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Doxorubicin (DOX), a commonly used chemotherapy drug, is hindered due to its tendency to induce cardiotoxicity (DIC). Ferroptosis, a novel mode of programmed cell death, has received substantial attention for its involvement in DIC. Recently, natural product-derived ferroptosis regulator emerged as a potential strategy for treating DIC. In this review, a comprehensive search was conducted across PubMed, Web of Science, Google Scholar, and ScienceDirect databases to gather relevant articles on the use of natural products for treating DIC in relation to ferroptosis. The available papers were carefully reviewed to summarize the therapeutic effects and underlying mechanisms of natural products in modulating ferroptosis for DIC treatment. It was found that ferroptosis plays an important role in DIC pathogenesis, with dysregulated expression of ferroptosis-related proteins strongly implicated in the condition. Natural products, such as flavonoids, polyphenols, terpenoids, and quinones can act as GPX4 activators, Nrf2 agonists, and lipid peroxidation inhibitors, thereby enhancing cell viability, attenuating myocardial fibrosis, improving cardiac function, and suppressing ferroptosis in both in vitro and in vivo models of DIC. This review demonstrates a strong correlation between DOX-induced cardiac ferroptosis and key proteins, such as GPX4, Keap1, Nrf2, AMPK, and HMOX1. Natural products are likely to exert therapeutic effects against DIC by modulating the activity of these proteins.

The mitochondrial unfolded protein response (UPRmt) is a cytoprotective response in response to cellular stress that is activated in response to mitochondrial stress to maintain intra-protein homeostasis, thereby protecting the cell from a variety of stimuli. The activation of this response has been linked to cardiovascular diseases. Here, we reviewed the current understanding of UPRmt and discussed its specific molecular mechanism, mainly in mammals, as well as addressing its protective role against cardiovascular diseases, so as to provide direction for further research on UPRmt and therapies targeting cardiovascular diseases in the future.

Ginseng, the dried root of Panax ginseng C.A. Mey., is widely used in Chinese herbal medicine. Ginsenosides, the primary active components of ginseng, exhibit diverse anticancer functions through various mechanisms, such as inhibiting tumor cell proliferation, promoting apoptosis, and suppressing cell invasion and migration. In this article, the mechanism of action of 20 ginsenoside subtypes in tumor therapy and the research progress of multifunctional nanosystems are reviewed, in order to provide reference for clinical prevention and treatment of cancer.

Cancer poses a substantial global health challenge, necessitating the widespread use of chemotherapy and radiotherapy. Despite these efforts, issues like resistance development and severe side effects remain. As such, the search for more effective alternatives is critical. Andrographolide, a naturally occurring compound, has recently gained attention for its extensive biological activities. This review explores the role of andrographolide in cancer therapy, especially focusing on the molecular mechanisms that drive its anti-tumor properties. It also examines innovative methods to enhance andrographolide's bioavailability, thus boosting its effectiveness against cancer. Notably, andrographolide has potential for use in combination with various clinical drugs, and both preclinical and clinical studies provide strong evidence supporting its broader anticancer applications. Additionally, this paper proposes future research directions for andrographolide's anti-cancer effects and discusses the challenges in its clinical usage along with current research efforts to address these issues. In summary, this review underscores andrographolide's potential roles and contributes to the development of improved cancer treatment strategies.

Noncoding RNAs (ncRNAs) do not participate in protein-coding. Ferroptosis is a newly discovered form of cell death mediated by reactive oxygen species and lipid peroxidation. Recent studies have shown that ncRNAs such as microRNAs, long noncoding RNAs, circular RNAs, and ferroptosis are involved in the occurrence and development of osteosarcoma (OS). Studies have confirmed that ncRNAs participate in the development of OS by regulating the ferroptosis. However, systematic summary on this topic are still lacking. This review summarises the potential role of ncRNAs in the diagnosis, treatment, drug resistance, and prognosis of OS and the basis for diagnosing, preventing, and treating clinical OS and developing effective drugs. This review summarises the latest research progress on ncRNAs that regulate ferroptosis in OS, attempts to clarify the molecular mechanisms by which ncRNAs regulate ferroptosis in the pathogenesis of OS, and elaborates on the involvement of ferroptosis in OS from the perspective of ncRNAs.

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP’s natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases.

RNA methylation modifications are widespread in eukaryotes and prokaryotes, with N6-methyladenosine (m6A) the most common among them. Demethylases, including Fat mass and obesity associated gene (FTO) and AlkB homolog 5 (ALKBH5), are important in maintaining the balance between RNA methylation and demethylation. Recent studies have clearly shown that demethylases affect the biological functions of tumors by regulating their m6A levels. However, their effects are complicated, and even opposite results have appeared in different articles. Here, we summarize the complex regulatory networks of demethylases, including the most important and common pathways, to clarify the role of demethylases in tumors. In addition, we describe the relationships between demethylases and the tumor microenvironment, and introduce their regulatory mechanisms. Finally, we discuss evaluation of demethylases for tumor diagnosis and prognosis, as well as the clinical application of demethylase inhibitors, providing a strong basis for their large-scale clinical application in the future.

Angiogenesis is the growth of new blood vessels on preexisting ones. It is the outcome of a multifactorial effect involving several cells, which can be brought on by different stress reactions.The accumulation of unfolded proteins in the endoplasmic reticulum occurs when cells are stressed due to environmental changes, where physical or chemical stimuli induce endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR), a homeostasis response designed to re-establish protein balance. Ferroptosis is a planned death of lipid peroxidation and anomalies in metabolism that is dependent on iron. Large concentrations of iron ions accumulate there, along with high concentrations of lipid peroxides and reactive oxygen species, all of which can contribute to the development of several diseases. Through the production of growth factors, adhesion factors, and inflammatory factors that trigger the start of angiogenesis, both UPR and Ferroptosis can be implicated in angiogenesis.To set the stage for further research on angiogenesis, this work concentrated on the effects of Ferroptosis and UPR on angiogenesis, respectively.

Optineurin (OPTN) is a widely expressed multifunctional articulatory protein that participates in cellular or mitochondrial autophagy, vesicular transport, and endoplasmic reticulum (ER) stress via interactions with various proteins. Skeletal development is a complex biological process that requires the participation of various osteoblasts, such as bone marrow mesenchymal stem cells (BMSCs), and osteogenic, osteoclastic, and chondrogenic cells. OPTN was recently found to be involved in the regulation of osteoblast activity, which affects bone metabolism. OPTN inhibits osteoclastogenesis via signaling pathways, including NF-κB, IFN-β, and NRF2. OPTN can promote the differentiation of BMSCs toward osteogenesis and inhibit lipogenic differentiation by delaying BMSC senescence and autophagy. These effects are closely related to the development of bone metabolism disorders, such as Paget's disease of bone, rheumatoid arthritis, and osteoporosis. Therefore, this review aims to explore the role and mechanism of OPTN in the regulation of bone metabolism and related bone metabolic diseases. Our findings will provide new targets and strategies for the prevention and treatment of bone metabolic diseases.

