BACKGROUND:Pancreatic ductal adenocarcinoma (PDAC) is characterized by a highly immunosuppressive tumour microenvironment (TME), which contributes to its resistance to immunotherapy. Although mast cells (MCs) have been implicated in PDAC progression, their functional heterogeneity and candidate signaling models of immune modulation remain poorly understood. METHODS:Through an integrated analysis of multiple single-cell RNA sequencing (scRNA-seq) datasets, we identified a significant enrichment of MCs in PDAC tissues and established a characteristic gene signature (TPSAB1, TPSB2, CPA3, HPGDS, KIT, LTC4S) for their precise identification. RESULTS:Single-cell RNA-seq analysis categorized MCs in PDAC into resting, activated, and proliferating subpopulations. To functionally validate these transcriptomic predictions, in vitro co-culture experiments showed that pancreatic cancer cells promote the activation and proliferation of MCs. Cell-cell communication analysis suggested that activated MCs preferentially interact with regulatory T cells (Tregs) via the MIF-(CD74/CXCR4) signaling axis. This interaction was associated with an immunosuppressive T-cell landscape, characterized by an expanded population of Tregs exhibiting a highly activated immunosuppressive phenotype. Spatial transcriptomics and immunofluorescence validated the confirmed the spatial proximity of MCs and Tregs in PDAC tissues. Clinically, high expression of MC-Treg signature genes correlated with poor patient survival. CONCLUSIONS:Our study suggests that MCs are key orchestrators of immunosuppression in PDAC, predicted to interact with Tregs through the MIF-CD74/CXCR4 axis, offering a novel rationale for targeting the MC-Treg axis in future immunotherapeutic strategies.

Nanoplastics (NPs) are emerging environmental contaminants that are pervasive in ecosystems and consumer products. When ingested orally, they may potentially cause enteric diseases. Although NPs undergo physicochemical alterations through environmental and biological transformations, which can modulate their toxicity in the gastrointestinal tract, most studies have overlooked these changes, as well as the uncertainties regarding their interaction and inflammatory mechanisms among different intestinal cells after entering the intestine. In this research, a Transwell™ co-culture model consisting of differentiated Caco-2 intestinal epithelial monolayers and Raw264.7 macrophages was employed to investigate the uptake, translocation, and inflammatory effects of food-relevant NPs, namely polystyrene (PS), polyvinyl chloride (PVC), and polyethylene terephthalate (PET), following in vitro gastrointestinal digestion. The results demonstrated that gastrointestinal digestion modified the physicochemical properties of PS, PET, and PVC NPs, promoting agglomeration, an increase in surface negative charge, and the formation of protein corona. These changes enhanced cellular uptake by both Caco-2 epithelial cells and Raw264.7 macrophages. Consequently, digested NPs caused more significant barrier disruption and stronger inflammatory responses, characterized by the activation of NF-κB/NLRP3 and an elevated release of IL-6 and IL-1β. These findings underscore the crucial importance of considering realistic digestive transformations and material-specific characteristics in future toxicity assessments of NPs, offering vital insights for evaluating the enteritis risks associated with ingested NPs.

Gastric cancer (GC) is a common gastrointestinal malignancy, with more than one million new cases diagnosed each year. Identifying biomarkers for early diagnosis and prognosis is crucial to improving clinical outcomes. However, existing biomarkers lack sufficient sensitivity and specificity. Gamma-glutamyltransferases (GGTs) are a family of enzymes involved in glutathione metabolism and cancer progression, and recent studies have suggested their potential as tumor markers. Among them, GGT5 (Gamma-glutamyltransferase 5) has been reported to play oncogenic roles in gastrointestinal cancers.This study aims to explore the regulatory relationship between miRNA-4722-3p and GGT5 and its impact on GC progression, evaluating the potential of miRNA-4722-3p as a diagnostic biomarker for GC. Bioinformatics tools, including TargetScan, miRWalk, and miRDB, were used to predict miRNAs that bind to the 3’ untranslated region (UTR) of GGT5. miRNA-4722-3p was selected due to its lowest binding free energy and was validated through dual-luciferase reporter assays. RT-qPCR and Western blotting confirmed that miRNA-4722-3p directly targets and inhibits GGT5 expression in GC cells. Functional assays demonstrated that miRNA-4722-3p upregulation significantly suppressed GC cell proliferation and migration, whereas its downregulation enhanced these processes. Furthermore, miRNA-4722-3p inhibited GGT5 expression through the PI3K/AKT-MAPK-MMPs signaling pathway, reinforcing its suppressive effects. Overall, miRNA-4722-3p and GGT5 may serve as promising biomarkers for the early diagnosis and targeted therapy of gastric cancer. Summary Bioinformatics and experiments identify miR-4722-3p as a gastric cancer biomarker. It suppresses tumor growth/metastasis by targeting oncogene GGT5 and inhibiting the PI3K/AKT-MAPK-MMPs pathway, revealing its tumor-suppressive role and offering a novel therapeutic target.

