Dysregulated microRNAs in type 2 diabetes and breast cancer: Potential associated molecular mechanisms.

Type 2 diabetes (T2D) is a multifaceted and heterogeneous syndrome associated with complications such as hypertension, coronary artery disease, and notably, breast cancer (BC). The connection between T2D and BC is established through processes that involve insulin resistance, inflammation and other factors. Despite this comprehension the specific cellular and molecular mechanisms linking T2D to BC, especially through microRNAs (miRNAs), remain elusive. miRNAs are regulators of gene expression at the post-transcriptional level and have the function of regulating target genes by modulating various signaling pathways and biological processes. However, the signaling pathways and biological processes regulated by miRNAs that are associated with T2D and BC have not yet been elucidated. This review aims to identify dysregulated miRNAs in both T2D and BC, exploring potential signaling pathways and biological processes that collectively contribute to the development of BC.

Molecular mechanisms of diabetic nephropathy: A narrative review.

Diabetic nephropathy (DN) is the predominant secondary nephropathy resulting in global end-stage renal disease. It is attracting significant attention in both domestic and international research due to its widespread occurrence, fast advancement, and limited choices for prevention and treatment. The pathophysiology of this condition is intricate and involves multiple molecular and cellular pathways at various levels. This article provides a concise overview of the molecular processes involved in the development of DN. It discusses various factors, such as signaling pathways, cytokines, inflammatory responses, oxidative stress, cellular damage, autophagy, and epigenetics. The aim is to offer clinicians a valuable reference for DN's diagnosis, treatment, and intervention.

Unraveling the effect of micro/nanoplastics on the occurrence and horizontal transfer of environmental antibiotic resistance genes: Advances, mechanisms and future prospects.

Microplastics can not only serve as vectors of antibiotic resistance genes (ARGs), but also they and even nanoplastics potentially affect the occurrence of ARGs in indigenous environmental microorganisms, which aroused great concern for the development of antibiotic resistance. This article specifically reviews the effects of micro/nanoplastics (concentration, size, exposure time, chemical additives) and their interactions with other pollutants on environmental ARGs dissemination. The changes of horizontal genes transfer (HGT, i.e., conjugation, transformation and transduction) of ARGs caused by micro/nanoplastics were also summarized. Further, this review systematically sums up the molecular mechanisms of micro/nanoplastics regulating HGT process of ARGs, including reactive oxygen species production, cell membrane permeability, transfer-related genes expression, extracellular polymeric substances production, and ARG donor-recipient adsorption/contaminants adsorption/biofilm formation. The underlying mechanisms in changes of bacterial communities induced by micro/nanoplastics were also discussed as it was an important factor for structuring the profile of ARGs in the actual environment, including causing environmental stress, providing carbon sources, forming biofilms, affecting pollutants distribution and environmental factors. This review contributes to a systematical understanding of the potential risks of antibiotic resistance dissemination caused by micro/nanoplastics and provokes thinking about perspectives for future research and the management of micro/nanoplastics and plastics.

Adipokinetic hormone signaling mediates the enhanced fecundity of Diaphorina citri infected by 'Candidatus Liberibacter asiaticus'.

Diaphorina citri serves as the primary vector for 'Candidatus Liberibacter asiaticus (CLas),' the bacterium associated with the severe Asian form of huanglongbing. CLas-positive D. citri are more fecund than their CLas-negative counterparts and require extra energy expenditure. Therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. In this study, we found adipokinetic hormone (DcAKH) and its receptor (DcAKHR) were essential for increasing lipid metabolism and fecundity in response to CLas infection in D. citri. Knockdown of DcAKH and DcAKHR not only resulted in the accumulation of triacylglycerol and a decline of glycogen, but also significantly decreased fecundity and CLas titer in ovaries. Combined in vivo and in vitro experiments showed that miR-34 suppresses DcAKHR expression by binding to its 3' untranslated region, whilst overexpression of miR-34 resulted in a decline of DcAKHR expression and CLas titer in ovaries and caused defects that mimicked DcAKHR knockdown phenotypes. Additionally, knockdown of DcAKH and DcAKHR significantly reduced juvenile hormone (JH) titer and JH signaling pathway genes in fat bodies and ovaries, including the JH receptor, methoprene-tolerant (DcMet), and the transcription factor, Krüppel homolog 1 (DcKr-h1), that acts downstream of it, as well as the egg development related genes vitellogenin 1-like (DcVg-1-like), vitellogenin A1-like (DcVg-A1-like) and the vitellogenin receptor (DcVgR). As a result, CLas hijacks AKH/AKHR-miR-34-JH signaling to improve D. citri lipid metabolism and fecundity, while simultaneously increasing the replication of CLas, suggesting a mutualistic interaction between CLas and D. citri ovaries.

