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The Role of the Ubiquitin System in Eye Diseases.

The ubiquitin-proteasome system (UPS) is a fundamental process that regulates various biological functions, including immune response, cell cycle, oxidative stress, migration, and cellular proliferation. This system is responsible for the degradation of proteins, while proteasomes play a significant role in mechanisms involved in health and human diseases. The participation of the UPS in immune response is particularly relevant, leading to the involvement of immunoproteasomes. This specialized proteasome is involved in the processing and presentation of antigenic peptides, making it crucial fo

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… During the process of aging and cellular senescence, ocular structures undergo important changes, especially those of the ocular surface. … Therefore, the accumulation of proteins in the macular area and its relationship with cellular senescence and aging can be explained by autophagy and UPS activity [ 114 , 115 ]. …

Growth differentiation factor-15 may be a novel biomarker in pancreatic cancer: A review.

Pancreatic cancer is a highly malignant and invasive gastrointestinal tumor that is often diagnosed at an advanced stage with a poor prognosis and high mortality. Currently, carbohydrate antigen199(CA199) is the only biomarker approved by the FDA for the diagnosis of pancreatic cancer, but it has great limitations. Growth differentiation factor-15 (GDF-15) is expected to be a novel biomarker for the diagnosis, efficacy prediction, and prognosis assessment of pancreatic cancer patients. In this paper, we searched the keywords GDF-15, macrophage inhibitory cytokine-1 (MIC-1), CA199, pancreatic c

Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.

Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, a

Nucleic acid aptamers in orthopedic diseases: promising therapeutic agents for bone disorders.

Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging as pivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution of Ligands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA, proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents, including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modificatio

Humanized Bone Model Identifies BMP6 as a Multifunctional Regulator in Myeloma Bone Disease.

Multiple myeloma (MM) is a plasma cell malignancy that disrupts bone homeostasis by suppressing osteogenesis and promoting osteoclast activity. While most therapeutic interventions to date have focused on targeting tumor cells and reducing osteolysis, we investigate whether osteoinductive strategies can restore bone formation and counteract disease progression. Using a human bone marrow-like scaffold model that enables direct in vivo evaluation of tumor-stroma interactions and human bone formation, we demonstrate that MM-derived mesenchymal stromal cells (MSCs) retain osteogenic potential but

Collateral Victim or Rescue Worker?-The Role of Histone Methyltransferases in DNA Damage Repair and Their Targeting for Therapeutic Opportunities in Cancer.

Disrupted DNA damage signaling greatly threatens cell integrity and plays significant roles in cancer. With recent advances in understanding the human genome and gene regulation in the context of DNA damage, chromatin biology, specifically biology of histone post-translational modifications (PTMs), has emerged as a popular field of study with great promise for cancer therapeutics. Here, we discuss how key histone methylation pathways contribute to DNA damage repair and impact tumorigenesis within this context, as well as the potential for their targeting as part of therapeutic strategies in ca

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… A small-molecule probe of the histone methyltransferase G9a induces cellular senescence in pancreatic adenocarcinoma. ACS Chem. Biol. 7 1152–1157. 10.1021/cb300139y Zhou X., Wang W., Du C., Yan F., Yang S., He K., et al. (2018). …

Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration.

Histone methyltransferases (HMTs) and histone demethylases (HDMs) are critical enzymes that regulate chromatin dynamics and gene expression through the addition and removal of methyl groups on histone proteins. HMTs, such as PRC2 and SETD2, are involved in the trimethylation of histone H3 at lysine 27 and lysine 36, influencing gene silencing and activation. Dysregulation of these enzymes often leads to abnormal gene expression and contributes to tumorigenesis. In contrast, HDMs including KDM7A and KDM2A reverse these methylation marks, and their dysfunction can drive disease progression. In c

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… Knockout SETD1A cultures have demonstrated that its absence induces cellular senescence, effectively halting cell division and limiting tumor progression. … Of note is that JARID1A, while exhibiting the qualities of an oncogene, can act as a tumor suppressor, as studies have demonstrated that it supports cellular senescence by mediating retinoblastoma-interacting proteins [ 47 ]. …

WT1 gene: a potential therapeutic target for multiple cancer treatment strategies.

