Myostatin's marvels: From muscle regulator to diverse implications in health and disease.

Myostatin, a member of the transforming growth factor-ß superfamily, is a pivotal regulator of skeletal muscle growth in mammals. Its discovery has sparked significant interest due to its multifaceted roles in various physiological processes and its potential therapeutic implications. This review explores the diverse functions of myostatin in skeletal muscle development, maintenance and pathology. We delve into its regulatory mechanisms, including its interaction with other signalling pathways and its modulation by various factors such as microRNAs and mechanical loading. Furthermore, we discuss the therapeutic strategies aimed at targeting myostatin for the treatment of muscle-related disorders, including cachexia, muscular dystrophy and heart failure. Additionally, we examine the impact of myostatin deficiency on craniofacial morphology and bone development, shedding light on its broader implications beyond muscle biology. Through a comprehensive analysis of the literature, this review underscores the importance of further research into myostatin's intricate roles and therapeutic potential in human health and disease.

Regulation of protein phosphorylation by PTPN2 and its small-molecule inhibitors/degraders as a potential disease treatment strategy.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is an enzyme that dephosphorylates proteins with tyrosine residues, thereby modulating relevant signaling pathways in vivo. PTPN2 acts as tumor suppressor or tumor promoter depending on the context. In some cancers, such as colorectal, and lung cancer, PTPN2 defects could impair the protein tyrosine kinase pathway, which is often over-activated in cancer cells, and inhibit tumor development and progression. However, PTPN2 can also suppress tumor immunity by regulating immune cells and cytokines. The structure, functions, and substrates of PTPN2 in various tumor cells were reviewed in this paper. And we summarized the research status of small molecule inhibitors and degraders of PTPN2. It also highlights the potential opportunities and challenges for developing PTPN2 inhibitors as anticancer drugs.

Cold shock treatment alleviates pitting in sweet cherry fruit by enhancing antioxidant enzymes activity and regulating membrane lipid metabolism.

BACKGROUND: In order to comprehend the regulatory mechanisms that result in the alleviation of sweet cherry pitting disorder through cold shock (0 °C ice-water mixture for 10 min), an investigation was conducted into the impacts of cold shock treatment (CST) on membrane lipid metabolism, antioxidant enzyme activity, as well as pitting of cold-stored sweet cherry fruit. RESULTS: CST significantly inhibited the increase in pitting incidence, pitting index, and decay incidence. The CST treatment provided greater titratable acidity, firmness as well as total content of soluble solids. The use of CST prevented the build-up of superoxide anions, hydrogen peroxide, malondialdehyde, and reduced permeability of cell membranes. When in contrast to control group, the CST also raised the expression levels along with activity of the antioxidant enzymes ascorbate peroxidase (APX), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT). Furthermore, CST reduced the amount of fruit cell membrane peroxidation, suppressed the activity of phospholipase and lipoxygenase, postponed the rise in saturated fatty acids (SFAs) and decrease in unsaturated fatty acids (USFAs), ultimately keeping a high ratio of USFAs to SFAs. CONCLUSION: CST can alleviating pitting disorder in sweet cherry fruit via preventing peroxidation of membrane lipid and elevating the antioxidant enzymes activity. © 2024 Society of Chemical Industry.

Transcriptomic analysis of mRNA and miRNA reveals new insights into the regulatory mechanisms of Anadara granosa responses to heat stress.

Temperature fluctuations resulting from climate change and global warming pose significant threats to various species. The blood clam, Anadara granosa, a commercially important marine bivalve, predominantly inhabits intertidal mudflats that are especially susceptible to elevated temperatures. This vulnerability has led to noticeable declines in the survival rates of A. granosa larvae, accompanied by an increase in malformations. Despite these observable trends, there is a lack of comprehensive research on the regulatory mechanisms underlying A. granosa's responses to heat stress. In this study, we examined the survival rates of A. granosa under varying high temperature conditions, selecting 34 °C as heat stress temperature. Enzyme activity assays have shed light on A. granosa's adaptive response to heat stress, revealing its ability to maintain redox balance and transition from aerobic to anaerobic metabolic pathways. Subsequently, mRNA and miRNA transcriptome analyses were conducted, elucidating several key responses of A. granosa to heat stress. These responses include the upregulation of transcription and protein synthesis, downregulation of proteasome activity, and metabolic pattern adjustments. Furthermore, we identified miRNA-mRNA networks implicated in heat stress responses, potentially serving as valuable candidate markers for A. granosa's heat stress response. Notably, we validated the involvement of agr-miR-3199 in A. granosa's heat stress response through its regulation of the target gene Foxj1. These findings not only deepen our understanding of the molecular mechanisms underlying the blood clam's response to heat stress but also offer valuable insights for enhancing heat stress resilience in the blood clam aquaculture industry. Moreover, they contribute to improved cultivation strategies for molluscs in the face of global warming and have significant implications for the conservation of marine resources and the preservation of ecological balance.

