Molecular Biology Reports最新文献

Immune thrombocytopenia (ITP) is an autoimmune hematologic disorder that arises from an imbalance in immune responses, disrupting the delicate equilibrium of the immune system. An increasing body of research has indicated that immune-related genes hold promise as biomarkers for diagnosis and prognosis, with a particular focus on the roles of B and T cells in ITP pathogenesis. Despite these advancements, a deeper understanding of the underlying regulatory mechanisms governing these immune-related genes remains essential. This review aims to integrate the current body of evidence and provide further insights into the epigenetic regulation of immune pathways involved in ITP development. The problem statement section highlights the complexity of ITP and its intricate connections with immune pathways. It also compares the epigenetic differences between pediatric and adult ITP based on existing evidence. Decoding epigenetic processes could potentially open up new avenues for improving diagnostic methods and therapeutic strategies for ITP.

Background: Ovarian Cancer (OC) prevention and early-stage detection represents a challenge due to the lack of effective surveillance. The identification of high-risk women is crucial as it provides access to prophylactic oophorectomy and reduces disease burden. Next-Generation Sequencing approaches enable the investigation of several genes associated with monogenic hereditary cancer predisposition, including ovarian cancer. For family members of patients affected by ovarian cancer without identification of a germline pathogenic variant, despite the increased empirical risk (3 times) of ovarian cancer incidence, prophylactic surgery is not indicated but may be suggested as the only efficient strategy.

Methods and results: We hereby present 2 cases of OC in which a germline heterozygous pathogenic variant in the ATM gene was identified: the first in the contest of Hereditary Breast and Ovarian Cancer (HBOC) family history and, in the other one, a late onset of neoplasms, to underline the importance of defining guidelines and management of moderate penetrance genes variants also for ovarian cancer prevention.

Conclusions: Carriers of heterozygous pathogenic variants in the ATM gene have an increased risk of neoplasms incidence, mostly breast but also of OC with an absolute estimated risk of 2-3 times greater than the general population. For these patients there is not well-established evidence of benefit in risk reducing bilateral Salpingo-oophorectomy.

The cattle industry is critical for agriculture's development, and reproductive technology has revolutionized its development over the past century. The core task of developing the beef cattle industry is to increase quantity and improve quality, which cannot be separated from the key link of reproduction. It involves artificial insemination (AI), semen collection and freezing, multiple ovulation embryo transfer (MOET), and genome editing. Each technology greatly contributed to the industry's development at the time. In this review, we systematically summarize the development process of beef cattle breeding technology and provide reasonable suggestions for the needs of enterprises and individual breeders of different scales. Additionally, we summarize the contributions of these technologies to industry development and their impact on cattle farming today. Scientific feeding methods combined with current reproductive technology can fully realize the production potential of beef cattle and improve economic benefits, which has positive significance for expanding the beef cattle industry scale and promoting sustainable cattle industry development.

Background: It is well acknowledged that neuroinflammation, mitochondrial dysfunction, and oxidative stress (OS) play a role in the etiology of Parkinson's disease (PD). Curcumin (CUR) protect neuronal cells by interfering with the production of reactive oxygen species (ROS) in neuronal cells and suppressing OS. In this study, we investigated the role of the TRPV4 channel under CUR stimulation in the PD model induced by MPP⁺ in SH-SY5Y cells.

Methods: The cells were divided into four groups: control, CUR, MPP⁺ and MPP⁺+CUR. In addition, incubations were performed with TRPV4 channel agonist GSK1016790A (GSK) and its antagonist Ruthenium red (Rr) to follow the Ca²⁺ current induced through the TRPV4 channel.

Results: MPP⁺ exposure increased mitochondrial and intracellular ROS production and mitochondrial membrane potential in the cell, while decreasing GSH levels. During CUR and Rr incubation, MPP⁺ exposure and TRPV4 agonist GSK-induced TRPV4 overstimulation were down-regulated. The effects of MPP⁺ on intracellular damage were changed by CUR treatment, as seen in changes in GSH levels, mROS, iROS, JC/1, apoptosis, and TRPV4 expression value compared to the MPP⁺ group.

