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Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy.

Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons and poses a great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it is of urgent need to explore other potential mechanism to develop a novel approach to delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), the versatile epigenetic regulators re

Посттрансляционные изменения в нейроиммунных клетках во время нейроинфламмации: комплексные сети регулирования и терапевтические возможности.

Нейроинфламмация представляет собой общий патологический механизм, лежащий в основе широкого спектра нарушений центральной нервной системы (КНС), включая нейродегенеративные расстройства (НДД), ишемический инсульт (ИС), травматическое повреждение мозга (ТБИ) и демиелионирующие заболевания, такие как множественный склероз (МС). Этот процесс начинается с организованной реакции микроглий, астроцитов, олигодендроцитов, нейронов, эндотелиальных клеток головного мозга и проникновения в периферийные иммунные клетки. Нейроинфламмация может облегчить ремонт тканей или, наоборот, увековечить хроническое

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… Alongside emerging evidence that EZH2 influences astrocyte morphogenesis and function, these findings suggest that this regulatory framework is biologically plausible in astrocytes and merits direct experimental investigation. … Enhances IKK/NF-κB pathway activity; Promotes astrocyte inflammatory gene expression | Astrocyte overexpression studies and mouse brain injury | Cell-specific functional evidence; PTM substrate unresolved | [ 91 ] | Methylation | EZH2–PRC2 complex | Establishes repressive chromatin; Controls astrocyte morphogenesis …

Annexin A1 affects tumor metastasis through epithelial-mesenchymal transition: a narrative review.

Background and objectiveAnnexin A1 (annexin I, ANXA1), the first discovered member of the annexin superfamily, plays important roles in tumor development, invasion, metastasis, apoptosis and drug resistance based on tumor type-specific patterns of expression. The acquisition of the epithelial-mesenchymal transition (EMT) characteristics is an essential mechanism of metastasis because they increase the mobility and invasiveness of cancer cells. Cancer invasion and metastasis remain major health problems worldwide. Elucidating the role and mechanism of ANXA1 in the occurrence of EMT will help ad

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… The first type is related to implantation, embryogenesis, and organ development, which are driven by the evolutionary need to remodel and diversify tissue to enable proper morphogenesis and generate a functional organism. …

Effects and mechanisms of Eps8 on the biological behaviour of malignant tumours (Review).

Epidermal growth factor receptor pathway substrate 8 (Eps8) was initially identified as the substrate for the kinase activity of EGFR, improving the responsiveness of EGF, which is involved in cell mitosis, differentiation and other physiological functions. Numerous studies over the last decade have demonstrated that Eps8 is overexpressed in most ubiquitous malignant tumours and subsequently binds with its receptor to activate multiple signalling pathways. Eps8 not only participates in the regulation of malignant phenotypes, such as tumour proliferation, invasion, metastasis and drug resistanc

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… Additionally, Eps8 plays a pivotal role in membrane flow, the formation of pseudopods, the morphogenesis of microvilli, the function and length of static cilia, cell adhesion and motility ( 15 ). …

New Generation of Meso and Antiprogestins (SPRMs) into the Osteoporosis Approach.

Receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) play key roles in bone metabolism and the immune system. The RANK/RANKL complex has also been shown to be critical in the formation of mammary epithelia cells. The female hormones estradiol and progesterone closely control the action of RANKL with RANK. Blood concentration of these sex hormones in the postmenopausal period leads to an increase in RANK/RANKL signaling and are a major cause of women's osteoporosis, characterized by altered bone mineralization. Knowledge of the biochemical relationships between hormones and RAN

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… Targeting RANKL to a specific subset of murine mammary epithelial cells induces ordered branching morphogenesis and alveologenesis in the absence of progesterone receptor expression. FASEB J. 2010;24:4408–4419. doi: 10.1096/fj.10-157982. 100. Tsubaki M., Komai M., Fujimoto S. …

Exploring the Potential of MicroRNA Let-7c as a Therapeutic for Prostate Cancer.

Prostate cancer (PCa) is one of the leading causes of mortality worldwide and often presents with aberrant microRNA (miRNA) expression. Identifying and understanding the unique expression profiles could aid in the detection and treatment of this disease. This review aims to identify miRNAs as potential therapeutic targets for PCa. Three bio-informatic searches were conducted to identify miRNAs that are reportedly implicated in the pathogenesis of PCa. Only hsa-Lethal-7 (let-7c), recognized for its role in PCa pathogenesis, was common to all three databases. Three further database searches were

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… significantly higher in PCa tissues than in normal prostate tissues. 54 Cancer cells share three main characteristics with embryonic cells: proliferation, invasion, and immortality. 53 Epithelial to mesenchymal transition (EMT) is a mechanism that occurs during embryonic development that allows for tissue morphogenesis …

Ancient genes establish stress-induced mutation as a hallmark of cancer.

Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cance

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… of COSMIC genes using DAVID [ 36 , 37 ] with all human genes as the background list revealed that COSMIC genes with dominant mutations were enriched for transcription factors and transcriptional regulation, immune system development, receptor tyrosine kinases and signal transduction, “stem”-ness and morphogenesis …

Recent advances in anti-angiogenic therapy of cancer.

Since angiogenesis is critical for tumor growth and metastasis, anti-angiogenic treatment is a highly promising therapeutic approach. Thus, for over last couple of decades, there has been a robust activity aimed towards the discovery of angiogenesis inhibitors. More than forty anti-angiogenic drugs are being tested in clinical trials all over the world. This review discusses agents that have approved by the FDA and are currently in use for treating patients either as single-agents or in combination with other chemotherapeutic agents.

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… Simoncini S Njock SM Jourde N Brunet P Camoin-Jau L Sampol J Dignat-George F Endothelial-derived microparticles: Biological conveyors at the crossroad of inflammation, thrombosis and angiogenesis Thromb Haemost 104 456 63 20664896 10.1160/TH10-02-0111 147 Carmeliet P De Smet F Loges S Mazzone M Branching morphogenesis …

TACC3, correlated with immune cell infiltrates, is a novel prognostic biomarker in BRCA.

Transforming acidic coiled-coil-containing protein 3 (TACC3) plays a crucial oncogenic role in various carcinomas and may act as a novel prognostic factor. However, its prognostic significance and underlying mechanisms in breast cancer (BRCA) remain unclear and require further investigation. This research included 181 breast cancer tissues, and the expression levels of TACC3 were analyzed by immunohistochemistry staining and grading. The mRNA expression of TACC3 in pan-cancer was analyzed with The Cancer Genome Atlas data platform. Receiver operating characteristic curve analysis assessed TACC

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… The remaining BP items that showed negative correlations with TACC3 included pattern specification process, negative regulation of locomotion, regulation of transporter activity, heat morphogenesis, response to transforming growth factor beta, and multicellular organismal signaling (Fig. 4 D). …

Integrative analysis of bulk and single-cell gene expression profiles to identify bone marrow mesenchymal cell heterogeneity and prognostic significance in multiple myeloma.

BackgroundMultiple myeloma is a hematologic malignancy characterized by complex interactions within the tumor microenvironment, where mesenchymal stem cells (MSCs) contribute significantly to disease progression, immune suppression, and drug resistance.MethodsThis study investigated the heterogeneity of MSCs in multiple myeloma using single-cell RNA sequencing (10X) and bulk transcriptomic data. Further analysis was performed by Seurat, SCENIC, CellChat. GSE4581 and GSE136337 were used as training set and validation set to construct a newly described prognostic model through COX and LASSO.Resu

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… JunD, a transcription factor that belongs to the family of activating protein-1 (AP-1) transcription factors, along with SOX4, which is associated with the Epithelial-mesenchymal transition (EMT) pathway, may promote the expression of genes involved in bone morphogenesis. …

Transcriptomic profiling identifies ferroptosis and NF-κB signaling involved in α-dimorphecolic acid regulation of microglial inflammation.

BACKGROUND: Microglia-evoked neuroinflammation contributes to neurodegenerative diseases such as multiple sclerosis (MS). Metabolic reprogramming, including changes in polyunsaturated fatty acids (PUFAs), plays a critical role in MS pathophysiology. Previous studies identified reduced plasma α-dimorphecolic acid (α-DIPA), a linoleic acid derivative, in MS patients. This study investigated the anti-inflammatory effects of α-DIPA on microglia and the underlying pathways. METHODS: Lipopolysaccharide (LPS)-induced BV-2 microglial inflammation was used as an in vitro model. α-DIPA effects were ass

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… FPKM: Fragments Per Kilobase of exon model per Million mapped reads GO enrichment analysis results showed that α-DIPA-regulated DEGs primarily involved in the biological processes of anatomical structure morphogenesis, animal organ development, cell adhesion, cell development, cell population proliferation …

Mesenchymal-Stem-Cell-Based Therapy against Gliomas.

Glioblastoma is the most aggressive, malignant, and lethal brain tumor of the central nervous system. Its poor prognosis lies in its inefficient response to currently available treatments that consist of surgical resection, radiotherapy, and chemotherapy. Recently, the use of mesenchymal stem cells (MSCs) as a possible kind of cell therapy against glioblastoma is gaining great interest due to their immunomodulatory properties, tumor tropism, and differentiation into other cell types. However, MSCs seem to present both antitumor and pro-tumor properties depending on the tissue from which they c

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… The content of MSC-derived exosomes consists of (a) proteins that control cell growth, proliferation, adhesion, migration, and morphogenesis capabilities of MSCs; (b) RNA involved in the regulation of cell survival, cell differentiation, and the modulation of the immune system; and (c) DNA [ 103 ]. …

Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision.

Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and

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… AWS, researcher, Biohaven Pharmaceuticals, Replimune, Morphogenesis, Shattuck Laboratories, Regeneron, and Merck; consultant/advisor/speaker, InStil Bio, Signatera, Merck, and Regeneron; royalty and patent beneficiary, UpToDate; and publicly traded stocks, Illumina. …

Окисляющий стресс и воспаление в патогенезе неврологических расстройств: механизмы и последствия.

Нейрозащита — это активный подход к защите нервной системы, включая мозг, спинной мозг и периферийные нервы, путем предотвращения или ограничения повреждения нервных клеток и других компонентов. Она защищает центральную нервную систему от повреждений от острых и прогрессивных нейродегенеративных расстройств. Окисляющий стресс, дисбаланс между естественными механизмами защиты тела и образованием реактивных видов кислорода, имеет решающее значение для развития неврологических расстройств. Из-за высокой скорости метаболизма и потребления кислорода мозг особенно уязвим к окисляющему стрессу. Чрезм

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… HD brains exhibit mitochondrial anomalies, including loss and altered morphogenesis characterized by increased fission and decreased fusion 95 . …

Don't eat me/eat me signals as a novel strategy in cancer immunotherapy.

Cancer stands as one of the prominent global causes of death, with its incidence burden continuously increasing, leading to a substantial rise in mortality rates. Cancer treatment has seen the development of various strategies, each carrying its drawbacks that can negatively impact the quality of life for cancer patients. The challenge remains significant within the medical field to establish a definitive cancer treatment that minimizes complications and limitations. In the forthcoming years, exploring new strategies to surmount the failures in cancer treatment appears to be an unavoidable pur

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… In the realm of multicellular organisms, the phenomenon of apoptosis, or programmed cell death, plays a pivotal role in various essential processes such as morphogenesis, cellular homeostasis, injury repair, immunological tolerance, and the mitigation of inflammation [ 14 , 15 ]. …

RANKL/RANK System-Based Mechanism for Breast Cancer Bone Metastasis and Related Therapeutic Strategies.

Breast cancer remains one of the most life-threatening tumors affecting women. Most patients with advanced breast cancer eventually develop metastatic diseases, which cause significant morbidity and mortality. Approximately two-thirds of patients with advanced breast cancer exhibit osteolytic-type bone metastasis, which seriously reduce the quality of life. Therefore, development of novel therapeutic strategies for treating breast cancer patients with bone metastasis is urgently required. The "seed and soil" theory, which describes the interaction between the circulating breast cancer cells (s

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… In addition, the RANKL/RANK signaling system can enhance the proliferation and division of mammary epithelial cells during lobulo-alveolar morphogenesis in an autocrine or paracrine fashion, as well as promote the formation of lactating mammary glands. …

Notch signaling deregulation in multiple myeloma: A rational molecular target.

Despite recent therapeutic advances, multiple myeloma (MM) is still an incurable neoplasia due to intrinsic or acquired resistance to therapy. Myeloma cell localization in the bone marrow milieu allows direct interactions between tumor cells and non-tumor bone marrow cells which promote neoplastic cell growth, survival, bone disease, acquisition of drug resistance and consequent relapse. Twenty percent of MM patients are at high-risk of treatment failure as defined by tumor markers or presentation as plasma cell leukemia. Cumulative evidences indicate a key role of Notch signaling in multiple

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… The Notch pathway regulates cell differentiation, apoptosis, proliferation, morphogenesis and it is essential for embryonic development of multicellular organisms [ 30 ]. …

Olive phenolics as c-Met inhibitors: (-)-Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.

Dysregulation of the Hepatocyte growth factor (HGF)/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT), angiogenesis, invasion, and metastasis. (-)-Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (-)-oleocanthal treatment and the potent

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… Under physiological conditions, HGF regulates epithelial development and morphogenesis in different organs [27] . In the human breast, HGF is produced primarily in the mammary stroma, whereas c-Met is expressed in the epithelium [28] . …

Immunologic tumor microenvironment modulators for turning cold tumors hot.

Tumors can be classified into distinct immunophenotypes based on the presence and arrangement of cytotoxic immune cells within the tumor microenvironment (TME). Hot tumors, characterized by heightened immune activity and responsiveness to immune checkpoint inhibitors (ICIs), stand in stark contrast to cold tumors, which lack immune infiltration and remain resistant to therapy. To overcome immune evasion mechanisms employed by tumor cells, novel immunologic modulators have emerged, particularly ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein

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… Besides their essential roles in innate immunity, macrophages contribute significantly to various developmental processes, including bone morphogenesis, neuronal patterning, angiogenesis, branching morphogenesis, and adipogenesis [ 16 ]. …

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound tr

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… The role of macrophages in development is often overlooked, including branching morphogenesis, neuronal patterning, angiogenesis, bone morphogenesis, generation of adipose tissue, and testicular organogenesis [ 194 , 195 ]. …