Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1

xlomafota13 shared this article with you from Inoreader Sorafenib prevents the proliferation and induces the apoptosis of liver cancer cells by regulating autophagy and hypoxia-inducible factor-1 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):980. doi: 10.3892/etm.2021.10412. Epub 2021 Jul 12. ABSTRACT Sorafenib has been approved as a systemic drug for advanced liver cancer; however, the underlying mechanisms remain unclear. The present study aimed to investigate the effects of sorafenib on the proliferation, autophagy and apoptosis of HepG2 cells under hypoxia. Briefly, reverse transcription-quantitative PCR and western blotting was performed to quantify HIF-1, LC3II/I, mTOR and p70s6K expression levels. Cell proliferation was determined using the Cell Counting Kit-8 assay and the cell apoptosis rate was evaluated using flow cytometry. The results demonstrated that autophagy and apoptosis were induced by hypoxia, and that sorafenib further enhanced hypoxia-induced autophagy and apoptosis in HepG2 cells in a dose-dependent manner. Furthermore, the mechanism of sorafenib-mediated autophagy in liver cancer cell were investigated by using chloroqui ne (CQ). The results showed that CQ significantly inhibited autophagy by decreasing LC3II/LC3I ratio in HepG2 cells treated with sorafenib and/or hypoxia. By contrast, sorafenib could increase the expression of hypoxia-inducible factor-1 (HIF-1) and of the autophagy marker (LC3II/I) and decrease the expression of mammalian target of rapamycin and p70 ribosomal S6 kinase in HepG2 cells under normoxia and hypoxia conditions, suggesting that sorafenib could induce hypoxia and autophagy in liver cancer cells. In addition, sorafenib was demonstrated to prevent proliferation and induce apoptosis of HepG2 cells under normoxia and hypoxia. Sorafenib could also prevent the malignant behavior of HepG2 by inducing hypoxia and autophagy. In summary, the findings from the present study suggested that sorafenib may inhibit liver cancer progression by activating autophagy and HIF-1 signaling pathway. PMID:34345262 | PMC:PMC8311259 | DOI:10.3892/etm.2021.10412 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-138 inhibits hypoxia-induced proliferation of endothelial progenitor cells via inhibition of HIF-1α-mediated MAPK and AKT signaling

xlomafota13 shared this article with you from Inoreader MicroRNA-138 inhibits hypoxia-induced proliferation of endothelial progenitor cells via inhibition of HIF-1α-mediated MAPK and AKT signaling Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):996. doi: 10.3892/etm.2021.10428. Epub 2021 Jul 14. ABSTRACT [This retracts the article DOI: 10.3892/etm.2017.4091.]. PMID:34345278 | PMC:PMC8313887 | DOI:10.3892/etm.2021.10428 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-16 regulates lipopolysaccharide-induced inflammatory factor expression by targeting TLR4 in normal human bronchial epithelial cells

xlomafota13 shared this article with you from Inoreader MicroRNA-16 regulates lipopolysaccharide-induced inflammatory factor expression by targeting TLR4 in normal human bronchial epithelial cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):982. doi: 10.3892/etm.2021.10414. Epub 2021 Jul 12. ABSTRACT Acute lung injury (ALI) is mainly caused by inflammation and is associated with high mortality rates. Emerging evidence has suggested that microRNAs (miRNAs or miRs) serve a significant function in ALI. However, the fundamental mechanism underlying ALI remain to be fully elucidated. Although miR-16 has been reported to be involved in the occurrence and development of a number of diseases its association with ALI has not been previously investigated. Therefore, the present study aimed to explore the role of miR-16 in the lipopolysaccharide (LPS)-induced ALI model. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were measured by ELISA in the blood samples of rats with ALI and in the normal human bronchial epithelial (NHBE) cell line. The role of miR-16 in inflammation was evaluated using gene overexpression and silencing experiments in NHBE cells by reverse transcription-quantitative PCR. In addition, the expression levels of inflammatory factors TNF-α, IL-1β and IL-6 were also determined using ELISA. The potential interaction between miR-16 and TLR4 was assessed using bioinformatics analysis by the TargetScan database and then verified in 293T cells using luciferase reporter assay. The expression of miR-16 was notably decreased in the lung tissues of rats with LPS-induced ALI compared with the PBS treated-group. Additionally, the levels of the proinflammatory cytokines TNF-α, IL-1β and IL-6 were reduced following transfection of NHBE cells with miR-16 mimics compared with those in the miR-negative control group. Western blot analysis revealed that miR-16 overexpression could downregulate TLR4 expression in NHBE cells compared with that in the miR-NC group. Luciferase reporter assay confirmed that TLR4 may be directly targeted by miR-16. The effect of miR-16 on TLR4 was rescued in NHBE cells following treatment with LPS. Overall, these aforementioned findings suggest that miR-16 may serve a protective role against LPS-mediated inflammatory responses in NHBE cells by regulating TLR4, where this mechanism may be considered to be a novel approach for treating ALI in the future. PMID:34345264 | PMC:PMC8311244 | DOI:10.3892/etm.2021.10414 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