Conclusions: The CUR treatment in the in vitro PD model created with MPP⁺ reduced cellular damage by regulating mitochondrial dysfunction, OS and TRPV4 channel activation in MPP⁺-induced neurotoxicity with the antioxidant properties of CUR.

Malignant tumors associated with drug resistance present a significant challenge for clinicians and drug developers. Mutations and alterations within the tumor microenvironment frequently drive cancer cell invasion and metastasis. Despite identifying numerous molecular targets and lead compounds, achieving sustained efficacy remains challenging due to the rapid mutation rates and the emergence of resistance. Recently, Focal Adhesion Kinase (FAK), a non-receptor tyrosine kinase, has emerged as a promising target for inhibiting cancer progression, with several lead molecules advancing through clinical trials. FAK plays a critical role in cancer pathology by regulating cell adhesion, migration, proliferation, and survival. Its structure comprises three domains- the N-terminal FERM domain, kinase domain, and C-terminal focal adhesion targeting domain- contributing to its functional versatility. Ligands targeting the FERM and kinase domains can suppress cancer cell proliferation, invasion, and migration. The FERM domain, a member of the ezrin, radixin, and moesin family, is particularly noteworthy for its ligand-binding capabilities and potential to inhibit tumor growth. While FAK is a compelling anticancer target, challenges such as tissue-specific physiological variability and broad ligand specificity remain. This review provides a detailed analysis of FAK's role in cancer progression and explores emerging molecules targeting FAK as potential treatments for drug-resistant malignant tumors.

Background: The transition from vegetative to floral development is a critical process regulated by a variety of complex internal and external factors. This study aims to characterize the Flowering Locus D (FLD) gene in relation to the floral induction pathway and examine its expression profiles under different photoperiodic conditions in Indian bean (Lablab purpureus (L.) Sweet).

Methods: The LprFLD gene was PCR-amplified and sequenced using gene-specific primers for both photosensitive (GNIB-22, GP-189) and photoinsensitive (GNIB-21) varieties of Indian bean. Exon prediction, phylogenetic analysis, and in silico domain prediction were performed, followed by gene expression analysis using qRT-PCR for contrasting phenotypes.

Results: The complete LprFLD gene sequence was characterized, containing five exons and showing significant similarity to GmFLD and VuFLD. Phylogenetic analysis of FLD homologs from 27 taxa revealed the closest evolutionary relationships among members of the Phaseoleae tribe, including Lablab purpureus, Vignaumbellata, Vigna angularis, Vignaradiata, Vigna unguiculata, Phaseolus vulgaris, Glycine max, Glycinesoja, and Cajanus cajan. In silico domain prediction identified two conserved domains, SWIRM and amino oxidase, in the FLD homologs of Indian bean, soybean, cowpea, Arabidopsis and rice. Gene expression analysis showed that the relative expression of LprFLD in trifoliate leaves corresponded with flowering in both photosensitive and photoinsensitive genotypes under long-day conditions. Overall, the expression level of LprFLD was lower in trifoliate leaves and shoot tips.

Conclusion: This is the first report on the characterization of the LprFLD locus in Indian bean. Phylogenetic analysis confirmed its close evolutionary relationship with other Phaseoleae species. qRT-PCR results suggest that the elevated expression of LprFLD in trifoliate leaves coincides with flowering time in both photosensitive and photoinsensitive genotypes under long-day conditions, indicating that other loci may also regulate floral transition under varying photoperiods in Indian bean.

Background: This study explores the mechanisms of colorectal cancer (CRC) through bioinformatics and in vitro experiments. The goal is to find differentially expressed genes (DEGs) and miRNA-gene interactions, especially between miR-16-5p and BIRC5, in order to find biomarkers that can be used to diagnose, predict, and treat CRC.

