When adipose-derived stem cells （ASCs） arc retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based...When adipose-derived stem cells （ASCs） arc retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based on their buoyancy, mature adipocytes can be easily isolated from the adipose cell suspension and dediffercn- tiated into lipid-frce fibroblast-like cells, named dediffercntiated fat （DFAT） cells. DFAT cells rc-establish active proliferation ability and undertake multipotent capacities. Compared with ASCs and other adult stem cells, DFAT cells showed unique advantages in their abundance, isolation and homogeneity. In this concise review, the establishment and culture methods of DFAT cells arc introduced and the current profiles of their cellular nature are summarized. Under proper inducti~,n culture in vitro or environment in vivo, DFAT cells could demonstrate adipogenic, osteogenic, chondrogenie and myogenic potentials. In angiogenie conditions, DFAT cells could exhibit perivascular characteristics antt elicit neovascularization. Our preliminary findings also suggested the pericyte phenotype underlying such cell lineage, which supported a novel interpretation about the common origin of mesenchymal stem cells and tissue-specific stem cells within blood vessel walls. Current research on DFAT cells indicated that this alternative source of adult multipotent cells has great potential in tissue engineering and regenerative medicine.展开更多
The identification of an ideal cell source for tissue regeneration remains a challenge in the stem cell field. The ability of progeny cells to differentiate into other cell types is important for the processes of tiss...The identification of an ideal cell source for tissue regeneration remains a challenge in the stem cell field. The ability of progeny cells to differentiate into other cell types is important for the processes of tissue reconstruction and tissue engineering and has clinical, biochemical or molecular implications. The adaptation of stem cells from adipose tissue for use in regenerative medicine has created a new role for adipocytes. Mature adipocytes can easily be isolated from adipose cell suspensions and allowed to dedifferentiate into lipidfree multipotent cells, referred to as dedifferentiated fat(DFAT) cells. Compared to other adult stem cells, the DFAT cells have unique advantages in their abundance, ease of isolation and homogeneity. Under proper condition in vitro and in vivo, the DFAT cells have exhibited adipogenic, osteogenic, chondrogenic, cardiomyogenc, angiogenic, myogenic, and neurogenic potentials. In this review, we first discuss the phenomena of dedifferentiation and transdifferentiation of cells, and then dedifferentiation of adipocytes in particular. Understanding the dedifferentiation process itself may contribute to our knowledge of normal growth processes, as well as mechanisms of disease. Second, we highlight new developments in DFAT cell culture and summarize the current understanding of DFAT cell properties. The unique features of DFAT cells are promising for clinical applications such as tissue regeneration.展开更多
Liposarcoma is one of the most common soft tissue sarcomas found in adults,and it usually occurs in the retroperitoneum and the extremities.Here,we describe a case of dedifferentiated liposarcoma originating from a we...Liposarcoma is one of the most common soft tissue sarcomas found in adults,and it usually occurs in the retroperitoneum and the extremities.Here,we describe a case of dedifferentiated liposarcoma originating from a well-differentiated liposarcoma of the mesorectum that presented as a protruding mass in the rectal lumen.Hartmann's operation with total mesorectal excision was performed and the tumor was removed radically.No management guidelines are currently available for liposarcoma of the rectum.We propose that complete surgical resection be required for the treatment of rectal liposarcoma and that a long-term detailed follow up is necessary.展开更多
Dedifferentiated liposarcoma(DDLPS) is a variant of liposarcoma but with a more aggressive course.It occurs most commonly in the retroperitoneum and rarely in any other anatomical location.We describe a case of DDLPS ...Dedifferentiated liposarcoma(DDLPS) is a variant of liposarcoma but with a more aggressive course.It occurs most commonly in the retroperitoneum and rarely in any other anatomical location.We describe a case of DDLPS arising from the small bowel mesentery presenting as submucosal mass of the small bowel.The current case is unusual as the tumor originated from the small bowel mesentery and a dedifferentiated component transmurally invaded the small bowel wall,including the small bowel submucosa.展开更多
Dedifferentiated liposarcoma is a variant of liposarcoma with a more aggressive course. Mutations of the p53 gene have been found in different types of soft tissue sarcoma. It is generally accepted that p53 mutations ...Dedifferentiated liposarcoma is a variant of liposarcoma with a more aggressive course. Mutations of the p53 gene have been found in different types of soft tissue sarcoma. It is generally accepted that p53 mutations in human malignant tumors are often related to a poor prognosis. In our case, analysis of p53 gene mutation in tumor samples was performed. p53 gene mutation was observed in dedifferentiated tumor tissue samples but not in well-differentiated tumor tissue samples. It has been reported that p53 gene mutation occurs most commonly in the retroperitoneum and rarely in other anatomic locations. Herein we report a case of dedifferentiated liposarcoma located at intraperitoneum.展开更多
Dedifferentiated liposarcoma is a variant of liposarcoma with a more aggressive course. It occurs most commonly in the retroperitoneum and rarely in other anatomic locations. In the present report, we describe a case ...Dedifferentiated liposarcoma is a variant of liposarcoma with a more aggressive course. It occurs most commonly in the retroperitoneum and rarely in other anatomic locations. In the present report, we describe a case of dedifferentiated liposarcoma that occurred in an unusual location, sigmoid mesocolon, which has not yet been documented.展开更多
