Unveiling ferroptosis: a new frontier in skin disease research.

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.

Precision therapy targeting CAMK2 to overcome resistance to EGFR inhibitors in FAT1-mutated oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca2+/calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 (FAT1)-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro. The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1-mutated OSCC cells and suppressed tumor growth in vivo. Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1-mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION: Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.

Understanding the relationship between HCV infection and progression of kidney disease.

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.

Mechanism and treatment of secondary glaucoma after corneal transplantation: a review.

Corneal transplantation is a common treatment for corneal diseases. Secondary glaucoma after corneal transplantation is the second leading cause of failure of keratoplasty. This article reviews the mechanism and treatment of secondary glaucoma after corneal transplantation.

Ferroptosis: a novel mechanism of cell death in ophthalmic conditions.

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.

Ferroptosis and hepatocellular carcinoma: the emerging role of lncRNAs.

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.

A Deep Insight into Ferroptosis in Renal Disease: Facts and Perspectives.

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-ß1 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.

The aging lung: microenvironment, mechanisms, and diseases.

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.

The impact of ageing mechanisms on musculoskeletal system diseases in the elderly.

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.

From gut to brain: understanding the role of microbiota in inflammatory bowel disease.

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".

Thioredoxin (Trx): A redox target and modulator of cellular senescence and aging-related diseases.

Thioredoxin (Trx) is a compact redox-regulatory protein that modulates cellular redox state by reducing oxidized proteins. Trx exhibits dual functionality as an antioxidant and a cofactor for diverse enzymes and transcription factors, thereby exerting influence over their activity and function. Trx has emerged as a pivotal biomarker for various diseases, particularly those associated with oxidative stress, inflammation, and aging. Recent clinical investigations have underscored the significance of Trx in disease diagnosis, treatment, and mechanistic elucidation. Despite its paramount importance, the intricate interplay between Trx and cellular senescence-a condition characterized by irreversible growth arrest induced by multiple aging stimuli-remains inadequately understood. In this review, our objective is to present a comprehensive and up-to-date overview of the structure and function of Trx, its involvement in redox signaling pathways and cellular senescence, its association with aging and age-related diseases, as well as its potential as a therapeutic target. Our review aims to elucidate the novel and extensive role of Trx in senescence while highlighting its implications for aging and age-related diseases.

Extracellular vesicles modulate key signalling pathways in refractory wound healing.

Chronic wounds are wounds that cannot heal properly due to various factors, such as underlying diseases, infection or reinjury, and improper healing of skin wounds and ulcers can cause a serious economic burden. Numerous studies have shown that extracellular vesicles (EVs) derived from stem/progenitor cells promote wound healing, reduce scar formation and have significant advantages over traditional treatment methods. EVs are membranous particles that carry various bioactive molecules from their cellular origins, such as cytokines, nucleic acids, enzymes, lipids and proteins. EVs can mediate cell-to-cell communication and modulate various physiological processes, such as cell differentiation, angiogenesis, immune response and tissue remodelling. In this review, we summarize the recent advances in EV-based wound healing, focusing on the signalling pathways that are regulated by EVs and their cargos. We discuss how EVs derived from different types of stem/progenitor cells can promote wound healing and reduce scar formation by modulating the Wnt/ß-catenin, phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin, vascular endothelial growth factor, transforming growth factor ß and JAK-STAT pathways. Moreover, we also highlight the challenges and opportunities for engineering or modifying EVs to enhance their efficacy and specificity for wound healing.

The role of N6-methyladenosine (m6A) in kidney diseases.

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.

Targeting Ferroptosis in Bone-Related Diseases: Facts and Perspectives.

Ferroptosis is a new cell fate decision discovered in recent years. Unlike apoptosis, autophagy or pyroptosis, ferroptosis is characterized by iron-dependent lipid peroxidation and mitochondrial morphological changes. Ferroptosis is involved in a variety of physiological and pathological processes. Since its discovery, ferroptosis has been increasingly studied concerning bone-related diseases. In this review, we focus on the latest research progress and prospects, summarize the regulatory mechanisms of ferroptosis, and discuss the role of ferroptosis in the pathogenesis of bone-related diseases, such as osteoporosis (OP), osteoarthritis (OA), rheumatoid arthritis (RA), and osteosarcoma (OS), as well as its therapeutic potential.

