Molecular Mechanisms Research Articles

Qingrexiaoji Recipe Regulates the Differentiation of M2 TAM via miR-29 in GC.

Gastric cancer, one of the most familiar adenocarcinomas of the gastrointestinal tract, ranks third in the world in cancer-related deaths. Traditional Chinese medicine can suppress the growth of tumors, and the underlying mechanism may be associated with the tumor microenvironment. Here, we investigated the anti-cancer effects of the Qingrexiaoji recipe on gastric cancer and the underlying molecular mechanism. An in vivo nude mouse model was established, and the expression of CD206, CD80, and M2 phenotype-related proteins (Arg-1, Fizz1) was obtained by flow cytometry and western blotting. The expressions of the M2 phenotype-related cytokines were examined by ELISA. Qingrexiaoji recipe inhibited gastric tumor growth and downregulated the expression of CD206, IFN-γ, IL-13, IL-4, and TNF-α in vivo. Qingrexiaoji recipe deceased M2 phenotypic polarization by upregulating microRNA (miR)-29a-3p level. Luciferase activity assays showed that HDAC4 is a potential target of miR-29a-3p. In cells co-transfected with HDAC4 siRNA and miR-29a-3p inhibitor and treated with IL-4 and Qingrexiaoji recipe, the miR-29a-3p inhibitorinduced increase of M2 phenotypic polarization was reversed. In summary, these results suggested that the Qingrexiaoji recipe regulated M2 macrophage polarization by regulating miR-29a-3p/HDAC4, providing a different and innovative treatment for gastric cancer.

Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidii Fructus in Treating Colorectal Cancer.

Cnidii Fructus (CF) is known for its antibacterial, anti-inflammatory, and antitumor properties, as well as its activities against kidney deficiency and impotence. In this study, we aimed to explore the anti-CRC cancer effect and molecular mechanism of CF via network pharmacology and in vitro antitumor experiments. Network pharmacology was used to investigate the anti-CRC mechanism of CF. First, a series of databases was used to screen the active phytochemical targets and anti-CRC core targets. Then, the GO and KEGG pathways were analyzed to predict possible mechanisms. Molecular docking analysis explore core targets-phytochemicals interactions. In vitro antitumor experiments were carried on verifying anti-CRC mechanism of CF. In this study, 20 active ingredient targets and 50 intersecting targets were analyzed by Cytoscape software 3.9.1 to obtain the core genes and phytochemicals. Then, the GO and KEGG pathways of 50 intersecting targets were analyzed to predict possible mechanisms. The results from GO and KEGG indicated that CF has significant antitumor efficacy, which involves many signaling pathways, such as PI3K/AKT and p53. The five core targets and five core phytochemicals were screened for molecular docking to show protein-ligand interactions. According to the results of molecular docking, the compound O-acetylcolumbianetin was selected for the anti- CRC functional verification in vitro. MTT assay showed that O-acetylcolumbianetin significantly inhibited the proliferation of colorectal HCT116 cells in a time- and quantity-dependent manner. O-acetylcolumbianetin can promote the expression of CASP3 protein, induce HCT116 cells apoptosis, thus exert anti-CRC effect. This study preliminarily verified the anti-CRC effect and molecular mechanism of CF and provided a reference for Traditional Chinese Medicine anti-tumor subsequent research.

Exploring the therapeutic potential of polysaccharide from Portulaca oleracea L.: A review of phytochemistry and immunomodulatory effect

Portulaca oleracea L., a plant with both edible and medicinal properties, is traditionally valued for its diuretic, antipyretic, antiseptic, antispasmodic, and anthelmintic functions in folk medicine. P. oleracea polysaccharide (POP), a pivotal bioactive component, has various biological activities. Notably, their immunomodulatory capabilities have emerged as a significant area of research. The extraction, purification, monosaccharide composition, structure characterization, and biological activity of POP have been extensively investigated to identify the active components and to clarify their pharmacological actions and underlying molecular mechanisms. It aims to delineate the pharmacological mechanisms and molecular pathways associated with these polysaccharides, thereby underscoring their therapeutic promise and nutritional significance. Furthermore, the review critically examines the current research landscape of POP, identifying gaps and proposing innovative perspectives to enrich the scientific discourse surrounding these bioactive compounds.

