut Microbiota and Neonatal Low Birth Weight.

The effects of gut microbiota on the association between carbohydrate intake during pregnancy and neonatal low birth weight (LBW) were investigated. A prospective cohort study was conducted with 257 singleton-born mother-child pairs in Taiwan, and maternal dietary intake was estimated using a questionnaire, with each macronutrient being classified as low, medium, or high. Maternal fecal samples were collected between 24 and 28 weeks of gestation, and gut microbiota composition and diversity were profiled using 16S rRNA amplicon gene sequencing.

Reprogramming Effects of Postbiotic Butyrate and Propionate on Maternal High-Fructose Diet-Induced Offspring Hypertension.

Maternal nutrition has a key role in the developmental programming of adult disease. Excessive maternal fructose intake contributes to offspring hypertension. Newly discovered evidence supports the idea that early-life gut microbiota are connected to hypertension later in life.

Tumor Vasculature as an Emerging Pharmacological Target to Promote Anti-Tumor Immunity.

Tumor vasculature abnormality creates a microenvironment that is not suitable for anti-tumor immune response and thereby induces resistance to immunotherapy. Remodeling of dysfunctional tumor blood vessels by anti-angiogenic approaches, known as vascular normalization, reshapes the tumor microenvironment toward an immune-favorable one and improves the effectiveness of immunotherapy. The tumor vasculature serves as a potential pharmacological target with the capacity of promoting an anti-tumor immune response.

Lymphocyte Subpopulations Associated with Neutralizing Antibody Levels of SARS-CoV-2 for COVID-19 Vaccination.

The comprehensive knowledge regarding the immune response during coronavirus disease 2019 (COVID-19) vaccination is limited. The aim of this study was to longitudinally investigate not only the dynamic changes of peripheral lymphocyte subpopulations and cytokine levels but parallel changes of antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Blood samples of 20 healthcare workers with two doses of COVID-19 vaccine were prospectively collected.

The AST-120 Recovers Uremic Toxin-Induced Cognitive Deficit via NLRP3 Inflammasome Pathway in Astrocytes and Microglia.

Chronic kidney disease (CKD) is characterized by the progressive loss of renal function; moreover, CKD progression commonly leads to multiple comorbidities, including neurological dysfunction and immune disorders. CKD-triggered neuroinflammation significantly contributes to cognitive impairment. This study aimed to investigate the contribution of uremic toxins to cognitive impairment.

Targeting the JAK-STAT pathway in autoimmune diseases and cancers: A focus on molecular mechanisms and therapeutic potential.

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway is characterized by diverse immune regulatory systems involving cell proliferation, survival, and inflammation and immune tolerance. Aberrant JAK/STAT transduction activates proinflammatory cytokine signaling that jeopardize the immune balance and thus contributes to the development of autoimmune diseases and cancer progression. The success of several small-molecule JAK inhibitors in the treatment of rheumatologic diseases demonstrates that targeting the JAK/STAT pathway is efficient in suppressing inflammation and sheds light on their therapeutic potential in several autoimmune diseases and cancers.

Converged Rab37/IL-6 trafficking and STAT3/PD-1 transcription axes elicit an immunosuppressive lung tumor microenvironment.

Increased IL-6 level, M2 macrophages and PD-1CD8 T cells in tumor microenvironments (TME) have been identified to correlate with resistance to checkpoint blockade immunotherapy, yet the mechanism remains poorly understood. Rab small GTPase-mediated trafficking of cytokines is critical in immuno-modulation. We have previously reported dysregulation of Rab37 in lung cancer cells, whereas the roles of Rab37 in tumor-infiltrating immune cells and cancer immunotherapy are unclear.

Inhibition of PAI-1 Blocks PD-L1 Endocytosis and Improves the Response of Melanoma Cells to Immune Checkpoint Blockade.

Immune checkpoint molecules, especially PD-1 and its ligand PD-L1, act as a major mechanism of cancer immune evasion. Although anti-PD-1/PD-L1 monotherapy increases therapeutic efficacy in melanoma treatment, only a subset of patients exhibits long-term tumor remission, and the underlying mechanism of resistance to PD-1/PD-L1 inhibitors remains unclear. In this study, we demonstrated that cell surface retention of PD-L1 is inversely correlated with PAI-1 expression in vitro, in vivo, and in clinical specimens.

Immunometabolism in systemic lupus erythematosus: Relevant pathogenetic mechanisms and potential clinical applications.

Systemic lupus erythematosus (SLE) is a complex, heterogeneous, systemic autoimmune disease involving a wide array of aberrant innate and adaptive immune responses. The immune microenvironment of SLE promotes the metabolic reprogramming of immune cells, leading to immune dyshomeostasis and triggering autoimmune inflammation. Different immune subsets switch from a resting state to a highly metabolic active state by alternating the redox-sensitive signaling pathway and the involved metabolic intermediates to amplify the inflammatory response, which is critical in SLE pathogenesis.

