Did you mean: oncosil
-
Microbiology and Molecular Biology... Nov 2020Brucellosis is a bacterial disease of domestic animals and humans. The pathogenic ability of organisms relies on their stealthy strategy and their capacity to replicate... (Review)
Review
Brucellosis is a bacterial disease of domestic animals and humans. The pathogenic ability of organisms relies on their stealthy strategy and their capacity to replicate within host cells and to induce long-lasting infections. organisms barely induce neutrophil activation and survive within these leukocytes by resisting microbicidal mechanisms. Very few -infected neutrophils are found in the target organs, except for the bone marrow, early in infection. Still, induces a mild reactive oxygen species formation and, through its lipopolysaccharide, promotes the premature death of neutrophils, which release chemokines and express "eat me" signals. This effect drives the phagocytosis of infected neutrophils by mononuclear cells that become thoroughly susceptible to replication and vehicles for bacterial dispersion. The premature death of the infected neutrophils proceeds without NETosis, necrosis/oncosis, or classical apoptosis morphology. In the absence of neutrophils, the Th1 response exacerbates and promotes bacterial removal, indicating that -infected neutrophils dampen adaptive immunity. This modulatory effect opens a window for bacterial dispersion in host tissues before adaptive immunity becomes fully activated. However, the hyperactivation of immunity is not without a price, since neutropenic -infected animals develop cachexia in the early phases of the disease. The delay in the immunological response seems a requirement for the development of long-lasting brucellosis. This property may be shared with other pathogenic alphaproteobacteria closely related to We propose a model in which -infected polymorphonuclear neutrophils (PMNs) function as "Trojan horse" vehicles for bacterial dispersal and as modulators of the Th1 adaptive immunity in infection.
Topics: Animals; Apoptosis; Brucella; Brucellosis; Host-Pathogen Interactions; Humans; Immunity, Innate; Lipopolysaccharides; Neutrophils; Phagocytosis; Th1 Cells; Virulence
PubMed: 33055283
DOI: 10.1128/MMBR.00048-20 -
International Journal of Molecular... Jul 2023Lung cancer is one of the leading causes of cancer death. Non-small-cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnoses. Dihydrotanshinone (DHT)...
Lung cancer is one of the leading causes of cancer death. Non-small-cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnoses. Dihydrotanshinone (DHT) is a compound extract from , which has favorable anti-inflammatory and anti-cancer activities. However, the role of DHT in NSCLC has not been fully studied. The anti-cancer drugs used for treating lung cancer often lead to apoptosis; however, the drug resistance of apoptosis restricts the effect of these drugs. Oncosis is a passive form of cell death that is different from apoptosis. It is characterized by cell swelling, and Porimin is a specific marker for oncosis. In this study, the role of DHT in mediating oncosis in A549 cells was investigated. In vitro, the MTS assay was used to detect cell activity after DHT treatment. Microscopy and electron microscopy were used to observe cell morphology changes. Western blotting was used to detect protein expression. Flow cytometry was used to detect intracellular reactive oxygen species (ROS) level, calcium ion (Ca) level, and cell mortality. The intracellular Lactic dehydrogenase (LDH) level was detected by an LDH detection kit after DHT treatment. The ATP level was detected using an ATP detection kit. In vivo, Lewis lung cancer (LLC) xenograft mice were used to evaluate the anti-tumor effect of DHT. Hematoxylin and eosin (HE) staining was used to detect the pathology of lung cancer tumors. The detection of Porimin in the tumor tissues of the mice after DHT administration was assessed by immunohistochemistry (IHC). The results of this study showed that DHT treatment changed the cell morphology; destroyed the mitochondrial structure; increased the expression of Porimin; increased the levels of LDH, ROS, and Ca; decreased the mitochondrial membrane potential and ATP level; and played an anti-tumor role in vitro by mediating oncosis in A549 cells. The in vivo studies showed that DHT could effectively inhibit tumor growth. The results of protein detection and IHC detection in the tumor tissues showed that the expression of Porimin was increased and that oncosis occurred in the tumor tissues of mice. DHT triggered Porimin-dependent oncosis by ROS-mediated mitochondrial dysfunction in NSCLC. The in vivo studies showed that DHT could inhibit tumor growth in LLC xenograft mice by triggering oncosis. This study indicates the potential for DHT to treat NSCLC.