The Wilms' Tumor 1 (WT1) gene has attracted significant attention in oncological research owing to its involvement in the pathogenesis of a variety of malignancies. Initially identified in association with Wilms' tumor, a pediatric renal carcinoma, WT1 is now recognized for its broader implications in the etiology of multiple cancers, including leukemia, ovarian cancer, and lung cancer. This review offers a comprehensive analysis of the historical development of WT1 research, explores its mechanisms in cancer progression, and assesses its potential as a therapeutic target, with an emphasis on

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… KRAS-driven cancers In KRAS-driven cancers, WT1 modulates oncogenic signaling and cellular senescence. WT1 interacts with KRAS, a key regulator of proliferation and survival, and exhibits context-dependent roles—either promoting tumor growth or inducing senescence. …

Миэлоидно-подавительские клетки в карциноме ларингеальных клеток: недостаточно изученная иммунодепрессивная ось и стратегическая цель преодоления ингибиторного сопротивления на контрольно-пропускных пунктах.

Углубленные клеточные карциномы (LSCC) указывают на неизменно низкий коэффициент объективной реакции на ингибиторы на контрольно-пропускных пунктах (ИКИ) в отношении запрограммированных death-1 (В тыс.PD-1Путь. Его иммуновосприимчивая опухоль (TME), обогащенная макрофагами, связанными с опухолью, иммунодепрессивными опухолью, связанными с нейтрофилами (TANs), и регуляционными Т клетками, является основным фактором отказа ICI. Пока что one Миелоидное население, имеющее центральное значение для сопротивления ИКИ во многих случаях, не получает особого внимания в связи с этим заболеванием. Миелиои

Roles of circadian clocks in cancer pathogenesis and treatment.

Circadian clocks are ubiquitous timing mechanisms that generate approximately 24-h rhythms in cellular and bodily functions across nearly all living species. These internal clock systems enable living organisms to anticipate and respond to daily changes in their environment in a timely manner, optimizing temporal physiology and behaviors. Dysregulation of circadian rhythms by genetic and environmental risk factors increases susceptibility to multiple diseases, particularly cancers. A growing number of studies have revealed dynamic crosstalk between circadian clocks and cancer pathways, providi

5-Hydroxymethylcytosine Profiles of cfDNA in Urine as Diagnostic, Differential Diagnosis and Prognostic Markers for Multiple Myeloma.

BackgroundAn effective urine-based method for the diagnosis, differential diagnosis and prognosis of multiple myeloma (MM) has not yet been developed. Urine cell-free DNA (cfDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive "liquid biopsy" for diagnosis and monitoring of cancer.MethodsWe first identified MM-specific hydroxymethylcytosine signatures by comparing 64 MM patients, 23 amyloidosis (AM) patients and 59 healthy cohort. Then, we applied a machine learning algorithm to develop diagnostic and differential diagnosis model. Finally, the prognosis of

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… T., et al., “Suppression of Ribose‐5‐Phosphate Isomerase a Induces ROS to Activate Autophagy, Apoptosis, and Cellular Senescence in Lung Cancer,” International Journal of Molecular Sciences 23 (2022): 7883. 49. …

MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy.

Inhibition of the MDM2/X-p53 interaction is recognized as a potential anti-cancer strategy, including the treatment of glioblastoma (GB). In response to cellular stressors, such as DNA damage, the tumor suppression protein p53 is activated and responds by mediating cellular damage through DNA repair, cell cycle arrest and apoptosis. Hence, p53 activation plays a central role in cell survival and the effectiveness of cancer therapies. Alterations and reduced activity of p53 occur in 25-30% of primary GB tumors, but this number increases drastically to 60-70% in secondary GB. As a result, reacti

CD8+ CD28-нормативные T клетки после вводного лечения предсказывают, что пациенты миэломы выживут без прогрессирования: результат GMMG-HD6 Исследование по многоцентральной фазе III.

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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

Effect of pilose antler polypeptide on the mechanism of bone homeostasis in osteoporosis.

Osteoporosis stands out as a prevalent metabolic disorder, bearing significant repercussions on human well-being and overall quality of life. It remains an urgent concern within the global public health framework due to its widespread occurrence. Osteoporosis arises from an abnormal metabolism in osteoblasts and osteoclasts, resulting in a disruption of the delicate equilibrium between bone formation and bone resorption. Within this context, deer antler peptides emerge as natural active compounds, wielding a pivotal role in governing the differentiation, proliferation, and mineralization of os

Вакцинация в множественных миеломах: проблемы и стратегии.

