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COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde

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… A number of proteins associated with cell-cycle progression in the SARS-CoV-2 interactome has been identified, including proteins associated with the centrosome, mitotic spindle, and cytokinesis control [ 168 ]. … Centrosome-associated proteins, nuclear pore proteins, ER quality control proteins, RNA processing proteins, respiratory electron transport proteins, and Ras-associated binding (RAB) signaling proteins have been identified as key targets of SARS-CoV-2 [ 26 ]. …

Exploring human plasma proteomic variations in mucolipidosis type IV.

Mucolipidosis IV (MLIV) is an autosomal-recessive pediatric disease that leads to motor and cognitive deficits and loss of vision. It is caused by loss of function of the lysosomal channel transient receptor potential mucolipin-1, TRPML1, and is associated with an early brain phenotype consisting of glial reactivity, hypomyelination, and lysosomal abnormalities. Although the field is approaching the first translationally relevant therapy, we currently lack a molecular signature of disease that can be used to detect therapeutic efficacy. Here, we analyzed 7,322 proteins in the plasma proteome f

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… Autophagy-related functions of GABARAPs, distinct from LC3, include autophagy initiation, cargo targeting, autophagosome-lysosomal fusion, TFEB-dependent coordination of lysosomal biogenesis and capacity and selective autophagy, such as mitophagy, ERphagy, as well as autophagic degradation of Golgi and centrosomes …

Identification of Potentially Pathogenic Variants Associated with Recurrence in Medication-Related Osteonecrosis of the Jaw (MRONJ) Patients Using Whole-Exome Sequencing.

Background: Bisphosphonates are antiresorptive and antiangiogenic drugs that prevent and treat bone loss and mineralization in women with postmenopausal osteoporosis and cancer patients. Medication-related osteonecrosis of the jaw (MRONJ) is commonly caused by tooth extraction and dental trauma. Although genetic and pathological studies about MRONJ have been conducted, the pathogenesis of MRONJ still remains unclear. Methods: We aimed to identify genetic variants associated with MRONJ, using whole-exome sequencing (WES). Ten MRONJ patients prescribed bisphosphonates were recruited for WES, and

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… Twenty-three of 942 nonsynonymous variants were distributed in PDE4DIP , which encodes anchoring the primary c-AMP-hydrolyzing enzyme and the phosphodiesterase 4D (PDE4D) protein, to the Gogi/centrosome region of the cell. …

Novel Non-Immunologic Agents for Relapsed and Refractory Multiple Myeloma: A Review Article.

Novel treatments are needed to address the lack of options for patients with relapsed or refractory multiple myeloma. Even though immunotherapy-based treatments have revolutionized the field in recent years, offering new opportunities for patients, there is still no curative therapy. Thus, non-immunologic agents, which have proven effective for decades, are still central to the treatment of multiple myeloma, especially for advanced disease. Building on their efficacy in myeloma, the development of proteasome inhibitors and immunomodulatory drugs has been pursued, and has led to the emergence o

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… Filanesib is a kinesin spindle protein (KSP) inhibitor that blocks the separation of centrosomes via KSPs during mitosis and induces cell cycle stoppage and apoptosis. KSP inhibition induces the degradation of MCL-1, which results in MM cell death. …

Antimitotic drugs in the treatment of cancer.

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell res

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… Regulating proteins of microtubules such as mitotic centrosome-associated kinesin (MCAK), stathmin and tau are associated with antimitotic drug resistance [ 91 ]. …

Unlocking the therapeutic potential of cellular mechanobiology.

Mechanobiology is a rapidly advancing field at the intersection of biology, physics, and engineering that reveals how mechanical forces shape cellular behavior, tissue architecture, and disease progression. By elucidating how cells sense and transduce mechanical cues, mechanobiology has fundamentally advanced our understanding of processes ranging from migration and differentiation to immune responses and tissue remodeling. These advances have driven the development of innovative biophysical tools and engineered biomaterials that enable precise modulation of the cellular microenvironment. Tran

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… Protein micropatterns have transformed mechanobiology, revealing fundamental processes such as, for instance, the relationship between cell shape ( 109 ) and function ( 110 ) ( Fig. 3C ), centrosome positioning ( 111 ), migration in confined spaces ( 48 , 49 , 112 – 114 ) ( Fig. 3D ), myoblast fusion …

Multi-omics tumor profiling technologies to develop precision medicine in multiple myeloma.

Multiple myeloma (MM), the second most common hematologic cancer, is caused by accumulation of aberrant plasma cells in the bone marrow. Its molecular causes are not fully understood and its great heterogeneity among patients complicates therapeutic decision-making. In the past decades, development of new therapies and drugs have significantly improved survival of MM patients. However, resistance to drugs and relapse remain the most common causes of mortality and are the major challenges to overcome. The advent of high throughput omics technologies capable of analyzing big amount of clinical a

KIF11 promotes rheumatoid arthritis pathogenesis by activating M1 macrophage polarization and promoting inflammatory cytokine secretion.

