Parkinson's disease (PD) is one of the most common progressive neurodegenerative pathologies that leads to dopaminergic deficiency and motor manifestations. Alpha-synuclein aggregation is a characteristic hallmark of PD pathogenesis. These aggregates facilitate the formation of Lewy bodies and degeneration. The epidemiological evidence demonstrates a definitive association of diabetes with PD risk. Considering this, many antidiabetic agents such as GLP-1 agonists and DPP-4 inhibitors are being explored as alternative PD therapeutics. This study evaluated the neuroprotective effect of the DPP-4 inhibitor sitagliptin mediated by the PI3K/AKT and Nrf2 pathways in PD models. In silico studies were conducted to determine the binding affinity, stability, and ADMET properties of DPP-4 inhibitors with target proteins. Sitagliptin (15 mg/kg p.o.) was administered in rotenone (30 mg/kg p.o. for 28 days)-induced and MPTP/P (25 mg/kg i.p. MPTP and 100 mg/kg probenecid i.p. twice a week for 5 weeks)-induced PD mouse (C57/BL6) models. Neurobehavioral assessments were carried out throughout the study. Biochemical (GSH, MDA), molecular estimations (AKT, Nrf2, PI3K, GSK-3β, GLP1, CREB, BDNF, NF-κB, alpha-synuclein), histopathological studies, and immunohistochemistry were carried out at the end of the study. The in silico studies demonstrate better binding, stability, and ADMET profile of sitagliptin with both target proteins. Sitagliptin restored cognitive and motor deficits in both rotenone- and MPTP/P-induced mouse models. There was upregulation of PI3K, AKT, Nrf2, CREB, and BDNF levels and downregulation of GSK-3β, NF-κB, and alpha-synuclein levels in both models after treatment with sitagliptin. However, GLP1 levels were not significantly restored, indicating a GLP1-independent mechanism. It also restored histopathological alterations and TH+ neuronal loss induced by rotenone and MPTP/P. These findings demonstrate that sitagliptin exhibits neuroprotective action mediated by upregulation of the PI3K/AKT and Nrf2 pathways in rotenone and MPTP/P mouse models of PD.

• Klíčová slova
• DPP-4 inhibitors, Nrf2, PI3K/AKT, Parkinson’s disease, alpha-synuclein, sitagliptin,
• MeSH
• faktor 2 související s NF-E2 * metabolismus   účinky léků   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   účinky léků   MeSH
• inhibitory dipeptidylpeptidasy 4 * farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neuroprotektivní látky * farmakologie   MeSH
• parkinsonské poruchy metabolismus   farmakoterapie   MeSH
• protoonkogenní proteiny c-akt * metabolismus   MeSH
• rotenon MeSH
• signální transdukce účinky léků   MeSH
• sitagliptin fosfát * farmakologie   MeSH
• upregulace účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• faktor 2 související s NF-E2 * MeSH
• fosfatidylinositol-3-kinasy * MeSH
• inhibitory dipeptidylpeptidasy 4 * MeSH
• neuroprotektivní látky * MeSH
• Nfe2l2 protein, mouse MeSH Prohlížeč
• protoonkogenní proteiny c-akt * MeSH
• rotenon MeSH
• sitagliptin fosfát * MeSH

Local nonequilibrium approach has been used for many purposes when dealing with biological systems. Not only for unraveling important features of cancer development, a disease that affects the lives of many people worldwide, but also to understand drug-target interactions in a more real scenario, which can help to combat this disease. Therefore, aiming to contribute to new strategies against cancer, the present work used this approach to investigate the spectroscopy of 2-(2'-hydroxy-4'-aminophenyl)benzothiazole (HABT) when interacting with the PI3K enzyme, a widely associated target for the mentioned illness. The study consisted of evaluating the Excited State Intramolecular Proton Transfer (ESIPT) performance of HABT, in spectroscopic terms, when interacting with the PI3K enzyme in a local nonequilibrium regime. This scenario could be considered by investigating the metastable states of HABT in this system. From this, it was possible to observe that the ESIPT performance of HABT considerably differs when comparing the solution and protein environments, where 63% have appropriate geometry in the protein environment, against 97% in the aqueous environment. Thus, from an entirely theoretical methodology, the present work provides insights when modeling biological systems and contributes significantly to a better comprehension of promising probes for cancer diagnosis.

