By using DNA-specific fluorescent dye and a confocal laser scanning microscope, the present study was designed to investigate the cytological characteristics of dedifferentiating initiation during pretreatment and em-...By using DNA-specific fluorescent dye and a confocal laser scanning microscope, the present study was designed to investigate the cytological characteristics of dedifferentiating initiation during pretreatment and em-bryogenesis during culture in freshly-isolated microspores of barley, and the difference in main developmental pathway between freshly-isolated and cold-treated microspores. The results revealed that ( i ) freshly-isolated microspores started the initiation within 12 h of mannitol pretreatment, whose main cytological characteristics were that: cell vol-ume was obviously extended; the volume of nuclei and nucleoli were also greatly increased; nucleoli were extremely clear and highly condensed; N/C ratio was very high; ( ii ) all the pretreatment methods led to the initiation of the mi-crospores, thus triggering the embryogenic process; ( iii ) pretreatment methods influenced the main developmental pathway of microspores by changing the pattern of the first mitosis. The cold-treated microspores formed main devel-opmental pathway via A patterns, but freshly-isolated microspores via B pattern.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
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
Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mic...Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cerebral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expression of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluorescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedifferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,significantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydrocholoride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedifferentiation and may be used to treat ischemic stroke.展开更多
BACKGROUND Sarcomatoid renal cell carcinoma(SRCC)is a rare variant of renal cell carcinoma associated with an unfavorable prognosis.The efficacy of conventional chemo-therapy and targeted therapies are limited,whereas...BACKGROUND Sarcomatoid renal cell carcinoma(SRCC)is a rare variant of renal cell carcinoma associated with an unfavorable prognosis.The efficacy of conventional chemo-therapy and targeted therapies are limited,whereas the emergence of immune checkpoint inhibitor has introduced new avenues for managing advanced SRCC.CASE SUMMARY A 77-year-old female patient was referred to our hospital following the incidental detection of a right kidney tumor without specific symptoms.The tumor was successfully resected,and subsequent pathological examination confirmed SRCC.She experienced both local recurrence and distant metastasis eight months after the initial laparoscopic resection.Following six cycles of toripalimab combined with pirarubicin chemotherapy,the patient achieved a partial response.Subse-quently,the patient attained an almost-complete continuous response to toripa-limab monotherapy maintenance for an additional six cycles.She has not experienced disease progression for 15 months,and her overall survival has reached 24 months thus far.CONCLUSION Combination therapy with programmed death 1 antibodies and cytotoxic agents may be a recommended first-line treatment approach for SRCC.展开更多
The ultracytochemical localization of ATPase in the secondary xylem cells during their differentiation and dedifferentiation in the girdled Eucommia ulmoides Oliv. was carried out using a lead phosphate precipitation ...The ultracytochemical localization of ATPase in the secondary xylem cells during their differentiation and dedifferentiation in the girdled Eucommia ulmoides Oliv. was carried out using a lead phosphate precipitation technique. Throughout the differentiation, which is a typical programmed cell death (PCD) process, ATPase deposits increased in the nucleus but decreased and progressively disappeared in the cell organelles. At the same time, the distribution of ATPase increased in the inner face of the cell wall and pits with cytoplasmic degeneration. The results demonstrated that the PCD was an energy dependent active process and was controlled by nuclear genes. On the other hand, the distribution of ATPase in the intercellular spaces increased with the formation of the new cambium resulted from the dedifferentiation of the secondary xylem cells after girdling. However, ATPase was not found in the nucleus of the dividing cells, suggesting that nutrients were transported through protoplast during differentiation, and through both protoplast and apoplast during dedifferentiation. Thus, the energy required in cell division was provided mainly by intercellular spaces. These findings indicate that the dynamic distribution of ATPase reflected which cell component was actively taking part in the cell metabolism at various stages of the plant development, and its distribution was associated with the physiological state of the cell. Based on the characteristic distributions of ATPase, the critical stage of cell differentiation and the relationship between the critical stage and dedifferentiation were discussed.展开更多
This paper summarizes the physiological and metabolic mechanism of a series of processes in the cereal microspore culture from the angle of plant physiological metabolism, explores the physiological or cytology mechan...This paper summarizes the physiological and metabolic mechanism of a series of processes in the cereal microspore culture from the angle of plant physiological metabolism, explores the physiological or cytology mechanism of several key processes, including microspore dedifferentiation and callus formation, differentiation and transformation, and sums up the current problems in this field and forecasts the direction of future development.展开更多
