AIM: To evaluate the undifferentiated embryonal sarcoma of liver (UESL) in adults in order to improve its diagnosis and treatment. METHODS: Four primary and one recurrent cases of UESL were clinicopathologically evalu...AIM: To evaluate the undifferentiated embryonal sarcoma of liver (UESL) in adults in order to improve its diagnosis and treatment. METHODS: Four primary and one recurrent cases of UESL were clinicopathologically evaluated and immunohistochemically investigated with a panel of antibodies using the EnVision+ system. Relevant literature about UESL in adults was reviewed. RESULTS: Three males and one female were enrolled in this study. Their chief complaints were abdominal pain, weight loss, or fever. Laboratory tests, imaging and pathological features of UESL in adults were similar to those in children. Immunohistochemistry showed evidence of widely divergent differentiation into mesenchymal and epithelial phenotypes. The survival time of patients who underwent complete tumor resection followed by adjuvant transcatheter arterial chemoembolization (TACE) was significantly longer than that of those who underwent surgical treatment alone.CONCLUSION: UESL in adults may undergo pluripotential differentiation and its diagnosis should be made based on its morphological and immunohistochemical features. Complete tumor resection after adjuvant TACE may improve the survival time of such patients.展开更多
BACKGROUND:Undifferentiated embryonal sarcoma (UES) of the liver is a rare,highly malignant neoplasm with a poor prognosis occurring almost exclusively in late childhood (6-10 years of age).Only a few cases have been ...BACKGROUND:Undifferentiated embryonal sarcoma (UES) of the liver is a rare,highly malignant neoplasm with a poor prognosis occurring almost exclusively in late childhood (6-10 years of age).Only a few cases have been reported in adults accounting for less than 1% of all primary liver neoplasms.METHODS:A 47-year-old woman presented with a palpable mass in the left upper abdomen.Magnetic resonance imaging revealed a 12×10 cm cystic mass with hemorrhage in the left lateral segment of the liver.The initial impression was a hemorrhagic cystic tumor of the liver.The patient underwent a left lateral sectionectomy of the liver.Histopathology and immunohistochemistry helped make a diagnosis of UES.RESULTS:The patient recovered uneventfully and received systemic chemotherapy.Radiologic examination for follow-up revealed a metastatic lesion in the lumbar spine (L5).She was subjected to radiotherapy at the lumbar spine.She survived 48 months.CONCLUSION:Although hepatic cyst as UES of the liver is difficult to diagnose because of its rarity in adults and lack of specific findings,it should be considered in a differential diagnosis.展开更多
BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare liver malignancy originating from primary mesenchymal tissue.The clinical manifestations,laboratory tests,and imaging examinations of the disea...BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare liver malignancy originating from primary mesenchymal tissue.The clinical manifestations,laboratory tests,and imaging examinations of the disease lack specificity and the preoperative misdiagnosis rate is high.The overall prognosis is poor and survival rate is low.AIM To investigate the diagnosis,treatment,and prognosis of UESL.METHODS We performed a retrospective,single-center cohort study in Shengjing Hospital of China Medical University,which is a central hospital in northeast China.From 2005 to 2017,we recruited 14 patients with pathologically confirmed UESL.We analyzed the clinical manifestations,laboratory tests,imaging examinations,pathological examinations,therapy,and prognosis of these patients.RESULTS There were nine males and five females aged 2-60 years old included in the study.The major initial symptoms were abdominal pain(71.43%)and fever(57.14%).Preoperative laboratory tests revealed that seven patients had increased leukocyte levels,four showed a decrease in hemoglobin levels,seven patients had increased glutamyl transpeptidase levels,nine had increased lactate dehydrogenase levels,and three showed an increase in carbohydrate antigen 199.There was no difference in the rate of misdiagnosis in preoperative imaging examinations of UESL between adults and children(6/6 vs 5/8,P=0.091).The survival rate after complete resection was 6/10,while that after incomplete resection was 0/4(P=0.040),suggesting that complete resection is important to improve survival rate.In total,five out of the eight children achieved survival.During the follow-up,the maximum survival time was shown to be 11 years and minimum survival time was 6 mo.Six adult patients relapsed late after surgery and all of them died.CONCLUSION Preoperative imaging examination for UESL has a high misdiagnosis rate.Multidisciplinary collaboration can improve the diagnostic accuracy of UESL.Complete surgical resection is the first choice for treatment of UESL.展开更多
This report presents a case of embryonal rhabdomyosarcoma(e RMS) located in the left maxillary sinus and invading the orbital cavity in a ten-year-old male patient who was treated at a referral hospital.The images pro...This report presents a case of embryonal rhabdomyosarcoma(e RMS) located in the left maxillary sinus and invading the orbital cavity in a ten-year-old male patient who was treated at a referral hospital.The images provided from the computed tomography showed a heterogeneous mass with soft-tissue density,occupying part of the left half of the face inside the maxillary sinus,and infiltrating and destroying the bone structure of the maxillary sinus,left orbit,ethmoidal cells,nasal cavity,and sphenoid sinus.An analysis of the histological sections revealed an undifferentiated malignant neoplasm infiltrating the skeletal muscle tissue.The immunohistochemical analysis was positive for the antigens:MyoD 1,myogenin,desmin,and Ki67(100% positivity in neoplastic cells),allowing the identification of the tumour as an eR MS.The treatment protocol included initial chemotherapy followed by radiotherapy and finally surgery.The total time of the treatment was nine months,and in 18-mo of follow-up period did not show no local recurrences and a lack of visual impairment.展开更多
Primary germ cell tumors of lung are extremely rare. The prognosis is usually poor, with various symptoms seriously affecting quality of life. In this paper we describe the unique case of a patient affected by an embr...Primary germ cell tumors of lung are extremely rare. The prognosis is usually poor, with various symptoms seriously affecting quality of life. In this paper we describe the unique case of a patient affected by an embryonal carcinoma of lung and a testicular seminoma after ten years. We also report literature about pulmonary extragonadal germ cell tumors.展开更多
BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare and aggressive mesenchymal tumor in children.Herein,we describe our experience in neoadjuvant therapy(NAT)and subsequent surgery for the treatm...BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare and aggressive mesenchymal tumor in children.Herein,we describe our experience in neoadjuvant therapy(NAT)and subsequent surgery for the treatment of UESL in children.AIM To evaluate the efficacy of NAT and explore a new choice for successful operation of UESL in children.METHODS We retrospectively analyzed six patients newly diagnosed with unresectable UESL who received NAT and then surgery at our center between January 2004 and December 2019.The tumor was considered unresectable if it involved a large part of both lobes of the liver or had invaded the main hepatic vessels or inferior vena cava.The NAT included preoperative transcatheter arterial chemoembol ization(TACE)and systemic chemotherapy.The patients were 4 boys and 2 girls with a mean age of 7 years.The longest tumor at presentation ranged from 8.6 to 14.8 cm(mean,12 cm).Extrahepatic metastases were present in 2 cases.Preoperative systemic chemotherapy was administered 3 wk after TACE.Tumor resection was performed 3 wk after one or two cycles of NAT.The patients received systemic chemotherapy after surgery.RESULTS All patients successfully underwent NAT and complete resection.The tumor volumes decreased by 18.2%–68.7%,with a mean decrease of 36%after 1 cycle of NAT(t=3.524,P=0.017).According to the Response Evaluation Criteria In Solid Tumors criteria,4 patients had a partial response and underwent surgery,while 2 had stable disease and received another cycle of NAT before surgery.Massive tumor necrosis was seen on pathological examination of the surgical specimen:>90%necrosis in two,>50%necrosis in three,and 25%necrosis in 1,with an average of 71.8%.Post-NAT complications included fever,nausea and vomiting,and mild bone marrow suppression.Elevated alanine transaminase levels occurred in all patients,which returned to normal within 7–10 d after treatment.No cardiac or renal toxicity,severe hepatic dysfunction,bleeding and nontarget embolization were observed in the patients.The median follow-up period was 8 years with an overall survival of 100%.CONCLUSION NAT effectively reduced tumor volume,cleared the tumor margin,and caused massive tumor necrosis.This may be a promising choice for successful surgery of UESL in children.展开更多
BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a neoplasm that rarely develops in adults.The main treatments for UESL are upfront gross total surgical resection and adjuvant multiagent chemotherapy...BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a neoplasm that rarely develops in adults.The main treatments for UESL are upfront gross total surgical resection and adjuvant multiagent chemotherapy.Here,we report a case of recurrent UESL in an adult treated with pembrolizumab and discuss a method to identify proper candidates for antibody of programmed cell death protein 1(anti-PD-1)treatment.CASE SUMMARY A 69-year-old woman was admitted for abdominal pain that developed for 1 wk.Computed tomography showed a 16 cm mass in the right lobe of the liver.Right hemihepatectomy and lymphadenectomy were performed,and histological diagnosis was UESL.Six months later,the patient suffered from painless obstructive jaundice,and positron emission tomography-computed tomography revealed multiple metastases.Then,percutaneous transhepatic cholangial drainage was applied to reduce jaundice,and radiofrequency ablation was used to control the lesion near the hepatic hilum.However,the patient suffered from a serious fever caused by the tumor.The patient received treatment with pembrolizumab,and the prescribed dosage was 2 mg/kg every 3 wk.After the seventh dose,positron emission tomography-computed tomography revealed that the multiple metastases had nearly disappeared.Radiologic exam was used to evaluate the disease state,and no new lesions were found.Next-generation sequencing and immunohistology were applied to determine the reason why the patient had such a favorable response to pembrolizumab.Tumor mutation burden,microsatellite instability,and programmed death ligand 1 expression can be combined to predict the effect of PD-1 antibodies. When every one of thesebiomarkers are detected in a tumor patient, the patient may be a proper candidatefor PD-1 antibodies.CONCLUSION Anti-PD-1 treatment for tumors needs further research to identify indications andproper biomarkers.展开更多
AIM:To study the expression of embryonal markers by fetal cardiac mesenchymal stem cells(fC-MSC)and their differentiation into cells of all the germ layers. METHODS:Ten independent cultures of rat fCMSC were set up fr...AIM:To study the expression of embryonal markers by fetal cardiac mesenchymal stem cells(fC-MSC)and their differentiation into cells of all the germ layers. METHODS:Ten independent cultures of rat fCMSC were set up from cells derived from individual or pooled fetal hearts and studies given below were carried out at passages 3,6,15 and 21.The phenotypic markers CD29,CD31,CD34,CD45,CD73,CD90, CD105,CD166 and HLA-DR were analyzed by flow cytometry.The expression of embryonal markers Oct-4, Nanog,Sox-2,SSEA-1,SSEA-3,SSEA-4,TRA-1-60 and TRA 1-81 were studied by immunocytochemistry.The fC-MSC treated with specific induction medium were evaluated for their differentiation into(1)adipocytes and osteocytes(mesodermal cells)by Oil Red O and Alizarin Red staining,respectively,as well as by expression of lipoprotein lipase,PPARγ2 genes in adipocytes and osteopontin and RUNX2 genes in osteocytes by reverse-transcription polymerase chain reaction(RT- PCR);(2)neuronal(ectodermal)cells by expression of neuronal Filament-160 and Glial Fibrillar Acidic Protein by RT-PCR and immunocytochemistry;and(3)hepa- tocytic(endodermal)cells by expression of albumin by RT-PCR and immunocytochemistry,glycogen deposits by Periodic Acid Schiff staining and excretion of urea into the culture supernatant. RESULTS:The fC-MSC expressed CD29,CD73,CD90, CD105,CD166 but lacked expression of CD31,CD34, CD45 and HLA-DR.They expressed embryonal markers,viz.Oct-4,Nanog,Sox-2,SSEA-1,SSEA-3,SSEA-4, TRA-1-81 but not TRA-1-60.On treatment with specific induction media,they differentiated into adipocytes and osteocytes,neuronal cells and hepatocytic cells. CONCLUSION:Our results together suggest that fCMSC are primitive stem cell types with a high degree of plasticity and,in addition to their suitability for cardiovascular regenerative therapy,they may have a wide spectrum of therapeutic applications in regenerative medicine.展开更多
We report here the case of a young man suffering from a rare germ cell tumour. The patient was a 25-yearold man who was referred to our centre for asthenia, stinging epigastric pain, and an iron deficiency anaemia. Ga...We report here the case of a young man suffering from a rare germ cell tumour. The patient was a 25-yearold man who was referred to our centre for asthenia, stinging epigastric pain, and an iron deficiency anaemia. Gastroscopy revealed a circumferential vegetating lesion on the second portion of the duodenum. The lesion was indurated at the third portion of the duodenum, responsible for a tight stenosis. A computerized tomography-scan of the chest, abdomen and pelvis, and a pancreatic MRI showed a circumferential lesion with a bi-ductal dilatation(i.e., of the common bile duct and Wirsung's duct) without metastatic localisation. The patient underwent a pancreaticoduodenectomy with lymph node dissection including all cellular adipose tissues of the hepatic pedicle from the hepatic common artery and of the retroportal lamina. Histological findings were suggestive of a duodenal embryonal carcinoma with pancreatic infiltration. This is the second published case highlighting the duodenal primitive localisation of an embryonal carcinoma with pancreatic infiltration.展开更多
Prostate embryonal rhabdomyosarcoma(ERMS) is characterized by a high degree of malignancy, both local rapid growth with formation of large pelvic masses, often leading to renal failure due to urethra obstruction, and ...Prostate embryonal rhabdomyosarcoma(ERMS) is characterized by a high degree of malignancy, both local rapid growth with formation of large pelvic masses, often leading to renal failure due to urethra obstruction, and systemic spread, commonly to the lungs, liver, and bone. ERMS of the prostate is a commonly occurring tumor in infants and children. It is rarely seen in adults. Here, we report on a case of the prostate ERMS in a 27-year-old man.展开更多