BACKGROUND Esophageal liposarcoma is a rare malignant tumor and an esophageal dedifferentiated liposarcoma(DDL)is extremely rare.There are no reports on the treatment of DDL by thoracoscopic surgery.CASE SUMMARY A 38-...BACKGROUND Esophageal liposarcoma is a rare malignant tumor and an esophageal dedifferentiated liposarcoma(DDL)is extremely rare.There are no reports on the treatment of DDL by thoracoscopic surgery.CASE SUMMARY A 38-year-old woman presented with dysphagia and dyspnea.Imaging examination showed a large mass in the posterior mediastinum.The patient also developed respiratory failure and it was unclear whether this was caused by a mass from inside or outside the esophagus.We decided to perform thoracoscopic exploration to relieve the obstruction caused by tracheal compression.The upper segment of the esophagus was split longitudinally,and most of the mass could be removed from the esophageal lumen to the thoracic cavity.The pedicle was excised by linear cutting closers under mirrors.Little residual mass was visualized by gastroscopy.The mucous and muscular layers were closed by interrupted sutures.Pathological examination showed that the mass was a DDL.The patient did not have any dysphagia or dyspnea 2 wk postoperatively and refused any further treatment.Computed tomography and esophagoscopy did not find any recurrence at up to 20 mo postoperatively.CONCLUSION Thoracoscopy can be used to treat large esophageal masses.展开更多
BACKGROUND Liposarcoma is one of the most common adult mesenchymal tumors but is uncommon in the gastrointestinal tract and extremely rare in the stomach.Furthermore,the histological subtypes of liposarcoma usually re...BACKGROUND Liposarcoma is one of the most common adult mesenchymal tumors but is uncommon in the gastrointestinal tract and extremely rare in the stomach.Furthermore,the histological subtypes of liposarcoma usually reported in the stomach are well-differentiated or myxoid,and few reports have been issued on small-sized gastric liposarcomas resected endoscopically and followed up.Herein,we report a case of primary gastric dedifferentiated liposarcoma(DL)that was resected endoscopically.CASE SUMMARY A 67-year-old female Korean patient was referred to our institution for further evaluation of a gastric submucosal tumor(SMT)located in the lesser curvature of the gastric body by esophagogastroduodenoscopy.Endoscopic ultrasound revealed a well-circumscribed,slightly heterogeneous,isoechoic,17 mm×10 mm sized mass originating from the third sonographic layer.Computed tomography showed no evidence of significant lymph node enlargement or distant metastasis.Endoscopic resection was undertaken using the snare resection technique after mucosal precutting to provide a definitive histopathologic diagnosis,which proved to be consistent with DL,based on its morphology and the immunoexpressions of MDM2 and CDK4.The patient was planned for surgery because the deep resection margin was positive for malignancy.After declining any invasive procedure or adjuvant treatment,the patient was placed under close follow-up,and at one year after endoscopic resection,remained disease free.CONCLUSION This is the first reported case of a small primary gastric DL resected endoscopically and followed up.This report demonstrates that when diagnosis of a SMT is uncertain,the use of invasive techniques,including endoscopic resection,should be considered.展开更多
BACKGROUND Primary dedifferentiated chondrosarcoma(DDCS)of the lung is extremely rare and has a poor prognosis,especially in patients with a history of carcinomas and related treatment.Herein,we report a case of prima...BACKGROUND Primary dedifferentiated chondrosarcoma(DDCS)of the lung is extremely rare and has a poor prognosis,especially in patients with a history of carcinomas and related treatment.Herein,we report a case of primary DDCS of the lung in a patient with a 4-year history of breast cancer and related treatment.CASE SUMMARY A 49-year-old woman was admitted to our hospital with complaints of headache,dizziness,slurred speech,and dyskinesia in May 2021.Computed tomography(CT)examinations showed multiple nodules in the brain,vertebral body,and both lungs with multiple enlarged lymph nodes in the right hilum and mediastinum,which were considered metastases of breast cancer.No obvious mass was discovered in the right hilum.After several months of related administration,the patient's headache disappeared,and her condition improved.However,new problems of asthma,dyspnea,cough,and restricted activity appeared in late November 2021.Although the CT scan indicated that the lesions in the brain,lung,and vertebral body had shrunk or disappeared,a soft tissue density lesion appeared in her right hilum and blocked the bronchial lumen.To relieve her dyspnea,part of the mass was resected,and a stent was placed via fiberoptic bronchoscopy.Following a complete pathological examination of the tumor,it was confirmed to be a primary DDCS of the lung.The patient then received two rounds of systemic chemotherapy with a regimen of cisplatin+ifosfamide+doxorubicin hydrochloride liposome,palliative radiotherapy for the tumor in her right lung,and four cycles of systemic chemotherapy and targeted therapy with a regimen of temozolomide combined with bevacizumab successively.She was in stable condition after the completion of the systemic chemotherapy and targeted therapy but underwent rapid progression after lung radiotherapy.The CT examinations showed multiple nodules in the brain and in both lungs,and the tumor in the right hilum was increased in size.CONCLUSION This case revealed a rare primary DDCS of the lung with a medical history of breast cancer,meaning a worse prognosis and making it more difficult to treat.展开更多
BACKGROUND Dedifferentiated chondrosarcoma(DDCS)accounts for 10%of all chondrosarcomas and has the poorest outcome,with a 5-year survival rate of 7%-25%.DDCS commonly occurs in the femur and pelvis,whereas DDCS of the...BACKGROUND Dedifferentiated chondrosarcoma(DDCS)accounts for 10%of all chondrosarcomas and has the poorest outcome,with a 5-year survival rate of 7%-25%.DDCS commonly occurs in the femur and pelvis,whereas DDCS of the finger is extremely rare.Furthermore,the histological findings of preexisting solitary enchondroma samples are important and valuable for diagnosing malignant transformations.CASE SUMMARY We report our experience with DDCS in the proximal phalanx of the left middle finger of an 87-year-old woman.She had undergone surgery for enchondroma,with curettage and artificial bone grafting,11 years ago,in the same location.Several years after the primary surgery,the left middle finger gradually started to enlarge,and the growth speed increased in the past year.Plain radiographs showed an expansive osteolytic lesion with calcifications and residual grafting material.Owing to the suspicion of malignancy,we performed ray amputation.Histological findings revealed an abrupt transition between the low-grade chondrosarcoma and dedifferentiated sarcoma components.The dedifferentiated components showed the features of a high-grade undifferentiated pleomorphic sarcoma.The patient was diagnosed with DDCS arising from a preexisting enchondroma.She had no local recurrence or distant metastasis and died of pneumonia 6 years and 10 months after the second surgery.CONCLUSION The histological findings of a precursor lesion showed a typical enchondroma,suggesting that DDCS can arise from enchondroma.展开更多
