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Unraveling the Potential of SGK1 in Osteoporosis: From Molecular Mechanisms to Therapeutic Targets.

Osteoporosis (OP) is a prevalent metabolic bone disease, with several million cases of fractures resulting from osteoporosis worldwide each year. This phenomenon contributes to a substantial increase in direct medical expenditures and poses a considerable socioeconomic burden. Despite its prevalence, our understanding of the underlying mechanisms remains limited. Recent studies have demonstrated the involvement of serum glucocorticoid-regulated protein kinase 1 (SGK1) in multiple signaling pathways that regulate bone metabolism and its significant role in the development of osteoporosis. There

Семья гистона деацетилазы в здравии и болезни.

Классические деацетилазы, включая классы I, II и IV, в зависимости от цинка, повсеместно присутствуют у млекопитающих и играют жизненно важную роль в многочисленных биологических процессах. На сегодняшний день eleven Были выявлены члены < < хисттон деацетилаза > > , а именно < < хиттон деацетилаза > > . 1 через гистонную деацетилазу 11. Растущий объем данных подчеркивает важнейшую роль этих гистоновых деацетилазов как в физиологических, так и патологических условиях. В частности, эти гистонные деацетилазы участвуют в различных клеточных процессах, включая воспаление, ме

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… Furthermore, the essential roles of HDAC1 and HDAC2 during development have been highlighted, as their loss in podocytes leads to sustained DNA damage, cellular senescence, and podocyte depletion. 226 Beyond DNA damage, HDACs also regulate the expression of senescence-associated proteins, including key …

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a

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… For example, overexpression of the SIRT6 gene could inhibit apoptosis and induce autophagy, which might be involved in repairing kidney damage caused by lipopolysaccharide (LPS). 312 Autophagy controls cellular senescence by eliminating damaged cellular components and is negatively regulated by Akt signaling …

Osteocytes and Bone Metastasis.

Bone is the most frequent site of breast cancer and prostate cancer metastasis, and one of the most common sites of metastasis for many solid tumors. Once cancer cells colonize in the bone, it imposes a major clinical challenge for the treatment of the disease, and fatality rates increase drastically. Bone, the largest organ in the body, provides a fertile microenvironment enriched with nutrients, growth factors and hormones, a generous reward for cancer cells. Dependent on cancer type, cancer cells can cause osteoblastic (bone forming) or osteolytic lesions to promote the net resorption and/o

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… Sci Trans Med ( 2018 ) 10 . 10.1126/scitranslmed.aan3464 PMC6364295 29643230 54 Campisi J d’Adda di Fagagna F Cellular senescence: when bad things happen to good cells . … Clin Cancer Res ( 2014 ) 20 : 2922–32 . 10.1158/1078-0432.CCR-13-1246 PMC4040234 24687923 59 Schosserer M Grillari J Breitenbach M The Dual Role of Cellular Senescence in Developing Tumors and Their Response to Cancer Therapy . …

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecu

Множество миеломных клеточных липидов повышают целевость и эффективность нанолипосомных формул In Vitro.

Множественная миелома (MM) — рак крови, характеризующийся накоплением аномальных плазменных клеток в костном мозге (BM). Неопластическое расширение постепенно нарушает нормальное производство клеток крови, вытесняя здоровые кровеносные клетки. Болезнь характеризуется неизмеримо дифференцированными клетками В, которые выделяют антитела как часть адаптивной иммунной реакции. Одной из серьезных угроз, с которой сталкивается терапия малых молекул наркотиков для MM, является отсутствие селективной наркодиагностики, что в конечном счете приводит к недостаточному накоплению лекарств для целевых клето

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… The prevalence and role of cellular senescence in hematological malignancies has been documented [ 23 ]. However, the separated population of suspension cells produced adherent and floating cells ( Figure 1 C). … Regardless of the cellular senescence of the adherent cell population, the decision was made to include the mixed cell population in the lipid extraction process, thus aligning with efforts to obtain the most effective LE material. …

Modulating CD8⁺ T cell immunity through exercise: mechanistic insights and implications for precision immunotherapy.