Currently, cancer is one of the main research topics, due to its high incidence and drug resistance to existing anti-cancer drugs. Formononetin, a natural product with phytoestrogenic properties and diverse biological functions, has attracted the attention of researchers working on anticancer drugs. Formononetin emerges as an intriguing bioactive substance compared to other isoflavones as it exhibits potent chemotherapeutic activity with less toxicity. Formononetin effectively plays a significant role in inhibiting cell proliferation, invasion, and metastatic abilities of cancer cells by targeting major signaling pathways at the junction of interconnected pathways. It also induces apoptosis and cell cycle arrest by modulating mediator proteins. It causes upregulation of key factors such as p-AKT, p38, p21, and p53 and downregulation of NF-κB. Furthermore, formononetin regulates the neoplastic microenvironment by inactivating the ERK1/2 pathway and lamin A/C signaling and has been reported to inactivate JAK/STAT, PKB or AKT, and mitogen-activated protein kinase pathways and to suppress cell migration, invasion, and angiogenesis in human cancer cells. To assist researchers in further exploring formononetin as a potential anticancer therapeutic candidate, this review focuses on both in vitro and in vivo proof of concept studies, patents, and clinical trials pertinent to formononetin's anticancer properties. Overall, this review discusses formononetin from a comprehensive perspective to highlight its potential benefits as an anticancer agent.

Ferroptosis is an iron-dependent regulated cell death, mainly manifested by the production of reactive oxygen species and accumulation of lipid peroxides. It is distinct from other forms of cell death with regard to morphology and biochemistry, particularly in disrupting mitochondrial function. Mitochondria are essential compartments where the organism generates energy and are closely associated with the fate of ferroptosis. Currently, researchers focus on the potential value of ferroptosis and mitochondria for overcoming drug sensitivity and assisting in cancer therapy. In this review, we summarize the main mechanisms of ferroptosis (the GPX4-realated pathway, FSP1-related pathway, and iron metabolism pathway) and the functions and regulating pathways of mitochondria (the TCA cycle, oxidative phosphorylation, mitochondrial regulation of iron ions, and mtDNA) in ferroptosis. We believe that exploring the role of mitochondria in ferroptosis will help us understand the potential regulatory mechanisms of ferroptosis in cancer and help us find new therapeutic targets.

High mobility group box protein B1 (HMGB1) belongs to the HMG family, is widely expressed in the nucleus of digestive mucosal epithelial cells, mesenchymal cells and immune cells, and binds to DNA to participate in genomic structural stability, mismatch repair and transcriptional regulation to maintain normal cellular activities. In the context of digestive inflammation and tumors, HMGB1 readily migrates into the extracellular matrix and binds to immune cell receptors to affect their function and differentiation, further promoting digestive tract tissue injury and tumor development. Notably, HMGB1 can also promote the antitumor immune response. Therefore, these seemingly opposing effects in tumors make targeted HMGB1 therapies important in digestive cancer. This review focuses on the role of HMGB1 in tumors and its effects on key pathways of digestive cancer and aims to provide new possibilities for targeted tumor therapy.

Protein acetylation modifications play a central and pivotal role in a myriad of biological processes, spanning cellular metabolism, proliferation, differentiation, apoptosis, and beyond, by effectively reshaping protein structure and function. The metabolic state of cells is intricately connected to epigenetic modifications, which in turn influence chromatin status and gene expression patterns. Notably, pathological alterations in protein acetylation modifications are frequently observed in diseases such as metabolic syndrome, cardiovascular disorders, and cancer. Such abnormalities can result in altered protein properties and loss of function, which are closely associated with developing and progressing related diseases. In recent years, the advancement of precision medicine has highlighted the potential value of protein acetylation in disease diagnosis, treatment, and prevention. This review includes provocative and thought-provoking papers outlining recent breakthroughs in acetylation modifications as they relate to cardiovascular disease, mitochondrial metabolic regulation, liver health, neurological health, obesity, diabetes, and cancer. Additionally, it covers the molecular mechanisms and research challenges in understanding the role of acetylation in disease regulation. By summarizing novel targets and prognostic markers for the treatment of related diseases, we aim to contribute to the field. Furthermore, we discuss current hot topics in acetylation research related to health regulation, including N4-acetylcytidine and liquid-liquid phase separation. The primary objective of this review is to provide insights into the functional diversity and underlying mechanisms by which acetylation regulates proteins in disease contexts.

Long non-coding RNAs (lncRNAs) are commonly known for their important characters in cancer progression. LncRNA MAFG-antisense 1 (AS1) (MAFG-AS1) has been discovered as a novel oncogenic lncRNA for several years. Accumulating data have demonstrated abnormal overexpression of MAFG-AS1 in various human cancers, including breast, bladder, liver, gastric, and lung. Importantly, through regulating various microRNAs and cell signaling pathways, MAFG-AS1 has been demonstrated to exhibit various biological effects, including proliferation, metastasis, and epithelial-mesenchymal transition (EMT). Meanwhile, abnormal overexpression of MAFG-AS1 is closely linked with histological grade, TNM stage, extensive depth of invasion, poor OS, and lymph node metastasis (LNM). In the present review, the authors summarized the previous studies on the biological properties, molecular mechanisms, and clinicopathological characters of MAFG-AS1 in human cancers. In summary, MAFG-AS1 is a promising prognostic biological marker and potential therapeutic target for cancer treatment.

Potassium channels play an important role in human physiological function. Recently, various molecular mechanisms have implicated abnormal functioning of potassium channels in the proliferation, migration, invasion, apoptosis, and cancer stem cell phenotype formation. Potassium channels also mediate the association of tumor cells with the tumor microenvironment. Meanwhile, potassium channels are important targets for cancer chemotherapy. A variety of drugs exert anti-cancer effects by modulating potassium channels in tumor cells. Therefore, there is a need to understand how potassium channels participate in tumor development and progression, which could reveal new, novel targets for cancer diagnosis and treatment. This review summarizes the roles of voltage-gated potassium channels, calcium-activated potassium channels, inwardly rectifying potassium channels, and two-pore domain potassium channels in tumorigenesis and the underlying mechanism of potassium channel-targeted drugs. Therefore, the study lays the foundation for rational and effective drug design and individualized clinical therapeutics.

