Emodin inhibits the proliferation of papillary thyroid carcinoma by activating AMPK

xlomafota13 shared this article with you from Inoreader Emodin inhibits the proliferation of papillary thyroid carcinoma by activating AMPK Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1075. doi: 10.3892/etm.2021.10509. Epub 2021 Jul 28. ABSTRACT Emodin has been demonstrated to serve antitumor roles in a variety of tumor types, but the effect of emodin on papillary thyroid carcinoma and its molecular mechanisms remain unclear. In the current study, the role of emodin on papillary thyroid carcinoma was analyzed in vitro and in vivo. TPC-1 cells were treated with emodin (0, 10, 25 or 50 µM), and cell viability and apoptosis were detected using Cell Counting Kit-8 and flow cytometry, respectively. The expression levels of AMPK-associated proteins were examined using western blot analysis. To study the effect of emodin on the AMPK pathway, AMPK activator, AICAR and an AMPK inhibitor, Dorsomorphin, were used in TPC-1 cells. In vivo, mice were used to confirm the mechanism of emodin on papillary thyroid carcinoma. The results of the current study indicated that emodin trea tment induced cell apoptosis and cell cycle arrest in TPC-1 cells. Furthermore, the inhibitory effect increased in a dose dependent manner. Following emodin treatment, the cell viability of TPC-1 cells was significantly decreased, and apoptosis rate increased (P<0.05). Furthermore, the expression levels of AMPK were increased in the emodin group compared with the control group (P<0.05). Similar effects were observed following AMPK activator treatment in TPC-1 cells. Following AMPK activator treatment, cell proliferation and the cell cycle were inhibited. Also, the AMPK inhibitor was demonstrated to mediate the therapeutic effect of emodin. In addition, the results of the present study demonstrated that emodin inhibited the MEK/ERK pathway. Additionally, the in vivo results of the current study were consistent with those in vitro. In conclusion, the current study demonstrated that the administration of Emodin inhibited the proliferation of papillary thyroid cancer cells via activating AMPK pathway activity. PMID:34447468 | PMC:PMC8355685 | DOI:10.3892/etm.2021.10509 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Herbal melanin induces interleukin-1β secretion and production by human THP-1 monocytes via Toll-like receptor 2 and p38 MAPK activation

xlomafota13 shared this article with you from Inoreader Herbal melanin induces interleukin-1β secretion and production by human THP-1 monocytes via Toll-like receptor 2 and p38 MAPK activation Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1081. doi: 10.3892/etm.2021.10515. Epub 2021 Jul 29. ABSTRACT Herbal melanin (HM), extracted from Nigella sativa, is known for its immunogenic properties through the modulation of cytokine production via Toll-like receptor (TLR)4. TLRs play a crucial role in the host defense through the regulation of innate and adaptive immune responses. However, the potential effect of HM on the production of interleukin-1β (IL-1β), the main immunoregulatory cytokine secreted by activated monocytes, has not been reported. The present study aimed to investigate the effects of HM on IL-1β secretion and production, detected by enzyme-linked immunosorbent assay, western blotting and mRNA expression monitored by reverse transcription-PCR, in human monocytes and a monocytic cell line, THP-1. Signaling pathways involved in the HM-induced IL-1β production was investigated in the THP-1 cells. It was shown that HM upregul ated the IL-1β mRNA in the THP-1 cells and induced the secretion of IL-1β in the monocytes and THP-1 cells, in a dose-dependent manner, compared to the untreated cells. HM increased the protein expression of IL-1β, TLR2, the main receptor for IL-1β production, and activated p38 mitogen-activated protein kinase (MAPK), a key mediator for stress-induced IL-1β gene expression. The blockade of the p38 MAPK pathway, with the pharmacological inhibitor SB202190, and TLR2 receptor with a neutralization antibody, resulted in the decrease of HM-induced IL-1β production in THP-1 cells. The TLR4 receptor blockade also decreased HM-induced IL-1β production, but to a lesser extent than TLR2 blockade. In conclusion, the present study demonstrated that HM stimulates IL-1β production in monocytes and THP-1 cells, in a TLR2/p38 MAPK pathway-dependent manner, suggesting promising immunoregulatory potentials of HM against inflammatory-associated diseases. PMID:34447474 | PMC:PMC8355711 | DOI:10.3892/etm.2021.10515 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-590-3p relieves hypoxia/reoxygenation induced cardiomyocytes apoptosis and autophagy by targeting HIF-1α

