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Thermal stress-induced cell death pathways in Drosophila: molecular insights into apoptosis, necrosis, and autophagy.

Climate change threatens ectotherms, yet the cellular mechanisms underlying thermal injury remain poorly characterized. Here, we used an int … from 82% to 13%. Cold stress induced upregulation of pro-apoptotic genes (reaper, grim, sickle) and caspases (Dronc, Dcp-1, Damm), whereas heat stress predominantly induced Hsps genes (upregulation over 4000-fold) and some autophagy-related genes (Atg1, Atg6). Larvae with black spots exhibited hallmarks of necrosis, including low cell viability, severe cyt …

Heme and hemozoin induce platelet cell death through UPR-induced apoptosis and ferroptosis in vivax malaria.

Malaria is a highly prevalent infectious disease caused by Plasmodium parasites. Plasmodium intraerythrocytic replication leads to hemolysis … death features, with stronger necrosis triggered by hemozoin. Heme and hemozoin activated apoptotic caspases, but only heme induced calpain-dependent BcL-xL degradation, which was not required for platelet apoptosis. We unmasked a caspase-independent intrinsic apoptosis program mechanism depending on the endoplasmic reticulum stress sensor and unfolded pro …

Innovative Multitarget Organoselenium Hybrids With Apoptotic and Anti-Inflammatory Properties Acting as JAK1/STAT3 Suppressors.

Herein, we report the design, synthesis, and characterization of novel organoselenium (OSe) hybrids (5-19) via modifications of the lead, N- … nalysis on the A549 cancer cell line on OSe compounds 5 and 19 showed upregulation of P53, BAX, and Caspases 3, 6, 8, and 9 as apoptotic proteins. However, both candidates expressed downregulation of the antiapoptotic proteins (BCL2, MMP2, and MMP9). Moreover, OSe compounds 5 and 19 described the downregulation of the examined inflammatory proteins: COX2, …

6-[(1,4-Naphthoquinone-2-yl)methyl]thio-Glucose Conjugates, a Novel Targeted Approach for Advanced Prostate Cancer.

The Warburg effect is a shift from oxidative phosphorylation to anaerobic glycolysis, accompanied by an enormous increase in glucose uptake … ochondrial membrane potential, release of cytochrome C and apoptosis-inducing factor, activation of caspases-3 and -9, PARP cleavage, and apoptotic cell death. This process was stipulated by downregulation of several antiapoptotic factors and induction of endoplasmic reticulum stress. Moreover, drug-induced activation of signaling pathway mediated by p38, …

Anticancer Activity of Ethanolic Extract of Tabernaemontana catharinensis in Breast Cancer Lines MCF-7 and MDA-MB-231.

Breast cancer is a serious public health problem worldwide. Although current treatments with drugs such as cisplatin and paclitaxel are effe … r protein p53. Significant induction of apoptosis was also observed, evidenced by the activation of caspases -3/7, -8, and -9, along with a decrease in intracellular ATP levels (37% in MCF-7 and 90% in MDA-MB-231), suggesting mitochondrial dysfunction. Finally, EET showed the ability to inhibit cell invasion. Taken together, these results indicate that the …

Modeling the HLH immune synapse uncovers critical roles for IS termination, cytokine intensity, and target cell death.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome arising in many contexts. Its underlying … necrosis factor production. Similarly, both target cell immortalization and inhibition of apoptotic caspases impaired IS termination and increased cytokine production. Strong CTL activation, through T-cell receptor or IL-18 signaling, also increased IFN-γ secretion but accelerated target cell death. Impaired IS termination synergized with strong CTL activa …

Natterin bridges IFN-φ1 and non-canonical inflammasome pathways via CRFB1/Gbp4 to license Caspy2-mediated antibacterial immunity.

The Natterin protein family represents an evolutionarily conserved group of immune effectors in teleosts, yet its broader regulatory role in … prevented the expression of the LPS sensor GBP4 and the proteolytic maturation of the inflammatory caspases Caspy and Caspy2. This disruption abolished downstream gsdme-a/b expression, which may result in the non-formation of pores. The critical role of IFN-I signaling was independently confirmed by its neutralization in wild-type embryos, which abolished …

Устранение неврологических расстройств путем борьбы с нейродегенеративными ассоциированными ферментами: естественные и синтетические молекулы.

