proliferative activity
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2022 ◽  
Vol 22 (1) ◽  
pp. 100601
Sara Falvo ◽  
Alessandra Santillo ◽  
Gabriella Chieffi Baccari ◽  
Federica Cioffi ◽  
Maria Maddalena Di Fiore

2022 ◽  
Vol 3 (1) ◽  
Kendra R. Vann ◽  
Dhananjaya Pal ◽  
Audrey L. Smith ◽  
Namood-e Sahar ◽  
Maddeboina Krishnaiah ◽  

AbstractMantle cell lymphoma (MCL) is a subtype of non-Hodgkin’s lymphoma characterized by poor prognosis. The complexity of MCL pathogenesis arises from aberrant activities of diverse signaling pathways, including BTK, PI3K–AKT–mTOR and MYC-BRD4. Here, we report that MCL-related signaling pathways can be altered by a single small molecule inhibitor, SRX3305. Binding and kinase activities along with resonance changes in NMR experiments reveal that SRX3305 targets both bromodomains of BRD4 and is highly potent in inhibition of the PI3K isoforms α, γ and δ, as well as BTK and the drug-resistant BTK mutant. Preclinical investigations herein reveal that SRX3305 perturbs the cell cycle, promotes apoptosis in MCL cell lines and shows dose dependent anti-proliferative activity in both MCL and drug-resistant MCL cells. Our findings underscore the effectiveness of novel multi-action small molecule inhibitors for potential treatment of MCL.

2022 ◽  
Anna Oleshkevich ◽  
Elena Yarygina

The functional activity stimulation of cell cultures was tested in MDBK cell culture, photobacteria AliivibriofischeriandHalobacteriumhalobium. Theaim of the investigation was to increase the ”yield” of the cells using an environmentallysafe stimulant and membrane-tropic agent that isalso safe for the experimenter. Ultrasonicwaves were used.Experimental ultrasonic exposure varied within the following limits: time from 1 to 300 sec, SATA-intensity of 0.01–2.0 W/cm2, generation frequency of 0.88 or 2.64 MHz, standing or traveling wave. The modulation frequency range was within 0.1–150 Hz. The devices used were: UST-1-01F, UST-5 and UST1.02C. The modulating generators were G3–112 and CP–110.Stimulation of MDBK cell growth was initiated by US-intensity of 0.03–0.05 W/cm2 , with an exposure of 5–30 sec.Exposure to ultrasound with an intensity of 0.2–0.4 W/cm2 (for 3 min) had a stimulating effect on bioluminescence and was associated with an increase in the growth rate ofA. fischeri. The findings indicated that 0.4 W/cm2ultrasonic intensity and modulation frequencies from 0.25 to 0.7 Hz can stimulate the growth of archaea.It was revealed that the maximum proliferation index in all cases of stimulant application was noted in cultures with minimal initial proliferative activity in the control.The authors expect thatthese results on the possibilities of acoustic continuous and modulated waves can be applied for biotechnological purposes to develop a new biotechnological method. Keywords: cell culture, ultrasound, proliferation, stimulation

2022 ◽  
Mikhail G Akimov ◽  
Natalia M Gretskaya ◽  
Polina V Dudina ◽  
Galina Sherstyanykh ◽  
Galina N Zinchenko ◽  

The objective of the project is to establish the mechanisms of multidirectional signal transmission through the same G-protein coupled receptor GPR55. Using the CRISPR-Cas9 system, clones of the MDA-MB-231 line knockout for the GPR55 (3 clones) and CB2 (CNR2 - 6 clones) receptor genes were obtained. On clones of the MDA-MB-231 line with a knockout CB2 receptor, the cytotoxic activity of the pro-apoptotic ligand docosahexaenoyldopamine (DHA-DA) did not change or slightly increased, while the pro-proliferative activity of the most active synthetic ligand of the GPR55 receptor (ML-184) completely disappeared. On the original line MDA-MB-231, the stimulatory effect of ML-184 is removed by the CB2 receptor blocker, but not by GPR55. At the same time, the stimulating effect of ML-184 is practically not manifested on cell lines knockout at the GPR55 receptor. Thus, it can be confidently assumed that when proliferation is stimulated with the participation of the GPR55 receptor, a signal is transmitted from the CB2 receptor to the GPR55 receptor due to the formation of a heterodimer. GPR18 and TRPV1 receptors are additionally involved in the implementation of the cytotoxic effect of DHA-DA, while the CB1 receptor is not involved. In the implementation of the cytotoxic action of DHA-DA, the predominant participation of one of the Ga subunits was not found, but the Ga13 subunit plays a decisive role in the implementation of the proproliferative action. The Gaq subunit is also important, although to a lesser extent than Ga13.

2022 ◽  
Vol 12 (2) ◽  
pp. 720
Beatriz Salesa ◽  
Alberto Tuñón-Molina ◽  
Alba Cano-Vicent ◽  
Marcelo Assis ◽  
Juan Andrés ◽  

