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Metabolic reprogramming, including increased glucose uptake and lactic acid excretion, is a hallmark of cancer. The glycolytic 'gatekeeper' enzyme phosphofructokinase-1 (PFK1), which catalyzes the step committing glucose to breakdown, is dysregulated in cancers. While altered PFK1 activity and expression in tumors have been demonstrated, little is known about the effects of cancer-associated somatic mutations. Somatic mutations in PFK1 inform our understanding of allosteric regulation by identifying key amino acid residues involved in the regulation of enzyme activity. Here, we characterized mutations disrupting an evolutionarily conserved salt bridge between aspartic acid and arginine in human platelet (PFKP) and liver (PFKL) isoforms. Using purified recombinant proteins, we showed that disruption of the Asp-Arg pair in two PFK1 isoforms decreased enzyme activity and altered allosteric regulation. We determined the crystal structure of PFK1 to 3.6 Å resolution and used molecular dynamic simulations to understand molecular mechanisms of altered allosteric regulation. We showed that PFKP-D564N had a decreased total system energy and changes in the electrostatic surface potential of the effector site. Cells expressing PFKP-D564N demonstrated a decreased rate of glycolysis, while their ability to induce glycolytic flux under conditions of low cellular energy was enhanced compared with cells expressing wild-type PFKP. Taken together, these results suggest that mutations in Arg-Asp pair at the interface of the catalytic-regulatory domains stabilizes the t-state and presents novel mechanistic insight for therapeutic development in cancer. [ABSTRACT FROM AUTHOR]

The paper shows composition and content of phenolic compounds in leaves of 4 Nitraria L. species from 58 populations of Russia, Kazakhstan, and Tajikistan studied with high-performance liquid chromatography(HPLC). The investigation has revealed 27 compounds of phenolic nature: the maximum number (18 components) is detected in leaves of N. sibirica Pall. from Kazakhstan (the Karatal river valley), 16-17 components – in plants from three populations of Siberia, the minimum (6 components) – in leaves of N. komaroviiilljin & Lava ex Bobrov. The analysis has identified hyperoside (quercetin O-glycoside), narcissin (isoramnetin O-glycoside), quercetin (flavonol) and luteolin (flavon). The studied plants accumulate a generous quantity of phenolic compounds. Their content reaches 4.64% in leaves of N. sibirica, 3.11% – in N. schoberi L., up to 3.96% – in N. komarovii. The research results allow speaking about the species-specific composition and content of phenolic compounds of N. sibirica, N. schoberi and N. komarovii. The component composition is weaker in extracts of N. komarovii leaves, but there is a higher content of total phenolic compounds compared to N. schoberi plants. N. pamirica L. Vassil sample is close to N. schoberi on multidimensional analysis of the phenolic compound composition and content.

The article presents a scientometric analysis of documentary arrays selected of the world science citation databases Scopus and Web of Science on the topic “Plant flow cytometry”. The analysis of documentary arrays shows their positive dynamics and especially active growth currently. It names countries and organizations actively carrying on research in the area, and leading in the publication amount; rating journals with high publication activity, authors who work productively on the topic. The paper reveals thematic structure of the studied corpus of documents and highly cited publications.

The article considers research of the phenolic compounds composition and content in leaves of Bistorta alopecuroides (Turcz. Ex Meissn.) Kom. from different populations using HPLC methods. It shows that B. alopecuroides component composition is quite variable and depends on many environmental factors, such as microclimate, altitude, technogenic pollution. Isovitixin, rutin and flavonolglycoside (tR = 9.2 min; UV 273, 355 nm) compounds are found in B. alopecuroides leaves of all studied populations. B. alopecuroides growing in high mountains and under technogenic pollution conditions have the highest content of phenolic compounds, which confirms their adaptive role in plant metabolism. The total content of phenolic compounds in leaves of B. alopecuroides plants reaches 20.82mg/g.

For the first time are search of nuclear DNA relative content in Nitraria schoberi L. seeds from 15 natural populations of Siberia, the Crimea, Kazakhstan, and Tajikistan has been conducted by the method of flow cytometry. High intra-and interpopulational variations of nuclear DNA content - 2,93-3,39 pg, at average value - 3,22±0,108 pg is revealed.

Chemotherapy resistance and tumor relapse are the major contributors to low patient survival, and both have been largely attributed to cancer stem-like cells (CSCs) or tumor CSCs, which necessitates the discovery of CSC-specific biomarkers and drug targets. Here, we demonstrated that the embryonic transcription factor SOX9 is an important regulator of acquired chemoresistance in non-small cell lung cancer (NSCLC). Our results show that SOX9 expression is elevated in NSCLC cells after treatment with the chemotherapeutic cisplatin and that overexpression of SOX9 correlates with worse overall survival in lung cancer patients. We further demonstrated that SOX9 knockdown increases cellular sensitivity to cisplatin, whereas its overexpression promotes drug resistance. Moreover, this transcription factor promotes stem-like properties of NSCLC cells and increases their ALDH activity, which was identified as the key mechanism of SOX9-induced chemoresistance. Finally, we showed that ALDH1A1 is a direct transcriptional target of SOX9 based on chromatin immunoprecipitation and luciferase reporter assays. Taken together, our novel findings on the role of SOX9-ALDH axis support the use of this CSC regulator as a prognostic marker of cancer chemoresistance and as a potential drug target for CSC therapy. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) represent a major class of engineered nanomaterials that are being used in diverse fields. However, their use has increasingly become a concern because of their carcinogenic potential. Accumulating evidence has demonstrated that certain types of CNTs are carcinogenic or tumor-promoting in animal models. However, the underlying molecular and cellular mechanisms are unclear. Here, we report that chronic exposure to single-walled (SW) CNTs results in the induction of Slug, a key transcription factor that induces an epithelial-mesenchymal transition (EMT), in human lung epithelial cells. We show that SWCNT-induced Slug upregulation plays a critical role in the aggressive phenotype of SWCNT-exposed cells, which includes increased cell migration, invasion, and anchorage-independent cell growth. Our in vivo studies also show that SWCNT-induced Slug upregulation and EMT activation play a pivotal role in tumor formation and metastasis. Our findings illustrate a direct link between CNT-induced Slug upregulation, EMT activation, and tumor formation and metastasis, and they highlight the potential of CNT-induced Slug upregulation as a target for future risk assessment and prevention of CNT-associated diseases. [ABSTRACT FROM AUTHOR]

KAP1 (TRIM28) is a transcriptional regulator in embryonic development that controls stem cell self-renewal, chromatin organization, and the DNA damage response, acting as an essential corepressor for KRAB family zinc finger proteins (KRAB-ZNF). To gain insight into the function of this large gene family, we developed an antibody that recognizes the conserved zinc fingers linker region (ZnFL) in multiple KRAB-ZNF. Here, we report that the expression of many KRAB-ZNF along with active SUMOlyated KAP1 is elevated widely inhuman breast cancers. KAP1 silencing in breast cancer cells reduced proliferation and inhibited the growth and metastasis of tumor xenografts. Conversely, KAP1 overexpression stimulated cell proliferation and tumor growth. In cells where KAP1 was silenced, we identified multiple downregulated genes linked to tumor progression and metastasis, including EREG/epiregulin, PTGS2/COX2, MMP1, MMP2, and CD44, along with downregulation of multiple KRAB-ZNF proteins. KAP1-dependent stabilization of KRAB-ZNF required direct interactions with KAP1. Together, our results show that KAP1-mediated stimulation of multiple KRAB-ZNF contributes to the growth and metastasis of breast cancer. [ABSTRACT FROM AUTHOR]