Infection of highly pathogenic coronaviruses triggers apoptosis that can be targeted to reduce disease severity.
Infection by highly pathogenic coronaviruses results in substantial apoptosis. ...However, the physiological relevance of apoptosis in the pathogenesis of coronavirus infections is unknown. Here, with a combination of in vitro, ex vivo, and in vivo models, we demonstrated that protein kinase R–like endoplasmic reticulum kinase (PERK) signaling mediated the proapoptotic signals in Middle East respiratory syndrome coronavirus (MERS-CoV) infection, which converged in the intrinsic apoptosis pathway. Inhibiting PERK signaling or intrinsic apoptosis both alleviated MERS pathogenesis in vivo. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV induced apoptosis through distinct mechanisms but inhibition of intrinsic apoptosis similarly limited SARS-CoV-2– and SARS-CoV–induced apoptosis in vitro and markedly ameliorated the lung damage of SARS-CoV-2–inoculated human angiotensin-converting enzyme 2 (hACE2) mice. Collectively, our study provides the first evidence that virus-induced apoptosis is an important disease determinant of highly pathogenic coronaviruses and demonstrates that this process can be targeted to attenuate disease severity.
Methionine (Met) is an essential amino acid, and its excessive dietary intake and/or its metabolism disturbance could lead to accumulation/depletion of hepatic Met and some of the key intermediates ...of these pathways, which would interfere normal liver function and would be associated with liver diseases. Biliary atresia (BA) is a life-threatening disease characterized by inflammatory fibrosclerosing changes of the intrahepatic and extrahepatic biliary systems and is the primary cause of obstructive neonatal cholestasis with a rapid course of liver failure. However, its pathogenesis remains unknown. Previous studies reported elevated Met level in patients with obstructive cholestasis, suggesting a potential link between Met and BA. This paper reviews the Met metabolism in normal conditions and its dysregulation under abnormal conditions, the possible causes of hypermethioninemia, and its connection to BA pathogenesis: Abnormal hepatic level of Met could lead to a perturbation of redox homeostasis and mitochondrial functions of hepatocytes, enhancement of viral infectivity, and dysregulation of innate and adaptative immune cells in response to infection/damage of the liver contributing to the initiation/progression of BA.
Introduction: Right lower quadrant pain is a usual presentation of many acute abdominal conditions. However, it could as well be the presentation of unusual conditions. To date, cecal perforation as ...a result of fish bone impaction has not been reported in pediatric patients. Case description: A 10-year-old Chinese girl presented with right sided abdominal pain and fever. Abdominal examination revealed tenderness and guarding in the right iliac fossa. She was initially thought to have acute appendicitis. Ultrasound of the abdomen was not conclusive. A computed tomography of the abdomen with contrast revealed that the appendix was not dilated. It also showed a faint 1.3-cm-long linear hyper-density in the cecum, with peritoneal thickening at the right iliac fossa. Laparoscopy confirmed a fish bone impaction causing cecal perforation. The fish bone was retrieved, and the cecal perforation repaired through a McBurney incision. She was discharged 3 days after operation. Conclusion: Although rare, it is important to consider the possibility of an intestinal perforation caused by swallowed foreign objects such as fish bone in children presenting with acute abdominal pain.
Induced pluripotent stem cell (iPSC) technology is one of the de novo approaches in regeneration medicine and has led to new research applications for wound healing in recent years. Fibroblasts have ...attracted wide attention as the first cell line used for differentiation into iPSCs. Researchers have found that fibroblasts can be induced into different types of cells in variable mediums or microenvironments. This indicates the potential “stem” characteristics of fibroblasts in terms of direct cellular reprogramming compared with the iPSC detour. In this review, we described the morphology and biological function of fibroblasts. The stem cell characteristics and activities of fibroblasts, including transdifferentiation into myofibroblasts, osteogenic cells, chondrogenic cells, neurons, and vascular tissue, are discussed. The biological values of fibroblasts are then briefly reviewed. Finally, we discussed the potential applications of fibroblasts in clinical practice.
The model of direct cellular reprogramming and the induced pluripotent stem cell (iPSC)
Highlights
We described the morphology and biological functions of fibroblasts and discussed the stem cell characteristics and activities of fibroblasts, including transdifferentiation into myofibroblasts, osteogenic cells, chondrogenic cells, neurons, and vascular tissue.
The biological value of fibroblasts is also briefly reviewed.
Finally, we provided an overview of the potential application of fibroblasts in clinical practice.
Fluorescence-guided surgery (FGS) is becoming a common practice as an intraoperative aid in both adult and pediatric populations. It makes use of fluorescent contrast agents to identify targeted ...structures intraoperatively for precise resection with the help of a near-infrared (NIR) light camera. A wide spectrum of contrast agents and imaging platforms has been developed throughout the years to enhance their use for intraoperative tissue differentiation. FGS is applied in pediatric surgery for various indications, including thoracic, gastrointestinal, hepatobiliary, urogenital, oncology, and vascular surgery. Despite the popularity of fluorescence-guided pediatric surgery, the current literature is limited. The present review offers an up-to-date appraisal of the development and current status of FGS in the field of pediatric surgery.
