BACKGROUND AND PURPOSE: Diffuse gliomas, a heterogeneous group of primary brain tumors, have traditionally been stratified by histology, but recent insights into their molecular features, especially the IDH mutation status, have fundamentally changed their classification and prognosis. Current diagnostic methods, still predominantly relying on invasive biopsy, necessitate the exploration of noninvasive imaging alternatives for glioma characterization. MATERIALS AND METHODS: In this prospective study, we investigated the utility of the spherical mean technique (SMT) in predicting the IDH status and histologic grade of adult-type diffuse gliomas. Patients with histologically confirmed adult-type diffuse glioma underwent a multiparametric MRI examination using a 3T system, which included a multishell diffusion sequence. Advanced diffusion parameters were obtained using SMT, diffusional kurtosis imaging, and ADC modeling. The diagnostic performance of studied parameters was evaluated by plotting receiver operating characteristic curves with associated area under curve, specificity, and sensitivity values. RESULTS: A total of 80 patients with a mean age of 48 (SD, 16) years were included in the study. SMT metrics, particularly microscopic fractional anisotropy (μFA), intraneurite voxel fraction, and μFA to the third power (μFA3), demonstrated strong diagnostic performance (all AUC = 0.905, 95% CI, 0.835-0.976; P < .001) in determining IDH status and compared favorably with diffusional kurtosis imaging and ADC models. These parameters also showed a strong predictive capability for tumor grade, with intraneurite voxel fraction and μFA achieving the highest diagnostic accuracy (AUC = 0.937, 95% CI, 0.880-0.993; P < .001). Control analyses on normal-appearing brain tissue confirmed the specificity of these metrics for tumor tissue. CONCLUSIONS: Our study highlights the potential of SMT for noninvasive characterization of adult-type diffuse gliomas, with a potential to predict IDH status and tumor grade more accurately than traditional ADC metrics. SMT offers a promising addition to the current diagnostic toolkit, enabling more precise preoperative assessments and contributing to personalized treatment planning.

• MeSH
• difuzní magnetická rezonance metody   MeSH
• dospělí MeSH
• gliom * diagnostické zobrazování   patologie   MeSH
• isocitrátdehydrogenasa * genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mutace MeSH
• nádory mozku * diagnostické zobrazování   patologie   MeSH
• prospektivní studie MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• stupeň nádoru MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• isocitrátdehydrogenasa * MeSH

PURPOSE: This phase 1/2 study aimed to evaluate the safety and preliminary efficacy of combining disulfiram and copper (DSF/Cu) with radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM). METHODS AND MATERIALS: Patients received standard RT and TMZ with DSF (250-375 mg/d) and Cu, followed by adjuvant TMZ plus DSF (500 mg/d) and Cu. Pharmacokinetic analyses determined drug concentrations in plasma and tumors using high-performance liquid chromatography-mass spectrometry. RESULTS: Thirty-three patients, with a median follow-up of 26.0 months, were treated, including 12 IDH-mutant, 9 NF1-mutant, 3 BRAF-mutant, and 9 other IDH-wild-type cases. In the phase 1 arm, 18 patients were treated; dose-limiting toxicity probabilities were 10% (95% CI, 3%-29%) at 250 mg/d and 21% (95% CI, 7%-42%) at 375 mg/d. The phase 2 arm treated 15 additional patients at 250 mg/d. No significant difference in overall survival or progression-free survival was noted between IDH- and NF1-mutant cohorts compared with institutional counterparts treated without DSF/Cu. However, extended remission occurred in 3 BRAF-mutant patients. Diethyl-dithiocarbamate-copper, the proposed active metabolite of DSF/Cu, was detected in plasma but not in tumors. CONCLUSIONS: The maximum tolerated dose of DSF with RT and TMZ is 375 mg/d. DSF/Cu showed limited clinical efficacy for most patients. However, promising efficacy was observed in BRAF-mutant GBM, warranting further investigation.