• Klíčová slova
• ESIPT, biased MD simulations, cancer, fluorescent sensors, spectroscopic probes,
• MeSH
• benzothiazoly * chemie   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   chemie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádory * enzymologie   MeSH
• simulace molekulární dynamiky * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzothiazoly * MeSH
• fosfatidylinositol-3-kinasy * MeSH

Berberine (BBR), a small molecule protoberberine isoquinoline alkaloid, is easy to cross the blood-brain barrier and is a potential drug for neurodegenerative diseases. Here, we explored the role and molecular mechanism of BBR in Alzheimer's disease (AD) progression. Weighted gene co-expression network analysis (WGCNA) was conducted to determine AD pathology-associated gene modules and differentially expressed genes (DEGs) were also identified. GO and KEGG analyses were performed for gene function and signaling pathway annotation. Cell counting kit-8 (CCK8) assay was applied to analyze cell viability. Immunofluorescence (IF) staining assay was conducted to measure the levels of polarization markers. The production of inflammatory cytokines was analyzed by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) were detected using a ROS detection kit and a MMP Detection Kit (JC-1), respectively. AD pathology-associated DEGs were applied for GO function annotation and KEGG enrichment analysis, and the results uncovered that AD pathology was related to immune and inflammation. Lipopolysaccharide (LPS) exposure induced the M1 phenotype of microglia, and BBR suppressed LPS-induced M1 polarization and induced microglia toward M2 polarization. Through co-culture of microglia and neuronal cells, we found that BBR exerted a neuro-protective role by attenuating the injury of LPS-induced HMC3 on SH-SY5Y cells. Mechanically, BBR switched the M1/M2 phenotypes of microglia by activating PI3K-AKT signaling. In summary, BBR protected neuronal cells from activated microglia-mediated neuro-inflammation by switching the M1/M2 polarization in LPS-induced microglia via activating PI3K-AKT signaling. Key words Alzheimer's Disease, Berberine, Microglia polarization, Neuroinflammation, PI3K-AKT signaling.

• MeSH
• Alzheimerova nemoc * metabolismus   farmakoterapie   patologie   MeSH
• berberin * farmakologie   terapeutické užití   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   MeSH
• lidé MeSH
• mikroglie * účinky léků   metabolismus   MeSH
• myši MeSH
• neuroprotektivní látky * farmakologie   MeSH
• polarita buněk účinky léků   MeSH
• protoonkogenní proteiny c-akt * metabolismus   MeSH
• signální transdukce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• berberin * MeSH
• fosfatidylinositol-3-kinasy * MeSH
• neuroprotektivní látky * MeSH
• protoonkogenní proteiny c-akt * MeSH

Fibroblast growth factor 21 (FGF21), a metabolic hormone with pleiotropic effects, is beneficial for various cardiac disorders. However, FGF21's role in heart failure with preserved ejection fraction (HFpEF) remains unclear. Here, we show that elevated circulating FGF21 levels are negatively associated with cardiac diastolic function in patients with HFpEF. Global or adipose FGF21 deficiency exacerbates cardiac diastolic dysfunction and damage in high-fat diet (HFD) plus N[w]-nitro-L-arginine methyl ester (L-NAME)-induced HFpEF mice, whereas these effects are notably reversed by FGF21 replenishment. Mechanistically, FGF21 enhances the production of adiponectin (APN), which in turn indirectly acts on cardiomyocytes, or FGF21 directly targets cardiomyocytes, to negatively regulate pyruvate dehydrogenase kinase 4 (PDK4) production by activating PI3K/AKT signals, then promoting mitochondrial bioenergetics. Additionally, APN deletion strikingly abrogates FGF21's protective effects against HFpEF, while genetic PDK4 inactivation markedly mitigates HFpEF in mice. Thus, FGF21 protects against HFpEF via fine-tuning the multiorgan crosstalk among the adipose, liver, and heart.