ChaC glutathione specific γ-glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis

xlomafota13 shared this article with you from Inoreader ChaC glutathione specific γ-glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):997. doi: 10.3892/etm.2021.10429. Epub 2021 Jul 15. ABSTRACT The present study aimed to determine the effects and mechanism of ChaC glutathione specific γ-glutamylcyclotransferase 1 (CHAC1) on cell viability and the sensitivity of prostate cancer cells to docetaxel. Compared with non-tumor human prostate epithelial RWPE-1 cells, the mRNA and protein levels of CHAC1 significantly decreased in two prostate cancer cell lines, DU145 and 22RV1, as measured by quantitative polymerase chain reaction and western blot analysis (P<0.05). The cell viability and glutathione (GSH) levels were significantly inhibited in prostate cancer cells following overexpression of CHAC1 (P<0.01), while they were significantly increased in DU145 cells transfected with CHAC1 siRNA (P<0.05), but not in 22RV1 cells (P>0.05). The expression levels of several endoplasmic reticulum (ER) stress-related factors were then measure d by western blot analysis. Following transfection with plasmid overexpressing CHAC1, ER markers, BIP and CHOP levels, were significantly upregulated (P<0.01), while GSH co-treatment decreased this upregulation. In addition, CHAC1 protein levels were significantly upregulated in cells treated with a ferroptosis activator (P<0.05). A liperflo reagent was then used to determine intracellular lipid peroxide levels. The intracellular lipid peroxides levels were significantly increased following CHAC1-overexpression (P<0.05), while GPX4 protein levels were significantly decreased (P<0.01). The cell viability was significantly inhibited (P<0.001) even with 1 nM docetaxel (DTX) and a plasmid overexpressing CHAC1, while the effect of inhibition was not significant at 1 nM of DTX alone (P>0.05). This inhibition was also eliminated following the addition of a ferroptosis inhibitor. In summary, CHAC1 may inhibit cell viability and increase the sensitivity of prostate cancer c ells to DTX. The cellular mechanism may involve the induction of ER stress and ferroptosis. The results of the present study identified a potentially novel therapeutic target for prostate cancer, which may be useful in patients with castration-resistant prostate cancer. PMID:34345279 | PMC:PMC8311285 | DOI:10.3892/etm.2021.10429 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hanta hemorrhagic fever with renal syndrome: A pathology in whose diagnosis kidney biopsy plays a major role (Review)

xlomafota13 shared this article with you from Inoreader Hanta hemorrhagic fever with renal syndrome: A pathology in whose diagnosis kidney biopsy plays a major role (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):984. doi: 10.3892/etm.2021.10416. Epub 2021 Jul 12. ABSTRACT Hantavirus infection belongs to a group of zoonoses rare in the Balkan Peninsula, causing two major syndromes, depending on the viral serotype involved: Hemorrhagic fever with renal syndrome (HFRS) also known as endemic nephropathy and cardiopulmonary syndrome (CPS). Because there is no specific treatment or vaccine for this condition approved in the USA or Europe, the key to minimizing the risk of adverse progression to chronic kidney disease, secondary hypertension or even death is primarily the recognition and early diagnosis of this condition with prompt therapeutic intervention. The aim of this study was to review the literature data on the epidemiology, pathogenesis and management of this disease and to identify several aspects related to the difficulties encountered in diagnosing this pathology, taking into consideration that the disease is not endemic in this geographical area. PMID:34345266 | PMC:PMC8311249 | DOI:10.3892/etm.2021.10416 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Suture repair of patellar inferior pole fracture: Transosseous tunnel suture compared with anchor suture

