Dual attack: targeting the rare co-occurrence of myasthenia gravis and Graves' disease with radioactive iodine therapy

xlomafota13 shared this article with you from Inoreader Dual attack: targeting the rare co-occurrence of myasthenia gravis and Graves' disease with radioactive iodine therapy Via radioactive iodine Endocrinol Diabetes Metab Case Rep. 2021 Jul 1;2021:EDM210046. doi: 10.1530/EDM-21-0046. Online ahead of print. ABSTRACT SUMMARY: Occasionally, autoimmune disorders can come in twos. This double trouble creates unique challenges. Myasthenia gravis co-existing with autoimmune thyroid disease occurs in only about 0.14-0.2% of cases. The patient is a 27-year-old man with a 2-month history of bilateral ptosis, diplopia, with episodes of easy fatigability, palpitations, and heat intoler ance. On physical exam, the patient had an enlarged thyroid gland. Myasthenia gravis was established based on the presence of ptosis with weakness of the intraocular muscles, abnormal fatigability, and a repetitive nerve stimulation study indicated neuromuscular junction disease. Episodes of fluctuating right shoulder weakness were also noted. He was also found to have elevated FT3, FT4, and a suppressed TSH. Thyroid ultrasound revealed thyromegaly with diffused parenchymal disease. Thyroid scintigraphy showed increased uptake function at 72.4% uptake at 24 h. TRAb was positive at 4.1 U/L. Patient was started on pyridostigmine which led to a significant reduction in the frequency of ocular muscle weakness. Methimazole was also initiated. Radioactive iodine at 14.9 mci was instituted for the definitive management of hyperthyroidism. After RAI, there was abatement of the hyperthyroid symptoms, as well as improvement in the status of the myasthenia gravis, with ptosis, diplopia, and ri ght arm weakness hardly occurring thereafter despite the reduction of the pyridostigmine dose based on a symptom diary and medication intake record. Two distinct autoimmune conditions displayed a markedly improved clinical course with the institution of radioactive iodine therapy for Graves' disease. LEARNING POINTS: The presence of ptosis, diplopia, and fluctuating muscle weakness are atypical in Graves' disease and should prompt an investigation on the existence of concurrent myasthenia gravis. A prompt diagnosis of both conditions will enable the institution of appropriate management that would target both rare and challenging autoimmune diseases. Selecting the therapeutic options with minimal risk of morbidity and mortality, which could lead to maximal benefit especially in a resource-limited setting is paramount. Targeted non-surgical management can lead to the remission of two autoimmune diseases which can result in patient satisfaction and improved quality of life. < p>PMID:34196278 | DOI:10.1530/EDM-21-0046 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ozone induces tolerance against cardiomyocytes oxygen-glucose deprivation/reperfusion through inhibition of autophagy pathway

xlomafota13 shared this article with you from Inoreader Ozone induces tolerance against cardiomyocytes oxygen-glucose deprivation/reperfusion through inhibition of autophagy pathway Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):869. doi: 10.3892/etm.2021.10301. Epub 2021 Jun 13. ABSTRACT Previous studies have reported that excess activation of autophagy in cardiomyocytes is associated with an increase in myocardial oxygen-glucose deprivation/reperfusion (OGD/R) injury. Ozone therapy affords significant cardio-protection against myocardial OGD/R injury. The present study was designed to determine whether ozone-induced tolerance to myocardial OGD/R injury was mediated by inhibiting autophagy. Subsequently, the rat cardio myoblast H9C2 cell line was used in the present study. A model of H9C2 cells under OGD/R was established. The cells were incubated with different concentrations of ozone (10-60 µg/ml) during reperfusion. Furthermore, to investigate the role of autophagy in OGD/R-induced injury, the autophagy inducer and inhibitor were applied. Cell viability was detected by Cell Counting kit-8 assay. Cell apoptosis was evaluated by flow cytometry. Oxidative stress was examined by superoxide dismutase, lactate dehydrogenase and malondialdehyde levels. The expressions of apoptosis regulator B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (BAX), cleaved caspase-3, markers of autophagy microtuble-associated protein 1 light chain 3 (LC3), autophagy-related protein 5 (Atg5) and Beclin-1 were measured by western blot analysis. As a result, OGD/R notably decreased cell viability and induced apoptosis in H9C2 cells, while ozone (10-40 µg/ml) reversed the noxious effects of OGD/R on H9C2 cells, and 20 µg/ml ozone was the most effective. Ozone inhibited the decrease in the ratio of Bcl-2/BAX and the expression of cleaved caspase-3, and inhibited the increase in the ratio of LC3-II/LC3-I and the expression of Atg5 and Beclin-1 elicited by OGD/R, as well as dose-dependently preventing OGD/R-induced oxidative stress. Furthermore, rapamycin markedly reversed the effects of ozone (20 µg/ml) on OGD/R-induced expressi on of autophagy marker proteins and 3-methyladenine further improved the effect of ozone. Taken together, the results of the present study provided a credible mechanism by which ozone treatment at low concentrations could protect the myocardium from OGD/R-induced injury by inhibiting autophagy. PMID:34194547 | PMC:PMC8237385 | DOI:10.3892/etm.2021.10301 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical relevance of donor-specific human leukocyte antigen antibodies after pediatric liver transplantation

