Lower Cell Proliferation Research Articles

Effect of Coffee Berry Extract on Anti-Aging for Skin and Hair—In Vitro Approach

The aging process encompasses gradual and continuous changes at the cellular level that slowly accumulate with age. The signs of aging include many physiological changes in both skin and hair such as fine lines, wrinkles, age spots, hair thinning and hair loss. The aim of the current study was to investigate the anti-aging potential of coffee berry extract (CBE) on human dermal fibroblast (HDF) and hair follicle dermal papilla (HFDP) cells. Coffee berry was extracted by 50% ethanol and determined for chemical constituents by HPLC technique. Cytotoxicity of the extract was examined on both cells by MTT assay. Then, HDF cells were used to evaluate antioxidant properties by using superoxide dismutase activity (SOD) and nitric oxide inhibition as well as anti-collagenase inhibition assays. The effectiveness of anti-hair loss properties was investigated in HFDP cells by considering cell proliferation, 5α-reductase inhibition (5AR), and growth factor expression. The results showed that caffeine and chlorogenic acid were identified as major constituents in CBE. CBE had lower toxicity and cell proliferation than caffeine and chlorogenic acid on both cells. CBE showed SOD and nitric oxide inhibition activities that were higher than those of caffeine but lower than those of chlorogenic acid. Interestingly, CBE had the highest significant anti-collagenase activity, and its 5AR inhibition activity was comparable to that of chlorogenic acid, which was higher than caffeine. CBE also stimulated hair-related gene expression, especially insulin-like growth factor 1 (IGF-1), keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF). The results confirmed that CBE provided anti-aging activity on both skin and hair cells and could be beneficial for applications in cosmeceuticals.

Abstract 3370: Fatty acid desaturase 1 (FADS1) is associated with cancer survival via altering cell growth and can be a novel drug target for cancer treatment

Abstract Polyunsaturated fatty acid (PUFA) plays an important role in cancer biology. Fatty acid desaturase1 (FADS1) is a key rate-limiting enzyme in omega-3 and omega-6 PUFA metabolism. We aim to investigate the association between FADS1 and survival outcomes among cancer patients. Univariable and multivariable Cox regression models were performed for FADS1 mRNA expression levels on disease-free survival (DFS) and overall survival (OS) using The Cancer Genome Atlas (TCGA) public datasets. We also investigated the pathways associated with altered FADS1 expression in the TCGA dataset. A FADS1 inhibitor (D5D-IN-326) was used to study the proliferation in vitro in 6 different cancer cell lines. FADS1-shRNA knockdown system was introduced in the renal cell carcinoma (RCC) 786-O cell line to further study the signaling pathway associated with proliferation. Transcriptomic, metabolomic, and lipidomic profiles of stable cell lines were studied. Our analysis showed that among all cancer patients (N=11,490), those with a higher FADS1 mRNA expression in their tumor have a significantly worse DFS and OS (p.value <0.001 and 0.01, respectively). This association was particularly significant in RCC subtypes. Pathway analysis demonstrated that cell cycle and DNA replication were significantly enriched as the top pathways associated with FADS1 expression. Administration of FADS1 inhibitor compound 326 decreased cell proliferation in cell lines of several major cancers in a dose-dependent manner. The proliferation result was confirmed in RCC FADS1 knockdown model. RNA-seq analysis of FADS1 knockdown stable cells also showed downregulation of DNA biosynthesis, cell division, and cell proliferation. In our metabolomic study, 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) was significantly reduced in FADS1 knockdown (KD) cells which may be attributed to altered purine metabolism (p-value < 0.001). As we expected, the total omega-6 and omega-3 fatty acids were lower in KD cells. We further identified lower P38 phosphorylation in KD cells which is consistent with lower cell proliferation. These results suggest that FADS1 overexpression is prognostic to lower survival in cancer patients via changing cancer metabolism, which is potentially mediated via altering cell proliferation through MAPK pathway. This study has a potential to discover a new mechanism of cancer biology and develop a novel precision treatment for cancer patients. The detailed causal relationship is warranted for continued investigation. Citation Format: Gioia Heravi, Hyejeong Jang, Seongho Kim, Wanqing Liu. Fatty acid desaturase 1 (FADS1) is associated with cancer survival via altering cell growth and can be a novel drug target for cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3370.

