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.

Autophagy promotes invadopodia formation in human ovarian cancer cells via the p62-extracellular signal-regulated kinase 1/2 pathway

xlomafota13 shared this article with you from Inoreader Autophagy promotes invadopodia formation in human ovarian cancer cells via the p62-extracellular signal-regulated kinase 1/2 pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):952. doi: 10.3892/etm.2021.10384. Epub 2021 Jul 5. ABSTRACT Invasiveness and metastatic potential are among the most essential characteristics of malignant tumors. Furthermore, it has been reported that autophagy and invasion are enhanced when tumor cells are grown in adverse conditions, such as nutritional deficiency and starvation. However, the association between autophagy and invasion remains largely unclear. In the present study, Earle's balanced salt solution (EBSS) was used to induce autophagy and an autophagy inhibitor was used to block autophagy. The results of Transwell assays revealed that autophagy inhibition limited the invasiveness of human ovarian cancer cells. Furthermore, the results of invadopodia formation assay indicated that autophagy stimulated invadopodia formation, and the selective autophagy receptor and signaling adaptor, sequestosome-1 (SQSTM1/p62 or simply p62), was closely assoc iated with invadopodia formation in human ovarian cancer SKOV3 cells. The results of western blot analysis indicated that autophagy induced changes in p62 protein levels and p62 then functioned as a negative regulator of extracellular signal-regulated kinase 1/2 (ERK1/2) activity and invadopodia formation. The interaction between autophagy and invasion may thus be a self-protective mechanism for tumor cells in an unfavorable environment of nutritional deficiency, that maintains their survival and leads to increased invasiveness. An exploration of the intrinsic link between autophagy and invasion may provide a novel theoretical basis to reverse the resistance of tumor cells to a nutritional deficient environment. PMID:34335894 | PMC:PMC8290436 | DOI:10.3892/etm.2021.10384 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anti-inflammatory effects of microRNA-223 on sepsis-induced lung injury in rats by targeting the Toll-like receptor signaling pathway

xlomafota13 shared this article with you from Inoreader Anti-inflammatory effects of microRNA-223 on sepsis-induced lung injury in rats by targeting the Toll-like receptor signaling pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):964. doi: 10.3892/etm.2021.10396. Epub 2021 Jul 7. ABSTRACT The aim of the present study was to investigate the mediation of micro RNA (miR)-223 on the anti-inflammatory effect of the Toll-like receptor (TLR) signaling pathway on sepsis-induced lung injury in rats via negatively regulating the expression of interleukin (IL)-6. Sprague-Dawley rats were used in the present study. It was determined whether miR-223 is differentially expressed in the lung using reverse transcription-quantitative PCR techniques and the content of cytokines in bronchoalveolar lavage (BAL) fluid was detected. The protein expression levels of TLR4 and nuclear factor (NF)-κB p65 were examined by western blotting and the pathological changes in the lung tissues of the sepsis group were observed. Hematoxylin and eosin was used to stain the lung tissues. The alveoli in the sham group exhibited a normal structure and morphology. In the sepsis group, the alveoli of the lung tissues were surrounded by numerous neutrophils, the mesenchyme was swollen, regions of the alveolar wall exhibited fibrosis and the alveolar wall was thickened. Furthermore, in the sepsis group, miR-223 expression was increased in the lung tissues when compared with that in the sham group. The content of cytokines, IL-6 and IL-1β in the BAL fluid was significantly increased when compared with that of the sham group and TLR4 and NF-κB were also highly expressed. In addition, when compared with RAW264.7 cells that were overexpressing miR-223, the content of IL-6 and IL-1β in the supernatant and protein expression of TLR and NF-κB in cells were markedly decreased. Thus, it was demonstrated that miR-223 negatively regulated the expression of IL-6, mediating the TLR4/NF-κB signaling pathway and exerting an anti-inflammatory effect in sepsis-induced lung injury. PMID:34335906 | PMC:PMC8290467 | DOI:10.3892/etm.2021.10396 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Diagnostic and prognostic computed tomography imaging markers in basilar artery occlusion (Review)