• MeSH
• antitumorózní látky alkylující terapeutické užití   farmakokinetika   MeSH
• chemoradioterapie * metody   MeSH
• disulfiram * terapeutické užití   farmakokinetika   aplikace a dávkování   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• glioblastom * radioterapie   genetika   mortalita   terapie   farmakoterapie   MeSH
• isocitrátdehydrogenasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• měď * krev   terapeutické užití   MeSH
• nádory mozku * radioterapie   mortalita   genetika   terapie   MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• senioři MeSH
• temozolomid * terapeutické užití   farmakokinetika   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• Názvy látek
• antitumorózní látky alkylující MeSH
• disulfiram * MeSH
• isocitrátdehydrogenasa MeSH
• měď * MeSH
• protoonkogenní proteiny B-Raf MeSH
• temozolomid * MeSH

Isocitrate dehydrogenase is an enzyme converting isocitrate to α-ketoglutarate in the canonical tricarboxylic acid (TCA) cycle. There are three different types of isocitrate dehydrogenase documented in eukaryotes. Our study points out the complex evolutionary history of isocitrate dehydrogenases across kinetoplastids, where the common ancestor of Trypanosomatidae and Bodonidae was equipped with two isoforms of the isocitrate dehydrogenase enzyme: the NADP+-dependent isocitrate dehydrogenase 1 with possibly dual localization in the cytosol and mitochondrion and NADP+-dependent mitochondrial isocitrate dehydrogenase 2. In the extant trypanosomatids, isocitrate dehydrogenase 1 is present only in a few species suggesting that it was lost upon separation of Trypanosoma spp. and replaced by the mainly NADP+-dependent cytosolic isocitrate dehydrogenase 3 of bacterial origin in all the derived lineages. In this study, we experimentally demonstrate that the omnipresent isocitrate dehydrogenase 2 has a dual localization in both mitochondrion and cytosol in at least four species that possess only this isoform. The apparent lack of the NAD+-dependent isocitrate dehydrogenase activity in trypanosomatid mitochondrion provides further support to the existence of the noncanonical TCA cycle across trypanosomatids and the bidirectional activity of isocitrate dehydrogenase 3 when operating with NADP+ cofactor instead of NAD+. This observation can be extended to all 17 species analyzed in this study, except for Leishmania mexicana, which showed only low isocitrate dehydrogenase activity in the cytosol. The variability in isocitrate oxidation capacity among species may reflect the distinct metabolic strategies and needs for reduced cofactors in particular environments.

• Klíčová slova
• Krebs cycle, NAD+, NADP+, TCA cycle, cofactor preference, isocitrate dehydrogenase,
• MeSH
• isocitrátdehydrogenasa * genetika   metabolismus   MeSH
• isocitráty metabolismus   MeSH
• NAD * metabolismus   MeSH
• NADP metabolismus   MeSH
• protein - isoformy MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• isocitrátdehydrogenasa * MeSH
• isocitráty MeSH
• isocitric acid MeSH Prohlížeč
• NAD * MeSH
• NADP MeSH
• protein - isoformy MeSH

Targeting mutations that trigger acute myeloid leukaemia (AML) has emerged as a refined therapeutic approach in recent years. Enasidenib (Idhifa) is the first selective inhibitor of mutated forms of isocitrate dehydrogenase 2 (IDH2) approved against relapsed/refractory AML. In addition to its use as monotherapy, a combination trial of enasidenib with standard intensive induction therapy (daunorubicin + cytarabine) is being evaluated. This study aimed to decipher enasidenib off-target molecular mechanisms involved in anthracycline resistance, such as reduction by carbonyl reducing enzymes (CREs) and drug efflux by ATP-binding cassette (ABC) transporters. We analysed the effect of enasidenib on daunorubicin (Daun) reduction by several recombinant CREs and different human cell lines expressing aldo-keto reductase 1C3 (AKR1C3) exogenously (HCT116) or endogenously (A549 and KG1a). Additionally, A431 cell models overexpressing ABCB1, ABCG2, or ABCC1 were employed to evaluate enasidenib modulation of Daun efflux. Furthermore, the potential synergism of enasidenib over Daun cytotoxicity was quantified amongst all the cell models. Enasidenib selectively inhibited AKR1C3-mediated inactivation of Daun in vitro and in cell lines expressing AKR1C3, as well as its extrusion by ABCB1, ABCG2, and ABCC1 transporters, thus synergizing Daun cytotoxicity to overcome resistance. This work provides in vitro evidence on enasidenib-mediated targeting of the anthracycline resistance actors AKR1C3 and ABC transporters under clinically achievable concentrations. Our findings may encourage its combination with intensive chemotherapy and even suggest that the effectiveness of enasidenib as monotherapy against AML could lie beyond the targeting of mIDH2.

