Articles
http://nur.nu.edu.kz:80/handle/123456789/4117
2024-03-29T05:25:17ZTO DIE OR NOT TO DIE—REGULATED CELL DEATH AND SURVIVAL IN CYANOBACTERIA
http://nur.nu.edu.kz:80/handle/123456789/7257
TO DIE OR NOT TO DIE—REGULATED CELL DEATH AND SURVIVAL IN CYANOBACTERIA
Barteneva, Natasha S.; Meirkhanova, Ayagoz; Malashenkov, Dmitry; Vorobjev, Ivan A.
Regulated cell death (RCD) is central to the development, integrity, and functionality
of multicellular organisms. In the last decade, evidence has accumulated that RCD is a universal
phenomenon in all life domains. Cyanobacteria are of specific interest due to their importance in
aquatic and terrestrial habitats and their role as primary producers in global nutrient cycling. Current
knowledge on cyanobacterial RCD is based mainly on biochemical and morphological observations,
often by methods directly transferred from vertebrate research and with limited understanding of
the molecular genetic basis. However, the metabolism of different cyanobacteria groups relies on
photosynthesis and nitrogen fixation, whereas mitochondria are the central executioner of cell death
in vertebrates. Moreover, cyanobacteria chosen as biological models in RCD studies are mainly
colonial or filamentous multicellular organisms. On the other hand, unicellular cyanobacteria have
regulated programs of cellular survival (RCS) such as chlorosis and post-chlorosis resuscitation.
The co-existence of different genetically regulated programs in cyanobacterial populations may
have been a top engine in life diversification. Development of cyanobacteria-specific methods for
identification and characterization of RCD and wider use of single-cell analysis combined with
intelligent image-based cell sorting and metagenomics would shed more light on the underlying
molecular mechanisms and help us to address the complex colonial interactions during these events.
In this review, we focus on the functional implications of RCD in cyanobacterial communities.
2022-01-01T00:00:00ZENHANCING AN OXIDATIVE “TROJAN HORSE” ACTION OF VITAMIN C WITH ARSENIC TRIOXIDE FOR EFFECTIVE SUPPRESSION OF KRAS-MUTANT CANCERS: A PROMISING PATH AT THE BEDSIDE
http://nur.nu.edu.kz:80/handle/123456789/7008
ENHANCING AN OXIDATIVE “TROJAN HORSE” ACTION OF VITAMIN C WITH ARSENIC TRIOXIDE FOR EFFECTIVE SUPPRESSION OF KRAS-MUTANT CANCERS: A PROMISING PATH AT THE BEDSIDE
Burska, Agata N.; Ilyassova, Bayansulu; Dildabek, Aruzhan; Khamijan, Medina; Begimbetova, Dinara; Molnár, Ferdinand
The turn-on mutations of the KRAS gene, coding a small GTPase coupling growth factor signaling, are contributing to nearly 25% of all human cancers, leading to highly malignant tumors with poor outcomes. Targeting of oncogenic KRAS remains a most challenging task in oncology. Recently, the specific G12C mutant KRAS inhibitors have been developed but with a limited clinical outcome because they acquire drug resistance. Alternatively, exploiting a metabolic breach of KRAS-mutant cancer cells related to a glucose-dependent sensitivity to oxidative stress is becoming a promising indirect cancer targeting approach. Here, we discuss the use of a vitamin C (VC) acting in high dose as an oxidative “Trojan horse” agent for KRAS-mutant cancer cells that can be potentiated with another oxidizing drug arsenic trioxide (ATO) to obtain a potent and selective cytotoxic impact. Moreover, we outline the advantages of VC’s non-natural enantiomer, D-VC, because of its distinctive pharmacokinetics and lower toxicity. Thus, the D-VC and ATO combination shows a promising path to treat KRAS-mutant cancers in clinical settings.
2022-01-01T00:00:00ZCO‑ADMINISTRATION OF FVIII WITH IVIG REDUCES IMMUNE RESPONSE TO FVIII IN HEMOPHILIA A MICE
http://nur.nu.edu.kz:80/handle/123456789/6966
CO‑ADMINISTRATION OF FVIII WITH IVIG REDUCES IMMUNE RESPONSE TO FVIII IN HEMOPHILIA A MICE
Afraz, Sajjad; Stevic, Ivan; Matino, Davide; Wen, Jianping; Atkinson, Helen; Chan, Anthony K. C.; Hortelano, Gonzalo
Hemophilia A is an X-linked recessive congenital bleeding disorder. Exogenous infusion of FVIII is the treatment of choice, and the development of immunoglobulins against FVIII (inhibitors) remains the major challenge in clinical management of the disease. Here, we investigated the effect of co-administration of FVIII with intravenous immunoglobulin (IVIG) on the development of inhibitors in previously untreated hemophilia A mice. A group of hemophilia A mice (C57BL/6FVIII−/−) received weekly injections of recombinant human FVIII (rFVIII) for twelve consecutive weeks while a second group received co-injections of rFVIII + IVIG. An in-house enzyme-linked immunosorbent assay (ELISA) was designed to detect antibodies to rFVIII. Every mouse in the first group developed antibodies to rFVIII. In contrast, mice treated with rFVIII + IVIG showed significantly lower antibody titers. Interestingly, when co-administration of IVIG was discontinued after 12 weeks in some mice (rFVIII continued), these mice experienced an increase in antibody titer. In contrast, mice that continued to receive rFVIII + IVIG retained significantly lower titers. In conclusion, prophylactic rFVIII co-administration with IVIG modulated the immune response to FVIII and resulted in decreased anti-FVIII antibody titer. These findings suggest that co-injection therapy with IVIG could potentially be effective in the management of hemophilia A patients at risk of inhibitor development.