The continuous accumulation of micro- and nanoplastics in the human living environment and their deposition in various organs of the body have become a global public health concern with the widespread use of plastic products. This review summarizes the main categories of micro- and nanoplastics entering the body through dietary intake and air inhalation, based on human exposure pathways. By integrating existing literature data, this review estimates the daily intake and excretion of micro- and nanoplastics in humans, summarizes evidence regarding their potential deposition patterns in blood cells and hematopoietic-related organs, mainly inferred from animal and in vitro studies, and discusses the possible impacts of such deposition on hematopoietic function. Furthermore, the toxic effects and potential hazards of micro- and nanoplastics on the human hematopoietic system at both cellular and animal levels, along with the underlying molecular mechanisms, are comprehensively reviewed. From the dual perspectives of environmental governance and bodily protection, exploratory research ideas are proposed, including biodegradation strategies and the application of medicinal and edible homologous substances. This review aims to provide insights for reducing the risk of hematopoietic system diseases and preventing harm caused by micro- and nanoplastics to the human body in the future.

Snakebite envenomation has become a global public health challenge due to the widespread distribution of venomous snakes. Snake venom, a complex mixture containing various bioactive components, exhibits distinct characteristics across different families. The core toxic components of snake venom are mainly Three-Finger Toxins (3FTxs), phospholipase A2(PLA2), and proteases, which together form the material basis of the venom’s multidimensional toxicity. Through synergistic effects, they activate common pathological pathways, enabling targeted disruption of multiple human organs., leading to acute injury and even multi-organ failure. Beyond the acute effects, some survivors may experience long-term sequelae such as chronic kidney disease or permanent musculoskeletal damage. Existing research suggests that snake venom may have modulatory effects on the immune system, however, the relevant evidence primarily comes from in vitro experiments or animal models, and its clinical significance requires further validation. In clinical management, treatment for snake envenomation involves immediate wound care, prompt medical attention, and rapid diagnosis to identify the snake species for the timely administration of specific antivenom, and a multidisciplinary collaborative treatment model. Moreover, adjunctive drug therapy is often necessary. Nevertheless, traditional antivenoms still face challenges in addressing local tissue damage and ensuring accessibility in resource-limited regions. This narrative review focuses on three major toxin families of snake venom toxins, analyzing their molecular characteristics and synergistic mechanisms to elucidate how these toxins induce systemic damage affecting the cardiovascular, neurological, and renal systems. It thereby reveals that multi-organ injury caused by snake venom is not an isolated event but rather a systemic process driven by the interplay and synergy of multiple common pathological pathways. This systematic analysis suggests that clinical management should shift from a single-organ treatment approach to a systemic intervention strategy.

