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Abstract Recently, N6-methyladenosine (m6A) has aroused widespread discussion in the scientific community as a mode of RNA modification. m6A comprises writers, erasers, and readers, which regulates RNA production, nuclear export, and translation and is very important for human health. A large number of studies have found that the regulation of m6A is closely related to the occurrence and invasion of tumors, while the homeostasis and function of the tumor microenvironment (TME) determine the occurrence and development of tumors to some extent. TME is composed of a variety of immune cells (T cells, B cells, etc.) and nonimmune cells (tumor-associated mesenchymal stem cells (TA-MSCs), cancer-associated fibroblasts (CAFs), etc.). Current studies suggest that m6A is involved in regulating the function of various cells in the TME, thereby affecting tumor progression. In this manuscript, we present the composition of m6A and TME, the relationship between m6A methylation and characteristic changes in TME, the role of m6A methylation in TME, and potential therapeutic strategies to provide new perspectives for better treatment of tumors in clinical work.

Hepatocellular carcinoma (HCC) represents the most prevalent form of primary liver cancer and has a high mortality rate. Caspase-8 plays a pivotal role in an array of cellular signaling pathways and is essential for the governance of programmed cell death mechanisms, inflammatory responses, and the dynamics of the tumor microenvironment. Dysregulation of caspase-8 is intricately linked to the complex biological underpinnings of HCC. In this manuscript, we provide a comprehensive review of the regulatory roles of caspase-8 in apoptosis, necroptosis, pyroptosis, and PANoptosis, as well as its impact on inflammatory reactions and the intricate interplay with critical immune cells within the tumor microenvironment, such as tumor-associated macrophages, T cells, natural killer cells, and dendritic cells. Furthermore, we emphasize how caspase-8 plays pivotal roles in the development, progression, and drug resistance observed in HCC, and explore the potential of targeting caspase-8 as a promising strategy for HCC treatment.

As a mechanism of cell death, ferroptosis has gained popularity since 2012. The process is distinguished by iron toxicity and phospholipid accumulation, in contrast to autophagy, apoptosis, and other cell death mechanisms. It is implicated in the advancement of multiple diseases across the body. Researchers currently know that osteosarcoma, osteoporosis, and other orthopedic disorders are caused by NRF2, GPX4, and other ferroptosis star proteins. The effective relief of osteoarthritis symptoms from deterioration has been confirmed by clinical treatment with multiple ferroptosis inhibitors. At the same time, it should be reminded that the mechanisms involved in ferroptosis that regulate orthopedic diseases are not currently understood. In this manuscript, we present the discovery process of ferroptosis, the mechanisms involved in ferroptosis, and the role of ferroptosis in a variety of orthopedic diseases. We expect that this manuscript can provide a new perspective on clinical diagnosis and treatment of related diseases.

The skin is the largest organ in the human body and is made up of various cells and structures. Over time, the skin will age, which is not only influenced by internal factors, but also by external environmental factors, especially ultraviolet radiation. Aging causes immune system weakening in the elderly, which makes them more susceptible to dermatosis, such as type 2 inflammatory mediated pruritus. The immune response in this condition is marked by senescent cells consistently releasing low amounts of pro-inflammatory cytokines through a senescence-associated secretory phenotype (SASP). This continuous inflammation may accelerate immune system aging and establish a connection between immune aging and type 2 inflammatory skin diseases. In addition, two chronic pigmentation disorders, vitiligo and chloasma, are also associated with skin aging. Aged cells escape the immune system and accumulate in tissues, forming a microenvironment that promotes cancer. At the same time, “photoaging” caused by excessive exposure to ultraviolet radiation is also an important cause of skin cancer. This manuscript describes the possible links between skin aging and type 2 inflammation, chronic pigmentation disorders, and skin cancer and suggests some treatment options.

