Exosome DNA: An untold story of cancer Bhattacharya, Bikramjit; Dhar, Rajib; Mukherjee, Sayantanee ...
Clinical and translational discovery,
August 2023, 2023-08-00, 20230801, 2023-08-01, Letnik:
3, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Exosome is nanosized tiny membrane‐bound vesicles and is a subpopulation of extracellular vesicles (EVs). In general, it participates in intercellular communication and acts as a messenger of several ...pathological complications. Exosome and cancer interlink is the most exciting domain of current cancer research. The internal molecular cargos (proteins, lipids, metabolites, miRNA, and DNA) of tumor derived exosomes (TEXs) are capable of transforming normal cells into tumor phenotypes. Exosome DNA is the less explored area of EVs research. It is involved in several events in cancer progression such as uncontrol cell growth, reprogramming of immune cells, metastasis, and therapeutic resistance. Exo‐DNA is also involved in epigenetic alteration, which promotes cancer. It has a great impact on cancer theranostics (biomarker and therapeutics) research. Exo‐DNA‐based cancer examination supports more detailed cancer research.
Theranostics clinical signature of ExoDNA in cancer.
Human Islet amyloid polypeptide (hIAPP) from pancreatic β cells in the islet of Langerhans has different physiological functions including inhibiting the release of insulin and glucagon. Type 2 ...diabetes mellitus (T2DM) is an endocrine disorder due to relative insulin insufficiency and insulin resistance (IR) is associated with increased circulating hIAPP. Remarkably, hIAPP has structural similarity with amyloid beta (Aβ) and can engage in the pathogenesis of T2DM and Alzheimer's disease (AD). Therefore, the present review aimed to elucidate how hIAPP acts as a link between T2DM and AD. IR, aging and low β cell mass increase expression of hIAPP which binds cell membrane leading to the aberrant release of Ca
and activation of the proteolytic enzymes leading to a series of events causing loss of β cells. Peripheral hIAPP plays a major role in the pathogenesis of AD, and high circulating hIAPP level increase AD risk in T2DM patients. However, there is no hard evidence for the role of brain-derived hIAPP in the pathogenesis of AD. Nevertheless, oxidative stress, mitochondrial dysfunction, chaperon-mediated autophagy, heparan sulfate proteoglycan (HSPG), immune response, and zinc homeostasis in T2DM could be the possible mechanisms for the induction of the aggregation of hIAPP which increase AD risk. In conclusion, increasing hIAPP circulating levels in T2DM patients predispose them to the development and progression of AD. Dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists attenuate AD in T2DM by inhibiting expression and deposition of hIAP.
Parkinson's disease (PD) is a progressive neurodegenerative disease as a result of the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The fundamental features of ...PD are motor and non-motor symptoms. PD symptoms develop due to the disruption of dopaminergic neurotransmitters and other neurotransmitters such as γ-aminobutyric acid (GABA). The potential role of GABA in PD neuropathology concerning the motor and non-motor symptoms of PD was not precisely discussed. Therefore, this review intended to illustrate the possible role of GABA in PD neuropathology regarding motor and non-motor symptoms. The GABA pathway is essential in regulating the inhibitory tone to prevent excessive stimulation of the cerebral cortex. Degeneration of dopaminergic neurons in PD is linked with reducing GABAergic neurotransmission. Decreasing GABA activity promotes mitochondrial dysfunction and oxidative stress, which are highly related to PD neuropathology. Hence, restoring GABA activity by GABA agonists may attenuate the progression of PD motor symptoms. Therefore, dysregulation of GABAergic neurons in the SNpc contributes to developing PD motor symptoms. Besides, PD non-motor symptoms are also related to the dysfunction of the GABAergic pathway, and amelioration of this pathway may reduce PD non-motor symptoms. In conclusion, the deregulation of the GABAergic pathway in PD might be intricate in developing motor and non-motor symptoms. Improving this pathway might be a novel, beneficial approach to control PD symptoms.
Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, ...and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial-mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC.
Role of fenofibrate in multiple sclerosis Abulaban, Ahmad A; Al-Kuraishy, Hayder M; Al-Gareeb, Ali I ...
European journal of medical research,
02/2024, Letnik:
29, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the central nervous system (CNS). The underlying pathophysiology of MS is the destruction of myelin sheath by ...immune cells. The formation of myelin plaques, inflammation, and injury of neuronal myelin sheath characterizes its neuropathology. MS plaques are multiple focal regions of demyelination disseminated in the brain's white matter, spinal cords, deep grey matter, and cerebral cortex. Fenofibrate is a peroxisome proliferative activated receptor alpha (PPAR-α) that attenuates the inflammatory reactions in MS. Fenofibrate inhibits differentiation of Th17 by inhibiting the expression of pro-inflammatory signaling. According to these findings, this review intended to illuminate the mechanistic immunoinflammatory role of fenofibrate in mitigating MS neuropathology. In conclusion, fenofibrate can attenuate MS neuropathology by modulating different pathways, including oxidative stress, autophagy, mitochondrial dysfunction, inflammatory-signaling pathways, and neuroinflammation.