Multidrug resistance (MDR) promotes tumor recurrence and metastasis and heavily reduces anticancer efficiency, which has become a primary reason for the failure of clinical chemotherapy. The mechanisms of MDR are so complex that conventional chemotherapy usually fails to achieve an ideal therapeutic effect and even accelerates the occurrence of MDR. In contrast, the combination of chemotherapy with dual-drug has significant advantages in tumor therapy. A novel dual-drug codelivery nanosystem, which combines dual-drug administration with nanotechnology, can overcome the application limitation of free drugs. Both the characteristics of nanoparticles and the synergistic effect of dual drugs contribute to circumventing various drug-resistant mechanisms in tumor cells. Therefore, developing dual-drug codelivery nanosystems with different multidrug-resistant mechanisms has an important reference value for reversing MDR and enhancing the clinical antitumor effect. In this review, the advantages, principles, and common codelivery nanocarriers in the application of dual-drug codelivery systems are summarized. The molecular mechanisms of MDR and the dual-drug codelivery nanosystems designed based on different mechanisms are mainly introduced. Meanwhile, the development prospects and challenges of codelivery nanosystems are also discussed, which provide guidelines to exploit optimized combined chemotherapy strategies in the future.

Lipotoxicity is the dysregulation of the lipid environment and/or intracellular composition that leads to accumulation of harmful lipids and ultimately to organelle dysfunction, abnormal activation of intracellular signaling pathways, chronic inflammation and cell death. It plays an important role in the development of acute kidney injury and chronic kidney disease, including diabetic nephropathy, obesity-related glomerulopathy, age-related kidney disease, polycystic kidney disease, and the like. However, the mechanisms of lipid overload and kidney injury remain poorly understood. Herein, we discuss two pivotal aspects of lipotoxic kidney injury. First, we analyzed the mechanism of lipid accumulation in the kidney. Accumulating data indicate that the mechanisms of lipid overload in different kidney diseases are inconsistent. Second, we summarize the multiple mechanisms by which lipotoxic species affect the kidney cell behavior, including oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, dysregulated autophagy, and inflammation, highlighting the central role of oxidative stress. Blocking the molecular pathways of lipid accumulation in the kidney and the damage of the kidney by lipid overload may be potential therapeutic targets for kidney disease, and antioxidant drugs may play a pivotal role in the treatment of kidney disease in the future.

Cancer is currently the most important problem endangering human health. As antitumor drugs have always been the most common methods for treating cancers, searching for new antitumor agents is of great significance. Brusatol, a quassinoid from the seeds of Brucea javanica, exhibits a potent tumor-suppressing effect with improved disease outcome. Studies have shown that brusatol not only shows potential tumor inhibition through multiple pharmacological effects, such as promoting apoptosis and inhibiting metastasis but also exhibits significant synergistic antitumor effects in combination with chemotherapeutic agents and overcoming chemical resistance in a wide range of cancer types. In this paper, the antitumor effects and mechanisms of brusatol were reviewed to provide evidence that brusatol has the exact antitumor efficacy of chemotherapeutic agents and show the potential of brusatol to be developed as a promising antitumor drug.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β outside neurons and Tau protein inside neurons. Various pathological mechanisms are implicated in AD, including brain insulin resistance, neuroinflammation, and endocrinal dysregulation of adrenal corticosteroids. These factors collectively contribute to neuronal damage and destruction. Recently, bile acids (BAs), which are metabolites of cholesterol, have shown neuroprotective potential against AD by targeting the above pathological changes. BAs can enter the systematic circulation and cross the blood–brain barrier, subsequently exerting neuroprotective effects by targeting several endogenous receptors. Additionally, BAs interact with the microbiota–gut–brain (MGB) axis to improve immune and neuroendocrine function during AD episodes. Gut microbes impact BA signaling in the brain through their involvement in BA biotransformation. In this review, we summarize the role and molecular mechanisms of BAs in AD while considering the MGB axis and propose novel strategies for preventing the onset and progression of AD. [Display omitted] • Alzheimer's disease is found to be associated with bile acids. • Bile acids can indirectly exert neuroprotective effects in Alzheimer's disease through bidirectional interaction with the microbiota-gut-brain axis. • Gut dysbiosis can lead to neurodegeneration. • Bile acid preparations, probiotics, prebiotics, postbiotics, anti-inflammatory therapy provide direction for the novel therapeutic strategies of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), a commonly used chemotherapy drug, is hindered due to its tendency to induce cardiotoxicity (DIC). Ferroptosis, a novel mode of programmed cell death, has received substantial attention for its involvement in DIC. Recently, natural product-derived ferroptosis regulator emerged as a potential strategy for treating DIC. In this review, a comprehensive search was conducted across PubMed, Web of Science, Google Scholar, and ScienceDirect databases to gather relevant articles on the use of natural products for treating DIC in relation to ferroptosis. The available papers were carefully reviewed to summarize the therapeutic effects and underlying mechanisms of natural products in modulating ferroptosis for DIC treatment. It was found that ferroptosis plays an important role in DIC pathogenesis, with dysregulated expression of ferroptosis-related proteins strongly implicated in the condition. Natural products, such as flavonoids, polyphenols, terpenoids, and quinones can act as GPX4 activators, Nrf2 agonists, and lipid peroxidation inhibitors, thereby enhancing cell viability, attenuating myocardial fibrosis, improving cardiac function, and suppressing ferroptosis in both in vitro and in vivo models of DIC. This review demonstrates a strong correlation between DOX-induced cardiac ferroptosis and key proteins, such as GPX4, Keap1, Nrf2, AMPK, and HMOX1. Natural products are likely to exert therapeutic effects against DIC by modulating the activity of these proteins. [Display omitted] • Ferroptosis plays a vital role in the pathogenesis of doxorubicin-induced cardiotoxicity. • Targeting ferroptosis as a promising therapeutic strategy for doxorubicin-induced cardiotoxicity. • Natural products hold potential as ferroptosis regulators in doxorubicin-induced cardiotoxicity. • Diverse therapeutic effects and multifaceted mechanisms of natural products in ferroptosis modulation. [ABSTRACT FROM AUTHOR]

Ginseng, the dried root of Panax ginseng C.A. Mey., is widely used in Chinese herbal medicine. Ginsenosides, the primary active components of ginseng, exhibit diverse anticancer functions through various mechanisms, such as inhibiting tumor cell proliferation, promoting apoptosis, and suppressing cell invasion and migration. In this article, the mechanism of action of 20 ginsenoside subtypes in tumor therapy and the research progress of multifunctional nanosystems are reviewed, in order to provide reference for clinical prevention and treatment of cancer. [Display omitted] • Ginsenosides are effective anti-tumor active components. • 20 subtypes of ginsenosides have great antitumor effect. • The hub gene targets of ginsenosides are enriched in the pathways in cancer, metastasis and cell apoptosis. • Ginsenoside-based multifunctional nanosystems have unique advantages in the prevention and treatment of tumors. [ABSTRACT FROM AUTHOR]

