Stimulate Cell Growth Research Articles

Nanoparticles in Growth Factor Therapy: A Promising Approach for Tissue Regeneration

Nanoparticles (NP) are being explored as a promising approach for growth factor therapy in tissue regeneration. Growth factors play a critical role in tissue regeneration by stimulating cell growth, proliferation, and differentiation. However, the use of conventional growth factor therapy is limited by their short half-lives, rapid clearance from the body, and difficulties in delivering them to the target site. To overcome these challenges, nanoparticles have been used to encapsulate growth factors, providing a sustained and localized delivery system. The aim of this article focuses on the most recent advancements in Growth Factor Therapy (GFT), where tissue generation (TR) and cell therapy depend heavily on iron oxide nanoparticles (IONPs). Additionally, the presence of magnetic fields can use mechanotransduction to drive cell differentiation into a particular cell type or to specifically route IONP-labeled cells to the site of action. Further research is needed to fully understand the safety and efficacy of using nanoparticles in therapeutic applications, but their potential to revolutionize tissue regeneration and provide better treatment options for patients suffering from various diseases and injuries is significant

The use of platelet lysate to increase the growth-stimulating effect of the amniotic membrane <i>in vitro</i>

AIM: To work out the technique of saturation of the preserved amniotic membrane (AM) with platelet rich plasma (PRP) lysate and to evaluate the growth-stimulating effect of a combination of AM and PRP lysate in vitro.
 MATERIALS AND METHODS: In the experiment, AM samples preserved in 3 ways were used: silicate drying, lyophilization, cryopreservation. PRP lysate was prepared on the basis of volunteers blood. During the exposure of AM with PRP lysate, the optimal saturation time of canned AM with lysate was determined, the volume of lysate that 1 cm2 of AM could adsorb was estimated. The growth-stimulating effect of AM transplants was evaluated in the culture of human buccal epithelium. The dynamics of cell growth was evaluated after 1, 2 and 3 days from the moment of sowing.
 RESULTS: In the presence of PRP lysate, the mass of silicatedried AM increased 4.2 times, lyophilized AM 4.8 times, cryopreserved AM 1.8 times. AM samples obtained by lyophilization adsorbed PRP lysate most effectively. Five minutes of exposure with PRP lysate are enough to fully saturate the AM. AM without PRP lysate did not give a growth-stimulating effect.
 CONCLUSIONS: When comparing experiments with PRP lysate without AM and AM with PRP lysate, it was found that the greatest stimulation of cell growth occurred when using lyophilized AM and PRP lysate. Saturation of cryopreserved AM with PRP lysate was ineffective, and when using silicate-dried AM impregnated with PRP lysate, the greatest growth-stimulating effect was observed on the 1st day.

The biological effect of a combination of platelet lysate and amniotic membrane in buccal epithelium culture

Purpose: To study the biological effect of a combination of platelet lysate and amniotic membrane, preserved by various techniques, on human buccal epithelium culture. Materials and methods. Human amnion transplants were preserved using 3 methods: silicate drying, lyophilization, cryopreservation. The blood of healthy volunteers was used as a source of platelets. Platelet-rich plasma (PRP) with a platelet content over 1000 thousand/mcl and more was isolated from the donors blood, frozen at -80 °С and defrosted at 0–4 °С to prepare platelet lysate. Growth-stimulating effect of the amnion transplants was studied in different groups: control group 1 — without amnion and without PRP lysate; control group 2 — PRP lysate without amnion; experimental group 1 — amnion without PRP lysate; experimental group 2 — amnion samples combined with PRP lysate. The study was carried out on the example of human buccal epithelium culture of 3–5 passages. The dynamics of cell growth was evaluated after 1, 2 and 3 days from the moment of seeding. The number of cells and their viability were evaluated using original methods based on vital cell staining and their examination in a fluorescent microscope. Results. All samples of preserved amnions were non-toxic and did not damage the structural and functional characteristics of the buccal epithelium. On the other hand, the use of amnion without PRP lysate did not have a growth-stimulating effect on cells. Among the amnion samples combined with PRP lysate, the combination of lyophilized amnion and PRP lysate was the most effective during the entire study period. Conclusions. Silicate drying, lyophilization and cryopreservation of the amniotic membrane makes it possible to obtain biocompatible and non-toxic transplants, based on human amnion. Lyophilized amnions are the most optimal for saturating PRP lysate. The combination of lyophilized amnion and PRP lysate stimulates cell growth in vitro without violating their structural integrity.

