N6-methyladenosine (m⁶A), the most abundant internal RNA modification in eukaryotes, plays a critical role in post-transcriptional regulation. METTL14, a core component of the methyltransferase complex, emerges as a key epigenetic regulator with diverse functions in physiology and disease. Accumulating evidence reveals that METTL14 governs pyroptosis, a pro-inflammatory form of programmed cell death, via m⁶A-dependent mechanisms across various diseases, including neurological, cardiovascular, skeletal, and metabolic disorders. Importantly, m⁶A modification is implicated in multiple forms of regulated cell death beyond pyroptosis, such as apoptosis, ferroptosis, and necroptosis, highlighting the broad regulatory potential of METTL14 in cell fate decisions.This review systematically synthesizes the current knowledge on how METTL14 modulates pyroptosis by targeting key components (e.g., NLR Family Pyrin Domain Containing 3 (NLRP3), gasdermin D (GSDMD)) or regulatory non-coding RNAs, thereby influencing disease progression. We highlight the context-dependent duality of METTL14, which can either promote or suppress pyroptosis depending on the specific pathological milieu. Furthermore, we discuss the associated challenges and future therapeutic prospects, emphasizing the need for context-specific strategies, advanced drug delivery systems, and integrated multi-omics approaches to harness the potential of targeting METTL14 in treating inflammatory and degenerative diseases.

Macroautophagy/autophagy, an evolutionarily conserved cellular degradation pathway, involves phagophores that sequester cytoplasmic constituents and mature into autophagosomes for subsequent lysosomal delivery. The ATG8 gene family, comprising the MAP1LC3/LC3 and GABARAP/GBR subfamilies in mammals, encodes ubiquitin-like proteins that are conjugated to phagophore membranes during autophagosome biogenesis. A central question in the field is how Atg8-family proteins are precisely involved in autophagosome formation, which remains controversial and challenging, at least in part due to the short lifespan of phagophores. In this study, we depleted the autophagosome closure regulator VPS37A to arrest autophagy at the vesicle completion step and determined the roles of mammalian Atg8-family proteins (mATG8s) in nutrient starvation-induced autophagosome biogenesis. Our investigation revealed that LC3 loss hinders phagophore formation, while GBR loss impedes both phagophore formation and expansion. The defect in membrane expansion by GBR loss appears to be attributed to compromised recruitment of ATG proteins containing an LC3-interacting region (LIR), including ULK1 and ATG3. Moreover, a combined deficiency of both LC3 and GBR subfamilies nearly completely inhibits phagophore formation, highlighting their redundant regulation of this process. Consequently, cells lacking all mATG8 members exhibit defects in downstream events such as ESCRT recruitment and autophagic flux. Collectively, these findings underscore the critical roles of mammalian Atg8-family proteins in phagophore formation and expansion during autophagy.Abbreviation: AIM: Atg8-family interacting motif; ADS: Atg8-interacting motif docking site; ATG: autophagy related; BafA1: bafilomycin A1; CL: control; ESCRT: endosomal sorting complex required for transport; FACS: fluorescence activated cell sorting; GBR: GABARAP; GBRL1: GABARAPL1; GBRL2: GABARAPL2; GBRL3: GABARAPL3; HKO: hexa-knockout; IP: immunoprecipitation; KO: knockout; LDS: LC3-interacting-region docking site; LIR: LC3-interacting region; mATG8: mammalian Atg8-family protein; MIL: membrane-impermeable ligands; MPL: membrane-permeable ligands; RT: room temperature; Stv: starved; TKO: triple-knockout; TMR: tetramethylrhodamine; UEVL: ubiquitin E2 variant-like; WCLs: whole cell lysates; WT: wild-type.

Ferroptosis is an iron-dependent, lipid peroxidation-driven form of regulated cell death that is mechanistically distinct from apoptosis and necrosis. In cancer, it plays a dual role: it can act as a tumor suppressor mechanism, yet may also contribute to therapy resistance and immune modulation. Methyltransferase-like 14 (METTL14), a key subunit of the N6-methyladenosine (m6A) methyltransferase complex, post-transcriptionally regulates gene expression by influencing RNA stability, splicing, and translation. Emerging evidence reveals that METTL14 modulates ferroptosis in a context-dependent manner by targeting core regulators, including Solute Carrier Family 7 Member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), and ferroptosis suppressor protein 1 (FSP1), through m6A modification. This review synthesizes recent progress on the METTL14-ferroptosis axis across multiple cancer types, such as colorectal, esophageal, hepatocellular, non-small cell lung, endometrial, and cervical cancers. We systematically outline the molecular mechanisms through which METTL14 either promotes or inhibits ferroptosis and evaluate its therapeutic relevance. Challenges and future perspectives for targeting this regulatory axis in oncology are also discussed.

Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that exhibits both transcriptional activation and inhibition effects. It participates in the occurrence and development of various diseases by regulating processes such as cell cycle arrest, differentiation, and the maintenance of stem cell pluripotency. Autophagy, as a conserved lysosome dependent degradation pathway in eukaryotes, maintains cellular homeostasis by clearing abnormal proteins and damaged organelles. Its dysfunction is closely related to tumors, neurodegenerative diseases, metabolic disorders, and so on. Growing evidence indicates that KLF4 participates in multiple physiological and pathological processes through regulating autophagy, however, the underlying mechanisms are not fully understood. This article systematically reviewed the understanding of KLF4 and autophagy in recent years, critically synthesized the complex and context-dependent roles of KLF4-mediated autophagy regulation in different physiological and pathological processes, and analyzed the relevant molecular mechanisms, with an emphasis on identifying overarching regulatory patterns and functional consequences, hoping to provide theoretical basis for future in-depth research.

N6-Methyladenosine (m6A), the most prevalent internal modification in eukaryotic messenger RNA (mRNA), plays crucial, context-dependent (e.g., tumor type, stage, or microenvironmental conditions like hypoxia) roles in cancers. Its dynamics are governed in part by the "eraser" protein alkB homolog 5 (ALKBH5), an Fe2+/α-ketoglutarate-dependent dioxygenase that removes m6A marks to regulate mRNA stability and translation. ALKBH5 activity is intricately modulated by its structural domains double-stranded β-helical (DSBH) and post-translational modifications (such as Small Ubiquitin-like Modifier modification (SUMOylation) and phosphorylation). Furthermore, it is regulated through interactions with RNA-binding proteins and non-coding RNAs (such as microRNAs(miRNAs) and circular RNAs(circRNAs)), as well as microenvironmental cues (such as hypoxia and oxidative stress). Crucially, ALKBH5 exerts the dualistic control over autophagy, a conserved lysosomal degradation pathway critical for cellular homeostasis, which paradoxically suppresses early tumorigenesis yet promotes progression and therapy resistance in established cancers. This review aims to synthesize recent paradigm-shifting advances elucidating the complex interplay between ALKBH5-mediated epitranscriptomic regulation and autophagy in cancers. We comprehensively examine the molecular structure and multifaceted regulatory networks of ALKBH5, delve into the core mechanisms linking ALKBH5 to autophagy machinery (such as. ALKBH5/epidermal growth factor receptor (EGFR)-phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR), ALKBH5/B-cell lymphoma-2 (BCL-2)/Beclin1, ALKBH5/ATP-binding cassette transporter A1 (ABCA1), ALKBH5/fatty acid binding protein 5 (FABP5)/fatty acid synthase (FASN), ALKBH5/tetraspanin 1 (TSPAN1), ALKBH5/yin yang 1 (YY1)/Autophagy-related protein 4B (ATG4B) pathways), explicitly highlighting their opposing impacts in specific malignancies: for instance, autophagy suppression driving progression in ovarian cancer (ALKBH5/EGFR-PI3K-AKT-mTOR, ALKBH5/BCL-2/Beclin1) versus autophagy activation exerting tumor-suppressive effects in colorectal cancer (ALKBH5/FABP5/FASN) and gastric cancer (ALKBH5/YY1/ATG4B). Finally, we discuss the therapeutic implications of targeting the ALKBH5-autophagy axis, identify unresolved mechanistic questions and knowledge gaps, and outline future research directions for leveraging this pathway in precision cancer therapy.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide, and its exact pathogenesis has not been fully studied. Hydrogen sulfide (H2S) is the third gas signaling molecule discovered in mammals, following nitric oxide and carbon monoxide. It has the effects of anti-inflammation, anti-apoptosis, and so on, thereby playing an important role in many diseases. However, the role and mechanism of exogenous H2S in NAFLD are not fully understood. In this study, we constructed in vitro and in vivo NAFLD models by feeding mice a high-fat diet and stimulating hepatocytes with palmitic acid, respectively, to investigate the improvement effect and mechanism of exogenous H2S on NAFLD. The results showed that NaHS (a donor of H2S) treatment alleviated lipid accumulation, inflammation, apoptosis and pyroptosis, and downregulated endoplasmic reticulum (ER) stress and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NRRP3) inflammasome in NAFLD. The activation of NLRP3 inflammasome weakened NaHS improvement of NAFLD, indicating that exogenous H2S ameliorated NAFLD by inhibiting NLRP3 inflammasome-mediated lipid synthesis, inflammation, apoptosis and pyroptosis. Similarly, the activation of ER stress weakened NaHS improvement of NAFLD and NaHS inhibition of NLRP3 inflammasome, indicating that exogenous H2S suppressed NLRP3 inflammasome by downregulating ER stress, thus improving NAFLD. Additionally, the protein expressions of NLRP3 and cleaved caspase-1 were downregulated after inhibiting the reactive oxygen species (ROS)/extracellular signal-regulated kinases (ERK) and ROS/thioredoxin-interacting protein (TXNIP) pathways, indicating that ER stress activated NLRP3 inflammasome through the ROS/ERK and ROS/TXNIP pathways. In conclusion, our results indicated that exogenous H2S inhibited NLRP3 inflammasome-mediated hepatocytes inflammation, lipid synthesis, apoptosis and pyroptosis by downregulating ER stress, thereby improving NAFLD; Furthermore, ER stress activated NLRP3 inflammasome through the ROS/ERK and ROS/TXNIP pathways in NAFLD. ER stress/NLRP3 inflammasome is expected to become a new target of H2S for treating NAFLD.