Transcriptome reveals the dysfunction of pancreatic islets after wound healing in severely burned mice.

Severely burned patients have a higher risk of diabetes mellitus after healing, but its mechanism remains unclear. Therefore, the purpose of the study was to explore the influence of burns on pancreatic islets of mice after wound healing. Forty-two male C57BL/6 mice were randomized into a sham group and a burn group and subjected to sham treatment or a third-degree burn model of 30% total body surface area. Fasting blood glucose was detected weekly for 8 weeks after severe burns. Glucose-stimulated insulin secretion was measured 8 weeks post severe burns. Islets of the two groups were isolated and mRNA libraries were sequenced by the Illumina sequencing platform. The expressions of differentially expressed genes (DEGs) related to the cell cycle and the amounts of mitochondrial DNA were detected by quantitative real-time polymerase chain reaction after gene ontology, gene set enrichment analysis, and protein-protein network analysis. Hematoxylin-eosin staining of pancreatic tail tissue and adenosine triphosphate (ATP) assay of islets were performed. The levels of fasting blood glucose were significantly higher within 8 weeks post severe burns. Glucose-stimulated insulin secretion was impaired at the eighth week post severe burns. Totally 128 DEGs were selected. Gene ontology and gene set enrichment analysis indicated that the pathways related to the cell cycle, protein processing, and oxidative phosphorylation were downregulated. The expressions of DEGs related to the cell cycle showed a consistent trend with mRNA sequencing data, and most of them were downregulated post severe burns. The cell mass of the burn group was less than that of the sham group. Also, the concentration of ATP and the amount of mitochondrial DNA were lower in the burn group. In the model of severe-burned mice, disorders in glucose metabolism persist for 8 weeks after burns, which may be related to low islet cell proliferation, downregulation of protein processing, and less ATP production.

Survival of HT29 cancer cells is influenced by hepatocyte growth factor receptor inhibition through modulation of self-DNA-triggered TLR9-dependent autophagy response.

HGFR activation drives the malignant progression of colorectal cancer, and its inhibition displays anti-autophagic activity. The interrelated role of HGFR inhibition and TLR9/autophagy signaling in HT29 cancer cells subjected to modified self-DNA treatments has not been clarified. We analyzed this complex interplay with cell metabolism and proliferation measurements, TLR9, HGFR and autophagy inhibitory assays and WES Simple Western blot-based autophagy flux measurements, gene expression analyses, immunocytochemistry, and transmission electron microscopy. The overexpression of MyD88 and caspase-3 was associated with enhanced HT29 cell proliferation, suggesting that incubation with self-DNAs could suppress the apoptosis-induced compensatory cell proliferation. HGFR inhibition blocked the proliferation-reducing effect of genomic and hypermethylated, but not that of fragmented DNA. Lowest cell proliferation was achieved with the concomitant use of genomic DNA, HGFR inhibitor, and chloroquine, when the proliferation stimulating effect of STAT3 overexpression could be outweighed by the inhibitory effect of LC3B, indicating the putative involvement of HGFR-mTOR-ULK1 molecular cascade in HGFR inhibitor-mediated autophagy. The most intense cell proliferation was caused by the co-administration of hypermethylated DNA, TLR9 and HGFR inhibitors, when decreased expression of both canonical and non-canonical HGFR signaling pathways and autophagy-related genes was present. The observed ultrastructural changes also support the context-dependent role of HGFR inhibition and autophagy on cell survival and proliferation. Further investigation of the influence of the studied signaling pathways and cellular processes can provide a basis for novel, individualized anti-cancer therapies.

