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MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

Neural Regeneration Research 2024年第12期19卷 2698-2707页

作者： Bhupender Sharma Melissa MTorres Sheryl Rodriguez Laxman Gangwani subodh kumar Center of Emphasis in Neuroscience Department of Molecular and Translational MedicinePaul L.Foster School of MedicineTexas Tech University Health Sciences CenterEl PasoTXUSA Bond Life Sciences Center and Department of Veterinary Pathobiology University of MissouriColumbiaMOUSA L.Frederick Francis Graduate School of Biomedical Sciences Texas Tech University Health Sciences CenterEl PasoTXUSA

Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse f

关键词： Alzheimer's disease GABAergic synapse gamma-aminobutyric acid type A receptor subunitα-1(GABRα1) microRNA-502-3p(miR-502-3p) miRNA in situ hybridization Patch-clamp

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Synaptosome microRNAs:emerging synapse players in aging and Alzheimer’s disease

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Neural Regeneration Research 2023年第6期18卷 1275-1276页

作者： subodh kumar Center of Emphasis in Neuroscience Department of Molecular and Translational Medicine Paul L.Foster School of Medicine Texas Tech University Health Sciences CenterEl PasoTXUSA

Synaptosome:Synapses are the most critical portion of neuron connections,necessary for cellular organization of the brain.Synapse integrity is uttermost important for healthy brain functioning.Any perturbation in the synapse structure and/or function initiates neurological disorders.Synapses are the prime targets that are smashed in almost all neurodegenerative diseases.The vital components of synapse are essential for neurotransmission,synaptic plasticity and overall synapse function.Synapse dysfunctions are well studied in Alzheimer’s disease(AD)and other neurodegenerative diseases(Gowda et al.,2021).The best way to study the synapse dysfunctions in neurological diseases is the biochemical analysis of“synaptosome”.

关键词： Alzheimer diseases

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Gastroduodenal artery aneurysm - A rare complication of traumatic pancreatic injury

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Chinese Journal of Traumatology 2016年第6期19卷 368-370页

作者： Annu Babu Amulya Rattan Maneesh Singhal Amit Gupta subodh kumar Division of Trauma Surgery & Critical Care JPN Apex Trauma Center Department of Surgical Disciplines All India Institute of Medical Sciences New Delhi India

Aneurysm of gastroduodenal artery (GDA) is rare. Most reported cases are due to pancreatitis and atherosclerosis; however, those following pancreatic trauma have not been reported. We encoun- tered GDA aneurysm in a patient of blunt abdominal trauma, who had pancreatic contusion and retroduodenal air on contrast enhanced computed tomography of abdomen. Emergency laparotomy for suspected duodenal injury revealed duodenal wall and pancreatic head contusion, mild hemo- peritoneum and no evidence of duodenal perforation. In the postoperative period, the patient developed upper gastrointestinal hemorrhage on day 5. Repeat imaging revealed GDA aneurysm, which was managed successfully by angioembolization. This case highlights, one, delayed presen- tation of GDA aneurysm after blunt pancreatic trauma and two, its successful management using endovascular technique.

关键词：十二指肠胰腺炎动脉瘤损伤并发症外伤性动脉粥样硬化上消化道出血

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Penetrating neck injury： Collaterals for another life after ligation of common carotid artery and subclavian artery

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Chinese Journal of Traumatology 2017年第1期20卷 56-58页

作者： Annu Babu Harshit Garg Sushma Sagar Amit Gupta subodh kumar Department of Surgery JPN Apex Trauma Centre All India Institute of Medical Science New Delhi India

Neck, being not protected by skeleton, is vulnerable to external trauma and injury which involves blood vessels, trachea, esophagus and other endocrine and nervous system organs. Vascular injuries can not only cause potentially life-threatening hemorrhage but also need profound surgical expertise in management. Development of collateral circulation in neck is well known; however, there is scarcity of literature on the role of collateral formation in neck trauma. Here, we present a unique case of penetrating gunshot injury to neck with right common carotid and right subclavian artery injury with hemorrhagic shock managed with ligation of these vessels as a life-saving procedure. The patient presented with no neurological or motor deficits in immediate postoperative period owing to the collateral circulation between right vertebral artery and right common carotid and right subclavian artery.