Advance on Chinese Medicine for Hypertensive Renal Damage: Focus on the Complex Molecular Mechanisms.

Hypertensive renal damage (HRD) is a major cause of end-stage renal disease. Among the causes of end-stage renal disease, HRD accounts for nearly 34% of the total number of cases. Antihypertensive treatment is primarily drug-based, but therapeutic efficacy is less effective and can have serious side effects. Chinese medicine (CM) has significant advantages in the treatment of HRD. CM is rich in various active ingredients and has the property of targeting multiple targets and channels. Therefore, the regulatory network of CM on disease is complex. A large number of CM have been employed to treat HRD, either as single applications or as part of compound formulations. The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system, antioxidation, anti-inflammation, rescue of endothelial function, regulation of vasoactive substance secretion and obesity-related factors, etc. This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects.

Insights into the role of glycerophospholipids on the iron export function of SLC40A1 and the molecular mechanisms of ferroportin disease.

SLC40A1 is the sole iron export protein reported in mammals. In humans, its dysfunction is responsible for ferroportin disease, an inborn error of iron metabolism transmitted as an autosomal dominant trait and observed in different ethnic groups. As a member of the major facilitator superfamily, SLC40A1 requires a series of conformational changes to enable iron translocation across the plasma membrane. The influence of lipids on protein stability and its conformational changes has been little investigated to date. Here, we combine molecular dynamics simulations of SLC40A1 embedded in membrane bilayers with experimental alanine scanning mutagenesis to analyze the specific role of glycerophospholipids. We identify four basic residues (Lys90, Arg365, Lys366, and Arg371) that are located at the membrane-cytosol interface and consistently interact with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) molecules. These residues surround a network of salt bridges and hydrogens bonds that play a critical role in stabilizing SLC40A1 in its basal outward-facing conformation. More deeply embedded in the plasma membrane, we identify Arg179 as a charged amino acid residue also tightly interacting with lipid polar heads. This results in a local deformation of the lipid bilayer. Interestingly, Arg179 is adjacent to Arg178, which forms a functionally important salt-bridge with Asp473 and is a recurrently associated with ferroportin disease when mutated to glutamine. We demonstrate that the two p.Arg178Gln and p.Arg179Thr missense variants have similar functional behaviors. These observations provide insights into the role of phospholipids in the formation/disruption of the SLC40A1 inner gate, and give a better understanding of the diversity of molecular mechanisms of ferroportin disease.

Exercise therapy in the application of sleep disorders.

Sleep disorders often accompany neurological injuries, significantly impacting patient recovery and quality of life.The efficacy and adherence of traditional treatment methods have certain limitations. Exercise has been found to be a highly beneficial treatment method, capable of preventing and alleviating neurological injuries and sleep disorders. This article reviews relevant research findings from both domestic and international sources over the past few decades, systematically summarizing and analyzing the application of exercise therapy in sleep disorders,strategy of exercise intervention program and the potential molecular mechanisms by which exercise therapy improves sleep disorders. Shortcomings in current research and suggestions are presented, providing a reference for future in-depth studies on exercise interventions for sleep disorders.

Enhancing aggregation of microalgae on polystyrene microplastics by high light: Processes, drivers, and environmental risk assessment.

