Protein kinase N1 promotes proliferation and invasion of liver cancer

xlomafota13 shared this article with you from Inoreader Protein kinase N1 promotes proliferation and invasion of liver cancer Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):651. doi: 10.3892/etm.2021.10083. Epub 2021 Apr 19. ABSTRACT Protein kinase (PK) N1, also called PKC-related protein 1, participates in the proliferation, invasion and metastasis of various malignant tumors. However, the role of PKN1 in liver cancer remains to be elucidated. The present study investigated the expression of PKN1 using immunohistochemistry in surgical specimens from 36 patients and analyzed the correlation with VEGF, microvascular density (MVD), cell proliferation index (Ki67) and clinicopathological parameters. PKN1 was highly expressed in hepatocellular carcinoma (HCC) and was positively correlated with histological grading of HCC, Ki67 expression and MVD. PKN1 expression in moderately and poorly differentiated HCC was significantly higher compared with highly differentiated HCC. Expression of PKN1 was positively correlated with Ki67 and MVD, and Ki67 expression was positively correlated wi th MVD. The effects of PKN1 on proliferation, invasion and apoptosis of liver cancer cells were detected in vitro. Cell viability, migration and invasion were reduced and the apoptosis rate was significantly improved when PKN1 expression was silenced in liver cancer cells. Thus, PKN1 serves an important role in the development and progression of liver cancer. Inhibition of PKN1 activity may provide a promising therapeutic target for liver cancer. PMID:33968181 | PMC:PMC8097187 | DOI:10.3892/etm.2021.10083 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Interleukin-1 induces receptor activator of nuclear factor-κB ligand-independent osteoclast differentiation in RAW264.7 cells

xlomafota13 shared this article with you from Inoreader Interleukin-1 induces receptor activator of nuclear factor-κB ligand-independent osteoclast differentiation in RAW264.7 cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):640. doi: 10.3892/etm.2021.10072. Epub 2021 Apr 16. ABSTRACT Interleukin-1 (IL-1) is a pro-inflammatory cytokine which induces bone destruction in various diseases, such as osteoporosis and rheumatoid arthritis. RAW264.7 cells are frequently used in studies as osteoclast precursors, however it remains unclear whether IL-1 can induce osteoclast differentiation from RAW264.7 cells without the stimulation of receptor activator of nuclear factor-κB ligand (RANKL). Hence, the present study aimed to investigate the effects of IL-1 on the formation of osteoclasts from RAW264.7 cells. The cell viability was determined via the Cell Counting Kit-8 (CCK-8) assay. Protein and gene expression were measured by western blotting and reverse transcription-quantitative PCR, respectively. Tartrate-resistant acid phosphatase (TRAP) staining and the resorption pit assay were performed to determine the formation and activity of osteoclasts. A significantly increased quantity of osteoclasts were found in the IL-1 group compared with the control group, and also in the RANKL+IL-1 group compared with the RANKL group. In addition IL-1 significantly increased both the protein and mRNA expression of specific genes associated with osteoclastogenesis, including nuclear factor of activated T cells cytoplasmic 1, matrix metalloprotein-9, cathepsin K and TRAP. The findings of the present study suggested that IL-1 can induce osteoclast differentiation and upregulate the quantity of osteoclasts differentiated from RAW264.7 cells. These results may lay a foundation for further study of diseases involving inflammation-associated bone loss. The combined blockade of IL-1 and RANKL may be effective for the prevention of inflammatory bone loss. PMID:33968171 | PMC:PMC8097200 | DOI:10.3892/etm.2021.10072 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

miR-221-3p and miR-222-3p regulate the SOCS3/STAT3 signaling pathway to downregulate the expression of NIS and reduce radiosensitivity in thyroid cancer