The mitochondrial unfolded protein response (UPRmt) is a cytoprotective response in response to cellular stress that is activated in response to mitochondrial stress to maintain intra-protein homeostasis, thereby protecting the cell from a variety of stimuli. The activation of this response has been linked to cardiovascular diseases. Here, we reviewed the current understanding of UPRmt and discussed its specific molecular mechanism, mainly in mammals, as well as addressing its protective role against cardiovascular diseases, so as to provide direction for further research on UPRmt and therapies targeting cardiovascular diseases in the future. ● UPRmt plays an important role in cardiac pathophysiology. ● Targeted UPRmt can delay the progress of cardiovascular diseases. ● Modern drugs and natural products can prevent and treat cardiovascular diseases by regulating UPRmt. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common malignant tumors in the world, and its incidence and mortality rate rank among the top malignant tumors worldwide, which has become an important killer threatening human survival rate and well-being. Modern medical treatment for lung cancer is mainly based on surgery and radiotherapy, with gene, targeted drugs and immunotherapy as auxiliary treatments, which are effective, but there are problems such as postoperative recurrence, resistance to radiotherapy, toxic side effects and poor compliance. In recent years, with the continuous development of TCM, TCM is popular among physicians and patients for its high efficiency, low toxicity, low side effects and economic benefits, etc. As a classical TCM formula, Qianjin Weijin Decoction(QJWJ) has certain value in the treatment of lung cancer. This paper summarizes and analyzes the clinical research, molecular mechanism, pharmacological effects and chemical composition of QJWJ in the treatment of lung cancer, in order to provide more ideas and theoretical basis for the treatment of lung cancer with QJWJ.

Influenza virus-induced pneumonia (IVP) is a high morbidity and contagiousness pulmonary infectious disease caused by invasion of the influenza virus into the lower respiratory tract. Currently, the treatment of IVP is mainly based on an anti-influenza virus infection strategy, which includes the use of anti-influenza vaccines and drugs. However, the clinical use of these treatment options is limited as the influenza virus has a high level of variability and drug resistance may occur. Traditional Chinese medicines (TCMs) for the treatment of IVP have unique advantages, a variety of precise curative effects and have been widely used in clinical practice in China both historically and in the present day. However, there are only few literature reviews on the prevention and treatment of IVP using TCMs. Therefore, we conducted a review of relevant literature from the past 10 years and a comprehensive analysis of various databases containing reports on TCMs used for IVP prevention and treatment to provide basic data for future research and development of drugs against IVP. Herein, we summarize research progress on the pathogenesis of IVP, the TCMs effective in prevention or treatment of IVP, their underlying molecular mechanisms and active components. Overall, we provide a theoretical basis for the clinical use of TCM in the prevention and treatment of IVP. Furthermore, we provide a reference for the development of new multi-component, multi-target, low-toxicity drugs, which is of great academic and clinical significance.

Ovarian cancer is one of the three most common female reproductive system cancers and has been a hot topic in the field of gynecology and oncology. Currently, surgery with chemotherapy is the common strategy in treatment of ovarian cancer, while it is always accompanied by drug resistance and some adverse effects. Over the past few years, traditional Chinese medicine (TCM) has been embraced by a large population of clinicians and researchers due to its high efficiency, low toxicity and minor side effects. Guizhi-Fuling Wan as a classical TCM formula has manifested certain efficacy in treating ovarian cancer. This article intends to further study the role and mechanism of Guizhi-Fuling Wan in treatment of ovarian cancer and explore the effective chemical components contained in the herbs of the formula. To this end, we reviewed the previous clinical studies and experiments to analyze the molecular mechanisms, pharmacological effects, active chemical components and their targets of action in treatment of ovarian cancer, thereby providing a theoretic basis for future studies and practices.

Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapy. However, the research and clinical application of MSCs are greatly hindered by the limited cells proliferation and replicative senescence. Therapeutic agents that can both enhance the proliferative ability and decrease the replicative senescence of MSCs are greatly needed, however, not been reported yet. Herein, for the first time, we identified 11 natural compounds from medicinal plants with both excellent proliferative and anti-senescence abilities in MSCs. The qPCR analysis indicated underlying mechanisms associated with fibroblast growth factor, transforming growth factor, Wnt/β-catenin and leukemia-induced factor in proliferation; the reactive oxygen species production, mitochondrial dysfunction autophagy and proteostasis are involved in cells senescence-related mechanism. Phytochemicals are demonstrated as novel therapeutic candidates with promising effects in both stimulating proliferation and retarding replicative senescence of stem cells with high safety.

Chronic liver injury could gradually progress to liver fibrosis, cirrhosis, and even hepatic carcinoma without effective treatment. The massive production and activation of abnormal cell differentiation is vital to the procession of liver diseases. Epithelial-mesenchymal transformation (EMT) is a biological process in which differentiated epithelial cells lose their epithelial characteristics and acquire mesenchymal cell migration capacity. Emerging evidence suggests that EMT not only occurs in the process of hepatocellular carcinogenesis, but also appears in liver cells transforming to myofibroblasts, a core event of liver disease. Non-coding RNA (ncRNA) such as microRNA (miRNA), long non-coding RNA (lncRNA) and circular RNA (circRNA) are important regulatory factors in EMT, which can regulate target gene expression by binding with RNA single-stranded. Various studies had shown that ncRNA regulation of EMT plays a key role in liver disease development, and many effective ncRNAs have been identified as promising biomarkers for the diagnosis and treatment of liver disease. In this review, we focus on the relationship between the different ncRNAs and EMT as well as the specific molecular mechanism in the liver diseases to enrich the pathological progress of liver diseases and provide reference for the treatment of liver diseases.

Noncoding RNAs (ncRNAs) do not participate in protein-coding. Ferroptosis is a newly discovered form of cell death mediated by reactive oxygen species and lipid peroxidation. Recent studies have shown that ncRNAs such as microRNAs, long noncoding RNAs, circular RNAs, and ferroptosis are involved in the occurrence and development of osteosarcoma (OS). Studies have confirmed that ncRNAs participate in the development of OS by regulating the ferroptosis. However, systematic summary on this topic are still lacking. This review summarises the potential role of ncRNAs in the diagnosis, treatment, drug resistance, and prognosis of OS and the basis for diagnosing, preventing, and treating clinical OS and developing effective drugs. This review summarises the latest research progress on ncRNAs that regulate ferroptosis in OS, attempts to clarify the molecular mechanisms by which ncRNAs regulate ferroptosis in the pathogenesis of OS, and elaborates on the involvement of ferroptosis in OS from the perspective of ncRNAs. [Display omitted] • NcRNAs play an important role in the treatment, diagnosis, prognosis, and drug resistance of osteosarcoma. • Ferroptosis involving ncRNAs provides a new direction for the pathogenesis of osteosarcoma. • NcRNAs may act as a hub for regulating the ferroptosis of osteosarcoma with other forms of cell metabolism and death. • The expression of ncRNAs related with ferroptosis is correlated with immune checkpoint, which can be explored as a new idea of immunotherapy for osteosarcoma. [ABSTRACT FROM AUTHOR]