Autophagy is a highly conserved cellular self-digestive process that underlies the maintenance of cellular homeostasis. Autophagy is classified into three types: macrophage, chaperone-mediated autophagy (CMA) and microphagy, which maintain cellular homeostasis through different mechanisms. Altered autophagy regulation affects the progression of various skin diseases, including psoriasis (PA), systemic lupus erythematosus (SLE), vitiligo, atopic dermatitis (AD), alopecia areata (AA) and systemic sclerosis (SSc). In this review, we review the existing literature focusing on three mechanisms of autophagy, namely macrophage, chaperone-mediated autophagy and microphagy, as well as the roles of autophagy in the above six dermatological disorders in order to aid in further studies in the future.

Lung disease development involves multiple cellular processes, including inflammation, cell death, and proliferation. Research increasingly indicates that autophagy and its regulatory proteins can influence inflammation, programmed cell death, cell proliferation, and innate immune responses. Autophagy plays a vital role in the maintenance of homeostasis and the adaptation of eukaryotic cells to stress by enabling the chelation, transport, and degradation of subcellular components, including proteins and organelles. This process is essential for sustaining cellular balance and ensuring the health of the mitochondrial population. Recent studies have begun to explore the connection between autophagy and the development of different lung diseases. This article reviews the latest findings on the molecular regulatory mechanisms of autophagy in lung diseases, with an emphasis on potential targeted therapies for autophagy.

Ferroptosis, a form of regulated cell death distinct from apoptosis, necrosis, and autophagy, is increasingly recognized for its role in skin disease pathology. Characterized by iron accumulation and lipid peroxidation, ferroptosis has been implicated in the progression of various skin conditions, including psoriasis, photosensitive dermatitis, and melanoma. This review provides an in-depth analysis of the molecular mechanisms underlying ferroptosis and compares its cellular effects with other forms of cell death in the context of skin health and disease. We systematically examine the role of ferroptosis in five specific skin diseases, including ichthyosis, psoriasis, polymorphous light eruption (PMLE), vitiligo, and melanoma, detailing its influence on disease pathogenesis and progression. Moreover, we explore the current clinical landscape of ferroptosis-targeted therapies, discussing their potential in managing and treating skin diseases. Our aim is to shed light on the therapeutic potential of modulating ferroptosis in skin disease research and practice.

N6-methyladenosine (m6A) is a chemical modification of RNA and has become a widely discussed topic among scientific researchers in recent years. It is distributed in various organisms, including eukaryotes and bacteria. It has been found that m6A is composed of writers, erasers and readers and is involved in biological functions such as splicing, transport and translation of RNA. The balance of the human immune microenvironment is important for human health abnormalities. Increasing studies have found that m6A affects the development of immune diseases such as inflammatory enteritis and systemic lupus erythematosus (SLE) by participating in the homeostatic regulation of the immune microenvironment in vivo. In this manuscript, we introduce the composition, biological function, regulation of m6A in the immune microenvironment and its progression in various immune diseases, providing new targets and directions for the treatment of immune diseases in clinical practice.

Background: Ferroptosis, a newly recognized form of programmed cell death, is distinguished by its reliance on reactive oxygen species and iron-mediated lipid peroxidation, setting it apart from established types like apoptosis, cell necrosis, and autophagy. Recent studies suggest its role in exacerbating or mitigating diseases by influencing metabolic and signaling pathways in conditions such as tumors and ischemic organ damage. Evidence also links ferroptosis to various kidney diseases, prompting a review of its research status and potential breakthroughs in understanding and treating these conditions. Summary: In acute kidney disease (AKI), ferroptosis has been confirmed in animal kidneys after being induced by various factors such as renal ischemia-reperfusion and cisplatin, and glutathione peroxidase 4 (GPX4) is linked with AKI. Ferroptosis is associated with renal fibrosis in chronic kidney disease (CKD), TGF-β1 being crucial in this regard. In diabetic nephropathy (DN), high SLC7A11 and low nuclear receptor coactivator 4 (NCOA4) expressions are linked to disease progression. For polycystic kidney disease (PKD), ferroptosis promotes the disease by regulating ferroptosis in kidney tissue. Renal cell carcinoma (RCC) and lupus nephritis (LN) also have links to ferroptosis, with mtDNA and iron accumulation causing RCC and oxidative stress causing LN. Key Messages: Ferroptosis is a newly identified form of programmed cell death that is associated with various diseases. It targets metabolic and signaling pathways and has been linked to kidney diseases such as AKI, CKD, PKD, DN, LN, and clear cell RCC. Understanding its role in these diseases could lead to breakthroughs in their pathogenesis, etiology, and treatment.