xlomafota13 shared this article with you from Inoreader MicroRNA-590-3p relieves hypoxia/reoxygenation induced cardiomyocytes apoptosis and autophagy by targeting HIF-1α Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1077. doi: 10.3892/etm.2021.10511. Epub 2021 Jul 28. ABSTRACT Autophagy and apoptosis are key factors in myocardial ischemia/reperfusion (I/R) injury. MicroRNAs (miRNAs or miRs) participate in occurrence and development of myocardial I/R injury by regulating autophagy and apoptosis. The purpose of the present study was to investigate the role of miR-590-3p in the regulation of autophagy and apoptosis in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. Following 6 h hypoxia and 6 h reoxygenation in primary rat cardiomyocytes, miR-590-3p was downregulated. Transfection of miR-590-3p mimic inhibited the increased autophagy and apoptosis following H/R treatment. Subsequent experiments demonstrated that miR-590-3p regulated induction of autophagy and apoptosis by targeting hypoxia inducible factor (HIF)-1α. Forced expression of HIF-1α rescued the protective effect of miR-590-3p on H/R-induced cardiomyocytes . In summary, the present study showed that miR-590-3p exhibited a protective effect on H/R-induced cardiomyocyte injury and may be a novel target for the treatment of myocardial ischemia disease. PMID:34447470 | PMC:PMC8355641 | DOI:10.3892/etm.2021.10511 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway

xlomafota13 shared this article with you from Inoreader Benazepril hydrochloride protects against doxorubicin cardiotoxicity by regulating the PI3K/Akt pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1082. doi: 10.3892/etm.2021.10516. Epub 2021 Jul 29. ABSTRACT Doxorubicin (DOX) stimulates the generation of reactive oxygen species, thereby impairing mitochondrial functions. Angiotensin-converting enzyme inhibitors (ACEIs) have been identified to exhibit protective effects on cardiovascular diseases. The present study aimed to test the hypothesis that an ACEI benazepril hydrochloride (HCl) may protect against DOX-induced cardiotoxicity. The DOX injury model was established using rat embryonic cardiac myoblast cells (H9c2 cell line) treated with DOX in vitro. H9c2 cells were treated with benazepril-HCl, DOX or a mixture of DOX and benazepril-HCl to measure the activities of myocardial enzymes including lactate dehydrogenase (LDH), superoxide dismutase, catalase and glutathione peroxidase, in addition to the concentration of malondialdehyde in the culture medium. Cells without any treatment were use d as a control. DOX treatment increased the levels of activity of myocardial enzymes in H9c2 cells compared with those in the untreated control cells. Additionally, co-treatment with benazepril-HCl significantly reduced the levels of apoptosis occurring due to DOX-mediated cellular damage. The mechanistic experiment revealed that pretreatment with benazepril-HCl counteracted the DOX-induced oxidative stress and suppressed the activation of apoptosis via the PI3K/Akt signaling pathway. By contrast, an Akt inhibitor (MK2206) inhibited the protective effects of benazepril-HCl against DOX-induced H9c2 cell injury, as revealed by increased LDH release in H9c2 cells. These results suggested that benazepril-HCl may potentially be administered as an adjuvant for DOX in long-term clinical use. PMID:34447475 | PMC:PMC8355712 | DOI:10.3892/etm.2021.10516 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A steroid-induced osteonecrosis model established using an organ-on-a-chip platform