The incidence of metabolic diseases has progressively increased, which has a negative impact on human health and life safety globally. Due to the good efficacy and limited side effects, there is growing interest in developing effective drugs to treat metabolic diseases from natural compounds. Kaempferol (KMP), an important flavonoid, exists in many vegetables, fruits, and traditional medicinal plants. Recently, KMP has received widespread attention worldwide due to its good potential in the treatment of metabolic diseases. To promote the basic research and clinical application of KMP, this review provides a timely and comprehensive summary of the pharmacological advances of KMP in the treatment of four metabolic diseases and its potential molecular mechanisms of action, including diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), and atherosclerosis. According to the research, KMP shows remarkable therapeutic effects on metabolic diseases by regulating multiple signaling transduction pathways such as NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. In addition, the most recent literature on KMP's natural source, pharmacokinetics studies, as well as toxicity and safety are also discussed in this review, thus providing a foundation and evidence for further studies to develop novel and effective drugs from natural compounds. Collectively, our manuscript strongly suggested that KMP could be a promising candidate for the treatment of metabolic diseases. [Display omitted] ● Dietary sources, pharmacokinetics and toxicity of kaempferol. ● Kaempferol has the potential to prevent and treat several metabolic diseases. ● Diabetes, obesity, nonalcoholic fatty liver disease/ non-alcoholic steatohepatitis, atherosclerosis. ● NF-κB, Nrf2, AMPK, PI3K/AKT, TLR4, and ER stress. ● Future perspectives of kaempferol. [ABSTRACT FROM AUTHOR]

RNA methylation modifications are widespread in eukaryotes and prokaryotes, with N6-methyladenosine (m6A) the most common among them. Demethylases, including Fat mass and obesity associated gene (FTO) and AlkB homolog 5 (ALKBH5), are important in maintaining the balance between RNA methylation and demethylation. Recent studies have clearly shown that demethylases affect the biological functions of tumors by regulating their m6A levels. However, their effects are complicated, and even opposite results have appeared in different articles. Here, we summarize the complex regulatory networks of demethylases, including the most important and common pathways, to clarify the role of demethylases in tumors. In addition, we describe the relationships between demethylases and the tumor microenvironment, and introduce their regulatory mechanisms. Finally, we discuss evaluation of demethylases for tumor diagnosis and prognosis, as well as the clinical application of demethylase inhibitors, providing a strong basis for their large-scale clinical application in the future. [Display omitted] • Demethylases regulate tumor biological functions. • Demethylases can regulate tumor progression by regulating tumor microenvironment(TME). • Demethylases regulate important tumor related pathways. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common malignant tumors in women globally, and its occurrence has surpassed lung cancer and become the biggest threat for women. At present, breast cancer treatment includes surgical resection or postoperative chemotherapy and radiotherapy. However, tumor relapse and metastasis usually lead to current therapy failure thanks to breast cancer stem cells (BCSCs)-mediated tumorigenicity and drug resistance. Drug resistance is mainly due to the long-term quiescent G0 phase, strong DNA repairability, and high expression of ABC transporter, and the tumorigenicity is reflected in the activation of various proliferation pathways related to BCSCs. Therefore, understanding the characteristics of BCSCs and their intracellular and extracellular molecular mechanisms is crucial for the development of targeted drugs for BCSCs. To this end, we discussed the latest developments in BCSCs research, focusing on the analysis of specific markers, critical signaling pathways that maintain the stemness of BCSCs，such as NOTCH, Wnt/β-catenin, STAT3, Hedgehog, and Hippo-YAP signaling, immunomicroenviroment and summarizes targeting therapy strategies for stemness maintenance and differentiation, which provides a theoretical basis for further exploration of treating breast cancer and preventing relapse derived from BCSCs.

Breast cancer (BC) is mostly observed in women and is responsible for huge mortality in women subjects globally. Due to the continued development of drug resistance and other contributing factors, the scientific community needs to look for new alternatives, and drug repurposing is one of the best opportunities. Here we light upon the drug repurposing with a major focus on breast cancer. BC is a division of cancer known as the leading cause of death of 2.3 million women globally, with 685,000 fatalities. This number is steadily rising, necessitating the development of a treatment that can extend survival time. All available treatments for BC are very costly as well as show side effects. This unfulfilled requirement of the anti-cancer drugs ignited an enthusiasm for drug repositioning, which means finding out the anti-cancer use of already marketed drugs for other complications. With the advancement in proteomics, genomics, and computational approaches, the drug repurposing process hastens. So many drugs are repurposed for the BC, including alkylating agents, antimetabolite, anthracyclines, an aromatase inhibitor, mTOR, and many more. The drug resistance in breast cancer is rising, so reviewing how the challenges in breast cancer can be combated with drug repurposing. This paper provides the updated information on all the repurposed drugs candidates for breast cancer with the molecular mechanism responsible for their anti-tumor activity. Additionally, all the challenges that occur during the repurposing of the drugs are discussed.

Cardiovascular diseases (CVD) are a significant cause of human health harm. In the past, stem cell therapy was reported to have functional defects, such as immune rejection, tumorigenicity, and infusion toxicity. Exosomes are extracellular vesicles with lipid bilayer membrane structure, containing proteins, lipids, mRNA, miRNA, DNA, and other molecules, which can mediate various biological functions such as immune response, inflammatory response, cell migration, and differentiation intercellular communication. Exosomal miRNAs have outstanding advantages in disease diagnosis and curative effect prediction. Likewise, paracrine factors could also mediate the main therapeutic effect of mesenchymal stem cells. Research has shown that mesenchymal stem cell-derived micro-exosomes, which may come from stem cells, accumulate in the ischemic tissue and regulate cell proliferation, apoptosis, inflammation, and angiogenesis sites of myocardial injury after being transplanted. This review reviewed the molecular mechanisms of exosomes and internal microRNAs derived from mesenchymal stem cells in cardiac ischemic injury repair.

Angiogenesis is the growth of new blood vessels on preexisting ones. It is the outcome of a multifactorial effect involving several cells, which can be brought on by different stress reactions.The accumulation of unfolded proteins in the endoplasmic reticulum occurs when cells are stressed due to environmental changes, where physical or chemical stimuli induce endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR), a homeostasis response designed to re-establish protein balance. Ferroptosis is a planned death of lipid peroxidation and anomalies in metabolism that is dependent on iron. Large concentrations of iron ions accumulate there, along with high concentrations of lipid peroxides and reactive oxygen species, all of which can contribute to the development of several diseases. Through the production of growth factors, adhesion factors, and inflammatory factors that trigger the start of angiogenesis, both UPR and Ferroptosis can be implicated in angiogenesis.To set the stage for further research on angiogenesis, this work concentrated on the effects of Ferroptosis and UPR on angiogenesis, respectively. • My article summarized the pro-angiogenic factors and anti-angiogenic factors of angiogenesis. • My article discusses the roles of the three UPR pathways in angiogenesis. • My article summarizes the various mechanisms and clinical trials linking ferroptosis and angiogenesis. [ABSTRACT FROM AUTHOR]