CREBRF regulates apoptosis and estradiol via ISG15/ISGylation in pig granulosa cells

Granulosa cells are pivotal in the reproductive processes of female animals; their proliferation, apoptosis, and hormonal secretion are crucial for follicular development and ovulation. Although the role and mechanisms of CREBRF in the reproductive system have garnered attention, its specific functions and underlying mechanisms in ovarian granulosa cells remain unexplored—this study aims to address these gaps. Using flow cytometry, transcriptome sequencing and other technologies, our research revealed elevated CREBRF expression in pig breeds correlated with diminished estrodiol (E2) levels. Further experimental results proved CREBRF could suppress apoptosis through the Bax/caspase3/caspase9 pathway and modulation of ISG15/ISGylation in porcine granulosa cells. When CREBRF was interfered with siRNA, the apoptosis of granulosa cells was increased. At the same time, the expression of apoptosis-related Bax, caspase3, caspase9 was significantly up-regulated, and the expression of anti-apoptotic factor BCL2 was significantly down-regulated. During this process, the expression of many genes changed in granulosa cells. Several genes (CMPK2, MX1, MX2, ZBP1, PML, CHAC1, and BAX) which were promoted apoptosis, were upregulated after CREBRF knockdown with siRNA. ISG15-protein conjugation genes (HERC5, UBA7, UBE2L6, ISG15) were also were upregulated. On the contrary, the expression of anti-apoptotic (RFK, SNAP23) genes decreased. In conclusion, CREBRF could regulate apoptosis of pig granulosa cells through BAX/caspase3/caspase9. Additionally, the study highlights significant alterations in the expression of ISG-related genes and other known apoptosis-related genes during this process. This discovery can novel insights for further elucidating the molecular mechanism of granulosa cells within ovarian granulosa cells and potentially identifies CREBRF as a molecular target for improvement of fertility.

Effective cracking of heavy crude oil by using shock-induced nanobubble collapse: A molecular dynamics study

We investigate molecular mechanisms of hydrocarbon cracking in heavy crude oil promoted by nanobubble collapse due to ultrasound-originated shock wave. Our millions-atom molecular dynamics simulations reveal rapid flow of molecules, causing nanobubble collapse and formation of energetic nanojet with a mushroom-like shape. The nanojet apex exhibits extremely high temperature before and just after the bubble collapse, which makes a favorable condition for effective cracking of paraffin molecules. The cracking rate and portion of nanobubble-containing systems are larger than those of perfect system before the bubble collapse, and larger size of nanobubble is preferable for the cracking. The cracking efficiency is improved for the paraffin molecules with longer carbon chain.

Inhibitors of the mTOR signaling pathway can play an important role in breast cancer immunopathogenesis.

This study explores the critical role of inhibitors targeting the mammalian target of rapamycin (mTOR) signaling pathway in breast cancer research and treatment. The mTOR pathway, a central regulator of cellular processes, has been identified as a crucial factor in the development and progression of breast cancer. The essay explains the complex molecular mechanisms through which mTOR inhibitors, such as rapamycin and its analogs, exert their anticancer effects. These inhibitors can stop cell growth, proliferation, and survival in breast cancer cells by blocking critical signaling pathways within the mTOR pathway. Furthermore, the essay discusses the implications of using mTOR inhibitors as a comprehensive therapeutic strategy. It emphasizes the potential benefits of combining mTOR inhibitors with other treatment approaches to enhance the effectiveness of breast cancer treatment. The evolving landscape of breast cancer research underscores the significance of mTOR as a therapeutic target and highlights ongoing efforts to improve and optimize mTOR inhibitors for clinical use. In conclusion, the essay asserts that inhibitors of the mTOR signaling pathway offer a promising approach in the fight against breast cancer. These inhibitors provide a focused and effective intervention targeting specific dysregulations within the mTOR pathway. As research advances, the integration of mTOR inhibitors into customized combination therapies holds excellent potential for shaping a more effective and personalized approach to breast cancer treatment, ultimately leading to improved outcomes for individuals affected by this complex and diverse disease.

The Common Denominators of Parkinson's Disease Pathogenesis and Methamphetamine Abuse.