• MeSH
• adiponektin * metabolismus   genetika   MeSH
• dieta s vysokým obsahem tuků * škodlivé účinky   MeSH
• energetický metabolismus * účinky léků   MeSH
• fibroblastové růstové faktory * metabolismus   genetika   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• kardiomyocyty * metabolismus   účinky léků   MeSH
• lidé MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• PDH-kinasa * metabolismus   genetika   MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• signální transdukce MeSH
• srdeční mitochondrie * metabolismus   účinky léků   MeSH
• srdeční selhání * metabolismus   prevence a kontrola   genetika   MeSH
• tepový objem účinky léků   MeSH
• tuková tkáň metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adiponektin * MeSH
• FGF21 protein, human MeSH Prohlížeč
• fibroblast growth factor 21 MeSH Prohlížeč
• fibroblastové růstové faktory * MeSH
• fosfatidylinositol-3-kinasy MeSH
• PDH-kinasa * MeSH
• Pdk4 protein, mouse MeSH Prohlížeč
• protoonkogenní proteiny c-akt MeSH

Coriolus versicolor (CV), known in traditional Chinese medicine for over 2000 years, is currently used in China and Japan to reduce chemotherapy or radiotherapy side effects in cancer patients. Despite extensive research, its effects still need improvement. This study aimed to determine if combining CV extract with LY294002, an inhibitor of the phosphatidylinositol-3-kinase (PI3K) signalling pathway, enhances cancer cell treatment, potentially leading to a novel therapeutic approach. Three human cancer cell lines (MCF-7, HeLa, and A549) were treated with CV extract alone or combined with LY294002. Cell viability was assessed using MTT assays. Then, HeLa and MCF-7 cells most sensitive to the co-treatment were used to evaluate colony formation, apoptosis, cell cycle, cell migration and invasion, and phospho-PI3K expression. The results demonstrated that LY294002 enhanced the CV extract's anti-tumour effects by reducing cell viability and colony formation. The combined treatment with CV extract and LY294002 more effectively induced G0/G1 cell cycle arrest, promoted apoptosis, reduced cell invasion and migration, and inhibited phospho-PI3K expression compared to each agent alone. This study highlights the potent cytotoxic enhancement between CV extract and LY294002 on cancer cells, primarily by inhibiting phospho-PI3K expression. These findings suggest promising avenues for developing novel combination therapies targeting cancer.

• Klíčová slova
• Coriolus versicolor, LY294002, cancer, phosphatidylinositol 3-kinase,
• MeSH
• apoptóza * účinky léků   MeSH
• buněčný cyklus účinky léků   MeSH
• buňky A549 MeSH
• chromony * farmakologie   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• HeLa buňky MeSH
• inhibitory fosfoinositid-3-kinasy * farmakologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• morfoliny * farmakologie   MeSH
• nádorové buněčné linie MeSH
• pohyb buněk * účinky léků   MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky farmakologie   MeSH
• rostlinné extrakty farmakologie   chemie   MeSH
• signální transdukce účinky léků   MeSH
• synergismus léků MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one MeSH Prohlížeč
• chromony * MeSH
• fosfatidylinositol-3-kinasy MeSH
• inhibitory fosfoinositid-3-kinasy * MeSH
• morfoliny * MeSH
• protinádorové látky MeSH
• rostlinné extrakty MeSH