Abstract Proteins in the plasma/serum mirror an individual’s physiology. Circulating extracellular vesicles (EVs) proteins constitute a large portion of the plasma/serum proteome. Thus, deep and unbiased proteomic analysis of circulating plasma/serum extracellular vesicles holds promise for discovering disease biomarkers as well as revealing disease mechanisms. We established a workflow for simple, deep, and reproducible proteome analysis of both serum large and small EVs enriched fractions by ultracentrifugation plus 4D-data-independent acquisition mass spectrometry (4D-DIA-MS). In our cohort study of obstetric antiphospholipid syndrome (OAPS), 4270 and 3328 proteins were identified from large and small EVs enriched fractions respectively. Both of them revealed known or new pathways related to OAPS. Increased levels of von Willebrand factor (VWF) and insulin receptor (INSR) were identified as candidate biomarkers, which shed light on hypercoagulability and abnormal insulin signaling in disease progression. Our workflow will significantly promote our understanding of plasma/serum-based disease mechanisms and generate new biomarkers.

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.

Ferroptosis, a new type of programmed cell death proposed in recent years, is characterized mainly by reactive oxygen species and iron-mediated lipid peroxidation and differs from programmed cell death, such as apoptosis, necrosis, and autophagy. Ferroptosis is associated with a variety of physiological and pathophysiological processes. Recent studies have shown that ferroptosis can aggravate or reduce the occurrence and development of diseases by targeting metabolic pathways and signaling pathways in tumors, ischemic organ damage, and other degenerative diseases related to lipid peroxidation. Increasing evidence suggests that ferroptosis is closely linked to the onset and progression of various ophthalmic conditions, including corneal injury, glaucoma, age-related macular degeneration, diabetic retinopathy, retinal detachment, and retinoblastoma. Our review of the current research on ferroptosis in ophthalmic diseases reveals significant advancements in our understanding of the pathogenesis, aetiology, and treatment of these conditions.

Hepatocellular carcinoma is the most common form of primary liver cancer and poses a significant challenge to the medical community because of its high mortality rate. In recent years, ferroptosis, a unique form of cell death, has garnered widespread attention. Ferroptosis, which is characterized by iron-dependent lipid peroxidation and mitochondrial alterations, is closely associated with the pathological processes of various diseases, including hepatocellular carcinoma. Long non-coding RNAs (lncRNAs), are a type of functional RNA, and play crucial regulatory roles in a variety of biological processes. In this manuscript, we review the regulatory roles of lncRNAs in the key aspects of ferroptosis, and summarize the research progress on ferroptosis-related lncRNAs in hepatocellular carcinoma.

Ageing is an inevitable process that affects various tissues and organs of the human body, leading to a series of physiological and pathological changes. Mechanisms such as telomere depletion, stem cell depletion, macrophage dysfunction, and cellular senescence gradually manifest in the body, significantly increasing the incidence of diseases in elderly individuals. These mechanisms interact with each other, profoundly impacting the quality of life of older adults. As the ageing population continues to grow, the burden on the public health system is expected to intensify. Globally, the prevalence of musculoskeletal system diseases in elderly individuals is increasing, resulting in reduced limb mobility and prolonged suffering. This review aims to elucidate the mechanisms of ageing and their interplay while exploring their impact on diseases such as osteoarthritis, osteoporosis, and sarcopenia. By delving into the mechanisms of ageing, further research can be conducted to prevent and mitigate its effects, with the ultimate goal of alleviating the suffering of elderly patients in the future.

With the development of global social economy and the deepening of the aging population, diseases related to aging have received increasing attention. The pathogenesis of many respiratory diseases remains unclear, and lung aging is an independent risk factor for respiratory diseases. The aging mechanism of the lung may be involved in the occurrence and development of respiratory diseases. Aging-induced immune, oxidative stress, inflammation, and telomere changes can directly induce and promote the occurrence and development of lung aging. Meanwhile, the occurrence of lung aging also further aggravates the immune stress and inflammatory response of respiratory diseases; the two mutually affect each other and promote the development of respiratory diseases. Explaining the mechanism and treatment direction of these respiratory diseases from the perspective of lung aging will be a new idea and research field. This review summarizes the changes in pulmonary microenvironment, metabolic mechanisms, and the progression of respiratory diseases associated with aging.