Based on selecting MS minimal medium, through changing the concentrations and additive amounts of two plant growth regulators of NAA and BA, the redifferentiation experiments of plant morphology on callus and embryos ...Based on selecting MS minimal medium, through changing the concentrations and additive amounts of two plant growth regulators of NAA and BA, the redifferentiation experiments of plant morphology on callus and embryos cell which got after the dedifferentiation of ＂Xianglin No.1＂ Camellia oleifera Abel. were carried out.The experimental results showed that callus lines with white, yellowish white or oyster colors, obvious uneven surface and loose texture were inoculated on the medium of MS ＋NAA（0.3 mg/L） ＋BA（2.0 mg/L） ＋saccharose（30 g/L） ＋agar（7 g/L）for 30 d,then multiple shoots were differentiated from the white protuberant part, moreover,the growth vigor was good. If inoculating using regeneration buds of C. oleifera, its multiplication coefficient was 6.50.展开更多
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
Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is W...Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is Wallerian degeneration （WD）, which occurs after acute axonal injury. In the peripheral nervous system （PNS）, WD is characterized by swift dismantling and clearance of injured axons with their myelin sheaths. This is a prerequisite for successful axonal regeneration. In the central nervous system （CNS）, WD is much slower, which significantly contributes to failed axonal regeneration. Although it is well documented that Schwann cells （SCs） have a critical role in the regenerative potential of the PNS, to date we have only scarce knowledge as to how SCs ＇sense＇ axonal injury and immediately respond to it. In this regard, it remains unknown as to whether SCs play the role of a passive bystander or an active director during the execution of the highly orchestrated disintegration program of axons. Older reports, together with more recent studies, suggest that SCs mount dynamic injury responses minutes after axonal injury, long before axonal breakdown occurs. The swift SC response to axonal injury could play either a pro degenerative role, or alternatively a supportive role, to the integrity of distressed axons that have not yet committed to degenerate. Indeed, supporting the latter concept, recent 昀ndings in a chronic PNS neurodegeneration model indicate that deactivation of a key molecule promoting SC injury responses exacerbates axonal loss. If this holds true in a broader spectrum of conditions, it may provide the grounds for the development of new glia-centric therapeutic approaches to counteract axonal loss.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
Type 2 diabetes(T2D)is caused by insulin resistance and insufficient insulin secretion.Evidence has increasingly indicated that pancreaticβ-cell dysfunction is the primary determinant of T2D disease progression and r...Type 2 diabetes(T2D)is caused by insulin resistance and insufficient insulin secretion.Evidence has increasingly indicated that pancreaticβ-cell dysfunction is the primary determinant of T2D disease progression and remission.High plasticity is an important feature of pancreaticβ-cells.During T2D development,pancreaticβ-cells undergo dynamic adaptation.Althoughβ-cell death/apoptosis in later-stage T2D is the major cause ofβ-cell dysfunction,recent studies have revealed thatβ-cell dedifferentiation and reprogramming,which play critical roles inβ-cell functional regulation in the early and middle T2D progression stages,are characterized by(i)a loss of matureβ-cell-enriched genes;(ii)dedifferentiation to a progenitor-like state;and(iii)transdifferentiation into other cell types.The roles of transcription factors(TFs)in the establishment and maintenance ofβ-cell identity during pancreatic development have been extensively studied.Here,we summarize the roles and underlying mechanisms of TFs in the maintenance ofβ-cell identity under physiological and type 2 diabetic conditions.Several feasible approaches for restoring islet functions are also discussed.A better understanding of the transcriptional control ofβ-cell identity and plasticity will pave the way for developing more effective strategies,such asβ-cell regeneration therapy,to treat T2D and associated metabolic disorders.展开更多
Aim： To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 （ERK1/ 2）, c-Jun N-terminal kinases （JNK） and p38 mitogen-activated protein kinases （MAPK） in respon...Aim： To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 （ERK1/ 2）, c-Jun N-terminal kinases （JNK） and p38 mitogen-activated protein kinases （MAPK） in response to heat stress in the cryptorchid testis, and to investigate a possible relation to Sertoli cell dedifferentiation. Methods： Immunohistochemistry and western blot were used to examine the expression and activation of ERK1/2, p38 and JNK in the cryptorchid testis at various stages after experimental cryptorchidism. Results： The abdominal temperature did not obviously change the total ERK1/2 expression but significantly activated phospho-ERK1/2 in the Sertoli cells of the cryptorchid testis. Heat stress increased total JNK expression in the Sertoli cells of the cryptorchid testis but did not activate phospho-JNK. Neither total p38 nor phospho-p38 was induced by heat stress in the Sertoli cells of the cryptorchid testis. Changes in the spatiotemporal expression of cytokeratin 18 （CK18）, a marker of immature or undifferentiated Sertoli cells, were induced in the cryptorchid testis in a pattern similar to the activation of ERK1/2. Condusion： The activation of ERK1/2 in the testis may be related to dedifferentiation of Sertoli cells under heat stress induced by experimental cryptorchidism.展开更多