2022-01-01T00:00:00ZHONGHUA EXTRACT MEDIATED POTENT INHIBITION OF COVID‑19 HOST CELL PATHWAYS
http://nur.nu.edu.kz:80/handle/123456789/6961
HONGHUA EXTRACT MEDIATED POTENT INHIBITION OF COVID‑19 HOST CELL PATHWAYS
Madikyzy, Malika; Tilegen, Meruyert; Nazarbek, Guldan; Mu, Chenglin; Kutzhanova, Aidana; Li, Xugang; Ma, Cuiping; Xie, Yingqiu
Honghua (Carthami flos) and Xihonghua (Croci stigma) have been used in anti-COVID-19 as Traditional
Chinese Medicine, but the mechanism is unclear. In this study, we applied network pharmacology
by analysis of active compounds and compound-targets networks, enzyme kinetics assay, signaling
pathway analysis and investigated the potential mechanisms of anti-COVID-19. We found that both
herbs act on signaling including kinases, response to inflammation and virus. Moreover, crocin likely
has an antiviral effect due to its high affinity towards the human ACE2 receptor by simulation. The
extract of Honghua and Xihonghua exhibited nanozyme/herbzyme activity of alkaline phosphatase,
with distinct fluorescence. Thus, our data suggest the great potential of Honghua in the development
of anti-COVID-19 agents.
2022-01-01T00:00:00ZNETWORK PHARMACOLOGY WITH EXPERIMENTAL INVESTIGATION OF THE MECHANISMS OF RHIZOMA POLYGONATI AGAINST PROSTATE CANCER WITH ADDITIONAL HERBZYMATIC ACTIVITY
http://nur.nu.edu.kz:80/handle/123456789/6952
NETWORK PHARMACOLOGY WITH EXPERIMENTAL INVESTIGATION OF THE MECHANISMS OF RHIZOMA POLYGONATI AGAINST PROSTATE CANCER WITH ADDITIONAL HERBZYMATIC ACTIVITY
Kazybay, Bexultan; Sun, Qinglei; Dukenbayev, Kanat; Nurkesh, Ayan Amantaiuly; Xu, Na; Kutzhanova, Aidana; Razbekova, Madina; Kabylda, Anar; Yang, Qing; Wang, Qian; Ma, Cuiping; Xie, Yingqiu
A combination therapy of Rhizoma Polygonati (RP) with goji (Lycium chinense) has earned a long history in the prescriptions to promote male health. However, the mechanisms at both molecular and nanoscale quantum levels are unclear. Here, we found that processed RP extract induces apoptosis and cell cycle arrest in cancer cells, thereby inhibiting prostate cancer cell proliferation enhanced by processed goji extract associated with an augment of the nanoscale herbzyme of phosphatase. For network pharmacology analysis, RP-induced PI3K-AKT pathways are essential for both benign prostatic hyperplasia and prostate cancer, and the RP/goji combination induces potent pathways which include androgen and estrogen response, kinase regulation, apoptosis, and prostate cancer singling. In addition, the experimental investigation showed that the prostate cancer cells are sensitive to RP extract for inhibiting colony formation. Finally, the natural compound baicalein found in RP ingredients showed a linked activity of top-ranked signaling targets of kinases including MAPK, AKT, and EGFR by the database of cMAP and HERB. Thus, both the nanozyme and ingredients might contribute to the RP in anti-prostate cancer which can be enhanced by goji extract. The proposed nanoscale RP extract might be of significance in developing novel anti-prostate cancer agents by combining goji compositions and targeted therapy compounds.
2022-01-01T00:00:00ZOMICRON N501Y MUTATION AMONG SARS-COV-2 LINEAGES: IN SILICO ANALYSIS OF POTENT BINDING TO TYROSINE KINASE AND HYPOTHETICAL REPURPOSED MEDICINE
http://nur.nu.edu.kz:80/handle/123456789/6945
OMICRON N501Y MUTATION AMONG SARS-COV-2 LINEAGES: IN SILICO ANALYSIS OF POTENT BINDING TO TYROSINE KINASE AND HYPOTHETICAL REPURPOSED MEDICINE
Kazybay, Bexultan; Ahmad, Ashfaq; Mu, Chenglin; Mengdesh, Diana; Xie, Yingqiu
Variants of SARS-CoV-2 lineages including the most recently circulated Omicron, and previous pandemic
B.1.351, B.1.1.7, which have been public concerns, contain a N501Y mutation located in the spike receptor
binding domain. However, the potential interactions with host cells linking N501Y mutation to pathogenic
relevance remain elusive. Recently, we and others report that kinases such as PI3K/AKT signaling are essential in
SARS-CoV-2 entry. Here we analyzed the predicted potential kinases interacting with the mutation. Bioinformatics
tools including structure-prediction based molecular docking analysis were applied. We found kinases
such as EGFR might potentially act as new factors involving the N501Y mutation binding through possible
phosphorylation at Y501 and enhanced affinity in certain variants. To our surprise, the Omicron receptor binding
domain harboring N501Y mutation did not enhance binding to EGFR which might be due to the mutations of
charged polar to uncharged polar side chains located on the interaction interfaces. Similarly, potent gains of
phosphorylation in B.1.351 and B.1.1.7 by mutations were predicted and interaction networks were analyzed
with enrichment of pathways. Given kinases might be elevated in cancer patients, the N501Y mutation containing
lineages may be possibly much more infectious and additional care for cancer management might be
taken into consideration by precision prevention, therapy or recovery.
2022-01-01T00:00:00Z