Background:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is routinely used for preoperative tissue confirmation; however, its potential for comprehensive lipidomic profiling in a preoperative diagnostic setting remains insufficiently explored. Given the critical role of lipid metabolic reprogramming in PDAC progression, we investigated whether lipidomic alterations could be reliably captured in EUS-FNA-derived specimens. Methods:Paired tumor and adjacent non-tumor tissues obtained via EUS-FNA from 13 PDAC patients were subjected to widely targeted (pseudo-targeted) liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipidomic analysis. Differential lipid species were identified through multivariate and univariate analyses. A composite lipid score was constructed based on principal component loadings. Serum samples from an independent cohort of 30 PDAC patients were included for exploratory projection analysis. Results:A total of 1822 lipid species across 47 lipid classes were detected in EUS-FNA-derived specimens. Tumor tissues displayed coordinated lipid alterations, including accumulation of storage lipids and structural remodeling of fatty acyl chains characterized by elongation and increased unsaturation. These alterations were readily detectable in EUS-FNA-derived specimens. These patterns showed a tendency to distinguish tumor from adjacent non-tumor samples within the FNA cohort. Exploratory projection suggested directionally consistent lipid changes in serum samples. Conclusion:Lipid metabolic remodeling in PDAC can be reliably detected in preoperative EUS-FNA-derived specimens. These findings support the feasibility of lipidomic profiling in minimally invasive diagnostic samples and highlight the translational potential of EUS-FNA-based metabolic assessment.

Acute pancreatitis (AP) is a severe inflammatory disorder of the pancreas, characterized by high morbidity and mortality rates. Despite significant advancements in understanding the pathophysiological mechanisms of AP, current treatment options still face considerable limitations. Recent studies have underscored the therapeutic potential of quercetin, a natural flavonoid, due to its potent antioxidant, anti-inflammatory, and immunomodulatory properties, positioning it as a promising therapeutic candidate for AP. This review explores the effects of quercetin on AP, highlighting its antioxidant activities, its role in immune modulation, and its protective effects on pancreatic tissue. Furthermore, it examines quercetin’s multi-target mechanisms and its advantages over conventional therapies, such as N-acetylcysteine and corticosteroids. Although preliminary studies suggest that quercetin can alleviate inflammation and oxidative stress in AP, clinical evidence remains limited. One of the main challenges for quercetin’s clinical application is its low bioavailability. Future research should focus on strategies to enhance its bioavailability and on conducting large-scale randomized controlled trials to more comprehensively assess its efficacy and safety in the treatment of AP.

Acute lung injury (ALI) is a devastating inflammatory lung disease with high morbidity and mortality. Characterized by diffuse alveolar damage, macrophages infiltration, and pulmonary edema, ALI currently lacks effective therapeutic strategies. Rebastinib is a small molecule inhibitor of the Tie2 receptor and an antineoplastic drug. This study investigated the effects of Rebastinib on lipopolysaccharide (LPS)-induced ALI and GSDMD-mediated pyroptosis and NLRP3 inflammasome activation in vitro and in vivo. Our results revealed that Rebastinib significantly attenuated GSDMD-dependent pyroptosis in macrophages, leading to reduced production of caspase-1, LDH and IL-1β. Mechanistically, Rebastinib promoted NLRP3 ubiquitination, thereby disrupting the connection between ASC and NLRP3 and effectively suppressing NLRP3 inflammasome assembly. Additionally, Rebastinib exhibited effective protection function on alveolar epithelial cells in a co-culture system. Furthermore, Rebastinib administration alleviated lung inflammatory damage in LPS-induced ALI mouse model. These findings suggest that Rebastinib holds promise as a therapeutic candidate for ALI by inhibiting the activation of pyroptosis and NLRP3 inflammasome on macrophages.

Pancreatic cancer is a highly malignant form of cancer that distinguishes itself from other gastrointestinal tumors through significant fibrosis and unique perineural invasion. These characteristics underscore the complexity of neural regulation within the pancreatic cancer Tumor Microenvironment (TME). This review aimed to explore the regulatory mechanisms and crosstalk among stromal cells and their factors within the pancreatic cancer microenvironment. We begin by reviewing the major components of the pancreatic cancer microenvironment, analyzing interactions among crucial cell types, such as Cancer-associated Fibroblasts (CAFs) and immune cells, and revealing the dynamic changes between tumor cells and surrounding nerves, immune, and stromal cells. We discuss the role of neural factors, including the Nerve Growth Factor (NGF) and Brain-derived Neurotrophic Factor (BDNF), in the progression of pancreatic cancer and the mechanisms by which the sympathetic and parasympathetic nervous systems regulate tumor cell growth, migration, and invasion. Interactions among stromal cells, cytokines, and neural factors in the pancreatic cancer microenvironment promote fibrosis and perineural invasion. A deeper understanding of the regulation and crosstalk among components in the pancreatic cancer microenvironment offers new perspectives for inhibiting fibrosis and perineural invasion in pancreatic cancer.