AIM： To investigate the mechanism behind β-cell regeneration in neonatal rat pancreas treated with strep- tozotocin （STZ）. METHODS： Neonatal Sprague Dawley rats were intra- peritoneally injected with 70 mg/kg STZ...AIM： To investigate the mechanism behind β-cell regeneration in neonatal rat pancreas treated with strep- tozotocin （STZ）. METHODS： Neonatal Sprague Dawley rats were intra- peritoneally injected with 70 mg/kg STZ. Body weight, pancreas weight and blood glucose were recorded every two days after the treatment. To identify the expression and location of transcription factors in the rat pancreas, double immunofluorescent staining was performed using antibodies to specific cell markers and transcription factors. RESULTS： Expression of Neurogenin 3 （Ngn3）, a marker for endocrine precursor cells, was observed by immunofluorescence in a few β-cells and many a-cells. The expression reached a peak 12 d after treatment. Pax4, a transcription factor that lies downstream of Ngn3 and plays an important role in β-cell differentiation, was also expressed in the α-cells of STZ-treated rats. We did not observe significant changes in Nkx6.1, which is essential for β-cell maturation in the treated rats. CONCLUSION： α-cells dedifferentiated into endocrine precursor cells and acquired the ability to dedifferentiate in the neonatal rat pancreas after STZ treatment.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
Diabetes,one of the most common chronic diseases in the modern world,has pancreaticβcell deficiency as a major part of its pathophysiological mechanism.Pancreatic regeneration is a potential therapeutic strategy for ...Diabetes,one of the most common chronic diseases in the modern world,has pancreaticβcell deficiency as a major part of its pathophysiological mechanism.Pancreatic regeneration is a potential therapeutic strategy for the recovery ofβcell loss.However,endocrine islets have limited regenerative capacity,especially in adult humans.Almost all hypoglycemic drugs can protectβcells by inhibitingβcell apoptosis and dedifferentiation via correction of hyperglycemia and amelioration of the consequent inflammation and oxidative stress.Several agents,including glucagon-like peptide-1 andγ-aminobutyric acid,have been shown to promoteβcell proliferation,which is considered the main source of the regeneratedβcells in adult rodents,but with less clarity in humans.Pancreatic progenitor cells might exist and be activated under particular circumstances.Artemisinins andγ-aminobutyric acid can induceα-to-βcell conversion,although some disputes exist.Intestinal endocrine progenitors can transdeterminate into insulin-producing cells in the gut after FoxO1 deletion,and pharmacological research into FoxO1 inhibition is ongoing.Other cells,including pancreatic acinar cells,can transdifferentiate intoβcells,and clinical and preclinical strategies are currently underway.In this review,we summarize the clinical and preclinical agents used in different approaches forβcell regeneration and make some suggestions regarding future perspectives for clinical application.展开更多
Decreased functional β-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10(GRB10), a negative re...Decreased functional β-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10(GRB10), a negative regulator of insulin and m TORC1 signaling, are markedly induced in islets of diabetic mice and high glucose-treated insulinoma cell line INS-1 cells. β-cell-specific knockout of Grb10 in mice increased β-cell mass and improved β-cell function. Grb10-deficient β-cells exhibit enhanced m TORC1 signaling and reduced β-cell dedifferentiation, which could be blocked by rapamycin. On the contrary, Grb10 overexpression induced β-cell dedifferentiation in MIN6 cells. Our study identifies GRB10 as a critical regulator of β-cell dedifferentiation and β-cell mass, which exerts its effect by inhibiting m TORC1 signaling.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
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
文摘By using DNA-specific fluorescent dye and a confocal laser scanning microscope, the present study was designed to investigate the cytological characteristics of dedifferentiating initiation during pretreatment and em-bryogenesis during culture in freshly-isolated microspores of barley, and the difference in main developmental pathway between freshly-isolated and cold-treated microspores. The results revealed that ( i ) freshly-isolated microspores started the initiation within 12 h of mannitol pretreatment, whose main cytological characteristics were that: cell vol-ume was obviously extended; the volume of nuclei and nucleoli were also greatly increased; nucleoli were extremely clear and highly condensed; N/C ratio was very high; ( ii ) all the pretreatment methods led to the initiation of the mi-crospores, thus triggering the embryogenic process; ( iii ) pretreatment methods influenced the main developmental pathway of microspores by changing the pattern of the first mitosis. The cold-treated microspores formed main devel-opmental pathway via A patterns, but freshly-isolated microspores via B pattern.