Proliferation of osteoblast precursor cells on the surface of TiO2 nanowires anodically grown on a β-type biomedical titanium alloy

Studies have shown that anodically grown TiO2 nanotubes (TNTs) exhibit excellent biocompatibility. However, TiO2 nanowires (TNWs) have received less attention. The objective of this study was to investigate the proliferation of osteoblast precursor cells on the surfaces of TNWs grown by electrochemical anodization of a Ti-35Nb-7Zr-5Ta (TNZT) alloy. TNT and flat TNZT surfaces were used as control samples. MC3T3-E1 cells were cultured on the surfaces of the samples for up to 5 days, and cell viability and proliferation were investigated using fluorescence microscopy, colorimetric assay, and scanning electron microscopy. The results showed lower cell proliferation rates on the TNW surface compared to control samples without significant differences in cell survival among experimental conditions. Contact angles measurements showed a good level of hydrophilicity for the TNWs, however, their relatively thin diameter and their high density may have affected cell proliferation. Although more research is necessary to understand all the parameters affecting biocompatibility, these TiO2 nanostructures may represent promising tools for the treatment of bone defects and regeneration of bone tissue, among other applications.

Maternal Gut Microbiome Decelerates Fetal Endochondral Bone Formation by Inducing Inflammatory Reaction.

To investigate the effect of the maternal gut microbiome on fetal endochondral bone formation, fetuses at embryonic day 18 were obtained from germ-free (GF) and specific-pathogen-free (SPF) pregnant mothers. Skeletal preparation of the fetuses’ whole bodies did not show significant morphological alterations; however, micro-CT analysis of the tibiae showed a lower bone volume fraction in the SPF tibia. Primary cultured chondrocytes from fetal SPF rib cages showed a lower cell proliferation and lower accumulation of the extracellular matrix. RNA-sequencing analysis showed the induction of inflammation-associated genes such as the interleukin (IL) 17 receptor, IL 6, and immune-response genes in SPF chondrocytes. These data indicate that the maternal gut microbiome in SPF mice affects fetal embryonic endochondral ossification, possibly by changing the expression of genes related to inflammation and the immune response in fetal cartilage. The gut microbiome may modify endochondral ossification in the fetal chondrocytes passing through the placenta.

PD12-11 CASTRATION IMPACT ON PATTERN RECOGNITION RECEPTORS (PRRS) BOOSTS TOLL-LIKE RECEPTOR-4 EXPRESSION IN AN IMMUNOCOMPETENT BLADDER CANCER MALE MODEL

You have accessJournal of UrologyCME1 May 2022PD12-11 CASTRATION IMPACT ON PATTERN RECOGNITION RECEPTORS (PRRS) BOOSTS TOLL-LIKE RECEPTOR-4 EXPRESSION IN AN IMMUNOCOMPETENT BLADDER CANCER MALE MODEL Leonardo Reis Leonardo ReisLeonardo Reis More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002538.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Among diverse Pattern Recognition Receptors (PRRs), the Toll-Like Receptor-4 (TLR-4) is the key urothelial trigger for innate immune response and plays a central role as Bacillus Calmette Guerin (BCG) main target. Also, its gene polymorphism and expression are associated to bladder cancer (BCa) prognosis. Androgen activation promotes immunotolerance, playing an immunoregulatory role, though by unknown mechanisms. METHODS: We described an efficient male immunocompetent BCa animal model. Intact (sham) versus castrated male Fisher-344 rats were evaluated in 2 scenarios: A) Carcinogenesis: After randomization to SHAM (n=5) and Castration (n=5), carcinogenesis was induced by four intravesical doses of 1.5 mg/kg n-methyl-n-nitrosourea (MNU) every 15 days. B) Treatment: After ultrasonographic confirmed MNU induced papillary BCa on week 8, rats were randomized to SHAM (n=5) and Castration (N=5) and offered 6 weekly intravesical treatment of 106 CFU of BCG in 0.2 ml saline. After 15 weeks of protocol, animals were euthanized and the urinary bladders submitted to histopathology, immunohistochemistry (IHC), and Western blotting (WB). Urothelial cell proliferation was measured by Ki-67 IHC and TLR-4 expression quantified by IHC and WB. RESULTS: Castration induced higher TLR-4 urothelial expression (p=.007) and anticarcinogenic effect with less urothelial tumors (60 vs. 80%) and lower urothelial cell proliferation compared to intact animals (p=.008). In the intravesical BCG treatment setting, castration has potentialized the BCG activation of TLR-4 (p=.007) with no residual in situ carcinoma compared to intact animals, suggesting the potential to amplify the immune initiation phase activated by BCG. CONCLUSIONS: To our knowledge, this is the first description of TLR-4 urothelial expression hormonal modulation. The described male immunocompetent animal model will help to improve the knowledge of urothelial cancer gender diversities and PRRs modulations with treatment implications. Source of Funding: none © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e199 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Leonardo Reis More articles by this author Expand All Advertisement PDF DownloadLoading ...

