Transitional cell carcinoma in a patient with X‐linked hyperimmunoglobulin M syndrome

Patients with X‐linked hyperimmunoglobulin M syndrome (XHIGM) have a defective CD40–CD40 ligand system and further immunoglobulin class‐switching. They may present with recurrent infection and malignancy involving the liver, pancreas or biliary tract. We report here a case of poorly differentiated transitional cell carcinoma in a young man with XHIGM even on regular treatment and discuss the possible pathogenesis. Given that the triggering of the CD40–CD40 ligand system has been found to improve tumor immunogenicity in recent studies, future immunotherapy targeting the CD40 ligand for these patients may be feasible to prolong their survival.     

Physiological concentrations of melatonin inhibit the nitridergic pathway in the Syrian hamster retina

In the present work, the effect of melatonin on the hamster retinal nitridergic pathway was examined. When the retinas were incubated in the presence of low concentrations (1 pM-10 nM) of melatonin for 15 min, a significant decrease of nitric oxide synthase (NOS) activity was observed. However, when crude retinal homogenates were preincubated with melatonin for 15 min, no changes in NOS activity were detected, despite the fact that under the same conditions trifluoperazine, a calmodulin inhibitor, significantly decreased enzymatic activity. Kinetic analysis showed that melatonin decreased the V(max) of retinal NOS without changes in the K(m). On the other hand, low concentrations (100 pM) of melatonin significantly reduced retinal L-arginine influx. A decrease in the V(max) of L-arginine uptake was observed in the presence of melatonin, whereas the K(m) remained unchanged. Melatonin significantly inhibited the accumulation of cyclic guanosine monophosphate (cGMP) levels induced by both L-arginine and sodium nitroprusside (SNP). In summary, the present results indicate that melatonin could be a potent inhibitor of the retinal nitridergic pathway.     

The efficiency of Poly(ADP‐Ribose) Polymerase (PARP) cleavage on detection of apoptosis in an experimental model of testicular torsion

The aim of this study was to evaluate the histopathological and apoptotic changes occurring in the rat ipsilateral and contralateral testes, after experimental spermatic cord torsion, and to explore and the role of poly(ADP‐ribose) polymerase (PARP) cleavage in testicular torsion–detorsion injury. A total of 37 Wistar albino rats were subjected to 720° unilateral spermatic cord torsion for 1, 2 and 4 h, followed by 4‐h reperfusion, or else to a sham operation (control group). Histology of the testicle was evaluated using haematoxylin–eosin (H&E) staining and Johnsen's scoring system. Germ cell apoptosis was evaluated via active caspase‐3 immunostaining, and PARP expression levels were evaluated via Western blotting. The mean Johnsen's tubular biopsy scores (JTBS) of the ipsilateral testicles were lower for all torsion groups than for the controls (P < 0.05), but the JTBS of the contralateral testicles were only lower in the 4‐h torsion group (P < 0.05). The mean apoptosis score (AS) of the ipsilateral and contralateral testicles was significantly higher in the torsion groups than in the sham group. AS increased correlatively with torsion time, in both testicles. The effect of testicular torsion on PARP cleavage was time dependent, with the highest effect observed after 4 h of testicular torsion (P < 0.05). Testicular torsion caused time‐dependent histological changes, apoptosis and increases in PARP cleavage. Our results suggest that testicular torsion–detorsion injury caused cell damage and germ cell apoptosis that apparently involved cleavage of PARP. Increased PARP cleavage could, in turn, lead to enhanced apoptosis.     

DCLK1, a promising colorectal cancer stem cell marker,regulates tumor progression and invasion through miR-137 and miR-15a dependent manner

Cancer stem cells (CSCs) are thought to be a major player in tumor initiation, progression, and metastasis. Targeting CSCs for elimination presents a promising therapeutic strategy; however, this approach will require a stronger understanding of CSC biology and identification of CSC-specific markers. The present study was conducted to examine the correlation between DCLK1 and miR-137 and miR-15a levels in colorectal cancer. A total of 222 samples, including 181 colorectal cancer specimens, 24 adenomatosis, and 17 non-adenomatosis colonic polyps, were stained for DCLK1 expression using immunohistochemistry. Also, expression of miR-137 and miR-15a was assessed in colorectal cancer with high and low DCLK1 expression levels. Most colorectal cancer specimens (76%) showed strong expression of DCLK1, whereas only 21% of adenomatous and none of non-adenomatous colonic polyps showed strong DCLK1 expression. A significant difference in DCLK1 expression was found between colorectal cancer, adenomatous, and non-adenomatous colonic polyps (P < 0.001). Higher expression of DCLK1 was more frequently detected in colorectal cases with larger tumor size (P = 0.03), poor differentiation (P = 0.03), and lymph node involvement (P = 0.04). Comparison of miR-137 and miR-15a in colorectal cancer cases revealed a significant inverse correlation with DCLK1 expression (P = 0.03 and P = 0.04, respectively). DCLK1 may act as a candidate marker for colorectal cancer stem cells. The critical role of DCLK1 in colorectal cancer suggests that it may represent an early diagnostic marker and therapeutic target; however, further investigation is warranted.