Objective To investigate the vascular endothelial growth factor(VEGF)expression level by chondrocytes isolated from patients with osteoarthritis (OA) in hip or femoral neck fracture (FNF) and explore the effect of syn...Objective To investigate the vascular endothelial growth factor(VEGF)expression level by chondrocytes isolated from patients with osteoarthritis (OA) in hip or femoral neck fracture (FNF) and explore the effect of synovial fluid from OA展开更多
BACKGROUND Dedifferentiated liposarcoma(DDLS)has a worse prognosis and occurs most commonly in the retroperitoneal region and rarely in the intraperitoneal region.Histological diagnosis was revolutionized by the combi...BACKGROUND Dedifferentiated liposarcoma(DDLS)has a worse prognosis and occurs most commonly in the retroperitoneal region and rarely in the intraperitoneal region.Histological diagnosis was revolutionized by the combined contributions of histoimmuno-chemistry and molecular biology.Aside from surgery,there is no consensus on the optimal treatment for this chemoresistant cancer.CASE SUMMARY A thirty-year-old black female presented with a large painful abdominal mass occupying nearly the entire abdomen and progressive weight loss was admitted for surgery.Abdominal computed tomography showed a large heterogeneous mass of the mesentery that was sized 18 cm×16 cm in size and had heterogeneous contrast enhancement.During laparotomy,en bloc excision of the large and multilobulated gastrocolic ligament mass was performed.The initial postoperative histopathological diagnosis was undifferentiated sarcoma.Finally,the results of immunohistochemistry and molecular biology allowed us to confirm the diagnosis of DDLS.The tumour followed an aggressive evolution with diffuse metastasis,causing the death of the patient less than 5 mo after the operation.CONCLUSION Dedifferentiated liposarcomas are rare tumours that typically originate in the retroperitoneum but may arise in unexpected locations.展开更多
BACKGROUND Dedifferentiated liposarcoma in the mediastinum is an extremely rare malignant neoplasm.A few previous case reports indicate that surgical resection is the major treatment,but frequent recurrence occurs loc...BACKGROUND Dedifferentiated liposarcoma in the mediastinum is an extremely rare malignant neoplasm.A few previous case reports indicate that surgical resection is the major treatment,but frequent recurrence occurs locally.Due to its rarity,its clinical characteristics,optimal treatment and clinical outcomes remain unclear.Here,we report a case of multifocal recurrent dedifferentiated liposarcoma in the posterior mediastinum treated by combining surgery with 125I brachytherapy,and summarize its clinical features,treatment and prognosis.CASE SUMMARY A 75-year-old man was admitted to our hospital with a history of gradual dysphagia for one year and aggravated dysphagia for 3 mo.Contrast-enhanced computed tomography(CT)revealed several large cystic-solid masses with lipomatous density,and calcification in the posterior-inferior mediastinum.The patient received a wide excision by video-assisted thoracoscopic surgery.Pathological analysis confirmed the tumors were dedifferentiated liposarcomas.The tumor locally relapsed 24 mo later,and another operation was performed by video-assisted thoracoscopic surgery.Fifteen months after the second surgery,the tumor recurred again,and the patient received CT-guided radioactive seeds 125I implantation.After 8 mo,follow-up chest CT showed an enlarged tumor.Finally,his condition exacerbated with severe dysphagia and dyspnea,and he died of respiratory failure in July 2018.CONCLUSION We reviewed the literature,and suggest that surgical resection provides beneficial effects for dedifferentiated liposarcoma in the mediastinum,even in cases with local recurrence.125I brachytherapy may be beneficial for recurrent unresectable patients.展开更多
This report presents a dedifferentiated chondrosarcoma with a unique pathologic feature. A 63-year-old man was referred with pain and a soft tissue mass in the left groin. A plain radiograph showed a mineralization in...This report presents a dedifferentiated chondrosarcoma with a unique pathologic feature. A 63-year-old man was referred with pain and a soft tissue mass in the left groin. A plain radiograph showed a mineralization in the proximal femur with partially osteolytic foci and an abnormal shadow in the soft tissue. Magnetic resonance imaging scans showed an inhomogeneous lesion with intermediate to partially low signal intensity on T1-weighted image and intermediate to high signal intensity on T2-weighted image. Microscopically, the tumor in the femur is a low-grade chondrosarcoma and the component of soft tissue was a high-grade sarcomatous lesion with an epithelial arrangement of tumor cells. A diffuse immunoreactivity to both vimentin and c-kit (CD117) antibodies was detected in the high-grade component. A dedifferentiated component is similar to those of gastrointestinal stromal tumor (GIST). This is the first case of dedifferentiated chondrosarcoma with a high-grade component mimicking a GIST.展开更多
Dedifferentiation, as one of the mechanisms rerouting cell fate, regresses cells from a differentiated status to a more primitive one. Due to its potential of amplifying the stem/progenitor cell pool and reproducing s...Dedifferentiation, as one of the mechanisms rerouting cell fate, regresses cells from a differentiated status to a more primitive one. Due to its potential of amplifying the stem/progenitor cell pool and reproducing sizable and desirable cellular elements, it has been attended in the field of regenerative medicine, which will hopefully provide novel therapeutic strategies for currently incurable diseases, such as varieties of central nervous system (CNS) diseases and injuries. In this article, we will first discuss naturally occurring and experimentally induced dedifferentiation, and then set forth principles in stem-cell based therapy in the neural field;beyond that, we will introduce two recent studies that show dedifferentiated stem cells contribute to neural regeneration. Moreover, we also present our recent research results of dedifferentiated muscle stem cells for neurogenic differentiation study in vitro. Further work will be conducted to elucidate the mechanism underlying the dedifferentiation process to facilitate the development of new strategies in regenerative medicine.展开更多