Introduction:?Embryonal rhabdomyosarcoma (RMS) of the uterine cervix is a rare and extremely aggressive malignant entity. However, prognosis seems to be improved with the use of multimodality approach treatment. Cases...Introduction:?Embryonal rhabdomyosarcoma (RMS) of the uterine cervix is a rare and extremely aggressive malignant entity. However, prognosis seems to be improved with the use of multimodality approach treatment. Cases: We report the cases of 50- and 51-year-old women, presenting with vaginal bleeding and mass. The two patients underwent radical surgery. Histological examination revealed RMS of uterine cervix. Treatment was effective in the first case but despite the chemotherapy, the second patient died two months later. Discussion and Conclusions: The prognosis of the cervical embryonal RMS depends on clinical and histological features. The current treatment protocols are based on trials done on pediatric patients. Studies on embryonal RMS treatment and outcomes are limited in women over forty years. In patients with unfavorable prognosis characteristics, the multimodality approach including surgery, adjuvant chemo and radiotherapy can be effective. Otherwise, surgery alone can effectively be proposed.展开更多
The literature on cervical embryonal rhabdomyosarcoma(RMS) is reviewed here to identify management guidelines for middle-aged women diagnosed with this rare type of gynecologic cancer. Specifically, the Pub Med, Web o...The literature on cervical embryonal rhabdomyosarcoma(RMS) is reviewed here to identify management guidelines for middle-aged women diagnosed with this rare type of gynecologic cancer. Specifically, the Pub Med, Web of Science and Google Scholar databases, were searched to find published case series on cervical embryonal RMS reporting on four or more patients, of whom at least one was > 40-year-old. The χ2 test was used to assess heterogeneity. Five articles published between 1986 and 2013 were identified, reporting on a total of 47 patients, of whom 22(46.8%) were older and 25(53.2%) younger than 40-year-old. Although the two age groups did not differ significantly by stage of disease or radiotherapy treatment, the older age groupreceived less chemotherapy(55% vs 90%, P = 0.008)and had more hysterectomy(86% vs 43%, P = 0.009).Follow-up data was missing for 18/47(38.3%) patients.Among the 29 patients with follow-up data, survival was shorter in the older group, with 8/12(67%) alive and3 with disease at a median follow-up of 2.6 years, as compared with the younger group that had 15/17(88%)alive and none with disease at a median follow-up of 3.5years. The longest survivals among the older women were observed in those who received radiotherapy,including one case with a resected lung metastasis.A prospective multi-institutional collaboration and better follow-up are needed to determine the optimal management of cervical embryonal RMS. Long-term survival appears feasible if management is accompanied by chemotherapy and radiotherapy.展开更多
Aural polyps are a common clinical entity encountered by otorhinolaryngologist in daily practice. Polyps are frequently seen in paediatric patients, usually inflammatory in nature. In children rhabdomyosarcomas (RMS) ...Aural polyps are a common clinical entity encountered by otorhinolaryngologist in daily practice. Polyps are frequently seen in paediatric patients, usually inflammatory in nature. In children rhabdomyosarcomas (RMS) can mimic all the cinical features of chronic suppurative otitis media which usually present as external auditory canal mass or polyp. Here we present a case where a male child presented with recurrence of polyp in left ear which was finally diagnosed as embryonal rhabdomyosarcoma which is a rare and invariably fatal disease in children. Through this article we intend to highlight the failures and delay committed in attaining diagnosis in this patient in spite of multispecialty evaluation involving repeated imaging and histopathological correlation. Our experience with embryonal rhabdomyosarcoma throws light on the high vigilance required in handling the aural polyps in pediatric population as early diagnosis and treatment are the key elements for successful outcomes.展开更多
<strong>Introduction:</strong> Rhabdomyosarcoma accounts for up to 60% of childhood soft tissue sarcoma, occurring mostly in the head and neck region but rarely in the ear and temporal areas. <strong>...<strong>Introduction:</strong> Rhabdomyosarcoma accounts for up to 60% of childhood soft tissue sarcoma, occurring mostly in the head and neck region but rarely in the ear and temporal areas. <strong>Case Report:</strong> A 4-year-old boy came to our hospital due to a purulent discharge, bleeding from his left ear. Also seen mass in the left ear along with facial weakness and diplopia. After histopathologic evaluation, it was diagnosed as embryonal rhabdomyosarcoma. <strong>Conclusion:</strong> Rhabdomyosarcoma should be kept in mind as a differential diagnosis in all children presenting with otitis media with mastoiditis. Biopsy should be considered who are not responding to medications and those worsening condition.展开更多
Importance:As the most common subtype of pediatric rhabdomyosarcoma(RMS),the prognosis of embryonal RMS has rarely been investigated solely.Objective:To perform a population-based study to characterize the prognosis o...Importance:As the most common subtype of pediatric rhabdomyosarcoma(RMS),the prognosis of embryonal RMS has rarely been investigated solely.Objective:To perform a population-based study to characterize the prognosis of embryonal RMS in children and adolescents.Methods:Demographic and clinical features were retrospectively evaluated in selected patients with embryonal RMS registered in the Surveillance,Epidemiology,and End Results(SEER)program from 1988 to 2016.Survival curves were compared using the log-rank test.A multivariate Cox proportional hazards model was developed to assess the impact of each factor on the overall survival.A nomogram was constructed based on the results of Cox regression model.Results:A total of 464 patients were included in the analysis,among which 64.6%were male and 70.2%were white patients.About 38.6%and 26.3%of the patients were at 1-4 years and 5-9 years,respectively.Cox analysis showed that patients at age group 5-9 years had the lowest risk of mortality(hazard ratio[HR],0.277;95%confidential interval[CI],0.123-0.620),compared with patients diagnosed at less than 1-year-old,and age group 1-4 years had the second-best prognosis.Patients having distant tumors had significantly higher mortality risk(HR,4.842;95%CI,2.804-8.362)than the patients with localized tumor.Compared with receiving no surgery or radiotherapy,receiving any combination of surgery and radiotherapy would lower the risk of mortality significantly(for surgery without radiotherapy:HR,0.418;for radiotherapy without surgery:HR,0.405;and for surgery plus radiotherapy:HR,0.410).Interpretation:Age,stage at diagnosis,and treatment received were found to be the most important predictors of the overall survival of pediatric embryonal RMS.展开更多
Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and t...Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.展开更多
