Myosin phosphatase target subunit 1 governs integrity of the embryonic gut epithelium to circumvent atresia development in medaka, Oryzias latipes

BackgroundIntestinal atresia (IA) is a congenital gut obstruction caused by the absence of gut opening. Genetic factors are assumed to be critical for the development of IA, in addition to accidental vascular insufficiency or mechanical strangulation. However, the molecular mechanism underlying IA remains poorly understood.ResultsIn this study, to better understand such a mechanism, we isolated a mutant of Oryzias latipes (the Japanese rice fish known as medaka) generated by N-ethyl-N-nitrosourea mutagenesis, in which IA develops during embryogenesis. Positional cloning identified a nonsense mutation in the myosin phosphatase target subunit 1 (mypt1) gene. Consistent with known Mypt1 function, the active form of myosin regulatory light chain (MRLC), which is essential for actomyosin contraction, and F-actin were ectopically accumulated in the intestinal epithelium of mutant embryos, whereas cell motility, proliferation and cell death were not substantially affected. Corresponding to the accumulation site of F-actin/active MRLC, the intestinal epithelium architecture was disordered. Importantly, blebbistatin, a non-muscle myosin inhibitor, attenuated the development of IA in the mutant.ConclusionsCytoskeletal contraction governed by mypt1 regulates the integrity of the embryonic intestinal epithelium. This study provides new insight into our understanding of the mechanism of IA development in humans.Bullet PointsMedaka mypt1 mutants display intestinal atresia.The level of phosphorylated myosin regulatory light chain was higher in mypt1 mutant embryos than in wild-type embryos.The levels of F-actin appeared elevated in the intestinal epithelium of mypt1 mutants.Blebbistatin, an inhibitor of non-muscle myosin II, rescued intestinal atresia in mypt1 mutant embryos.

Fresh Osteochondral Allograft Transplantation in Osteochondritis Dissecans in the Knee Joint

Osteochondritis dissecans (OCD) is a chronic and painful joint condition that can occur from childhood through to adult life. Microtrauma, vascular insufficiency, or abnormal endochondral ossification are the most common causes of OCD. Reconstructive techniques for OCD of the knee are typically necessary when either non-operative or reparative/regenerative operative treatments fail, or when the OCD is irreversible. To analyze the clinical outcomes and failure rates of fresh osteochondral allograft transplantation (FOCA) used as a reconstructive strategy in OCD patients, an in-depth search was carried out on the PubMed, Scopus, and Web of Science databases concerning the existing evidence related to the use of FOCA for OCD patients in the knee joint. A total of 646 studies were found through the search and 2 studies were added after a cross-referenced examination of the articles within the bibliography. Six studies with a total of 303 OCD lesions treated with FOCA, with a mean follow-up of 6.3 years, were included. Although a limited number of low-level evidence studies on this topic are available in previous research, satisfactory clinical results and survival rates of the reconstruction are reported. However, to better define the real advantages of FOCA in the healing process of OCD lesions, comparative studies with different techniques are needed.

Hyperbaric oxygen therapy as an adjunctive treatment for pyoderma gangrenosum: a case report

<p class="abstract">Pyoderma gangrenosum is an uncommon inflammatory dermatosis associated with chronic wounds. Diagnosis and management can be challenging to clinicians due to the relapsing nature of the disorder, atypical presentations, and exclusion of other conditions before diagnosis. Hyperbaric oxygen therapy is not a mainstay of treatment for pyoderma gangrenosum, but it is used for non-healing wounds associated with diabetes and vascular insufficiency due to its primary mechanism of tissue hyperoxia, resultant angiogenesis, and reduction of edema and inflammation. This case report presents two patients with pyoderma gangrenosum who were provided adjunctive therapy with hyperbaric oxygen with favorable outcomes.</p>

Spontaneous regression of laryngeal squamous cell carcinoma: an unknown occurrence: a rare case report

Background Spontaneous regression of squamous cell carcinoma is extremely rare and a very challenging phenomenon. Here, we are presenting such a rare case of biopsy-proven laryngeal squamous cell carcinoma who underwent tracheostomy and later the growth regressed without any treatment. Case presentation A histologically proven laryngeal squamous cell carcinoma where the tumour initially leads to the tracheostomy as it compromised the airway and later on the patient presented with the accidental decannulation and the laryngoscopy showed regression of the tumour to the extent that the patient did not require retracheostomy before undergoing radiotherapy. Here, vascular insufficiency of large tumour could have necrosed the tumour along with other factors. Conclusion This case shows the existence of endogenous control in the host against the tumour. A greater understanding of these controlling factors may help us in the future.