Review of dermatofibrosarcoma protuberans.

The clinical features, histological subtypes and management of dermatofibrosarcoma protuberans (DFSP) are reviewed in this article. DFSP is an uncommon cutaneous sarcoma first described in 1890. It has a high local recurrence rate, low metastatic rate and low mortality. The crude incidence rate in England in 2019 was reported as 3.0 per million person-years. A fusion of platelet-derived growth factor subunit B (PDGFB) and COL1A1, t(17;22)(q22;q13), has been found in over 90% of people with DFSP. This fusion is thought to upregulate PDGFB expression, stimulating cell growth by activation of Ras mitogen-activated protein kinases and PI3K-AKT-mTOR, potentiating oncogenesis. DFSP usually presents as an asymptomatic flesh-coloured, thickened, rubbery plaque or nodule with an uneven surface. The most common sites are the trunk followed by lower limbs, head and neck and upper limbs. Larger tumours can infiltrate underlying local structures and around 1% metastasize. Key histological features in DFSP are spindle cells arranged in a storiform pattern with intense CD34 staining. Histological subtypes include classical DFSP, Bednar, myxoid, giant cell fibroblastoma, atrophic and DFSP-fibrosarcomatous. The gold standard management for localized tumours is surgical: current recommendations favour Mohs micrographic surgery over wide local excision. Adjuvant radiotherapy may be offered after surgery. Imatinib can be used as neoadjuvant therapy and in patients with inoperable or metastatic tumours. Further research should be conducted to better understand pathogenesis of DFSP, identify associated risk factors and standardize management.

Non-thermal atmospheric-pressure plasma potentiates mesodermal differentiation of human induced pluripotent stem cells

Non-thermal atmospheric-pressure plasma has been used for biological applications, including sterilization and stimulation of cell growth and differentiation. Here, we demonstrate that plasma exposure influences the differentiation pattern of human induced pluripotent stem cells (hiPSCs). We treated hiPSCs with dielectric barrier-discharge air plasma and found an exposure dose that does not kill hiPSCs. Immunohistochemical staining for E-CADHERIN showed that the exposure affected cell-cell attachment and doubled the average size of the hiPSCs. Analysis of mRNAs in embryoid bodies (EBs) from plasma-treated hiPSCs revealed repression of ectoderm genes, including WNT1, and increased expression of mesoderm genes. Importantly, hiPSCs deficient in DNA repair only displayed minimal damage after plasma exposure. Collectively, our results suggest that plasma treatment can be another tool for directing the fate of pluripotent stem cells without disrupting their genomic integrity.

Article Review: Biochemical Aspect of Survivin Hormone

A cancer gene called survivin is muted in cells which have undergone differentiation, but it is highly qualitative sample in the overwhelming proportion of malignancies. Over subsequent decades, there has been a lot of curiosity in it. Inhibiting apoptotic, encouraging mitotic, and increasing vascular formation while producing cytotoxic drugs are several crucial characteristics that define it is a good target. These processes, that together promote carcinogenic behaviour, cover the whole spectrum of carcinogenesis, encompassing growth, migratory, or infiltration. Survivin identification independently or coupled in blood and/or urine has become a diagnostic tool for prostate cancer. Furthermore, a number of researches showed that abnormal survivin transcription is linked to a poor prognosis or radiation/drug resistance. Early findings from approaches that target survivin in the treatment of breast carcinoma are encouraging. In order to clarify how this intriguing chemical performs such contradictory function, researchers outline its involvement in the detection, prognosis, as well as therapy of melanoma in this review.
 The IAP enzyme group, which includes the survival protein (SVN), stimulates cell growth or prevents apoptosis. As a biomarker for autoimmune conditions, hyper plasia, or malignancies, accumulation of Survivin is linked to these conditions. Increasingly acknowledged like a tumor-associated antigen (TAA), SVN has emerged as a crucial focus for the detection or management of malignancy.

The Effects of Amino Acids, Phenols and Protein Hydrolysates as Biostimulants on Sustainable Crop Production and Alleviated Stress.

