Combination treatment with cisplatin, paclitaxel and olaparib has synergistic and dose reduction potential in ovarian cancer cells

xlomafota13 shared this article with you from Inoreader Combination treatment with cisplatin, paclitaxel and olaparib has synergistic and dose reduction potential in ovarian cancer cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):935. doi: 10.3892/etm.2021.10367. Epub 2021 Jul 1. ABSTRACT Ovarian cancer is the most lethal type of gynecological cancer. Due to its high heterogeneity and complicated pathological mechanisms, the 5-year survival rate of patients with ovarian cancer is <40%. Tumor cytoreductive surgery and systemic chemotherapy of platinum combined with paclitaxel are currently considered the gold standard for the treatment of ovarian cancer, and chemotherapy resistance has become a key constraint in improving the cure rate of ovarian cancer. Therefore, it is important to identify novel treatment methods and strategies for ovarian cancer. Targeted drugs can not only be used in combination with chemotherapy, but also act as maintenance therapy to promote patient survival time. PARP inhibitor is a novel type of ovarian cancer treatment targeted drug, which can induce an anticancer effect by inhibiting DNA damage and repa ir of ovarian cancer cells. The present study investigated the different effects of olaparib, cisplatin and paclitaxel in several dosages by single use and combinations on the proliferation of different human ovarian cancer cell lines, in order to verify the synergistic effects of the combinations of the three anticancer agents in pairs. The proliferation inhibitory rate of the cell lines was determined using a Cell Counting Kit-8 assay, while the combination index (CI) value of the combination of three agents in pairs was analyzed using Compusyn software. The proliferation was observed using a crystal violet assay, and the apoptosis ratio was measured via flow cytometry. The results of the present study revealed that the combination of cisplatin with olaparib group had a higher inhibition effect than each single group and had a higher dose-reduction index of >1 than the other two combinations at all concentrations in A2780 and OVCAR-3 cell lines. The difference in proliferation inhibition and induced apoptosis rate of A2780 cell lines was significant in the combination of cisplatin with olaparib group and the control group (P<0.01) at 0.25x IC50. For the OVCAR-3 cell line, the difference was also significant between two groups (P<0.05). The CI values in the A2780 cell line revealed significant differences between the low-dose group (0.0625x, 0.125x and 0.25x IC50) and the high-dose group (0.5x, 1.0x and 2.0x IC50) for the group that received the combination of cisplatin with olaparib (P<0.05). The present study highlighted that the group receiving a combination of cisplatin with olaparib exhibited the most significant synergistic effects among the three combinations, particularly at low doses. PMID:34335884 | PMC:PMC8290430 | DOI:10.3892/etm.2021.10367 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Attitude of the surgical approach in hyperparathyroidism: A retrospective study

xlomafota13 shared this article with you from Inoreader Attitude of the surgical approach in hyperparathyroidism: A retrospective study Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):959. doi: 10.3892/etm.2021.10391. Epub 2021 Jul 7. ABSTRACT The present study constitutes a retrospective study for patients with hyperparathyroidism surgically operated on at the Department of Thoracic Surgery of the Central Military Emergency University Hospital 'Dr. Carol Davila', Bucharest, Romania (SUUMC), over a period of 6 years. The study aimed to elucidate the diagnostic and surgical attitude for an effective treatment, practiced at SUUMC, Romania. The study group included 55 patients: 41 women and 14 men, diagnosed at the endocrinology department, who underwent various personalized surgeries (Kocher modified incision) for typical and ectopic locations of parathyroid pseudotumor formations (hyperplasia and parathyroid adenoma), to cure the disease. The recommended protocol was followed by immediate and 30-day postoperative evaluation which showed normalization of the blood tests, and improved clini cal and imaging anomalies. In conclusion, the thoracic surgeon has the necessary knowledge to perform surgery at the cervical, thoracic-cervical and mediastinal levels. Postoperative, the results of laboratory tests for calcium (Ca) and parathyroid hormone (PTH) gradually returned to normal, as can be seen from the statistical study. PMID:34335901 | PMC:PMC8290464 | DOI:10.3892/etm.2021.10391 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-146a overexpression alleviates intestinal ischemia/reperfusion-induced acute lung injury in mice