BACKGROUND AND OBJECTIVE: KIF11, a mitotic kinesin, has been implicated in oncogenesis, but its specific role and mechanism in RA pathogenesis remain largely unexplored. We aim to explore functional role and molecular mechanism of KIF11 to promote RA progression. METHODS: Bioinformatics analysis was first performed on public RA datasets (GSE55457, GSE55235, GSE2053, GSE12021, and GSE1919) to identify KIF11-associated DEGs and their enriched pathways using GO/KEGG and GSEA analysis. Lentivirus-mediated shRNA was employed to knock down KIF11 expression in MH7A cells and M1-polarized macrophages

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… Kinesins regulate the heterogeneity in centrosome clustering after whole-genome duplication. Life Sci Alliance. 2024;7(10):e202402670. doi: 10.26508/lsa.202402670 38. Sun R-F, He N, Zhang G-Y, Yu Z-Y, Li L-S, Ma Z-J, et al. …

Centromere protein E as a novel biomarker and potential therapeutic target for retinoblastoma.

Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub

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… Knockdown of integrin-linked kinase (ILK), a protein that mediates microtubule dynamics and centrosome clustering in the cell cycle process and tumor transformation, results in mitotic arrest[ 50 ]. …

miRNA-seq identification and clinical validation of CD138+ and circulating miR-25 in treatment response of multiple myeloma.

BackgroundDespite significant advancements in multiple myeloma (MM) therapy, the highly heterogenous treatment response hinders reliable prognosis and tailored therapeutics. Herein, we have studied the clinical utility of miRNAs in ameliorating patients' management.MethodsmiRNA-seq was performed in bone marrow CD138+ plasma cells (PCs) of 24 MM and smoldering MM (sMM) patients to analyze miRNAs profile. CD138+ and circulating miR-25 levels were quantified using in house RT-qPCR assays in our screening MM/sMM cohort (CD138+ plasma cells n = 167; subcohort of MM peripheral plasma samples n = 69)

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… Kryukov F Nemec P Radova L Kryukova E Okubote S Minarik J Centrosome associated genes pattern for risk sub-stratification in multiple myeloma J Transl Med 2016 14 1 150 10.1186/s12967-016-0906-9 27234807 PMC4884414 22. …

SETD2 and EZH2: Two epigenetic drivers of prostate cancer.

Prostate cancer is a prevalent malignancy among men, characterized by complex mechanisms underlying metastasis and treatment resistance. Epigenetic modifications play a crucial role in regulating prostate cancer progression, particularly involving histone methyltransferases such as SET-domain containing 2 (SETD2) and Enhancer of Zeste homolog 2 (EZH2). SETD2 contributes to chromatin stability by catalyzing the trimethylation of histone H3 lysine 36 (H3K36me3), and its downregulation is strongly correlated with increased invasiveness and epithelial-mesenchymal transition in prostate cancer. Con

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… Oncogenic PIK3CA induces centrosome amplification and tolerance to genome doubling. Nat Commun. 2017;8(1):1773. doi: 10.1038/s41467-017-02002-4. 115. Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP. et al. The mutational landscape of lethal castration-resistant prostate cancer. …

Aspects of vincristine-induced neuropathy in hematologic malignancies: a systematic review.

PurposeVincristine is widely used as anticancer therapy for a variety of hematological malignancies. The treatment is limited by progressive vincristine-induced neuropathy, possibly including both peripheral sensory and motor nerves, autonomic nervous functions, and the central nervous system. This dose-limiting side-effect can diminish quality of life and, furthermore, cause discontinuation of vincristine treatment. The present review elucidates the current knowledge regarding vincristine-induced neuropathy in hematologic malignancies, focusing on neuropathy assessment, clinical and molecular

Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer.

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogeno

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… Nucleophosmin 1 Nucleophosmin 1 (NPM1) is a nucleolar phosphoprotein involved in numerous cellular processes, including centrosome duplication, histone assembly, protein chaperoning and cell proliferation[ 113 , 114 ]. …

Clinical epigenetics settings for cancer and cardiovascular diseases: real-life applications of network medicine at the bedside.

Despite impressive efforts invested in epigenetic research in the last 50 years, clinical applications are still lacking. Only a few university hospital centers currently use epigenetic biomarkers at the bedside. Moreover, the overall concept of precision medicine is not widely recognized in routine medical practice and the reductionist approach remains predominant in treating patients affected by major diseases such as cancer and cardiovascular diseases. By its' very nature, epigenetics is integrative of genetic networks. The study of epigenetic biomarkers has led to the identification of num

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… Epigenetic modifications to centrosome proteins led to tumor development and drug resistance. …

The potential of dibenzazepine carboxamides in cancer therapy.

