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Programmed Cell Death (PCD) is considered to be a pathological form of cell death when mediated by an intracellular program and it balances cell death with survival of normal cells. Pyroptosis, a type of PCD, is induced by the inflammatory caspase cleavage of gasdermin D (GSDMD) and apoptotic caspase cleavage of gasdermin E (GSDME). This review aims to summarize the latest molecular mechanisms about pyroptosis mediated by pore-forming GSDMD and GSDME proteins that permeabilize plasma and mitochondrial membrane activating pyroptosis and apoptosis. We also discuss the potentiality of pyroptosis as a therapeutic target in human diseases. Blockade of pyroptosis by compounds can treat inflammatory disease and pyroptosis activation contributes to cancer therapy.

Resveratrol (RES), a polyphenolic compound present in grapes and red wine, has potential anticancer properties. The present study aimed to examine the effects of resveratrol and its underlying mechanism on hepatocellular carcinoma (HCC) cell lines HepG2, Bel-7402 and SMMC-7721. It was demonstrated that resveratrol inhibited the viability and proliferation of HCC cells assessed by MTT and EdU assays. TUNEL assay revealed that resveratrol induced cell apoptosis by increasing HCC apoptosis rate from 3±0.78% to 16±1.12% with upregulation of B-cell lymphoma (Bcl)-2 associated X, apoptosis regulator and cleaved-poly (ADP-Ribose) polymerase 1 (PARP), and downregulation of Bcl-2, caspase-3, caspase-7 and PARP. As a sirtuin (SIRT) 1 activator, resveratrol elevated SIRT1 protein expression and its enzyme activity and decreased expression levels of phosphorylated (p)-phosphoinositide-3-kinase (PI3K), p-AKT Serine/Threonine Kinase 1 (AKT), and its downstream target p-Forkhead Box O3a in HepG2 cells. Furthermore, inhibition of SIRT1 enzymatic activity by EX527 resulted in increased phosphorylation levels of PI3K and AKT. This demonstrated that resveratrol inhibited the PI3K/AKT pathway by SIRT1 activation. In addition to inhibition of cancer cell migration, tumor suppressor gene DLC1 Rho GTPase activating protein level was upregulated and its phosphorylation was enhanced by AKT with resveratrol treatment. These findings suggested that resveratrol inhibits proliferation and migration through SIRT1 mediated post-translational modification of PI3K/AKT pathway in HCC cells.

The defense mechanisms of the vertebrate brain against infections are at the forefront of immunological studies. Unlike other body parts, the brain not only fends off pathogenic infections but also minimizes the risk of self-damage from immune cell induced inflammation. Some neuropeptides produced by either nerve or immune cells share remarkable similarities with antimicrobial peptides (AMPs) in terms of size, structure, amino acid composition, amphiphilicity, and net cationic charge. These similarities extend to a wide range of antibacterial activities demonstrated in vitro , effectively protecting nerve tissue from microbial threats. This review systematically examines 12 neuropeptides, pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), orexin-B (ORXB), ghrelin, substance P (SP), adrenomedullin (AM), calcitonin-gene related peptide (CGRP), urocortin-II (UCN II), neuropeptide Y (NPY), NDA-1, and catestatin (CST), identified for their antimicrobial properties, summarizing their structural features, antimicrobial effectiveness, and action mechanisms. Importantly, the majority of these antimicrobial neuropeptides (9 out of 12) also possess significant anti-inflammatory properties, potentially playing a key role in preserving immune tolerance in various disorders. However, the connection between this anti-inflammatory property and the brain’s infection defense strategy has rarely been explored. Our review suggests that the combined antimicrobial and anti-inflammatory actions of neuropeptides could be integral to the brain’s defense strategy against pathogens, marking an exciting direction for future research.