Characterization of the Structure, Stability, Bioactivity of Recombinant FGF19

Fibroblast growth factor 19 (FGF19) is a member of the endocrine fibroblast growth factor family, secreted in the small intestine. FGF19 binds to the fibroblast growth factor receptor 4 (FGFR4) in the presence of β klotho to downregulate the secretion of bile acid. All endocrine FGFs, including FGF19 are unstable. In this study, we examine structure, stability, and bioactivity using a wide range of biophysical and biochemical experiments. The protein has been successfully overexpressed in Escherichia coli (E. coli), and optimal conditions for storage have been established. Results of thermal denaturation of recombinant FGF19, using circular‐dichroism and differential scanning calorimetry, suggest that the thermal unfolding of the protein is reversible, and the Tm (melting temperature; temperature at which half of the protein is denatured) was found to be 55 oC. Far UV circular‐dichroism data indicate that the backbone of the protein is predominantly in the beta‐sheet conformation. In addition, cell proliferation and cell metabolism data show that FGF19 exhibits low cell proliferation, but significant metabolic activity. These results will be discussed in details.

The SUMO E3 Ligase MdSIZ1 Sumoylates a Cell Number Regulator MdCNR8 to Control Organ Size.

Plant growth and organ size putatively associated with crop yield are regulated by a complex network of genes including ones for controlling cell proliferation. The gene fw2.2 was first identified in tomatoes and reported to govern fruit size variation through controlling cell division. In this study, we isolated a putative ortholog of the tomato fw2.2 gene from apple, Cell Number Regulator 8 (MdCNR8). Our functional analysis showed that MdCNR8 may control fruit size and root growth. MdCNR8 was mediated by the SUMO E3 ligase MdSIZ1, and SUMOylation of MdCNR8 at residue-Lys39 promoted the translocation of MdCNR8 from plasma membrane to the nucleus. The effect of MdCNR8 in inhibiting root elongation could be completely counteracted by the coexpression of MdSIZ1. Moreover, the lower cell proliferation of apple calli due to silencing MdSIZ1 could be rescued by silencing MdCNR8. Collectively, our results showed that the MdSIZ1-mediated SUMOylation is required for the fulfillment of MdCNR8 in regulating cell proliferation to control plant organ size. This regulatory interaction between MdSIZ1 and MdCNR8 will facilitate understanding the mechanism underlying the regulation of organ size.

Influence of Diabetes-Induced Glycation and Oxidative Stress on the Human Rotator Cuff.