With the proposal of the “biological-psychological-social” model, clinical decision-makers and researchers have paid more attention to the bidirectional interactive effects between psychological factors and diseases. The brain-gut-microbiota axis, as an important pathway for communication between the brain and the gut, plays an important role in the occurrence and development of inflammatory bowel disease. This article reviews the mechanism by which psychological disorders mediate inflammatory bowel disease by affecting the brain-gut-microbiota axis. Research progress on inflammatory bowel disease causing “comorbidities of mind and body” through the microbiota-gut-brain axis is also described. In addition, to meet the needs of individualized treatment, this article describes some nontraditional and easily overlooked treatment strategies that have led to new ideas for “psychosomatic treatment”.

ObjectiveWe aimed to evaluate the effects of different exercise rehabilitation (ER) programs on LVEF and the incidence of restenosis in patients after percutaneous coronary intervention (PCI) through a systematic review and an integrated network meta-analysis (NMA) to provide a reference for the clinical formulation of ER programs for PCI patients.MethodsMeta-analyses of the effects of different types of ER programs on LVEF and the incidence of reinfarction in post-PCI patients were retrieved from 11 domestic and foreign databases. The methodological and reporting quality of the included systematic reviews were evaluated using the AMSTAR 2 and PRISMA statements. The GRADE scoring system was used to evaluate the quality of evidence found in the studies included in the meta-analysis, and studies with high and intermediate-quality evidence were qualitatively analyzed. Stata software (version 16.0) was used to conduct an integrated NMA of the original RCTs with moderate and low risk of bias.ResultSixteen meta-analyses were included in this evaluation. The reporting quality of the included meta-analyses was relatively complete, and the methodological quality was low. Seventy RCTs were included in the NMA. The results showed that all types of rehabilitative exercises were safe and effectively increased LVEF and reduced the incidence of coronary restenosis in patients. The comprehensive exercise program was the most likely to improve LVEF, and the comprehensive exercise program, early exercise program, and high-intensity interval exercise were better than aerobic exercise. Comprehensive exercise programs, early exercise programs, and aerobic exercise reduced the incidence of restenosis in patients. However, Chinese Qigong did not reduce the incidence of restenosis in patients, and there was a risk of bias and inconsistency in the quantitative analysis of restenosis incidence.ConclusionComprehensive exercise programs have the greatest therapeutic significance in improving cardiac output and reducing restenosis rates in post-PCI patients. The early exercise program has great potential but requires kinesiologists to work with physicians to structure the program and strengthen out-of-hospital management. Aerobic exercise has the least therapeutic significance, and Chinese Qigong is suitable for promotion based on its better efficacy than aerobic exercise and may be an alternative to aerobic exercise, but more experimental evidence is needed.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, PROSPERO CRD42022374590.

Abstract Cancer has always been a worldwide problem, and the application of radiotherapy has greatly improved the survival rate of cancer patients. Radiotherapy can modulate multiple cell fate decisions to kill tumor cells and achieve its therapeutic effect. With the development of radiotherapy technology, how to increase the killing effect of tumor cells and reduce the side effects on normal cells has become a new problem. In this review, we summarize the mechanisms by which radiotherapy induces tumor cell apoptosis, necrosis, necroptosis, pyroptosis, ferroptosis, autophagy, senescence, mitotic catastrophe, and cuproptosis. An in-depth understanding of these radiotherapy-related cell fate decisions can greatly improve the efficiency of radiotherapy for cancer.