The role of melatonin in delaying senescence and maintaining quality in postharvest horticultural products.

The postharvest lifespan of horticultural products is closely related to loss of nutritional quality, accompanied by a rapid decline in shelf life, commercial value, and marketability. Melatonin (MT) application not only maintains quality but also delays senescence in horticultural products. This paper reviews biosynthesis and metabolism of endogenous MT, summarizes significant effects of exogenous MT application on postharvest horticultural products, examines regulatory mechanisms of MT-mediated effects, and provides an integrated review for understanding the positive role of MT in senescence delay and quality maintenance. As a multifunctional molecule, MT coordinates other signal molecules, such as ABA, ETH, JA, SA, NO, and Ca2+, to regulate postharvest ripening and senescence. Several metabolic pathways are involved in regulation of MT during postharvest senescence, including synthesis and signal transduction of plant hormones, redox homeostasis, energy metabolism, carbohydrate metabolism, and degradation of pigment and cell wall components. Moreover, MT regulates expression of genes related to plant hormones, antioxidant systems, energy generation, fruit firmness and colour, membrane integrity, and carbohydrate storage. Consequently, MT could become an emerging and eco-friendly preservative to extend shelf life and maintain postharvest quality of horticultural products.

RNA-binding proteins in bone pathophysiology.

Bone remodelling is a highly regulated process that maintains mineral homeostasis and preserves bone integrity. During this process, intricate communication among all bone cells is required. Indeed, adapt to changing functional situations in the bone, the resorption activity of osteoclasts is tightly balanced with the bone formation activity of osteoblasts. Recent studies have reported that RNA Binding Proteins (RBPs) are involved in bone cell activity regulation. RBPs are critical effectors of gene expression and essential regulators of cell fate decision, due to their ability to bind and regulate the activity of cellular RNAs. Thus, a better understanding of these regulation mechanisms at molecular and cellular levels could generate new knowledge on the pathophysiologic conditions of bone. In this Review, we provide an overview of the basic properties and functions of selected RBPs, focusing on their physiological and pathological roles in the bone.

Natural Compounds as Protease Inhibitors in Therapeutic Focus on Cancer Therapy.

Proteases are implicated in every hallmark of cancer and have complicated functions. For cancer cells to survive and thrive, the process of controlling intracellular proteins to keep the balance of the cell proteome is essential. Numerous natural compounds have been used as ligands/ small molecules to target various proteases that are found in the lysosomes, mitochondria, cytoplasm, and extracellular matrix, as possible anticancer therapeutics. Promising protease modulators have been developed for new drug discovery technology through recent breakthroughs in structural and chemical biology. The protein structure, function of significant tumor-related proteases, and their natural compound inhibitors have been briefly included in this study. This review highlights the most current frontiers and future perspectives for novel therapeutic approaches associated with the list of anticancer natural compounds targeting protease and the mode and mechanism of proteinase-mediated molecular pathways in cancer.

Pathogenesis of cardiovascular diseases: effects of mitochondrial CF6 on endothelial cell function.

Cardiovascular disease (CVD) stands as a predominant global cause of morbidity and mortality, necessitating effective and cost-efficient therapies for cardiovascular risk reduction. Mitochondrial coupling factor 6 (CF6), identified as a novel proatherogenic peptide, emerges as a significant risk factor in endothelial dysfunction development, correlating with CVD severity. CF6 expression can be heightened by CVD risk factors like mechanical force, hypoxia, or high glucose stimuli through the NF-κB pathway. Many studies have explored the CF6-CVD relationship, revealing elevated plasma CF6 levels in essential hypertension, atherosclerotic cardiovascular disease (ASCVD), stroke, and preeclampsia patients. CF6 acts as a vasoactive and proatherogenic peptide in CVD, inducing intracellular acidosis in vascular endothelial cells, inhibiting nitric oxide (NO) and prostacyclin generation, increasing blood pressure, and producing proatherogenic molecules, significantly contributing to CVD development. CF6 induces an imbalance in endothelium-dependent factors, including NO, prostacyclin, and asymmetric dimethylarginine (ADMA), promoting vasoconstriction, vascular remodeling, thrombosis, and insulin resistance, possibly via C-src Ca2+ and PRMT-1/DDAH-2-ADMA-NO pathways. This review offers a comprehensive exploration of CF6 in the context of CVD, providing mechanistic insights into its role in processes impacting CVD, with a focus on CF6 functions, intracellular signaling, and regulatory mechanisms in vascular endothelial cells.