xlomafota13 shared this article with you from Inoreader Suture repair of patellar inferior pole fracture: Transosseous tunnel suture compared with anchor suture Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):998. doi: 10.3892/etm.2021.10430. Epub 2021 Jul 15. ABSTRACT Patellar inferior pole fracture is difficult to treat due to the inherent weakness of small comminuted distal fragments. However, suture fixation was recently introduced and reported. The aim of the present study was to evaluate and compare the clinical outcomes of two suture techniques, transosseous tunnel suture (TTS) and anchor suture (AS), for the fixation of patellar inferior pole fracture. A total of 35 patients with patellar inferior pole fracture treated at the Second Affiliated Hospital of Nanchang University (Nanchang, China) between June 2014 and April 2018 were retrospectively reviewed. Of these, 14 were treated with the TTS technique and 21 using AS fixation. The operation time, incision length and total cost were determined and compared. Functional outcomes were analyzed with the visual analog scale (VAS), Bostman and Lysholm scores and knee joint ranges of motion (ROMs). Postoperative complications were also observed and recorded. The mean follow-up was 22.6±9.7 and 18.7±5.9 months for TTS and AS, respectively. The groups were similar regarding age, sex, operative side and time to surgery. A smaller incision length and shorter operation time but higher hospital costs were observed in the AS group (P<0.01). For functional evaluation, there was no significant difference in VAS, Bostman and Lysholm scores or ROM between the 2 groups (P>0.05). No postoperative complications were observed in the TTS group. Only one patient in the AS group experienced a superficial minor wound infection. The TTS and AS techniques provided similarly satisfactory clinical outcomes for treating patellar inferior pole fracture. TTS had the advantage of cost-effectiveness due to saving anchors, while AS had a shorter operation time and a smaller incision length. PMID:34345280 | PMC:PMC8311267 | DOI:10.3892/etm.2021.10430 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The dynamic changes in the pattern of liver function tests in pregnant obese women

xlomafota13 shared this article with you from Inoreader The dynamic changes in the pattern of liver function tests in pregnant obese women Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):986. doi: 10.3892/etm.2021.10418. Epub 2021 Jul 13. ABSTRACT Obesity is an important problem in healthcare regarding gestating women. The objective of the present study was to highlight the impact that obesity has on the hepatic function in pregnant women by comparing the functional tests used in current practice. In addition, the aim was to identify possible predictors of liver damage by analyzing specific anthropometric data. The present study was descriptive, observational, retrospective, and based on the observation sheets found in the database of the Institute for the Health of the Mother and Child, the Obstetrics Gynecology Department of Polizu Hospital. Patients who presented for consultation in each trimester of pregnancy were included in the study. Demographic data taken into account included age, body mass index (BMI), provenance environment, anthropometric data: Abdominal circumference and the co mplete set of paraclinical data from which we extracted these specific liver tests: Aspartate aminotransferase (AST), alanine transferase (ALT), direct bilirubin (BD), serum albumin and gamma-glutamyl transferase (GGT). The present study included 157 patients divided into two groups, distributed as follows: Group A: 66 obese pregnant women (BMI >25 kg/m2) and group B: 91 patients with normal weight (BMI <25 kg/m2). Measurement of serum ALT and AST were the most useful tests for routine diagnosis of liver disease. The effects of pregnancy on serum levels of ALT and AST are controversial. In some studies, there was a slight increase in ALT and AST during the second and third trimesters, a fact confirmed by our study, albeit the result was not statistically significant Most published studies claim that serum ALT and AST levels do not change during pregnancy. In conclusion, obesity during pregnancy does not drastically influence liver function. However, patie nts with greater abdominal circumference are prone to developing minor hepatic cytolysis syndrome during the gestation period. The liver functional tests described in the aforementioned groups agree with the results provided by the specialized studies. PMID:34345268 | PMC:PMC8311227 | DOI:10.3892/etm.2021.10418 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Metabolites of intestinal microflora upregulate microRNA-200c-3p expression level to suppress airway epithelial inflammation via the IL6ST/JNK/STAT3 signaling pathway