Biostimulants which contain substances or products, including natural compounds, special formulations and microorganisms have gained considerable attention as sustainable methods for heavy metal detoxification, stimulating natural toxins, controlling diseases and pests, and increasing both water and nutrient efficiency. Biostimulants are important products in modern agriculture, which are composed of different heterogeneous classes of compounds with a broad spectrum of action to increase both qualitative and quantitative productions. Amino acids can be useful in stress defense, photosynthesis, for increasing nutrient uptake, pollination and fruit formation, and as precursors to hormones and growth parameters. Amino acids are considered as precursors and constituents of proteins, which are well-known for the stimulation of cell growth. Because they are the basic building blocks of proteins, amino acids are very important in plant growth, development and metabolite synthesis. One of the diverse, notable and large group of secondary metabolites is phenolic compounds, which have important function in regulation of the plants' physiological activities, oxidation-reduction processes, and photosynthesis. Protein hydrolysates contain amino acids and peptides, one of the most important kinds of biostimulants. Protein hydrolysates have a notable capability to increase crop performance, particularly under environmental stress conditions. This review article is aimed to introduce and find more about the roles of different types of biostimulants in plant growth and final yield production, leading to sustainable agriculture.

Growth-Stimulating Effect of Platelet Preparations Obtained by Different Methods on Human Fibroblast Culture.

We studied the growth-stimulating effect of platelet-based preparations obtained by different methods on cultured human fibroblasts M-22. Platelet lysates prepared from platelet-rich plasma, platelet-poor plasma, concentrated suspension of platelets washed from plasma, and platelet-rich plasma activated with calcium chloride (ActPRP) were used. The volume of the platelet preparations was 10-500 μl per 104 cells. The most effective dose of platelet-rich and platelet-poor plasma in cell culture was 20 μl, whereas for ActPRP, the most effective dose was 500 μl. Lysates of platelet-rich and platelet-poor plasma in doses of 100-500 μl inhibited fibroblast growth and disturbed their structural integrity. At the same time, lysates of washed platelets in doses of 10-500 μl stimulated cell growth and preserved their viability. An inverse correlation was found between the number of cells in culture and the level of proinflammatory cytokines in the platelet preparations.

Silencing of lncRNA KLF3-AS1 represses cell growth in osteosarcoma via miR-338-3p/MEF2C axis.

Osteosarcoma (OS) is a highly recurrent malignancy occurring among adolescents. The goal of this research was to scrutinize the role and action mechanism of KLF3-AS1 in OS. Western blotting and quantitative reverse transcription real-time PCR were conducted to ascertain the mRNA expressions of miR-338-3p, KLF3-AS1, and MEF2C in OS cell lines and tissue samples. Colony formation and CCK-8 experiments were done to evaluate the proliferative capacity of the cells. Western blotting was also executed to measure the relative expressions of the proteins Bcl-2 and Bax. RNA immunoprecipitation and dual luciferase reporter experiments were carried out to validate the target relationships among MEF2C, KLF3-AS1, and miR-338-3p. Mouse xenograft models were created to assess the influences of KLF3-AS1 on the growth of tumors in vivo. Elevated levels of KLF3-AS1 and MEF2C and reduced amounts of miR-338-3p were identified in OS. KLF3-AS1 targeted miR-338-3p, and miR-338-3p further targeted MEF2C. Silencing KLF3-AS1 induced apoptosis and attenuated proliferation in vitro and repressed the tumor growth in vivo. Inhibiting miR-338-3p inverted the cancer-suppressing effects of KLF3-AS1 silencing. Meanwhile, loss of MEF2C partially eliminated the effects brought about by miR-338-3p downregulation, namely the stimulation of cell growth and suppression of apoptosis. Silencing of KLF3-AS1 could repress the growth of cells and induce apoptosis by regulating miR-338-3p/MEF2C in OS. This suggests that the regulatory axis KLF3-AS1/miR-338-3p/MEF2C is a prospective target for OS treatment.

Glucose 6-P Dehydrogenase-An Antioxidant Enzyme with Regulatory Functions in Skeletal Muscle during Exercise.

