Primary Ewing's sarcoma with orbit involvement: Survival and visual outcomes after eye‐sparing multidisciplinary management in eight patients

xlomafota13 shared this article with you from Inoreader Primary Ewing's sarcoma with orbit involvement: Survival and visual outcomes after eye‐sparing multidisciplinary management in eight patients Via Head & Neck Abstract Background To describe the clinical presentation, treatment, and overall prognosis in eight patients with primary Ewing's sarcoma (ES) involving the orbit. Methods A retrospective interventional study of all biopsy-proven cases of primary ES involving the orbit was done. Results There were seven males and one female with a median age of 14 years. Imaging showed osseous involvement in all eight cases with extraorbital extension in four. Complete tumor resection was done in four, partial resection in three, and biopsy followed by sinus surgery in one. EWSR1 gene rearrangement analysis was done to confirm diagnosis. All patients received multidrug systemic chemotherapy and seven patients received adjuvant radiotherapy. Eye salvage was achieved in all patients. At a mean follow-up duration of 52.63 months, seven patients were doing well with no evidence of disease. Conclusions ES involving the orbit is sensitive to chemotherapy and radiation. Aggressive multimodality treatment can help salvage the globe and improve overall survival. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Renal tumor biomarkers (Review)

xlomafota13 shared this article with you from Inoreader Renal tumor biomarkers (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1297. doi: 10.3892/etm.2021.10732. Epub 2021 Sep 14. ABSTRACT One of the most common types of cancer worldwide (9th most commonly diagnosed) is renal cell carcinoma (RCC). It is more common in developed countries and it usually develops in individuals between 60 and 70 years of age. The earlier the disease is identified, the lower the morbidity. Therefore molecular markers that exist in blood and urine may be used for earlier detection and diagnosis but also for the follow-up of the patient after treatment, whether surgical or oncological. The trend is to analyze the gene and protein expression as they constitute a source for new biomarkers. These markers are promising but in clinical practice regarding disease management, they are rarely used. Biological markers can be employed in many tumors because they can identify the prognostic value for individual treatment. However, markers for RCC are not validated , and their analysis is currently under investigation. Previous findings have demonstrated that the metastatic potential of RCC can be predicted using the biological features of the tumor cell. It is believed that the transformation from epithelial to mesenchymal phenotype gives the tumor cell the ability to metastasize. The purpose of this review was to identify the most valuable tumor markers that can be clinically used for the prognosis, treatment and follow-up of patients with renal tumors. PMID:34630652 | PMC:PMC8461509 | DOI:10.3892/etm.2021.10732 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

miR-489-3p overexpression inhibits lipopolysaccharide-induced nucleus pulposus cell apoptosis, inflammation and extracellular matrix degradation via targeting Toll-like receptor 4

xlomafota13 shared this article with you from Inoreader miR-489-3p overexpression inhibits lipopolysaccharide-induced nucleus pulposus cell apoptosis, inflammation and extracellular matrix degradation via targeting Toll-like receptor 4 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1323. doi: 10.3892/etm.2021.10758. Epub 2021 Sep 20. ABSTRACT Intervertebral disc degeneration (IDD) is a common disease with a high morbidity rate, which results in a significant deterioration in the quality of life of patients. MicroRNAs (miRNAs/miRs) are a class of endogenous small non-coding RNAs that influence target genes and serve critical roles in numerous biological processes. However, the role of miR-489-3p in lumbar disc degeneration is yet to be elucidated. In the present study, human NP cells were treated with 10 ng/ml lipopolysaccharide (LPS) for 24 h to investigate the role of miR-489-3p in IDD in an in vitro model. Reverse transcription-quantitative (RT-q)PCR was performed to determine the expression levels of miR-489-3p. Then, the TargetScan database was used to predict the potential binding sites between miR-489-3p and Toll-like receptor (TLR)4, and a dual-luciferase reporter assay was performed to verify the findings. Subsequently, RT-qPCR and western blotting were used to analyze the expression levels of TLR4. In addition, human nucleus pulposus (NP) cells were transfected with a miR-489-3p mimic and TLR4 overexpression plasmid to study the effects of miR-489-3p on LPS-induced human NP cells. Cell apoptosis and cell viability were also determined using flow cytometry and MTT assays, respectively. Finally, ELISAs were performed to analyze the levels of inflammatory factors. The expression levels of miR-489-3p were discovered to be downregulated in LPS-treated human NP cells. In addition, TLR4 was revealed to be a direct target gene of miR-489-3p, and its expression levels were upregulated in LPS-treated human NP cells. miR-489-3p was found to inhibit the LPS-induced decreases in cell viability and increases in apoptosis, and the concentration of inflammatory cytokines. Furthermore, miR-489-3p suppressed the LPS-induced decreases in extracellular matrix deposi tion via decreasing the expression levels of aggrecan and collagen type II in human NP cells. Finally, the results revealed that miR-489-3p inhibited the LPS-induced activation of the NF-κB signaling pathway in human NP cells. Conversely, all of the effects of miR-489-3p on LPS-induced human NP cells were reversed by the TLR4 overexpression plasmid. These findings suggested that miR-489-3p may represent a novel therapeutic target for the treatment of IDD. PMID:34630677 | PMC:PMC8495590 | DOI:10.3892/etm.2021.10758 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Honokiol combined with curcumin sensitizes multidrug-resistant human lung adenocarcinoma A549/DDP cells to cisplatin