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.
文摘Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cerebral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expression of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluorescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedifferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,significantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydrocholoride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedifferentiation and may be used to treat ischemic stroke.
基金The Health Research Program of Anhui Province,China,No.AHWJ2022b048The Research Foundation of Anhui Medical University,China,No.2021xkj164The Clinical Scientific Research Cultivation Project of the Second Affiliated Hospital of Anhui Medical University,China,No.2021LCZD04.
文摘BACKGROUND Sarcomatoid renal cell carcinoma(SRCC)is a rare variant of renal cell carcinoma associated with an unfavorable prognosis.The efficacy of conventional chemo-therapy and targeted therapies are limited,whereas the emergence of immune checkpoint inhibitor has introduced new avenues for managing advanced SRCC.CASE SUMMARY A 77-year-old female patient was referred to our hospital following the incidental detection of a right kidney tumor without specific symptoms.The tumor was successfully resected,and subsequent pathological examination confirmed SRCC.She experienced both local recurrence and distant metastasis eight months after the initial laparoscopic resection.Following six cycles of toripalimab combined with pirarubicin chemotherapy,the patient achieved a partial response.Subse-quently,the patient attained an almost-complete continuous response to toripa-limab monotherapy maintenance for an additional six cycles.She has not experienced disease progression for 15 months,and her overall survival has reached 24 months thus far.CONCLUSION Combination therapy with programmed death 1 antibodies and cytotoxic agents may be a recommended first-line treatment approach for SRCC.
文摘The ultracytochemical localization of ATPase in the secondary xylem cells during their differentiation and dedifferentiation in the girdled Eucommia ulmoides Oliv. was carried out using a lead phosphate precipitation technique. Throughout the differentiation, which is a typical programmed cell death (PCD) process, ATPase deposits increased in the nucleus but decreased and progressively disappeared in the cell organelles. At the same time, the distribution of ATPase increased in the inner face of the cell wall and pits with cytoplasmic degeneration. The results demonstrated that the PCD was an energy dependent active process and was controlled by nuclear genes. On the other hand, the distribution of ATPase in the intercellular spaces increased with the formation of the new cambium resulted from the dedifferentiation of the secondary xylem cells after girdling. However, ATPase was not found in the nucleus of the dividing cells, suggesting that nutrients were transported through protoplast during differentiation, and through both protoplast and apoplast during dedifferentiation. Thus, the energy required in cell division was provided mainly by intercellular spaces. These findings indicate that the dynamic distribution of ATPase reflected which cell component was actively taking part in the cell metabolism at various stages of the plant development, and its distribution was associated with the physiological state of the cell. Based on the characteristic distributions of ATPase, the critical stage of cell differentiation and the relationship between the critical stage and dedifferentiation were discussed.
文摘This paper summarizes the physiological and metabolic mechanism of a series of processes in the cereal microspore culture from the angle of plant physiological metabolism, explores the physiological or cytology mechanism of several key processes, including microspore dedifferentiation and callus formation, differentiation and transformation, and sums up the current problems in this field and forecasts the direction of future development.
基金Supported by China Hunan Provincial Science&Technology Department(2012NK3118)~~
文摘Based on selecting MS minimal medium, through changing the concentrations and additive amounts of two plant growth regulators of NAA and BA, the redifferentiation experiments of plant morphology on callus and embryos cell which got after the dedifferentiation of ＂Xianglin No.1＂ Camellia oleifera Abel. were carried out.The experimental results showed that callus lines with white, yellowish white or oyster colors, obvious uneven surface and loose texture were inoculated on the medium of MS ＋NAA（0.3 mg/L） ＋BA（2.0 mg/L） ＋saccharose（30 g/L） ＋agar（7 g/L）for 30 d,then multiple shoots were differentiated from the white protuberant part, moreover,the growth vigor was good. If inoculating using regeneration buds of C. oleifera, its multiplication coefficient was 6.50.