Multi-layer graphene (2–10 layers), also called graphene nanoplatelets (GNPs), is a carbon-based nanomaterial (CBN) type with excellent properties desirable for many biomedical applications. Despite the promising advantages reported of GNPs, nanoscale materials may also present a potential hazard to humans. Therefore, in this study, the in vivo toxicity of these nanomaterials at a wide range of concentrations from 12.5 to 500 µg/mL was evaluated in the Caenorhabditis elegans model for 24 h (acute toxicity) and 72 h (chronic toxicity). Furthermore, their in vitro toxicity (from 0 to 10 µg/mL for 12 and 24 h), proliferative activity at 72 and 96 h, and their effect on the expression of thirteen genes in human keratinocytes HaCaT cells were studied. The physico-chemical and morphological aspects of the GNPs used in this study were analyzed by Raman scattering spectroscopy, electron microscopy, zeta potential as a function of pH, and particle size measurements by dynamic light scattering. The results of this study showed that GNPs showed in vivo non-toxic concentrations of 25 and 12.5 µg/mL for 24 h, and at 12.5 µg/mL for 72 h. Moreover, GNPs present time-dependent cytotoxicity (EC50 of 1.142 µg/mL and 0.760 µg/mL at 12 h and 24 h, respectively) and significant proliferative activity at the non-toxic concentrations of 0.005 and 0.01 μg/mL in the HaCaT cell line. The gene expression study showed that this multi-layer-graphene is capable of up-regulating six of the thirteen genes of human keratinocytes (SOD1, CAT, TGFB1, FN1, CDH1, and FBN), two more genes than other CBNs in their oxidized form such as multi-layer graphene oxide. Therefore, all these results reinforce the promising use of these CBNs in biomedical fields such as wound healing and skin tissue engineering.

2022 ◽  
pp. 089875642110666
Natália Goulart Leite ◽  
Thiago Henrique Moroni Vargas ◽  
Daniel Giberne Ferro ◽  
Renata Afonso Sobral ◽  
Michèle Alice Françoise Anita Venturini ◽  

The majority of the melanocytic neoplasms are considered malignant and highly metastatic. However, a subset of the melanocytic tumors has a more favorable prognosis and the identification of precise prognostic markers for this neoplasm may be useful to guide treatment. The collagen architecture and density have been shown to correlate with tumor progression in human breast cancer and canine mast cell tumors. The purpose of the present study was to investigate the prognostic value of the intratumoral collagen index (ICI) as an indicator of postsurgical survival and its relation with other prognostic markers for canine oral melanomas (OMs). Twenty-two cases were tested for intratumoral collagen density using Masson's trichrome stain and morphometry. No differences were found between dogs regarding survival. The ICI was not correlated with proliferative activity or nuclear atypia. The results presented herein indicate that the quantity of intratumoral collagen in canine OMs is not an efficient indicator of postsurgical survival. Complementary studies about the expression and activity of enzymes that are capable of degrading extracellular matrix (ECM) components are necessary.

A. Smekalova ◽  
O. Mityashova ◽  
O. Aleinikova ◽  
E. Montvila ◽  
I. Lebedeva

Somatotropic hormone (STH) is an important positive modulator of ovarian function in mammals. Local production of STH and the expression of the corresponding specific receptors were also detected in hen ovarian follicles, which indicates the participation of this hormone in the endocrine/paracrine control of folliculogenesis in birds. Nevertheless, the role of STH in the regulation of growth of avian follicles at the final stage of maturation is still not clear.Objective: To study in vitro the effect of STH on the proliferative activity and apoptotic changes of granulosa and theca cells from preovulatory follicles of domestic hens.Materials and methods. Young laying hens aged 34-35 weeks with a long clutch were used in the experiments. Granulosa and theca cells were isolated from the largest yellow follicle in the hierarchy (F1). The cells were cultured in a medium containing 10% fetal bovine serum until a monolayer was formed, and then for 24 h in the medium without serum in the absence (control) or in the presence of STH at various concentrations (1-100 ng/ml). The proliferative activity and apoptotic changes in the cells were assessed by immunocytochemical assay, based on the expression level of proliferating cell nuclear antigen PCNA and pro-apoptotic protein Bax, respectively.Results. The proportion of PCNA-positive granulosa cells increased 1.3-1.8 times (P<0.01-0.05) as compared to control with increasing the content of STH in the medium to 10-100 ng/ml. Furthermore, within this concentration range, the studied hormone reduced 1.2-1.6 times (P<0.05) the relative number of granulosa cells with the positive reaction to Bax. The sensitivity of theca cells to the growth-stimulating effect of STH was lower than that of granulosa cells. Such the effect of STH led to an increase in the proportion of PCNA-positive thecal cells by 1.2-1.3 times (P<0.05) and was detected only at concentrations of 25 and 100 ng/ml. Meanwhile, STH (25-100 ng/ml) increased 1.3 times (P<0.05) the level of Bax expression in theca cells.Conclusions. The results of the present study indicate the stimulating effect of STH in vitro on the proliferative activity of granulosa and theca cells from the most mature hen preovulatory follicle. In addition, STH is able to reduce the expression of the pro-apoptotic protein Bax in granulosa cells and increase this expression in thecal cells. Thus, the data obtained indicate the possible participation of STH in the regulation of growth and development of follicles at the final stage of maturation during the period of maximum egg-laying intensity in laying hens.

2022 ◽  
Vol 9 ◽  
Nuzhat Parveen ◽  
Yan-Liang Lin ◽  
Ruey-Hwang Chou ◽  
Chung-Ming Sun ◽  
Chin Yu

A promising approach in cancer therapy is the inhibition of cell proliferation using small molecules. In this study, we report the synthesis of suramin derivatives and their applications. We used NMR spectroscopy and docking simulations to confirm binding sites and three-dimensional models of the ligand-protein complex. The WST-1 assay was used to assess cell viability and cell proliferation in vitro to evaluate the inhibition of protein–protein interactions and to investigate the anti-proliferative activities in a breast cancer cell line. All the suramin derivatives showed anti-proliferative activity by blocking FGF1 binding to its receptor FGFRD2. The dissociation constant was measured by fluorescence spectroscopy. The suramin compound derivatives synthesized herein show potential as novel therapeutic agents for their anti-proliferative activity via the inhibition of protein–protein interactions. The cytotoxicity of these suramin derivatives was lower than that of the parent suramin compound, which may be considered a significant advancement in this field. Thus, these novel suramin derivatives may be considered superior anti-metastasis molecules than those of suramin.

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