Optineurin (OPTN) is a widely expressed multifunctional articulatory protein that participates in cellular or mitochondrial autophagy, vesicular transport, and endoplasmic reticulum (ER) stress via interactions with various proteins. Skeletal development is a complex biological process that requires the participation of various osteoblasts, such as bone marrow mesenchymal stem cells (BMSCs), and osteogenic, osteoclastic, and chondrogenic cells. OPTN was recently found to be involved in the regulation of osteoblast activity, which affects bone metabolism. OPTN inhibits osteoclastogenesis via signaling pathways, including NF-κB, IFN-β, and NRF2. OPTN can promote the differentiation of BMSCs toward osteogenesis and inhibit lipogenic differentiation by delaying BMSC senescence and autophagy. These effects are closely related to the development of bone metabolism disorders, such as Paget's disease of bone, rheumatoid arthritis, and osteoporosis. Therefore, this review aims to explore the role and mechanism of OPTN in the regulation of bone metabolism and related bone metabolic diseases. Our findings will provide new targets and strategies for the prevention and treatment of bone metabolic diseases. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a progressive and lethal cardiopulmonary. Pulmonary vascular remodeling (PVR) caused by excessive proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) is the chief pathological feature of PAH. Dioscin is a natural product that possesses multiple pharmacological activities, but its effect on PAH remains unclear. In this study, effect of dioscin on vascular remodeling in PAH was assessed in hypoxia-induced PASMCs, hypoxia-induced and monocrotaline (MCT)-induced rats. Western blot, Real-time PCR and siRNA transfection tests were applied to evaluate the possible mechanisms of dioscin. In vitro experiments, results showed dioscin markedly inhibited the proliferation and migration, and promoted apoptosis of hypoxic PASMCs. In vivo, dioscin significantly decreased the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI), and improved pulmonary vascular stenosis in rats induced by hypoxia or MCT. Molecular mechanism studies showed that dioscin significantly reduced the expression of growth factor receptor-bound protein 2 (GRB2). Subsequently, dioscin reduced the expressions of Ras, Cyclin D1, CDK4, c-Fos, PCNA and p-ERK to inhibit proliferation and migration of PASMCs, inhibited p-PI3K and p-AKT levels and increased Bax/Bcl2 ratio to promote cell apoptosis. GRB2 siRNA transfection in PASMCs further confirmed that the inhibitory action of dioscin in PAH was evoked by adjusting GRB2/ERK/PI3K-AKT signal. Taken together, our study indicated that dioscin attenuates PAH through adjusting GRB2/ERK/PI3K-AKT signal to inhibit PASMCs proliferation and migration, and promote apoptosis, and dioscin may be developed as a therapeutic strategy for treating PAH in the future.

Leukopenia is the most common hallmark of hematopoietic diseases in clinic. Sanguisorba Officinalis L., a traditional Chinese medicine, has long been used for alleviating leukopenia. However, its associated mechanism still remains unknown. In this study, a network pharmacology approach was used to elucidate the underlying mechanisms of Sanguisorba Officinalis L. against leukopenia. Firstly, 12 active compounds of Sanguisorba Officinalis L. were identified through TCMSP database with absorption, distribution, metabolism, excretion (ADME) screening, and UHPLC-MS analysis. Then, 258 leukopenia related targets of the identified active compounds were predicted via the Swiss Target Prediction database, GeneCards database and DisGeNET database, respectively. After taking the intersection of two related targets, 72 common targets were selected. Among them, 8 core targets (VEGFA, HSP90AA1, EGFR, PTGS2, MTOR, ESR1, ERBB2, MDM2) of Sanguisorba Officinalis L. against leukopenia were obtained through the topological analysis. Meanwhile, both the GO and KEGG pathway analysis reveal that the core targets are mainly enriched in PI3K-Akt, HIF-1, VEGF and estrogen signaling pathways. In addition, molecular docking simulation was performed to explore the binding ability between the 12 active compounds of Sanguisorba Officinalis L. with 8 core targets. Furthermore, a myelosuppressive mice model was established to evaluate the protective effect of Sanguisorba Officinalis L. against leukopenia. The results showed that the ethanol extract of Sanguisorba Officinalis L. significantly raised the number of peripheral white blood cells. Overall, this study provides an insight into the underlying mechanisms of Sanguisorba Officinalis L. against leukopenia, which lays a theoretical foundation for the further experimental verification and clinical application.

Icariin has a variety of biological activities, such as lipid-lowering effects, and has attracted widespread attention in recent years. However, it is not clear whether lipid-lowering effect is that multiple metabolites or a particular component plays a major role. It is known that icariin has a variety of metabolites in the body, including icariside I, icariside II, icaritin, desmethylicaritin, and other metabolites. Many of these studies have shown that the metabolites of icariin have a lipid-lowering effect. This paper focuses on the lipid-regulating effects of icariin and its metabolites in vitro and in vivo, and highlights the mechanisms involved. Icariin may have potential in the development of therapeutic strategies to regulate lipid metabolism.

PDB-1 is a new C-27-carboxylated-lupane-triterpenoid derivative isolated from Potentilla discolor Bunge. In our previous research, PDB-1 was suggested to have an obvious selectivity for tumor cells. This study focused on clarifying PDB-1’s anticancer mechanism in the inhibition of proliferation and in the induction of apoptosis and autophagy in A549 cells. In general, A549 cells were treated with PDB-1 for different times, and cell survival was assessed by a CCK8 assay. The assessment of intracellular reactive oxygen species, a mitochondrial membrane potential assay, a cell cycle assay, an annexin V-FITC/PI assay, and MDC staining were performed in A549 cells treated with PDB-1. Moreover, the mRNA and protein expression of cell cycle-, apoptosis- and autophagy-related factors were detected by RT-qPCR and western blotting. The results showed that PDB-1 inhibited A549 cell proliferation and colony formation in a dose- and time-dependent manner. The decrease in the viability of A549 cells was due to a G2/M cell cycle arrest. Moreover, PDB-1 induced cell apoptosis, accompanied by an increase in the Bax/Bcl-2 ratio and an increase in the expression levels of cleaved caspase-3/caspase-9. We also found that PDB-1 induced autophagy by increasing the conversion of LC3-I to LC3-II and elevating Beclin-1. In addition, further studies indicated that pretreatment with a specific PI3K inhibitor (LY294002) enhanced the effects of PDB-1 on the expression of proteins associated with apoptosis and autophagy, demonstrating that the PI3K/Akt/mTOR pathway was related to PDB-1-induced apoptosis and autophagy. These results indicated that PDB-1 may be considered a potential candidate for the future treatment of lung adenocarcinoma. These findings should benefit the development of the C14-COOH type of pentacyclic triterpenoids.