Pancreatic cancer induces intense abdominal pain through the infiltration of cancer cells into surrounding nerve tissues, leading to sensory neuron damage. The research aims to identify pivotal molecules involved in PNI, contributing to clinical strategies that alleviate pain and enhance the quality of life for patients. This study used shRNA interference lentivirus to downregulate LRP1 expression in pancreatic cancer and neural cells, comparing perineural invasion (PNI) and neurotrophic factor level changes. An in vitro co-culture model of pancreatic cancer cells with dorsal root ganglia (DRG) assessed the impact of reduced LRP1 on DRG synaptic growth. Additionally, an animal model of neural invasion studied the effects of LRP1 downregulation on neural function. The mutual attraction between Panc-1 and SK-N-SH cells was suppressed upon the downregulation of LRP1 levels in both cell lines. Subsequent investigations revealed a reduction in the autocrine and paracrine secretion of neurotrophic factors and their receptors between Panc-1 and SK-N-SH with the decrease in LRP1 levels. At the tissue level, a significant inhibition of DRG growth was observed. The reduction of LRP1 expression effectively inhibits pancreatic cancer PNI. Concurrently, levels of neurotrophic factors and their receptors in the tumor-neural microenvironment decrease. Mechanistically, LRP1 knockdown suppressed PI3K/AKT and ERK signaling pathways, leading to reduced GDNF secretion and impaired perineural invasion. LRP1 may act as an important molecule in modulating communication between pancreatic cancer cells and neural tissues. Our study offers new potential targets for the treatment of pancreatic cancer neural invasion.

The H9N2 avian influenza virus (AIV) represents a considerable threat to both poultry industries and public health, not only due to its widespread prevalence but also because of its potential to facilitate the emergence of more virulent influenza strains through genetic reassortment. Recent studies have highlighted the pivotal role of hypoxia-inducible factor 1-alpha (HIF-1α) in viral pathogenesis, immune modulation, and the regulation of inflammatory responses, positioning it as a promising target for antiviral strategies. In this study, we identified that HIF-1α actively contributes to the inflammatory response triggered by H9N2 AIV infection in MH-S cells. Notably, silencing HIF-1α led to reduced morbidity and mortality in infected mouse models, underscoring its involvement in disease progression. Furthermore, we explored the anti-inflammatory potential of Panaxadiol, an potent HIF-1α inhibitor, against H9N2-induced pathology. In vitro, Panaxadiol treatment markedly diminished the production of key pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, by attenuating HIF-1α signaling. Moreover, Panaxadiol mitigates the cGAS-STING signaling activation through suppressing HIF-1α. Additionally, in vivo administration of Panaxadiol alleviated clinical symptoms and lung inflammation in H9N2-infected mice, while simultaneously enhancing alveolar epithelial regeneration, as evidenced by the upregulation of alveolar type II (ATII) cell markers, Abca3 and Sftpb. Collectively, these findings support Panaxadiol as a promising candidate for controlling influenza-associated inflammation and promoting lung repair.

Oncolytic virotherapy represents a highly promising in situ antitumor vaccine, using natural or engineered oncolytic viruses to specifically target and eradicate tumors. Malignant tumors overexpress the surface protein CD24, which signals "don't eat me" to inhibit macrophage phagocytosis of tumor cells. Oncolytic viruses are designed to express CD24 inhibitors to augment tumor elimination, serving as a potential antitumor vaccine for cancer immunotherapy. Therefore, we have developed an engineered oncolytic adenovirus that incorporates interfering RNA targeting CD24 for silencing (oAd-shCD24). The oAd-shCD24 vaccine induces sustained tumor suppression and long-term survival in tumor-bearing mice across various tumor models by inhibiting CD24 expression. Mechanistic analysis demonstrates that oAd-shCD24 increases the quantity of tumor-infiltrating immune cells that possess an activated immune phenotype while reducing the proportion of immunosuppressive cells, thus reshaping the tumor immune microenvironment. The combination of oAd-shCD24 with PD1 inhibitors shows superior antitumor efficacy. In summary, the oAd-shCD24 tumor vaccine exhibits effective antitumor efficacy and may represent a potential antitumor therapeutic agent.