Eva-1 homolog A (EVA1A) is a transmembrane protein localized on the endoplasmic reticulum and lysosomes. As a key regulator of autophagy and apoptosis, EVA1A regulates neurogenesis, cardioprotection, tumor suppression, and metabolic homeostasis. In this review, we synthesize the multifaceted signaling networks through which EVA1A modulates physiological and pathological processes. These include the PI3K/AKT/mTOR axis (governing neural stem cell maintenance and hepatocellular carcinoma drug resistance), LKB1/AMPK/mTOR pathway (mediating mitochondrial quality control in cardiac injury), mTOR/RPS6KB1 signaling (suppressing glioblastoma proliferation via autophagy-apoptosis crosstalk), and the Hippo-YAP/TAZ cascade (influencing epithelial-mesenchymal transition in thyroid cancer). Crucially, EVA1A exhibits context-dependent dual roles: promoting autophagic flux for homeostasis or triggering apoptosis under stress. Most of these findings are derived from preclinical studies using cell lines and animal models, with limited validation in human tissues or clinical cohorts.We emphasize EVA1A paradoxical effects in cancers, where EVA1A acts as either a tumor suppressor or a modulator of therapy resistance, depending on the tissue-specific microenvironment. Furthermore, EVA1A’s involvement in neurodegenerative and metabolic diseases, such as Alzheimer’s, Parkinson’s, obesity, and diabetes, remains underexplored, despite its relevance to autophagy and inflammation. Understanding the spatiotemporal dynamics of EVA1A interactions with autophagy-related complexes (such as ATG16L1/ATG5/ATG12) and stress-responsive pathways is important to explore its therapeutic potential. However, EVA1A-targeted therapy is still in the early discovery phase, with no current clinical applications.Future studies should focus on the molecular crosstalk between EVA1A-mediated autophagy and metabolic/inflammatory pathways, aiming to facilitate EVA1A-targeted therapeutic development.

Autophagy is a conservative process of self degradation, in which abnormal organelles, proteins and other macromolecules are encapsulated and transferred to lysosomes for subsequent degradation. It maintains the intracellular balance, and responds to cellular conditions such as hunger or stress. To date, there are mainly three types of autophagy: macroautophagy, microautophagy and chaperone-mediated autophagy. Autophagy plays a key role in regulating multiple physiological and pathological processes, such as cell metabolism, development, energy homeostasis, cell death and hunger adaptation, and so on. Increasing evidence indicates that autophagy dysfunction participates in many kinds of cancers, such as liver cancer, pancreatic cancer, prostate cancer, and so on. However, the relevant mechanisms are not yet fully understood. Baicalin is a natural flavonoid compound extracted from the traditional Chinese medicine Scutellaria baicalensis. The research has shown that after oral or intravenous administration of baicalin, it is delivered to various organs through the systemic circulation, with the highest volume in the kidneys and lungs. More and more evidence suggests that baicalin has antioxidant, anticancer, anti-inflammatory, anti-apoptotic, immunomodulatory and antiviral effects. Therefore, baicalin plays an important role in various diseases, such as cancers, lung diseases, liver diseases, cardiovascular diseases, ans so on. However, the relevant mechanisms have not yet been fully clear. Recently, increasing evidence indicates that baicalin participates in different cancer by regulating autophagy. Herein, we reviewed the current knowledge about the role and mechanism of baicalin regulation of autophagy in multiple types of cancers to lay the theoretical foundation for future related researches.