xlomafota13 shared this article with you from Inoreader Metabolites of intestinal microflora upregulate microRNA-200c-3p expression level to suppress airway epithelial inflammation via the IL6ST/JNK/STAT3 signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):999. doi: 10.3892/etm.2021.10431. Epub 2021 Jul 15. ABSTRACT Intestinal microfloras are involved in various types of cancer; however, there is a limited amount of research into the involvement of metabolites of intestinal microflora (MIM) in asthmatic airway epithelial cells (AECs). The present study was designed to reveal the functions and mechanisms of MIM in the asthmatic inflammation of AECs. House dust mite (HDM)-induced asthma cell models were established and treated with mouse MIM. A MTT assay was used to investigate AEC viability, while reverse transcription-quantitative PCR and western blot analysis were used to measure the expression levels of miR-200c-3p, IL6ST, JNK and STAT3 in asthmatic AECs. ELISA was used to measure the concentration of IL-5 and IL-6. Furthermore, the targeting relationship between microRNA(miR)-200c-3p and IL6ST was investigated using a luciferase reporter gene assay. Compar ed with normal human bronchial epithelial cells, HDM-induced AECs had lower expression level of miR-200c-3p, higher mRNA and protein expression levels of IL6ST and an increase in IL-5 and IL-6 concentration. Both MIM and miR-200c-3p mimics suppressed the secretion of IL-5 and L-6 and promoted the proliferation of HDM-induced AECs. MIM could also upregulate miR-200c-3p and downregulate IL6ST and proteins in the JNK/STAT3 pathway. IL6ST was found to be a downstream target of miR-200c-3p. Inhibition of miR-200c-3p reversed the suppression of asthmatic inflammation by MIM. In summary, MIM upregulated miR-200c-3p expression level to reduce the protein and mRNA expression levels of IL6ST and suppress its downstream JNK/STAT3 signaling pathway, therefore inhibiting the asthmatic inflammation of AECs. PMID:34345281 | PMC:PMC8311286 | DOI:10.3892/etm.2021.10431 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Differences in epidemiology of patients with preeclampsia between China and the US (Review)

xlomafota13 shared this article with you from Inoreader Differences in epidemiology of patients with preeclampsia between China and the US (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1012. doi: 10.3892/etm.2021.10435. Epub 2021 Jul 15. ABSTRACT Preeclampsia (PE) is a complex complication that occurs during pregnancy. Studies indicated that morbidity from PE exhibits marked variations among geographical areas. Disparities in the incidence of PE between China and the US may be due to differences in ethnicity and genetic susceptibility, maternal age, sexual culture, body mass index, diet, exercise, multiple pregnancies and educational background. These epidemiological differences may give rise to differences between the two countries in terms of diagnostic and therapeutic criteria for PE. PE may be largely attributed to susceptibility genes and lifestyles, such as diet, body mass index and cultural norms regarding sexual relationships. The epidemiologic differences of patients with PE between the two countries indicated that appropriate prevention plans for PE require to be developed accor ding to local conditions. PMID:34345294 | PMC:PMC8311229 | DOI:10.3892/etm.2021.10435 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Expression profiling of genes in rheumatoid fibroblast-like synoviocytes regulated by Fas ligand via cDNA microarray analysis

xlomafota13 shared this article with you from Inoreader Expression profiling of genes in rheumatoid fibroblast-like synoviocytes regulated by Fas ligand via cDNA microarray analysis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1000. doi: 10.3892/etm.2021.10432. Epub 2021 Jul 15. ABSTRACT Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation in synovial tissues. Hyperplasia of synovial tissues leads to the formation of pannus that invades the joint cartilage and bone, resulting in joint destruction. Fas ligand (FasL), which is a member of the tumor necrosis factor superfamily, contributes to the pathogenesis of autoimmune diseases, including RA. The current study attempted to identify genes whose expressions in rheumatoid fibroblast-like synoviocytes (RA-FLS) were regulated by FasL, using cDNA microarray. A total of four individual lines of primary cultured RA-FLS were incubated either with recombinant human FasL protein or PBS as an unstimulated control for 12 h. Gene expression was detected using a microarray assay. The results revealed the expression profiles of genes in RA-FLS regulated by Fas and investigated the functions of the genes that were regulated. Among the genes in this profile, the mRNA expression changes of the following genes were indicated to be of note using RT-qPCR: Dual specificity phosphatase 6, epiregulin, interleukin 11, angiopoietin-like 7, protein inhibitor of activated STAT 2 and growth differentiation factor 5. These genes may affect the pathogenesis of RA by affecting apoptosis, proliferation, cytokine production, cytokine-induced inflammation, intracellular signaling, angiogenesis, bone destruction and chondrogenesis. To the best of our knowledge, the current study is the first study to reveal the expression profile of genes in RA-FLS regulated by FasL. The data demonstrated that FasL may regulate the expression of a number of key molecules in RA-FLS, thus affecting RA pathogenesis. Further studies of the genes detected may improve the understanding of RA pathogenesis and provide novel treatment targets for RA. PMID:34345282 | PMC:PMC8311246 | DOI:10.3892/etm.2021.10432 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.