Pseudoaneurysm formation often complicates transfemoral interventional procedures. Nonsurgical treatment consists of femoral compression and thrombin injection under ultrasound guidance. We report a ...74-year-old man who was diagnosed with a pseudoaneurysm, following coronary angiography. Duplex ultrasound revealed deep vein thrombosis of the ipsilateral common femoral vein. Ultrasound-guided thrombin injection was unsuccessfully performed, and the patient subsequently underwent surgical exploration for repair of the pseudoaneurysm and release of the venous compression. The increased local inflammation, because of the thrombosis, added in surgical difficulties. We conclude that early surgical intervention should be considered as a primary strategy in patients with femoral pseudoaneurysms and deep vein thrombosis secondary to femoral compression.
Pancreatitis is an inflammatory disorder resulting from the autoactivation of trypsinogen in the pancreas. The genetic basis of the disease is an old phenomenon, and evidence is accumulating for the ...involvement of synonymous/non-synonymous codon variants in disease initiation and progression.
The present study envisaged a panel of 26 genes involved in pancreatitis for their codon choices, compositional analysis, relative dinucleotide frequency, nucleotide disproportion, protein physical properties, gene expression, codon bias, and interrelated of all these factors. In this set of genes, gene length was positively correlated with nucleotide skews and codon usage bias. Codon usage of any gene is dependent upon its AT and GC component; however, AGG, CGT, and CGA encoding for Arg, TCG for Ser, GTC for Val, and CCA for Pro were independent of nucleotide compositions. In addition, Codon GTC showed a correlation with protein properties, isoelectric point, instability index, and frequency of basic amino acids. We also investigated the effect of various evolutionary forces in shaping the codon usage choices of genes.
This study will enable us to gain insight into the molecular signatures associated with the disease that might help identify more potential genes contributing to enhanced risk for pancreatitis. All the genes associated with pancreatitis are generally associated with physiological function, and mutations causing loss of function, over or under expression leads to an ailment. Therefore, the present study attempts to envisage the molecular signature in a group of genes that lead to pancreatitis in case of malfunction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Parkinson's disease (PD) is the second most frequent neurodegenerative brain disease (NBD) after Alzheimer's disease (AD). Statins are the most common lipid‐lowering agents used in the management of ...dyslipidemia and the prevention of primary and secondary cardiovascular diseases (CVD) events. In addition, there is a controversial point regarding the role of serum lipids in the pathogenesis of PD. In this bargain, as statins reduce serum cholesterol so they affect the PD neuropathology in bidirectional ways either protective or harmful. Statins are not used in the management of PD, but they are frequently used in the cardiovascular disorders commonly associated with PD in the elderly population. Therefore, the use of statins in that population may affect PD outcomes. Concerning the potential role of statins on PD neuropathology, there are conflicts and controversies either protective against the development of PD or harmful by increasing the risk for the development of PD. Therefore, this review aimed to clarify the precise role of statins in PD regarding the pros and cons from published studies. Many studies suggest a protective role of statins against PD risk through the modulation of inflammatory and lysosomal signaling pathways. Nevertheless, other observations suggest that statin therapy may increase PD risk by diverse mechanisms including reduction of CoQ10. In conclusion, there are strong controversies regarding the protective role of statins in PD neuropathology. Therefore, retrospective and prospective studies are necessary in this regard.
Abstract Chromosomal instability (CIN) is a pivotal factor in gliomas, contributing to their complexity, progression, and therapeutic challenges. CIN, characterized by frequent genomic alterations ...during mitosis, leads to genetic abnormalities and impacts cellular functions. This instability results from various factors, including replication errors and toxic compounds. While CIN’s role is well documented in cancers like ovarian cancer, its implications for gliomas are increasingly recognized. CIN influences glioma progression by affecting key oncological pathways, such as tumor suppressor genes (e.g., TP53), oncogenes (e.g., EGFR), and DNA repair mechanisms. It drives tumor evolution, promotes inflammatory signaling, and affects immune interactions, potentially leading to poor clinical outcomes and treatment resistance. This review examines CIN’s impact on gliomas through a narrative approach, analyzing data from PubMed/Medline, EMBASE, the Cochrane Library, and Scopus. It highlights CIN’s role across glioma subtypes, from adult glioblastomas and astrocytomas to pediatric oligodendrogliomas and astrocytomas. Key findings include CIN’s effect on tumor heterogeneity and its potential as a biomarker for early detection and monitoring. Emerging therapies targeting CIN, such as those modulating tumor mutation burden and DNA damage response pathways, show promise but face challenges. The review underscores the need for integrated therapeutic strategies and improved bioinformatics tools like CINdex to advance understanding and treatment of gliomas. Future research should focus on combining CIN-targeted therapies with immune modulation and personalized medicine to enhance patient outcomes.