Ischemia-reperfusion injury (IRI) is a critical pathological process affecting multiple organs, including the heart, brain, kidney, and liver. Recent studies have highlighted the dual roles of AlkB homolog 5 (ALKBH5), an N6-methyladenosine (m⁶A) RNA demethylase, in regulating cellular responses to IRI through epigenetic mechanisms. This review synthesizes current evidence on ALKBH5 involvement in metabolic reprogramming, autophagy, apoptosis, pyroptosis, and inflammation across organ-specific IRI models. We establish a unifying framework in which ALKBH5 functions as a double-edged sword, exerting either protective effects (such as sirtuin 1 (SIRT1) activation in the heart) or detrimental outcomes (such as tricarboxylic acid (TCA) cycle suppression), depending on tissue-specific microenvironments, disease stage dynamics, and downstream effector crosstalk (e.g., TCA cycle, SIRT1, PANoptosis). Despite its therapeutic potential, challenges in translation persist due to ALKBH5’s bidirectional effects and the lack of tissue-specific delivery systems. Future research should aim to resolve these controversies through advanced techniques such as single-cell m⁶A epitranscriptomics and develop spatiotemporally targeted modulators for precise intervention.

The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome consists of pro-caspase-1, NLRP3 and apoptosis-related speckle-like protein (ASC). It can detect multiple microorganisms, endogenous danger signals and environmental stimulus including adenosine triphosphate (ATP), urate, cholesterol crystals, and so on, thereby forming activated NLRP3 inflammasome. During the course of the activation of NLRP3 inflammasome, pro-caspase-1 is transformed into activated caspase-1 that results in the maturation and secretion of interleukin-1beta (IL-1β) and IL-18. The dysfunction of NLRP3 inflammasome participates in multiple diseases such as liver diseases, renal diseases, nervous system diseases and diabetes. Baicalin is the primary bioactive component of Scutellaria baicalensis, which has been used since ancient times. Baicalin has many types of biological functions, such as anti-bacterial, anti-tumor and antioxidant. More and more evidence suggests that baicalin regulation of NLRP3 inflammasome is involved in different diseases. However, the mechanism is still elusive. Here, we reviewed the progress of baicalin regulation of NLRP3 inflammasome in many kinds of diseases to lay a foundation for future researches.

MicroRNAs (miRNAs) are the short endogenous non-coding RNAs that regulate the expression of the target gene at posttranscriptional level through degrading or inhibiting the specific target messenger RNAs (mRNAs). MiRNAs regulate the expression of approximately one-third of protein coding genes, and in most cases inhibit gene expression. MiRNAs have been reported to regulate various biological processes, such as cell proliferation, apoptosis and differentiation. Therefore, miRNAs participate in multiple diseases, including ischemia-reperfusion (I/R) injury. Hydrogen sulfide (H2S) was once considered as a colorless, toxic and harmful gas with foul smelling. However, in recent years, it has been discovered that it is the third gas signaling molecule after carbon monoxide (CO) and nitric oxide (NO), with multiple important biological functions. Increasing evidence indicates that H2S plays a vital role in I/R injury through regulating miRNA, however, the mechanism has not been fully understood. In this review, we summarized the current knowledge about the role of H2S in I/R injury by regulating miRNAs, and analyzed its mechanism in detail.

Necroptosis is a programmed cell death form executed by receptor-interacting protein kinase (RIPK) 1, RIPK3 and mixed lineage kinase domain-like protein (MLKL), which assemble into an oligomer called necrosome. Accumulating evidence reveals that necroptosis participates in many types of pathological processes. Hence, clarifying the mechanism of necroptosis in pathological processes is particularly important for the prevention and treatment of various diseases. For over 300 years, hydrogen sulfide (H2S) has been widely known in the scientific community as a toxic and foul-smelling gas. However, after discovering the important physiological and pathological functions of H2S, human understanding of this small molecule changed, believing that H2S is the third gas signaling molecule after carbon monoxide (CO) and nitric oxide (NO). H2S plays an important role in various diseases, but the related mechanisms are not yet fully understood. In recent years, more and more studies have shown that H2S regulation of necroptosis is involved in various pathological processes. Herein, we focus on the recent progress on the role of H2S regulation of necroptosis in different pathological processes and profoundly analyze the related mechanisms.