xlomafota13 shared this article with you from Inoreader Clinical relevance of donor-specific human leukocyte antigen antibodies after pediatric liver transplantation Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):867. doi: 10.3892/etm.2021.10299. Epub 2021 Jun 13. ABSTRACT Donor-specific human leukocyte antigen (HLA) antibodies (DSAs) have a significant role in graft survival after pediatric liver transplantation. To understand the significance of DSAs, a retrospective cohort study of 48 pediatric liver transplant recipients with posttransplant serum samples that were analyzed for DSAs was performed. According to their test results, the recipients were divided into a DSA-positive group and a DSA-negative group. Postoperative liver transplantation biopsies were performed in patients with abnormal liver function. The liver condition and prognosis of the recipients were recorded, and their association was analyzed. A total of 48 recipients were followed up for 2.7±0.8 years. DSA positivity was detected in 10 cases (20.8%). One case was positive for HLA class I and HLA class II antibodies, whereas 9 cases were positive for HLA class II antibodies, and the gene loci were HLA-DR and/or DQ. Antibody-mediated rejection (AMR) occurred in four of 10 patients in the DSA-positive group. Liver function was abnormal in 3 of 38 cases in the DSA-negative group. Multivariate analysis revealed that DSA positivity was an independent risk factor for liver insufficiency and long-term survival of recipients. In addition, Kaplan-Meier survival analysis demonstrated that there were significant differences in the survival of graft recipients between the DSA-positive group and the DSA-negative group (P<0.05). The positivity of DSAs after pediatric liver transplantation was closely related to the occurrence of AMR. These results suggested that DSAs should be routinely monitored post-operatively, and that DSA-positive recipients should be screened as soon as possible and given appropriate treatment. PMID:34194545 | PMC:PMC8237393 | DOI:10.3892/etm.2021.10299 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow-derived mesenchymal stem cells via the PKA-AMPK-SIRT1 axis

xlomafota13 shared this article with you from Inoreader Uncarboxylated osteocalcin promotes osteogenesis and inhibits adipogenesis of mouse bone marrow-derived mesenchymal stem cells via the PKA-AMPK-SIRT1 axis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):880. doi: 10.3892/etm.2021.10312. Epub 2021 Jun 15. ABSTRACT Osteoporosis is a bone disease characterized by reduced bone density, thin cortical bone and large gaps in the bone's honeycomb structure, which increases the risk of bone fragility. Uncarboxylated osteocalcin (unOC), a vitamin K-dependent bone protein, is known to regulate carbohydrate and energy metabolism. A previous study demonstrated that unOC promotes the differentiation of mouse bone marrow-derived mesenchymal stem cells (BMSCs) into osteoblasts, but inhibits their differentiation into adipocytes. However, the underlying mechanism remains unknown. The present study showed that unOC regulated the differentiation potential of BMSCs via protein kinase A (PKA)/AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling. SIRT1, a member of the sirtuin family with deacetylation functions, was upregulated by unOC in BMSCs. Transfection analyse s with SIRT1 small interfering RNA indicated that the unOC-induced differentiation shift in BMSCs required SIRT1. Examination of SIRT1 downstream targets revealed that unOC regulated the acetylation levels of runt-related transcription factor (RUNX) 2 and peroxisome proliferator-activated receptor γ (PPARγ). Therefore, unOC inhibited adipogenic differentiation by PPARγ acetylation and promoted osteogenic differentiation by RUNX2 deacetylation. Moreover, phosphorylated PKA and AMPK protein levels increased after unOC treatment, which led to the upregulation of SIRT1. Western blot analysis with PKA and AMPK inhibitors indicated that the PKA-AMPK signaling pathway functioned upstream of SIRT1 and positively regulated SIRT1 expression. These findings led us to propose a model in which unOC regulated BMSC osteogenic differentiation through the PKA-AMPK-SIRT1 axis, giving evidence towards the therapeutic potential of unOC in osteoporosis treatment. PMID:34194558 | PMC:PMC8237271 | DOI:10.3892/etm.2021.10312 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Trichinellosis in hospitalized patients from Western Romania: A retrospective study