xlomafota13 shared this article with you from Inoreader miR-221-3p and miR-222-3p regulate the SOCS3/STAT3 signaling pathway to downregulate the expression of NIS and reduce radiosensitivity in thyroid cancer Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):652. doi: 10.3892/etm.2021.10084. Epub 2021 Apr 19. ABSTRACT The expression levels of microRNA (miR)-221-3p and miR-222-3p in thyroid cancer have been found to be upregulated compared with those in normal tissues. The present study aimed to determine the effects and potential underlying mechanisms of miR-221-3p and miR-222-3p on the regulation of radioactive iodine (131I) uptake and radiosensitivity of thyroid cancer cells. The potential regulatory target genes of miR-221-3p and miR-222-3p were predicted by bioinformatics analysis, and reverse transcription-quantitative polymerase chain reaction was used to verify miR-221-3p, miR-222-3p and target gene expression levels in thyroid cancer tissues and cell lines. Overexpression of miR-221-3p or miR-222-3p in cell models was performed using lentivirus infection. Knockdown of miR-221-3p and miR-222-3p in cells was achieved using oligonucleotide inhib itor transfection. Western blotting was used to analyze the expression levels of target proteins. In addition, the effects of miR-221-3p and miR-222-3p on the radiosensitivity of thyroid cancer cells were verified using a colony formation assay. The results of the present study revealed that the expression levels of miR-221-3p and miR-222-3p were significantly upregulated, while the expression levels of suppressor of cytokine signaling 3 (SOCS3) were downregulated in thyroid cancer tissues. Furthermore, miR-221-3p and miR-222-3p overexpression downregulated the expression levels of SOCS3, E-cadherin and solute carrier family 5 member 5 (NIS), and upregulated the expression levels of phosphorylated STAT3 and vimentin. Following the overexpression of miR-221-3p or miR-222-3p in the FTC133 and TPC1 cell lines, their radiosensitivity was suppressed. In conclusion, the findings of the present study suggested that miR-221-3p and miR-222-3p may downregulate the expression levels of NIS and promote radioresistance. The potential mechanism was hypothesized to be associated with the miR-221-3p and miR-222-3p targeting of the SOCS3 gene, which may subsequently activate the STAT3 signaling pathway. PMID:33968182 | PMC:PMC8097237 | DOI:10.3892/etm.2021.10084 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Life-threatening complications of hyperemesis gravidarum

xlomafota13 shared this article with you from Inoreader Life-threatening complications of hyperemesis gravidarum Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):642. doi: 10.3892/etm.2021.10074. Epub 2021 Apr 16. ABSTRACT Hyperemesis gravidarum (HG) refers to severe nausea and emesis noted during pregnancy. However, no consensus exists on the specific diagnostic criteria that can be used for this condition. The aim of the present systematic review was to summarize the available evidence regarding the severe complications observed during HG with a heightened risk of fatality. A systematic search was conducted on PubMed, Cochrane Library, EMBASE and WILEY databases for the relevant publications regarding the severe and life-threatening complications of HG. The search terms were as follows: '(Hyperemesis gravidarum)' AND ('complications' OR 'severe' OR 'adverse pregnancy outcomes' OR 'stroke' OR 'seizures' OR 'Wernicke's encephalopathy' OR 'arrhythmias' OR 'pneumomediastinum' OR 'coagulopathy' OR 'electrolytic imbalance'). Abstracts, conference presentations, letters to the editor, studies written in languages other than English and editorials were all excluded. This search identified 43 studies analyzing life-threatening complications of HG, of which 11, seven, eight and 17 articles analyzed neurological, cardiovascular, thoracic and systemic complications, respectively. Reports on life-threatening complications were exceptionally rare in HG. The most frequent severe complications noted were Wernicke's encephalopathy, electrolyte imbalance and vitamin K deficiency. The low mortality rate for patients with HG over the last decade could be explained by the high efficiency of modern therapy, and the precise management of every complication according to current guidelines. PMID:339 68173 | PMC:PMC8097228 | DOI:10.3892/etm.2021.10074 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anticancer activity of bergenin against cervical cancer cells involves apoptosis, cell cycle arrest, inhibition of cell migration and the STAT3 signalling pathway