Chemical modifications are a specific and efficient way to regulate the function of biological macromolecules. Among them, RNA molecules exhibit a variety of modifications that play important regulatory roles in various biological processes. More than 170 modifications have been identified in RNA molecules, among which the most common internal modifications include N6-methyladenine (m6A), n1-methyladenosine (m1A), 5-methylcytosine (m5C), and 7-methylguanine nucleotide (m7G). The most widely affected RNA modification is m6A, whose writers, readers, and erasers all have regulatory effects on RNA localization, splicing, translation, and degradation. These functions, in turn, affect RNA functionality and disease development. RNA modifications, especially m6A, play a unique role in renal cell carcinoma disease. In this manuscript, we will focus on the biological roles of m6A in renal diseases such as acute kidney injury, chronic kidney disease, lupus nephritis, diabetic kidney disease, and renal cancer.

Cardiovascular and cerebrovascular diseases are the number one killer threatening people's life and health, among which cardiovascular thrombotic events are the most common. As the cause of particularly serious cardiovascular events, thrombosis can trigger fatal crises such as acute coronary syndrome (myocardial infarction and unstable angina), cerebral infarction and so on. Circulating monocytes are an important part of innate immunity. Their main physiological functions are phagocytosis, removal of injured and senescent cells and their debris, and development into macrophages and dendritic cells. At the same time, they also participate in the pathophysiological processes of pro-coagulation and anticoagulation. According to recent studies, monocytes have been found to play a significant role in thrombosis and thrombotic diseases of the immune system. In this manuscript, we review the relationship between monocyte subsets and cardiovascular thrombotic events and analyze the role of monocytes in arterial thrombosis and their involvement in intravenous thrombolysis. Finally, we summarize the mechanism and therapeutic regimen of monocyte and thrombosis in hypertension, antiphospholipid syndrome, atherosclerosis, rheumatic heart disease, lower extremity deep venous thrombosis, and diabetic nephropathy.

The most extensively and well-investigated sequences in the human genome are protein-coding genes, while large numbers of non-coding sequences exist in the human body and are even more diverse with more potential roles than coding sequences. With the unveiling of non-coding RNA research, long-stranded non-coding RNAs (lncRNAs), a class of transcripts >200 nucleotides in length primarily expressed in the nucleus and rarely in the cytoplasm, have drawn our attention. LncRNAs are involved in various levels of gene regulatory processes, including but not limited to promoter activity, epigenetics, translation and transcription efficiency, and intracellular transport. They are also dysregulated in various pathophysiological processes, especially in diseases and cancers involving genomic imprinting. In recent years, numerous studies have linked lncRNAs to the pathophysiology of various kidney diseases. This review summarizes the molecular mechanisms involved in lncRNAs, their impact on kidney diseases, and associated complications, as well as the value of lncRNAs as emerging biomarkers for the prevention and prognosis of kidney diseases, suggesting their potential as new therapeutic tools.

Kidney disease encompasses a complex set of diseases that can aggravate or start systemic pathophysiological processes through their complex metabolic mechanisms and effects on body homoeostasis. The prevalence of kidney disease has increased dramatically over the last two decades. CD4+CD25+ regulatory T (Treg) cells that express the transcription factor forkhead box protein 3 (Foxp3) are critical for maintaining immune homeostasis and preventing autoimmune disease and tissue damage caused by excessive or unnecessary immune activation, including autoimmune kidney diseases. Recent studies have highlighted the critical role of metabolic reprogramming in controlling the plasticity, stability, and function of Treg cells. They are also likely to play a vital role in limiting kidney transplant rejection and potentially promoting transplant tolerance. Metabolic pathways, such as mitochondrial function, glycolysis, lipid synthesis, glutaminolysis, and mammalian target of rapamycin (mTOR) activation, are involved in the development of renal diseases by modulating the function and proliferation of Treg cells. Targeting metabolic pathways to alter Treg cells can offer a promising method for renal disease therapy. In this review, we provide a new perspective on the role of Treg cell metabolism in renal diseases by presenting the renal microenvironment、relevant metabolites of Treg cell metabolism, and the role of Treg cell metabolism in various kidney diseases.