The pervasiveness and mortality associated with methamphetamine abuse have doubled during the past decade, suggesting a possible worldwide substance use crisis. Epitomizing the pathophysiology and toxicology of methamphetamine abuse proclaims severe signs and symptoms of neurotoxic and neurobehavioral manifestations in both humans and animals. Most importantly, chronic use of this drug enhances the probability of developing neurodegenerative diseases manifolds. Parkinson's disease is one such neurological disorder, which significantly and evidently not only shares a number of toxic pathogenic mechanisms induced by methamphetamine exposure but is also interlinked both structurally and genetically. Methamphetamine-induced neurodegeneration involves altered dopamine homeostasis that promotes the aggregation of α-synuclein protofibrils in the dopaminergic neurons and drives these neurons to make them more vulnerable to degeneration, as recognized in Parkinson's disease. Moreover, the pathologic mechanisms such as mitochondrial dysfunction, oxidative stress, neuroinflammation and decreased neurogenesis detected in methamphetamine abusers dramatically resemble to what is observed in Parkinson's disease cases. Therefore, the present review comprehensively cumulates a holistic illustration of various genetic and molecular mechanisms putting across the notion of how methamphetamine administration and intoxication might lead to Parkinson's disease-like pathology and Parkinsonism.

Elucidation of the role of XBP1 in the progression of complete hydatidiform mole to invasive mole through RNA-seq

ObjectiveA complete hydatidiform mole (CHM) is a common disease and is known to develop post-molar gestational trophoblast neoplasia (GTN). However, the molecular mechanisms underlying the progression of CHM to post-molar GTN remain largely unknown. In this study, we investigated the molecular factors associated with the progression using RNA-seq. MethodsWe included 13 patients with CHM and performed RNA-seq using freshly frozen samples. We identified differentially expressed genes between patients who developed GTN (GTN group) and those who achieved spontaneous remission after uterine evacuation (SR group), and performed pathway analysis. Then, functional analyses were performed on choriocarcinoma (JAR and JEG-3) and CHM (Hmol1-3B and Hmol1-2C) cells. Moreover, we evaluated the in vivo tumorigenicity of XBP1-overexpressed Hmol1-3B cells. ResultsThe gene expression profiles were separated into two groups, and an upstream regulator analysis was performed using 281 differentially expressed genes. We focused on transcription factors and identified that 33 transcription factors were activated in the GTN group. Then, excluding those with low expression levels in clinical samples and cell lines, XBP1 was selected for further analysis. Additionally, XBP1 downregulation significantly decreased the migration and invasive abilities of choriocarcinoma cells, whereas XBP1 overexpression significantly increased the migration and invasive abilities of CHM cells. Furthermore, animal experiments showed that tumor weight and blood human chorionic gonadotropin (hCG) levels were significantly higher in the XBP1-overexpressing Hmol1-3B-bearing mice than those in the control mice. ConclusionRNA-seq identified XBP1 as a key factor in post-molar GTN, suggesting it contributes to the development of post-molar GTN.

An Overview of Pathological Pathway of Asthma and Molecular Mechanisms of Anti-Asthmatic Phytoconstituents

: Asthma presents with chronic inflammation and airway constriction triggered by allergens or pollution. Inflammatory mediators such as histamine and leukotrienes, released in response to inflammation, prompt bronchoconstriction, contracting the smooth muscles around the airways. This constriction obstructs airflow and worsens symptoms such as coughing, wheezing, and breathlessness. Additionally, airways become hyperresponsive, reacting excessively even to harmless stimuli. Persistent inflammation leads to the production of thick mucus, further blocking airflow and worsening symptoms. Mast cell-released histamine triggers bronchoconstriction, leukotrienes, and prostaglandins (eg, Interleukin-4, Interleukin-13) and promotes airway inflammation while cytokines drive Th2-mediated immune responses. Current therapies in asthma include long-acting beta agonists, leukotriene modifiers, inhaled corticosteroids, and immunomodulators. Natural products, due to their anti-inflammatory, antioxidant and immunomodulatory properties, have emerged as promising anti-asthmatic candidates. Polyphenols (quercetin, resveratrol, curcumin, etc.) and Omega-3 fatty acids offer anti-inflammatory benefits by suppressing cytokines and oxidative stress. Natural products intervene at various levels of these pathways. Quercetin inhibits the release of mast cell histamines, alleviating bronchoconstriction. Curcumin suppresses Th2 cytokines, mitigating the allergic response. Omega-3 fatty acids modulate leukotriene and prostaglandin production, reducing airway inflammation. This review concludes that natural phytobioactives have potential in asthma management due to their complex mechanisms that target various immuno-inflammatory mediators.

OGG1: An emerging multifunctional therapeutic target for the treatment of diseases caused by oxidative DNA damage.