xlomafota13 shared this article with you from Inoreader A steroid-induced osteonecrosis model established using an organ-on-a-chip platform Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1070. doi: 10.3892/etm.2021.10504. Epub 2021 Jul 28. ABSTRACT Bone microvascular endothelial cells (BMECs) constitute the central part of the femoral head's intramural microenvironment network and have an essential role in the development of steroid-induced osteonecrosis of the femoral head. Recently, the rapid development of microfluidic technology has led to innovations in the fields of chemistry, medicine and life sciences. It is now possible to use microfluidics organ-on-a-chip techniques to assess osteonecrosis. In the present study, BMECs were cultured on a microfluidic organ-on-a-chip platform to explore the pathogenesis of femoral-head necrosis. The aim of the present study was to explore the effects of different interventions on BMECs and study the pathogenesis of steroid-induced osteonecrosis through a microfluidic organ-on-a-chip platform. Methods including SU-8 lithography were used to produce a microfluidic organ-on-a-chip and human umbilical vein endothelial cells (HUVECs) were used to test whether it was possible to culture cells on the chip. Subsequently, a set of methods were applied for the isolation, purification, culture and identification of BMECs. Hydroxyapatite (HA) was used for co-culture, dexamethasone was used at different concentrations as an intervention in the cells and icariin was used for protection. BMECs were isolated and cultured from the femoral head obtained following total hip arthroplasty and were then inoculated into the microfluidic organ-on-a-chip for further treatment. In part I of the experiment, HUVECs and BMECs both successfully survived on the chip and a comparison of the growth and morphology was performed. HA and BMECs were then co-cultured for comparison with the control group. The cell growth was observed by confocal microscopy after 24 h. In part II, the effects of different concentrations of glucocorticoid (0.4 or 0.6 mg/ml dexametha sone) and the protection of icariin were evaluated. The morphology of BMECs and the cleaved caspase-3/7 content were observed by immunofluorescence staining and confocal microscopy after 24 h. In the microfluidic organ-on-a-chip, the response of the cells was able to be accurately observed. In part I, at the same concentration of injected cells, BMECs exhibited improved viability compared with HUVECs (P<0.05). In addition, it was indicated that HA was not only able to promote the germination and growth of BMECs but also improve the survival of the cells (P<0.05). In part II, it was identified that dexamethasone was able to induce BMECs to produce cleaved caspase 3/7; the caspase 3/7 content was significantly higher than that in the blank control group (P<0.05) and a dose correlation was observed. Icariin was able to inhibit this process and protect the microvascular structure of BMECs. The content of cleaved caspase 3/7 in the icariin-protected group was significantly lower than that in the group without icariin (P<0.05). It was concluded that BMECs are more likely to survive than HUVECs and HA promoted the growth of BMECs on the microfluidic organ-on-a-chip platform. Glucocorticoid caused damage to BMECs through the production of cleaved caspase 3/7, which was observed through the microfluidic organ-on-a-chip platform, and icariin protected BMECs from damage. PMID:34447463 | PMC:PMC8355687 | DOI:10.3892/etm.2021.10504 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Gastro-intestinal dysfunctions in Parkinson's disease (Review)

xlomafota13 shared this article with you from Inoreader Gastro-intestinal dysfunctions in Parkinson's disease (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1083. doi: 10.3892/etm.2021.10517. Epub 2021 Jul 29. ABSTRACT In patients with Parkinson's disease (PD), gastrointestinal dysfunction occurs from the early stages of the disease and even in the pre-motor phase. This condition can include the entire digestive tract, with symptoms ranging from delays in gastric emptying to dysphagia, constipation and even malnutrition. Excess saliva accumulates in the mouth due to the low frequency of swallowing. Dysphagia develops in about 50% of patients and may be a reflection of both central nervous system and enteric nervous system disorder. Gastroparesis can cause a variety of symptoms, including nausea, and also may be responsible for some of the motor fluctuations observed with levodopa therapy. Intestinal dysfunction in PD may be the result of both delayed colon transit and impaired anorectal muscle coordination. In addition, recent studies have demonstrated the role of Helicobacter pylori infection in the pathogenesis of diseases but also the occurrence of motor fluctuations by affecting the absorption of anti-parkinsonian medication. In this review, the main gastrointestinal dysfunctions associated with PD are presented. PMID:34447476 | PMC:PMC8355716 | DOI:10.3892/etm.2021.10517 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Protectin D1 protects against lipopolysaccharide-induced acute lung injury through inhibition of neutrophil infiltration and the formation of neutrophil extracellular traps in lung tissue