Hypomorphic Glucose 6-P dehydrogenase (G6PD) alleles, which cause G6PD deficiency, affect around one in twenty people worldwide. The high incidence of G6PD deficiency may reflect an evolutionary adaptation to the widespread prevalence of malaria, as G6PD-deficient red blood cells (RBCs) are hostile to the malaria parasites that infect humans. Although medical interest in this enzyme deficiency has been mainly focused on RBCs, more recent evidence suggests that there are broader implications for G6PD deficiency in health, including in skeletal muscle diseases. G6PD catalyzes the rate-limiting step in the pentose phosphate pathway (PPP), which provides the precursors of nucleotide synthesis for DNA replication as well as reduced nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is involved in the detoxification of cellular reactive oxygen species (ROS) and de novo lipid synthesis. An association between increased PPP activity and the stimulation of cell growth has been reported in different tissues including the skeletal muscle, liver, and kidney. PPP activity is increased in skeletal muscle during embryogenesis, denervation, ischemia, mechanical overload, the injection of myonecrotic agents, and physical exercise. In fact, the highest relative increase in the activity of skeletal muscle enzymes after one bout of exhaustive exercise is that of G6PD, suggesting that the activation of the PPP occurs in skeletal muscle to provide substrates for muscle repair. The age-associated loss in muscle mass and strength leads to a decrease in G6PD activity and protein content in skeletal muscle. G6PD overexpression in Drosophila Melanogaster and mice protects against metabolic stress, oxidative damage, and age-associated functional decline, and results in an extended median lifespan. This review discusses whether the well-known positive effects of exercise training in skeletal muscle are mediated through an increase in G6PD.

SAUR63 stimulates cell growth at the plasma membrane.

In plants, regulated cell expansion determines organ size and shape. Several members of the family of redundantly acting Small Auxin Up RNA (SAUR) proteins can stimulate plasma membrane (PM) H+-ATPase proton pumping activity by inhibiting PM-associated PP2C.D phosphatases, thereby increasing the PM electrochemical potential, acidifying the apoplast, and stimulating cell expansion. Similarly, Arabidopsis thaliana SAUR63 was able to increase growth of various organs, antagonize PP2C.D5 phosphatase, and increase H+-ATPase activity. Using a gain-of-function approach to bypass genetic redundancy, we dissected structural requirements for SAUR63 growth-promoting activity. The divergent N-terminal domain of SAUR63 has a predicted basic amphipathic α-helix and was able to drive partial PM association. Deletion of the N-terminal domain decreased PM association of a SAUR63 fusion protein, as well as decreasing protein level and eliminating growth-promoting activity. Conversely, forced PM association restored ability to promote H+-ATPase activity and cell expansion, indicating that SAUR63 is active when PM-associated. Lipid binding assays and perturbations of PM lipid composition indicate that the N-terminal domain can interact with PM anionic lipids. Mutations in the conserved SAUR domain also reduced PM association in root cells. Thus, both the N-terminal domain and the SAUR domain may cooperatively mediate the SAUR63 PM association required to promote growth.

Effect of explant type (leaf, stem) and 2,4-D concentration on callus induction: influence of elicitor type (biotic, abiotic), elicitor concentration and elicitation time on biomass growth rate and costunolide biosynthesis in gazania (Gazania rigens) cell suspension cultures

Gazania rigens (L.) Gaertn. (Asteraceae) is a medicinal plant with high ornamental potential and use in landscaping. The therapeutic potential of sesquiterpene lactones (SLs) as plant natural products for pharmaceutical development has gained extensive interest with costunolide (chemical name: 6E,10E,11aR-6,10-dimethyl-3-methylidene-3a,4,5,8,9,11a-hexahydrocyclodeca[b]furan-2-one) used as a popular herbal remedy due to its anti-cancer, antioxidant, anti-inflammatory, anti-microbial, anti-allergic, and anti-diabetic activities, among others. In the present study, two explant types (leaf, stem) and four 2,4-dichlorophenoxy acetic acid (2,4-D) concentrations (0, 0.5, 1 and 2 mg/L) were tested for callusing potential. The results showed that stem explants treated with 1.5 mg/L 2,4-D exhibited higher callus induction percentage (90%) followed by leaf explants (80%) with 1 mg/L 2,4-D, after a 4-week period. Cell suspension cultures were established from friable callus obtained from stem explants following a sigmoid pattern of growth curve with a maximum fresh weight at 20 days of subculture and a minimum one at 5 days of subculture. In the following stage, the effects of elicitation of cell suspension cultures with either yeast extract (YE) or methyl jasmonate (MeJA), each applied in five concentrations (0, 100, 150, 200 and 250 mg/L) on cell growth (fresh and dry biomass) and costunolide accumulation were tested. After 20 days of culture, YE or MeJA suppressed cell growth as compared to the non-elicited cells, while costunolide accumulation was better enhanced under the effect of 150 mg/L MeJA followed by 200 mg/L YE, respectively. In the subsequent experiment conducted, the optimal concentration of the two elicitors (200 mg/L YE, 150 mg/L MeJA) was selected to investigate further elicitation time (0, 5, 10, 15 and 20 days). The results revealed that YE biotic elicitation stimulated cell growth and costunolide production, being maximum on day 20 for fresh biomass, on day 5 for dry biomass and on day 15 for the bioactive compound. Accordingly, cell growth parameters were maximized under the effect of abiotic elicitation with MeJA for 15 days, while highest costunolide content was achieved after 10 days. Overall, MeJA served as a better elicitor type than YE for biomass and costunolide production. Irrespective of elicitor type, elicitor concentration and elicitation time, maximal response was obtained with 150 mg/L MeJA for 10 days regarding costunolide accumulation (18.47 ppm) and 15 days for cell growth (fresh weight: 954 mg and dry weight: 76.3 mg). The application of elicitors can lead the large quantity of costunolide to encounter extensive range demand through marketable production without endangering of G. rigens.Graphical