xlomafota13 shared this article with you from Inoreader Anticancer activity of bergenin against cervical cancer cells involves apoptosis, cell cycle arrest, inhibition of cell migration and the STAT3 signalling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):653. doi: 10.3892/etm.2021.10085. Epub 2021 Apr 19. ABSTRACT [This retracts the article DOI: 10.3892/etm.2019.7380.]. PMID:33968183 | PMC:PMC8097232 | DOI:10.3892/etm.2021.10085 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Upregulation of long non-coding RNA MYU promotes proliferation, migration and invasion of esophageal squamous cell carcinoma cells

xlomafota13 shared this article with you from Inoreader Upregulation of long non-coding RNA MYU promotes proliferation, migration and invasion of esophageal squamous cell carcinoma cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):644. doi: 10.3892/etm.2021.10076. Epub 2021 Apr 18. ABSTRACT Esophageal squamous cell carcinoma (ESCC) is a common malignant tumour type of the digestive system. Long non-coding RNA (lncRNA) c-Myc upregulated (MYU), also known as VPS9 domain-containing 1 antisense 1, was recently discovered. However, the expression of lncRNA MYU in ESCC and its role in tumour progression have remained elusive. In the present study, the expression of lncRNA MYU, Ki-67 and the epithelial-mesenchymal transition-related proteins E-cadherin and Vimentin in ESCC tissues was detected by reverse transcription-quantitative PCR. The expression of Ki-67, E-cadherin and Vimentin in ESCC tissues was also detected by immunohistochemistry. A small interfering RNA plasmid was employed to establish a TE-2 cell line with knockdown on lncRNA MYU. The results indicated that the expression of lncRNA MYU was higher in ESCC tissues than in normal adjacent tissues and that upregulation of lncRNA MYU was a potential biomarker for poor prognosis. The results also suggested that the expression levels of lncRNA MYU were correlated with the histological grade, lymph node metastasis and TNM stage (P<0.05). Silencing of lncRNA MYU expression inhibited the proliferation, migration and invasion, while the expression of lncRNA MYU increased as cell proliferation increased. In addition, the mRNA expression of Vimentin and Ki-67 was decreased in TE-2 cells after lncRNA MYU was knocked down, while E-cadherin mRNA expression was elevated. In conclusion, the present results indicated that lncRNA MYU may regulate the proliferation, migration and invasion of ESCC cells, and may serve as a prognostic biomarker for ESCC. PMID:33968175 | PMC:PMC8097213 | DOI:10.3892/etm.2021.10076 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Apatinib inhibits gastric carcinoma development by regulating the expression levels of IL-17 via the Bax/Bcl-2 signaling pathway