Microplastics (MPs) are emerging pollutants, causing potential threats to aquatic ecosystems and serious concern in aggregating with microalgae (critical primary producers). When entering water bodies, MPs are expected to sink below the water surface and disperse into varying water compartments with different light intensities. However, how light influences the aggregation processes of algal cells onto MPs and the associated molecular coupling mechanisms and derivative risks remain poorly understood. Herein, we investigated the aggregation behavior between polystyrene microplastics (mPS, 10 µm) and Chlorella pyrenoidosa under low (LL, 15 µmol·m-2·s-1), normal (NL, 55 µmol·m-2·s-1), and high light (HL, 150 µmol·m-2·s-1) conditions from integrated in vivo and in silico assays. The results indicated that under LL, the mPS particles primarily existed independently, whereas under NL and HL, C. pyrenoidosa tightly bounded to mPS by secreting more protein-rich extracellular polymeric substances. Infrared spectroscopy analysis and density functional theory calculation revealed that the aggregation formation was driven by non-covalent interaction involving van der Waals force and hydrogen bond. These processes subsequently enhanced the deposition and adherence capacity of mPS and relieved its phytotoxicity. Overall, our findings advance the practical and theoretical understanding of the ecological impacts of MPs in complex aquatic environments.

Electrical Stimulation: How It Works and How to Apply It.

Electrical stimulation is emerging as a perioperative strategy to improve peripheral nerve regeneration and enhance functional recovery. Despite decades of research, new insights into the complex multifaceted mechanisms of electrical stimulation continue to emerge, providing greater understanding of the neurophysiology of nerve regeneration. In this study, we summarize what is known about how electrical stimulation modulates the molecular cascades and cellular responses innate to nerve injury and repair, and the consequential effects on axonal growth and plasticity. Further, we discuss how electrical stimulation is delivered in preclinical and clinical studies and identify knowledge gaps that may provide opportunities for optimization.

Spur development and evolution: An update.

Floral spurs, widely recognized as a classic example of key morphological and functional innovation and thought to have promoted the origin and adaptive evolution of many flowering plant lineages, have attracted the attention of researchers for centuries. Despite this, the mechanisms underlying the development and evolution of these structures remain poorly understood. Recent studies have discovered the phytohormones and transcription factor genes that play key roles in regulating patterns of cell division and cell expansion during spur morphogenesis. Spur morphogenesis was also found to be tightly linked with the programs specifying floral zygomorphy, floral organ identity determination, and nectary development. Independent origins and losses of spurs in different flowering plant lineages, therefore, may be attributed to changes in the spur program and/or its upstream ones.

Effects of Jasmonic Acid on Stress Response and Quality Formation in Vegetable Crops and Their Underlying Molecular Mechanisms.

The plant hormone jasmonic acid plays an important role in plant growth and development, participating in many physiological processes, such as plant disease resistance, stress resistance, organ development, root growth, and flowering. With the improvement in living standards, people have higher requirements regarding the quality of vegetables. However, during the growth process of vegetables, they are often attacked by pests and diseases and undergo abiotic stresses, resulting in their growth restriction and decreases in their yield and quality. Therefore, people have found many ways to regulate the growth and quality of vegetable crops. In recent years, in addition to the role that JA plays in stress response and resistance, it has been found to have a regulatory effect on crop quality. Therefore, this study aims to review the jasmonic acid accumulation patterns during various physiological processes and its potential role in vegetable development and quality formation, as well as the underlying molecular mechanisms. The information provided in this manuscript sheds new light on the improvements in vegetable yield and quality.

Coronary Plaque Erosion: Epidemiology, Diagnosis, and Treatment.