The interaction between the neuroendocrine system and the immune system plays a key role in the onset and progression of various diseases. Neuropeptides, recognized as common biochemical mediators of communication between these systems, are receiving increasing attention because of their potential therapeutic applications in immune-related disorders. Additionally, many neuropeptides share significant similarities with antimicrobial peptides (AMPs), and evidence shows that these antimicrobial neuropeptides are directly involved in innate immunity. This review examines 10 antimicrobial neuropeptides, including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), ghrelin, adrenomedullin (AM), neuropeptide Y (NPY), urocortin II (UCN II), calcitonin gene-related peptide (CGRP), substance P (SP), and catestatin (CST). Their expression characteristics and the immunomodulatory mechanisms mediated by their specific receptors are summarized, along with potential drugs targeting these receptors. Future studies should focus on further investigating antimicrobial neuropeptides and advancing the development of related drugs in preclinical and/or clinical studies to improve the treatment of immune-related diseases.

Metformin, a widely used antidiabetic drug, exhibits anticancer effects which are mediated by the phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (AKT) signaling pathway. However, its use in anticancer therapy combined with other natural products remains unclear. Flavone as the core structure of flavonoids has been demonstrated to induce cell apoptosis without causing serious side effect. Murine double minute X (MDMX) inhibits tumor suppressor gene p53 whose function is associated with the PI3K/AKT pathway. The results presented herein revealed that the combination of metformin and flavone significantly inhibited cell viability, and increased apoptosis of human breast cancer cells compared with metformin or flavone alone. The combination decreased the protein expression of MDMX, activated p53 through the PI3K/AKT signaling pathway, regulated p53 downstream target genes Bcl-2 apoptosis regulator, BCL2 associated X apoptosis regulator and cleaved caspase3, subsequently inducing apoptosis in MDA-MB-231 and MCF-7 breast cancer cells. These results indicated that dietary flavone may potentiate breast cancer cell apoptosis induced by metformin, and PI3K/AKT is involved in regulating MDMX/p53 signaling. This data suggests that dietary supplementary of flavone is a promising strategy for metformin mediated anticancer effects.

Tumor suppressor protein deleted in liver cancer 1 (DLC1) is a RhoGTPase-activating protein (RhoGAP) and inhibits cancer cell migration by inactivating downstream target protein RhoA. A few studies have reported the regulations of reactive oxygen species (ROS) on RhoGAP. In this study, we investigated flavone (the core structure of flavonoids)-induced regulation on ROS generation and DLC1/RhoA pathway in MCF-7 and MDA-MB-231 breast cancer cells and explored whether flavone-induced upregulation of DLC1 is mediated by ROS. Our results showed that flavone decreased ROS production and inhibited cell migration through DLC1/RhoA pathway. To further investigate the role of ROS in flavone-induced regulation on DLC1/RhoA pathway, hydrogen peroxide was added to restore the ROS levels. Flavone-induced upregulation of DLC1 expression, downregulation of RhoA activity, and inhibition of cell migration were all restrained by hydrogen peroxide. We also found that flavone increased DLC1 stability by inhibiting DLC1 protein degradation in breast cancer cells. In summary, our study demonstrated that flavone inhibited cell migration through DLC1/RhoA pathway by decreasing ROS generation and suppressed DLC1 degradation in MCF-7 and MDA-MB-231 breast cancer cells.

The aim of our present study was to elucidate the effects of up-regulation and down-regulation of intracellular reactive oxygen species (ROS) level on proliferation, migration, and related molecular mechanism. Breast cancer cells were treated by catalase or H2O2. MTT, colony formation assay, and Hoechst/PI staining were used to evaluate proliferation and apoptosis. The level of intracellular ROS was measured by dichlorodihydrofluorescein diacetate probes. The ability of migration was detected by wound healing. Western blotting and coimmunoprecipitation (co-IP) were used to determine the expression of DLC1 and CAV-1 and their interaction. Our data indicated that up-regulation of intracellular ROS induced by H2O2 significantly inhibited proliferation and induced apoptosis accompanying G1 cell cycle arrest and elevated expression of p53. For cell migration, either up-regulation or down-regulation of ROS induced migration inhibition with reduction of interaction between DLC1 and CAV-1. Our results suggested that up-regulation of intracellular ROS inhibited proliferation by promoting expression of p53 and induced G1 cycle arrest and apoptosis. Fluctuation of ROS inhibited migration through reducing the interaction between DLC1 and CAV-1.