xlomafota13 shared this article with you from Inoreader Trichinellosis in hospitalized patients from Western Romania: A retrospective study Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):895. doi: 10.3892/etm.2021.10327. Epub 2021 Jun 18. ABSTRACT Trichinellosis is a public health problem and an economic issue in porcine animal production and food safety. The aim of this retrospective study was to evaluate the current epidemiologic, laboratory, clinical and therapeutic aspects of human trichinellosis in Western Romania. We retrospectively investigated the medical records of patients hospitalized in infectious diseases hospitals from three counties in Western Romania, between January 1st, 2012 and December 31st, 2016. A total of 83 patients diagnosed with trichinellosis were included in the study. Pork meat was the food source of infection in 76 (91.6%) patients and wild boar meat in 4 (4.8%). Patients were aged between 2 and 78 years; 48 (57.8%) were males and 27 (32.5%) came from an urban area. The most frequent symptoms included myalgia in 66 (79.5%) patients, fever in 55 (66.3%), eyelid edema in 40 (48.2%) and asthenia in 35 (42.2%). Two patients died and the others had favorable outcome. Although the number of reported cases has decreased in the past years, trichinellosis remains an important public health problem in Western Romania. Educational programs for both swine breeders and consumers are imperative, and implementation of strict hygienic measures aimed to control infection transmission are strongly recommended. PMID:34194571 | PMC:PMC8237275 | DOI:10.3892/etm.2021.10327 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Advancement in research on the role of the transient receptor potential vanilloid channel in cerebral ischemic injury (Review)

xlomafota13 shared this article with you from Inoreader Advancement in research on the role of the transient receptor potential vanilloid channel in cerebral ischemic injury (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):881. doi: 10.3892/etm.2021.10313. Epub 2021 Jun 15. ABSTRACT Stroke is a common critical disease occurring in middle-aged and elderly individuals, and is characterized by high morbidity, lethality and mortality. As such, it is of great concern to medical professionals. The aim of the present review was to investigate the effects of transient receptor potential vanilloid (TRPV) subtypes during cerebral ischemia in ischemia-reperfusion animal models, oxygen glucose deprivation and in other administration cell models in vitro to explore new avenues for stroke research and clinical treatments. TRPV1, TRPV2 and TRPV4 employ different methodologies by which they confer protection against cerebral ischemic injury. TRPV1 and TRPV4 are likely related to the inhibition of inflammatory reactions, neurotoxicity and cell apoptosis, thus promoting nerve growth and regulation of intracellular calcium ions (Ca2 +). The mechanisms of neuroprotection of TRPV1 are the JNK pathway, N-methyl-D-aspartate (NMDA) receptor and therapeutic hypothermia. The mechanisms of neuroprotection of TRPV4 are the PI3K/Akt pathways, NMDA receptor and p38 MAPK pathway, amongst others. The mechanisms by which TRPV2 confers its protective effects are predominantly connected with the regulation of nerve growth factor, MAPK and JNK pathways, as well as JNK-dependent pathways. Thus, TRPVs have the potential for improving outcomes associated with cerebral ischemic or reperfusion injuries. The protection conferred by TRPV1 and TRPV4 is closely related to cellular Ca2+ influx, while TRPV2 has a different target and mode of action, possibly due to its expression sites. However, in light of certain contradictory research conclusions, further experimentation is required to clarify the mechanisms and specific pathways by which TRPVs act to alleviate nerve injuries. PMID:34194559 | PMC:PMC8237269 | DOI:10.3892/etm.2021.10313 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E-selectin/VCAM-1