Most shoulder rotator cuff tears (RCTs) are caused by non-traumatic age-related rotator cuff degeneration, of which hyperglycemia is a risk factor due to its glycation reaction and oxidative stress. We aimed to identify the influence of diabetes-induced glycation and oxidative stress in patients with non-traumatic shoulder RCTs. Twenty patients, aged over 50 years, with non-traumatic shoulder RCTs participated in this study. Patients with a history of diabetes mellitus or preoperative HbA1c ≥ 6.5% were assigned to the diabetic group (n = 10), and the rest to the non-diabetic group (n = 10). Cell proliferation; expression of genes related to oxidative stress, glycation reaction, inflammation, and collagen; intracellular reactive oxygen species (ROS) levels; and apoptosis rates were analyzed. The diabetic group had significantly lower cell proliferation than the non-diabetic group. In the diabetic group, the mRNA expression levels of NOX1, NOX4, IL6, RAGE, type III collagen, MMP2, TIMP1, and TIMP2 were significantly higher; type I collagen expression was significantly lower; and the rate of ROS-positive cells and apoptotic cells, as well as the expression of advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE), was significantly higher. In conclusion, hyperglycemia caused by diabetes mellitus increased AGE and RAGE expression, and led to increased NOX expression, ROS production, and apoptosis in the human rotator cuff. This provides scope to find a preventive treatment for non-traumatic RCTs by inhibiting glycation and oxidative stress.

Ibuprofen-Loaded Electrospun PCL/PEG Nanofibrous Membranes for Preventing Postoperative Abdominal Adhesion

Electrospun nanofibrous membranes are a widely used physical barrier for reducing postoperative adhesion. However, these physical barriers could not prevent adhesion formation completely. Because a high-intensity inflammation occurs in the surgical area, the presence of relevant drugs to control such an inflammation is desperately needed. In this study, we fabricated an electrospun composite ibuprofen-loaded poly(ethylene glycol) (PEG)/polycaprolactone (PCL) nanofibrous membrane (NFM) to prevent abdominal adhesions. This membrane aimed to act as a barrier between the abdominal wall and surrounding tissues, without interrupting mass transfer and normal wound healing. Among various fabricated composite NFMs, PCL/25PEG-6% NFMs showed the lowest fiber diameter (448.8 ± 124.4 nm), the smallest pore size (<2 μm), and moderate ultimate stress and strain. The PCL/25PEG-6% NFMs had the lowest water contact angle (≈75°) and the highest drug profile release (≈80%) within 14 days. Furthermore, in vitro toxicity examination of PCL/25PEG-6% toward fibroblast cells demonstrated a cell viability of ≈82% after 3 days, proving its prolonged antiadhesion ability. In addition, the low number of adherent cells with a rounded shape and low cell proliferation on these NFMs indicated their special antiadhesive effects. Collectively, these results indicated that the PCL/25PEG-6% membrane might be a suitable barrier to prevent abdominal adhesion.

Multi-site desmoplastic small round cell tumors are genetically related and immune-cold

Desmoplastic small round cell tumor (DSRCT) is a highly aggressive soft tissue sarcoma that is characterized by the EWSR1-WT1 fusion protein. Patients present with hundreds of tumor implants in their abdominal cavity at various sites. To determine the genetic relatedness among these sites, exome and RNA sequencing were performed on 22 DSRCT specimens from 14 patients, four of whom had specimens from various tissue sites. Multi-site tumors from individual DSRCT patients had a shared origin and were highly related. Other than the EWSR1-WT1 fusion, very few secondary cancer gene mutations were shared among the sites. Among these, ARID1A, was recurrently mutated, which corroborates findings by others in DSRCT patients. Knocking out ARID1A in JN-DSRCT cells using CRISPR/CAS9 resulted in significantly lower cell proliferation and increased drug sensitivity. The transcriptome data were integrated using network analysis and drug target database information to identify potential therapeutic opportunities in EWSR1-WT1-associated pathways, such as PI3K and mTOR pathways. Treatment of JN-DSRCT cells with the PI3K inhibitor alpelisib and mTOR inhibitor temsirolimus reduced cell proliferation. In addition, the low mutation burden was associated with an immune-cold state in DSRCT. Together, these data reveal multiple genomic and immune features of DSRCT and suggest therapeutic opportunities in patients.