NOTCH receptor 3 (NOTCH3) is known to regulate the transcription of oncogenes or tumor suppressor genes, thereby playing a crucial role in tumor development, invasion, maintenance, and chemotherapy resistance. However, the specific mechanism of how NOTCH3 drives immune infiltration in gastrointestinal cancer remains uncertain. The expression of NOTCH3 was analyzed through Western blot, PCR, Oncomine database, and the Tumor Immune Estimation Resource (TIMER) site. Kaplan-Meier plotter, PrognoScan database, and gene expression profile interactive analysis (GEPIA) were used to assess the impact of NOTCH3 on clinical prognosis. The correlation between NOTCH3 expression and immune infiltration gene markers was investigated using TIMER and GEPIA. NOTCH3 was found to be commonly overexpressed in various types of gastrointestinal tumors and was significantly associated with poor prognosis. Furthermore, the expression level of NOTCH3 showed a significant correlation with the tumor purity of gastrointestinal tumors and the extent of immune infiltration by different immune cells. Our findings suggest that NOTCH3 may act as a crucial regulator of tumor immune cell infiltration and can serve as a valuable prognostic biomarker in gastrointestinal cancers.

Pancreatic cancer is one of the highly malignant gastrointestinal tumors in humans, and patients suffer from cancer pain in the process of cancer. Most patients suffer from severe pain in the later stages of the disease. The latest studies have shown that the main cause of pain in patients with pancreatic cancer is neuroinflammation caused by tumor cells invading nerves and triggering neuropathic pain on this basis, which is believed to be the result of nerve invasion. Peripheral nerve invasion (PNI), defined as the presence of cancer cells along the nerve or in the epineurial, perineural, and endoneurial spaces of the nerve sheath, is a special way for cancer to spread to distant sites. However, due to limited clinical materials, the research on the mechanism of pancreatic cancer nerve invasion has not been carried out in depth. In addition, perineural invasion is considered to be one of the underlying causes of recurrence and metastasis after pancreatectomy and an independent predictor of prognosis. This article systematically reviewed the neural invasion of pancreatic cancer through bioinformatics analysis, clinical manifestations and literature reviews

Nanoplastics (NPs) present in food and water poses a genuine risk of their accumulation in humans through the diet. Preferential contact between ingested NPs and the intestine as well as the liver has the potential to induce enteritis and hepatitis. However, there is still a lack of comprehensive understanding regarding the inter-organ crosstalk between the intestine and liver when exposed to NPs, as well as the underlying signaling pathways involved. In this study, we employed a 21-day mice exposure model to investigate the accumulation profile of PS-NPs and elucidate the mechanism of intestinal and hepatic inflammation induced by NPs. After exposure, notable fluorescent signals originating from PS-NPs were detected not only in the stomach and intestine but also in other organs such as liver, lung, kidney, brain, and testes. Histopathological analysis along with routine blood tests both revealed an acute inflammatory reaction in mice. Further mechanistic investigations demonstrated that PS-NPs activated inflammatory NF-κB/NLRP3 pathways and induced the expression of cytokines IL-1β and IL-18 in the intestine, which recruited macrophages and neutrophils into the intestine. Concurrently, a significant decrease in the expression levels of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1) was observed, resulting in an increase in intestinal permeability and elevated endotoxin (LPS) levels. The high levels of LPS further activated TLR4/NF-κB/NLRP3/GSDMD pathways in the liver, inducing liver inflammation and hepatocyte pyroptosis. The impairment of liver function was positively correlated with intestinal inflammation and barrier disruption. These findings underscore that exposure to NPs can instigate enteritis and hepatitis while emphasizing the crucial role played by the indirect gut-liver axis in elucidating the potential mechanism underlying NP-induced liver pathogenesis.