xlomafota13 shared this article with you from Inoreader Protectin D1 protects against lipopolysaccharide-induced acute lung injury through inhibition of neutrophil infiltration and the formation of neutrophil extracellular traps in lung tissue Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1074. doi: 10.3892/etm.2021.10508. Epub 2021 Jul 28. ABSTRACT Protectin D1 (PD1), a DHA-derived lipid mediator, has recently been shown to possess anti-inflammatory and pro-resolving properties. To date, little is known about the effect of PD1 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The aim of the present study was to investigate the therapeutic effects of PD1 on LPS-induced ALI and its potential mechanisms of action. ALI was induced via an intraperitoneal injection of LPS, where PD1 (2 ng/mouse) was administered intravenously 30 min after LPS challenge. Mice were sacrificed 24 h after modeling. Lung histopathological changes were assessed using hematoxylin and eosin staining and myeloperoxidase (MPO) activity was tested using immunohistochemistry. Tumor necrosis-α and interleukin-6 levels in the bronchoalveolar lavage fluid (BALF) and serum were measured using ELISA. To detect neutrophil extracellular traps produced by infiltrated neutrophils in the lung tissue, immunofluorescence staining was performed using anti-MPO and anti-histone H3 antibodies. The results indicated that PD1 significantly attenuated histological damage and neutrophil infiltration in lung tissue, reduced the lung wet/dry weight ratio, protein concentration and proinflammatory cytokine levels in BALF and decreased proinflammatory cytokine levels in serum. Moreover, neutrophil citrullinated histone H3 (CitH3) expression was also reduced after PD1 administration. In conclusion, PD1 attenuated LPS-induced ALI in mice via inhibition of neutrophil extracellular trap formation in lung tissue. Therefore, PD1 administration may serve to be a new strategy for treating ALI. PMID:34447467 | PMC:PMC8355679 | DOI:10.3892/etm.2021.10508 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Factors influencing the articular eminence of the temporomandibular joint (Review)

xlomafota13 shared this article with you from Inoreader Factors influencing the articular eminence of the temporomandibular joint (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1084. doi: 10.3892/etm.2021.10518. Epub 2021 Jul 30. ABSTRACT The temporomandibular joint (TMJ), the most complex and evolved joint in humans, presents two articular surfaces: the condyle of the mandible and the articular eminence (AE) of the temporal bone. AE is the anterior root of the zygomatic process of the temporal bone and has an anterior and a posterior slope, the latter being also known as the articular surface. AE is utterly important in the biomechanics of the TMJ, as the mandibular condyle slides along the posterior slope of the AE while the mandible moves. The aim of this review was to assess significant factors influencing the inclination of the AE, especially modifications caused by aging, biological sex or edentulism. Studies have reported variations in the angles of the slopes of the AE between medieval and recent human dry skulls, as well as between subjects of different racial origin. Rec ent articles have emphasized the significant role that tooth loss has on the flattening of the AE. Although some papers have described biological sex or age as factors which could be associated with differences in AE angulations, edentulism seems to be a significant factor impacting on the inclination of the AE. PMID:34447477 | PMC:PMC8355702 | DOI:10.3892/etm.2021.1 0518 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Risk of sudden coronary death based on genetic background in Chinese Han population