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 Muscular Dystrophy Association grants#292306 and#236648Empire State Development Corporation for HJKRI Grants W753 and U446+1 种基金Hunter’s Hope FoundationUniversity at Buffalo IMPACT funding
文摘Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is Wallerian degeneration （WD）, which occurs after acute axonal injury. In the peripheral nervous system （PNS）, WD is characterized by swift dismantling and clearance of injured axons with their myelin sheaths. This is a prerequisite for successful axonal regeneration. In the central nervous system （CNS）, WD is much slower, which significantly contributes to failed axonal regeneration. Although it is well documented that Schwann cells （SCs） have a critical role in the regenerative potential of the PNS, to date we have only scarce knowledge as to how SCs ＇sense＇ axonal injury and immediately respond to it. In this regard, it remains unknown as to whether SCs play the role of a passive bystander or an active director during the execution of the highly orchestrated disintegration program of axons. Older reports, together with more recent studies, suggest that SCs mount dynamic injury responses minutes after axonal injury, long before axonal breakdown occurs. The swift SC response to axonal injury could play either a pro degenerative role, or alternatively a supportive role, to the integrity of distressed axons that have not yet committed to degenerate. Indeed, supporting the latter concept, recent 昀ndings in a chronic PNS neurodegeneration model indicate that deactivation of a key molecule promoting SC injury responses exacerbates axonal loss. If this holds true in a broader spectrum of conditions, it may provide the grounds for the development of new glia-centric therapeutic approaches to counteract axonal loss.
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.
基金supported by grants from the Training Program of the Major Research Plan of the National Natural Science Foundation of China (91857110)the National Key Research and Development Programme of China (2018YFA0800403 and 2016YFC1305303)+5 种基金the National Natural Science Foundation of China (81670740)the National Natural Science Fund for Excellent Young Scholars of China (81722012)the Zhejiang Provincial Natural Science Foundation of China (LZ21H070001)the Innovative Institute of Basic Medical Sciences of Zhejiang University, and the Fundamental Research Funds for the Central Universities, the Construction Fund of Medical Key Disciplines of Hangzhou (No. OO20200055)the Hangzhou Science and Technology Bureau (20150733Q13 and ZD20200129)the support from K.C. Wong Education Foundation
文摘Type 2 diabetes(T2D)is caused by insulin resistance and insufficient insulin secretion.Evidence has increasingly indicated that pancreaticβ-cell dysfunction is the primary determinant of T2D disease progression and remission.High plasticity is an important feature of pancreaticβ-cells.During T2D development,pancreaticβ-cells undergo dynamic adaptation.Althoughβ-cell death/apoptosis in later-stage T2D is the major cause ofβ-cell dysfunction,recent studies have revealed thatβ-cell dedifferentiation and reprogramming,which play critical roles inβ-cell functional regulation in the early and middle T2D progression stages,are characterized by(i)a loss of matureβ-cell-enriched genes;(ii)dedifferentiation to a progenitor-like state;and(iii)transdifferentiation into other cell types.The roles of transcription factors(TFs)in the establishment and maintenance ofβ-cell identity during pancreatic development have been extensively studied.Here,we summarize the roles and underlying mechanisms of TFs in the maintenance ofβ-cell identity under physiological and type 2 diabetic conditions.Several feasible approaches for restoring islet functions are also discussed.A better understanding of the transcriptional control ofβ-cell identity and plasticity will pave the way for developing more effective strategies,such asβ-cell regeneration therapy,to treat T2D and associated metabolic disorders.
基金Acknowledgment This study was supported by the National Natural Science Foundation of China （30230190）, the National Basic Science Research and Development Project （973） （G1999055901） and the Chinese Academy of Sciences （CAS） Knowledge Innovation Program （KSCX-2-SW-201）.