Topics: Animals; Humans; Mice; Adenosine Triphosphate; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Lung Neoplasms; Mitochondria; Reactive Oxygen Species
PubMed: 37569328
DOI: 10.3390/ijms241511953 -
Molecules (Basel, Switzerland) Nov 2022The potentially therapeutic effects of the naturally abundant plant flavonoid quercetin have been extensively studied. An extensive body of literature suggests that... (Review)
Review
The potentially therapeutic effects of the naturally abundant plant flavonoid quercetin have been extensively studied. An extensive body of literature suggests that quercetin's powerful antioxidant effects may relate to its ability to treat disease. Glutamate excitotoxicity occurs when a neuron is overstimulated by the neurotransmitter glutamate and causes dysregulation of intracellular calcium concentrations. Quercetin has been shown to be preventative against many forms of neuronal cell death resulting from glutamate excitotoxicity, such as oncosis, intrinsic apoptosis, mitochondrial permeability transition, ferroptosis, phagoptosis, lysosomal cell death, parthanatos, and death by reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation. The clinical importance for the attenuation of glutamate excitotoxicity arises from the need to deter the continuous formation of tissue infarction caused by various neurological diseases, such as ischemic stroke, seizures, neurodegenerative diseases, and trauma. This review aims to summarize what is known concerning glutamate physiology and glutamate excitotoxic pathophysiology and provide further insight into quercetin's potential to hinder neuronal death caused by cell death pathways activated by glutamate excitotoxicity. Quercetin's bioavailability may limit its use clinically, however. Thus, future research into ways to increase its bioavailability are warranted.
Topics: Humans; Glutamic Acid; Quercetin; Antioxidants; Reactive Oxygen Species; Neurodegenerative Diseases
PubMed: 36364448
DOI: 10.3390/molecules27217620 -
Burns & Trauma 2023Globally, ischemic stroke causes millions of deaths per year. The outcomes of ischemic stroke are largely determined by the amount of ischemia-related and... (Review)
Review
Globally, ischemic stroke causes millions of deaths per year. The outcomes of ischemic stroke are largely determined by the amount of ischemia-related and reperfusion-related neuronal death in the infarct region. In the infarct region, cell injuries follow either the regulated pathway involving precise signaling cascades, such as apoptosis and autophagy, or the nonregulated pathway, which is uncontrolled by any molecularly defined effector mechanisms such as necrosis. However, numerous studies have recently found that a certain type of necrosis can be regulated and potentially modified by drugs and is nonapoptotic; this type of necrosis is referred to as regulated necrosis. Depending on the signaling pathway, various elements of regulated necrosis contribute to the development of ischemic stroke, such as necroptosis, pyroptosis, ferroptosis, pathanatos, mitochondrial permeability transition pore-mediated necrosis and oncosis. In this review, we aim to summarize the underlying molecular mechanisms of regulated necrosis in ischemic stroke and explore the crosstalk and interplay among the diverse types of regulated necrosis. We believe that targeting these regulated necrosis pathways both pharmacologically and genetically in ischemia-induced neuronal death and protection could be an efficient strategy to increase neuronal survival and regeneration in ischemic stroke.
PubMed: 38026442
DOI: 10.1093/burnst/tkad016 -
Biomedicine & Pharmacotherapy =... Apr 2022Since the discovery of the kahalalide family of marine depsipeptides in 1993, considerable work has been done to develop these compounds as new and biologically distinct... (Review)
Review
Since the discovery of the kahalalide family of marine depsipeptides in 1993, considerable work has been done to develop these compounds as new and biologically distinct anti-cancer agents. Clinical trials and laboratory research have yielded a wealth of data that indicates tolerance of kahalalides in healthy cells and selective activity against diseased cells. Currently, two molecules have attracted the greates level of attention, kahalalide F (KF) and isokahalalide F (isoKF, Irvalec, PM 02734, elisidepsin). Both compounds were originally isolated from the sarcoglossan mollusk Elysia rufescens but due to distinct structural characteristics it has been hypothesized and recently shown that the ultimate origin of the molecules is microbial. The search for their true source has been a subject of considerable research in the anticipation of finding new analogs and a culturable expression system that can produce sufficient material through fermentation to be industrially relevant.