Mitochondrial DNA-targeted therapy: A novel approach to combat cancer.

Mitochondrial DNA (mtDNA) encodes proteins and RNAs that are essential for mitochondrial function and cellular homeostasis, and participates in important processes of cellular bioenergetics and metabolism. Alterations in mtDNA are associated with various diseases, especially cancers, and are considered as biomarkers for some types of tumors. Moreover, mtDNA alterations have been found to affect the proliferation, progression and metastasis of cancer cells, as well as their interactions with the immune system and the tumor microenvironment (TME). The important role of mtDNA in cancer development makes it a significant target for cancer treatment. In recent years, many novel therapeutic methods targeting mtDNA have emerged. In this study, we first discussed how cancerogenesis is triggered by mtDNA mutations, including alterations in gene copy number, aberrant gene expression and epigenetic modifications. Then, we described in detail the mechanisms underlying the interactions between mtDNA and the extramitochondrial environment, which are crucial for understanding the efficacy and safety of mtDNA-targeted therapy. Next, we provided a comprehensive overview of the recent progress in cancer therapy strategies that target mtDNA. We classified them into two categories based on their mechanisms of action: indirect and direct targeting strategies. Indirect targeting strategies aimed to induce mtDNA damage and dysfunction by modulating pathways that are involved in mtDNA stability and integrity, while direct targeting strategies utilized molecules that can selectively bind to or cleave mtDNA to achieve the therapeutic efficacy. This study highlights the importance of mtDNA-targeted therapy in cancer treatment, and will provide insights for future research and development of targeted drugs and therapeutic strategies.

The role of monocytes in thrombotic diseases: a review.

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 role of thyroid hormone in the renal immune microenvironment.

Thyroid hormones are essential for proper kidney growth and development. The kidney is not only the organ of thyroid hormone metabolism but also the target organ of thyroid hormone. Kidney disease is a common type of kidney damage, mainly including different types of acute kidney injury, chronic kidney disease, diabetic nephropathy, lupus nephritis, and renal cell carcinoma. The kidney is often damaged by an immune response directed against its antigens or a systemic immune response. A variety of immune cells in the innate and adaptive immune systems, including neutrophils, macrophages, dendritic cells, T lymphocytes, and B lymphocytes, is essential for maintaining immune homeostasis and preventing autoimmune kidney disease. Recent studies have found that thyroid hormone plays an indispensable role in the immune microenvironment of various kidney diseases. Thyroid hormones regulate the activity of neutrophils, and dendritic cells express triiodothyronine receptors. Compared to hypothyroidism, hyperthyroidism has a greater effect on neutrophils. Furthermore, in adaptive immune systems, thyroid hormone may activate T lymphocytes through several underlying mechanisms, such as mediating NF-κB, protein kinase C signalling pathways, and ß-adrenergic receptors, leading to increased T lymphocyte activation. The present review discusses the effects of thyroid hormone metabolism regulation in the immune microenvironment on the function of various immune cells, especially neutrophils, macrophages, dendritic cells, T lymphocytes, and B lymphocytes. Although there are not enough data at this stage to conclude the clinical relevance of these findings, thyroid hormone metabolism may influence autoimmune kidney disease by regulating the renal immune microenvironment.

Informativeness across Interpreting Types: Implications for Language Shifts under Cognitive Load.

Previous quantitative studies discussing interpreting types have focused on various features of linguistic forms in outputs. However, none of them has examined their informativeness. Entropy, as a measure of the average information content and the uniformity of the probability distribution of language units, has been applied to quantitative linguistic research on different types of language texts. In the present study, entropy and repeat rate were used to investigate the difference of overall informativeness and concentration of output texts between simultaneous interpreting and consecutive interpreting. We intend to figure out the frequency distribution patterns of word and word category in two types of interpreting texts. Analyses of linear mixed-effects models showed that entropy and repeat rate can distinguish the informativeness of consecutive and simultaneous interpreting outputs, and consecutive interpreting outputs entail a higher word entropy value and a lower word repeat rate than simultaneous interpreting outputs. We propose that consecutive interpreting is a cognitive process which reaches an equilibrium between production economy for interpreters and comprehension sufficiency for listeners, especially in the case where input speeches are more complex. Our findings also shed lights on the selection of interpreting types in application scenarios. The current research is the first of its kind in examining informativeness across interpreting types, demonstrating a dynamic adaptation of language users to extreme cognitive load.