CD8⁺ T lymphocytes are pivotal effectors of adaptive immunity, executing cytotoxic mechanisms essential for pathogen clearance, tumor surveillance and tissue protection. Their activity is shaped by antigenic stimulation, cytokine networks and the metabolic and structural architecture of the tissue microenvironment. Physical exercise has emerged as a potent, non-pharmacological modulator of CD8⁺ T cell biology, capable of influencing recruitment, activation, differentiation and functional persistence. Acute exercise mobilizes effector and memory subsets, enhances trafficking to peripheral tissu

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… In pre-diabetic individuals, three weeks of concentric or eccentric endurance exercise remodulates T cell immunity by reversing hallmarks of cellular senescence and reshaping the CD8⁺ T cell compartment. …

Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects.

Resveratrol (RES), a naturally occurring polyphenolic compound, has garnered significant attention due to its diverse biological activities, which include anti-inflammatory, antioxidant, and antiaging properties. This review synthesizes current evidence concerning the molecular mechanisms, therapeutic efficacy, and safety profile of RES across a variety of pathologies, with an emphasis on the latest research conducted in recent years. Mechanistically, RES is known to modulate critical signaling pathways such as the activation of sirtuin 1. These actions collectively contribute to the attenuati

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… RES also appears to induce S‐phase arrest and cellular senescence, where DNA double‐strand breaks are significantly increased. Additionally, it activates the chemokine receptor C‐X‐C motif chemokine receptor 2 (CXCR2)–p53 axis [ 205 ]. …

Deciphering transcriptomic changes in chemobrain: a comprehensive review.

Chemotherapy-induced cognitive impairments (CICI), colloquially known as "chemobrain," represents a profound and debilitating side effect experienced by a significant number of cancer survivors, impacting their memory, multitasking, and quality of life. This review critically evaluates the molecular mechanisms underlying CICI, with a particular focus on the insights gained from transcriptomic analyses. As cancer incidence rises globally, understanding the complex interplay between chemotherapy agents and their cognitive repercussions becomes increasingly vital. Key mechanisms implicated in CIC

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… Paclitaxel treatment induced cellular senescence predominantly in capillary endothelial cells, a phenomenon that can compromise the blood-brain barrier (BBB) permeability and can contribute to neuroinflammation. …

Molecular and epigenetic regulatory mechanisms of normal stem cell radiosensitivity.

Ionizing radiation (IR) therapy is a major cancer treatment modality and an indispensable auxiliary treatment for primary and metastatic cancers, but invariably results in debilitating organ dysfunctions. IR-induced depletion of neural stem/progenitor cells in the subgranular zone of the dentate gyrus in the hippocampus where neurogenesis occurs is considered largely responsible for deficiencies such as learning, memory, and spatial information processing in patients subjected to cranial irradiation. Similarly, IR therapy-induced intestinal injuries such as diarrhea and malabsorption are commo

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… No significant alterations in cellular senescence and apoptosis were detected in HSCs after exposure to low dose of radiation 107 . … Ko E Lee K Hwang D Human umbilical cord blood-derived mesenchymal stem cells undergo cellular senescence in response to oxidative stress Stem. Cells Dev. 2012 21 1877 1886 10.1089/scd.2011.0284 22066510 PMC3396141 70. …

The Crosstalk Between B Cells and the Skeletal System During Development, Aging, and in Pathological Conditions.

Purpose of reviewIn this review, we describe the interaction between B cells and bone during development, aging, and disease. RECENT FINDINGS: There is an increased interest in identifying the mechanisms of interaction between immune cells and the skeletal system. This knowledge is critical for understanding the pathology of autoimmune diseases and developing therapeutic interventions. Humoral immunity depends on B cells and their secreted immunoglobulin (antibodies). Earlier studies described B cell influence on the skeletal system, with a major focus on the role of plasma cells and secreted

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… PPARγ promotes cellular senescence through induction of p16 INK4α expression [ 117 ]. Interestingly, expression of PPARγ by B cells is important for their optimum function. … PPARgamma accelerates cellular senescence by inducing p16INK4alpha expression in human diploid fibroblasts. J Cell Sci. 2008;121(Pt 13):2235–45. 118. Ramon S, Bancos S, Thatcher TH, Murant TI, Moshkani S, Sahler JM, et al. …

Hallmarks of Cancer Affected by the MIF Cytokine Family.

