Salidroside overcomes dexamethasone resistance in T-acute lymphoblastic leukemia cells

xlomafota13 shared this article with you from Inoreader Salidroside overcomes dexamethasone resistance in T-acute lymphoblastic leukemia cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):636. doi: 10.3892/etm.2021.10068. Epub 2021 Apr 15. ABSTRACT The aim of the present study was to analyze whether the use of salidroside (SAL) could overcome dexamethasone (DEX) resistance in T-acute lymphocytic leukemia cells. The human T-ALL DEX-resistant cell line, CEM-C1 and the DEX-sensitive cell line, CEM-C7 were used in the current study. The proliferation inhibition rates in these cells, treated with SAL and DEX alone, and in combination were detected using a Cell Counting Kit-8 assay, while the morphological changes of the cells were observed using an inverted microscope. Reverse transcription-quantitative PCR was used to detect the mRNA expression levels of the c-Myc and LC3 genes, while flow cytometry was used to detect the cell cycle distribution and the rate of apoptosis. In addition, western blot analysis was used to detect the protein expression levels of c-Myc, BCL-2, Bax, cleaved PARP and LC 3. and acridine orange staining was used to detect the changes in acidic autophagy vesicles. It was found that SAL could effectively inhibit cell proliferation and induce apoptosis in the CEM-C1 and CEM-C7 cells. In addition, SAL promoted the induction of autophagy. The protein expression levels of c-Myc in the CEM-C1 cells were significantly higher compared with that in the CEM-C7 cells. SAL downregulated the mRNA expression levels of the c-Myc gene and protein in a dose-dependent manner. This suggested that SAL could inhibit the proliferation of the CEM-C1 and CEM-C7 cells, induce apoptosis and autophagy and overcome DEX resistance in the CEM-C1 cells. The mechanism may be associated with the downregulation of c-Myc. PMID:33968167 | PMC:PMC8097222 | DOI:10.3892/etm.2021.10068 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Changes in peri-ocular anatomy and physiology in pseudoexfoliation syndrome (Review)

xlomafota13 shared this article with you from Inoreader Changes in peri-ocular anatomy and physiology in pseudoexfoliation syndrome (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):650. doi: 10.3892/etm.2021.10082. Epub 2021 Apr 19. ABSTRACT Pseudoexfoliation syndrome (PEX) is characterized by the deposition of proteinaceous material in the anterior ocular segment (resulting in ophthalmic pathologies such as glaucoma and increased risk of complications in cataract surgery), but also by several systemic manifestations. The involvement of peri-ocular tissues in PEX, including the eyelid skin, lacrimal gland, conjunctiva, orbital fat and vessels, as well as the optic nerve, has been reported by several previous studies. The peri-ocular effects of PEX include the development of eyelid laxity, conjunctival chalasis, tear film abnormalities, pronounced orbital fat atrophy in response to the administration of prostaglandin analogues in pseudoexfoliative glaucoma, deficient orbital vascular supply and biomechanical changes in both the eyeball and the optic nerve. These effects may have import ant clinical implications, including increased difficulty in cataract surgery, ocular surface disease and eyelid margin malpositions. PMID:33968180 | PMC:PMC8097227 | DOI:10.3892/etm.2021.10082 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Gallic acid suppresses colon cancer proliferation by inhibiting SRC and EGFR phosphorylation

xlomafota13 shared this article with you from Inoreader Gallic acid suppresses colon cancer proliferation by inhibiting SRC and EGFR phosphorylation Via Experimental and therapeutic medicine Exp Ther Med. 2021 Jun;21(6):638. doi: 10.3892/etm.2021.10070. Epub 2021 Apr 16. ABSTRACT The aim of the present study was to investigate the effects of gallic acid (GA) on the proliferation and apoptosis of colon cancer cells and to further clarify the mechanism of GA function associated with SRC and EGFR phosphorylation. HCT116 and HT29 cells were treated with different concentrations of GA for 24 h. Cell proliferation and apoptosis were analyzed using plate clone formation and flow cytometry assays, respectively. In addition, the expression of apoptosis-related proteins was examined by western blotting. Furthermore, the level of STAT3, AKT, SRC and EGFR phosphorylation was analyzed by western blotting and immunofluorescence. Subsequently, the SRC inhibitor PP2 and the EGFR inhibitor gefitinib were used to analyze the GA-associated mechanisms. In addition, a xenograft tumor model was established to confirm the effects of GA in viv o. The results indicated that GA inhibited cell proliferation and promoted cell apoptosis by upregulating the ratio of cleaved caspase-3/pro-caspase-3 and cleaved caspase-9/pro-caspase-9. Concurrently, GA decreased the level of phosphorylated (p)-SRC, p-EGFR, p-AKT and p-STAT3. Following treatment with PP2 and gefitinib in both cancer cell lines and animal model, GA was demonstrated to inhibit EGFR and SRC phosphorylation to downregulate STAT3 and AKT phosphorylation. In vivo, GA prevented tumor growth, promoted tumor apoptosis and decreased the level of p-SRC, p-EGFR, p-STAT3 and p-AKT. In conclusion, GA was indicated to suppress colon cancer proliferation by inhibiting SRC and EGFR phosphorylation. PMID:33968169 | PMC:PMC8097205 | DOI:10.3892/etm.2021.10070 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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.