Vein graft(VG)failure(VGF)is associated with VG intimal hyperplasia,which is characterized by abnormal accumulation of vascular smooth muscle cells(VSMCs).Most neointimal VSMCs are derived from pre-existing VSMCs via ...Vein graft(VG)failure(VGF)is associated with VG intimal hyperplasia,which is characterized by abnormal accumulation of vascular smooth muscle cells(VSMCs).Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition,also known as dedifferentiation.There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation,exerting vasoprotective functions;however,the precise mechanisms have not been fully characterized.Therefore,we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation.Ginger significantly inhibited neointimal hyperplasia and promoted lumen(L)opening in a 3-month VG,which was primarily achieved by reducing ferroptotic stress.Ferroptotic stress is a pro-ferroptotic state.Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type,forming neointima(NI)after vein transplantation.Ginger and its two main vasoprotective ingredients(6-gingerol and 6-shogaol)inhibit VSMC dedifferentiation by reducing ferroptotic stress.Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53,while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase(Alox5),both promoting ferroptosis.Furthermore,both ingredients co-target peroxisome proliferator-activated receptor gamma(PPARγ),decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 1(Nox1)expression.Nox1 promotes intracellular reactive oxygen species(ROS)production and directly induces VSMC dedifferentiation.In addition,Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production,indirectly leading to VSMC dedifferentiation.Ginger,a natural multi-targeted ferroptotic stress inhibitor,finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.展开更多
Plant cells retain the ability for cellular reprogramming,including totipotency and pluripotency,enabling them to revert their cell fate from differentiated to dedifferentiated one and subsequently redifferentiate und...Plant cells retain the ability for cellular reprogramming,including totipotency and pluripotency,enabling them to revert their cell fate from differentiated to dedifferentiated one and subsequently redifferentiate under specific physiological and environmental cues.In response to these cues,endogenous phytohormones,genetic landscapes,and epigenetic remodeling play a significant role in initiating the reprogramming of somatic cells and re-establishment of an organized structure.Detailed studies on dedifferentiation have gradually unraveled the involvement of stem-like cells during early callus formation,along with the existence of QC-like transcriptional features in the middle cell layer of callus,which exhibits organ regeneration ability.Tracking natural variations and real-time regeneration dynamics across species,combined with single-cell RNA sequencing,will enable the identification of key developmental regulators and small peptides.These breakthroughs can be applied to enhance regeneration efficiency,improve transformation in recalcitrant species,and accelerate next-generation crop development.The current review summarizes the longstanding history and ongoing research progress in two pathways:dedifferentiation and redifferentiation.It also highlights how hormonal effects on the genetic factors and provides insights into how genetic signatures interact with epigenetic landscapes to drive these processes.It highlights the potential applications of developmental regulators for efficient gene transformation to enhance plant genetic engineering,while also addressing fundamental questions and identifying research gaps to guide future studies.展开更多
BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but th...BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but the detailed mechanism is still unclear.Most studies ofβ-cell dedifferentiation rely on rodent models and human pathological specimens.The development of in vitro systems can facilitate the exploration ofβ-cell dedifferentiation.AIM To investigate the molecular mechanism ofβ-cell dedifferentiation.Hence,an in vitro model ofβ-cell dedifferentiation induced by palmitic acid and high glucose was established using the INS-1832/13 cell line.METHODS The study was further analyzed using RNA-sequencing,transmission electron microscopy,quantitative real-time polymerase chain reaction and Western blot.RESULTS Results showed that the treatment of palmitic acid and high glucose significantly up-regulatedβ-cell forbidden genes and endocrine precursor cell marker genes,and down-regulated the expression ofβ-cell specific markers.Data showed that dedifferentiated INS-1 cells up-regulated the expression of endoplasmic reticulum(ER)stressrelated genes.Moreover,the results also showed that forkhead box O1(Foxo1)inhibition potentiated genetic changes inβ-cell dedifferentiation induced by palmitic acid and high glucose.CONCLUSION ER stress is sufficient to triggerβ-cell dedifferentiation and is necessary for palmitic acid and high glucose-inducedβ-cell dedifferentiation.Foxo1 inhibition can further enhance these phenomena.展开更多
Type 2 diabetes mellitus (T2DM) and obesity are growing global pandemics thatshares the common characteristic of insulin resistance (IR). IR leads to progressive β-cell failure, worsening T2DM and its cardiovascular ...Type 2 diabetes mellitus (T2DM) and obesity are growing global pandemics thatshares the common characteristic of insulin resistance (IR). IR leads to progressive β-cell failure, worsening T2DM and its cardiovascular complications. Thus, earlydiagnosis of IR is important to prevent and reverse β-cell dedifferentiation.However, there is a lack of accessible, non-invasive and affordable tools to earlydiagnose and stratify IR. The gold standard method used in the research setting isthe hyperinsulinemic-euglycemic clamp, however it is invasive, laborious,expensive and difficult to apply at a large scale. Hou et al presents a potentialnovel surrogate biomarker for diagnosing IR in T2DM. Magnetic resonanceimaging derived biomarkers can potentially become the accessible and noninvasivealternative to the hyperinsulinemic-euglycemic clamp, enabling thetimely diagnosis of IR with potential clinical applications in T2DM treatments andpreventative care.展开更多