Background Mitochondrial dysfunction induced by excessive mitochondrial reactive oxygen species(ROS)damages embryonic development and leads to growth arrest.Objective The purpose of this study is to elucidate whether ...Background Mitochondrial dysfunction induced by excessive mitochondrial reactive oxygen species(ROS)damages embryonic development and leads to growth arrest.Objective The purpose of this study is to elucidate whether maternal zinc(Zn)exert protective effect on oxidative stress targeting mitochondrial function using an avian model.Result In ovo injected tert-butyl hydroperoxide(BHP)increases(P<0.05)hepatic mitochondrial ROS,malondialdehyde(MDA)and 8-hydroxy-2-deoxyguanosine(8-OHdG),and decreases(P<0.05)mitochondrial membrane potential(MMP),mitochondrial DNA(mtDNA)copy number and adenosine triphosphate(ATP)content,contributing to mitochondrial dysfunction.In vivo and in vitro studies revealed that Zn addition enhances(P<0.05)ATP synthesis and metallothionein 4(MT4)content and expression as well as alleviates(P<0.05)the BHP-induced mitochondrial ROS generation,oxidative damage and dysfunction,exerting a protective effect on mitochondrial function by enhancing antioxidant capacity and upregulating the mRNA and protein expressions of Nrf2 and PGC-1α.Conclusions The present study provides a new way to protect offspring against oxidative damage by maternal Zn supplementation through the process of targeting mitochondria involving the activation of Nrf2/PGC-1αsignaling.展开更多
Avian embryos,which develop within eggs,exhibit remarkable tolerance to extremely low temperatures.Despite being a common trait among all birds,the mechanisms underlying this cold tolerance in avian embryos remain lar...Avian embryos,which develop within eggs,exhibit remarkable tolerance to extremely low temperatures.Despite being a common trait among all birds,the mechanisms underlying this cold tolerance in avian embryos remain largely unknown.To gain a better understanding of this phenomenon and the coping mechanisms involved,we reviewed the literature on severe cold tolerance in embryos of both wild and domestic birds.We found that embryos of different bird orders exhibit tolerance to severe cold during their development.In response to cold stress,embryos slow down their heartbeat rates and metabolism.In severe cold temperatures,embryos can suspend these processes,entering a torpid-like state of cardiac arrest.To compensate for these developmental delays,embryos extend their regular incubation periods.Depending on their embryonic age,embryos of all bird species can tolerate acute severe cold regimes;only a few tolerate chronic severe cold regimes.We also discussed various extrinsic and intrinsic factors that affect the tolerance of bird embryos to low temperatures before and after incubation.Cold tolerance appears to be a heritable trait shared by wild and domestic embryos of all bird classes,regardless of egg size or development(altricial/precocial).Driven by environmental variability,cold tolerance in avian embryos is an optimal physiological and ecological strategy to mitigate the adverse effects of cold conditions on their development in response to fluctuating environmental temperatures.展开更多
Objective Vascular smooth muscle cell(VSMC)differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension,atherosclerosis...Objective Vascular smooth muscle cell(VSMC)differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension,atherosclerosis,and restenosis.MicroRNA-146a(miR-146a)has been proven to be involved in cell proliferation,migration,and tumor metabolism.However,little is known about the functional role of miR-146a in VSMC differentiation from embryonic stem cells(ESCs).This study aimed to determine the role of miR-146a in VSMC differentiation from ESCs.Methods Mouse ESCs were differentiated into VSMCs,and the cell extracts were analyzed by Western blotting and RT-qPCR.In addition,luciferase reporter assays using ESCs transfected with miR-146a/mimic and plasmids were performed.Finally,C57BL/6J female mice were injected with mimic or miR-146a-overexpressing ESCs,and immunohistochemistry,Western blotting,and RT-qPCR assays were carried out on tissue samples from these mice.Results miR-146a was significantly upregulated during VSMC differentiation,accompanied with the VSMC-specific marker genes smooth muscle-alpha-actin(SMαA),smooth muscle 22(SM22),smooth muscle myosin heavy chain(SMMHC),and h1-calponin.Furthermore,overexpression of miR-146a enhanced the differentiation process in vitro and in vivo.Concurrently,the expression of Kruppel-like factor 4(KLF4),predicted as one of the top targets of miR-146a,was sharply decreased in miR-146a-overexpressing ESCs.Importantly,inhibiting KLF4 expression enhanced the VSMC-specific gene expression induced by miR-146a overexpression in differentiating ESCs.In addition,miR-146a upregulated the mRNA expression levels and transcriptional activity of VSMC differentiation-related transcription factors,including serum response factor(SRF)and myocyte enhancer factor 2c(MEF-2c).Conclusion Our data support that miR-146a promotes ESC-VSMC differentiation through regulating KLF4 and modulating the transcription factor activity of VSMCs.展开更多
Stem cells are a group of cells with unique self-renewal and differentiation abilities that have great prospects in the repair of spinal cord injury. However, stem cell renewal and differentiation require strict contr...Stem cells are a group of cells with unique self-renewal and differentiation abilities that have great prospects in the repair of spinal cord injury. However, stem cell renewal and differentiation require strict control of protein turnover in the stem cells to achieve cell remodeling. As a highly conserved “gatekeeper” of cell homeostasis, autophagy can regulate cell remodeling by precisely controlling protein turnover in cells. Recently, it has been found that the expression of autophagy markers changes in animal models of spinal cord injury. Therefore, understanding whether autophagy can affect the fate of stem cells and promote the repair of spinal cord injury is of considerable clinical value. This review expounds the importance of autophagy homeostasis control for the repair of spinal cord injury from three aspects—pathophysiology of spinal cord injury, autophagy and stem cell function, and autophagy and stem cell function in spinal cord injury—and proposes the synergistic therapeutic effect of autophagy and stem cells in spinal cord injury.展开更多
文摘AIM: To evaluate the undifferentiated embryonal sarcoma of liver (UESL) in adults in order to improve its diagnosis and treatment. METHODS: Four primary and one recurrent cases of UESL were clinicopathologically evaluated and immunohistochemically investigated with a panel of antibodies using the EnVision+ system. Relevant literature about UESL in adults was reviewed. RESULTS: Three males and one female were enrolled in this study. Their chief complaints were abdominal pain, weight loss, or fever. Laboratory tests, imaging and pathological features of UESL in adults were similar to those in children. Immunohistochemistry showed evidence of widely divergent differentiation into mesenchymal and epithelial phenotypes. The survival time of patients who underwent complete tumor resection followed by adjuvant transcatheter arterial chemoembolization (TACE) was significantly longer than that of those who underwent surgical treatment alone.CONCLUSION: UESL in adults may undergo pluripotential differentiation and its diagnosis should be made based on its morphological and immunohistochemical features. Complete tumor resection after adjuvant TACE may improve the survival time of such patients.