Costunolide (COS) and dehydrocostus lactone (DEH) are two natural sesquiterpene lactones with potential antitcancer activity against a range of cancer cell types both in vitro and in vivo, particularly for breast cancer and leukemia. There are many researches that have been taken to characterize these pathways and to reveal their anticancer mechanisms of action of COS and DEH. However, while there is a great deal of evidence detailing the effects of COS and DEH on considerable signaling pathways and cellular functions, a global view of their mechanism of action remains elusive. This review systematically summarizes the antitumor activity and mechanism of COS and DEH in the recent reports, and discusses the effect of the key active part (α-methylene-γ-butyrolactone) of COS and DEH against cancer. Moreover, we also discuss the antineoplastic activity of COS and DEH derivatives to improve the cytotoxicity and safety index. We believe this review can provide a systemic reference to develop COS and DEH as anticancer agents.

Long noncoding RNAs (lncRNAs) are a group of RNAs that lack protein-coding ability, with lengths greater than 200 nucleotides. Increasing evidence has indicated that they mediate multiple physiological and pathological processes by regulating gene expression at the epigenetic, transcriptional, post-transcriptional, and translational levels. The deregulation of lncRNAs was demonstrated to have tumor suppressive or oncogenic effects, and thus, these molecules play vital regulatory roles in tumor initiation and progression. Small nucleolar RNA hostgene 7 (SNHG7) is a lncRNA located on chromosome 9q34.3. Different studies have explored the potential role of SNHG7 in the development and progression of multiple human malignancies such as bladder, breast, colorectal, esophageal, gastric, and prostate cancer, as well as osteosarcoma, among others, and high expression predicts poor prognosis and poor survival for such patients. Moreover, this molecule can promote proliferation and metastasis, while inhibiting apoptosis in cancer cells. The present review highlights the latest insights into the expression, functional roles, and molecular mechanisms of SNHG7 in different human malignancies.

Ferroptosis is an iron-dependent regulated cell death, mainly manifested by the production of reactive oxygen species and accumulation of lipid peroxides. It is distinct from other forms of cell death with regard to morphology and biochemistry, particularly in disrupting mitochondrial function. Mitochondria are essential compartments where the organism generates energy and are closely associated with the fate of ferroptosis. Currently, researchers focus on the potential value of ferroptosis and mitochondria for overcoming drug sensitivity and assisting in cancer therapy. In this review, we summarize the main mechanisms of ferroptosis (the GPX4-realated pathway, FSP1-related pathway, and iron metabolism pathway) and the functions and regulating pathways of mitochondria (the TCA cycle, oxidative phosphorylation, mitochondrial regulation of iron ions, and mtDNA) in ferroptosis. We believe that exploring the role of mitochondria in ferroptosis will help us understand the potential regulatory mechanisms of ferroptosis in cancer and help us find new therapeutic targets. [Display omitted] • Studies illuminated the main mechanisms of ferroptosis in cancer over the past few years. • Mitochondria play a vital role in the process of ferroptosis, the TCA cycle, the OXPHS pathway, mitochondrial regulation of iron ions, and mtDNA. • Targeting mitochondria-related function to influence ferroptosis associated pathways in cancer cells, and how these mechanisms can be an effective strategy for cancer therapy. [ABSTRACT FROM AUTHOR]

Currently, cancer is one of the main research topics, due to its high incidence and drug resistance to existing anti-cancer drugs. Formononetin, a natural product with phytoestrogenic properties and diverse biological functions, has attracted the attention of researchers working on anticancer drugs. Formononetin emerges as an intriguing bioactive substance compared to other isoflavones as it exhibits potent chemotherapeutic activity with less toxicity. Formononetin effectively plays a significant role in inhibiting cell proliferation, invasion, and metastatic abilities of cancer cells by targeting major signaling pathways at the junction of interconnected pathways. It also induces apoptosis and cell cycle arrest by modulating mediator proteins. It causes upregulation of key factors such as p-AKT, p38, p21, and p53 and downregulation of NF-κB. Furthermore, formononetin regulates the neoplastic microenvironment by inactivating the ERK1/2 pathway and lamin A/C signaling and has been reported to inactivate JAK/STAT, PKB or AKT, and mitogen-activated protein kinase pathways and to suppress cell migration, invasion, and angiogenesis in human cancer cells. To assist researchers in further exploring formononetin as a potential anticancer therapeutic candidate, this review focuses on both in vitro and in vivo proof of concept studies, patents, and clinical trials pertinent to formononetin's anticancer properties. Overall, this review discusses formononetin from a comprehensive perspective to highlight its potential benefits as an anticancer agent. [Display omitted] • Formononetin, a phytoestrogen isoflavonoid found in a wide range of food plants and therapeutic herbs. • Formononetin exhibits numerous biological and pharmacological effects. • Formononetin significantly reduces the detrimental toxic effects caused by chemotherapeutic drugs. • Identifying formononetin's specific targets and pathways is crucial. • Formononetin is a promising agent to treat various types of cancers and tumors. [ABSTRACT FROM AUTHOR]

High mobility group box protein B1 (HMGB1) belongs to the HMG family, is widely expressed in the nucleus of digestive mucosal epithelial cells, mesenchymal cells and immune cells, and binds to DNA to participate in genomic structural stability, mismatch repair and transcriptional regulation to maintain normal cellular activities. In the context of digestive inflammation and tumors, HMGB1 readily migrates into the extracellular matrix and binds to immune cell receptors to affect their function and differentiation, further promoting digestive tract tissue injury and tumor development. Notably, HMGB1 can also promote the antitumor immune response. Therefore, these seemingly opposing effects in tumors make targeted HMGB1 therapies important in digestive cancer. This review focuses on the role of HMGB1 in tumors and its effects on key pathways of digestive cancer and aims to provide new possibilities for targeted tumor therapy. [Display omitted] • We summarized the molecular mechanism of HMGB1 in digestive cancers. • We summarized the structure, function, and receptors of HMGB1 in the digestive system. 3. We provide new insights into targeted therapy strategies. [ABSTRACT FROM AUTHOR]

Protein acetylation modifications play a central and pivotal role in a myriad of biological processes, spanning cellular metabolism, proliferation, differentiation, apoptosis, and beyond, by effectively reshaping protein structure and function. The metabolic state of cells is intricately connected to epigenetic modifications, which in turn influence chromatin status and gene expression patterns. Notably, pathological alterations in protein acetylation modifications are frequently observed in diseases such as metabolic syndrome, cardiovascular disorders, and cancer. Such abnormalities can result in altered protein properties and loss of function, which are closely associated with developing and progressing related diseases. In recent years, the advancement of precision medicine has highlighted the potential value of protein acetylation in disease diagnosis, treatment, and prevention. This review includes provocative and thought-provoking papers outlining recent breakthroughs in acetylation modifications as they relate to cardiovascular disease, mitochondrial metabolic regulation, liver health, neurological health, obesity, diabetes, and cancer. Additionally, it covers the molecular mechanisms and research challenges in understanding the role of acetylation in disease regulation. By summarizing novel targets and prognostic markers for the treatment of related diseases, we aim to contribute to the field. Furthermore, we discuss current hot topics in acetylation research related to health regulation, including N4-acetylcytidine and liquid-liquid phase separation. The primary objective of this review is to provide insights into the functional diversity and underlying mechanisms by which acetylation regulates proteins in disease contexts. [Display omitted] • Enrichment of Nε-acetylation-specific sites is an early clue to disease development. • Non-histone acetylation also emerges as a key 'enforcer' of altered gene regulation. • Chromatin recruits acetylation effectors, crucial for precise gene expression control. • Exploring the key site acetylation elucidates disease-metabolic causal links. [ABSTRACT FROM AUTHOR]