xlomafota13 shared this article with you from Inoreader Apatinib inhibits gastric carcinoma development by regulating the expression levels of IL-17 via the Bax/Bcl-2 signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):654. doi: 10.3892/etm.2021.10086. Epub 2021 Apr 19. ABSTRACT Gastric carcinoma is a common type of gastrointestinal tumor with high morbidity and mortality rates. IL-17 is a newly discovered cytokine that has been reported to serve an important role in the development of gastric carcinoma. The potential effect of apatinib on IL-17 expression levels in the development of gastric carcinoma has been rarely reported. The present study aimed to investigate the potential mechanism of IL-17 and apatinib in the development of gastric carcinoma. A total of 30 tumor and para-carcinoma tissues were collected from 30 patients with gastric carcinoma between January 2019 and December 2019 and the expression levels of IL-17 in the tissues were analyzed by reverse transcription-quantitative PCR and western blotting. An in vitro model of gastric carcinoma was also established using the HGC-27 cell line, in which the cells were divided into control, IL-17, IL-17-apatinib and apatinib groups. The expression levels of IL-17, Bax, Bcl-2 and caspase-3 were analyzed using reverse transcription-quantitative PCR and western blotting. An MTT assay and flow cytometry were used to analyze the proliferation and apoptosis of HGC-27 cells, respectively, and a Transwell assay was used to analyze the invasive ability of HGC-27 cells. The results revealed that the expression levels of IL-17 were significantly upregulated in the gastric carcinoma tissues compared with the para-carcinoma tissues. In vitro, IL-17 treatment promoted the proliferation and invasive ability of HGC-27 cells, but inhibited the apoptosis with the significantly downregulated expression levels of Bax and caspase-3 and the upregulated expression levels of Bcl-2 than control group. Conversely, apatinib treatment significantly inhibited the proliferative and invasive abilities of HGC-27 cells, but promoted cell apoptosis in the IL-17 a nd IL-17-apatinib groups.. Collectively, the present results suggested that the upregulation of IL-17 may be associated with the occurrence and development of gastric carcinoma. The findings indicated that apatinib may inhibit gastric carcinoma development by regulating IL-17 expression via the Bax/Bcl-2 signaling pathway. Therefore, the present findings may enhance the current knowledge of the effect of apatinib on gastric carcinoma cells. PMID:33968184 | PMC:PMC8097188 | DOI:10.3892/etm.2021.10086 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hypoxia-inducible factor-1α regulates PI3K/AKT signaling through microRNA-32-5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis

xlomafota13 shared this article with you from Inoreader Hypoxia-inducible factor-1α regulates PI3K/AKT signaling through microRNA-32-5p/PTEN and affects nucleus pulposus cell proliferation and apoptosis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):646. doi: 10.3892/etm.2021.10078. Epub 2021 Apr 18. ABSTRACT Intervertebral disc degeneration and resulting low back pain arises from the programmed apoptosis of nucleus pulposus cells (NPCs). Recent studies show that hypoxia-inducible factor-1α plays a vital role in the etiology and pathogenesis of disc degeneration. However, the underlying mechanism of HIF-1α in NPCs is unclear. The present study identified 994 significant differentially expressed miRNAs by analyzing microarray data downloaded from the Gene Expression Omnibus database. MicroRNA(miR)-32-5p expression was 2.81-fold upregulated in NPCs compared with that of the healthy control tissues (P<0.05). A total of 331 significant differentially expressed mRNAs were identified, and PTEN was downregulated in NPCs of non-degenerative disc tissues from young patients. miR-32-5p was predicted to target the PTEN 3'-untranslated region (UTR). To confir m these results, in-vitro experiments investigating the molecular function of miR-32-5p and PTEN were performed. Furthermore, hypoxia induced miR-32-5p and PTEN expression. HIF-1α inhibited NPC proliferation and promoted cell apoptosis by regulating miR-32-5p and PTEN. miR-32-5p promoted NPC proliferation and decreased cell apoptosis. Next, it was verified whether miR-32-5p targeted the PTEN 3'-UTR using dual-luciferase reporter assays. Finally, it was observed that PI3K/AKT/mTOR signaling pathway was upregulated by a miR-32-5p mimic, which improved cell proliferation and decreased apoptosis. Importantly, PTEN was downregulated in these experiments; and inhibition of miR-32-5p had the opposite effect. Overall, these results demonstrate that HIF-1α regulates cell proliferation and apoptosis by controlling the miR-32-5p/PTEN/PI3K/AKT/mTOR axis in NPCs. PMID:33968177 | PMC:PMC8097185 | DOI:10.3892/etm.2021.10078 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of Porphyromonas gingivalis lipopolysaccharide on calcification of human umbilical artery smooth muscle cells co-cultured with human periodontal ligament cells