Systemic lupus erythematosus (SLE) is an archetype autoimmune disease characterized by a myriad of immunoregulatory abnormalities that drives injury to multiple tissues and organs. Due to the involvement of various immune cells, inflammatory cytokines, and related signaling pathways, researchers have spent a great deal of effort to clarify the complex etiology and pathogenesis of SLE. Nevertheless, current understanding of the pathogenesis of SLE is still in the early stages, and available nonspecific treatment options for SLE patients remain unsatisfactory. First discovered in 1993, microRNAs (miRNAs) are small RNA molecules that control the expression of 1/3 of human genes at the post-transcriptional level and play various roles in gene regulation. The aberrant expression of miRNAs in SLE patients has been intensively studied, and further studies have suggested that these miRNAs may be potentially relevant to abnormal immune responses and disease progression in SLE. The aim of this review was to summarize the specific miRNAs that have been observed aberrantly expressed in several important pathogenetic processes in SLE, such as DCs abnormalities, overactivation and autoantibody production of B cells, aberrant activation of CD4+ T cells, breakdown of immune tolerance, and abnormally increased production of inflammatory cytokines. Our summary highlights a novel perspective on the intricate regulatory network of SLE, which helps to enrich our understanding of this disorder and ignite future interest in evaluating the molecular regulation of miRNAs in autoimmunity SLE.

Kidney disease is a general term for heterogeneous damage that affects the function and the structure of the kidneys. The rising incidence of kidney diseases represents a considerable burden on the healthcare system, so the development of new drugs and the identification of novel therapeutic targets are urgently needed. The pathophysiology of kidney diseases is complex and involves multiple processes, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Heme oxygenase-1 (HO-1), an enzyme involved in the process of heme degradation, has attracted widespread attention in recent years due to its cytoprotective properties. As an enzyme with known anti-oxidative functions, HO-1 plays an indispensable role in the regulation of oxidative stress and is involved in the pathogenesis of several kidney diseases. Moreover, current studies have revealed that HO-1 can affect cell proliferation, cell maturation, and other metabolic processes, thereby altering the function of immune cells. Many strategies, such as the administration of HO-1-overexpressing macrophages, use of phytochemicals, and carbon monoxide-based therapies, have been developed to target HO-1 in a variety of nephropathological animal models, indicating that HO-1 is a promising protein for the treatment of kidney diseases. Here, we briefly review the effects of HO-1 induction on specific immune cell populations with the aim of exploring the potential therapeutic roles of HO-1 and designing HO-1-based therapeutic strategies for the treatment of kidney diseases.

Fabricating ideal scaffolds for bone tissue engineering is a great challenge to researchers. To better mimic the mineral component and the microstructure of natural bone, several kinds of materials were adopted in our study, namely gelatin, polycaprolactone (PCL), nanohydroxyapatite (nHA), and bone powder. Three types of scaffolds were fabricated using electrospinning; gelatin/PCL, gelatin/PCL/nHA, and gelatin/PCL/bone powder. Scaffolds were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations. Then, Adipose-derived Stem Cells (ADSCs) were seeded on these scaffolds to study cell morphology, cell viability, and proliferation. Through this study, we found that nHA and bone powder can be successfully united in gelatin/PCL fibers. When compared with gelatin/PCL and gelatin/PCL/nHA, the gelatin/PCL/bone powder scaffolds could provide a better environment to increase ADSCs’ growth, adhesion, and proliferation. Thus, we think that gelatin/PCL/bone powder has good biocompatibility, and, when compared with nHA, bone powder may be more effective in bone tissue engineering due to the bioactive factors contained in it.

N6-methyladenosine (m6A) is a chemical modification of RNA and has become a widely discussed topic among scientific researchers in recent years. It is distributed in various organisms, including eukaryotes and bacteria. It has been found that m6A is composed of writers, erasers and readers and is involved in biological functions such as splicing, transport and translation of RNA. The balance of the human immune microenvironment is important for human health abnormalities. Increasing studies have found that m6A affects the development of immune diseases such as inflammatory enteritis and systemic lupus erythematosus (SLE) by participating in the homeostatic regulation of the immune microenvironment in vivo. In this manuscript, we introduce the composition, biological function, regulation of m6A in the immune microenvironment and its progression in various immune diseases, providing new targets and directions for the treatment of immune diseases in clinical practice. [ABSTRACT FROM AUTHOR]