xlomafota13 shared this article with you from Inoreader MicroRNA-146a overexpression alleviates intestinal ischemia/reperfusion-induced acute lung injury in mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):937. doi: 10.3892/etm.2021.10369. Epub 2021 Jul 1. ABSTRACT Previous studies have shown that microRNAs (miRs), such as miR-146a play an important role in the pathogenesis of intestinal ischemia/reperfusion (I/R)-induced injury; however, the role of miR-146a in intestinal I/R-induced acute lung injury has not been elucidated. An intestinal I/R-induced injury mouse model was established in the present study by clamping the superior mesenteric artery and expression levels of miR-146a in intestinal and lung tissue samples were evaluated using reverse transcription-quantitative PCR (RT-qPCR). Intestinal and lung histopathological characteristics in mice with intestinal I/R-induced injury were assessed by hematoxylin and eosin staining, and mRNA and protein expression levels in intestinal and lung tissue samples were evaluated using RT-qPCR and western blotting, respectively. miR-146a expression was significantly downregulated in the intestinal and lung tissue samples of mice with intestinal I/R-induced injury. Intestinal I/R injury-induced histopathological changes in the lung and intestines, and pulmonary edema in mice transduced with an adenoviral miR-146a-overexpression vector (the miR-146a overexpression group) were alleviated. mRNA expression levels of TNF-α, IL-1β, IFN-γ and TGF-β1, and protein expression levels of TNF receptor-associated factor 6, phosphorylated-p65 NF-κB, cleaved caspase-3 and cleaved caspase-9 in lung and intestinal tissue samples were downregulated in I/R-miR-146a-overexpressing mice, compared with those from the I/R-negative control group. Thus, the present study identified that pre-treatment with the miR-146a overexpression vector alleviated intestinal I/R-induced acute lung injury in mice. PMID:34335886 | PMC:PMC8290461 | DOI:10.3892/etm.2021.10369 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hyperthyroidism management during pregnancy and lactation (Review)

xlomafota13 shared this article with you from Inoreader Hyperthyroidism management during pregnancy and lactation (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):960. doi: 10.3892/etm.2021.10392. Epub 2021 Jul 7. ABSTRACT Thyroid dysfunction is a significant public health issue, affecting 5-10 more women compared to men. The estimated incidence is up to 12% and only for women the treatment rises up to 4.3 billion dollars annually. Thyroid pathology can have a major impact on female fertility and it can only be detected when preconception tests are performed. Untreated or poorly treated hyperthyroidism in a mother can affect the fetal development and pregnancy outcome. Between 0.1 and 0.4% of the pregnancies are affected by clinical hyperthyroidism. Thyroid dysfunction is associated with higher rates of pregnancy loss. Hyperthyroidism can complicate fetal health problems intrauterinely and in the neonatal period. The TSH receptor is stimulated by TSH and HCG which has a similar structure. This can lead to gestational thyrotoxicosis. Hyperthyroidism can be treated wit h propylthiouracil or methimazole and in selected cases, surgical treatment or radioactive iodine can be chosen. In pregnancy, the most used treatment is represented by propylthiouracil which can be used from the first trimester. The aim of this review is to assess the current data regarding the impact of thyroid dysfunction on pregnancy and to synthesize the treatment options during pregnancy and lactation. PMID:34335902 | PMC:PMC8290437 | DOI:10.3892/etm.2021.10392 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Applicability and implementation of the collagen-induced arthritis mouse model, including protocols (Review)

xlomafota13 shared this article with you from Inoreader Applicability and implementation of the collagen-induced arthritis mouse model, including protocols (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):939. doi: 10.3892/etm.2021.10371. Epub 2021 Jul 1. ABSTRACT Animal models of rheumatoid arthritis (RA) are essential for studying the pathogenesis of RA in vivo and determining the efficacy of anti-RA drugs. During the past decades, numerous rodent models of arthritis have been evaluated as potential models and the modeling methods are relatively well-developed. Among these models, the collagen-induced arthritis (CIA) mouse model is the first choice and the most widely used because it may be generated rapidly and inexpensively and is relatively similar in pathogenesis to human RA. To date, there have been numerous classic studies and reviews discussing related pathogeneses and modeling methods. Based on this knowledge, combined with the latest convenient and effective methods for CIA model construction, the present review aims to introduce the model to beginners and clarify important details regardin g its use. Information on the origin and pathogenesis of the CIA model, the protocol for establishing it, the rate of successful arthritis induction and the methods used to evaluate the severity of arthritis are briefly summarized. With this information, it is expected that researchers who have recently entered the field or are not familiar with this information will be able to start quickly, avoid unnecessary errors and obtain reliable results. PMID:34335888 | PMC:PMC8290431 | DOI:10.3892/etm.2021.10371 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Corneal endothelial changes induced by pars plana vitrectomy with silicone oil tamponade for retinal detachment