Iron Homeostatic Regulation in Saccharomyces cerevisiae: Introduction to a Computational Modeling Method.

Over the past 30 years, much has been learned regarding iron homeostatic regulation in budding yeast, S. cerevisiae, including the identity of many of the proteins and molecular-level regulatory mechanisms involved. Most advances have involved inferring such mechanisms based on the analysis of iron-dysregulation phenotypes arising in various genetic mutant strains. Still lacking is a cellular- or system-level understanding of iron homeostasis. These experimental advances are summarized in this review, and a method for developing cellular-level regulatory mechanisms in yeast is presented. The method employs the results of Mössbauer spectroscopy of whole cells and organelles, iron quantification of the same, and ordinary differential equation-based mathematical models. Current models are simplistic when compared to the complexity of iron homeostasis in real cells, yet they hold promise as a useful, perhaps even required, complement to the popular genetics-based approach. The fundamental problem in comprehending cellular regulatory mechanisms is that, given the complexities involved, different molecular-level mechanisms can often give rise to virtually indistinguishable cellular phenotypes. Mathematical models cannot eliminate this problem, but they can minimize it.

Advances in CircRNAs in the Past Decade: Review of CircRNAs Biogenesis, Regulatory Mechanisms, and Functions in Plants.

Circular RNA (circRNA) is a type of non-coding RNA with multiple biological functions. Whole circRNA genomes in plants have been identified, and circRNAs have been demonstrated to be widely present and highly expressed in various plant tissues and organs. CircRNAs are highly stable and conserved in plants, and exhibit tissue specificity and developmental stage specificity. CircRNAs often interact with other biomolecules, such as miRNAs and proteins, thereby regulating gene expression, interfering with gene function, and affecting plant growth and development or response to environmental stress. CircRNAs are less studied in plants than in animals, and their regulatory mechanisms of biogenesis and molecular functions are not fully understood. A variety of circRNAs in plants are involved in regulating growth and development and responding to environmental stress. This review focuses on the biogenesis and regulatory mechanisms of circRNAs, as well as their biological functions during growth, development, and stress responses in plants, including a discussion of plant circRNA research prospects. Understanding the generation and regulatory mechanisms of circRNAs is a challenging but important topic in the field of circRNAs in plants, as it can provide insights into plant life activities and their response mechanisms to biotic or abiotic stresses as well as new strategies for plant molecular breeding and pest control.

Regulatory mechanisms and potential therapeutic targets in precancerous lesions of gastric cancer: A comprehensive review.

Precancerous lesions of gastric cancer (PLGC) represent a critical pathological stage in the transformation from normal gastric mucosa to gastric cancer (GC). The global incidence of PLGC has been rising over the past few decades, with a trend towards younger onset ages. Increasing evidence suggests that early prevention and treatment of PLGC can effectively reverse the malignant development of gastric mucosal epithelial cells. However, there is currently a lack of effective therapeutic drugs and methods. Recent years have witnessed substantial advancements in PLGC research, with the elucidation of novel regulatory mechanisms offering promising avenues for clinical intervention and drug development. This review aims to delineate potential targets for early prevention and diagnosis of GC while exploring innovative approaches to PLGC management. This article focuses on elucidating the regulatory mechanisms of the inflammatory microenvironment, bile acids (BA), glycolysis, autophagy, apoptosis, ferroptosis, and cellular senescence. We pay particular attention to potential therapeutic targets for PLGC, with the goal of providing insights and theoretical basis for clinical research on PLGC.

Regulation of anthocyanin synthesis in red lettuce in plant factory conditions: A review.