Неврологические расстройства, включая нейродегенеративные и нейро-воспалительные заболевания, создают значительные проблемы в области здравоохранения и клинических проблем. Недавние исследования показали, что различные ферменты играют ключевую роль в наступлении и развитии этих расстройств. В этом обзоре изучается терапевтический потенциал адресации этих ферментов естественными и синтетическими молекулами. К таким заболеваниям, как болезнь Альцгеймера, болезнь Паркинсона и множественный склероз, причастны основные ферменты, включая ацетилхолинестеразу, оксидазу моноамина, бета-секретазу, тау к

Совпадение в аннотации оригинала
Neurological disorders, encompassing neurodegenerative and neuroinflammatory conditions, present significant public health and clinical chal … cules. Key enzymes, including acetylcholinesterase, monoamine oxidase, beta-secretase, tau kinases, caspases, and cyclooxygenase-2, are implicated in diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Modulating these enzymes can alleviate symptoms, slow disease progression, or reverse pathological changes. Natural molecules …

[Molecular mechanisms of the effect of standardized placental hydrolysate peptides on mitochondria functioning].

BACKGROUND: Human placenta hydrolysates (HPH), the study of which was initiated by the scientific school of Vladimir P. Filatov, are current … is regulated by the identified peptides and significantly affects the function of mitochondria, are caspases (CASP1, CASP3, CASP4) and other proteins regulating apoptosis (BCL2, CANPL1, PPARA), MAP kinases (MAPK1, MAPK3, MAPK4, MAPK8, MAPK9 , MAPK10, MAPK14), AKT1/GSK3B/MTOR cascade kinases, and a number of other target proteins (ADGRG6 receptor, inhibitor …

Progress of Metal-Based Anticancer Chemotherapeutic Agents in Last two Decades and their Comprehensive Biological (DNA/RNA Binding, Cleavage and Cytotoxicity Activity) Studies.

During last two decades, there has been an enormous growth in the discovery of innovative active inorganic anticancer complexes (exerting re … xic action involving angiogenesis, ROS-induced DNA damage, apoptosis by p53 mitochondrial genes and caspases etc. The results observed a positive correlation between the binding affinity of complexes with DNA (as quantified by intrinsic binding constant values) and their cytotoxic behavior. Complexes with high DNA binding propensity were typically lethal a …

A human pilot study on positive electrostatic charge effects in solid tumors of the late-stage metastatic patients.

BACKGROUND: Correlative interactions between electrical charges and cancer cells involve important unknown factors in cancer diagnosis and treatment. We previously reported the intrinsic suppressive effects of pure positive electrostatic charges (PEC) on the proliferation and metabolism of invasive cancer cells without any effect on normal cells in cell lines and animal models. The proposed mechanism was the suppression of pro-caspases 3 and 9 with an increase in Bax/Bcl2 ratio in exposed malignant cells and perturbation induced in the KRAS pathway of malignant cells by electrostatic charges d…

The Effect of Thymus vulgaris on Hepatic Enzymes Activity and Apoptosis-Related Gene Expression in Streptozotocin-Induced Diabetic Rats.

Many diseases, including diabetes, are involved in the development of liver disorders through changes in the expression of genes such as apo … tioxidant compounds, thyme improves the liver tissue cells in STZ-induced diabetic mice by reducing caspases 3 and 9 as well as increasing Bcl-2.

Seed extract of Thai Mucuna pruriens reduced male reproductive damage in rats induced by chronic stress.

CONTEXT: Thai Mucuna pruriens (L.) DC. var. pruriens (Fabaceae) (TMP) is known to enrich reproduction but preventive effects on stress relat … genic acute regulatory (StAR), cytochrome P450 family 11 subfamily a member 1 (CYP11A1), AR, HSP70, caspases (3 and 9) and tyrosine phosphorylation (TyrPho) proteins were investigated. RESULTS: TMP extract improved cortisol level (0.84 ± 0.02 µg/dL) and protected against the damage of reproductive tissues and sperm parameters (count [49.78 ± 3.74 million …

A new synthetic antitumor naphthoquinone induces ROS-mediated apoptosis with activation of the JNK and p38 signaling pathways.