文摘BACKGROUND:Undifferentiated embryonal sarcoma (UES) of the liver is a rare,highly malignant neoplasm with a poor prognosis occurring almost exclusively in late childhood (6-10 years of age).Only a few cases have been reported in adults accounting for less than 1% of all primary liver neoplasms.METHODS:A 47-year-old woman presented with a palpable mass in the left upper abdomen.Magnetic resonance imaging revealed a 12×10 cm cystic mass with hemorrhage in the left lateral segment of the liver.The initial impression was a hemorrhagic cystic tumor of the liver.The patient underwent a left lateral sectionectomy of the liver.Histopathology and immunohistochemistry helped make a diagnosis of UES.RESULTS:The patient recovered uneventfully and received systemic chemotherapy.Radiologic examination for follow-up revealed a metastatic lesion in the lumbar spine (L5).She was subjected to radiotherapy at the lumbar spine.She survived 48 months.CONCLUSION:Although hepatic cyst as UES of the liver is difficult to diagnose because of its rarity in adults and lack of specific findings,it should be considered in a differential diagnosis.
基金The National Science and Technology Major Project,No.2017ZX10201201 and No.2017ZX10202202Liaoning Provincial Natural Science Foundation,No.20180550096。
文摘BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare liver malignancy originating from primary mesenchymal tissue.The clinical manifestations,laboratory tests,and imaging examinations of the disease lack specificity and the preoperative misdiagnosis rate is high.The overall prognosis is poor and survival rate is low.AIM To investigate the diagnosis,treatment,and prognosis of UESL.METHODS We performed a retrospective,single-center cohort study in Shengjing Hospital of China Medical University,which is a central hospital in northeast China.From 2005 to 2017,we recruited 14 patients with pathologically confirmed UESL.We analyzed the clinical manifestations,laboratory tests,imaging examinations,pathological examinations,therapy,and prognosis of these patients.RESULTS There were nine males and five females aged 2-60 years old included in the study.The major initial symptoms were abdominal pain(71.43%)and fever(57.14%).Preoperative laboratory tests revealed that seven patients had increased leukocyte levels,four showed a decrease in hemoglobin levels,seven patients had increased glutamyl transpeptidase levels,nine had increased lactate dehydrogenase levels,and three showed an increase in carbohydrate antigen 199.There was no difference in the rate of misdiagnosis in preoperative imaging examinations of UESL between adults and children(6/6 vs 5/8,P=0.091).The survival rate after complete resection was 6/10,while that after incomplete resection was 0/4(P=0.040),suggesting that complete resection is important to improve survival rate.In total,five out of the eight children achieved survival.During the follow-up,the maximum survival time was shown to be 11 years and minimum survival time was 6 mo.Six adult patients relapsed late after surgery and all of them died.CONCLUSION Preoperative imaging examination for UESL has a high misdiagnosis rate.Multidisciplinary collaboration can improve the diagnostic accuracy of UESL.Complete surgical resection is the first choice for treatment of UESL.
文摘This report presents a case of embryonal rhabdomyosarcoma(e RMS) located in the left maxillary sinus and invading the orbital cavity in a ten-year-old male patient who was treated at a referral hospital.The images provided from the computed tomography showed a heterogeneous mass with soft-tissue density,occupying part of the left half of the face inside the maxillary sinus,and infiltrating and destroying the bone structure of the maxillary sinus,left orbit,ethmoidal cells,nasal cavity,and sphenoid sinus.An analysis of the histological sections revealed an undifferentiated malignant neoplasm infiltrating the skeletal muscle tissue.The immunohistochemical analysis was positive for the antigens:MyoD 1,myogenin,desmin,and Ki67(100% positivity in neoplastic cells),allowing the identification of the tumour as an eR MS.The treatment protocol included initial chemotherapy followed by radiotherapy and finally surgery.The total time of the treatment was nine months,and in 18-mo of follow-up period did not show no local recurrences and a lack of visual impairment.
文摘Primary germ cell tumors of lung are extremely rare. The prognosis is usually poor, with various symptoms seriously affecting quality of life. In this paper we describe the unique case of a patient affected by an embryonal carcinoma of lung and a testicular seminoma after ten years. We also report literature about pulmonary extragonadal germ cell tumors.