SHP2 regulates adipose maintenance and adipocyte-pancreatic cancer cell crosstalk via PDHA1.

Adipocytes are the most abundant cell type in the adipose tissue, and their dysfunction is a significant driver of obesity-related pathologies, such as cancer. The mechanisms that (1) drive the maintenance and secretory activity of adipocytes and (2) mediate the cancer cellular response to the adipocyte-derived factors are not fully understood. To address that gap of knowledge, we investigated how alterations in Src homology region 2-containing protein (SHP2) activity affect adipocyte function and tumor crosstalk. We found that phospho-SHP2 levels are elevated in adipose tissue of obese mice, obese patients, and differentiating adipocytes. Immunofluorescence and immunoprecipitation analyses as well as in-silico protein-protein interaction modeling demonstrated that SHP2 associates with PDHA1, and that a positive association promotes a reactive oxygen species (ROS)-driven adipogenic program. Accordingly, this SHP2-PDHA1-ROS regulatory axis was crucial for adipocyte maintenance and secretion of interleukin-6 (IL-6), a key cancer-promoting cytokine. Mature adipocytes treated with an inhibitor for SHP2, PDHA1, or ROS exhibited an increased level of pro-lipolytic and thermogenic proteins, corresponding to an increased glycerol release, but a suppression of secreted IL-6. A functional analysis of adipocyte-cancer cell crosstalk demonstrated a decreased migration, invasion, and a slight suppression of cell cycling, corresponding to a reduced growth of pancreatic cancer cells exposed to conditioned media (CM) from mature adipocytes previously treated with inhibitors for SHP2/PDHA1/ROS. Importantly, PDAC cell growth stimulation in response to adipocyte CM correlated with PDHA1 induction but was suppressed by a PDHA1 inhibitor. The data point to a novel role for (1) SHP2-PDHA1-ROS in adipocyte maintenance and secretory activity and (2) PDHA1 as a regulator of the pancreatic cancer cells response to adipocyte-derived factors.

The stimulatory effect and mechanism of low-dose lanthanum on soybean leaf cells

Light rare earth elements (LREEs) have been long used in agriculture (i.e., mainly via aerially applied LREE fertilizers) based on the fact that low-dose LREEs promote plant growth. Meanwhile, the toxic effects of low-dose LREEs on organisms have also been found. However, the cellular and molecular mechanism of low-dose LREEs acting on organisms remain unclear. Plants are at the beginning of food chains, so it is critical to uncover the cellular and molecular mechanism of low-dose LREEs on plants. Here, lanthanum (La) and soybean were the representatives of LREEs and plants, respectively. The effects of low-dose La on soybean leaves were investigated, and the stimulatory effect and mechanism of low-dose LREEs on leaf cells were revealed. Specifically, clathrin-mediated endocytosis (CME) activated by low-dose La is an influx channel for La in soybean leaf cells. The intracellular La and La-activated CME jointly disturbed multiple forms of intracellular homeostasis, including metallic element homeostasis, redox homeostasis, gene expression homeostasis. The disturbed homeostasis either stimulated cell growth or caused damage to the plasma membrane of soybean leaf cells. These results provide new insights for clarifying the cellular and molecular mechanisms of low-dose LREEs as a class of stimulators instead of nutrients to stimulate plants.