Uncontrolled haemorrhage is a leading cause of trauma-related fatalities, highlighting the critical need for rapid and effective haemostasis. Current haemostatic materials encounter limitations such as slow clotting and weak mechanical strength, while most of bioadhesives compromise their adhesion performance to wet tissues for biocompatibility and degradability. In this study, a molecular self-assembly strategy is proposed, developing a biocompatible and biodegradable protein-based patch with excellent adhesion performance. This strategy utilizes fibrinogen modified with hydrophobic groups to induce self-assembly into a hydrogel, which is converted into a dry patch. The protein patch enhances adhesion performance on the wet tissue through a dry cross-linking method and robust intra/inter-molecular interactions. This patch demonstrates excellent haemostatic efficacy in  both porcine oozing wound and porcine severe acute haemorrhage. It maintains biological functionality, and ensures sustained wound sealing while gradually degrading in vivo, making it a promising candidate for clinical tissue sealing applications. Bioadhesives can be used as potential haemostatic agents. Here, the authors report on a dry crosslinking protein patch, using a molecular self-assembly strategy, to create a biocompatible and biodegradable haemostatic material, demonstrating application in acute haemorrhage models.

Clastic rock aquifer of the coal seam roof often constitutes the direct water-filling aquifer of the coal seam and its water-richness is closely related to the risk of roof water inrush. Therefore, the evaluation of the water-richness of clastic rock aquifer is the basic work of coal seam roof water disaster prevention. This article took the 4th coal seam in Huafeng mine field as an example. It combined the empirical formula method and generalized regression neural network (GRNN) to calculate the development height of water-conducting fracture zone, determined the vertical spatial range of water-richness evaluation. Depth of the sandstone floor, brittle rock ratio, lithological structure index, fault strength index, and fault intersections and endpoints density were selected as the main controlling factors. A combination weighting method based on the analytic hierarchy process (AHP), rough set theory (RS), and minimum deviation method (MD) was proposed to determine the weight of the main controlling factors. Introduced the theory of unascertained measures and confidence recognition criteria to construct an evaluation model for the water-richness of clastic rock aquifers, the study area was divided into three zones: relatively weak water-richness zones, medium water-richness zones, and relatively strong water-richness zones. By comparing with the water inrush points and the water inflow of workfaces, the evaluation model's water yield zoning was consistent with the actual situation, and the prediction effect was good. This provided a new idea for the evaluation of the water-richness of the clastic rock aquifer on the roof of the mining coal seam.

Plant-derived nanovesicles (NVs) and extracellular vesicles (EVs) are the next generation of nanocarrier platforms for biotherapeutics and drug delivery. EVs exist not only in the extracellular space, but also within the cell wall. Due to the limitations of existing isolation methods, the EVs extraction efficiency is low, and a large amount of plant material is wasted, which is of concern for rare and expensive medicinal plants. We proposed and validated a novel method for isolation of plant EVs by enzyme degradation of the plant cell wall to release the EVs. The released EVs can easily be collected. The new method was used for extraction of EVs from the roots of Morinda officinalis (MOEVs). For comparison, nanoparticles from the roots (MONVs) were extracted using the grinding method. The new method yielded a greater amount of MOEVs, and the vesicles had a smaller diameter compared to MONVs. Both MOEVs and MONVs were readily absorbed by endothelial cells without cytotoxic effect and promoted the expression of miR-155. The promotion of miR-155 by MOEVs was dose-dependent. More importantly, we found that MOEVs and MONVs were enriched toward bone tissue. These results support our hypothesis that EVs in plants could be efficiently extracted by enzymatic cell wall digestion and confirm the potential of MOEVs as therapeutic agents and drug carriers.