In this editorial,we highlight the study by Wang et al published in a recent issue of the World Journal of Diabetes.Type 2 diabetes is increasingly recognized as a β-cell dysfunction disorder,with apoptosis and dedif...In this editorial,we highlight the study by Wang et al published in a recent issue of the World Journal of Diabetes.Type 2 diabetes is increasingly recognized as a β-cell dysfunction disorder,with apoptosis and dedifferentiation being key factors in insulin secretion loss.β-cell dedifferentiation is a regression from a mature insulin-secretory phenotype to a progenitor-like state,characterized by the loss of key transcription factors such as pancreatic and duodenal homeobox 1 and MAF bZIP transcription factor A,and the ectopic expression of developmental markers such as neurogenin 3 and aldehyde dehydrogenase 1 family member A3.This editorial discusses the key role of metabolic stress-saturated fatty acids and high glucose-in triggering dedifferentiation through endoplasmic reticulum(ER)stress and repression of the forkhead box protein O1(FoxO1)transcription factor.The study by Wang et al demonstrated how ER dysfunction and FoxO1 suppression collaborate to destabilizeβ-cell identity.Notably,evidence suggests that this process can be reversed under certain circumstances,with potential for therapies aiming to redifferentiateβ-cells or prevent identity loss.We also outline the therapeutic potential of modulating ER stress pathways,controlling FoxO1 activity,and developing biomarkers to trackβ-cell plasticity in patients.Overall,β-cell dedifferentiation knowledge and manipulation offer new avenues for the treatment of diabetes by restoring functionalβ-cell mass.展开更多
文摘When adipose-derived stem cells （ASCs） arc retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based on their buoyancy, mature adipocytes can be easily isolated from the adipose cell suspension and dediffercn- tiated into lipid-frce fibroblast-like cells, named dediffercntiated fat （DFAT） cells. DFAT cells rc-establish active proliferation ability and undertake multipotent capacities. Compared with ASCs and other adult stem cells, DFAT cells showed unique advantages in their abundance, isolation and homogeneity. In this concise review, the establishment and culture methods of DFAT cells arc introduced and the current profiles of their cellular nature are summarized. Under proper inducti~,n culture in vitro or environment in vivo, DFAT cells could demonstrate adipogenic, osteogenic, chondrogenie and myogenic potentials. In angiogenie conditions, DFAT cells could exhibit perivascular characteristics antt elicit neovascularization. Our preliminary findings also suggested the pericyte phenotype underlying such cell lineage, which supported a novel interpretation about the common origin of mesenchymal stem cells and tissue-specific stem cells within blood vessel walls. Current research on DFAT cells indicated that this alternative source of adult multipotent cells has great potential in tissue engineering and regenerative medicine.
基金Supported by In part by the American Heart Association(Medet Jumabay)NIH grants P01 HL30568,R01 HL81397,and R01 HL112839(Kristina I Bostrom)
文摘The identification of an ideal cell source for tissue regeneration remains a challenge in the stem cell field. The ability of progeny cells to differentiate into other cell types is important for the processes of tissue reconstruction and tissue engineering and has clinical, biochemical or molecular implications. The adaptation of stem cells from adipose tissue for use in regenerative medicine has created a new role for adipocytes. Mature adipocytes can easily be isolated from adipose cell suspensions and allowed to dedifferentiate into lipidfree multipotent cells, referred to as dedifferentiated fat(DFAT) cells. Compared to other adult stem cells, the DFAT cells have unique advantages in their abundance, ease of isolation and homogeneity. Under proper condition in vitro and in vivo, the DFAT cells have exhibited adipogenic, osteogenic, chondrogenic, cardiomyogenc, angiogenic, myogenic, and neurogenic potentials. In this review, we first discuss the phenomena of dedifferentiation and transdifferentiation of cells, and then dedifferentiation of adipocytes in particular. Understanding the dedifferentiation process itself may contribute to our knowledge of normal growth processes, as well as mechanisms of disease. Second, we highlight new developments in DFAT cell culture and summarize the current understanding of DFAT cell properties. The unique features of DFAT cells are promising for clinical applications such as tissue regeneration.
文摘Liposarcoma is one of the most common soft tissue sarcomas found in adults,and it usually occurs in the retroperitoneum and the extremities.Here,we describe a case of dedifferentiated liposarcoma originating from a well-differentiated liposarcoma of the mesorectum that presented as a protruding mass in the rectal lumen.Hartmann's operation with total mesorectal excision was performed and the tumor was removed radically.No management guidelines are currently available for liposarcoma of the rectum.We propose that complete surgical resection be required for the treatment of rectal liposarcoma and that a long-term detailed follow up is necessary.
文摘Dedifferentiated liposarcoma(DDLPS) is a variant of liposarcoma but with a more aggressive course.It occurs most commonly in the retroperitoneum and rarely in any other anatomical location.We describe a case of DDLPS arising from the small bowel mesentery presenting as submucosal mass of the small bowel.The current case is unusual as the tumor originated from the small bowel mesentery and a dedifferentiated component transmurally invaded the small bowel wall,including the small bowel submucosa.
文摘Dedifferentiated liposarcoma is a variant of liposarcoma with a more aggressive course. Mutations of the p53 gene have been found in different types of soft tissue sarcoma. It is generally accepted that p53 mutations in human malignant tumors are often related to a poor prognosis. In our case, analysis of p53 gene mutation in tumor samples was performed. p53 gene mutation was observed in dedifferentiated tumor tissue samples but not in well-differentiated tumor tissue samples. It has been reported that p53 gene mutation occurs most commonly in the retroperitoneum and rarely in other anatomic locations. Herein we report a case of dedifferentiated liposarcoma located at intraperitoneum.
文摘Dedifferentiated liposarcoma is a variant of liposarcoma with a more aggressive course. It occurs most commonly in the retroperitoneum and rarely in other anatomic locations. In the present report, we describe a case of dedifferentiated liposarcoma that occurred in an unusual location, sigmoid mesocolon, which has not yet been documented.