New diagnostic methods and treatments have significantly decreased the mortality rates of cancer patients, but further improvements are warranted based on the identification of novel tumor-promoting molecules that can serve as therapeutic targets. The macrophage migration inhibitory factor (MIF) family of cytokines, comprising MIF and DDT (also known as MIF2), are overexpressed in almost all cancer types, and their high expressions are related to a worse prognosis for the patients. MIF is involved in 9 of the 10 hallmarks of cancer, and its inhibition by antibodies, nanobodies, or small synthe

Является ли изменение миелинодегенеративное изменение, связанное с возрастом, первоначальным фактором риска нейродегенеративных заболеваний?

Myelination, непрерывное покрытие нейронных аксонов, является пожизненным процессом в нервной системе, который необходим для точного, темпорального пространственного проведения потенциалов действий между нейронами. Myelin также оказывает межклеточную метаболическую поддержку аксонам. Даже незначительные нарушения целостности миелина могут ухудшить нейронные характеристики и повысить подверженность неврологическим заболеваниям. На самом деле, дегенерация миелина — это хорошо известное нейропологическое заболевание, связанное с нормальным старением и несколькими нейродегенеративными заболеваниям

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… We earlier stated that aged OPCs exhibit increased mRNA levels of cellular senescence markers (Neumann et al., 2019) and have poor differentiation ability. … Similarly, cellular senescence contributes to remyelination failure in progressive MS through the functional inhibition of OPC differentiation in demyelinated lesions in MS (Nicaise et al., 2019). …

Genomic instability and genetic heterogeneity in aging: insights from clonal hematopoiesis (CHIP), monoclonal gammopathy (MGUS), and monoclonal B-cell lymphocytosis (MBL).

Aging is a multifaceted process characterized by a gradual decline in physiological function and increased susceptibility to a range of chronic diseases. Among the molecular and cellular mechanisms driving aging, genomic instability is a fundamental hallmark, contributing to increased mutation load and genetic heterogeneity within cellular populations. This review explores the role of genomic instability and genetic heterogeneity in aging in the hematopoietic system, with a particular focus on clonal hematopoiesis of indeterminate potential (CHIP), monoclonal gammopathy of undetermined signifi

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… Cellular senescence, a state of permanent cell cycle arrest in response to stress, is closely linked to DNA damage. … Additionally, genomic instability can induce cellular senescence, a state of irreversible growth arrest, contributing to the depletion of stem cell pools and impairing tissue regeneration [ 29 ]. …

Metronomic chemotherapy.

Toxic effects and chemoresistance are major hurdles in chemotherapy and to avoid these problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called "metronomic chemotherapy" has emerged. Such regimen involves the frequent administration of conventional chemotherapeutic agents at very low doses to target activated endothelial cells in tumors, the advantages of which include minimal adverse effects and a rare chance of developing acquired drug resistance. Previously it was thought that they act by targeting angiogenesis, but recently additional mechanism

Transcriptomic analysis of mRNAs in human whole blood identified age-specific changes in healthy individuals.