Oxidative DNA damage-related diseases, such as incurable inflammation, malignant tumors, and age-related disorders, present significant challenges in modern medicine due to their complex molecular mechanisms and limitations in identifying effective treatment targets. Recently, 8-oxoguanine DNA glycosylase 1 (OGG1) has emerged as a promising multifunctional therapeutic target for the treatment of these challenging diseases. In this review, we systematically summarize the multiple functions and mechanisms of OGG1, including pro-inflammatory, tumorigenic, and aging regulatory mechanisms. We also highlight the potential of OGG1 inhibitors and activators as potent therapeutic agents for the aforementioned life-limiting diseases. We conclude that OGG1 serves as a multifunctional hub; the inhibition of OGG1 may provide a novel approach for preventing and treating inflammation and cancer, and the activation of OGG1 could be a strategy for preventing age-related disorders. Furthermore, we provide an extensive overview of successful applications of OGG1 regulation in treating inflammatory, cancerous, and aging-related diseases. Finally, we discuss the current challenges and future directions of OGG1 as an emerging multifunctional therapeutic marker for the aforementioned challenging diseases. The aim of this review is to provide a robust reference for scientific researchers and clinical drug developers in the development of novel clinical targeted drugs for life-limiting diseases, especially for incurable inflammation, malignant tumors, and age-related disorders.

Rosehip (Rosa rugosa Thunb.) ethanol extract ameliorates liver fibrosis through upregulation of the PPAR signaling pathway

The objective of this study was to examine the effect of rosehip (Rosa rugosa Thunb.) ethanol extract (RRE) on liver fibrosis in mice and the underlying molecular mechanisms. RRE has no acute oral toxicity, and the MTD in mice is 46.14 g/kg. Histopathological analysis showed that RRE significantly ameliorated inflammation, necrosis, and apoptosis of hepatocytes and collagen deposition caused by CCl4. Further assays indicated that RRE significantly suppressed the production of MDA while markedly increasing the levels of SOD and GSH in the liver. The AST, ALT, IL-6, IL-1β, TNF-α, HA, LN, PCIII, and IVC levels in serum were decreased by RRE. Transcriptome analysis shows that RRE significantly upregulates the PPAR signaling pathway. The RT-q PCR results further confirmed the RRE up-regulating Pparγ, Rxrα, and Plin5 in the PPAR signaling pathway. The Western blot and immunohistochemical results indicate that RRE upregulated PPARγ, RXRα, and Perilipin 5 while downregulating α-SMA and COL1A1 expression. The results indicate that RRE can ameliorate liver fibrosis in mice by upregulating the PPAR signaling pathway.

Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2.

Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has been associated with numerous neurological disorders including autism, epilepsy, and Alzheimer's disease. Nonetheless, the molecular mechanisms underlying abnormal neuronal connectivity remain unclear. We previously found that the serine/threonine kinase Microtubule Affinity Regulating Kinase 2 (MARK2), also known as Partitioning Defective 1b (Par1b), is important for the formation of dendritic spines invitro. However, despite its genetic association with several neurological disorders, the invivo impact of MARK2 on neuronal connectivity and cognitive functions remains unclear. Here, we demonstrate that the loss of MARK2 invivo results in changes to dendritic spine morphology, which in turn leads to a decrease in excitatory synaptic transmission. Additionally, the loss of MARK2 produces substantial impairments in learning and memory, reduced anxiety, and defective social behavior. Notably, MARK2 deficiency results in heightened seizure susceptibility. Consistent with this observation, electrophysiological analysis of hippocampal slices indicates underlying neuronal hyperexcitability in MARK2-deficient neurons. Finally, RNAseq analysis reveals transcriptional changes in genes regulating synaptic transmission and ion homeostasis. These results underscore the invivo role of MARK2 in governing synaptic connectivity, neuronal excitability, and cognitive functions.

The role of physical chemistry in food and beverage

Physical chemistry is a fundamental science that underpins many critical processes in food and beverage production. This paper explores the influence of physico-chemical properties on basic reactions such as crystallization, enzyme kinetics in fermentation, and the Maillard reaction, all of which play a significant role in determining the flavor, texture, stability, and quality of food products. By examining the effects of factors like temperature, pH, solute concentration, and the presence of additives, we demonstrate physical chemistry principles guide the manipulation of these processes to optimize product characteristics. Understanding these interactions allows for greater control over food production techniques, leading to innovations in texture enhancement, flavor development, and preservation. This study highlights the importance of physical chemistry in advancing the food and beverage industry by providing insights into the molecular mechanisms that influence the sensory and functional properties of products.