Множественная миелома (ММ) — гематологическая халатность, характеризующаяся глубоким иммунодепрессией, вызванной как механизмами, связанными с заболеваниями, так и иммунной дисфункцией, вызванной лечением. Это скомпрометировало иммунный статус, что значительно повышает подверженность инфекциям, что является одной из основных причин заболеваемости и смертности у пациентов с ОМ. Хотя вакцинация является краеугольным камнем профилактики инфекции, стандартные стратегии иммунизации часто дают неоптимальную реакцию для этой группы населения. ЦЕЛИ: В настоящем обзоре обобщены имеющиеся данные об имму

Short-chain acyl post-translational modifications in cancers: Mechanisms, roles, and therapeutic implications.

Post-translational modifications (PTMs) play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality. PTMs involve the covalent attachment of distinct chemical groups, such as succinyl, crotonyl, and lactyl, at specific protein sites, which alter protein structure, function, stability, and activity, ultimately influencing biological processes. Recently, metabolically derived short-chain acylation modifications (with acyl groups containing fewer than six carbon atoms) have been progressively identified, such as butyrylation, succinylation, crotonylation

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… In hepatic cancer, crotonylation at the K265/K270 sites of lamin A aids in maintaining its nuclear localization, preventing cellular senescence, and thus accelerating hepatic cancer cell proliferation [ 15 ]. … Kcr ↑ | HDAC6 | Lamin A | K265, K270 | Maintains subcellular position of lamin A | Promotes cell proliferation, and prevents cellular senescence | Hepatocellular carcinoma | [ 15 ] Kla ↑ | AARS1 | YAP | K90 | Promotes nuclear localization and stabilization | Promotes cell proliferation | Gastric cancer …

Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.

The tumor suppressor p53, often referred to as the “guardian of the genome,” is mutated in more than half of human cancers. These mutations have a significant impact on cancer biology and response to therapy. p53 mutations involve a range of changes that interfere with DNA binding, eliminate tumor suppressor functions, and, in many cases, confer dominant-negative or gain-of-function characteristics that actively promote oncogenesis. These mutations are closely linked to poor clinical outcomes and resistance to standard treatments. This review examines the impact of p53 mutations on cancer ther

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… As a key transcription factor, p53 integrates signals from DNA damage, oncogenic stress, and metabolic imbalances to manage essential processes such as cell cycle arrest, DNA repair, cellular senescence, and apoptosis [ 4 – 7 ]. … Although this mutation primarily leads to a loss of transcriptional activity, it retains residual antiproliferative effects and can induce cellular senescence [ 25 ]. (4) Splice-site mutations in the TP53 gene are genetic changes that occur at the junctions between exons and introns, disrupting the normal …

Frailty and the risk of ICU-acquired infections in a randomised trial: a protocol and statistical analysis plan.

IntroductionDysregulated immunity may account for an increased risk of infection and other adverse outcomes among frail hospitalised persons. The primary objective of this study is to examine whether baseline frailty is associated with the risk of developing ventilator-associated pneumonia (VAP) or other intensive care unit (ICU)-acquired infections among invasively ventilated adults. Additional objectives are to examine the relationship between frailty and hospital length of stay, discharge to a long-term care facility and vital status. We hypothesise that persons with frailty compared with o

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… senescence. 16 The COVID-19 pandemic highlighted the interdependency of frailty, immunity and infections. 17 To examine the relationship between frailty and infectious complications, we will perform a preplanned secondary analysis of a randomised trial database. … Cellular senescence in acute human infectious disease: a systematic review. Front Aging. 2024;5:1500741. doi: 10.3389/fragi.2024.1500741. 17. Vetrano DL, Triolo F, Maggi S, et al. Fostering healthy aging: The interdependency of infections, immunity and frailty. …

Unraveling the Anticancer Effect of Curcumin and Resveratrol.

Resveratrol and curcumin are natural products with important therapeutic properties useful to treat several human diseases, including cancer. In the last years, the number of studies describing the effect of both polyphenols against cancer has increased; however, the mechanism of action in all of those cases is not completely comprehended. The unspecific effect and the ability to interfere in assays by both polyphenols make this challenge even more difficult. Herein, we analyzed the anticancer activity of resveratrol and curcumin reported in the literature in the last 11 years, in order to unr

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… In some cancer cell lines, inhibition of PLK leads to cellular senescence correlating to the number of cells arrested in mitosis [ 79 ]. 2.2.3. Phosphatidylinositol 3-Kinase (PI3K) Pathway PI3K is a protein that acts in the mechanism of cell survival. …