Triphlorethol‐A attenuates U251 human glioma cancer cell proliferation and ameliorates apoptosis through JAK2/STAT3 and p38 MAPK/ERK signaling pathways

Glioma is the foremost recurrent type of brain tumor in humans;in particular, glioblastoma (GBM) is the main formof brain tumor(GBM)that is highly proliferative and impervious to apoptosis. Triphlorethol-A (TA),a phlorotanninisolated from Ecklonia cava, exhibited cytoprotective, antioxidant, and anticancer properties. However, the exact molecular action of TA in the U251 human GBM cells remains unknown. This may be the first report on the antiproliferative and apoptotic mechanisms of TA on GBM. The cytotoxicity, intracellular reactive oxygen species (ROS), matrix metalloproteinase(MMP), and cell apoptosis activity of TA havebeen evaluated by theMTT assayand byDCFH-DA, Rh-123, AO/EB, and western blot analysis. Theresults obtained showed that TA abridged the viability of U251 cells, whileMMP increased apoptosis by increasing theROS levels in a time-dependent manner. The results showed that a reduction in U251 cellproliferation wasassociated with the regulation of JAK2/STAT3 and p38 MAPK/ERK signaling pathways. TA was found tosuppresspJAK, pSTAT3, p38 MAPK, and pERK phosphorylation, therebycausing Bax/Bcl-2 imbalance, activatingthe caspase cascadeand cytochromec, and inducingapoptosis. Our findings showed that the suppression of JAK2/STAT3 and p38 MAPK/ERK signaling by TA results in cell growth arrest and stimulation of apoptosis in GBM cells. These studies justify the protective remedy of TA against GBM.

Boosting β-carotene and storage materials productivities by two-stage mixed and monochromatic exposure stresses on Dunaliella salina

Growth and product formation of Dunaliella salina, a potent β-carotene source, were investigated under single and two-stage monochromic and mixed illuminations using two LEDs, each emitting red (R), blue (B), or white (W) light. Targeting cell growth in single-stage, WW, RR, and BB, as well as RB illumination, were compared and mixed RB illumination was found most supportive showing the highest cell growth of 1.81 ± 0.008 g/L. Subsequently, new two-stage illuminations (RB-BB and RB-RR) were designed to investigate growth and bio-product formation using RB illumination similarly in the 1st stage followed by separate BB and RR illuminations within the 2nd stage. RB-BB strategy resulted in enhanced productivities of lipid (7.6 mg/L/day), starch (20 mg/L/day), and β-carotene (0.4 mg/L/day) which were respectively higher by 80, 70, and 81% compared to single-stage control (WW). RB-RR strategy stimulated cell growth while it resulted in decreased productivities of products (other than chlorophyll). The highest biomass level of 2.2 g/L and nitrate removal of 80% were obtained in RB-RR while RB-BB resulted in the lowest values of 1.2 g/L and 48%, respectively. Appropriate selection of illuminations in two-stage strategies, therefore, functions to enhance the productivity of important metabolites or cell growth which can have generic applications in other microalgae. NOVELTY STATEMENT Although the effects of a variety of stressful conditions on microalgae product lines have been investigated so far, the effects of two-stage mixed and monochromatic exposure as a light management strategy have not yet been considered. This strategy was inspired by the fact that cell mass alongside the cell content of a product contributes to product productivity. Accordingly, the growth of Dunaliella salina was first examined under single-stage mixed and monochromatic exposure where mixed red-blue light led to the highest biomass formation. Shifting from mixed to different monochromatic exposures was then examined as a stress factor to stimulate product formation. Higher cell factories obtained under mixed exposure in the 1st stage escalated product productivities within the 2nd stage when exposed to monochromatic light.

Critical Review on 3D Scaffolds Materials

New strategies have been developed to design advanced functional biomimetic structures. This paper reviewed the benefits and drawbacks of biomaterials that are used to manufacture 3D scaffolds in tissue engineering. In this paper, latest technological methods, scaffold requirements in development of single form, composite form and cell-laden based scaffolds, classification on the basis of geometry and main material is explained elaborately. These scaffolds promote different molecules can be delivered to tissue and stimulate cell growth. These cells have a therapeutic effect. The paper discusses the various 3D bio printed structures and the difficulties they encounter. The impacts of biologically functionalized biomaterials on soft and hard tissue engineering in vitro and in vivo are discussed. The paper summarized the future prospects for bioactive scaffolds, that can be used in clinical therapy.