Neurons in the CNS lose regenerative potential with maturity, leading to minimal corticospinal tract (CST) axon regrowth after spinal cord injury (SCI). In young rodents, knockdown of PTEN, which antagonizes PI3K signaling by hydrolyzing PIP3, promotes axon regeneration following SCI. However, this effect diminishes in adults, potentially due to lower PI3K activation leading to reduced PIP3. This study explores whether increased PIP3 generation can promote long-distance regeneration in adults. We used a hyperactive PI3K, PI3Kδ (PIK3CD), to boost PIP3 levels in mature cortical neurons and assessed CST regeneration after SCI. Adult rats received AAV1-PIK3CD and AAV1-eGFP, or AAV1-eGFP alone, in the sensorimotor cortex concurrent with a C4 dorsal SCI. Transduced neurons showed increased pS6 levels, indicating elevated PI3K/Akt/mTOR signaling. CST regeneration, confirmed with retrograde tracing, was evaluated up to 16 weeks post injury. At 12 weeks, ∼100 axons were present at lesion sites, doubling to 200 by 16 weeks, with regeneration indices of 0.1 and 0.2, respectively. Behavioral tests showed significant improvements in paw reaching, grip strength, and ladder-rung walking in PIK3CD-treated rats, corroborated by electrophysiological recordings of cord dorsum potentials and distal flexor muscle electromyography. Thus, PI3Kδ upregulation in adult cortical neurons enhances axonal regeneration and functional recovery post SCI.

• Klíčová slova
• CST, PI3K, axon regeneration, c-Fos, electrophysiology, pS6, signaling, skilled paw reaching, spinal cord, spinal cord injury,
• MeSH
• axony metabolismus   fyziologie   MeSH
• Dependovirus genetika   MeSH
• fosfatidylinositol-3-kinasy třídy I metabolismus   genetika   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• genetické vektory genetika   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• neurony metabolismus   MeSH
• obnova funkce MeSH
• poranění míchy * metabolismus   terapie   genetika   MeSH
• pyramidové dráhy * metabolismus   MeSH
• regenerace nervu * MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfatidylinositol-3-kinasy třídy I MeSH
• fosfatidylinositol-3-kinasy MeSH

BACKGROUND: Juvenile granulosa cell tumor (JGCT) of the ovary is a rare tumor with distinct clinicopathological and hormonal features primarily affecting young women and children. We conducted a complex clinicopathological, immunohistochemical, and molecular analysis of five cases of JGCT. METHODS: The immunohistochemical examination was performed with 32 markers, including markers that have not been previously investigated. Moreover, DNA next-generation sequencing (NGS) and PTEN methylation analysis was performed. RESULT: We found the expression of calretinin, inhibin A, SF1, FOXL2, CD99, CKAE1/3, ER, PR, AR in all cases. WT1 was expressed in one case. Conversely, the expression of p16, OCT3/4, SALL4, GATA3, Napsin A, SATB2, MUC4, TTF1, and CAIX was completely negative. All tumors showed the wild-type pattern of p53 expression. Regarding predictive markers, all tumors were HER2 negative and did not express PD-L1. Mismatch repair proteins (MMR) showed no loss or restriction of expression, similarly to ARID1A, DPC4, BRG1, and INI1. The molecular analysis revealed AKT1 internal tandem duplication in two tumors. Two other cases exhibited mutations in TERT and EP400 and both developed recurrence. All AKT1-wild type tumors exhibited immunohistochemical loss of PTEN expression. However, no mutations, deletions (as assessed by CNV analysis), or promoter hypermethylation in the PTEN gene were detected. CONCLUSION: The results of our study further support the hypothesis that the pathogenesis of JGCT may be driven by activation of the PIK3/AKT/mTOR pathway. These findings could potentially have future therapeutic implications, as treatment strategies targeting the PTEN/mTOR pathways are currently under investigation.

