Establishment of acquired tracheoesophageal fistula using a modified magnetic compression technique in rabbits and its postmodeling evaluation

BACKGROUND Previous studies have validated the efficacy of both magnetic compression and surgical techniques in creating rabbit tracheoesophageal fistula(TEF)models.Magnetic compression achieves a 100%success rate but requires more time,while surgery,though less frequently successful,offers rapid model establishment and technical maturity in larger animal models.AIM To determine the optimal approach for rabbit disease modeling and refine the process.METHODS TEF models were created in 12 rabbits using both the modified magnetic compression technique and surgery.Comparisons of the time to model establishment,success rate,food and water intake,weight changes,activity levels,bronchoscopy findings,white blood cell counts,and biopsies were performed.In response to the failures encountered during modified magnetic compression modeling,we increased the sample size to 15 rabbit models and assessed the repeatability and stability of the models,comparing them with the original magnetic compression technique.RESULTS The modified magnetic compression technique achieved a 66.7%success rate,whereas the success rate of the surgery technique was 33.3%.Surviving surgical rabbits might not meet subsequent experimental requirements due to TEF-related inflammation.In the modified magnetic compression group,one rabbit died,possibly due to magnet corrosion,and another died from tracheal magnet obstruction.Similar events occurred during the second round of modified magnetic compression modeling,with one rabbit possibly succumbing to aggravated lung infection.The operation time of the first round of modified magnetic compression was 3.2±0.6 min,which was significantly reduced to 2.1±0.4 min in the second round,compared to both the first round and that of the original technique.CONCLUSION The modified magnetic compression technique exhibits lower stress responses,a simple procedure,a high success rate,and lower modeling costs,making it a more appropriate choice for constructing TEF models in rabbits.

MELLT3 protects against cerebral ischemia-reperfusion (I/R) injury through up-regulation of m6A modification

Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury(CIRI).The exact mechanisms underlying I/R injury are unclear.In this study,we aimed to determine the role of m6A-modified methylase complex methyltransferase-like 3(METTL3)in cerebral ischemiareperfusion(I/R)injury.We found that m6A and METTL3 levels increased in OGD/RX-induced mouse astrocytescerebellar(MA-C)and the brain of middle cerebral artery occlusion(MCAO)model mice.METTL3 siRNA treatment reduced OGD-RX-induced MAC cell viability and proliferation,which increased with METTL3 over-expression.Flow cytometry analysis showed that silencing METTL3 significantly enhanced OGD/RX-induced MAC apoptosis,which was significantly reduced with METTL3 up-regulation.In an MCAO model,METTL3 overexpression significantly reduced cerebral infarction area and decreased brain cell apoptosis,indicating that METTL3 OE treatment could ameliorate brain edema and injury.Thus,METTL3 could be used as a target to treat I/R injury.

Nutraceutical with Anti-Inflammatory Activity for the Management of Airway Remodeling in Bronchial Asthma: <i>Kalanchoe integra</i>Var. Crenata (Andr.) Cuf Leaf Extract

Background: Kalanchoe integra is widely used in folklore medicine as an antiasthmatic agent. Previous studies have shown the ameliorating effect of Kalanchoe integra leaf extract [KILE] on bronchial hyperesponsiveness and inflammation. Further, the stabilizing effect of Kalanchoe sp on mast cell degranulation, suggests that Kalanchoe species are suitable candidates for allergic asthma therapy. This study is designed to investigate the anti-asthmatic potential of KILE and monitor the accompanying histopathological and immunobiochemical changes that occur in an animal model of bronchial asthma using ovalbumin sensitized guinea pigs. Method: Thirty male guinea pigs were divided into five groups of six animals each. Bronchial asthma was simulated in guinea pigs using ovalbumin. Both low dose (300 mg/kg) and high dose extract (900 mg/kg) were administered daily for 42 days. Prednisolone (2.5 mg/kg) was the standard drug used. Results: Guinea pigs in all KILE treated groups maintained the integrity of their airway structures: bronchial folds and walls, alveoli, alveolar ducts and sacs. KILE and prednisolone caused a reduction in immune parameters (p 0.001), extent of bronchoconstriction, bronchial wall thickness and goblet cell accumulation in the sensitized guinea pigs. Conclusion: This study demonstrates the anti-asthmatic potential of KILE during prolonged administration by the oral route.

Contribution of the Advanced Research Laboratories at the Noguchi Memorial Institute for Medical Research (NMIMR) to SARS-CoV-2 Testing in Ghana

In March 2020, the first cases of SARS-CoV-2 were reported in Accra, Ghana. These initial cases were diagnosed at the Advanced Research Laboratories (ARL) of the Noguchi Memorial Institute for Medical Research (NMIMR), University of Ghana. The ARL which hitherto was used for routine clinical research in viral, bacteria and immunological studies has since been the facility of choice for testing for all suspected cases of COVID-19 submitted from across Ghana and beyond. The success of testing at the ARL hinged on the availability of several laboratory spaces furnished with state-of-the-art diagnostic equipment and working aids. During the “peak season” where overwhelming numbers of clinical specimens were received, the ARL processed and got results for close to four thousand samples daily. After general disinfection and re-bagging into smaller numbers, at the entrance of the ARL, the samples are taken to a central receiving laboratory, where they are received and entered in a database with accompanying case investigation forms. All samples that are successfully sorted and matched are sent to general laboratories for nucleic acid extraction and then referred to the Instrumentation laboratory for real time reverse-transcription polymerase chain reaction (RT-PCR). When the RT-PCRs were completed, results were analysed and transmitted via email and/or local network to the data reporting office. The data managers then reported results to the investigators and the Ghana Health Service (GHS). Additionally, the ARL provided a next-generation Genome Sequencing platform in partnership with the West African Centre for Cell Biology of Infectious Pathogens at the University of Ghana, which was essential in reporting the genome data of the circulating variants of SARS-CoV-2 in Ghana. Conclusively, it is worth noting, that the NMIMR fulfilled its mandate of supporting the country with specialized diagnostics through the judicious use of the ARL for SARS-CoV-2 testing, from sample receipt to data reporting. The ARL facility and the research faculty have trained and continue to train budding laboratories on biosafety, biosecurity, best practices and testing protocols. It is obvious that the success story of SARS-CoV-2 testing in Ghana, cannot be complete without the mention of the ARL at NMIMR.