xlomafota13 shared this article with you from Inoreader HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E-selectin/VCAM-1 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):871. doi: 10.3892/etm.2021.10303. Epub 2021 Jun 13. ABSTRACT Atherosclerosis (AS) is a chronic pathophysiological process that causes high mortality and morbidity. It has previously been reported that homeobox A9 (HOXA9) may participate in regulation of the cardiovascular system and the pathology of AS by upregulating E-selectin and vascular cell adhesion molecule-1 (VCAM-1). Thus, inhibiting HOXA9 could promote microcirculation of coronary arteries and could act as a potential therapy for AS treatment. Sprague-Dawley rats were randomly divided into four groups, as follows: i) AS; ii) AS + HOXA9 inhibitor; iii) AS + small interfering RNA-HOXA9 and iv) normal control. ELISA was used to measure the levels of TNF-α, IL-1β, IL-12, C-C motif chemokine ligand 25 (CCL25), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL). Flow cytometry was employed to detect t he content of M1 macrophages. Hematoxylin & eosin (H&E) staining was performed to observe the morphology of the coronary arteries. Oil red O staining was conducted for the evaluation of lipid accumulation. Immunohistochemistry was used to visualize the protein expression levels of HOXA9 in the coronary arteries. Western blotting was utilized to determine the protein expression levels of HOXA9, platelet factor-4 (PF4), E-selectin and VCAM-1. HOXA9 inhibitors were found to downregulate the levels of TNF-α, IL-1β, IL-12, CCL25, LDL and VLDL, and upregulate HDL levels in the blood of AS rats. The content of M1 macrophages was also decreased following injection of HOXA9 inhibitors in the AS group. H&E and oil red O staining analysis indicated that HOXA9 inhibitors attenuated vascular symptoms and lipid formation in AS rats. Furthermore, western blotting suggested that inhibition of HOXA9 reduced the expression levels of PF4, E-selectin and VCAM-1, while overexpression of PF 4 resulted in the opposite effects. The present study revealed that inhibiting HOXA9 alleviated the symptoms of AS via downregulation of the PF4 and E-selectin/VCAM-1 pathway to promote microcirculation in the coronary arteries of AS rats. These findings indicated that HOXA9 inhibitors may have the potential to succeed in the treatment of AS. PMID:34194549 | PMC:PMC8237395 | DOI:10.3892/etm.2021.10303 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Protective effects of miR-155-5p silencing on IFN-γ-induced apoptosis and inflammation in salivary gland epithelial cells

xlomafota13 shared this article with you from Inoreader Protective effects of miR-155-5p silencing on IFN-γ-induced apoptosis and inflammation in salivary gland epithelial cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):882. doi: 10.3892/etm.2021.10314. Epub 2021 Jun 15. ABSTRACT Previous studies have demonstrated that microRNAs (miRNAs/miRs) serve a vital role in the pathogenesis of Sjögren's syndrome (SS). The present study aimed to investigate the role of miR-155-5p in SS and determine its underlying molecular mechanism. An inflammatory lesion model was established by stimulating salivary gland epithelial cells (SGECs) with interferon-γ (IFN-γ). The apoptosis of SGECs was measured by using flow cytometry. Levels of proinflammatory factors were detected by reverse transcription-quantitative PCR and ELISA, respectively. Immunofluorescence was used for p65 staining. Dual-luciferase reporter assay was performed to verify the interaction between miR-155-5p and arrestin β2 (ARRB2). The protein levels in the NF-κB signaling pathway were assessed by western blotting. The results of the present study demonstrated that treat ment with IFN-γ increased miR-155-5p expression, in addition to inducing apoptosis and inflammation in SGECs. Furthermore, overexpression of miR-155-5p promoted IFN-γ-induced apoptosis and inflammation in SGECs. Overexpression of miR-155-5p also increased Bax protein expression, enzyme activities of caspase 3 and caspase 9, release of inflammatory cytokines interleukin-6 and tumor necrosis factor-α, and decreased Bcl-2 protein expression in IFN-γ-treated SGECs. By contrast, all of the effects aforementioned were reversed following miR-155-5p knockdown. These results demonstrated that miR-155-5p activated the NF-κB signaling pathway, where treatment with the NF-κB inhibitor, pyrrolidine dithiocarbamate, reversed the effects of miR-155-5p overexpression on the inflammatory factors in IFN-γ-induced SGECs. miR-155-5p was demonstrated to target ARRB2 and negatively regulated its expression levels, such that overexpression of ARRB2 reversed the effects of miR-155-5p overexpression on the inflammatory response, apoptosis and the NF-κB signaling pathway in IFN-γ-treated SGECs. Collectively, results from the present study suggest that miR-155-5p may activate the NF-κB signaling pathway by negatively regulating ARRB2 to promote salivary gland damage during SS pathogenesis. This suggests that miR-155-5p may serve to be a potential target for the treatment of SS. PMID:34194560 | PMC:PMC8237265 | DOI:10.3892/etm.2021.10314 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

miR-320a in serum exosomes promotes myocardial fibroblast proliferation via regulating the PIK3CA/Akt/mTOR signaling pathway in HEH2 cells