Plaque erosion (PE), a distinct etiology of acute coronary syndromes (ACSs), is often overshadowed by plaque ruptures (PRs). Concerning its epidemiology, PE has garnered increasing recognition, with recent studies revealing its prevalence to be approximately 40% among ACS patients, challenging earlier assumptions based on autopsy data. Notably, PE exhibits distinct epidemiological features, preferentially affecting younger demographics, particularly women, and often manifesting as a non-ST-segment elevation myocardial infarction. There are seasonal variations, with PE events being less common in winter, potentially linked to physiological changes and cholesterol solidification, while peaking in summer, warranting further investigation. Moving to molecular mechanisms, PE presents a unique profile characterized by a lesser degree of inflammation compared to PR, with endothelial shear stress emerging as a plausible molecular mechanism. Neutrophil activation, toll-like receptor-2 pathways, and hyaluronidase 2 expression are among the factors implicated in PE pathophysiology, underscoring its multifactorial nature. Advancements in intravascular imaging diagnostics, particularly optical coherence tomography and near-infrared spectroscopy coupled with intravascular ultrasound, offer unprecedented insights into plaque composition and morphology. Artificial intelligence algorithms show promise in enhancing diagnostic accuracy and streamlining image interpretation, augmenting clinician decision-making. Therapeutically, the management of PE evolves, with studies exploring less invasive approaches such as antithrombotic therapy without stenting, particularly in cases identified early through intravascular imaging. Additionally, the potential role of drug-coated balloons in reducing thrombus burden and minimizing future major adverse cardiovascular events warrants further investigation. Looking ahead, the integration of advanced imaging modalities, biomarkers, and artificial intelligence promises to revolutionize the diagnosis and treatment of coronary PE, ushering in a new era of personalized and precise cardiovascular care.

Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy.

Endometrial cancer is one the most prevalent gynecological cancers and, unfortunately, has a poor prognosis due to low response rates to traditional treatments. However, the progress in molecular biology and understanding the genetic mechanisms involved in tumor processes offers valuable information that has led to the current classification that describes four molecular subtypes of endometrial cancer. This review focuses on the molecular mechanisms involved in the pathogenesis of endometrial cancers, such as genetic mutations, defects in the DNA mismatch repair pathway, epigenetic changes, or dysregulation in angiogenic or hormonal signaling pathways. The preclinical genomic and molecular investigations presented allowed for the identification of some molecules that could be used as biomarkers to diagnose, predict, and monitor the progression of endometrial cancer. Besides the therapies known in clinical practice, targeted therapy is described as a new cancer treatment that involves identifying specific molecular targets in tumor cells. By selectively inhibiting these targets, key signaling pathways involved in cancer progression can be disrupted while normal cells are protected. The connection between molecular biomarkers and targeted therapy is vital in the fight against cancer. Ongoing research and clinical trials are exploring the use of standard therapy agents in combination with other treatment strategies like immunotherapy and anti-angiogenesis therapy to improve outcomes and personalize treatment for patients with endometrial cancer. This approach has the potential to transform the management of cancer patients. In conclusion, enhancing molecular tools is essential for stratifying the risk and guiding surgery, adjuvant therapy, and cancer treatment for women with endometrial cancer. In addition, the information from this review may have an essential value in the personalized therapy approach for endometrial cancer to improve the patient's life.

The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes.

Cancer driver genes are either oncogenes or tumour suppressor genes that are classically activated or inactivated, respectively, by driver mutations. Alternative splicing-which produces various mature mRNAs and, eventually, protein variants from a single gene-may also result in driving neoplastic transformation because of the different and often opposed functions of the variants of driver genes. The present review analyses the different alternative splicing events that result in driving neoplastic transformation, with an emphasis on their molecular mechanisms. To do this, we collected a list of 568 gene drivers of cancer and revised the literature to select those involved in the alternative splicing of other genes as well as those in which its pre-mRNA is subject to alternative splicing, with the result, in both cases, of producing an oncogenic isoform. Thirty-one genes fall into the first category, which includes splicing factors and components of the spliceosome and splicing regulators. In the second category, namely that comprising driver genes in which alternative splicing produces the oncogenic isoform, 168 genes were found. Then, we grouped them according to the molecular mechanisms responsible for alternative splicing yielding oncogenic isoforms, namely, mutations in cis splicing-determining elements, other causes involving non-mutated cis elements, changes in splicing factors, and epigenetic and chromatin-related changes. The data given in the present review substantiate the idea that aberrant splicing may regulate the activation of proto-oncogenes or inactivation of tumour suppressor genes and details on the mechanisms involved are given for more than 40 driver genes.