Computer especially AI-assisted drug virtual screening and design in traditional Chinese medicine.

BACKGROUND: Traditional Chinese medicine (TCM), as a significant part of the global pharmaceutical science, the abundant molecular compounds it contains is a valuable potential source of designing and screening new drugs. However, due to the un-estimated quantity of the natural molecular compounds and diversity of the related problems drug discovery such as precise screening of molecular compounds or the evaluation of efficacy, physicochemical properties and pharmacokinetics, it is arduous for researchers to design or screen applicable compounds through old methods. With the rapid development of computer technology recently, especially artificial intelligence (AI), its innovation in the field of virtual screening contributes to an increasing efficiency and accuracy in the process of discovering new drugs. PURPOSE: This study systematically reviewed the application of computational approaches and artificial intelligence in drug virtual filtering and devising of TCM and presented the potential perspective of computer-aided TCM development. STUDY DESIGN: We made a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Then screening the most typical articles for our research. METHODS: The systematic review was performed by following the PRISMA guidelines. The databases PubMed, EMBASE, Web of Science, CNKI were used to search for publications that focused on computer-aided drug virtual screening and design in TCM. RESULT: Totally, 42 corresponding articles were included in literature reviewing. Aforementioned studies were of great significance to the treatment and cost control of many challenging diseases such as COVID-19, diabetes, Alzheimer's Disease (AD), etc. Computational approaches and AI were widely used in virtual screening in the process of TCM advancing, which include structure-based virtual screening (SBVS) and ligand-based virtual screening (LBVS). Besides, computational technologies were also extensively applied in absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction of candidate drugs and new drug design in crucial course of drug discovery. CONCLUSIONS: The applications of computer and AI play an important role in the drug virtual screening and design in the field of TCM, with huge application prospects.

Emerging natural recombinant Marek's disease virus between vaccine and virulence strains and their pathogenicity.

Marek's disease virus (MDV), an oncogenic virus belonging to the subfamily Alphaherpesvirinae, causes Marek's disease (MD). Vaccines can control MD but cannot block the viral infection; they are considered imperfect vaccines, which carry the risk of recombination. In this study, six natural recombinant MDV strains were isolated from infected chickens in commercial flocks in China. We sequenced and analysed the genetic characteristics of the isolates (HC/0803, CH/10, SY/1219, DH/1307, DH/1504 and Hrb/1504). We found that the six strains resulted from recombination between the vaccine CVI988/Rispens (CVI988) strain skeleton and the virulence strain's partial unique short region. Additionally, a pathogenicity study was performed on recombinant strains (HC/0803 and DH/1307) and reference strains (CVI988 and LHC2) to evaluate their virulence. LHC2 induced 84.6% mortality in infected chickens; however, no mortality was recorded in chickens inoculated with HC/0803, DH/1307 or CVI988. However, HC/0803 and DH/1307 induced a notable spleen enlargement, and mild thymus and bursa atrophy at 11-17 days post-challenge (dpc). The viral genome load in the HC/0803- and DH/1307-challenged chickens peaked at approximately 107 viral copies per million host cells at 17 dpc and was similar to that in LHC2-challenged chickens, but significantly higher than that of CVI988-challenged chickens. In summary, HC/0803 and DH/1307 displayed mild virulence with temporal damage to the immune organs of chicken and a higher reproduction capability than the vaccine strain CVI988. Our study provides direct evidence of the emergence of recombinant MDV strains between vaccine and virulence strains in nature. The emergence of natural recombinant strains suggests that live vaccines can act as genetic donors for genomic recombination, and recombination may be a safety concern when administering live vaccines. These findings demonstrate that recombination promotes genetic diversity and increases the complexity of disease diagnosis, prevention and control.