THE ROLE OF THE ADRENAL GLANDS IN TUMOR METASTATIC SPREADING (LITERATURE REVIEW)

Oncopathology is one of the main mortality causes in the population. The immediate cause of death in a patient with cancer is metastatic spreading. The study of this pathological process is difficult due to asymptomatic course of the metastatic process, non-specificity of the main clinical analyses, impossibility of in-life studying the process of metastatic spreading. For this reason, laboratory models of metastatic spreading are being investigated, which can be connected both with direct introduction of tumor strains into the organ and with the development of metastases during experimental carcinogenesis. The issue of studying the endocrine system and its influence on the processes of metastatic spreading remains relevant. One of the organs that react to changes in the internal environment is the adrenal glands. The adrenal cortex plays an important role in the body's homeostasis, controlling the amount of cortisol, aldosterone and sex hormones (androgens and a small amount of estrogens), while the adrenal medulla controls stress reactions by discharging adrenaline and norepinephrine. Each of the hormones synthesized by the adrenal glands is somehow involved in the processes of carcinogenesis and metastatic spreading. Thus, cortisol, one of the hormones formed in the adrenal cortex, has a pronounced immunosuppressive effect, it affects the rate of cell proliferation, angiogenesis, differentiation and apoptosis, has a destructive effect on connective tissue. An increase in catecholamines in the blood leads to the damage to biological membranes, which stimulates adhesion and extravasation of tumor cells. In addition, catecholamines stimulate lymphoproliferation. Sex hormones affect not only hormone-dependent tumors of the reproductive system by stimulating cell growth, enhancing uncontrolled cell proliferation and angiogenesis, but tumors of other organs as well. Aldosterone, acting on the vascular wall, promotes the penetration of tumor cells into the vascular bed and their spread throughout the body.

SOX5 promotes cell growth and migration through modulating the DNMT1/p21 pathway in bladder cancer.

Bladder cancer (BC) is one of the most prevalent and life-threatening cancers among the male population worldwide. Sex determining region Y-box protein 5 (SOX5) plays important roles in a variety of human cancers. However, little research has been conducted on the function and underlying mechanism of SOX5 in BC. In the present study, we first reveal the increased expression of SOX5 in BC tissues and in vitro cells lines. Second, we discover that inhibition of SOX5 inhibits cell growth and migration but promotes cell apoptosis. Meanwhile, ectopic SOX5 expression stimulates cell growth and migration in BC cells. Then, we show that suppressing SOX5 inhibits the expression of DNA methyltransferase 1 (DNMT1), and that overexpressing DNMT1 alleviates the cell progress of BC cells inhibited by SOX5. Furthermore, we demonstrate that DNMT1 inhibits p21 expression by affecting DNA methylation of the p21 promoter. Collectively, we demonstrate that SOX5 exerts its functions in BC cells by modulating the SOX5/DNMT1/p21 pathway. Finally, we demonstrate that SOX5 knockdown inhibits xenograft tumor growth in vivo. In conclusion, our study elucidates the oncogenic role of SOX5 and its underlying molecular mechanism in BC, and reveals a novel pathway which has the potential to serve as a diagnostic biomarker and therapeutic target for BC.

Preclinical and Clinical Role of Coenzyme Q10 Supplementation in Various Pathological States.

Coenzyme Q10 (CoQ10) is an efficient antioxidant produced endogenously in a living organism. It acts as an important cofactor in the electron transport system of mitochondria and reported as a safe supplement in humans and animals with minimal adverse effect. CoQ10 is found naturally, as a trans configuration, chemical nomenclature of which is 2,3- dimethoxy-5- methyl-6-decaprenyle -1,4-benzoquinone. It is found in the body in two forms. In quinone form (oxidized form), it serves as an electron transporter that transfers the electrons in the electron transport chain between various complexes, and in ubiquinol form (reduced form), it serves as potent antioxidants by scavenging free radicals or by tocopherol regeneration in the living organism. Its primary roles include synthesis of adenosine triphosphate (ATP), stabilizes lipid membrane, antioxidant activity, cell growth stimulation, and cell death inhibition. CoQ10 has shown a variety of pharmacological and clinical effects including neuroprotective, hepatoprotective, anti-atherosclerotic, anticonvulsant, antidepressant, anti-inflammatory, antinociceptive, cardiovascular, antimicrobial, immunomodulatory, and various effects on the central nervous system. Present review has set about to bring updated information regarding to clinical and preclinical activities of CoQ10, which may be helpful to researchers to explore a new bioactive molecules for various therapeutic application.