Anthocyanins, natural pigments known for their vibrant hues and beneficial properties, undergo intricate genetic control. However, red vegetables grown in plant factories frequently exhibit reduced anthocyanin synthesis compared to those in open fields due to factors like inadequate light, temperature, humidity, and nutrient availability. Comprehending these factors is essential for optimizing plant factory environments to enhance anthocyanin synthesis. This review insights the impact of physiological and genetic factors on the production of anthocyanins in red lettuce grown under controlled conditions. Further, we aim to gain a better understanding of the mechanisms involved in both synthesis and degradation of anthocyanins. Moreover, this review summarizes the identified regulators of anthocyanin synthesis in lettuce, addressing the gap in knowledge on controlling anthocyanin production in plant factories, with potential implications for various crops beyond red lettuce.

Accumulation characteristics of plant flavonoids and effects of cultivation measures on their biosynthesis: A review.

Flavonoids, a kind of secondary metabolites with both edible, medicinal and antioxidant purposes, could be widely used in food, drug processing, forest products, chemical industry and many other fields. Flavonoid production in plant organs were influenced by numerous internal and external factors at various stages, leading to differential gene expression and transcription factors activity. This study reviews the characteristics of major flavonoids categories, their distribution and accumulation in different plant parts and analyzing their molecular mechanisms. The results showed that: (1) Flavonoids exhibited wide distribution in all parts of the plants, with higher concentrations found in shoots system compared to roots sytem, across most species (predominantly accumulated in leaves and flowers). Plant sex, specific growth and development stages are both impacting indicators; (2) Cultivation methods and abiotic stress could affect plants flavonoid biosynthesis, while inappropriate physical treatments and cultivation methods induced stress in plants, prompting the activation of antioxidant mechanisms for flavonoid synthesis as a defence strategy via indirect pathways; (3) Various key genes and transcription factors collaboratively influenced key enzymes activities and regulate flavonoid biosynthesis, forming a complex regulatory network among these genes and transcription factors; (4) Further studies are required to elucidate whether flavonoid synthesis under various cultivation measures follows direct or indirect pathways. Furthermore, exploring methods for flavonoid biosynthesis and accumulation in specific organs or tissues, as well as identifying plant tissues and microorganisms with high efficiency in flavonoid biosynthesis, is essential for achieving targeted cultivation of plants and quantitative flavonoid production.

Linc00265 in human disease: A comprehensive analysis of its implications in human disease pathobiology and therapeutic prospect.

Linc00265, a long intergenic non-coding RNA, has garnered significant research attention due to its involvement in various human diseases, particularly cancer. It exhibits tissue-specific and dysregulated expression across multiple cancer types, including blood malignancies, colorectal, gastric, bladder, osteosarcoma, and hepatocellular carcinoma. This dysregulation is often associated with tumor aggressiveness, metastasis, and poor prognosis. Moreover, aberrant expression of Linc00265 has been reported in inflammation-related diseases such as osteoarthritis and sepsis. Mechanistically, Linc00265 acts as a competing endogenous RNA (CeRNA), sequestering specific microRNAs and thereby modulating their downstream targets. Additionally, it influences critical signaling pathways by mediating the key effectors within these pathways. Importantly, the dysregulation of Linc00265 shows promising potential as a diagnostic and prognostic biomarker in several human diseases. This review aims to comprehensively analyze the expression patterns, regulatory mechanisms, and potential biomarker roles of Linc00265 in human diseases, with a particular focus on cancer. By elucidating the functional implications of Linc00265, we can deepen our understanding of its roles in human diseases, potentially paving the way for novel therapeutic interventions in disease management.

Exploring the enigma: history, present, and future of long non-coding RNAs in cancer.

Long noncoding RNAs (lncRNAs), which are more than 200 nucleotides in length and do not encode proteins, play crucial roles in governing gene expression at both the transcriptional and posttranscriptional levels. These molecules demonstrate specific expression patterns in various tissues and developmental stages, suggesting their involvement in numerous developmental processes and diseases, notably cancer. Despite their widespread acknowledgment and the growing enthusiasm surrounding their potential as diagnostic and prognostic biomarkers, the precise mechanisms through which lncRNAs function remain inadequately understood. A few lncRNAs have been studied in depth, providing valuable insights into their biological activities and suggesting emerging functional themes and mechanistic models. However, the extent to which the mammalian genome is transcribed into functional noncoding transcripts is still a matter of debate. This review synthesizes our current understanding of lncRNA biogenesis, their genomic contexts, and their multifaceted roles in tumorigenesis, highlighting their potential in cancer-targeted therapy. By exploring historical perspectives alongside recent breakthroughs, we aim to illuminate the diverse roles of lncRNA and reflect on the broader implications of their study for understanding genome evolution and function, as well as for advancing clinical applications.