文摘BACKGROUND Esophageal liposarcoma is a rare malignant tumor and an esophageal dedifferentiated liposarcoma(DDL)is extremely rare.There are no reports on the treatment of DDL by thoracoscopic surgery.CASE SUMMARY A 38-year-old woman presented with dysphagia and dyspnea.Imaging examination showed a large mass in the posterior mediastinum.The patient also developed respiratory failure and it was unclear whether this was caused by a mass from inside or outside the esophagus.We decided to perform thoracoscopic exploration to relieve the obstruction caused by tracheal compression.The upper segment of the esophagus was split longitudinally,and most of the mass could be removed from the esophageal lumen to the thoracic cavity.The pedicle was excised by linear cutting closers under mirrors.Little residual mass was visualized by gastroscopy.The mucous and muscular layers were closed by interrupted sutures.Pathological examination showed that the mass was a DDL.The patient did not have any dysphagia or dyspnea 2 wk postoperatively and refused any further treatment.Computed tomography and esophagoscopy did not find any recurrence at up to 20 mo postoperatively.CONCLUSION Thoracoscopy can be used to treat large esophageal masses.
文摘BACKGROUND Liposarcoma is one of the most common adult mesenchymal tumors but is uncommon in the gastrointestinal tract and extremely rare in the stomach.Furthermore,the histological subtypes of liposarcoma usually reported in the stomach are well-differentiated or myxoid,and few reports have been issued on small-sized gastric liposarcomas resected endoscopically and followed up.Herein,we report a case of primary gastric dedifferentiated liposarcoma(DL)that was resected endoscopically.CASE SUMMARY A 67-year-old female Korean patient was referred to our institution for further evaluation of a gastric submucosal tumor(SMT)located in the lesser curvature of the gastric body by esophagogastroduodenoscopy.Endoscopic ultrasound revealed a well-circumscribed,slightly heterogeneous,isoechoic,17 mm×10 mm sized mass originating from the third sonographic layer.Computed tomography showed no evidence of significant lymph node enlargement or distant metastasis.Endoscopic resection was undertaken using the snare resection technique after mucosal precutting to provide a definitive histopathologic diagnosis,which proved to be consistent with DL,based on its morphology and the immunoexpressions of MDM2 and CDK4.The patient was planned for surgery because the deep resection margin was positive for malignancy.After declining any invasive procedure or adjuvant treatment,the patient was placed under close follow-up,and at one year after endoscopic resection,remained disease free.CONCLUSION This is the first reported case of a small primary gastric DL resected endoscopically and followed up.This report demonstrates that when diagnosis of a SMT is uncertain,the use of invasive techniques,including endoscopic resection,should be considered.
文摘BACKGROUND Primary dedifferentiated chondrosarcoma(DDCS)of the lung is extremely rare and has a poor prognosis,especially in patients with a history of carcinomas and related treatment.Herein,we report a case of primary DDCS of the lung in a patient with a 4-year history of breast cancer and related treatment.CASE SUMMARY A 49-year-old woman was admitted to our hospital with complaints of headache,dizziness,slurred speech,and dyskinesia in May 2021.Computed tomography(CT)examinations showed multiple nodules in the brain,vertebral body,and both lungs with multiple enlarged lymph nodes in the right hilum and mediastinum,which were considered metastases of breast cancer.No obvious mass was discovered in the right hilum.After several months of related administration,the patient's headache disappeared,and her condition improved.However,new problems of asthma,dyspnea,cough,and restricted activity appeared in late November 2021.Although the CT scan indicated that the lesions in the brain,lung,and vertebral body had shrunk or disappeared,a soft tissue density lesion appeared in her right hilum and blocked the bronchial lumen.To relieve her dyspnea,part of the mass was resected,and a stent was placed via fiberoptic bronchoscopy.Following a complete pathological examination of the tumor,it was confirmed to be a primary DDCS of the lung.The patient then received two rounds of systemic chemotherapy with a regimen of cisplatin+ifosfamide+doxorubicin hydrochloride liposome,palliative radiotherapy for the tumor in her right lung,and four cycles of systemic chemotherapy and targeted therapy with a regimen of temozolomide combined with bevacizumab successively.She was in stable condition after the completion of the systemic chemotherapy and targeted therapy but underwent rapid progression after lung radiotherapy.The CT examinations showed multiple nodules in the brain and in both lungs,and the tumor in the right hilum was increased in size.CONCLUSION This case revealed a rare primary DDCS of the lung with a medical history of breast cancer,meaning a worse prognosis and making it more difficult to treat.
文摘BACKGROUND Dedifferentiated chondrosarcoma(DDCS)accounts for 10%of all chondrosarcomas and has the poorest outcome,with a 5-year survival rate of 7%-25%.DDCS commonly occurs in the femur and pelvis,whereas DDCS of the finger is extremely rare.Furthermore,the histological findings of preexisting solitary enchondroma samples are important and valuable for diagnosing malignant transformations.CASE SUMMARY We report our experience with DDCS in the proximal phalanx of the left middle finger of an 87-year-old woman.She had undergone surgery for enchondroma,with curettage and artificial bone grafting,11 years ago,in the same location.Several years after the primary surgery,the left middle finger gradually started to enlarge,and the growth speed increased in the past year.Plain radiographs showed an expansive osteolytic lesion with calcifications and residual grafting material.Owing to the suspicion of malignancy,we performed ray amputation.Histological findings revealed an abrupt transition between the low-grade chondrosarcoma and dedifferentiated sarcoma components.The dedifferentiated components showed the features of a high-grade undifferentiated pleomorphic sarcoma.The patient was diagnosed with DDCS arising from a preexisting enchondroma.She had no local recurrence or distant metastasis and died of pneumonia 6 years and 10 months after the second surgery.CONCLUSION The histological findings of a precursor lesion showed a typical enchondroma,suggesting that DDCS can arise from enchondroma.