xlomafota13 shared this article with you from Inoreader Diagnostic and prognostic computed tomography imaging markers in basilar artery occlusion (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):954. doi: 10.3892/etm.2021.10386. Epub 2021 Jul 6. ABSTRACT Acute ischemic stroke treatment has been revolutionized by the addition of mechanical and aspiration thrombectomy. Randomized controlled trials have proven beyond doubt, the substantial clinical impact of endovascular interventions in anterior circulation territory strokes. Unfortunately, patients with vertebrobasilar ischemic stroke could not be included in these early trials due to inherent clinical, radiological, and prognostic particularities of posterior circulation ischemia; thus, indications for the treatment of posterior fossa strokes and basilar artery occlusion (BAO) are mainly based on retrospective studies and registries. BAO carries high morbidity and mortality, despite the new improvements in endovascular therapy. Identifying patients who will likely benefit from invasive treatment and have a good clinical outcome resides in discoveri ng clinical, biological, or imaging markers, that have prognostic implications. Such imaging markers have been described, especially in the last decade. Hyperdense Basilar Artery Sign (HDBA), Posterior Circulations-Alberta Stroke Program Early CT Score (pc-ASPECTS), Pons-Midbrain Index (PMI), Posterior Circulation Collateral Score (pc-CS), Posterior Circulation CT Angiography Score (pc-CTA), and Basilar Artery on CT Prognostic Score (BATMAN), are computed tomography (CT) markers with properties that can aid the diagnosis of BAO and can independently predict clinical outcome. This paper aims to present a comprehensive review of these imaging signs to have a thorough understanding of their diagnostic and prognostic attributes. PMID:34335896 | PMC:PMC8290397 | DOI:10.3892/etm.2021.10386 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tail suspension delays ectopic ossification in proteoglycan-induced ankylosing spondylitis in mice via miR-103/DKK1

xlomafota13 shared this article with you from Inoreader Tail suspension delays ectopic ossification in proteoglycan-induced ankylosing spondylitis in mice via miR-103/DKK1 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):965. doi: 10.3892/etm.2021.10397. Epub 2021 Jul 7. ABSTRACT Ankylosing spondylitis (AS), characterized by inflammatory lesions and osteophyte formation, is a common immune rheumatic disease affecting the sacroiliac and axial joints. A high-intensity mechanical load is known to accelerate the heterotopic ossification associated with enthesitis in AS. Thus, the present study explored whether decreased mechanical load could delay the heterotopic ossification in AS. First, 24-week-old female BALB/c mice were induced with proteoglycan (PG) to establish an AS model. The AS-induced pathological and bone morphological changes of the sacroiliac joint were confirmed by hematoxylin and eosin staining and microCT analysis, respectively. Subsequently, the mice were treated with interventions of different mechanical loads. Using reverse transcription-quantitative PCR, it was revealed that expression levels of the osteoge nesis-related genes bone morphogenetic protein-2, runt-related transcription factor 2 and osteocalcin were significantly reduced in sacroiliac bone tissue after intervention with a reduced mechanical load. The level of mechanosensory microRNA (miR)-103 increased in response to reduced mechanical loads. Consistently, in groups with reduced mechanical load, proteins with mechanical functions, including ρ-associated coiled-coil-containing protein kinase 1 (ROCK1), phosphorylated (p)-Erk1/2 and β-catenin, were reduced compared with the PG control. A dual-luciferase assay verified that miR-103 binds to the 3'-untranslated region end of Rock1 mRNA, thus negatively regulating the activity of Rock1 and affecting pathological ossification during AS. However, immunohistochemical staining indicated that the expression of dickkopf Wnt signaling pathway inhibitor 1, an inhibitor of the Wnt/β-catenin pathway, was increased in sacroiliac tissues. The results indicated that tail su spension decreased the mechanical load, thus reducing the bone formation in AS mice. Furthermore, tail suspension could inhibit the activation of mechanical kinase ROCK1 and p-Erk1/2 in the MAPK signaling pathway by upregulating miR-103, thereby inhibiting the classical osteogenesis-related Wnt/β-catenin pathway in AS. In summary, the present study uncovered the ameliorative effect of suspension on AS and its therapeutic potential for AS. PMID:34335907 | PMC:PMC8290398 | DOI:10.3892/etm.2021.10397 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Professional ethics, VBAC and COVID-19 pandemic: A challenge to be resolved (Review)