xlomafota13 shared this article with you from Inoreader miR-320a in serum exosomes promotes myocardial fibroblast proliferation via regulating the PIK3CA/Akt/mTOR signaling pathway in HEH2 cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):873. doi: 10.3892/etm.2021.10305. Epub 2021 Jun 14. ABSTRACT MicroRNAs (miRNAs/miRs) serve an important role in the pathogenesis of chronic heart failure (CHF). A number of reports have illustrated the regulatory effect of serum exosomal miRNA on myocardial fibrosis. The present study aimed to investigate the expression of miR-320a in serum exosomes, as well as the effect of miR-320a on myocardial fibroblast proliferation. Serum exosome samples from 10 patients with CHF and 5 healthy volunteers were obtained and characterized. mRNA and protein expression levels were measured via reverse transcription-quantitative PCR and western blotting, respectively. The content of soluble growth stimulation expressed gene 2 (sST2) was determined via ELISA. HEH2 cell viability and apoptosis were detected by performing MTT assays and flow cytometry, respectively. The results demonstrated that serum miR-320a expression leve ls and sST2 content were significantly increased in patients with CHF compared with healthy controls, and the expression of serum miR-320a was significantly correlated with clinical CHF indexes. miR-320a expression levels were significantly increased in exosomes isolated from patients with CHF compared with those isolated from healthy controls. Phosphoinositide-3-kinase catalytic α polypeptide gene (PIK3CA) expression levels and sST2 content were increased in HEH2 cells following transfection with miR-320a mimics compared with NC-mimic, whereas miR-320a inhibitor displayed contrasting effects by reduced the cell viability and apoptosis in myocardial fibroblasts compared with the NC-inhibitor group. The protein expression levels of collagen I, collagen III, α-smooth muscle actin, phosphorylated (p)-mTOR (ser 2448)/mTOR, p-Akt (ser 473)/Akt, p-Akt (thr 308)/Akt and PIK3CA were significantly increased in miR-320a mimic-transfected HEH2 cells compared with the NC-mimics groups. By con trast, miR-320a inhibitor notably downregulated the expression levels of these proteins compared with the NC-inhibitor group. Collectively, the results of the present study demonstrated that miR-320a promoted myocardial fibroblast proliferation via regulating the PIK3CA/Akt/mTOR signaling pathway in HEH2 cells, suggesting that serum exosomal miR-320a may serve as a potential biomarker for the diagnosis of CHF. PMID:34194551 | PMC:PMC8237386 | D OI:10.3892/etm.2021.10305 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cerebral revascularization for the management of complex middle cerebral artery aneurysm: A case series

xlomafota13 shared this article with you from Inoreader Cerebral revascularization for the management of complex middle cerebral artery aneurysm: A case series Via Experimental and therapeutic medicine Exp Ther Med. 2021 Aug;22(2):883. doi: 10.3892/etm.2021.10315. Epub 2021 Jun 15. ABSTRACT Complex middle cerebral artery (MCA) aneurysms, including aneurysms that are sizeable (large or giant), fusiform, wide-necked or calcified, remain a significant challenge during microsurgical clipping or endovascular coiling as treatment strategies. In the present study, a retrospective analysis of cases of this type of aneurysm treated between August 2012 and December 2019 was performed. From the hospital's database, a total of 13 patients (7 males and 6 females) with a mean age of 39.0 years (range, 13-65 years) were identified. The mean size of the aneurysms was 17.5 mm (range, 3.9-35.0 mm). A total of four patients (30.8%) had ruptured aneurysms and nine (69.2%) had unruptured aneurysms. All aneurysms were treated by proximal occlusion of the parent artery, trapping or excision combined with cerebral revascularization. The bypasses performed i ncluded 10 extracranial-intracranial bypasses and 3 intracranial-intracranial bypasses (1 end-to-end re-anastomosis, 1 interpositional graft and 1 end-to-side reimplantation). Postoperative angiography confirmed that the bypass patency was 92.3% and the clinical outcomes were indicated to be favorable, with a modified Rankin Scale score ≤2 in 12 out of 13 patients (92.3%) at the last follow-up. Taken together, the results of the present analysis suggested that treatment strategies for complex MCA aneurysms should depend on the status and characteristics of the aneurysm, including aneurysm size, location and morphology. For aneurysms that lack perforating arteries in the aneurysm dome, clip trapping or aneurysm excision with or without bypass are preferred as treatment strategies. When there are perforating arteries (particularly the lenticulostriate artery) arising from the aneurysm dome, however, the aneurysms should be treated with bypass followed by proximal occlusion of the pa rent artery or clip reconstruction. PMID:34194561 | PMC:PMC8237261 | DOI:10.3892/etm.2021.10315 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.