Background Ethyl acetate extracts from Tetrastigma hemsleyanum (Sanyeqing) (EFT), a member of the Vitaceae plant family, have been shown to exhibit efficacy against a variety of cancers. In this light, our current study seeks to examine the mechanism of efficacy between EFT extracts and human pancreatic cancer PANC-1 cells. Methods The chemical components of EFT were analyzed by gas chromatography–mass spectrometry. The cytotoxicity of EFT on PANC-1 cells was measured using an MTT assay. In order to investigate EFT induction of cell cycle arrest, changes in cell-cycle distribution were monitored by flow cytometry. Wound healing and transwell assays were employed to investigate whether migration and invasion of PANC-1 cells were inhibited by EFT. Relative protein expression was detected using Western blot. Results GC-MS analysis of the chemical composition of EFT revealed that the majority of constituents were organic acids and their corresponding esters. EFT exhibits measurable cytotoxicity and inhibition of PANC-1 invasion. Growth inhibition was primarily attributed to downregulation of CDK2 which induces cell cycle arrest in the S-phase. Inhibition of metastasis is achieved through downregulation of mesenchymal-associated genes/activators, including ZEB1, N-cadherin, Vimentin, and Fibronectin. Meanwhile, the expression of E-cadherin was significantly increased by EFT treatment. Furthermore, downregulation of MMP-2 and MMP-9 were observed. Conclusion Treatment of PANC-1 with EFT demonstrated measurable cytotoxic effects. Furthermore, EFT evoked S phase arrest while inhibiting the migration and invasion of PANC-1 cells. Additionally, EFT inhibited the epithelial to mesenchymal transition and MMPs expression in PANC-1 cells. This study serves to confirm the strong therapeutic potential of EFT while identifying the mechanisms of action.

Background: Staphylococcus aureus is a common pathogenic microorganism in humans and animals. Type II NADH oxidoreductase (NDH-2) is the only NADH:quinone oxidoreductase present in this organism and represents a promising target for the development of anti-staphylococcal drugs. Recently, myricetin, a natural flavonoid from vegetables and fruits, was found to be a potential inhibitor of NDH-2 of S. aureus. The objective of this study was to evaluate the inhibitory properties of myricetin against NDH-2 and its impact on the growth and expression of virulence factors in S. aureus. Results: A screening method was established to identify effective inhibitors of NDH-2, based on heterologously expressed S. aureus NDH-2. Myricetin was found to be an effective inhibitor of NDH-2 with a half maximal inhibitory concentration (IC50) of 2 μM. In silico predictions and enzyme inhibition kinetics further characterized myricetin as a competitive inhibitor of NDH-2 with respect to the substrate menadione (MK). The minimum inhibitory concentrations (MICs) of myricetin against S. aureus strains ranged from 64 to 128 μg/mL. Time–kill assays showed that myricetin was a bactericidal agent against S. aureus. In line with being a competitive inhibitor of the NDH-2 substrate MK, the anti-staphylococcal activity of myricetin was antagonized by MK-4. In addition, myricetin was found to inhibit the gene expression of enterotoxin SeA and reduce the hemolytic activity induced by S. aureus culture on rabbit erythrocytes in a dose-dependent manner. Conclusions: Myricetin was newly discovered to be a competitive inhibitor of S. aureus NDH-2 in relation to the substrate MK. This discovery offers a fresh perspective on the anti-staphylococcal activity of myricetin.