     

Substantial regional differences in the biomechanical behavior of molar treated with selective caries tissue removal technique: a finite element study

ObjectivesSelective caries removal (SCR) is recommended over non-selective removal for managing deep carious lesions to avoid pulp exposure and maintain pulp vitality. During SCR, residual carious dentin is left behind and sealed beneath the restoration. The biomechanical effects of such residual lesions on the restored tooth remain unclear and were assessed using finite element modeling (FEM).MethodsBased on μ-CT images of a healthy permanent human third molar, we developed five finite element models. Generic class I and II cavity restorations were modeled where residual lesions of variable sizes were either left or fully removed on occlusal and proximal surfaces. The cavities were restored with adhesive composite. All 3D-FE models were compared with a model of a healthy, non-treated molar. A vertical load of 100 N was applied onto the occlusal surface.ResultsRegardless of the lesion size, in molars with occlusal lesions higher mean stresses were predicted along the filling-lesion interface than in all other models. The smallest occlusal lesion (Ø₁ = 1 mm) resulted in the highest maximum stresses at the filling-lesion interface with large stress concentrations at the filling walls indicating failure risk. In conclusion, lesion site and extent are influencing parameters affecting the filling-lesion interactions and thus the biomechanical behavior of the tooth after SCR.SignificanceRetaining carious lesions around the pulpal floor affects the deformation and stress states in tooth-filling complexes. The higher stresses observed in molars with occlusal lesions may affect restoration stability and longevity. Suprisingly, more extended occlusal lesions may provide a more favorable tooth performance than less extended ones. In contrast, in molars with proximal lesions the residual lesion had only limited effect on the tooth’s biomechanical condition.     

Haemorrhage control beyond Advanced Trauma Life Support (ATLS) protocol in life threatening maxillofacial trauma – experience from a level Ⅰ trauma centre

Maxillofacial injuries are usually not life-threatening and do not get priority over other associated injuries. However, some maxillofacial injuries with active oral or nasal bleeding need immediate management due to threatened airway and blood loss. In the case of major active vascular bleeding, measures such as local pressure, anterior nasal packing, posterior nasal packing, and balloon tamponade are ineffective. In these cases, angiography and transcatheter arterial embolisation (TAE) are used to treat life-threatening haemorrhage caused by maxillofacial trauma. We analysed the medical records of 39 patients with severe maxillofacial trauma and life-threatening haemorrhage that was a result of intractable oral or nasal bleeding. These patients were considered for TAE from January 2010 to December 2019. A total of 1668 patients was admitted, out of which 39 (2.3%) had severe maxillofacial injuries with life-threatening oral or nasal bleeding and underwent TAE. Out of a total of 39 patients, 38 were male and one female. Ages ranged from 16 to 65 years. Road traffic injury was the most common cause of injury (79.5%), Lefort I and II were the most common facial fractures, and traumatic brain injury was the most common associated injury. Embolisation and bleeding control were done successfully in all 39 patients with no procedure-related complications. A total of 17 deaths during the study period were due to severe traumatic brain injuries or haemorrhagic shock.     

Venous thromboembolism in patients with COVID-19. A prevalent and a preventable complication of the pandemic

Coronavirus disease 2019 or most commonly known as COVID-19 is a trending global infectious disease which a few months ago was affirmed as a global health emergency or a pandemic by the WHO Emergency Committee. The common symptoms manifested in this pandemic disease are high grade fever, cough, fatigue, shortness of breath and flu like symptom which can evolve into severe respiratory disorders such as pneumonia, acute respiratory distress syndrome (ARDS) and/or end-organ failure. Factors that contribute to the severity or high mortality rate in COVID-19 include old age, comorbidities like hypertension, diabetes, hyperlipidaemia, neutrophilia, and organ and coagulation dysfunction. Disseminated intravascular coagulation and other various coagulopathies including Venous thromboembolism have known to become a major contributing factor to high mortality rate. Venous thromboembolism is a disease which is a combination of deep vein thrombosis and pulmonary embolism. Prophylactic anticoagulation in patients prone to or with a pre-existing history of venous thromboembolism is associated with decreased mortality in severe COVID-19 pneumonia. This review article focuses upon COVID-19 and increased incidence of venous thromboembolism in patients infected by COVID-19 along with the role it has in high mortality rate in COVID-19 patients.     

Differentiation of Wharton's jelly mesenchymal stem cells into neurons in alginate scaffold

Alginate scaffold has been considered as an appropriate biomaterial for promoting the differentiation of embryonic stem cells toward neuronal cell lineage. We hypothesized that alginate scaffold is suitable for culturing Wharton's jelly mesenchymal stem cells(WJMSCs) and can promote the differentiation of WJMSCs into neuron-like cells. In this study, we cultured WJMSCs in a three-dimensional scaffold fabricated by 0.25% alginate and 50 m M Ca Cl2 in the presence of neurogenic medium containing 10 μM retinoic acid and 20 ng/m L basic fibroblast growth factor. These cells were also cultured in conventional two-dimensional culture condition in the presence of neurogenic medium as controls. After 10 days, immunofluorescence staining was performed for detecting β-tubulin(marker for WJMSCs-differentiated neuron) and CD271(motor neuron marker). β-Tubulin and CD271 expression levels were significantly greater in the WJMSCs cultured in the three-dimensional alginate scaffold than in the conventional two-dimensional culture condition. These findings suggest that three-dimensional alginate scaffold cell culture system can induce neuronal differentiation of WJMSCs effectively.