xlomafota13 shared this article with you from Inoreader Honokiol combined with curcumin sensitizes multidrug-resistant human lung adenocarcinoma A549/DDP cells to cisplatin Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1301. doi: 10.3892/etm.2021.10736. Epub 2021 Sep 16. ABSTRACT The aim of the present study was to discuss the effects and underlying mechanisms of honokiol (HNK) and/or curcumin (CUR) in sensitization of multidrug-resistant human lung adenocarcinoma A549/DDP cells to cisplatin (DDP). An MTS assay was performed to detect the cytotoxicity of HNK, CUR and DDP in A549 and A549/DDP cells and compare their sensitivity. The A549/DDP cells were then divided into 8 groups: Control, HNK, CUR, DDP, HNK + CUR, HNK + DDP, CUR + DDP and HNK + CUR + DDP. Cell proliferation was measured by MTS assay and colony formation assay, cell apoptosis was detected by flow cytometry, cell invasion was evaluated by Transwell assay and cell migration was determined by a wound healing assay. In order to investigate the possible mechanisms, P-glycoprotein (P-gp) protein expression was measured by western blotting and immunofluorescence a ssays. The mRNA expression levels of AKT, Erk1/2, cyclin-dependent kinase inhibitor 1 (P21), caspase 3, cleaved caspase 3, caspase 9, cleaved caspase 9, poly (ADP-ribose) polymerase (PARP), cleaved PARP, matrix metalloproteinase (MMP)-2 and MMP-9 were examined by reverse transcription-quantitative (RT-q) PCR assay, and the protein expression levels of phosphorylated (p)-AKT, p-Erk1/2, P21, caspase 3, cleaved caspase 3, caspase 9, cleaved caspase 9, PARP, cleaved PARP, MMP-2 and MMP-9 proteins expression by western blot assay. The MTS assay demonstrated that HNK (5 µg/ml), CUR (10 µg/ml) and DDP (5 µg/ml) had no obvious toxicity to A549/DDP cells, and HNK, CUR and DDP were more sensitive in A549 cells compared with A549/DDP cells. The optimal concentrations of HNK (5 µg/ml), CUR (10 µg/ml) and DDP (5 µg/ml) were chosen to carry out the further experiments. Compared with the control group, no significant change was observed in cell proliferation, apoptosis, migration, invasion a nd related mRNA and protein expression in HNK, CUR, DDP and HNK + CUR groups. The cell proliferation rate in the HNK + DDP and CUR + DDP groups was significantly suppressed with cell apoptosis significantly increased, respectively. The invasion cell number and wound healing rate of HNK + DDP and CUR + DDP groups were significantly depressed compared with the control group, respectively. Immunofluorescence demonstrated that the nuclear volume of P-gp in HNK + DDP and CUR + DDP groups were significantly downregulated compared with the control group, respectively. The RT-qPCR assay demonstrated that the AKT, Erk1/2 and P21 mRNA expression levels were significantly decreased and cleaved caspase 3, cleaved caspase 9 and cleaved PARP were increased in HNK + DDP and CUR + DDP groups compared with the control group. The western blotting results were consistent with the RT-qPCR results. NK + CUR + DDP had improved effects on A549/DDP compared with HNK + DDP or CUR + DDP group, respectively. HNK and/or CUR could improve the sensitivity of DDP to A549/DDP cell by the regulation of P-gp, inducing apoptosis, and inhibiting migration and invasion via AKT/ERK signal pathway in an in vitro study. PMID:34630656 | PMC:PMC8461625 | DOI:10.3892/etm.2021.10736 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy and safety of tenofovir alafenamide fumarate in nucleoside analogue treatment-naïve patients with chronic hepatitis B