基金Youth Program of Natural Science Foundation of Zhejiang Province,No.LQ20H160027National Natural Science Foundation of China,No.U20A20137。
文摘BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare and aggressive mesenchymal tumor in children.Herein,we describe our experience in neoadjuvant therapy(NAT)and subsequent surgery for the treatment of UESL in children.AIM To evaluate the efficacy of NAT and explore a new choice for successful operation of UESL in children.METHODS We retrospectively analyzed six patients newly diagnosed with unresectable UESL who received NAT and then surgery at our center between January 2004 and December 2019.The tumor was considered unresectable if it involved a large part of both lobes of the liver or had invaded the main hepatic vessels or inferior vena cava.The NAT included preoperative transcatheter arterial chemoembol ization(TACE)and systemic chemotherapy.The patients were 4 boys and 2 girls with a mean age of 7 years.The longest tumor at presentation ranged from 8.6 to 14.8 cm(mean,12 cm).Extrahepatic metastases were present in 2 cases.Preoperative systemic chemotherapy was administered 3 wk after TACE.Tumor resection was performed 3 wk after one or two cycles of NAT.The patients received systemic chemotherapy after surgery.RESULTS All patients successfully underwent NAT and complete resection.The tumor volumes decreased by 18.2%–68.7%,with a mean decrease of 36%after 1 cycle of NAT(t=3.524,P=0.017).According to the Response Evaluation Criteria In Solid Tumors criteria,4 patients had a partial response and underwent surgery,while 2 had stable disease and received another cycle of NAT before surgery.Massive tumor necrosis was seen on pathological examination of the surgical specimen:>90%necrosis in two,>50%necrosis in three,and 25%necrosis in 1,with an average of 71.8%.Post-NAT complications included fever,nausea and vomiting,and mild bone marrow suppression.Elevated alanine transaminase levels occurred in all patients,which returned to normal within 7–10 d after treatment.No cardiac or renal toxicity,severe hepatic dysfunction,bleeding and nontarget embolization were observed in the patients.The median follow-up period was 8 years with an overall survival of 100%.CONCLUSION NAT effectively reduced tumor volume,cleared the tumor margin,and caused massive tumor necrosis.This may be a promising choice for successful surgery of UESL in children.
基金National Natural Science Foundation of China,No.31971249.
文摘BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a neoplasm that rarely develops in adults.The main treatments for UESL are upfront gross total surgical resection and adjuvant multiagent chemotherapy.Here,we report a case of recurrent UESL in an adult treated with pembrolizumab and discuss a method to identify proper candidates for antibody of programmed cell death protein 1(anti-PD-1)treatment.CASE SUMMARY A 69-year-old woman was admitted for abdominal pain that developed for 1 wk.Computed tomography showed a 16 cm mass in the right lobe of the liver.Right hemihepatectomy and lymphadenectomy were performed,and histological diagnosis was UESL.Six months later,the patient suffered from painless obstructive jaundice,and positron emission tomography-computed tomography revealed multiple metastases.Then,percutaneous transhepatic cholangial drainage was applied to reduce jaundice,and radiofrequency ablation was used to control the lesion near the hepatic hilum.However,the patient suffered from a serious fever caused by the tumor.The patient received treatment with pembrolizumab,and the prescribed dosage was 2 mg/kg every 3 wk.After the seventh dose,positron emission tomography-computed tomography revealed that the multiple metastases had nearly disappeared.Radiologic exam was used to evaluate the disease state,and no new lesions were found.Next-generation sequencing and immunohistology were applied to determine the reason why the patient had such a favorable response to pembrolizumab.Tumor mutation burden,microsatellite instability,and programmed death ligand 1 expression can be combined to predict the effect of PD-1 antibodies. When every one of thesebiomarkers are detected in a tumor patient, the patient may be a proper candidatefor PD-1 antibodies.CONCLUSION Anti-PD-1 treatment for tumors needs further research to identify indications andproper biomarkers.
基金Supported by Department of Biotechnology,Government of India,BT/PR6519/MED/14/826/2005,to Dr.Nityanand S
文摘AIM:To study the expression of embryonal markers by fetal cardiac mesenchymal stem cells(fC-MSC)and their differentiation into cells of all the germ layers. METHODS:Ten independent cultures of rat fCMSC were set up from cells derived from individual or pooled fetal hearts and studies given below were carried out at passages 3,6,15 and 21.The phenotypic markers CD29,CD31,CD34,CD45,CD73,CD90, CD105,CD166 and HLA-DR were analyzed by flow cytometry.The expression of embryonal markers Oct-4, Nanog,Sox-2,SSEA-1,SSEA-3,SSEA-4,TRA-1-60 and TRA 1-81 were studied by immunocytochemistry.The fC-MSC treated with specific induction medium were evaluated for their differentiation into(1)adipocytes and osteocytes(mesodermal cells)by Oil Red O and Alizarin Red staining,respectively,as well as by expression of lipoprotein lipase,PPARγ2 genes in adipocytes and osteopontin and RUNX2 genes in osteocytes by reverse-transcription polymerase chain reaction(RT- PCR);(2)neuronal(ectodermal)cells by expression of neuronal Filament-160 and Glial Fibrillar Acidic Protein by RT-PCR and immunocytochemistry;and(3)hepa- tocytic(endodermal)cells by expression of albumin by RT-PCR and immunocytochemistry,glycogen deposits by Periodic Acid Schiff staining and excretion of urea into the culture supernatant. RESULTS:The fC-MSC expressed CD29,CD73,CD90, CD105,CD166 but lacked expression of CD31,CD34, CD45 and HLA-DR.They expressed embryonal markers,viz.Oct-4,Nanog,Sox-2,SSEA-1,SSEA-3,SSEA-4, TRA-1-81 but not TRA-1-60.On treatment with specific induction media,they differentiated into adipocytes and osteocytes,neuronal cells and hepatocytic cells. CONCLUSION:Our results together suggest that fCMSC are primitive stem cell types with a high degree of plasticity and,in addition to their suitability for cardiovascular regenerative therapy,they may have a wide spectrum of therapeutic applications in regenerative medicine.
文摘We report here the case of a young man suffering from a rare germ cell tumour. The patient was a 25-yearold man who was referred to our centre for asthenia, stinging epigastric pain, and an iron deficiency anaemia. Gastroscopy revealed a circumferential vegetating lesion on the second portion of the duodenum. The lesion was indurated at the third portion of the duodenum, responsible for a tight stenosis. A computerized tomography-scan of the chest, abdomen and pelvis, and a pancreatic MRI showed a circumferential lesion with a bi-ductal dilatation(i.e., of the common bile duct and Wirsung's duct) without metastatic localisation. The patient underwent a pancreaticoduodenectomy with lymph node dissection including all cellular adipose tissues of the hepatic pedicle from the hepatic common artery and of the retroportal lamina. Histological findings were suggestive of a duodenal embryonal carcinoma with pancreatic infiltration. This is the second published case highlighting the duodenal primitive localisation of an embryonal carcinoma with pancreatic infiltration.
文摘Prostate embryonal rhabdomyosarcoma(ERMS) is characterized by a high degree of malignancy, both local rapid growth with formation of large pelvic masses, often leading to renal failure due to urethra obstruction, and systemic spread, commonly to the lungs, liver, and bone. ERMS of the prostate is a commonly occurring tumor in infants and children. It is rarely seen in adults. Here, we report on a case of the prostate ERMS in a 27-year-old man.