Receptor tyrosine kinase-like orphan receptor 1: A novel antitumor target in gastrointestinal cancers.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a member of the type I receptor tyrosine kinase family. ROR1 is pivotal in embryonic development and cancer, and serves as a biomarker and therapeutic target. It has soluble and membrane-bound subtypes, with the latter highly expressed in tumors. ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms. Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis. Additionally, ROR1 may regulate the cell cycle, stem cell characteristics, and interact with other signaling pathways to affect cancer progression. This review explores the structure, expression and role of ROR1 in the development of gastrointestinal cancers. It discusses current antitumor strategies, outlining challenges and prospects for treatment.

Endoplasmic reticulum stress in pancreatic ß-cell dysfunction: The potential therapeutic role of dietary flavonoids.

Diabetes mellitus (DM) is a global health burden that is characterized by the loss or dysfunction of pancreatic ß-cells. In pancreatic ß-cells, endoplasmic reticulum (ER) stress is a fact of life that contributes to ß-cell loss or dysfunction. Despite recent advances in research, the existing treatment approaches such as lifestyle modification and use of conventional therapeutics could not prevent the loss or dysfunction of pancreatic ß-cells to abrogate the disease progression. Therefore, targeting ER stress and the consequent unfolded protein response (UPR) in pancreatic ß-cells may be a potential therapeutic strategy for diabetes treatment. Dietary phytochemicals have therapeutic applications in human health owing to their broad spectrum of biochemical and pharmacological activities. Flavonoids, which are commonly obtained from fruits and vegetables worldwide, have shown promising prospects in alleviating ER stress. Dietary flavonoids including quercetin, kaempferol, myricetin, isorhamnetin, fisetin, icariin, apigenin, apigetrin, vitexin, baicalein, baicalin, nobiletin hesperidin, naringenin, epigallocatechin 3-O-gallate hesperidin (EGCG), tectorigenin, liquiritigenin, and acacetin have shown inhibitory effects on ER stress in pancreatic ß-cells. Dietary flavonoids modulate ER stress signaling components, chaperone proteins, transcription factors, oxidative stress, autophagy, apoptosis, and inflammatory responses to exert their pharmacological effects on pancreatic ß-cells ER stress. This review focuses on the role of dietary flavonoids as potential therapeutic adjuvants in preserving pancreatic ß-cells from ER stress. Highlights of the underlying mechanisms of action are also presented as well as possible strategies for clinical translation in the management of DM.

Identifying the regulatory network of microRNAs and mRNAs to clarify molecular mechanisms in stroke by bioinformatics analysis.

BACKGROUND: Stroke is one of the leading causes of disability and mortality worldwide. OBJECTIVE: To identify the regulatory network of microRNAs (miRNAs) and mRNAs to clarify molecular mechanisms in stroke. METHODS: Four miRNA datasets and two mRNA datasets of stroke were downloaded from the GEO database. R-Studio was utilized to analyze differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) in the blood of stroke and control patients. FunRich software was utilized to conduct GO and biological pathway analysis on DEmiRNAs, and to search for transcription factors (TFs) of DEmiRNAs. Subsequently, we used miRDB, miRTarBase, and TargetScan to identify DEmiRNAs target genes and intersected with DEmRNAs to find common target genes. The miRNA-mRNA regulatory network of common target genes was constructed by using the Cytoscape. The biological and functional roles of target genes in the regulatory network were predicted using GO and KEGG pathway analyses. RESULTS: 464 DEmiRNAs and 329 DEmRNAs were screened. The top ten TFs (SP1, SP4, EGR1, TCF3, NKX6-1, ZFP161, RREB1, MEF2A, NFIC, POU2F1) were visualized. 16747 target genes of DEmiRNAs were predicted. Target genes were intersected with DEmRNAs, 107 common target genes and 162 DEmiRNAs regulating these common genes were obtained, and then a regulatory network was constructed. Target genes of the regulatory network were primarily enriched in VEGF signaling pathway, lipid and atherosclerosis, T cell receptor signaling pathway. CONCLUSION: This study found that VEGF signaling pathway, lipid and atherosclerosis, T cell receptor signaling pathway are implicated in the biological process of stroke by constructing the regulatory network of miRNAs-mRNAs, which may have guide significance for the pathogenesis and treatment of stroke.