Topics: Animals; Antineoplastic Agents; Depsipeptides; Mollusca; Neoplasms
PubMed: 35149387
DOI: 10.1016/j.biopha.2022.112676 -
Advanced Science (Weinheim,... Sep 2021Oncosis, depending on DNA damage and mitochondrial swelling, is an important approach for treating cancer and other diseases. However, little is known about the behavior...
Oncosis, depending on DNA damage and mitochondrial swelling, is an important approach for treating cancer and other diseases. However, little is known about the behavior of mitochondria during oncosis, due to the lack of probes for in situ visual illumination of the mitochondrial membrane and mtDNA. Herein, a mitochondrial lipid and mtDNA dual-labeled probe, MitoMN, and a continuous add-on assay, are designed to image the dynamic process of mitochondria in conditions that are unobservable with current mitochondrial probes. Meanwhile, the MitoMN can induce oncosis in a light-activated manner, which results in the enlargement of mitochondria and the death of cancer cells. Using structured illumination microscopy (SIM), MitoMN-stained mitochondria with a dual-color response reveals, for the first time, how swelled mitochondria interacts and fuses with each other for a nonlinear enlargement to accelerate oncosis into an irreversible stage. With this sign of irreversible oncosis revealed by MitoMN, oncosis can be segregated into three stages, including before oncosis, initial oncosis, and accelerated oncosis.
Topics: Cell Death; Cells, Cultured; DNA, Mitochondrial; Equipment Design; Light; Microscopy; Mitochondria; Mitochondrial Membranes
PubMed: 34197052
DOI: 10.1002/advs.202004566 -
Experimental and Molecular Pathology Aug 2021This review explores the developments leading up to the establishment of the cell theory and cellular pathology and their subsequent refinements and applications while... (Review)
Review
This review explores the developments leading up to the establishment of the cell theory and cellular pathology and their subsequent refinements and applications while focusing on the individuals who have made seminal advances in the field. The links between cell biology, cell pathology and cell injury research are emphasized. Recognition also is given to the importance of technological advances in microscopy, histology, biochemical and molecular methods for discovery in cell biology and cell pathology. Particular attention is focused on the work of Rudolph Virchow and his former students in the formulation of the cell theory in biology and pathology and John F. R. Kerr and colleagues who identified and developed a comprehensive characterization of apoptosis, thereby giving impetus to the contemporary field of cell injury research. Cell injury research remains an important and fruitful field of ongoing inquiry and discovery.
Topics: Animals; Biology; Cell Death; Humans; Medicine; Necrosis
PubMed: 34116021
DOI: 10.1016/j.yexmp.2021.104660 -
Oncology Letters Feb 2023Colorectal cancer (CRC) has high morbidity and mortality, particularly if diagnosed at an advanced stage. Although there have been several studies on CRC, few have...