文摘Introduction:?Embryonal rhabdomyosarcoma (RMS) of the uterine cervix is a rare and extremely aggressive malignant entity. However, prognosis seems to be improved with the use of multimodality approach treatment. Cases: We report the cases of 50- and 51-year-old women, presenting with vaginal bleeding and mass. The two patients underwent radical surgery. Histological examination revealed RMS of uterine cervix. Treatment was effective in the first case but despite the chemotherapy, the second patient died two months later. Discussion and Conclusions: The prognosis of the cervical embryonal RMS depends on clinical and histological features. The current treatment protocols are based on trials done on pediatric patients. Studies on embryonal RMS treatment and outcomes are limited in women over forty years. In patients with unfavorable prognosis characteristics, the multimodality approach including surgery, adjuvant chemo and radiotherapy can be effective. Otherwise, surgery alone can effectively be proposed.
文摘The literature on cervical embryonal rhabdomyosarcoma(RMS) is reviewed here to identify management guidelines for middle-aged women diagnosed with this rare type of gynecologic cancer. Specifically, the Pub Med, Web of Science and Google Scholar databases, were searched to find published case series on cervical embryonal RMS reporting on four or more patients, of whom at least one was > 40-year-old. The χ2 test was used to assess heterogeneity. Five articles published between 1986 and 2013 were identified, reporting on a total of 47 patients, of whom 22(46.8%) were older and 25(53.2%) younger than 40-year-old. Although the two age groups did not differ significantly by stage of disease or radiotherapy treatment, the older age groupreceived less chemotherapy(55% vs 90%, P = 0.008)and had more hysterectomy(86% vs 43%, P = 0.009).Follow-up data was missing for 18/47(38.3%) patients.Among the 29 patients with follow-up data, survival was shorter in the older group, with 8/12(67%) alive and3 with disease at a median follow-up of 2.6 years, as compared with the younger group that had 15/17(88%)alive and none with disease at a median follow-up of 3.5years. The longest survivals among the older women were observed in those who received radiotherapy,including one case with a resected lung metastasis.A prospective multi-institutional collaboration and better follow-up are needed to determine the optimal management of cervical embryonal RMS. Long-term survival appears feasible if management is accompanied by chemotherapy and radiotherapy.
文摘Aural polyps are a common clinical entity encountered by otorhinolaryngologist in daily practice. Polyps are frequently seen in paediatric patients, usually inflammatory in nature. In children rhabdomyosarcomas (RMS) can mimic all the cinical features of chronic suppurative otitis media which usually present as external auditory canal mass or polyp. Here we present a case where a male child presented with recurrence of polyp in left ear which was finally diagnosed as embryonal rhabdomyosarcoma which is a rare and invariably fatal disease in children. Through this article we intend to highlight the failures and delay committed in attaining diagnosis in this patient in spite of multispecialty evaluation involving repeated imaging and histopathological correlation. Our experience with embryonal rhabdomyosarcoma throws light on the high vigilance required in handling the aural polyps in pediatric population as early diagnosis and treatment are the key elements for successful outcomes.
文摘<strong>Introduction:</strong> Rhabdomyosarcoma accounts for up to 60% of childhood soft tissue sarcoma, occurring mostly in the head and neck region but rarely in the ear and temporal areas. <strong>Case Report:</strong> A 4-year-old boy came to our hospital due to a purulent discharge, bleeding from his left ear. Also seen mass in the left ear along with facial weakness and diplopia. After histopathologic evaluation, it was diagnosed as embryonal rhabdomyosarcoma. <strong>Conclusion:</strong> Rhabdomyosarcoma should be kept in mind as a differential diagnosis in all children presenting with otitis media with mastoiditis. Biopsy should be considered who are not responding to medications and those worsening condition.
基金Beihang University&Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan(BHME-201801)。
文摘Importance:As the most common subtype of pediatric rhabdomyosarcoma(RMS),the prognosis of embryonal RMS has rarely been investigated solely.Objective:To perform a population-based study to characterize the prognosis of embryonal RMS in children and adolescents.Methods:Demographic and clinical features were retrospectively evaluated in selected patients with embryonal RMS registered in the Surveillance,Epidemiology,and End Results(SEER)program from 1988 to 2016.Survival curves were compared using the log-rank test.A multivariate Cox proportional hazards model was developed to assess the impact of each factor on the overall survival.A nomogram was constructed based on the results of Cox regression model.Results:A total of 464 patients were included in the analysis,among which 64.6%were male and 70.2%were white patients.About 38.6%and 26.3%of the patients were at 1-4 years and 5-9 years,respectively.Cox analysis showed that patients at age group 5-9 years had the lowest risk of mortality(hazard ratio[HR],0.277;95%confidential interval[CI],0.123-0.620),compared with patients diagnosed at less than 1-year-old,and age group 1-4 years had the second-best prognosis.Patients having distant tumors had significantly higher mortality risk(HR,4.842;95%CI,2.804-8.362)than the patients with localized tumor.Compared with receiving no surgery or radiotherapy,receiving any combination of surgery and radiotherapy would lower the risk of mortality significantly(for surgery without radiotherapy:HR,0.418;for radiotherapy without surgery:HR,0.405;and for surgery plus radiotherapy:HR,0.410).Interpretation:Age,stage at diagnosis,and treatment received were found to be the most important predictors of the overall survival of pediatric embryonal RMS.
基金supported by the National Natural Science Foundation of China,No.82171380(to CD)Jiangsu Students’Platform for Innovation and Entrepreneurship Training Program,No.202110304098Y(to DJ)。
文摘Spinal cord injury is considered one of the most difficult injuries to repair and has one of the worst prognoses for injuries to the nervous system.Following surgery,the poor regenerative capacity of nerve cells and the generation of new scars can make it very difficult for the impaired nervous system to restore its neural functionality.Traditional treatments can only alleviate secondary injuries but cannot fundamentally repair the spinal cord.Consequently,there is a critical need to develop new treatments to promote functional repair after spinal cord injury.Over recent years,there have been seve ral developments in the use of stem cell therapy for the treatment of spinal cord injury.Alongside significant developments in the field of tissue engineering,three-dimensional bioprinting technology has become a hot research topic due to its ability to accurately print complex structures.This led to the loading of three-dimensional bioprinting scaffolds which provided precise cell localization.These three-dimensional bioprinting scaffolds co uld repair damaged neural circuits and had the potential to repair the damaged spinal cord.In this review,we discuss the mechanisms underlying simple stem cell therapy,the application of different types of stem cells for the treatment of spinal cord injury,and the different manufa cturing methods for three-dimensional bioprinting scaffolds.In particular,we focus on the development of three-dimensional bioprinting scaffolds for the treatment of spinal cord injury.