Cutaneous metastatic osteosarcoma – A rare case report

Introduction/Objective Osteosarcoma is an aggressive malignant primary bone tumor with common metastases to lungs via hematogenous spread. Other common sites of metastasis include bone and kidneys. Metastasis (excluding extraskeletal) to the skin is extremely rare. To date, roughly 12 cases of cutaneous metastasis have been reported in the literature. Methods/Case Report We report a 44-year-old female patient with a history of osteosarcoma of proximal tibia who underwent wide local excision in 2018 and subsequent chemotherapy. Approximately 2 years after her initial diagnosis, she presented with a painful mass in the left mid-thigh. Imaging studies revealed a 1.7 cm calcified nodule suspicious for metastatic osteosarcoma or a partially calcified granuloma. Fat necrosis and old hematoma were also considered in the radiographic differential, although less likely. An excisional biopsy was performed, which showed a high grade osteoid-producing tumor involving the deep dermis and subcutaneous adipose tissue confirming a metastasis of osteosarcoma. A new skin nodule developed at the same site six months later; though radiographic imaging studies were suggestive of subcutaneous fat stranding in the setting of cellulitis or vascular insufficiency. Given her prior history, another excisional biopsy was performed, which showed recurrent metastatic osteosarcoma. Results (if a Case Study enter NA) NA Conclusion Metastatic osteosarcoma to the skin is a rarely reported event in the literature. The prior clinical history and high index of clinical suspicion are essential in rendering the correct diagnosis. As the skin may be the first site of metastases it is important to include metastatic osteosarcoma in the differential in patients with a prior history of osteosarcoma who develops new skin or subcutaneous lesions. This case highlights the importance of providing history to the pathologist, as other tumors and non-neoplastic lesions can mimic osteosarcoma, particularly in small biopsy specimens. The easier access to the skin/ subcutis could also aid in obtaining tissue for molecular testing.

Ginkgo Biloba, a famous living fossil tree and an ancient herbal traditional Chinese medicine

Background: Ginkgo (Ginkgo biloba) is a living fossil and a deciduous tree, which has extracts with antidiabetic, antioxidant anticancer, antihypertensive, immunestimulative, hepato-protective and antimicrobial activities, memory enhancement efficiency and beneficial effects against neurodegenerative disease. Objective: The goal of this manuscript is survey on medicinal values and natural benefits of Ginkgo. Methods: This review evaluated publication in MEDLINE/PubMEd database and Google Scholar. The keywords used to electronically search were Ginkgo biloba, living fossil, bioactive components and traditional Chinese medicine. Results: Its main active constituents extracts are flavones glycosides such kaempferol, quercetin and isorhamnetin, terpene lactones, alkyphenols, proanthocyanadins, rhamnose, glucose, D-glucaric acid, ginkgolic acid, organic acids such as hydroxykinurenic, kynurenic, protocatechic, shikimic and vanillic. Ginkgo kernels have been used as medicine or eaten as nut in traditional medicinal science. The most notable pharmaceutical application of Ginkgo are in cardiovascular disease, Alzheimer, impaired cerebral performance, vascular insufficiency, antidepressant-induced sexual dysfunction, premenstrual syndrome, liver fibrosis, vascular disease, tinnitus, macular degeneration, memory and vertigo. Conclusion: Development of modern drugs from Ginkgo by considering the importance of traditional medicinal Asian science with further researches should be emphasized.

Recurrent Facial Focal Seizures With Chronic Striatopathy and Caudate Atrophy—A Double Whammy in an Elderly Woman With Diabetes Mellitus

Seizures and involuntary movements are relatively rare, but well-known neurological complications of non-ketotic hyperglycemia. While hemichorea-hemiballism secondary to diabetic striatopathy is increasingly being reported, unilateral caudate atrophy resulting from chronic vascular insufficiency/insult in a backdrop of poorly controlled diabetes mellitus is sparsely described in literature. We herein report a 75-year-old woman with poorly controlled diabetes mellitus who presented with concurrent epilepsia partialis continua involving left side of her face and hemichorea on the right side in the context of non-ketotic hyperglycemia. Neuroimaging revealed a space-occupying lesion suggestive of low-grade glioma in the right superior frontal cortex and left-sided caudate atrophy as well. Possibly, space-occupying lesion in motor cortex acted as an inciting factor for seizures and non-ketotic hyperglycemia further lowered the seizures threshold. On the other hand, atrophied left caudate had led to persistent choreiform movements secondary to chronic uncontrolled hyperglycemia. The simultaneous presence of acute and chronic neurological complications of diabetes mellitus makes this case unique. It also highlights the need for strict control of blood glucose and utility of appropriate neuroimaging to rapidly diagnose and prevent further complications.