xlomafota13 shared this article with you from Inoreader Corneal endothelial changes induced by pars plana vitrectomy with silicone oil tamponade for retinal detachment Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):961. doi: 10.3892/etm.2021.10393. Epub 2021 Jul 7. ABSTRACT Silicone oils are effective intraocular tamponade agents in the treatment of severe retinal detachments, because they maintain the adhesion between neurosensory retina and retinal pigment epithelium, thanks to their ability to remove aqueous humor from the surface of the retina. To understand their effectiveness, it is important to know the characteristics of silicone oils. Patients should be closely monitored due to many complications associated with intraocular silicon oil, such as inflammatory reaction, raised intraocular pressure, refraction disorders, cataract, and emulsification. This study presents corneal endothelial changes and some intraocular complications caused by silicone oil used as an intraocular tamponade agent in the case of vitrectomy for complex retinal detachments. The aim of the study was to demonstrate the damage of corneal e ndothelial cells after the use of silicone oil in patients with retinal detachment surgery. Endothelial specular microscopy measurements were performed and the changes of the following parameters demonstrated the corneal damage: Mean cell density, coefficient of variation, average cell area, percentage of hexagonal cells, and corneal thickness. Three months postoperatively, a statistically significant decrease was observed in the following analyzed parameters: Mean cell density (P=0.04), and percentage of hexagonal cells (P=0.002); the remaining parameters also had a linear decrease (coefficient of variation, average cell area), but were statistically insignificant. Three months postoperatively, the corneal thickness presented a slight increase. Silicone oils are powerful tools when used wisely and within the limits of their use. These are often recommended in cases of severe detachment of the retina in patients at high risk of experiencing intraoperative complications. PMID:< a href="https://pubmed.ncbi.nlm.nih.gov/34335903/?utm_source=Inoreader&utm_medium=rss&utm_content=1ba2t84FK1dz-fAY5g7-lbp7yzA9oSsgU2XptRGyGkyx-wIkEA&ff=20210802165103&v=2.14.5" target="_blank" rel="noopener" class="underlink bluelink">34335903 | PMC:PMC8290465 | DOI:10.3892/etm.2021.10393 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinicopathological features of gastric inflammatory myofibroblastic tumor: Report of five cases

xlomafota13 shared this article with you from Inoreader Clinicopathological features of gastric inflammatory myofibroblastic tumor: Report of five cases Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):948. doi: 10.3892/etm.2021.10380. Epub 2021 Jul 1. ABSTRACT The present study reported on the histomorphological observations and immunohistochemical features of five cases of gastric inflammatory myofibroblastic tumor (IMT). Loosely arranged fat fusiform myofibroblast-fibroblasts and diffusely or patchily distributed inflammatory cells, which formed a diverse morphological structure, were observed. In the mucous vascular structure, mucoid or collagenous areas, fibromatosis- or scar-like lesions were generally <10 mm in size and both had diffuse or patchy plasma cells, lymphocytes and other inflammatory-cell infiltration backgrounds. The immunophenotype was vimentin- and smooth muscle actin-positive with pan-cytokeratin, desmin and calponin expression and CD34-positive foci; furthermore, three cases were positive for anaplastic lymphoma kinase expression. Gastric IMT is rare, with unique histopathologica l changes and corrosion-like invasion of the smooth muscle of the stomach wall, blood vessels, nerves and adipose tissue. It should be differentiated from a variety of spindle cell tumor types and tumor-like lesions. PMID:34335890 | PMC:PMC8290396 | DOI:10.3892/etm.2021.10380 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The effects of compound centella formula on OxInflammation and silent information regulator 1 in a high-fat diet/streptozotocin-induced diabetic kidney disease rat model