Plasminogen Activator Inhibitor-1 Secretion by Autophagy Contributes to Melanoma Resistance to Chemotherapy through Tumor Microenvironment Modulation.

Autophagy plays a crucial role in maintenance of cellular homeostasis via intracellular signaling pathways, lysosomal degradation of selective cargo and mediating protein secretion. Dysregulation of autophagy has been implicated in tumorigenesis, tumor progression, and resistance to therapy. However, the mechanism of autophagy-dependent secretion involved in the responsiveness to chemotherapy is poorly understood.

Shaping of Innate Immune Response by Fatty Acid Metabolite Palmitate.

Innate immune cells monitor invading pathogens and pose the first-line inflammatory response to coordinate with adaptive immunity for infection removal. Innate immunity also plays pivotal roles in injury-induced tissue remodeling and the maintenance of tissue homeostasis in physiological and pathological conditions. Lipid metabolites are emerging as the key players in the regulation of innate immune responses, and recent work has highlighted the importance of the lipid metabolite palmitate as an essential component in this regulation.

Signaling Pathways of Type I and Type III Interferons and Targeted Therapies in Systemic Lupus Erythematosus.

Type I and type III interferons (IFNs) share several properties in common, including the induction of signaling pathways, the activation of gene transcripts, and immune responses, against viral infection. Recent advances in the understanding of the molecular basis of innate and adaptive immunity have led to the re-examination of the role of these IFNs in autoimmune diseases. To date, a variety of IFN-regulated genes, termed IFN signature genes, have been identified.

VAMP8, a vesicle-SNARE required for RAB37-mediated exocytosis, possesses a tumor metastasis suppressor function.

We previously identified a metastasis suppressor RAB37 small GTPase that regulated exocytosis of tissue inhibitor of metalloproteinases 1 (TIMP1) to suppress lung cancer metastasis. Here, we show that vesicle-associated membrane protein 8 (VAMP8), a v-SNARE (vesicle soluble N-ethylmaleimide-sensitive factor activating protein receptor), interacts with RAB37 and drives the secretion of TIMP1 to inhibit tumor metastases. Confocal and total internal reflection fluorescence microscopic images demonstrated that VAMP8 co-localized with RAB37 and facilitated trafficking of RAB37-TIMP1 vesicles.

Rab37 mediates exocytosis of secreted frizzled-related protein 1 to inhibit Wnt signaling and thus suppress lung cancer stemness.

Recent studies have revealed that dysregulated Rab small GTPase-mediated vesicle trafficking pathways are associated with cancer progression. However, whether any of the Rabs plays a suppressor role in cancer stemness is least explored. Rab37 has been postulated as a tumor suppressive small GTPase for trafficking anti-tumor cargos.

Rab37 in lung cancer mediates exocytosis of soluble ST2 and thus skews macrophages toward tumor-suppressing phenotype.

Interplay between cancer epithelial cells and the surrounding immune cells shape the tumor microenvironment to promote cancer progression. Tumor-associated macrophages are well recognized for their roles in cancer progression. Accumulating evidence also indicates implication of Rab small GTPase-mediated exocytosis in tumorigenesis.

Phosphorylation of Rab37 by protein kinase C alpha inhibits the exocytosis function and metastasis suppression activity of Rab37.

We previously identified a novel Rab small GTPase protein, Rab37, which plays a critical role in regulating exocytosis of secreted glycoproteins, tissue inhibitor of metalloproteinases 1 (TIMP1) to suppress lung cancer metastasis. Patients with preserved Rab37 protein expression were associated with better prognosis. However, a significant number of the patients with preserved Rab37 expression showed poor survival.

Dysregulation of Rab37-Mediated Cross-talk between Cancer Cells and Endothelial Cells via Thrombospondin-1 Promotes Tumor Neovasculature and Metastasis.

Accumulating evidence indicates that factors secreted by cancer epithelial cells shape the tumor microenvironment to promote cancer invasion and metastasis. Recent studies also shed light on alterations of Rab small GTPase-mediated exocytosis in tumorigenesis. However, the mechanisms for Rab-mediated exocytosis in tumor microenvironment remain elusive.

Rab-mediated vesicle trafficking in cancer.

A large group of small Rab GTPases which mediate secretory and endosomal membrane transport, as well as autophagosome biogenesis, are essential components of vesicle trafficking machinery. Specific Rab protein together with the cognate effectors coordinates the dynamics of trafficking pathway and determines the cargo proteins destination. Functional impairments of Rab proteins by mutations or post-translational modifications disrupting the regulatory network of vesicle trafficking have been implicated in tumorigenesis.