xlomafota13 shared this article with you from Inoreader Efficacy and safety of tenofovir alafenamide fumarate in nucleoside analogue treatment-naïve patients with chronic hepatitis B Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1325. doi: 10.3892/etm.2021.10760. Epub 2021 Sep 20. ABSTRACT Tenofovir alafenamide fumarate (TAF) is a first-line drug for the antiviral treatment of patients with chronic hepatitis B (CHB) in China. In the present study, the efficacy and renal safety of TAF were evaluated in treatment-naive patients with CHB. Patients with CHB who had not been previously treated with nucleoside analogues (NAs) were recruited before TAF treatment was initiated. Changes in the levels of hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were analyzed at 24 and 48 weeks using immunoassays. In addition, liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were analyzed using transient elastography, while alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels, calcium (Ca) and inorga nic phosphorus (IP) levels were measured using biochemistry assay. In addition, the estimated glomerular filtration rate (eGFR) was calculated. After 48 weeks, the ALT normalization rate was 95.24% (40/42), the complete virological response (HBV DNA <20 IU/ml) rate was 69.05% (29/42) and the HBeAg seroconversion rate was 8.57% (3/35). The levels of HBV DNA and HBsAg were significantly decreased from the baseline at 5.49±1.95 to 1.26±0.66 log10 IU/ml and from 3.59±0.81 to 3.32±0.55 log10 IU/ml after 48 weeks of treatment, respectively. Compared with that in the baseline measurements, LSM at 48 weeks was significantly decreased from 13.00±8.15 to 8.66±4.45 kPa. No significant differences were observed in the TG, TC, LDL-C, CAP, eGFR, Ca and IP measurements. According to the baseline ALT levels, patients were divided into group A [ALT ≤1 x upper limit of normal (ULN); ULN=50 U/l; n=21], group B (1 x ULN < ALT <2 x ULN; n=22) and group C (ALT ≥2 x ULN; n=18). A significant decrease in HBsAg levels was observed in group B (3.63±0.68 vs. 3.53±0.63 log10 IU/ml) and group C (4.15±0.57 vs. 3.66±0.48 log10 IU/ml) at 24 weeks compared with the baseline. In conclusion, TAF was found to be effective and safe in NA treatment-naive patients with CHB. Moreover, the higher the ALT levels, the more prominent the curative effect from TAF treatment. Therefore, NA treatment-naive CHB patients could benefit from TAF treatment in real world. PMID:34630679 | PMC:PMC8495544 | DOI:10.3892/etm.2021.10760 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Yiqi Huoxue preserves heart function by upregulating the Sigma-1 receptor in rats with myocardial infarction

xlomafota13 shared this article with you from Inoreader Yiqi Huoxue preserves heart function by upregulating the Sigma-1 receptor in rats with myocardial infarction Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1308. doi: 10.3892/etm.2021.10743. Epub 2021 Sep 16. ABSTRACT Yiqi Huoxue (YQHX) is widely used in traditional Chinese medical practice due to its reported cardioprotective effects. The aim of the present study was to investigate the mechanism underlying these effects of YQHX via the regulation of the Sigma-1 receptor. The Sigma-1 receptor is a chaperone protein located on the mitochondrion-associated endoplasmic reticulum (ER) membrane. It serves an important role in heart function by regulating intracellular Ca2+ homeostasis and enhancing cellular bioenergetics. In the present study, male Sprague Dawley rats with myocardial infarction (MI)-induced heart failure were used. MI rats were administered different treatments, including normal saline, YQHX and fluvoxamine, an agonist of the Sigma-1 receptor. Following four weeks of treatment, YQHX was revealed to improve heart function and attenuate my ocardial hypertrophy in MI rats. Additionally, YQHX increased the ATP content and improved the mitochondrial ultrastructure in the heart tissues of MI rats in comparison with acontrol. Treatment was revealed to attenuate the decreased expression of the Sigma-1 receptor and increase the expression of inositol triphosphate type 2 receptors (IP3R2) in MI rats. By exposing H9c2 cells to angiotensin II (Ang II), YQHX prevented cell hypertrophy and normalized the decreased ATP content. However, these positive effects were partially inhibited when the Sigma-1 receptor was knocked down via small interfering RNA transfection. The results of the present study suggested that the Sigma-1 receptor serves an important role in the cardioprotective efficacy of YQHX by increasing ATP content and attenuating cardiomyocyte hypertrophy. PMID:34630662 | PMC:PMC8461621 | DOI:10.3892/etm.2021.10743 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Dietary Bacillus subtilis supplementation alleviates alcohol-induced liver injury by maintaining intestinal integrity and gut microbiota homeostasis in mice