文摘Objective To investigate the vascular endothelial growth factor(VEGF)expression level by chondrocytes isolated from patients with osteoarthritis (OA) in hip or femoral neck fracture (FNF) and explore the effect of synovial fluid from OA
文摘BACKGROUND Dedifferentiated liposarcoma(DDLS)has a worse prognosis and occurs most commonly in the retroperitoneal region and rarely in the intraperitoneal region.Histological diagnosis was revolutionized by the combined contributions of histoimmuno-chemistry and molecular biology.Aside from surgery,there is no consensus on the optimal treatment for this chemoresistant cancer.CASE SUMMARY A thirty-year-old black female presented with a large painful abdominal mass occupying nearly the entire abdomen and progressive weight loss was admitted for surgery.Abdominal computed tomography showed a large heterogeneous mass of the mesentery that was sized 18 cm×16 cm in size and had heterogeneous contrast enhancement.During laparotomy,en bloc excision of the large and multilobulated gastrocolic ligament mass was performed.The initial postoperative histopathological diagnosis was undifferentiated sarcoma.Finally,the results of immunohistochemistry and molecular biology allowed us to confirm the diagnosis of DDLS.The tumour followed an aggressive evolution with diffuse metastasis,causing the death of the patient less than 5 mo after the operation.CONCLUSION Dedifferentiated liposarcomas are rare tumours that typically originate in the retroperitoneum but may arise in unexpected locations.
文摘BACKGROUND Dedifferentiated liposarcoma in the mediastinum is an extremely rare malignant neoplasm.A few previous case reports indicate that surgical resection is the major treatment,but frequent recurrence occurs locally.Due to its rarity,its clinical characteristics,optimal treatment and clinical outcomes remain unclear.Here,we report a case of multifocal recurrent dedifferentiated liposarcoma in the posterior mediastinum treated by combining surgery with 125I brachytherapy,and summarize its clinical features,treatment and prognosis.CASE SUMMARY A 75-year-old man was admitted to our hospital with a history of gradual dysphagia for one year and aggravated dysphagia for 3 mo.Contrast-enhanced computed tomography(CT)revealed several large cystic-solid masses with lipomatous density,and calcification in the posterior-inferior mediastinum.The patient received a wide excision by video-assisted thoracoscopic surgery.Pathological analysis confirmed the tumors were dedifferentiated liposarcomas.The tumor locally relapsed 24 mo later,and another operation was performed by video-assisted thoracoscopic surgery.Fifteen months after the second surgery,the tumor recurred again,and the patient received CT-guided radioactive seeds 125I implantation.After 8 mo,follow-up chest CT showed an enlarged tumor.Finally,his condition exacerbated with severe dysphagia and dyspnea,and he died of respiratory failure in July 2018.CONCLUSION We reviewed the literature,and suggest that surgical resection provides beneficial effects for dedifferentiated liposarcoma in the mediastinum,even in cases with local recurrence.125I brachytherapy may be beneficial for recurrent unresectable patients.
文摘This report presents a dedifferentiated chondrosarcoma with a unique pathologic feature. A 63-year-old man was referred with pain and a soft tissue mass in the left groin. A plain radiograph showed a mineralization in the proximal femur with partially osteolytic foci and an abnormal shadow in the soft tissue. Magnetic resonance imaging scans showed an inhomogeneous lesion with intermediate to partially low signal intensity on T1-weighted image and intermediate to high signal intensity on T2-weighted image. Microscopically, the tumor in the femur is a low-grade chondrosarcoma and the component of soft tissue was a high-grade sarcomatous lesion with an epithelial arrangement of tumor cells. A diffuse immunoreactivity to both vimentin and c-kit (CD117) antibodies was detected in the high-grade component. A dedifferentiated component is similar to those of gastrointestinal stromal tumor (GIST). This is the first case of dedifferentiated chondrosarcoma with a high-grade component mimicking a GIST.
文摘Dedifferentiation, as one of the mechanisms rerouting cell fate, regresses cells from a differentiated status to a more primitive one. Due to its potential of amplifying the stem/progenitor cell pool and reproducing sizable and desirable cellular elements, it has been attended in the field of regenerative medicine, which will hopefully provide novel therapeutic strategies for currently incurable diseases, such as varieties of central nervous system (CNS) diseases and injuries. In this article, we will first discuss naturally occurring and experimentally induced dedifferentiation, and then set forth principles in stem-cell based therapy in the neural field;beyond that, we will introduce two recent studies that show dedifferentiated stem cells contribute to neural regeneration. Moreover, we also present our recent research results of dedifferentiated muscle stem cells for neurogenic differentiation study in vitro. Further work will be conducted to elucidate the mechanism underlying the dedifferentiation process to facilitate the development of new strategies in regenerative medicine.
基金supported by grants from the Natural Science Foundation of Shandong Province,China(Grant Nos.:ZR2019ZD28 and ZR2022QH008)the National Natural Science Foundation of China(Grant Nos.:82270301 and 82200465)+1 种基金China Postdoctoral Science Foundation(Grant No.:2023M731842)Shandong Postdoctoral Science Foundation,China(Grant No.:SDCX-ZG-202203013).
文摘Vein graft(VG)failure(VGF)is associated with VG intimal hyperplasia,which is characterized by abnormal accumulation of vascular smooth muscle cells(VSMCs).Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition,also known as dedifferentiation.There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation,exerting vasoprotective functions;however,the precise mechanisms have not been fully characterized.Therefore,we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation.Ginger significantly inhibited neointimal hyperplasia and promoted lumen(L)opening in a 3-month VG,which was primarily achieved by reducing ferroptotic stress.Ferroptotic stress is a pro-ferroptotic state.Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type,forming neointima(NI)after vein transplantation.Ginger and its two main vasoprotective ingredients(6-gingerol and 6-shogaol)inhibit VSMC dedifferentiation by reducing ferroptotic stress.Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53,while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase(Alox5),both promoting ferroptosis.Furthermore,both ingredients co-target peroxisome proliferator-activated receptor gamma(PPARγ),decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate(NADPH)oxidase 1(Nox1)expression.Nox1 promotes intracellular reactive oxygen species(ROS)production and directly induces VSMC dedifferentiation.In addition,Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production,indirectly leading to VSMC dedifferentiation.Ginger,a natural multi-targeted ferroptotic stress inhibitor,finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.