Background:Gastric cancer (GC) is a gastric malignant tumor with over 1 million new cases globally each year. There are many diagnostic methods for GC, but due to the hidden early symptoms of GC, early GC is easy to be missed and misdiagnosed, which affects the follow-up treatment of patients. The early and accurate diagnosis of GC is of great significance for the treatment and survival of GC patients. Our laboratory study found that gamma-glutamyl transferase (GGT) was highly expressed in GC patients, but the mechanism of GGT family genes in the occurrence and development of GC remained to be further studied. Therefore, this study aimed to explore the mechanism of GGT family functional gene GGT5 regulating the proliferation and migration of GC cells, and provide a possible new biomarker for the early diagnosis of GC. Methods:The value of serum GGT in GC patients was first statistically analyzed. Then, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to analyze the mRNA expression of GGT5 in GC, and its clinical relationship and function. Furthermore, expression of GGT5 was reduced by lentivirus RNA interference and verified by polymerase chain reaction (PCR), Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation after GGT5 knockdown. Scratch and Transwell assays were applied to observe cell migration after knockdown of GGT5. Finally, Western blot assays were observed to demonstrate PI3K/AKT-MAPK and MMPs expression levels after knockdown of GGT5. Results:Serum GGT was expressed at a high level in GC patients. GGT5 was highly expressed in GC tissues, and was associated with poor prognosis and clinical stage of GC. GGT5 might be involved in the regulation of vascular development and angiogenesis, as well as in the mechanisms of cell motility and migration, and it was positively correlated with the PI3K/AKT pathway. The proliferation and migration capacity of GC cells was dampened by downregulation of GGT5. GGT5 mediated proliferation and migration of GC cells by directly targeting PI3K/AKT-MAPK-MMPs pathways. Conclusions:Low expression of GGT5 reduced proliferation and migration in GC cells by modulating the PI3K/AKT-MAPK-MMPs pathway, and GGT5 might be a new target for GC.

Thioacetamide (TAA), a widely employed hepatotoxic substance, has gained significant traction in the induction of liver failure disease models. Upon administration of TAA to experimental animals, the production of potent oxidative derivatives ensues, culminating in the activation of oxidative stress and subsequent infliction of severe damage upon multiple organs via dissemination through the bloodstream. This review summarized the various organ damages and corresponding mechanistic explanations observed in previous studies using TAA in toxicological animal experiments. The principal pathological consequences arising from TAA exposure encompass oxidative stress, inflammation, lipid peroxidation, fibrosis, apoptosis induction, DNA damage, and osteoclast formation. Recent in vivo and in vitro studies on TAA bone toxicity have confirmed that long-term high-dose use of TAA not only induces liver damage in experimental animals but also accompanies bone damage, which was neglected for a long time. By using TAA to model diseases in experimental animals and controlling TAA dosage, duration of use, and animal exposure environment, we can induce various organ injury models. It should be noted that TAA-induced injuries have a time-dependent effect. Finally, in our daily lives, especially for researchers, we should take precautions to minimize TAA exposure and reduce the probability of related organ injuries.

Increasing amounts of nanoplastics (NPs) in the environment are a great threat to human health, causing intestinal inflammation when consumed through seafood and water. There is, however, still a lack of understanding of the immunomodulatory role of NPs in immune cells, especially the early signal events behind inflammation resulting from NPs ingestion. In this study, we explored the dynamic internalization of polystyrene NPs and their carboxy and amino-functionalized products (PS, PS-COOH and PS-NH2) followed by activation of ROS-MAPK/NF-κB signaling pathways in macrophage RAW 264.7. The inflammatory and cytotoxic potentials of NPs were evaluated by ELISA and apoptosis assays. Results showed that PS-COOH accumulated most in cells and induced more pronounced ROS and apoptosis than PS, PS-NH2 and PS-μm. PS-COOH and PS-NH2 showed stronger MAPK/NF-κB activation potential to at a low concentration of 10 μg/mL than unmodified PS, followed by production of IL-6 and TNF-α cytokines. Furthermore, PS-COOH induced MAPK/NF-κB activation and cytokine secretion could be inhibited by NAC, indicating that ROS was responsible for signal dysregulation and immunogenicity of PS-COOH, but not for PS-NH2. The results suggested that the MAPK and NF-κB pathways were involved in NPs-induced macrophage inflammation, which was influenced by surface functionalization of NPs, with carboxylated PS NPs exhibiting a greater pro-inflammatory and cytotoxic potential.