Enigmatic role of auxin response factors in plant growth and stress tolerance.

Abiotic and biotic stresses globally constrain plant growth and impede the optimization of crop productivity. The phytohormone auxin is involved in nearly every aspect of plant development. Auxin acts as a chemical messenger that influences gene expression through a short nuclear pathway, mediated by a family of specific DNA-binding transcription factors known as Auxin Response Factors (ARFs). ARFs thus act as effectors of auxin response and translate chemical signals into the regulation of auxin responsive genes. Since the initial discovery of the first ARF in Arabidopsis, advancements in genetics, biochemistry, genomics, and structural biology have facilitated the development of models elucidating ARF action and their contributions to generating specific auxin responses. Yet, significant gaps persist in our understanding of ARF transcription factors despite these endeavors. Unraveling the functional roles of ARFs in regulating stress response, alongside elucidating their genetic and molecular mechanisms, is still in its nascent phase. Here, we review recent research outcomes on ARFs, detailing their involvement in regulating leaf, flower, and root organogenesis and development, as well as stress responses and their corresponding regulatory mechanisms: including gene expression patterns, functional characterization, transcriptional, post-transcriptional and post- translational regulation across diverse stress conditions. Furthermore, we delineate unresolved questions and forthcoming challenges in ARF research.

The role of ferroptosis in acute kidney injury: mechanisms and potential therapeutic targets.

Acute kidney injury (AKI) is one of the most common and severe clinical renal syndromes with high morbidity and mortality. Ferroptosis is a form of programmed cell death (PCD), is characterized by iron overload, reactive oxygen species accumulation, and lipid peroxidation. As ferroptosis has been increasingly studied in recent years, it is closely associated with the pathophysiological process of AKI and provides a target for the treatment of AKI. This review offers a comprehensive overview of the regulatory mechanisms of ferroptosis, summarizes its role in various AKI models, and explores its interaction with other forms of cell death, it also presents research on ferroptosis in AKI progression to other diseases. Additionally, the review highlights methods for detecting and assessing AKI through the lens of ferroptosis and describes potential inhibitors of ferroptosis for AKI treatment. Finally, the review presents a perspective on the future of clinical AKI treatment, aiming to stimulate further research on ferroptosis in AKI.

The dual role of SUSD2 in cancer development.

Sushi domain-containing protein 2 (SUSD2, also known as the complement control protein domain) is a representative and vital protein in the SUSD protein family involved in many physiological and pathological processes beyond complement regulation. Cancer is one of the leading causes of death worldwide. The complex role of SUSD2 in tumorigenesis and cancer progression has raised increasing concerns. Studies suggest that SUSD2 has different regulatory tendencies among different tumors and exerts its biological effects in a cancer type-specific manner; for instance, it has oncogenic effects on breast cancer, gastric cancer, and glioma and has tumor-suppression effects on lung cancer, bladder cancer, and colon cancer. Moreover, SUSD2 can be regulated by noncoding RNAs, its promoter methylation and other molecules, such as Galectin-1 (Gal-1), tropomyosin alpha-4 chain (TPM4), and p63. The therapeutic implications of targeting SUSD2 have already been preliminarily revealed in some malignancies, including melanoma, colon cancer, and breast cancer. This article reviews the role and regulatory mechanisms of SUSD2 in cancer development, as well as its structure and distribution. We hope that this review will advance the understanding of SUSD2 as a diagnostic and/or prognostic biomarker and provide new avenues for the development of novel cancer therapies.

Exploring the role of m 6 A writer RBM15 in cancer: a systematic review.

In the contemporary epoch, cancer stands as the predominant cause of premature global mortality, necessitating a focused exploration of molecular markers and advanced therapeutic strategies. N6-methyladenosine (m6A), the most prevalent mRNA modification, undergoes dynamic regulation by enzymes referred to as methyltransferases (writers), demethylases (erasers), and effective proteins (readers). Despite lacking methylation activity, RNA-binding motif protein 15 (RBM15), a member of the m6A writer family, assumes a crucial role in recruiting the methyltransferase complex (MTC) and binding to mRNA. Although the impact of m6A modifications on cancer has garnered widespread attention, RBM15 has been relatively overlooked. This review briefly outlines the structure and operational mechanism, and delineates the unique role of RBM15 in various cancers, shedding light on its molecular basis and providing a groundwork for potential tumor-targeted therapies.