The AT1 Receptor Blocker Telmisartan Reduces Intestinal Mucus Thickness in Obese Mice

The angiotensin II (type 1) (AT1) receptor blocker telmisartan (TEL) is beneficial for the treatment of individuals suffering from metabolic syndrome. As we have shown that TEL has an impact on gut microbiota, we investigated here whether TEL influences gut barrier function. C57BL/6N mice were fed with chow or high-fat diet (HFD) and treated with vehicle or TEL (8 mg/kg/day). Mucus thickness was determined by immunohistochemistry. Periodic Acid-Schiff staining allowed the number of goblet cells to be counted. Using western blots, qPCR, and immunohistochemistry, factors related to mucus biosynthesis (Muc2, St6galnac), proliferation (Ki-67), or necroptosis (Rip3) were measured. The influence on cell viability was determined in vitro by using losartan, as the water solubility of TEL was too low for in vitro experiments. Upon HFD, mice developed obesity as well as leptin and insulin resistance, which were prevented by TEL. Mucus thickness upon HFD-feeding was diminished. Independent of feeding, TEL additionally reduced mucus thickness. Numbers of goblet cells were not affected by HFD-feeding and TEL. St6galnac expression was increased by TEL. Rip3 was increased in TEL-treated and HFD-fed mice, while Ki-67 decreased. Cell viability was diminished by using >1 mM losartan. The anti-obese effect of TEL was associated with a decrease in mucus thickness, which was likely not related to a lower expression of Muc2 and goblet cells. A decrease in Ki-67 and increase in Rip3 indicates lower cell proliferation and increased necroptosis upon TEL. However, direct cell toxic effects are ruled out, as in vivo concentrations are lower than 1 mM.

Mechanical Stress Signaling in Pancreatic Cancer Cells Triggers p38 MAPK- and JNK-Dependent Cytoskeleton Remodeling and Promotes Cell Migration via Rac1/cdc42/Myosin II.

Our findings highlight that mechanical stress activated the p38 MAPK and JNK signaling axis and stimulated pancreatic cancer cell migration via upregulation of the actin cytoskeleton remodelers cdc42 and Rac1.

Long non-coding RNA HAGLROS facilitates tumorigenesis and progression in hepatocellular carcinoma by sponging miR-26b-5p to up-regulate karyopherin α2 (KPNA2) and inactivate p53 signaling

ABSTRACT Hepatocellular carcinoma (HCC) is a principal histologic type of liver cancer with high mortality. Long non-coding RNAs (LncRNAs) exert a crucial role in the pathogenesis of human tumors. To date, the functions and mechanisms of lncRNA HAGLROS in HCC are rarely reported. In the current study, HAGLROS exhibited a higher level in HCC tissues and cells. HAGLROS expression was positively correlated with tumor size, TNM stage and poor clinical prognosis. Loss-of-function experiments showed that knockdown of HAGLROS significantly lowered cell proliferation, cell cycle progression, migration, invasion and epithelial to mesenchymal transition (EMT) but induced apoptosis in vitro. Consistently, tumor growth in the nude mice was effectively slowed by the depletion of HAGLROS. Mechanistically, HAGLROS could competitively bind to miR-26b-5p to prevent the suppression of miR-26b-5p on its downstream target gene Karyopherin α2 (KPNA2). Moreover, the inhibitory effects of HAGLROS knockdown on cell malignant behaviors were reversed due to the miR-26b-5p down-regulation or KPNA2 overexpression. It was interesting to note that HAGLROS inactivated p53 signaling through targeting miR-26b-5p/KPNA2. In conclusion, our results demonstrated that HAGLROS contributed to the malignant progression of HCC via serving as a sponge for miR-26b-5p to facilitate KPNA2 expression and inactivate p53 signaling. Targeting HAGLROS/miR-26b-5p/KPNA2 axis might be an alternative therapeutic strategy for HCC patients.