• Klíčová slova
• ABC transporters, AKR1C3, AML, Enasidenib, IDH inhibitor,
• MeSH
• ABC transportéry metabolismus   MeSH
• adenosintrifosfát MeSH
• akutní myeloidní leukemie * farmakoterapie   genetika   MeSH
• antibiotika antitumorózní terapeutické užití   MeSH
• antracykliny MeSH
• cytarabin terapeutické užití   MeSH
• daunomycin * farmakologie   MeSH
• isocitrátdehydrogenasa genetika   metabolismus   terapeutické užití   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABC transportéry MeSH
• adenosintrifosfát MeSH
• antibiotika antitumorózní MeSH
• antracykliny MeSH
• cytarabin MeSH
• daunomycin * MeSH
• enasidenib MeSH Prohlížeč
• isocitrátdehydrogenasa MeSH

Patients below 55 years were genetically studied because the prevalence of isocitrate dehydrogenase 1 (IDH1) decreases in older patients and on grounds of cost-effectiveness, as suggested by the World Health Organization (WHO) in 2016. The aim of our study was to use novel massively parallel sequencing (MPS) approaches to examine rare variants of IDH1/2 in Czech diffuse astrocytic and oligodendroglial tumors (gliomas) patients below 55 years of age who had been immunohistochemically (IHC) diagnosed as IDH1 R132H negative. The IHC IDH1 status (wild type or mutant) of 275 tissue samples was analyzed using antibodies against the IDH1 R132H protein. Sixty-three samples of 55 years old patients with IHC IDH1 WT status were genotyped using two different MPS technologies to detect rare IDH1 and IDH2 variants. The tiered IHC (60 positive) and molecular (10 positive) approach thus revealed that 70 of the 275 samples (25%) bore IDH1/IDH2 mutations. The combined molecular and IHC approach thus revealed that 70 of the 275 samples (25%) considered in the study bore IDH1/IDH2 mutations. IHC detection of the IDH1 R132H variant should be routinely complemented with MPS to detect rare IDH1/2 variants in glioma patients below 55 years of age with negative IHC result of IDH R132H variant.

• MeSH
• gliom * patologie   MeSH
• isocitrátdehydrogenasa genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádory mozku * diagnóza   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• IDH1 protein, human MeSH Prohlížeč
• IDH2 protein, human MeSH Prohlížeč
• isocitrátdehydrogenasa MeSH

Mitochondrial retrograde signaling is a mitochondria-to-nucleus communication pathway, conserved from yeast to humans, by which dysfunctional mitochondria relay signals that lead to cell stress adaptation in physiopathological conditions via changes in nuclear gene expression. The most comprehensive picture of components and regulation of retrograde signaling has been obtained in Saccharomyces cerevisiae, where retrograde-target gene expression is regulated by RTG genes. In this chapter, we describe methods to measure mitochondrial retrograde pathway activation at the level of mRNA and protein products in yeast model systems, including cell suspensions and microcolonies. In particular, we will focus on three major procedures: mRNA levels of RTG-target genes, such as those encoding for peroxisomal citrate synthase (CIT2), aconitase, and NAD+-specific isocitrate dehydrogenase subunit 1 by real-time PCR; expression analysis of CIT2-gene protein product (Cit2p-GFP) by Western blot and fluorescence microscopy; the phosphorylation status of transcriptional factor Rtg1/3p which controls RTG-target gene transcription.

• Klíčová slova
• ACO1, CIT2, IDH1, Mitochondrial retrograde pathway, RTG genes, Yeast,
• MeSH
• akonitáthydratasa genetika   metabolismus   MeSH
• buněčné jádro genetika   metabolismus   MeSH
• citrátsynthasa genetika   metabolismus   MeSH
• fosforylace MeSH
• intracelulární signální peptidy a proteiny metabolismus   MeSH
• isocitrátdehydrogenasa genetika   metabolismus   MeSH
• mitochondrie metabolismus   patologie   MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae genetika   metabolismus   MeSH
• signální transdukce MeSH
• transkripční faktory BHLH-Zip metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akonitáthydratasa MeSH
• citrátsynthasa MeSH
• intracelulární signální peptidy a proteiny MeSH
• isocitrátdehydrogenasa MeSH
• RTG1 protein, S cerevisiae MeSH Prohlížeč
• RTG2 protein, S cerevisiae MeSH Prohlížeč
• RTG3 protein, S cerevisiae MeSH Prohlížeč
• Saccharomyces cerevisiae - proteiny MeSH
• transkripční faktory BHLH-Zip MeSH