xlomafota13 shared this article with you from Inoreader Risk of sudden coronary death based on genetic background in Chinese Han population Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1068. doi: 10.3892/etm.2021.10502. Epub 2021 Jul 28. ABSTRACT Associations between gene variations and sudden cardiac arrest or coronary artery disease have been reported by genome-wide association studies. However, the implication of the genetic status in cases of sudden coronary death (SCD) from the Chinese Han population has remained to be investigated. The present study established a mini-sequencing system to examine putative death-causing single nucleotide polymorphisms (SNPs) using multiplex PCR, single base extension reaction and capillary electrophoresis techniques. A total of 198 samples from the Chinese Han population (age range, 34-71 years; mean age, 53.86 years) were examined using this method. Samples were classified into three groups: Coronary heart disease (CHD, n=70), SCD (n=53) and control (n=75) group. Significant associations were identified for 10, 4 and 6 SNPs in CHD, SCD and sudden de ath from CHD, respectively, using the χ2 test. The SNPs obtained by binary logistic regression may be used to assess and predict the risk of disease. The predictive accuracy of the SNPs in each prediction model and their area under the receiver operating characteristic curve (AUC) values were determined. The AUC of the four SNPs (rs12429889, rs10829156, rs16942421 and rs12155623) to predict CHD was 0.928, the AUC of the six SNPs (rs2389202, rs2982694, rs10183640, rs597503, rs16942421 and rs12155623) to predict SCD was 0.922 and the AUC of the four SNPs (rs16866933, rs4621553, rs10829156 and rs12155623) to predict sudden death from CHD was 0.912. The multifactor dimensionality reduction values were as follows: 0.8690 (prediction model of CHD), 0.7601 (prediction model of SCD) and 0.7628 (prediction model of sudden death from CHD). Taken together, the results of the present study suggested that these SNPs have considerable potential for application in genetic tests to pred ict CHD or SCD. However, further studies are required to investigate the putative functions of these SNPs. PMID:34447461 | PMC:PMC8355668 | DOI:10.3892/etm.2021.10502 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Insights into multidrug-resistant K. pneumoniae urinary tract infections: From susceptibility to mortality

xlomafota13 shared this article with you from Inoreader Insights into multidrug-resistant <em>K. pneumoniae</em> urinary tract infections: From susceptibility to mortality Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1086. doi: 10.3892/etm.2021.10520. Epub 2021 Jul 30. ABSTRACT The incidence of urinary tract infections (UTIs) caused by Klebsiella pneumoniae has exhibited an increasing trend and has become a high burden for many public health systems, especially in hospital settings. Multidrug resistance associated with the production of extended-spectrum β-lactamases (ESBL) among K. pneumoniae isolates is endemic in Southeastern Europe. We retrospectively analyzed 75 cases admitted to 'St. Parascheva' Clinical Hospital of Infectious Diseases in Iasi, Romania, during the first 6 months of 2019 (January 1 to June 30), who had a confirmed diagnosis of K. pneumoniae UTI at discharge. From a total of 75 patients, 34 (45.3%) presented ESBL+ K. pneumoniae. The mean age was 66 years (70.1 for the ESBL+ patients vs. 62.6 for the ESBL- patients, P=0.0365). There was a symmetrical sex distribution (37 men vs. 38 women). Of these, 22 men had ESBL+ K. pneumoniae UTIs, compared to only 15 with an ESBL- strain, P=0.0087. Another risk factor for ESBL+ K. pneumoniae UTIs was the presence of hospitalization in the past 6 months; 20 (58.82%) patients with ESBL+ infections were previously hospitalized, compared to only 5 (12.19%) patients with ESBL- strains, P<0.0001. The urinary catheter carriers presented an increased prevalence of ESBL+ infections (15/34 vs. 5/41, P=0.0012). Regarding mortality, ESBL+ infections caused 6 fatalities, compared to only 1 death in the ESBL- group, P=0.0166. ESBL+ K. pneumoniae strains represent an important cause of healthcare-related UTIs, with a significantly higher mortality rate compared to ESBL- strains. Early identification and adequate management of the risk factors incriminated in ESBL+ UTIs should be a priority for physicians in order to limit the dissemination of the ESBL-producing strains and thus to improve the outcome of these patients. PMID:34447478 | PMC:PMC8355719 | DOI:10.3892/etm.2021.10520 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.