• Klíčová slova
• Immunohistochemistry, Juvenile granulosa cell tumor, NGS, Ovary, Sex cord-stromal tumors,
• MeSH
• dítě MeSH
• fosfatidylinositol-3-kinasy genetika   metabolismus   MeSH
• fosfohydroláza PTEN genetika   metabolismus   MeSH
• imunohistochemie * MeSH
• lidé MeSH
• metylace DNA MeSH
• mladiství MeSH
• nádor z folikulárních buněk * patologie   genetika   metabolismus   MeSH
• nádorové biomarkery * genetika   analýza   metabolismus   MeSH
• nádory vaječníků * patologie   genetika   metabolismus   MeSH
• protoonkogenní proteiny c-akt * metabolismus   genetika   MeSH
• signální transdukce * MeSH
• TOR serin-threoninkinasy * metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfatidylinositol-3-kinasy MeSH
• fosfohydroláza PTEN MeSH
• MTOR protein, human MeSH Prohlížeč
• nádorové biomarkery * MeSH
• protoonkogenní proteiny c-akt * MeSH
• PTEN protein, human MeSH Prohlížeč
• TOR serin-threoninkinasy * MeSH

This current study seeks to examine the pre-protective function of Quercetin in Cadmium (Cd)-induced liver damage, along with its modulation of the PI3K/Akt/NF-kappaB signaling pathway. A total of 60 male C57BL/6J mice were randomly assigned to four groups: control (C), quercetin (Q, 100 mg/kg/day), Cd (Cd, 2.5 mg/kg/day), and quercetin and Cd (Q+Cd). Before receiving Cd treatment, quercetin was administered intragastrically for 4 weeks. In the present study, liver markers, oxidative stress parameters, pro-inflammatory cytokines, liver histopathology, apoptotic markers and PI3K/Akt/NF-kappaB signaling molecules were examined. We observed that the body weight of the Cd-treated mice dramatically rise after 4 weeks of quercetin pre-administration, and the Cd concentration was significantly decreased. Liver function markers like alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly reduced in quercetin treatment in Cd-induced mice. Additionally, we observed that quercetin reduced Cd-mediated liver injury in mice by assessing the level of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) concentrations and the histological alterations. By monitoring tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta), quercetin successfully reduced the inflammatory cytokines that the Cd metal caused in the liver. Additionally, in the liver tissues of Cd-mediated, quercetin could enhance the expression of Bcl-2 and decrease the expression of p-Akt, p-PI3K, Bax, Caspase-9, Caspase-3, NF-kappaB. In conclusion, quercetin protects against Cd induced liver injury via several pathways, including oxidative stress, inflammation and apoptosis, and its protective effect correlates with antioxidant activity.

• MeSH
• antioxidancia * farmakologie   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   MeSH
• játra účinky léků   patologie   metabolismus   MeSH
• kadmium * toxicita   MeSH
• lékové postižení jater * prevence a kontrola   metabolismus   patologie   MeSH
• myši inbrední C57BL * MeSH
• myši MeSH
• NF-kappa B * metabolismus   MeSH
• oxidační stres účinky léků   MeSH
• protoonkogenní proteiny c-akt * metabolismus   MeSH
• quercetin * farmakologie   terapeutické užití   MeSH
• signální transdukce * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia * MeSH
• fosfatidylinositol-3-kinasy * MeSH
• kadmium * MeSH
• NF-kappa B * MeSH
• protoonkogenní proteiny c-akt * MeSH
• quercetin * MeSH