A comprehensive meta-analysis of in vitro studies on polycystic ovary syndrome cell lines

Introduction: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. In vitro studies using PCOS cell lines have been instrumental in understanding the pathophysiology and identifying potential therapeutic targets. This meta-analysis aims to synthesize and evaluate the existing literature on PCOS cell line research. Methods: A systematic search of PubMed, Scopus, and Web of Science databases up to January 2024, using relevant keywords and medical subject headings. Inclusion criteria were original research articles in English, focusing on PCOS cell lines and reporting quantitative data. Data extraction included study design, cell line model, outcomes, and main findings. Results: A total of 48 studies met the inclusion criteria, involving human granulosa-derived (KGN, COV434), theca-derived (HsTE-1, HsTE-10), and ovarian surface epithelial (IOSE-80) cell lines. These studies focused on the evaluation of hormonal imbalances, insulin resistance, and inflammation. The meta-analysis revealed that PCOS cell lines exhibited increased androgen production, elevated insulin resistance markers, and pro-inflammatory cytokine expression compared to control cell lines. Conclusion: In vitro studies using PCOS cell lines have provided valuable insights into the molecular mechanisms underlying PCOS pathogenesis. These cell lines serve as valuable tools for understanding the complex interplay between hormonal dysregulation, insulin resistance, and inflammation.

Pathogenesis of psoriatic arthritis: new insights from a bone marrow perspective.

Psoriatic arthritis is an immune-mediated disease that primarily affects the skin and joints. It falls under the umbrella term of rheumatic diseases, which describes a group of closely related yet distinct disorders with many common underlying molecular pathways. Despite the distinct clinical manifestation of each disorder, the shared therapeutic strategies attest to the commonality of cellular and molecular underpinnings. Herein we provide a concise yet comprehensive overview of the interleukin (IL)-23/IL-17 axis and its involvement in mechanistic pathways leading to the pathogenesis of this dual skin and joint clinical manifestation which is characteristic of psoriatic arthritis and other rheumatic diseases. The interconnection between activated innate immune cells and adaptive immunity has transformed current thinking to include other organs such as the bone marrow as potential tissue of disease origin. A plethora of animal models and genetic studies converge on the critical role of IL-23/IL-17 axis, and highlight the importance of myeloid cell activation as common pathways between autoinflammatory and autoimmune diseases and chronic inflammation. These findings underscore the intricate immune mechanisms involved in inflammatory arthritis and highlight molecular mechanisms in disease pathogenesis. These insights pave the way for the development of novel diagnostic and therapeutic strategies, with a focus on translating these findings into improved clinical practice.

Identifying Hub Genes and Metabolic Pathways in Collagen VI-Related Dystrophies: A Roadmap to Therapeutic Intervention

Collagen VI-related dystrophies (COL6RD) are a group of rare muscle disorders caused by mutations in specific genes responsible for type VI collagen production. It affects muscles, joints, and connective tissues, leading to weakness, joint problems, and structural issues. Currently, there is no effective treatment for COL6RD; its management typically addresses symptoms and complications. Therefore, it is essential to decipher the disease’s molecular mechanisms, identify drug targets, and develop effective treatment strategies to treat COL6RD. In this study, we employed differential gene expression analysis, weighted gene co-expression network analysis, and genome-scale metabolic modeling to investigate gene expression patterns in COL6RD patients, uncovering key genes, significant metabolites, and disease-related pathophysiological pathways. First, we performed differential gene expression and weighted gene co-expression network analyses, which led to the identification of 12 genes (CHCHD10, MRPS24, TRIP10, RNF123, MRPS15, NDUFB4, COX10, FUNDC2, MDH2, RPL3L, NDUFB11, PARVB) as potential hub genes involved in the disease. Second, we utilized a drug repurposing strategy to identify pharmaceutical candidates that could potentially modulate these genes and be effective in the treatment. Next, we utilized context-specific genome-scale metabolic models to compare metabolic variations between healthy individuals and COL6RD patients. Finally, we conducted reporter metabolite analysis to identify reporter metabolites (e.g., phosphatidates, nicotinate ribonucleotide, ubiquinol, ferricytochrome C). In summary, our analysis revealed critical genes and pathways associated with COL6RD and identified potential targets, reporter metabolites, and candidate drugs for therapeutic interventions.

Germ cell progression through zebrafish spermatogenesis declines with age.