Identification of a HOXD13 mutation in a VACTERL patient Garcia‐Barceló, Maria‐Mercè; Wong, Kenneth Kak‐yuen; Lui, Vincent Chi‐hang ...
American journal of medical genetics. Part A,
15 December 2008, Letnik:
146A, Številka:
24
Journal Article
Background: We explored the feasibility of creating BA-like organoids by treating human liver organoids with Polyinosinic:Polycytidylic acid (Poly I:C). Methods: Organoids were developed from the ...liver parenchyma collected during Kasai portoenterostomy (BA) and surgery for other liver disorders (non-BA). The non-BA organoids were co-cultured with poly I:C (40 µg/mL). The organoid morphology from both samples was compared on day 17. RNA-sequencing was performed to examine the transcriptomic differences. Results: Non-BA liver organoids developed into well-expanded spherical organoids with a single-cell layer of epithelial cells and a single vacuole inside. After poly I:C treatment, the majority of these organoids developed into an aberrant morphology with a high index of similarity to BA organoids which are multi-vacuoled and/or unexpanded. RNA-sequencing analysis revealed that 19 inflammatory genes were commonly expressed in both groups. Conditional cluster analysis revealed several genes (SOCS6, SOCS6.1, ARAF, CAMK2G, GNA1C, ITGA2, PRKACA, PTEN) that are involved in immune-mediated signaling pathway had a distinct pattern of expression in the poly I:C treated organoids. This resembled the expression pattern in BA organoids (p < 0.05). Conclusions: Poly I:C treated human liver organoids exhibit morphology and genetic signature highly compatible to organoids developed from BA liver samples. They are potential research materials to study immune-mediated inflammation in BA.
The article reports the application of total oesophagogastric dissociation as an alternative to fundoplication for the treatment of severe gastro‐oesophageal reflux in children.
Introduction
Biliary Atresia (BA) requires prompt diagnosis and surgical intervention to optimize its outcome. The aim of this study was to evaluate the accuracy of EHIDA in distinguishing between BA ...and other causes of cholestatic jaundice.
Methods
This was a retrospective study of all patients who underwent EHIDA in a tertiary center from 1997 to 2019. The sensitivity, specificity, Negative Predictive Value (NPV) and Positive Predictive Value (PPV) of EHIDA were evaluated. Factors that can potentially affect its accuracy were also analyzed.
Results
During the study period, 93 patients aged 10 to 110 days with cholestasis and suspected BA underwent EHIDA. The sensitivity and NPV were 91.2 and 85.3% while specificity and PPV were 80.6 and 88.1%. These results suggested that EHIDA is suboptimal in both diagnosing or excluding BA. Out of 59 patients who showed no tracer activities in the intestines after 24 h, 56 were subjected to surgical exploration and 52 (92.9%) were eventually diagnosed BA. The accuracy of EHIDA scan were different by the maturity of the patient, age at testing and severity of cholestasis.
Conclusions
EHIDA has a limited accuracy and surgical exploration remains the gold standard to establish the diagnosis of BA. Potential confounding factors that may affect the accuracy of EHIDA were identified but require further studies with larger sample sizes to validate.
Thoracoscopy, which has an increasing role in the treatment of indexed neonatal surgical conditions, requires adequate training. To support this, the current study aimed to evaluate the feasibility ...and effectiveness of using live rabbit models in neonatal thoracoscopic skills training among paediatric surgeons.
Following didactic lectures and demonstrations, the participants were given hands-on opportunities to perform thoracoscopic procedures. The feasibility and effectiveness of using live rabbit models in neonatal thoracoscopic skills training among paediatric surgeons were evaluated with pre-/post-course procedural confidence scores and a questionnaire.
This study included 13 paediatric surgeons—2 (15 %) males and 11 (85 %) females—who were evenly distributed. There were four basic surgical trainees, five higher surgical trainees and four fellows in paediatric surgery (mean surgical practice experience: 4.5 ± 3.7 years). Most had experience assisting paediatric (70 %) and neonatal (62 %) thoracoscopic surgery. Only 30 % had experience as the chief surgeon of paediatric thoracoscopic surgery, with none on neonates. Significant improvement was seen in procedural confidence as the assistant and chief surgeon of all procedures post-workshop. The surgeons rated the model positively.
The procedural confidence level of paediatric surgeons improved significantly after workshop participation. This realistic and easily reproducible model can help perfect thoracoscopic skills. Therefore, its integration into paediatric surgical training would promote surgical skill proficiency and could improve surgeons’ confidence in neonate operations.
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