xlomafota13 shared this article with you from Inoreader Dietary <em>Bacillus subtilis</em> supplementation alleviates alcohol-induced liver injury by maintaining intestinal integrity and gut microbiota homeostasis in mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1312. doi: 10.3892/etm.2021.10747. Epub 2021 Sep 16. ABSTRACT Alcoholic liver disease (ALD) is a worldwide health problem with limited therapeutic options, which is associated with gut-derived endotoxins, particularly lipopolysaccharide (LPS) and intestinal microbiota dysbiosis. Recently, probiotics, synbiotics and other food additive interventions have been shown to be effective in decreasing or preventing the progression of ALD. Bacillus subtilis (B. subtilis) and its metabolic products are widely used as food additives to maintain intestinal health, but the protective effects of B. subtilis against alcohol-induced liver injury are poorly understood. In the present study a chronic alcohol-induced liver injury model was constructed based on the Lieber-DeCarli diet and it aimed to determine whether dietary B. subtilis supplementation may alleviate alcohol-induced liver injury. Re sults revealed that prophylactic B. subtilis supplementation partially restored gut microbiota homeostasis and relieved alcohol-induced intestinal barrier injury, which significantly decreased the translocation of bacterial endotoxins to the blood. In addition, the decreased serum LPS alleviated hepatic inflammation via the toll-like receptor 4 pathway, resulting in improved hepatic structure and function. These results demonstrated that dietary B. subtilis supplementation imparts novel hepatoprotective functions by improving intestinal permeability and homeostasis. PMID:34630666 | PMC:PMC8461600 | DOI:10.3892/etm.2021.10747 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Skin anomalies in acromegalic patients (Review of the practical aspects)

xlomafota13 shared this article with you from Inoreader Skin anomalies in acromegalic patients (Review of the practical aspects) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1330. doi: 10.3892/etm.2021.10765. Epub 2021 Sep 20. ABSTRACT Acromegaly is a hormonal disorder which occurs as the result of growth hormone (GH) and insulin growth factor 1 (IGF-1) over-secretion; both hormones are related to skin anomalies. The skin acts as a large endocrine organ, hosting GH receptors in every cell while IGF-1 receptors are expressed only in keratinocytes. This review is a literature review of skin anomalies found in acromegaly, either related to the disease itself or associated with related complications such as secondary diabetes mellitus, or involving associated conditions such as genetic syndromes. The following clinical points are mentioned as follows. Excessive skin and enlargement of soft tissue are due to glycosaminoglycan deposits, edema, and hyperhidrosis (mostly facial and acral). Acanthosis nigricans, a body fold dermatosis associated with insulin resistance, involves local o r diffuse hyperkeratotic plaques with or without hyperpigmentation, caused by growth factors including GH/IGF-1. Other findings include cherry angiomas (due to the effects of lipid anomalies on small vessels); oily skin features with keratosis, epidermoid cysts, crochordons, pseudo-acanthosis nigricans; a potentially higher prevalence of varicose veins and psoriasis; low level of evidence for basal cell carcinoma, respective hidroadenitis suppurativa has been noted. In addition, complicated uncontrolled secondary diabetes mellitus (DM) may result in necrobiosis lipoidica diabeticorum, diabetic dermopathy, skin bacterial infections, dermatological complications of diabetic neuropathy, and nephropathy. Finally, associated hereditary syndromes may cause collagenomas, fibromas/angiofibromas, lipomas in multiple endocrine neoplasia type 1 (MEN1) syndrome; café-au-lait macules, early onset neurofibromas, juvenile xanthogranuloma (involving non-Langerhans cell histiocytes), and intertrigi nous freckling in neurofibromatosis type 1. Clinical findings are differentiated from pseudo-acromegaly such as pachydermoperiostosis. Iatrogenic rash, lipodystrophy (lipoatrophy with/without lipohypertrophy) are rarely reported after pegvisomant/somatostatin analogues or after insulin use for DM. Experiments using human cell lines have shown that GH/IGF-1 over-secretion are prone to epithelial-to-mesenchymal transition (EMT) in melanoma. In non-acromegalic subjects, the exact role of GH/IGF-1 in skin tumorigenesis is yet to be determined. Skin in acromegaly speaks for itself, either as the first step of disease identification or as a complication or part of a complex syndromic context. PMID:34630684 | PMC:PMC8495547 | DOI:10.3892/etm.2021.10765 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Metformin attenuates H2O2-induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway

xlomafota13 shared this article with you from Inoreader Metformin attenuates H<sub>2</sub>O<sub>2</sub>-induced osteoblast apoptosis by regulating SIRT3 via the PI3K/AKT pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1316. doi: 10.3892/etm.2021.10751. Epub 2021 Sep 17. ABSTRACT Osteoporosis is a common metabolic disease that has a high incidence in postmenopausal women. Studies have indicated that oxidative damage plays an important role in the development of postmenopausal osteoporosis. Metformin has been showed to have the ability to relieve excessive oxidation. The aim of the present was to determine the therapeutic effect and potential mechanism of metformin in postmenopausal osteoporosis. Oxidative damage was stimulated in vitro by the addition of H2O2 to MC3T3-E1 cells and a mouse menopausal model was also constructed. Cell viability and flow cytometry experiments were performed to determine the effects of H2O2 and metformin treatment on apoptosis. Mitochondrial membrane potential was tested by JC-1 assays. Western blotting was used to detect the expression of mit ochondrial apoptosis markers and antioxidant enzymes. Small interfering RNA was used to knockdown sirtuin3 (SIRT3), which was verified at the mRNA and protein levels. Bilateral ovariectomy was used to prepare menopausal mice, which were analyzed using micro-computed tomography. The results indicated that metformin is able to repair mitochondrial damage and inhibit the apoptosis of osteoblasts induced by H2O2, and also reverse bone mass loss in ovariectomized mice. Western blotting results demonstrated the involvement of SIRT3 in the production of antioxidant enzymes that are essential in protecting against mitochondrial injury. In addition, experiments with SIRT3 knockdown indicated that metformin reverses H2O2-induced osteoblast apoptosis by upregulating the expression of SIRT3 via the PI3K/AKT pathway. The results of the present reveal the pathogenesis of oxidative damage and the therapeutic effect of metformin in postmenopausal osteopor osis. They also suggest that SIRT3 is a potential drug target in the treatment of osteoporosis, with metformin being a candidate drug for modification and/or clinical application. PMID:34630670 | PMC:PMC8495548 | DOI:10.3892/etm.2021.10751 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of Psoralea corylifolia L. seed extract on AGEs-induced cell proliferation and fibrotic factor expression in mesangial cells

xlomafota13 shared this article with you from Inoreader Effects of <em>Psoralea corylifolia</em> L. seed extract on AGEs-induced cell proliferation and fibrotic factor expression in mesangial cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1332. doi: 10.3892/etm.2021.10767. Epub 2021 Sep 20. ABSTRACT Diabetic nephropathy is a microvascular complication of diabetes that is characterized by mesangial expansion and thickening of the glomerular basement membrane. The production of advanced glycation end products (AGEs) increases in diabetic patients. Activation of the receptor of AGE (RAGE) signaling pathway induces mesangial expansion via the reactive oxygen species (ROS)-mediated production of pro-inflammatory and extracellular matrix molecules. The Psoralea corylifolia L. seed (PCS) is a widely used herbal medicine with various biological activities. The current study investigated the effect of PCS extract on mesangial cell proliferation and the RAGE signaling pathway in SV40 MES 13 cells. SV40 MES 13 cells were harvested after treatment with various concentrations of PCS extract at 10 µg/ml AGEs for 24 h. The results revealed that the PCS extract inhibited AGEs-induced mesangial cell proliferation and cyclin protein expression in a concentration-dependent manner. In addition, the AGEs-induced expression of fibrotic factors, such as transforming growth factor β, fibronectin and collagen, was reduced in mesangial cells after exposure to the PCS extract. The PCS extract also reduced RAGE expression and inhibited the expression of its downstream signaling pathways, such as NADPH oxidase, intracellular ROS and phospho-NF-κB. In conclusion, the data suggested that the PCS extract attenuated AGEs-induced renal mesangial cell proliferation and fibrosis via the suppression of oxidative stress and the downregulation of inflammatory and fibrotic factor expression. PMID:34630686 | PMC:PMC8495585 | DOI:10.3892/etm.2021.10767 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.