关键词： Collaterals Common carotid artery Neck injury Subclavian artery

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Traumatic cardiac injury： Experience from a level-1 trauma centre

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Chinese Journal of Traumatology 2016年第6期19卷 333-336页

作者： Biplab Mishra Amit Gupta Sushma Sagar Maneesh Singhal subodh kumar Division of Trauma Surgery & Critical Care. JPN Apex Trauma Centre. All India Institute of Medical Sciences. New Delhi India

OBJECTIVE:Traumatic cardiac injury (TCI) is a challenge for trauma surgeons as it provides a short thera- peutic window and the management is often dictated by the underlying mechanism and hemodynamic status. The current study is to evaluate the factors influencing the outcome of TCI.;METHODS:Prospectively maintained database of TCI cases admitted at a Level-1 trauma center from July 2008 to June 2013 was retrospectively analyzed. Hospital records were reviewed and statistical analysis was performed using the SPSS version 15.;RESULTS:Out of 21 cases of TCI, 6 (28.6%) had isolated and 15 (71.4%) had associated injuries. Ratio be- tween blunt and penetrating injuries was 2:1 with male preponderance. Mean ISS was 31.95. Thirteen patients (62%) presented with features suggestive of shock. Cardiac tamponade was present in 12 (57%) cases and pericardiocentesis was done in only 6 cases of them. Overall 19 patients underwent surgery. Perioperatively 8 (38.1%) patients developed cardiac arrest and 7 developed cardiac arrhythmia. Overall survival rate was 71.4%. Mortality was related to cardiac arrest (p = 0.014), arrhythmia (p = 0.014), and hemorrhagic shock (p =0.04). The diagnostic accuracy of focused assessment by sonography in trauma (FAST) was 95.24%.;CONCLUSIONS:High index of clinical suspicion based on the mechanism of injury, meticulous examination by FAST and early intervention could improve the overall outcome.

关键词：穿透性损伤外伤性创伤心脏失血性休克手术治疗心律失常损伤机制

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Comparison of ISS, NISS, and RTS score as predictor of mortality in pediatric fall

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Burns & Trauma 2017年第3期5卷 209-214页

作者： Kapil Dev Soni Santosh Mahindrakar Amit Gupta subodh kumar Sushma Sagar Ashish Jhakal Department of Trauma Surgery and Critical Care Jai Prakash Narayan Trauma Centre AIIMS New Delhi India

Background:Studies to identify an ideal trauma score tool representing prediction of outcomes of the pediatric fall patient remains elusive. Our study was undertaken to identify better predictor of mortality in the pediatric fall patients. Methods:Data was retrieved from prospectively maintained trauma registry project at level 1 trauma center developed as part of Multicentric Project—Towards Improving Trauma Care Outcomes (TITCO) in India. Single center data retrieved from a prospectively maintained trauma registry at a level 1 trauma center, New Delhi, for a period ranging from 1 October 2013 to 17 February 2015 was evaluated. Standard anatomic scores Injury Severity Score (ISS) and New Injury Severity Score (NISS) were compared with physiologic score Revised Trauma Score (RTS) using receiver operating curve (ROC). Results:Heart rate and RTS had a statistical difference among the survivors to nonsurvivors. ISS, NISS, and RTS were having 50, 50, and 86% of area under the curve on ROCs, and RTS was statistically significant among them. Conclusions: Physiologically based trauma score systems (RTS) are much better predictors of inhospital mortality in comparison to anatomical based scoring systems (ISS and NISS) for unintentional pediatric falls.

关键词： Pediatric fall Trauma score system ISS NISS RTS

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Varied presentations, magnitude, and outcome of traumatic neck injuries at a level I trauma center

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Emergency and Critical Care Medicine 2022年第2期2卷 45-49页

作者： Parvez Mohi Ud Din Dar Jogendra Boddeda Supreet Kaur Pratyusha Priyadarshini Abhinav kumar Dinesh Bagaria Narendra Choudhary Junaid Alam Sushma Sagar subodh kumar Amit Gupta Biplab Mishra Division of Trauma Surgery and Critical Care Jai Prakash Narayan Apex Trauma CentreAll India Institute of Medical Sciences(AIIMS)New DelhiIndia Department of General Surgery All India Institute of Medical Sciences(AIIMS)JodhpurRajasthanIndia

Introduction:Traumatic neck injuries(TNIs)constitute 5%–10%of all trauma cases.These injuries can be caused by either penetrating or blunt trauma.Patients can have a varied presentation like cut injury over the neck,bleeding,neck swelling,breathing difficulty,dysphagia,etc.Methods:This was a retrospective observational study conducted at a level I trauma center in India from January 2016 to March 2020.One hundred thirty patients who required admission and intervention due to TNIs were included in this study.Results:One hundred thirty patients with neck injuries were included in this study.Males were predominant(91.5%)with the age ranging from 10 to 70years.The most common mechanism of injury was physical assault(40.7%),followed by road traffic injury(23.8%)and self-inflicted injuries(18.4%).Penetrating trauma was predominant.Open neck wound with bleeding was the most common presenting symptom.Zone II injuries were more common(83.8%)followed by zone I(12.3%)and zone III(3.8%).Soft tissue injury including skin,platysma breach,and strap muscle injury was present in 46.9% of patients.Laryngopharyngeal injury was present in 13.8%,tracheal injury in 28.5%,vascular injury in 13.8%,and esophageal injury in 4.6% of patients.Conclusion:Penetrating neck trauma is more common than blunt in developing countries like India.Advanced Trauma Life Support(ATLS)protocol guides the initial management.The definitive management depends on the type and mechanism of injury,anatomical level,severity,and the organ injured.