基金funded by National Key R&D Program of China(Grant No.2024YFD2200600)Science and Technology Project of Hebei Education Department(Grant No.QN2022017)+3 种基金Natural Science Foundation of Hebei Province(Grant No.C2023204062)Fundamental Scientific Research Fund of Universities in Hebei Province(KY2021059)China Agriculture Research System(Grant No.CARS-30-2-07)Hebei Agriculture Research System(Grant Nos.HBCT2024190201,HBCT2024190203).
文摘Plant cells retain the ability for cellular reprogramming,including totipotency and pluripotency,enabling them to revert their cell fate from differentiated to dedifferentiated one and subsequently redifferentiate under specific physiological and environmental cues.In response to these cues,endogenous phytohormones,genetic landscapes,and epigenetic remodeling play a significant role in initiating the reprogramming of somatic cells and re-establishment of an organized structure.Detailed studies on dedifferentiation have gradually unraveled the involvement of stem-like cells during early callus formation,along with the existence of QC-like transcriptional features in the middle cell layer of callus,which exhibits organ regeneration ability.Tracking natural variations and real-time regeneration dynamics across species,combined with single-cell RNA sequencing,will enable the identification of key developmental regulators and small peptides.These breakthroughs can be applied to enhance regeneration efficiency,improve transformation in recalcitrant species,and accelerate next-generation crop development.The current review summarizes the longstanding history and ongoing research progress in two pathways:dedifferentiation and redifferentiation.It also highlights how hormonal effects on the genetic factors and provides insights into how genetic signatures interact with epigenetic landscapes to drive these processes.It highlights the potential applications of developmental regulators for efficient gene transformation to enhance plant genetic engineering,while also addressing fundamental questions and identifying research gaps to guide future studies.
基金Supported by the Natural Science Foundation of China,No.81471081the Natural Science Foundation of Fujian Province,No.2023D009+1 种基金the Natural Science Foundation of Xiamen City,No.3502Z202373104 and No.3502Z20227162Scientific Research Foundation for Advanced Talents,Xiang’an Hospital of Xiamen University,No.PM201809170005。
文摘BACKGROUND Type 2 diabetes mellitus is characterized by pancreaticβ-cell dysfunction and insulin resistance.Studies have suggested thatβ-cell dedifferentiation is one of the pathogeneses ofβ-cell dysfunction,but the detailed mechanism is still unclear.Most studies ofβ-cell dedifferentiation rely on rodent models and human pathological specimens.The development of in vitro systems can facilitate the exploration ofβ-cell dedifferentiation.AIM To investigate the molecular mechanism ofβ-cell dedifferentiation.Hence,an in vitro model ofβ-cell dedifferentiation induced by palmitic acid and high glucose was established using the INS-1832/13 cell line.METHODS The study was further analyzed using RNA-sequencing,transmission electron microscopy,quantitative real-time polymerase chain reaction and Western blot.RESULTS Results showed that the treatment of palmitic acid and high glucose significantly up-regulatedβ-cell forbidden genes and endocrine precursor cell marker genes,and down-regulated the expression ofβ-cell specific markers.Data showed that dedifferentiated INS-1 cells up-regulated the expression of endoplasmic reticulum(ER)stressrelated genes.Moreover,the results also showed that forkhead box O1(Foxo1)inhibition potentiated genetic changes inβ-cell dedifferentiation induced by palmitic acid and high glucose.CONCLUSION ER stress is sufficient to triggerβ-cell dedifferentiation and is necessary for palmitic acid and high glucose-inducedβ-cell dedifferentiation.Foxo1 inhibition can further enhance these phenomena.
文摘Type 2 diabetes mellitus (T2DM) and obesity are growing global pandemics thatshares the common characteristic of insulin resistance (IR). IR leads to progressive β-cell failure, worsening T2DM and its cardiovascular complications. Thus, earlydiagnosis of IR is important to prevent and reverse β-cell dedifferentiation.However, there is a lack of accessible, non-invasive and affordable tools to earlydiagnose and stratify IR. The gold standard method used in the research setting isthe hyperinsulinemic-euglycemic clamp, however it is invasive, laborious,expensive and difficult to apply at a large scale. Hou et al presents a potentialnovel surrogate biomarker for diagnosing IR in T2DM. Magnetic resonanceimaging derived biomarkers can potentially become the accessible and noninvasivealternative to the hyperinsulinemic-euglycemic clamp, enabling thetimely diagnosis of IR with potential clinical applications in T2DM treatments andpreventative care.
基金Supported by Kuwait Foundation for the Advancement of Sciences,No.RACB-2021-007.
文摘In this editorial,we highlight the study by Wang et al published in a recent issue of the World Journal of Diabetes.Type 2 diabetes is increasingly recognized as a β-cell dysfunction disorder,with apoptosis and dedifferentiation being key factors in insulin secretion loss.β-cell dedifferentiation is a regression from a mature insulin-secretory phenotype to a progenitor-like state,characterized by the loss of key transcription factors such as pancreatic and duodenal homeobox 1 and MAF bZIP transcription factor A,and the ectopic expression of developmental markers such as neurogenin 3 and aldehyde dehydrogenase 1 family member A3.This editorial discusses the key role of metabolic stress-saturated fatty acids and high glucose-in triggering dedifferentiation through endoplasmic reticulum(ER)stress and repression of the forkhead box protein O1(FoxO1)transcription factor.The study by Wang et al demonstrated how ER dysfunction and FoxO1 suppression collaborate to destabilizeβ-cell identity.Notably,evidence suggests that this process can be reversed under certain circumstances,with potential for therapies aiming to redifferentiateβ-cells or prevent identity loss.We also outline the therapeutic potential of modulating ER stress pathways,controlling FoxO1 activity,and developing biomarkers to trackβ-cell plasticity in patients.Overall,β-cell dedifferentiation knowledge and manipulation offer new avenues for the treatment of diabetes by restoring functionalβ-cell mass.