Besides many other mutations in known cancer driver genes, mantle cell lymphoma (MCL) is characterized by recurrent genetic alterations of important regulators of the phosphoinositol-3-kinase (PI3K) cascade including PIK3CA gains and PTEN losses. To evaluate the biological and functional consequences of these aberrations in MCL, we have introduced transgenic expression of PIK3CA (PIK3CA UP) and performed knockout/knockdown of PTEN gene (PTEN KO/KD) in 5 MCL cell lines. The modified cell lines were tested for associated phenotypes including dependence on upstream B-cell receptor (BCR) signaling (by an additional BCR knockout). PIK3CA overexpression decreased the dependence of the tested MCL on prosurvival signaling from BCR, decreased levels of oxidative phosphorylation, and increased resistance to 2-deoxy-glucose, a glycolysis inhibitor. Unchanged protein kinase B (AKT) phosphorylation status and unchanged sensitivity to a battery of PI3K inhibitors suggested that PIK3CA gain might affect MCL cells in AKT-independent manner. PTEN KO was associated with a more distinct phenotype: AKT hyperphosphorylation and overactivation, increased resistance to multiple inhibitors (most of the tested PI3K inhibitors, Bruton tyrosine kinase inhibitor ibrutinib, and BCL2 inhibitor venetoclax), increased glycolytic rates with resistance to 2-deoxy-glucose, and significantly decreased dependence on prosurvival BCR signaling. Our results suggest that the frequent aberrations of the PI3K pathway may rewire associated signaling with lower dependence on BCR signaling, better metabolic and hypoxic adaptation, and targeted therapy resistance in MCL.

• MeSH
• chemorezistence genetika   MeSH
• cílená molekulární terapie MeSH
• fosfatidylinositol-3-kinasy třídy I * genetika   metabolismus   MeSH
• fosfatidylinositol-3-kinasy metabolismus   MeSH
• fosfohydroláza PTEN * metabolismus   genetika   MeSH
• lidé MeSH
• lymfom z plášťových buněk * farmakoterapie   genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• protoonkogenní proteiny c-akt metabolismus   MeSH
• receptory antigenů B-buněk metabolismus   MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfatidylinositol-3-kinasy třídy I * MeSH
• fosfatidylinositol-3-kinasy MeSH
• fosfohydroláza PTEN * MeSH
• PIK3CA protein, human MeSH Prohlížeč
• protoonkogenní proteiny c-akt MeSH
• PTEN protein, human MeSH Prohlížeč
• receptory antigenů B-buněk MeSH

The modulation of autophagy has been presented as a very useful strategy in anticancer treatments. In this sense, the vanadium complex (VC) bis(2,2'-bipyridine)chlorooxovanadium(IV), [VO(bpy)2Cl], is known for its ability to induce autophagy in triple-negative breast cancer cells (TNBC). An excellent resource to investigate the role of VC in the induction of autophagy is to make use of Molecular Dynamics (MD) simulations. However, until now, the scarcity of force field parameters for the VC prevented a reliable analysis. The autophagy signaling pathway starts with the PI3K protein and ends with ULK1. Therefore, in the first stage of this work, we developed a new AMBER force field for the VC (VCFF) from a quantum structure, obtained by DFT calculations. In the second stage, the VCFF was validated through structural analyses. From this, it was possible to investigate, through docking and MD (200 ns), the performance of the PI3K-VC and ULK1-VC systems (third stage). The analyses of this last stage involved RMSD, hydrogen bonds, RMSF and two pathways for the modulation of autophagy. In general, this work fills in the absence of force field parameters (FF) for VC by proposing an efficient and new FF, in addition to investigating, at the molecular level, how VC is able to induce autophagy in TNBC cells. This study encourages new parameterizations of metallic complexes and contributes to the understanding of the duality of autophagic processes.Communicated by Ramaswamy H. Sarma.

• Klíčová slova
• AMBER force field, Autophagy, modulation, molecular dynamics, vanadium complex,
• MeSH
• autofagie * účinky léků   MeSH
• fosfatidylinositol-3-kinasy * metabolismus   chemie   MeSH
• homolog Atg1 * metabolismus   chemie   MeSH
• intracelulární signální peptidy a proteiny metabolismus   chemie   MeSH
• komplexní sloučeniny chemie   farmakologie   MeSH
• lidé MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• vanad chemie   metabolismus   MeSH
• vazba proteinů MeSH
• vodíková vazba MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fosfatidylinositol-3-kinasy * MeSH
• homolog Atg1 * MeSH
• intracelulární signální peptidy a proteiny MeSH
• komplexní sloučeniny MeSH
• ULK1 protein, human MeSH Prohlížeč
• vanad MeSH