xlomafota13 shared this article with you from Inoreader The effects of compound centella formula on OxInflammation and silent information regulator 1 in a high-fat diet/streptozotocin-induced diabetic kidney disease rat model Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):962. doi: 10.3892/etm.2021.10394. Epub 2021 Jul 7. ABSTRACT The Chinese decoction compound centella formula (CCF) is clinically effective against diabetic kidney disease (DKD), but the exact mechanism remains unclear. The present study aimed to investigate the effects of CCF on OxInflammation and silent information regulator 1 (SIRT1) levels in rats with streptozotocin (STZ)-induced diabetes. Sprague-Dawley rats were divided into CCF, losartan, diabetic control (DC) and normal control (NC) groups (n=7). Except for the NC, all subgroups of rats were fed a high-fat diet for 112 days and received a single intraperitoneal injection of 35 mg/kg STZ on day 29. All rats were sacrificed on day 112. High-performance liquid chromatography was performed to analyse asiaticoside, astragaloside and triptolide levels in CCF (0.3400, 0.0640 and 0.0001 mg/ml, respectively). Fasting blood glucose, urine protein-to-creatinine ratio, serum creatinine and blood urea nitrogen were quantified. Periodic acid Schiff staining, H&E staining and transmission electron microscopy were used to examine kidney pathological changes. The mRNA and protein expression levels of SIRT1 in renal tissues were analysed by reverse transcription-quantitative PCR, western blotting and immunohistochemistry. Oxidative stress was evaluated by measuring the levels of superoxide dismutase (SOD), malondialdehyde (MDA) and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in renal tissues. TNF-α and NF-κB p65 subunit in renal tissues were assessed for inflammation. Compared with the rats in the NC group, the rats in the DC group exhibited renal injury with proteinuria, decreased expression levels of SIRT1 and SOD (P<0.01) and increased levels of MDA, NOX4, TNF-α and NF-κB p65 (P<0.01). CCF treatment reduced proteinuria (P<0.01), alleviated renal damage, decreased MDA, NOX4, TNF-α and NF-κB p65 levels (P< 0.01), increased SOD levels (P<0.05) and increased SIRT1 mRNA and protein expression levels (P<0.01). The present study indicates that CCF effectively protects the kidney from diabetes by inhibiting OxInflammation and upregulating SIRT1. PMID:34335904 | PMC:PMC8290408 | DOI:10.3892/etm.2021.10394 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of intermittent fasting on liver physiology and metabolism in mice

xlomafota13 shared this article with you from Inoreader Effects of intermittent fasting on liver physiology and metabolism in mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):950. doi: 10.3892/etm.2021.10382. Epub 2021 Jul 5. ABSTRACT A broad spectrum of health benefits from intermittent fasting have been reported in studies on animal models and human subjects. However, the underlying mechanisms of these beneficial effects remain largely elusive. The present study aimed to explore the effects and potential mode of action of intermittent fasting in mouse models with a focus on the liver. C57BL/6 mice were subjected to intermittent fasting or ad libitum feeding as controls. It was determined that 12 h of daily intermittent fasting for 30 days significantly reduced the cumulative food intake compared with that in mice with ad libitum feeding. Fasting resulted in a significantly reduced liver mass but only had a minimal effect on bodyweight. The effects on the liver by 30 days of fasting were not reversed by subsequent ad libitum refeeding for 30 days. Among the measured blood biochemical parameters, the levels of blood glucose were decreased, while the levels of alkaline phosphatase were increased in fasting mice. Of note, targeted metabolic profiling revealed global elevation of metabolites in the livers of fasting mice. These metabolic molecules included adenosine triphosphate, nicotinamide adenine dinucleotide phosphate (NADP), reduced NADP and succinate, which are essentially involved in the citric acid cycle and oxidative phosphorylation. Thus, it was concluded that daily 12 h of intermittent fasting for one month significantly reduced the liver weight of mice, which is associated with enhanced liver metabolism. PMID:34335892 | PMC:PMC8290466 | DOI:10.3892/etm.2021.10382 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Application of TGF-β1, TIMP-1 and TIMP-2 small interfering RNAs can alleviate CCl4-induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines

xlomafota13 shared this article with you from Inoreader Application of TGF-β1, TIMP-1 and TIMP-2 small interfering RNAs can alleviate CCl<sub>4</sub>-induced hepatic fibrosis in rats by rebalancing Th1/Th2 cytokines Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):963. doi: 10.3892/etm.2021.10395. Epub 2021 Jul 7. ABSTRACT The present study aimed to investigate the effects of TGF-β1, tissue inhibitor of metalloproteinase (TIMP)-1 small interfering (si)RNA and TIMP-2 siRNA on hepatic fibrosis in rats and explore the T helper (Th)1/Th2 balance. Moreover, IFN-γ, IL-4 and IL-13 are the main cytokines associated with Th1/Th2 responses and have significant influence on the progression of hepatic fibrosis. The expression levels of IFN-γ, IL-4 and IL-13 in rats with hepatic fibrosis that were treated with siRNAs against the aforementioned molecules were measured using various techniques including immunohistochemical staining, western blotting and reverse transcription-quantitative PCR. The principal outcomes revealed the downregulation of IFN-γ and the upregulation of IL-4 and IL-13 in the model group compared with the normal group. Moreover, the expression of IFN-γ was significantly increased, while IL-4 and IL-13 demonstrated no significant difference in the TGF-β1 siRNA treatment group compared with the model group. The TIMP-1 and TIMP-2 siRNA treatment groups exhibited significantly increased expression levels of IFN-γ, but lower expression levels of IL-4 and IL-13 compared with the model group. These results indicated that TIMP-1 and TIMP-2 were improved antifibrotic targets compared with TGF-β1. PMID:34335905 | PMC:PMC8290469 | DOI:10.3892/etm.2021.10395 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.