基金sponsored by the National Key R&D Program of China(2022YFD1301800 and1300400)National Natural Science Foundation of China(31802080 and 3197200131)+1 种基金Key Open Laboratory of Chinese Veterinary Medicine of State Ethnic Affairs Commission&National Local Joint Engineering Research Centre for the Separation and Purification Technology of Ethnic Chinese Veterinary Medicine([2022]09)Guangdong Provincial Science and Technology Special Foundation(210723106900762 and 2021020103-2)。
文摘Background Mitochondrial dysfunction induced by excessive mitochondrial reactive oxygen species(ROS)damages embryonic development and leads to growth arrest.Objective The purpose of this study is to elucidate whether maternal zinc(Zn)exert protective effect on oxidative stress targeting mitochondrial function using an avian model.Result In ovo injected tert-butyl hydroperoxide(BHP)increases(P<0.05)hepatic mitochondrial ROS,malondialdehyde(MDA)and 8-hydroxy-2-deoxyguanosine(8-OHdG),and decreases(P<0.05)mitochondrial membrane potential(MMP),mitochondrial DNA(mtDNA)copy number and adenosine triphosphate(ATP)content,contributing to mitochondrial dysfunction.In vivo and in vitro studies revealed that Zn addition enhances(P<0.05)ATP synthesis and metallothionein 4(MT4)content and expression as well as alleviates(P<0.05)the BHP-induced mitochondrial ROS generation,oxidative damage and dysfunction,exerting a protective effect on mitochondrial function by enhancing antioxidant capacity and upregulating the mRNA and protein expressions of Nrf2 and PGC-1α.Conclusions The present study provides a new way to protect offspring against oxidative damage by maternal Zn supplementation through the process of targeting mitochondria involving the activation of Nrf2/PGC-1αsignaling.
基金supported by the National Natural Science Foundation of China(NSFC,31971413)granted to DLthe Second Tibetan Plateau Scientific Expedition and Research Program(STEP,2019QZKK0501)granted to DL。
文摘Avian embryos,which develop within eggs,exhibit remarkable tolerance to extremely low temperatures.Despite being a common trait among all birds,the mechanisms underlying this cold tolerance in avian embryos remain largely unknown.To gain a better understanding of this phenomenon and the coping mechanisms involved,we reviewed the literature on severe cold tolerance in embryos of both wild and domestic birds.We found that embryos of different bird orders exhibit tolerance to severe cold during their development.In response to cold stress,embryos slow down their heartbeat rates and metabolism.In severe cold temperatures,embryos can suspend these processes,entering a torpid-like state of cardiac arrest.To compensate for these developmental delays,embryos extend their regular incubation periods.Depending on their embryonic age,embryos of all bird species can tolerate acute severe cold regimes;only a few tolerate chronic severe cold regimes.We also discussed various extrinsic and intrinsic factors that affect the tolerance of bird embryos to low temperatures before and after incubation.Cold tolerance appears to be a heritable trait shared by wild and domestic embryos of all bird classes,regardless of egg size or development(altricial/precocial).Driven by environmental variability,cold tolerance in avian embryos is an optimal physiological and ecological strategy to mitigate the adverse effects of cold conditions on their development in response to fluctuating environmental temperatures.
基金funded by the National Natural Science Foundation of China(No.82070376 and No.81873491)the Natural Science Foundation of Zhejiang Province(No.LY21H020005)+1 种基金the Zhejiang Medical Science and Technology Project(No.2019KY376 and No.2018KY071)a Ningbo Science and Technology Project(No.202002N3173).
文摘Objective Vascular smooth muscle cell(VSMC)differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension,atherosclerosis,and restenosis.MicroRNA-146a(miR-146a)has been proven to be involved in cell proliferation,migration,and tumor metabolism.However,little is known about the functional role of miR-146a in VSMC differentiation from embryonic stem cells(ESCs).This study aimed to determine the role of miR-146a in VSMC differentiation from ESCs.Methods Mouse ESCs were differentiated into VSMCs,and the cell extracts were analyzed by Western blotting and RT-qPCR.In addition,luciferase reporter assays using ESCs transfected with miR-146a/mimic and plasmids were performed.Finally,C57BL/6J female mice were injected with mimic or miR-146a-overexpressing ESCs,and immunohistochemistry,Western blotting,and RT-qPCR assays were carried out on tissue samples from these mice.Results miR-146a was significantly upregulated during VSMC differentiation,accompanied with the VSMC-specific marker genes smooth muscle-alpha-actin(SMαA),smooth muscle 22(SM22),smooth muscle myosin heavy chain(SMMHC),and h1-calponin.Furthermore,overexpression of miR-146a enhanced the differentiation process in vitro and in vivo.Concurrently,the expression of Kruppel-like factor 4(KLF4),predicted as one of the top targets of miR-146a,was sharply decreased in miR-146a-overexpressing ESCs.Importantly,inhibiting KLF4 expression enhanced the VSMC-specific gene expression induced by miR-146a overexpression in differentiating ESCs.In addition,miR-146a upregulated the mRNA expression levels and transcriptional activity of VSMC differentiation-related transcription factors,including serum response factor(SRF)and myocyte enhancer factor 2c(MEF-2c).Conclusion Our data support that miR-146a promotes ESC-VSMC differentiation through regulating KLF4 and modulating the transcription factor activity of VSMCs.
基金supported by the National Natural Science Foundation of China,Nos. 32170825 and 31971108 (both to GW)。
文摘Stem cells are a group of cells with unique self-renewal and differentiation abilities that have great prospects in the repair of spinal cord injury. However, stem cell renewal and differentiation require strict control of protein turnover in the stem cells to achieve cell remodeling. As a highly conserved “gatekeeper” of cell homeostasis, autophagy can regulate cell remodeling by precisely controlling protein turnover in cells. Recently, it has been found that the expression of autophagy markers changes in animal models of spinal cord injury. Therefore, understanding whether autophagy can affect the fate of stem cells and promote the repair of spinal cord injury is of considerable clinical value. This review expounds the importance of autophagy homeostasis control for the repair of spinal cord injury from three aspects—pathophysiology of spinal cord injury, autophagy and stem cell function, and autophagy and stem cell function in spinal cord injury—and proposes the synergistic therapeutic effect of autophagy and stem cells in spinal cord injury.