As a classical traditional Chinese medicine, Wuzi-Yanzong-Wan (WZYZW) has been widely applied for several centuries to treat non-obstructive oligoasthenozoospermia (NOA), although its pharmacological mechanisms remain largely unknown. In this study, both plasma and urine metabolomics profiling was first analysed to explore the therapeutic mechanisms of WZYZW in NOA rats induced by removal of the unilateral testicle. Then, 106 identified compounds comprising WZYZW (our previous work), for which putative targets were discovered using systems pharmacology, were systematically analysed via mRNA microarrays to validate their putative targets. Finally, metabolomics-tested WZYZW-regulated metabolites were connected with validated targets using Spearman correlation analysis to further confirm the targets from a biological perspective. The results suggested that WZYZW plays key roles in modulating the concentrations of 18 metabolites in the metabolism of amino acids, lipids and so on, normalizing the metabolic phenotype and regulating metabolic disorders. Moreover, 27 targets of WZYZW (23 compounds) against NOA were validated, and metabolomics-tested metabolites were also found to be significantly related to these identified targets, suggesting that these targets and compounds are worthy of further research. This work offers the first systematic investigation of the efficacy of WZYZW against NOA and illustrates a practicable approach for explaining the molecular mechanisms of multicomponent drugs.

Autophagy has been regarded as an inflammation-associated defensive mechanism against chronic liver disease, which has been highlighted as a novel therapeutic target for the treatment of liver fibrosis. We herein aimed to study the effects of catalpol on liver fibrosis in vivo and in vitro , and to elucidate the role of autophagy in catalpol-induced anti-inflammation. Catalpol protected the liver against CCl 4 -induced injury, as evidenced by mitigated hepatic steatosis, necrosis, and fibrotic septa. Catalpol decreased the serum levels of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and bilirubin as well as the liver/body weight ratio. Masson and sirius red staining along with hydroxyproline detection showed that catalpol decreased collagen deposition significantly compared to that of the model group. Catalpol inhibited CCl 4 -induced liver fibrosis, manifested as decreased expressions of α-SMA, fibronectin and α1(I)-procollagen at both transcriptional and translational levels. Inflammatory factors, such as IL-1β, TNF-α, IL-18, IL-6 and COX-2, were significantly elevated in rats receiving CCl 4 and down-regulated by catalpol in a dose-dependent manner in vivo . Western blot and immunofluorescence assay revealed that catalpol activated the autophagy of rats with CCl 4 -caused liver fibrosis, as indicated by up-regulation of LC3-II and beclin1 and down-regulation of P62. The results of in vitro experiments were consistent. Interestingly, inhibition or depletion of autophagy by LY294002 or Atg5 siRNA significantly attenuated catalpol-induced anti-inflammatory effects on activated hepatic stellate cells in vitro . In conclusion, catalpol relieved liver fibrosis mainly by inhibiting inflammation, and autophagy inhibition attenuated the catalpol-induced anti-inflammatory effect on liver fibrosis. [ABSTRACT FROM AUTHOR]

Cellular senescence is a fundamental cell fate caused by several cellular injuries which results in irreversible cell cycle arrest yet remaining metabolically active across all species. Cellular senescence not only can prevent tumor occurrence by inhibiting the proliferation of injured cells, but also can affect the surrounding cells through the senescence-associated secretory phenotype (SASP). Attractively, accumulating evidence shows that cellular senescence is closely related to various liver diseases. Therapeutic opportunities based on targeting senescent cells and the SASP are considered to be potential strategy for liver diseases. However, although research on cell senescence has attracted widespread attention, the overview on detailed mechanism and biological function of cell senescence in liver disease is still largely unknown. The present review summarizes the specific role of cell senescence in various liver diseases, and updates the molecular mechanisms underlying cell senescence. Moreover, the review also explores new strategies for prevention and treatment of liver disease through promoting senescence or counteracting excessive pathological senescence. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are commonly known for their important characters in cancer progression. LncRNA MAFG-antisense 1 (AS1) (MAFG-AS1) has been discovered as a novel oncogenic lncRNA for several years. Accumulating data have demonstrated abnormal overexpression of MAFG-AS1 in various human cancers, including breast, bladder, liver, gastric, and lung. Importantly, through regulating various microRNAs and cell signaling pathways, MAFG-AS1 has been demonstrated to exhibit various biological effects, including proliferation, metastasis, and epithelial-mesenchymal transition (EMT). Meanwhile, abnormal overexpression of MAFG-AS1 is closely linked with histological grade, TNM stage, extensive depth of invasion, poor OS, and lymph node metastasis (LNM). In the present review, the authors summarized the previous studies on the biological properties, molecular mechanisms, and clinicopathological characters of MAFG-AS1 in human cancers. In summary, MAFG-AS1 is a promising prognostic biological marker and potential therapeutic target for cancer treatment. [Display omitted] • Hyperexpression of MAFG-AS1 has been verified in different kinds of cancers. • MAFG-AS1 plays an important role in cancer proliferation, metastasis, and EMT. • The expression level of MAFG-AS1 is closely linked with clinicopathological characteristics of cancer patients. [ABSTRACT FROM AUTHOR]

Potassium channels play an important role in human physiological function. Recently, various molecular mechanisms have implicated abnormal functioning of potassium channels in the proliferation, migration, invasion, apoptosis, and cancer stem cell phenotype formation. Potassium channels also mediate the association of tumor cells with the tumor microenvironment. Meanwhile, potassium channels are important targets for cancer chemotherapy. A variety of drugs exert anti-cancer effects by modulating potassium channels in tumor cells. Therefore, there is a need to understand how potassium channels participate in tumor development and progression, which could reveal new, novel targets for cancer diagnosis and treatment. This review summarizes the roles of voltage-gated potassium channels, calcium-activated potassium channels, inwardly rectifying potassium channels, and two-pore domain potassium channels in tumorigenesis and the underlying mechanism of potassium channel-targeted drugs. Therefore, the study lays the foundation for rational and effective drug design and individualized clinical therapeutics. [Display omitted] • Potassium channels play an important role in tumorigenesis. • Potassium channels are involved in tumor proliferation, metastasis, and apoptosis through multiple molecular pathways. • Drugs exert anticancer effects by targeting potassium channels. [ABSTRACT FROM AUTHOR]