关键词： Bleeding Neck trauma Resuscitation Trachea Vascular injury

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An overview of pancreatic trauma

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Journal of Pancreatology 2020年第3期3卷 139-146页

作者： Harshit Agarwal Amit Gupta subodh kumar Division of Trauma Surgery&Critical Care JPN Apex Trauma CenterAll India institute of Medical SciencesNew DelhiIndia

Pancreatic trauma remains a challenge to a trauma surgeon even with extensive advancement in medicine.The mortality and morbidity associated with this injury remain high.A high index of suspicion,mechanism of injury,and early identification hold key in the final outcome.The management of pancreatic injury should involve a multidisciplinary team comprising of trauma surgeons,radiologists,and gastroenterologists.This review highlights the burden of the pancreatic injury and its management.

关键词： Distal pancreatectomy ERCP Pancreatic trauma

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Innocuous cardiac gunshot that proved fatal： A bitter lesson learned

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Chinese Journal of Traumatology 2017年第2期20卷 122-124页

作者： Biplab Mishra Mohit kumar Joshi subodh kumar Atin kumar Amit Gupta Amulya Rattan Sushma Sagar Maneesh Singhal Mahesh Chandra Misra Department of Surgical Disciplines. JPN Apex Trauma Centre. All India Institute of Medical Sciences New Delhi 110029. India Department of Radiodiagnosis. JPN Apex Trauma Centre. All India Institute of Medical Sciences New Delhi 110029 India

有保留的 intra 心囊的外国身体的血液动力学地正常的病人的管理仍然是一件事推测。可得到的文学支持如此的无害的外国身体的非起作用的管理。我们从火器损害与一个保留的 intra 心囊的小团报导我们一个血液动力学地正常的病人的经验。... 详细信息

有保留的 intra 心囊的外国身体的血液动力学地正常的病人的管理仍然是一件事推测。可得到的文学支持如此的无害的外国身体的非起作用的管理。我们从火器损害与一个保留的 intra 心囊的小团报导我们一个血液动力学地正常的病人的经验。他开始收到了成功的非起作用的管理，但是开发了致命的 hemopericardium 在损害以后的 21 天。在这份报纸，我们考虑到可得到的文学在如此的损害的管理讨论了陷井并且总结了临床的经验。

关键词：心包心创伤射击火器

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Management and outcome of pancreatic trauma:a 6-year experience at a level I trauma center

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Emergency and Critical Care Medicine 2023年第1期3卷 6-11页

作者： Abhinav Anand Parvez Mohi Ud Din Dar Preksha Rani Supreet Kaur Joses Dany James Junaid Alam Pratyusha Priyadarshini Abhinav kumar Dinesh Bagaria Narendra Choudhary subodh kumar Amit Gupta Sushma Sagar Biplab Mishra Division of Trauma Surgery and Critical Care Jai Prakash Narayan Apex Trauma CentreAll India Institute of Medical Sciences(AIIMS)New DelhiIndia Department of Trauma and Emergency Medicine All India Institute of Medical Science(AIIMS)VijaypurJammuJammu and KashmirIndia Department of General Surgery All India Institute of Medical Science(AIIMS)JodhpurRajasthanIndia

Background: Pancreatic trauma (PT) accounts for less than 1% of all trauma admissions. Occasionally, PT is undetected during theprimary survey and becomes apparent only when complications arise. It occurs in up to 5% of blunt abdominal trauma cases and 12%of individuals with penetrating abdominal injuries. Management is determined by the status of the main pancreatic duct and associatedinjuries.Methods: This was an ambispective study conducted at the Jai Prakash Narayan Apex Trauma Center, All India Institute ofMedical Sciences,New Delhi, from January 2015 to December 2017 (retrospective), and January 2019 to December 2020 (prospective). In total, 113patients with PT were included in this study.Results:We analyzed the data of 113 patients with PT included in this study, of whichmales predominated (93.7%). Blunt PT was presentin 101 patients (89.4%) and penetrating PT in 12 patients (10.6%). Half of the patients (51.3%) had the American Association for theSurgery of Trauma grade III PT, followed by grade II (18.6%), and grade I (15%). Of the total 113 patients, 68 (60.2%) were treated withoperative management, and 45 (39.8%) with nonoperative management. Distal pancreatectomy, with or without splenectomy, was themost common procedure performed in our study, followed by drainage. There were 27 mortalities (23.8%) during the study period, ofwhich 7 were directly related to PT and 20 were due to other organ-related sepsis and hemorrhagic shock.Conclusion: Pancreatic trauma is rare but challenging for trauma surgeons, with persistent management controversies. Early diagnosisis important for favorable results;however, a delay in diagnosis has been associated with higher morbidity and mortality. Low-grade pancreaticinjuries can be successfully managed nonoperatively, whereas high-grade pancreatic injuries require surgical intervention.

关键词： Abdominal trauma Distal pancreatectomy Management Pancreatic trauma

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