Colorectal cancer (CRC) has high morbidity and mortality, particularly if diagnosed at an advanced stage. Although there have been several studies on CRC, few have investigated the relationship between oncosis and CRC. Thus, the purpose of the present study was to identify oncosis-related long noncoding RNAs (lncRNAs) and to establish a clinical prognostic model. Original data were acquired from The Cancer Genome Atlas database and PubMed. Differentially expressed oncosis-related lncRNAs (DEorlncRNAs) were identified and were subsequently formed into pairs. Next, a series of tests and analyses, including both univariate and multivariate analyses, as well as Lasso and Cox regression analyses, were performed to establish a receiver operating characteristic curve. A cut-off point was subsequently used to divide the samples into groups labelled as high- or low-risk. Thus, a model was established and evaluated in several dimensions. Six pairs of DEorlncRNAs associated with prognosis according to the algorithm were screened out and the CRC cases were divided into high- and low-risk groups. Significant differences between patients in the different risk groups were observed for several traits, including survival outcomes, clinical pathology characteristics, immune cell infiltration status and drug sensitivity. In addition, PCR and flow cytometry were performed to further verify the model. In summary, a new risk model algorithm based on six pairs of DEorlncRNAs in CRC, which does not require specific data regarding the level of gene expression, was established and validated. This algorithm may be used to predict patient prognosis, immune cell infiltration and drug sensitivity.
PubMed: 36644148
DOI: 10.3892/ol.2022.13650 -
Animal Models and Experimental Medicine Apr 2023Multiple mitochondrial dysfunction syndromes (MMDS) are rare mitochondrial diseases caused by mutation of mitochondrial iron-sulfur cluster synthesis proteins. This...
BACKGROUND
Multiple mitochondrial dysfunction syndromes (MMDS) are rare mitochondrial diseases caused by mutation of mitochondrial iron-sulfur cluster synthesis proteins. This study established a rat model simulating MMDS5 disease in the nervous system to investigate its pathological features and neuronal death.
METHODS
We generated neuron-specific Isca1 knockout rat (Isca1 -NeuN-Cre) using CRISPR-Cas9 technology. The brain structure changes of CKO rats were studied with MRI, and the behavior abnormalities were analyzed through gait analysis and open field tests, Y maze tests and food maze tests. The pathological changes of neurons were analyzed through H&E staining, Nissl staining, and Golgi staining. Mitochondrial damage was assessed by TEM, western blot and ATP assay, and the morphology of neurons was assessed by WGA immunofluorescence to detect the death of neurons.
RESULTS
This study established the disease model of MMDS5 in the nervous system for the first time, and found that after Isca1 loss, the rats suffered from developmental retardation, epilepsy, memory impairment, massive neuronal death, reduced number of Nissl bodies and dendritic spines, mitochondrial fragmentation, cristae fracture, reduced content of respiratory chain complex protein, and reduced production of ATP. Isca1 knockout caused neuronal oncosis.
CONCLUSIONS
This rat model can be used to study the pathogenesis of MMDS. In addition, compared with human MMDS5, the rat model can survive up to 8 weeks of age, effectively extending the window of clinical treatment research, and can be used for the treatment of neurological symptoms in other mitochondrial diseases.
Topics: Rats; Humans; Animals; Syndrome; Mitochondrial Diseases; Iron-Sulfur Proteins; Mitochondria; Neurons; Adenosine Triphosphate; Mitochondrial Proteins
PubMed: 37140997
DOI: 10.1002/ame2.12318 -
Frontiers in Pharmacology 2020Artemisinin and its derivatives have shown broad-spectrum antitumor activities and . Furthermore, outcomes from a limited number of clinical trials provide encouraging... (Review)
Review
Artemisinin and its derivatives have shown broad-spectrum antitumor activities and . Furthermore, outcomes from a limited number of clinical trials provide encouraging evidence for their excellent antitumor activities. However, some problems such as poor solubility, toxicity and controversial mechanisms of action hamper their use as effective antitumor agents in the clinic. In order to accelerate the use of ARTs in the clinic, researchers have recently developed novel therapeutic approaches including developing novel derivatives, manufacturing novel nano-formulations, and combining ARTs with other drugs for cancer therapy. The related mechanisms of action were explored. This review describes ARTs used to induce non-apoptotic cell death containing oncosis, autophagy, and ferroptosis. Moreover, it highlights the ARTs-caused effects on cancer metabolism, immunosuppression and cancer stem cells and discusses clinical trials of ARTs used to treat cancer. The review provides additional insight into the molecular mechanism of action of ARTs and their considerable clinical potential.
PubMed: 33117153
DOI: 10.3389/fphar.2020.529881