Pyroptosis is one kind of programmed cell death in which the cell membrane ruptures and subsequently releases cell contents and pro-inflammatory cytokines including IL-1β and IL-18. Pyroptosis is caused by many types of pathological stimuli, such as hyperglycemia (HG), oxidative stress, and inflammation, and is mediated by gasdermin (GSDM) protein family. Increasing evidence indicates that pyroptosis plays an important role in multiple diseases, such as cancer, kidney diseases, inflammatory diseases, and cardiovascular diseases. Therefore, the regulation of pyroptosis is crucial for the occurrence, development, and treatment of many diseases. Hydrogen sulfide (H2S) is a biologically active gasotransmitter following carbon monoxide (CO) and nitrogen oxide (NO) in mammalian tissues. So far, three enzymes, including 3‐mercaptopyruvate sulphurtransferase (3-MST), cystathionine γ- Lyase (CSE), and Cystine β-synthesis enzyme (CBS), have been found to catalyze the production of endogenous H2S in mammals. H2S has been reported to have multiple biological functions including anti-inflammation, anti-oxidative stress, anti-apoptosis and so on. Hence, H2S is involved in various physiological and pathological processes. In recent years, many studies have demonstrated that H2S plays a critical role by regulating pyroptosis in various pathological processes, such as ischemia-reperfusion injury, alcoholic liver disease, and diabetes cardiomyopathy. However, the relevant mechanism has not been completely understood. Therefore, elucidating the mechanism by which H2S regulates pyroptosis in diseases will help understand the pathogenesis of multiple diseases and provide important new avenues for the treatment of many diseases. Here, we reviewed the progress of H2S regulation of pyroptosis in different pathological processes, and analyzed the molecular mechanism in detail to provide a theoretical reference for future related research.

The endoplasmic reticulum (ER) is an important organelle in eukaryotic cells, responsible for a range of biological functions such as the secretion, modification and folding of proteins, maintaining Ca2+ homeostasis and the synthesis of steroids/lipids, secreted proteins and membrane proteins. When cells are affected by internal or external factors, including abnormal energy metabolism, disrupted Ca2+ balance, altered glycosylation, drug toxicity, and so on, the unfolded or misfolded proteins accumulate in the ER, leading to the unfolded protein response (UPR) and ER stress. The abnormal ER stress has been reported to be involved in various pathological processes. MicroRNAs (miRNAs) are non-coding RNAs with the length of approximately 19-25 nucleotides. They control the expression of multiple genes through posttranscriptional gene silencing in eukaryotes or some viruses. Increasing evidence indicates that miRNAs are involved in various cellular functions and biological processes, such as cell proliferation and differentiation, growth and development, and metabolic homeostasis. Hence, miRNAs participate in multiple pathological processes. Recently, many studies have shown that miRNAs play an important role by regulating ER stress in ischemia-reperfusion (I/R) injury, but the relevant mechanisms are not fully understood. In this review, we reviewed the current understanding of ER stress, as well as the biogenesis and function of miRNAs, and focused on the role of miRNAs regulation of ER stress in I/R injury, with the aim of providing new targets for the treatment of I/R injury.

NLRP3 inflammasome is a key component of the innate immune system, mediating the activation of caspase-1, and the maturity and secretion of the pro-inflammatory cytokine interleukin (IL)-1beta (IL-1β) and IL-18 to cope with microbial infections and cell injury. The NLRP3 inflammasome is activated by various endogenous danger signals, microorganisms and environmental stimuli, including urate, extracellular adenosine triphosphate (ATP) and cholesterol crystals. Increasing evidence indicates that the abnormal activation of NLRP3 is involved in multiple diseases including renal diseases. Hence, clarifying the mechanism of action of NLRP3 inflammasome in different diseases can help prevent and treat various diseases. Endoplasmic reticulum (ER) is an important organelle which participates in cell homeostasis maintenance and protein quality control. The unfolded protein response (UPR) and ER stress are caused by the excessive accumulation of unfolded or misfolded proteins in ER to recover ER homeostasis. Many factors can cause ER stress, including inflammation, hypoxia, environmental toxins, viral infections, glucose deficiency, changes in Ca2+ level and oxidative stress. The dysfunction of ER stress participates in multiple diseases, such as renal diseases. Many previous studies have shown that NLRP3 inflammasome and ER stress play an important role in renal diseases. However, the relevant mechanisms are not yet fully clear. Herein, we focus on the current understanding of the role and mechanism of ER stress and NLRP3 inflammasome in renal diseases, hoping to provide theoretical references for future related researches.