xlomafota13 shared this article with you from Inoreader Professional ethics, VBAC and COVID-19 pandemic: A challenge to be resolved (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):956. doi: 10.3892/etm.2021.10388. Epub 2021 Jul 6. ABSTRACT Since the declaration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic by the World Health Organization (WHO) on March 11, 2020, the entire healthcare system is trying to adapt its capabilities to a challenge that induces a deep and continuous metamorphosis of people, strategies and policies. The right to proper health care is universal, and the patient's autonomy must be respected even in ambiguous times. In the context of increased Cesarean section (CS) rates, the women's desire to achieve vaginal birth after Cesarean section (VBAC) is becoming more articulate, and healthcare professionals need to adapt their approaches regarding the mode of delivery. But how to balance this aspect with respect to the paucity of resources during the pandemic, without infringing the fundamental rights and ethical principles is a demandi ng question. This article describes a clinical ethical decision-making framework for recommending trial of labor after Cesarean section (TOLAC), and individualized management of VBAC cases tailored upon the new circumstances dictated by the SARS-CoV-2 pandemic. PMID:34335898 | PMC:PMC8290459 | DOI:10.3892/etm.2021.10388 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

One, No One and One Hundred Thousand: Patterns of chronic prostatic inflammation and infection

xlomafota13 shared this article with you from Inoreader One, No One and One Hundred Thousand: Patterns of chronic prostatic inflammation and infection Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):966. doi: 10.3892/etm.2021.10398. Epub 2021 Jul 7. ABSTRACT Chronic prostatic inflammation may be classified into three types that share similar symptoms and are distinguished on the basis of microbiological findings. In the present study, consecutive cases of chronic prostatic inflammation and infection were retrospectively reviewed in order to explore the clinical course and long-term outcomes. The cohort consisted of patients with symptoms of prostatitis who visited the Urology Clinic of the Tzaneion Hospital (Piraeus, Greece) between March 2009 and March 2019. The patients were subjected to the Meares and Stamey '4-glass' test and patients with febrile prostatitis were evaluated with a single mid-stream 'clean' urine sample culture. Bacterial identification was performed using the Vitek 2 Compact system and the sensitivity test with the disc and the Vitek 2 system. A total of 656 patients with prostatit is-like symptoms with 1,783 visits for investigation and follow-up were reviewed and patients were divided into two major groups. Group 1 consisted of 549 cases with a single set of chronic prostatitis (CP)-like symptoms assessed in up to three visits. National Institutes of Health (NIH) category II CP (NIH-II) was most frequently diagnosed in those patients (37,6%). At the follow-up, 125 patients were identified as having a type of CP different from that determined initially. Group 2 (107 cases) had recurring episodes of prostatitis-like symptoms assessed or confirmed over the course of 4-18 visits. Most patients (54.2%) were initially diagnosed with NIH-II followed by disease-free periods and recurrence/reinfection or by shifts to NHI-IIIB. In conclusion, CP remains a poorly understood n medical condition characterized by a variety of clinical manifestations and by transitions between different CP classes during its course. PMID:34335908 | PMC:PMC8290471 | DOI:10.3892/etm.2021.10398 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Role of liver-X-receptors in airway remodeling in mice with chronic allergic asthma

xlomafota13 shared this article with you from Inoreader Role of liver-X-receptors in airway remodeling in mice with chronic allergic asthma Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):920. doi: 10.3892/etm.2021.10352. Epub 2021 Jun 30. ABSTRACT Liver X receptors (LXRs) exert anti-inflammatory effects in animal models of certain respiratory diseases. In the present study, a model of chronic airway remodeling was established in wild-type and LXR-deficient mice. Ovalbumin (OVA)-sensitized mice were chronically administered OVA via inhalation for 8 weeks. Prior to each stimulation, certain wild-type mice were treated with GW3965, which is a highly selective LXR agonist. The influence of LXRs on airway inflammation, airway hyperresponsiveness and airway remodeling was evaluated. LXRs were indicated to increase airway inflammation and airway hyperresponsiveness, as well as promote airway remodeling. These results suggest that inhibiting LXRs may be a potential method for the treatment of allergic asthma. PMID:34335881 | PMC:PMC8290420 | DOI:10.3892/etm.2021.10352 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.