Vertebrate spermatogonial stem cells maintain sperm production over the lifetime of an animal but fertility declines with age. While morphological studies have informed our understanding of typical spermatogenesis, the molecular and cellular mechanisms underlying the maintenance and decline of spermatogenesis are not yet understood. We used single-cell RNA sequencing to generate a developmental atlas of the aging zebrafish testis. All testes contained spermatogonia, but we observed a progressive decline in spermatogenesis that correlates with age. Testes from some older males only contained spermatogonia and a reduced population of spermatocytes. Spermatogonia in older males are transcriptionally distinct from spermatogonia in testes capable of robust spermatogenesis. Immune cells including macrophages and lymphocytes drastically increase in abundance in testes that cannot complete spermatogenesis. Our developmental atlas reveals the cellular changes as the testis ages and defines a molecular roadmap for the regulation of spermatogenesis.

Cognitive Impact of Neurotropic Pathogens: Investigating Molecular Mimicry through Computational Methods

Neurotropic pathogens, notably, herpesviruses, have been associated with significant neuropsychiatric effects. As a group, these pathogens can exploit molecular mimicry mechanisms to manipulate the host central nervous system to their advantage. Here, we present a systematic computational approach that may ultimately be used to unravel protein–protein interactions and molecular mimicry processes that have not yet been solved experimentally. Toward this end, we validate this approach by replicating a set of pre-existing experimental findings that document the structural and functional similarities shared by the human cytomegalovirus-encoded UL144 glycoprotein and human tumor necrosis factor receptor superfamily member 14 (TNFRSF14). We began with a thorough exploration of the Homo sapiens protein database using the Basic Local Alignment Search Tool (BLASTx) to identify proteins sharing sequence homology with UL144. Subsequently, we used AlphaFold2 to predict the independent three-dimensional structures of UL144 and TNFRSF14. This was followed by a comprehensive structural comparison facilitated by Distance-Matrix Alignment and Foldseek. Finally, we used AlphaFold-multimer and PPIscreenML to elucidate potential protein complexes and confirm the predicted binding activities of both UL144 and TNFRSF14. We then used our in silico approach to replicate the experimental finding that revealed TNFRSF14 binding to both B- and T-lymphocyte attenuator (BTLA) and glycoprotein domain and UL144 binding to BTLA alone. This computational framework offers promise in identifying structural similarities and interactions between pathogen-encoded proteins and their host counterparts. This information will provide valuable insights into the cognitive mechanisms underlying the neuropsychiatric effects of viral infections.Graphical

Early T-cell precursor acute lymphoblastic leukemia: diagnostic pitfalls, genomic alteration, novel therapeutics, and minimal residual disease monitoring

Early precursor T-cell acute lymphoblastic leukemia (ETP-ALL) is a rare type of T-cell ALL (T-ALL) that was initially described in 2009. Since its initial description, it has been formally recognized as a distinct entity, according to the 2016 World Health Organization classification. ETP-ALL is characterized by unique immunophenotypic and genomic profiles. The diagnosis and management of ETP-ALL remain challenging. Poorer outcomes, high incidence of induction failure and relapsed/refractory disease demand novel therapies. This review emphasizes the challenges of initial diagnosis, the molecular mechanisms underlying leukemogenesis, and the available therapeutic options. Additionally, it discusses the importance of induction failure, the prognostic value of detecting minimal residual disease, and the implications of hematopoietic stem cell transplantation, along with emerging novel therapies.

Genome-wide identification of a MADS-box transcription factor family and their expression during floral development in Coptis teeta wall

BackgroundMADS-box transcription factors have been shown to be involved in multiple developmental processes, including the regulation of floral organ formation and pollen maturation. However, the role of the MADS-box gene family in floral development of the alpine plant species Coptis teeta Wall, which is widely used in Traditional Chinese Medicine (TCM), is unknown.ResultsSixty-six MADS-box genes were identified in the C. teeta genome. These genes were shown to be unevenly distributed throughout the genome of C. teeta. The majority of which (49) were classified as type I MADS-box genes and were further subdivided into four groups (Mα, Mβ, Mγ and Mδ). The remainder were identified as belonging to the type II MADS-box gene category. It was observed that four pairs of segmental and tandem duplication had occurred in the C. teeta MADS-box gene family, and that the ratios of Ka/Ks were less than 1, suggesting that these genes may have experienced purifying selection during evolution. Gene expression profiling analysis revealed that 38 MADS-box genes displayed differential expression patterns between the M and F floral phenotypes. Sixteen of these MADS-box genes were further verified by RT-qPCR. The 3D structure of each subfamily gene was predicted, further indicating that MADS-box genes of the same type possess structural similarities to the known template.ConclusionsThese data provide new insights into the molecular mechanism of dichogamy and herkogamy formation in C. teeta and establish a solid foundation for future studies of the MADS-box genes family in this medicinal plant species.