xlomafota13 shared this article with you from Inoreader Effect of <em>Porphyromonas gingivalis</em> lipopolysaccharide on calcification of human umbilical artery smooth muscle cells co-cultured with human periodontal ligament cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):655. doi: 10.3892/etm.2021.10087. Epub 2021 Apr 20. ABSTRACT Periodontitis is an independent risk factor for coronary heart disease. Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) was considered to be one of the main virulence factors. In addition, vascular smooth muscle cells transform into osteoblast-like cells in an arterial calcification process under chronic inflammatory conditions. The present study aimed to determine the calcification induced by Pg-LPS in human umbilical artery smooth muscle cells (HUASMCs) co-cultured with human periodontal ligament cells (HPDLCs). An in vitro co-culture system was established using Transwell inserts. HUASMC proliferation and alkaline phosphatase (ALP) activity were measured with a Cell Counting Kit-8 and an ALP kit, respectively. Calcium nodule formation was detected using alizarin red S staining. The effects of Pg-LPS on the mRNA expression of the calcification genes of ALP, core-binding factor α1 (Runx2) and bone sialoprotein (BSP) were assessed using reverse transcription-quantitative PCR. The results indicated that Pg-LPS increased HUASMC proliferation and ALP activity. Furthermore, among all of the groups, calcium nodule formation was most extensive in co-cultured cells in the mineralization-inducing medium containing Pg-LPS. In addition, the expression of specific osteogenic genes (Runx2, ALP and BSP) significantly increased in the presence of Pg-LPS and mineralization-inducing medium, which was further enhanced in co-culture with HPDLCs. In conclusion, co-culture with HPDLCs increased the effect of Pg-LPS to stimulate the calcification of HUASMCs. It was suggested that besides the inflammation, periodontitis may promote the occurrence of vascular calcification. The study indicated that periodontal treatment of subgingival scaling to reduce and/or control Porphyromonas gingivalis may decrease the occurrence o r severity of vascular calcification. PMID:33968185 | PMC:PMC8097230 | DOI:10.3892/etm.2021.10087 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Differential proteomic analysis of tibial subchondral bone from male and female guinea pigs with spontaneous osteoarthritis

xlomafota13 shared this article with you from Inoreader Differential proteomic analysis of tibial subchondral bone from male and female guinea pigs with spontaneous osteoarthritis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):633. doi: 10.3892/etm.2021.10065. Epub 2021 Apr 15. ABSTRACT A proteomic study on the tibial subchondral bone in guinea pigs with spontaneous osteoarthritis was performed to investigate the molecular alterations that occur in early osteoarthritis. A total of 132 healthy Hartley guinea pigs (aged 1 month; 66 female and 66 male) were randomly divided into 11 groups of six. Changes in articular cartilage and tibial subchondral bone were assessed using macroscopic examinations and micro-computed tomography. iTRAQ-integrated liquid chromatography-tandem mass spectrometry was used to identify differentially altered proteins in the tibial subchondral bone between 1- and 3-month-old guinea pigs, which were then validated using western blotting. A gradual progression of cartilage degeneration was observed in the knee joints of the subject animals from 5-11 months. With aging, the tibial subchondral trabecular bone a cquired more plate-like and less anisotropic properties, with increased bone mineral density, bone volume, trabecular thickness and numbers. The proteomic study identified 138 and 113 proteins significantly differentially expressed between 3- and 1-month old guinea pigs in both the male and female animals, respectively. Western blotting confirmed the increased expression of osteoblast-associated protein S100 calcium-binding protein A8 (S100A8) and the deregulated expression of osteoclast-associated proteins coronin 1A (CORO1A) and T-cell immune regulator 1 (TCIRG1) in the 3-month old guinea pigs in comparison to the 1-month old guinea pigs. Spontaneous cartilage degeneration in the knee joints of male Hartley guinea pigs tended to be more serious compared with the females during the development of osteoarthritis. Together, the results suggest that osteoblast-associated protein S100A8 and osteoclast-associated proteins CORO1A and TCIRG1 are potentially key regulators of early osteoar thritic development in tibial subchondral bone. PMID:33968164 | PMC:PMC8097192 | DOI:10.3892/etm.2021.10065 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.