Ferroptosis is a programmed cell death that relies on iron and lipid peroxidation. It differs from other forms of programmed cell death such as necrosis, apoptosis and autophagy. More and more evidence indicates that ferroptosis participates in many types of diseases, such as neurodegenerative diseases, ischemia-reperfusion injury, cardiovascular diseases and so on. Hence, clarifying the role and mechanism of ferroptosis in diseases is of great significance for further understanding the pathogenesis and treatment of some diseases. Hydrogen sulfide (H2S) is a colorless and flammable gas with the smell of rotten eggs. Many years ago, H2S was considered as a toxic gas. however, in recent years, increasing evidence indicates that it is the third important gas signaling molecule after nitric oxide and carbon monoxide. H2S has various physiological and pathological functions such as antioxidant stress, anti-inflammatory, anti-apoptotic and anti-tumor, and can participate in various diseases. It has been reported that H2S regulation of ferroptosis plays an important role in many types of diseases, however, the related mechanisms are not fully clear. In this review, we reviewed the recent literature about the role of H2S regulation of ferroptosis in diseases, and analyzed the relevant mechanisms, hoping to provide references for future in-depth researches. Whether H2S can regulate cell ferroptosis through selective autophagy other than ferritinophagy is a topic worth studying in the future; The role and mechanism of H2S regulation of ferroptosis in various tumors require future research to elucidate. Further researches are needed to determine whether different concentrations of H2S can promote ferroptosis in different tissues and disease types.

Hepatocellular carcinoma (HCC) is a major type of liver cancer and an important cause of cancer death. It has been reported that the hepatocyte death plays an important role in HCC. Ferroptosis is an iron-dependent programmed cell death characterized by the accumulation of free iron and lipid peroxidation. A series of studies have shown that ferroptosis contributes to the occurrence and development of HCC. MicroRNAs (miRNAs) are non-coding RNAs with a length of approximately 222 nt. In recent years, miRNAs have been shown to participate in regulating ferroptosis to play a vital role in HCC, but the related mechanisms are not fully understood. This review summarized the current understanding of ferroptosis, as well as the biogenesis and function of miRNAs, and focused on the role of miRNAs regulation of ferroptosis in HCC, with the hope of providing new targets and ideas for the treatment of HCC.

Ferroptosis is a new kind of cell death discovered in recent years, usually accompanied by a large number of lipid peroxidation and iron accumulation in the process of cell death. Ferroptosis has been proven to play an important role in various diseases, including ischemic reperfusion injury, cancer, and neurodegeneration. Therefore, the regulation of ferroptosis will have a vital impact on the occurrence and development of diseases. Baicalin is a flavonoid compound extracted and isolated from the dried roots of Scutellaria baicalensis Georgi, a plant in the family Lamiaceae. It has various biological activities such as antioxidant, anti-proliferative, anti-inflammatory, anti-thrombotic, and regulates apoptosis and ferroptosis. Recently, increasing evidence indicates that baicalin regulation of ferroptosis is involved in multiple diseases. However, the relevant mechanisms are not yet fully understood. Here, we summarized the role of baicalin regulation of ferroptosis in different kinds of diseases, and conducted an in-depth analysis of the relevant mechanisms, hoping to provide the theoretical references for future related researches.

Inflammasomes play an important role in innate immunity. As a signal platform, they deal with the excessive pathogenic products and cellular products related to stress and injury. So far, the best studied and most characteristic inflammasome is the NLR-family pyrin domain-containing protein 3(NLRP3) inflammasome, which is composed of NLRP3, apoptosis associated speck like protein (ASC) and pro-caspase-1. The formation of NLRP3 inflammasome complexes results in the activation of caspase-1, the maturation of interleukin (IL)-1β and IL-18, and pyroptosis. Many studies have demonstrated that NLRP3 inflammasome not only participates in tumorigenesis, but also plays a protective role in some cancers. Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality. Currently, due to the lack of effective treatment methods for HCC, the therapeutic effect of HCC has not been ideal. Therefore, it is particularly urgent to explore the pathogenesis of HCC and find its effective treatment methods. The increasing evidences indicate that NLRP3 inflammasome plays a vital role in HCC, however, the related mechanisms are not fully understood. Hence, we focused on the recent progress about the role of NLRP3 inflammasome in HCC, and analyzed the relevant mechanisms in detail to provide reference for the future in-depth researches.