Methods and results: Microarray data (GSE52060) from the GEO database was analysed using R software, applying LIMMA for log2 transformation and quantile normalization. Significant DEGs were identified, and miRNA targets were predicted with miRWalk v.3 and validated in CRC cell lines. Statistical analyses were conducted using R and GraphPad Prism. BIRC5's impact on survival was analysed via GEPIA2, and correlated genes were identified using Correlation AnalyzeR. The treatment of miR-16-5p mimic significantly reduced BIRC5 expression in HT-29, SW480, and HCT116 cells in a dose-dependent manner. Correlational analyses revealed a strong negative association between miR-16-5p levels and BIRC5 expression, emphasizing miR-16-5p's role as a tumor suppressor. While BIRC5 inhibits apoptosis and regulates cell division, miR-16-5p impacts apoptosis, the cell cycle, and angiogenesis. GEPIA2 analysis indicated that BIRC5 expression had no significant impact on CRC survival outcomes.

Conclusions: This study demonstrates miR-16-5p's regulatory role on BIRC5 in CRC cells and its therapeutic potential. Restoring miR-16-5p or targeting BIRC5 could improve CRC treatment strategies. To learn more about how miR-16-5p and BIRC5 can be used to diagnose and predict CRC, more clinical testing is needed. This will help us learn more about how CRC works at the molecular level.

Background: The South American fruit fly Anastrepha fraterculus sp. 1 belongs to a cryptic species complex with only a single morphotype present in Argentina, which possess polymorphisms in the sex chromosomes, identified by two X (X₁, X₂) and two Y (Y₅, Y₆) variants. Our aim was to explore the molecular composition of the sex chromosomes identified in the laboratory strain Af-Y-short due to it possesses the most frequent sex chromosomes variants, and the smallest Y chromosome found in wild populations and laboratory colonies of A. fraterculus sp. 1.

Methods and results: Whole Comparative Genomic Hybridization (W-CGH) was applied to the Af-Y-short laboratory strain to identify potential differences in the size and composition of highly repetitive DNA blocks between individuals, morphs or sexes. Our results showed that the X₁ and X₂ share complete homology in euchromatic regions, also sharing similar sequences with the Y₅ chromosome in the centromeric region. Females X₁X₁ and X₁X₂ exhibited repetitive DNA in telomeric regions which contributed to their morphological differentiation, while the Y chromosome evidenced the accumulation of specific and differential repetitive sequences. In contrast, autosomes showed balanced signal with no sex-chromosome-specific sequence accumulation.

Conclusions: Our findings highlight the role of repetitive DNA in the differentiation and evolution of sex chromosomes in A. fraterculus sp. 1, shedding new light on the origin and diversification of Anastrepha species in South America and providing valuable cytogenetic insights for future research.

Plants, as sessile organisms, must adapt to dynamic environmental changes through a range of response strategies that confer phenotypic flexibility. Breakthroughs in next-generation sequencing technologies have led to significant improvements in our understanding of the genomic and molecular mechanisms underlying plant growth, development and stress responses. Non-coding RNAs (ncRNAs), have emerged as pivotal regulators in these processes. This article reviews the roles of regulatory ncRNAs in plant stress responses and development, highlighting their intricate molecular interactions. It presents a comprehensive atlas of differentially regulated ncRNAs across key crop genomes, enhancing our understanding of their roles in stress responses, growth, and development. The atlas presented herein offers a foundation for further research in agronomically important crops, paving the way for crop improvement through genetic engineering and sustainable agricultural practices. Additionally, we discuss the role of ncRNAs that have already been functionally characterized in growth, development and stress tolerance, providing insights into their potential for developing stress-resistant and high-yielding crops.

Rheumatoid arthritis (RA) is an enduring autoimmune illness characterized by persistent inflammation and joint damage. Recent advancements in B cell depletion therapies (BCDTs) have provided new avenues for managing RA. This review article delves into the pathophysiology of RA, highlighting the pivotal role of B cells in disease progression. We explore the mechanisms underlying B cell depletion, focusing on monoclonal antibodies such as rituximab as well as innovative approaches like chimeric antigen receptor (CAR) T cell therapies. An in-depth analysis of clinical studies reveals the efficacy and limitations of these therapies, including success rates, side effects, and cost implications for patients. Despite promising outcomes, the incomplete depletion of B cells and associated risks underscore the need for further research. This review aims to provide a comprehensive understanding of BCDTs in RA, shed light on their potential and challenges, and guide future therapeutic strategies.