Older age is one of the most important shared risk factors for multiple chronic diseases, increasing the medical burden to contemporary societies. Current research focuses on identifying aging biomarkers to predict aging trajectories and developing interventions aimed at preventing and delaying the progression of multimorbidity with aging. Here, a transcriptomic changes analysis of whole blood genes with age was conducted. The age-related whole blood gene-expression profiling datasets were downloaded from the Gene Expression Omnibus (GEO) database. We screened the differentially expressed gene

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… Cellular senescence in immunity against infections. Int J Mol Sci . 2022;23:11845. [15] Gasparoto TH, Dalboni TM, Amor NG, et al. Fcgamma receptors on aging neutrophils. J Appl Oral Sci. 2021;29:e20200770. [16] Kim C, Jin J, Weyand CM, et al. … Cellular senescence in lymphoid organs and immunosenescence. Aging (Albany NY). 2021;13:19920–41. [18] Lin H, Lunetta KL, Zhao Q, et al. Whole blood gene expression associated with clinical biological age. J Gerontol A Biol Sci Med Sci. 2019;74:81–8. [19] Jeong I, Lim J-H, Park J-S, et al. …

Targeting HDACs with dacinostat amplifies radiation-induced DNA damage via sustained phosphorylated p53 and repair inhibition in aggressive meningioma.

The lack of standard systemic treatments in meningioma presents a therapeutic challenge, making radiotherapy a crucial intervention for recurrent, high-grade, or inoperable tumours. Nonetheless, the efficacy of radiotherapy is constrained by the inherent radioresistance of meningiomas, attributed to their proficient DNA damage repair and robust cell cycle checkpoint regulation. These biological barriers, along with anatomical constraints of avoiding damage to adjacent neural tissues, restrict dose escalation and therapeutic gains. Histone deacetylases (HDACs) are mediators of radioresistance i

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… β-galactosidase (SA-gal) assay Cellular senescence was measured using a β-galactosidase staining kit as per the manufacturer’s instructions (Cell Signalling Technology). Cells were fixed, rinsed, and stained and then incubated overnight at 37 °C without CO 2 . … Radiation-induced cellular senescence results from a slippage of long-term G2 arrested cells into G1 phase. Cell Cycle. 2013;12:1424–32. 24. Amano T, Nakamizo A, Mishra SK, Gumin J, Shinojima N, Sawaya R, et al. …

Downregulation of SLC40A1 leads to iron accumulation in fibrotic lung fibroblasts.

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbe

Autophagic mechanisms in longevity intervention: role of natural active compounds.

The term 'autophagy' literally translates to 'self-eating' and alterations to autophagy have been identified as one of the several molecular changes that occur with aging in a variety of species. Autophagy and aging, have a complicated and multifaceted relationship that has recently come to light thanks to breakthroughs in our understanding of the various substrates of autophagy on tissue homoeostasis. Several studies have been conducted to reveal the relationship between autophagy and age-related diseases. The present review looks at a few new aspects of autophagy and speculates on how they m

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… Hallmarks of aging Hallmarks of aging are mainly loss of proteostasis, mitochondrial dysfunction, disordered nutrient perception, genomic instability, telomere attrition, cellular senescence, cellular stemness. … Autophagy and senescence Oxidative stress, DNA damage, telomere shortening lead to cellular senescence. While autophagy over-stimulation induces cell death, its deficiency can trigger cellular senescence (Ref. 31 ). …

Biological Age, Aging Clocks, and the Interplay with Lymphoid Neoplasms: Mechanisms and Clinical Frontiers.

Lymphoid neoplasms (LN), a diverse group of malignancies arising from lymphocytes, exhibit a striking increase in incidence with chronological age, suggesting a deep connection with the aging process. While chronological age remains a primary risk factor, the concept of biological age, reflecting an individual's physiological state and susceptibility to age-related diseases, offers a more nuanced understanding of this relationship. Aging clocks, particularly epigenetic clocks based on DNA methylation, provide quantitative measures of biological age and have revealed associations between accele

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… Tchkonia T ; Zhu Y ; van Deursen JV ; Campisi J ; Kirkland J Cellular senescence and the senescent secretory phenotype: Therapeutic opportunities . J. Clin. Investig 2013 , 123 , 966 – 972 . 23454759 10.1172/JCI64098 PMC3582125 31. … Vicente R ; Mausset-Bonnefont A ; Jorgensen C ; Louis-Plence P ; Brondello J Cellular senescence impact on immune cell fate and function . Aging Cell 2016 , 15 , 400 – 406 . 26910559 10.1111/acel.12455 PMC4854915 45. …