This prospective population-based study on a group of 132 resected IDH-wildtype (IDH-wt) glioblastoma (GBM) patients assesses the prognostic and predictive value of selected genetic biomarkers and clinical factors for GBM as well as the dependence of these values on the applied therapeutic modalities. The patients were treated in our hospital between June 2006 and June 2015. Clinical data and tumor samples were analyzed to determine the frequencies of TP53, MDM2, EGFR, RB1, BCR, and CCND1 gene aberrations and the duplication/deletion statuses of the 9p21.3, 1p36.3, 19q13.32, and 10p11.1 chromosome regions. Cut-off values distinguishing low (LCN) and high (HCN) copy number status for each marker were defined. Additionally, MGMT promoter methylation and IDH1/2 mutation status were investigated retrospectively. Young age, female gender, Karnofsky scores (KS) above 80, chemoradiotherapy, TP53 HCN, and CCND1 HCN were identified as positive prognostic factors, and smoking was identified as a negative prognostic factor. Cox proportional regression models of the chemoradiotherapy patient group revealed TP53 HCN and CCND1 HCN to be positive prognostic factors for both progression-free survival and overall survival. These results confirmed the influence of key clinical factors (age, KS, adjuvant oncotherapy, and smoking) on survival in GBM IDH-wt patients and demonstrated the prognostic and/or predictive importance of CCND1, MDM2, and 22q12.2 aberrations.

• Klíčová slova
• biomarkers, glioblastoma, multimodal therapy,
• MeSH
• DNA modifikační methylasy genetika   MeSH
• glioblastom * genetika   terapie   MeSH
• isocitrátdehydrogenasa genetika   MeSH
• lidé MeSH
• metylace DNA MeSH
• mutace MeSH
• nádory mozku * genetika   terapie   MeSH
• prospektivní studie MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA modifikační methylasy MeSH
• isocitrátdehydrogenasa MeSH

The most recent genome-editing system called CRISPR-Cas9 (clustered regularly interspaced short palindromic repeat system with associated protein 9-nuclease) was employed to delete four non-essential genes (i.e., Caeco1, Caidh1, Carom2, and Cataf10) individually to establish their gene functionality annotations in pathogen Candida albicans. The biological roles of these genes were investigated with respect to the cell wall integrity and biogenesis, calcium/calcineurin pathways, susceptibility of mutants towards temperature, drugs and salts. All the mutants showed increased vulnerability compared to the wild-type background strain towards the cell wall-perturbing agents, (antifungal) drugs and salts. All the mutants also exhibited repressed and defective hyphal growth and smaller colony size than control CA14. The cell cycle of all the mutants decreased enormously except for those with Carom2 deletion. The budding index and budding size also increased for all mutants with altered bud shape. The disposition of the mutants towards cell wall-perturbing enzymes disclosed lower survival and more rapid cell wall lysis events than in wild types. The pathogenicity and virulence of the mutants was checked by adhesion assay, and strains lacking rom2 and eco1 were found to possess the least adhesion capacity, which is synonymous to their decreased pathogenicity and virulence.

• MeSH
• acetyltransferasy nedostatek   genetika   fyziologie   MeSH
• antifungální látky farmakologie   MeSH
• buněčná adheze MeSH
• buněčná stěna účinky léků   MeSH
• buněčný cyklus MeSH
• Candida albicans účinky léků   genetika   patogenita   fyziologie   MeSH
• chitinasy farmakologie   MeSH
• CRISPR-Cas systémy MeSH
• delece genu MeSH
• endo-1,3-beta-glukanasa farmakologie   MeSH
• faktory asociované s proteinem vázajícím TATA box nedostatek   genetika   fyziologie   MeSH
• fungální proteiny genetika   fyziologie   MeSH
• geny hub * MeSH
• hyfy růst a vývoj   MeSH
• isocitrátdehydrogenasa nedostatek   genetika   fyziologie   MeSH
• kationty farmakologie   MeSH
• nepohlavní rozmnožování MeSH
• otevřené čtecí rámce MeSH
• poškození DNA MeSH
• vápník fyziologie   MeSH
• virulence genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetyltransferasy MeSH
• antifungální látky MeSH
• chitinasy MeSH
• endo-1,3-beta-glukanasa MeSH
• faktory asociované s proteinem vázajícím TATA box MeSH
• fungální proteiny MeSH
• isocitrátdehydrogenasa MeSH
• kationty MeSH
• vápník MeSH