MiR-557 downregulation lowered cell proliferation and malignancy in glioblastoma by targeting ADAM17

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To examine the role of miR-557 in the pathogenesis and development of glioblastoma (GBM) and its potential regulatory mechanism.&#x0D; Methods: Dysregulation of miR-557 in GBM cells was determined using quantitative (real-time) PCR (qPCR). Cell proliferative ability, migratory activity and invasive ability were measured using the MTT colorimetric assay, wound healing assay and Transwell chambers assay. The direct target mRNA of miR-557 was predicted, and further validated using TargetScan and luciferase assay, respectively.&#x0D; Results: Compared with human astrocytes (HAs), the downregulation of miR-557 was observed in human GBM cell lines. In U-251MG and A172 cells that overexpressed miR-557 mimics, the level of proliferation was significantly reduced, the wound width was larger, and the number of invaded cells wan decreased than that of NC mimics. Predictive results from TargetScan and results of luciferase assay demonstrated that miR-557 directly targets the 3’-untranslated region (3’-UTR) of ADAM17. In A172 cells and U-251MG cells, the upregulation E-cadherin (E-cad) and the downregulation of N- cadherin (N-cad) and vimentin (Vim) were caused by miR-557 mimics as compared with NC mimics. Expression of ADAM17, NICD, HES1, and EGFR was downregulated by miR-557 mimics and upregulated by miR-557 inhibitors in A172 cells and U-251MG cells.&#x0D; Conclusion: Downregulation of miR-557 accelerates GBM cell growth and malignancy by directly targeting ADAM17 3’-UTR, providing a prognostic and potential therapeutic factor for new drug discovery in GBM.&#x0D; &#x0D; &#x0D; &#x0D;

Effect of Hypoxia-Inducible Factor-1α on Osteogenesis of Titanium Dioxide Nanotube Bone Marrow Mesenchymal Stem Cells with Different Diameters Under Periodic Tensile Stress.

Bone marrow mesenchymal stem cells (BMSC) have the ability to multi polarize with multiple tropisms and participate in tissue remodeling. This study assessed the effect of titanium dioxide nanotubes with different diameters on ossification of BMSC cells and HIF-1α expression in BMSC ossification. Titanium dioxide nanotubes with different diameters were prepared and then the following groups were set according to the size of pressure; Ti group, NT10 group, NT30 group, and NT60 group. Analysis of cell morphology was done by fluorescence microscope, while adhesion and proliferation were assessed by MTT assay. Moreover, ALP activity, collagen secretion and outer matrix mineralization and expression of HIF-1α, VEGF, and TWIST were assessed by RT-PCR and Western blot. The P3 generation of BMSC cells was successfully obtained. Three types of nanotubes were arranged regularly and contact angle showed NT60<NT30<NT10<Ti, protein adsorption presented NT10>Ti>NT30>NT60 (P < 0.05). Cells from NT30 and N60 groups showed obvious expansion with pseudopodia and pseudo plates of cells. Cell adhesion showed changes in sizes of NT10>Ti>NT30>NT66. NT60 group showed lower cell proliferation and higher ALP activity and collagen secretion than the other groups. NT30 and NT60 group presented higher mineralization level, larger diameter, and higher degree of promotion. The NT30 group presented lowest content of HIF-1α (0.12 ± 0.03), VEGF (0.013 ± 0.004), and TWIST (0.014 ± 0.003). Inoculation of BMSCs on titanium dioxide nanotubes of different diameters under cyclical tensile stress environment can promote growth of BMSC cells in a diameter-dependent manner.

MiR-140-Modified Bone Marrow Mesenchymal Stem Cells Enhance Chemotherapy Sensitization in Cervical Squamous Cell Carcinoma Cells via Targeting Microtubule Depolymerization Protein 1 (STMN1)