文摘Aim： To assess the spatiotemporal changes in the expression of extracellular signal-regulated kinases 1 and 2 （ERK1/ 2）, c-Jun N-terminal kinases （JNK） and p38 mitogen-activated protein kinases （MAPK） in response to heat stress in the cryptorchid testis, and to investigate a possible relation to Sertoli cell dedifferentiation. Methods： Immunohistochemistry and western blot were used to examine the expression and activation of ERK1/2, p38 and JNK in the cryptorchid testis at various stages after experimental cryptorchidism. Results： The abdominal temperature did not obviously change the total ERK1/2 expression but significantly activated phospho-ERK1/2 in the Sertoli cells of the cryptorchid testis. Heat stress increased total JNK expression in the Sertoli cells of the cryptorchid testis but did not activate phospho-JNK. Neither total p38 nor phospho-p38 was induced by heat stress in the Sertoli cells of the cryptorchid testis. Changes in the spatiotemporal expression of cytokeratin 18 （CK18）, a marker of immature or undifferentiated Sertoli cells, were induced in the cryptorchid testis in a pattern similar to the activation of ERK1/2. Condusion： The activation of ERK1/2 in the testis may be related to dedifferentiation of Sertoli cells under heat stress induced by experimental cryptorchidism.
基金Supported by The National Natural Science Foundation of China,No. 81070620
文摘AIM： To investigate the mechanism behind β-cell regeneration in neonatal rat pancreas treated with strep- tozotocin （STZ）. METHODS： Neonatal Sprague Dawley rats were intra- peritoneally injected with 70 mg/kg STZ. Body weight, pancreas weight and blood glucose were recorded every two days after the treatment. To identify the expression and location of transcription factors in the rat pancreas, double immunofluorescent staining was performed using antibodies to specific cell markers and transcription factors. RESULTS： Expression of Neurogenin 3 （Ngn3）, a marker for endocrine precursor cells, was observed by immunofluorescence in a few β-cells and many a-cells. The expression reached a peak 12 d after treatment. Pax4, a transcription factor that lies downstream of Ngn3 and plays an important role in β-cell differentiation, was also expressed in the α-cells of STZ-treated rats. We did not observe significant changes in Nkx6.1, which is essential for β-cell maturation in the treated rats. CONCLUSION： α-cells dedifferentiated into endocrine precursor cells and acquired the ability to dedifferentiate in the neonatal rat pancreas after STZ treatment.
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.
基金Supported by the National Key Research and Development Program of China,No.2016YFA0100501the National Natural Science Foundation of China,No.81770768 and No.81970671and the Natural Science Foundation of Beijing,No.7192225.
文摘Diabetes,one of the most common chronic diseases in the modern world,has pancreaticβcell deficiency as a major part of its pathophysiological mechanism.Pancreatic regeneration is a potential therapeutic strategy for the recovery ofβcell loss.However,endocrine islets have limited regenerative capacity,especially in adult humans.Almost all hypoglycemic drugs can protectβcells by inhibitingβcell apoptosis and dedifferentiation via correction of hyperglycemia and amelioration of the consequent inflammation and oxidative stress.Several agents,including glucagon-like peptide-1 andγ-aminobutyric acid,have been shown to promoteβcell proliferation,which is considered the main source of the regeneratedβcells in adult rodents,but with less clarity in humans.Pancreatic progenitor cells might exist and be activated under particular circumstances.Artemisinins andγ-aminobutyric acid can induceα-to-βcell conversion,although some disputes exist.Intestinal endocrine progenitors can transdeterminate into insulin-producing cells in the gut after FoxO1 deletion,and pharmacological research into FoxO1 inhibition is ongoing.Other cells,including pancreatic acinar cells,can transdifferentiate intoβcells,and clinical and preclinical strategies are currently underway.In this review,we summarize the clinical and preclinical agents used in different approaches forβcell regeneration and make some suggestions regarding future perspectives for clinical application.
基金supported by grants from the National Natural Science Foundation of China (91749118, 82070807, 81770775, 81730022)Natural Science Foundation of Hunan Province, China (2021JJ30976)National Key Research and Development Program (2019YFA0801903, 2018YFC2000100)。
文摘Decreased functional β-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10(GRB10), a negative regulator of insulin and m TORC1 signaling, are markedly induced in islets of diabetic mice and high glucose-treated insulinoma cell line INS-1 cells. β-cell-specific knockout of Grb10 in mice increased β-cell mass and improved β-cell function. Grb10-deficient β-cells exhibit enhanced m TORC1 signaling and reduced β-cell dedifferentiation, which could be blocked by rapamycin. On the contrary, Grb10 overexpression induced β-cell dedifferentiation in MIN6 cells. Our study identifies GRB10 as a critical regulator of β-cell dedifferentiation and β-cell mass, which exerts its effect by inhibiting m TORC1 signaling.
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.