Quinones are plant-derived secondary metabolites that present diverse pharmacological properties, including antibacterial, antifungal, antiv … apoptosis, such as cell shrinkage, chromatin condensation, phosphatidylserine exposure, increase of caspases-9 and-3 activation, increase of internucleosomal DNA fragmentation without affecting the cell membrane permeabilization, increase of ROS production, and loss of mitochondrial membrane potential induced by CNFD. Moreover, gene expression experiments …

Recapitulating Cholangiopathy-Associated Necroptotic Cell Death In Vitro Using Human Cholangiocyte Organoids.

BACKGROUND & AIMS: Liver and bile duct diseases often are associated with extensive cell death of cholangiocytes. Necroptosis represents a c … be specifically evoked using tumor necrosis factor α and second mitochondrial-derived activator of caspases mimetic, with or without caspase inhibition in healthy and patient-derived ICOs. Necroptosis also was induced by ethanol metabolites or human bile in ICOs from donors and patients. The organoid cultures further uncovered interdonor variable and spec …

Effects of the methanol fraction of modified Seonghyangjeongki-san water extract on transient ischaemic brain injury in mice.

CONTEXT: Recently in Korean medicine, the antioxidant and anti-inflammatory activities of Seonghyangjeongki-san (SHJKS) were reported. Howev … ssed the expression of inducible nitric oxide synthase, reactive oxygen species, interleukin 1, and caspases-8 and -9 and increased the B-cell lymphoma 2/Bcl-2-associated X protein ratio (Bcl-2/Bax) in ischaemic mouse brain. The hippocampal pyramidal cell densities were significantly increased in the 300 mg/kg SHJKSmex-administered group compared to the MC …

JKST6, a novel multikinase modulator of the BCR-ABL1/STAT5 signaling pathway that potentiates direct BCR-ABL1 inhibition and overcomes imatinib resistance in chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is a hematological malignancy that highly depends on the BCR-ABL1/STAT5 signaling pathway for cell surviv … control of mitosis and DNA damage. Rapid increases in Annexin V staining and activation/cleavage of caspases 8, 9 and 3 were observed after JKST6 treatment in CML cells. Of interest, JKST6 inhibited BCR-ABL1/STAT5 signaling through oncokinase downregulation that was preceded by rapid polyubiquitination. In addition, JKST6 caused a transient increase in JNK …

Panax notoginseng saponins reduces the cisplatin-induced acute renal injury by increasing HIF-1α/BNIP3 to inhibit mitochondrial apoptosis pathway.

Cisplatin (CDDP) may induce apoptosis of renal tubular epithelial cells (RTEC) and cause CDDP-induced acute kidney injury (CAKI) during canc … nction, cell apoptosis ratio and the expression of apoptosis-associated proteins (Cyt C, Bcl2, Bax, caspases 3) were determined. In order to elucidate the underlying mechanism, the expression of HIF-1α and BNIP3 were assessed. Our results showed that treatment of PNS rescued the cell viability of CDDP-injured HK-2 or HIF-1α-knockdown HK-2 cells, and increa …

Methotrexate and theaflavin-3, 3'-digallate synergistically restore the balance between apoptosis and autophagy in synovial fibroblast of RA: an ex vivo approach with cultured human RA FLS.

BACKGROUND: Imbalance between apoptosis and autophagy in fibroblast-like synoviocytes (FLS) is one of the pathogenic mechanisms responsible … tting (Grp78, Hsp70, CHOP, HIF-1α). Immunoblot studies were done to evaluate apoptotic (Bcl-2, Bax, Caspases) and autophagic (Beclin1, LC3b, p62) proteins. RESULTS: MTX (IC25) and TF3 (IC50) both in single doses could down-regulate the levels of pro-inflammatory and angiogenic markers. Combinatorial treatment modulated autophagosomal proteins in fd-FLS an …

In vitro cellular uptake and neuroprotective efficacy of poly-arginine-18 (R18) and poly-ornithine-18 (O18) peptides: critical role of arginine guanidinium head groups for neuroprotection.

We have previously demonstrated that Cationic Arginine-Rich Peptides (CARPs) and in particular poly-arginine-18 (R18; 18-mer of arginine) ex … iffered in neurons. Following glutamic acid excitotoxicity, only R18 was neuroprotective, prevented caspases and calpain activation, and was more effective at reducing neuronal intracellular calcium influx. Overall, this study demonstrated that for long chain cationic poly-arginine peptides, the guanidinium head groups provided by arginine residues are an …