Cancer is a leading cause of mortality worldwide, with most conventional treatments lacking efficacy and having significant challenges like drug resistance. Finding new molecules is quite challenging in terms of cost, time and setbacks. Hence, drug repurposing is considered sensible for skipping the long process of drug development. Dibenzazepine carboxamides, as traditional anticonvulsants, primarily function by blocking voltage-gated sodium channels, which not only mitigate seizures but also influence mood disorders through modulation of serotonin and dopamine. Recent studies have uncovered

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… Also, it inhibited centrosome separation by reducing Polo-like kinase 1 (PLK1) activation and inducing apoptosis in NRK-52E cells via abnormal spindle formation ( Ota et al., 2021 ). Cancer studies have demonstrated the induction of apoptosis by dibenzazepines. …

PLP2 Could Be a Prognostic Biomarker and Potential Treatment Target in Glioblastoma Multiforme.

ObjectiveThis study aimed to discern the association between PLP2 expression, its biological significance, and the extent of immune infiltration in human GBM.MethodsUtilizing the GEPIA2 and TCGA databases, we contrasted the expression levels of PLP2 in GBM against normal tissue. We utilized GEPIA2 and LinkedOmics for survival analysis, recognized genes co-expressed with PLP2 via cBioPortal and GEPIA2, and implemented GO and KEGG analyses. The STRING database facilitated the construction of protein-protein interaction networks. We evaluated the relationship of PLP2 with tumor immune infiltrates

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… Beclin 1 and UVRAG confer protection from radiation-induced DNA damage and maintain centrosome stability in colorectal cancer cells . Available from : https://pubmed.ncbi.nlm.nih.gov/24956373/ . Accessed October 5 , 2023 . 10.1371/journal.pone.0100819 PMC4067383 24956373 97. …

The Battlefield of Chemotherapy in Pediatric Cancers.

The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved chemotherapy drugs that can be used in children have expanded, but patients still face numerous side effects from the treatment. In addition, multidrug resistance (MDR) continues to pose a major challenge in improving the survival rates for a significant number of patients. This review focuses

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… The CEP72 genetic variant is an optimistic VIPN signature marker since the CEP72 gene encodes centrosome proteins that participate in the development of microtubules. Patients that carry CEP72 TT genotype take potentially higher risk and severity of VIPN than CC or CT genotype patients [ 69 ]. …

Role of Fibroblast Growth Factors Receptors (FGFRs) in Brain Tumors, Focus on Astrocytoma and Glioblastoma.

Despite pharmacological treatments and surgical practice options, the mortality rate of astrocytomas and glioblastomas remains high, thus representing a medical emergency for which it is necessary to find new therapeutic strategies. Fibroblast growth factors (FGFs) act through their associated receptors (FGFRs), a family of tyrosine kinase receptors consisting of four members (FGFR1-4), regulators of tissue development and repair. In particular, FGFRs play an important role in cell proliferation, survival, and migration, as well as angiogenesis, thus their gene alteration is certainly related

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… The TACC proteins: TACC-ling microtubule dynamics and centrosome function Trends Cell Biol. 2008 18 379 388 10.1016/j.tcb.2008.06.005 18656360 152. Costa R. Carneiro B.A. Taxter T. Tavora F.A. Kalyan A. Pai S.A. Chae Y.K. Giles F.J. …

Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.

The tumor microenvironment (TME) has been extensively investigated; however, it is complex and remains unclear, especially in elderly patients. Senescence is a cellular response to a variety of stress signals, which is characterized by stable arrest of the cell cycle and major changes in cell morphology and physiology. To the best of our knowledge, senescence leads to consistent arrest of tumor cells and remodeling of the tumor-immune microenvironment (TIME) by activating a set of pleiotropic cytokines, chemokines, growth factors, and proteinases, which constitute the senescence-associated sec

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… In addition, centrosome dysfunction may regulate aging, tumorigenesis, and tumor immunity [ 54 ]. …

Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.

Autosomal dominant polycystic kidney disease (ADPKD), with an estimated genetic prevalence between 1:400 and 1:1,000 individuals, is the third most common cause of end stage kidney disease after diabetes mellitus and hypertension. Over the last 3 decades there has been great progress in understanding its pathogenesis. This allows the stratification of therapeutic targets into four levels, gene mutation and polycystin disruption, proximal mechanisms directly caused by disruption of polycystin function, downstream regulatory and signaling pathways, and non-specific pathophysiologic processes sha

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… SIRT2 regulates cilia formation and disassembly and contributes to aberrant centrosome amplification and polyploidy in PKD ( Zhou et al., 2014 ). These preclinical studies have provided the rationale to support that SIRT1 is an attractive therapeutic target of ADPKD. …