Bow hunter syndrome in rheumatoid arthritis: illustrative case

BACKGROUND Rheumatoid arthritis (RA) frequently features degeneration and instability of the cervical spine. Rarely, this degeneration manifests as symptoms of bow hunter syndrome (BHS), a dynamic cause of vertebrobasilar insufficiency. OBSERVATIONS The authors reviewed the literature for cases of RA associated with BHS and present a case of a man with erosive RA with intermittent syncopal episodes attributable to BHS as a result of severe extrinsic left atlantooccipital vertebral artery compression from RA-associated cranial settling. A 72-year-old man with RA-associated cervical spine disease who experienced gradual, progressive functional decline was referred to a neurosurgery clinic for evaluation. He also experienced intermittent syncopal events and vertiginous symptoms with position changes and head turning. Vascular imaging demonstrated severe left vertebral artery compression between the posterior arch of C1 and the occiput as a result of RA-associated cranial settling. He underwent left C1 hemilaminectomy and C1–4 posterior cervical fusion with subsequent resolution of his syncope and vertiginous symptoms. LESSONS This is an unusual case of BHS caused by cranial settling as a result of RA. RA-associated cervical spine disease may rarely present as symptoms of vascular insufficiency. Clinicians should consider the possibility, though rare, of cervical spine involvement in patients with RA experiencing symptoms consistent with vertebral basilar insufficiency.

Fetal Cardiac Lipid Sensing Triggers an Early and Sex-Related Metabolic Energy Switch in Intrauterine Growth Restriction

CONTEXT Intrauterine growth restriction (IUGR) is an immediate outcome of an adverse womb environment, exposing newborns to developing cardiometabolic disorders later in life. This study investigates the cardiac metabolic consequences and underlying mechanism of energy expenditure in developing fetuses under conditions of IUGR. METHODS Using an animal model of IUGR characterized by uteroplacental vascular insufficiency, mitochondrial function, gene profiling, lipidomic analysis, and transcriptional assay were determined in fetal cardiac tissue and cardiomyocytes. RESULTS IUGR fetuses exhibited an upregulation of key genes associated with fatty acid breakdown and β-oxidation (Acadvl, Acadl, Acaa2), and mitochondrial carnitine shuttle (Cpt1a, Cpt2), instigating a metabolic gene reprogramming in the heart. Induction of Ech1, Acox1, Acox3, Acsl1, and Pex11a indicated a coordinated interplay with peroxisomal β-oxidation and biogenesis mainly observed in females, suggesting sexual dimorphism in peroxisomal activation. Concurring with the sex-related changes, mitochondrial respiration rates were stronger in IUGR female fetal cardiomyocytes, accounting for enhanced ATP production. Mitochondrial biogenesis was induced in fetal hearts with elevated expression of Ppargc1a transcript specifically in IUGR females. Lipidomic analysis identified accumulation of arachidonic, eicosapentaenoic, and docosapentaenoic polyunsaturated long-chain fatty acids in IUGR fetal hearts, which lead to nuclear receptor PPARα transcriptional activation in cardiomyocytes. Also, enrichment of H3K27ac chromatin marks to PPARα responsive metabolic genes in IUGR fetal hearts outlines an epigenetic control in the early metabolic energy switch. CONCLUSION These data are consistent with a premature and sex-related remodeling of cardiac metabolism in response to an unfavorable intrauterine environment, with specific long-chain fatty acids that may serve as predictive effectors leading to IUGR.

Potential Activity Mechanisms of Aesculus hippocastanum Bark: Antioxidant Effects in Chemical and Biological In Vitro Models

The bark of Aesculus hippocastanum is an herbal remedy used in conditions connected with vascular insufficiency; however, there is a lack of data concerning its mechanisms of action. The present work is a preliminary investigation into some of the potential directions of the bark activity. The phytochemically (qualitative UHPLC-PDA-MS/MS and quantitative UHPLC-PDA assays) characterized extract and its four main constituents (esculin, fraxin, (‒)-epicatechin and procyanidin A2) were first evaluated in terms of their antioxidant capacity. All analytes demonstrated dose-dependent scavenging potential towards the most common in vivo oxidants, with particularly advantageous capacity of the extract and its flavan-3-ol constituents against peroxynitrite (3.37–13.26 mmol AA/g), hydroxyl radical (5.03–8.91 mmol AA/g) and superoxide radical (3.50–5.50 mmol AA/g). Moreover, even at low concentrations (1–5 µg/mL), they protected components of human plasma against oxidative damage inflicted by peroxynitrite, preventing oxidation of plasma protein thiols and diminishing the tyrosine nitration and lipid peroxidation. High efficiency of the analytes was also demonstrated in preventing the peroxynitrite-induced nitrative changes of fibrinogen (up to 80% inhibition for (−)-epicatechin at 50 µg/mL), an important protein of coagulation cascade. Additionally, the extract and its constituents had, at most, moderate inhibitory activity towards platelet aggregation induced by ADP and only negligible influence on clotting times. The results show that, among the investigated properties, the antioxidant activity might, to the highest extent, be responsible for the bark efficacy in vascular disorders, thus supporting its application in those conditions; they also indicate the directions for future research that would allow for better understanding of the bark activity.