Significance: Cancer cells are stabilized in an undifferentiated state similar to stem cells. This leads to profound modifications of their metabolism, which further modifies their genetics and epigenetics as malignancy progresses. Specific metabolites and enzymes may serve as clinical markers of cancer progression. Recent Advances: Both 2-hydroxyglutarate (2HG) enantiomers are associated with reprogrammed metabolism, in grade III/IV glioma, glioblastoma, and acute myeloid leukemia cells, and numerous other cancer types, while acting also in the cross talk of tumors with immune cells. 2HG contributes to specific alternations in cancer metabolism and developed oxidative stress, while also inducing decisions on the differentiation of naive T lymphocytes, and serves as a signal messenger in immune cells. Moreover, 2HG inhibits chromatin-modifying enzymes, namely 2-oxoglutarate-dependent dioxygenases, and interferes with hypoxia-inducible factor (HIF) transcriptome reprogramming and mammalian target of rapamycin (mTOR) pathway, thus dysregulating gene expression and further promoting cancerogenesis. Critical Issues: Typically, heterozygous mutations within the active sites of isocitrate dehydrogenase isoform 1 (IDH1)R132H and mitochondrial isocitrate dehydrogenase isoform 2 (IDH2)R140Q provide cells with millimolar r-2-hydroxyglutarate (r-2HG) concentrations, whereas side activities of lactate and malate dehydrogenase form submillimolar s-2-hydroxyglutarate (s-2HG). However, even wild-type IDH1 and IDH2, notably under shifts toward reductive carboxylation glutaminolysis or changes in other enzymes, lead to "intermediate" 0.01-0.1 mM 2HG levels, for example, in breast carcinoma compared with 10-8M in noncancer cells. Future Directions: Uncovering further molecular metabolism details specific for given cancer cell types and sequence-specific epigenetic alternations will lead to the design of diagnostic approaches, not only for predicting patients' prognosis or uncovering metastases and tumor remissions but also for early diagnostics.

• Klíčová slova
• 2-hydroxyglutarate, DNA and histone hypermethylation, immune system, isocitrate dehydrogenase 1 and 2, metabolic marker, metabolic reprogramming in cancer, tumor cross talk,
• MeSH
• energetický metabolismus MeSH
• epigeneze genetická MeSH
• glutaráty metabolismus   MeSH
• imunomodulace MeSH
• isocitrátdehydrogenasa genetika   metabolismus   MeSH
• lidé MeSH
• mutace MeSH
• náchylnost k nemoci * MeSH
• nádorové kmenové buňky metabolismus   MeSH
• nádory etiologie   metabolismus   patologie   MeSH
• oxidace-redukce MeSH
• progrese nemoci MeSH
• regulace genové exprese u nádorů MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• alpha-hydroxyglutarate MeSH Prohlížeč
• glutaráty MeSH
• IDH1 protein, human MeSH Prohlížeč
• IDH2 protein, human MeSH Prohlížeč
• isocitrátdehydrogenasa MeSH

Wild type mitochondrial isocitrate dehydrogenase (IDH2) was previously reported to produce oncometabolite 2-hydroxyglutarate (2HG). Besides, mitochondrial deacetylase SIRT3 has been shown to regulate the oxidative function of IDH2. However, regulation of 2HG formation by SIRT3-mediated deacetylation was not investigated yet. We aimed to study mitochondrial IDH2 function in response to acetylation and deacetylation, and focus specifically on 2HG production by IDH2. We used acetylation surrogate mutant of IDH2 K413Q and assayed enzyme kinetics of oxidative decarboxylation of isocitrate, 2HG production by the enzyme, and 2HG production in cells. The purified IDH2 K413Q exhibited lower oxidative reaction rates than IDH2 WT. 2HG production by IDH2 K413Q was largely diminished at the enzymatic and cellular level, and knockdown of SIRT3 also inhibited 2HG production by IDH2. Contrary, the expression of putative mitochondrial acetylase GCN5L likely does not target IDH2. Using mass spectroscopy, we further identified lysine residues within IDH2, which are the substrates of SIRT3. In summary, we demonstrate that 2HG levels arise from non-mutant IDH2 reductive function and decrease with increasing acetylation level. The newly identified lysine residues might apply in regulation of IDH2 function in response to metabolic perturbations occurring in cancer cells, such as glucose-free conditions.

• MeSH
• acetylace MeSH
• glutaráty metabolismus   MeSH
• isocitrátdehydrogenasa genetika   metabolismus   MeSH
• isocitráty chemie   MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• nádorové buněčné linie MeSH
• NADP metabolismus   MeSH
• oxidace-redukce MeSH
• proteiny nervové tkáně metabolismus   MeSH
• sirtuin 3 metabolismus   MeSH
• umlčování genů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alpha-hydroxyglutarate MeSH Prohlížeč
• BLOC1S1 protein, human MeSH Prohlížeč
• glutaráty MeSH
• IDH2 protein, human MeSH Prohlížeč
• isocitrátdehydrogenasa MeSH
• isocitráty MeSH
• isocitric acid MeSH Prohlížeč
• NADP MeSH
• proteiny nervové tkáně MeSH
• SIRT3 protein, human MeSH Prohlížeč
• sirtuin 3 MeSH