Effect of bone marrow mesenchymal stem cells (BMSCs) on the sensitivity of chemotherapy drugs and microRNAs (miRNAs) is still unclear. This study explored the role of miR-140 modified BMSCs in enhancing paclitaxel sensitivity of cervical squamous cell carcinoma (CSCC). Hela cells, BMSCs cells, and miR-140 modified BMSCs were transfected with miR-140 mimic, miR-140 inhibitor, and miR-140 NC, respectively. After transfection, they were co-cultured with Hela cells and paclitaxel to set up miR-140 mimic group, miR-140 inhibitor group, and miR-140 NC group (without paclitaxel treatment) followed by analysis of cell proliferation, apoptosis, ROS generation, expression of miR-140, STMN1, STAT3, p-STAT3, and survivin mRNA and protein. miR-140 inhibitor group showed lowest cell proliferation number and expressions of miR-140, STMN1, STAT3, p-STAT3, and survivin mRNA and protein with highest number of apoptotic cells, which were all reversed in miR-140 mimic group. There was a positive correlation between STMN1 level and miR-140 expression (r = 0.449, P = 0.108). BMSCs modified with miR-140 inhibitor can target STMN1, enhance the sensitivity of chemotherapy drugs, and exert an inhibitory effect on CSCC cell proliferation, suggesting that STMN1 might be a therapy target for treating CSCC.

Clinical outcomes of follicular tumor of uncertain malignant potential of the thyroid: real-world data.

Thyroid tumors arising from follicular cells can generally be divided into malignant and benign tumors. However, some cases are difficult to clearly diagnose whether they are benign or malignant. Therefore, in the most recent version of World Health Organization (WHO) classification, some borderline lesions such as follicular tumor of uncertain malignant potential (FT-UMP), well-differentiated tumor of uncertain malignant potential (WDT-UMP), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were proposed. In this study, we investigated the clinical aspects, including the prognosis, of FT-UMP patients. We investigated the clinical features of 339 patients with FT-UMP. On ultrasound, 68% of the tumors were diagnosed as intermediate, and only 5% of those tumors were diagnosed as malignant. On cytology, 40% of the tumors were diagnosed as follicular neoplasm, and only 1% of these were suspected to be or diagnosed as malignancy. The diagnosis was based on questionable capsular invasion for 332 patients, questionable vascular invasion for 2 patients, and both for 5 patients. Eighty-six percent of the tumors showed low cell proliferation activity. To date, five patients (1%) have shown distant recurrence during postoperative follow-up and underwent various treatments such as radioactive iodine therapy, orthopedic surgery, and denosumab injection. None of these patients have died due to thyroid carcinoma. Our findings suggest that FT-UMP is generally an indolent disease, but some patients show distant recurrence. Physicians should carefully follow patients, although it remains unknown how long they should be observed after surgery.

Carcinoma de células acinares de glándulas salivales: estudio clínico e histopatológico de 12 casos

Objective:Acinic cell carcinoma (CCA) is the third malignant epithelial tumor of the salivary glands in adults; low-grade tumor of malignancy, composed of neoplastic cells with serous acinar differentiation. The objective of this work was to analyze 12 cases of CCA according to their location, clinical characteristics, histological and immunohistochemical pattern and cell types, following the latest classification of the World Health Organization. Methods: The study included 12 cases of CCA from the files of salivary tumor biopsies of our work team, corresponding to the period 1997-2020. A numerical code was used to identify the samples, preserving the identity of the patients. Histological sections of the paraffin-embedded biopsies were evaluated with H/E, PAS and Toluidine blue and immunostained with the monoclonal antibodies pancytokeratin AE1 / AE3, Ki67, MUC-1 and mammaglobin. Results: The most frequent histologic pattern was the solid type as a single pattern or integrated with other patterns of lesser development, with almost exclusive location in the parotid gland and more frequent in women. Cells like normal acinar serocytes predominated in the solid growth pattern. The most frequent cell type in the microcystic patternwas the nonspecific glandular cell together with a lower proportion of acinar and intercalated duct-like cells. The papillary-cystic pattern was lined by nonspecific glandular cells. No clear cells found. With Ki67 a low cell proliferation was demonstrated in all the cases studied. Cell labeling for MUC-1 was grade 1 positive (less than 10% immunoreactive cells) and negative for mammaglobin.Conclusions: Patient follow-up is a priority because CCA tends to recur and metastasize and its behavior can become aggressive. We must deepen the study of its proliferative capacity as a treatment and prognosis tool, especially with immunohistochemistry and standardized molecular biology methods.