BACKGROUND Ependymoma with lipomatous differentiation is a rare type of ependymoma.The ZFTA fusion-positive supratentorial ependymoma is a novel tumor type in the 2021 World Health Organization classification of centr...BACKGROUND Ependymoma with lipomatous differentiation is a rare type of ependymoma.The ZFTA fusion-positive supratentorial ependymoma is a novel tumor type in the 2021 World Health Organization classification of central nervous system tumors.ZFTA fusion-positive lipomatous ependymoma has not been reported to date.CASE SUMMARY We reported a case of a 15-year-old Chinese male who had a sudden convulsion lasting approximately six minutes.Magnetic resonance imaging showed a round cystic shadow of approximately 1.9 cm×1.5 cm×1.9 cm under the right parieto-occipital cortex.Microscopic examination showed characteristic perivascular pseudorosettes and adipose differentiation in the cytoplasm.Immunohisto-chemical staining showed that the tumor cells were negative for cytokeratin,NeuN,Syn and p53,but positive for GFAP,vimentin and S-100 protein.Signi-ficant punctate intracytoplasmic EMA immunoreactivity was observed.The level of Ki-67 was about 5%.Genetic analysis revealed ZFTA:RELA fusion.A cranio-tomy with total excision of the tumor was performed.The follow-up time was 36 months,no evidence of disease recurrence was found in magnetic resonance imaging.CONCLUSION Based on these findings,the patient was diagnosed as a ependymoma with ZFTA fusion and lipomatous differentiation.This case report provides information on the microscopic morphological features of ependymoma with ZFTA fusion and lipomatous differentiation,which can help pathologists to make a definitive diagnosis of this tumor.展开更多
[Objectives]To develop a pair of specific primers for the PCR amplification of the full-length relA gene from Vibrio alginolyticus strain HY9901,as well as to conduct bioinformatics analysis.[Methods]The relA gene was...[Objectives]To develop a pair of specific primers for the PCR amplification of the full-length relA gene from Vibrio alginolyticus strain HY9901,as well as to conduct bioinformatics analysis.[Methods]The relA gene was amplified through PCR,and the resulting gene sequence was subsequently analyzed using bioinformatics tools,including amino acid sequence prediction,functional site analysis,subcellular localization prediction,and homology comparison.[Results]The relA gene had a total length of 2220 bp and encoded 739 amino acid residues.The molecular weight was approximately 84.1261 kDa,and its isoelectric point was 5.95.The protein lacked a signal peptide and transmembrane regions,while exhibiting multiple phosphorylation sites.Predictions regarding its subcellular localization suggested that it was predominantly situated in the cytoplasm.The amino acid sequence demonstrated a homology of 97%to 99%with other species within the genus Vibrio,and it clustered within the same subfamily as V.antiquarius and V.diabolicus.In the prediction of secondary structure,the proportions ofα-helix,extended strand,random coil,andβ-sheet were 54.13%,12.04%,28.15%and 5.68%,respectively.The similarity between the tertiary structure model and template 5kpw.1.w was 66%.[Conclusions]In this study,the relA gene of V.alginolyticus strain HY9901 has been successfully amplified and analyzed.The structural characteristics and potential functions of the encoded protein have been elucidated,thereby providing foundational data for understanding the role of this gene in V.alginolyticus.展开更多
BACKGROUND Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017.Its diagnosis is often challenging because of its relative rarity,lack of known genetic abnormalities,and expression of m...BACKGROUND Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017.Its diagnosis is often challenging because of its relative rarity,lack of known genetic abnormalities,and expression of muscle markers that can be confused with sarcomas that have myogenic differentiation.Currently,scholars have limited knowledge of this disease,and published cases are few.Further accumulation of diagnostic and treatment experiences is required.CASE SUMMARY A 16-year-old girl experienced left upper limb swelling for 3 years.She sought medical attention at a local hospital 10 months ago,where magnetic resonance imaging revealed a 5-cm soft tissue mass.Needle biopsy performed at a local hospital resulted in the diagnosis of a spindle cell soft tissue sarcoma.The patient was referred to our hospital for limb salvage surgery with endoprosthetic replacement.She was initially diagnosed with a synovial sarcoma.Consequently,clinical management with chemotherapy was continued for the malignant sarcoma.Our pathology department also performed fluorescence in situ hybridization for result validation,which returned negative for SS18 gene breaks,indicating that it was not a synovial sarcoma.Next-generation sequencing was used to identify the SRF-RELA rearrangement.The final pathological diagnosis was a cellular/myofibroblastic neoplasm with an SRF-RELA gene fusion.The patient had initially received two courses of chemotherapy;however,chemotherapy was discontinued after the final diagnosis.CONCLUSION This case was misdiagnosed because of its rare occurrence,benign biological behavior,and pathological similarity to soft tissue sarcoma.展开更多
Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AF...Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.展开更多
Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-tran...Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-translocation-associated (ZFTA, ST-EPN-ZFTA), exhibits the expression of a fusion protein comprising ZFTA and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-kappa B (NF-κB) pathway (ZFTA-RELA). The expression of ZFTA-RELA results in the hyperactivation of the oncogenic NF-κB signaling pathway, which ultimately leads to the development of ST-EPN-ZFTA. To identify inhibitors of the NF-κB signaling pathway activated by the expression of ZFTA-RELA, we used a doxycycline-inducible ZFTA-RELA-expressing NF-κB reporter cell line and found that extracts of the fungus Neosartorya spinosa IFM 47025 exhibited NF-κB inhibitory activity. We identified eight compounds [aszonapyrone A (2), sartorypyrone A (3), epiheveadride (4), acetylaszonalenin (5), (R)-benzodiazepinedione (6), aszonalenin (7), sartorypyrone E (8) and (Z, Z)-N,N’-(1,2-bis[(4-methoxyphenyl)methylene]-1,2-ethanediyl)bis-formamide (9)] from N. spinosa IFM 47025 culture extract using a variety of chromatographic techniques. The structures of these compounds were identified through the analysis of various instrumental data (1D, 2D-NMR, MS, and optical rotation). The NF-κB responsive reporter assay indicated that compounds 2, 3, 5, 7, and 9 exhibited inhibitory activity. We further evaluated the inhibitory activity of these compounds against the expression of endogenous NF-κB responsive genes (CCND1, L1CAM, ICAM1, and TNF) and found that compound 2 showed significant inhibitory activity. Further studies are required to elucidate the mechanism of action of compound 2, which may serve as a lead compound for the development of a novel therapy for ST-EPN-ZFTA.展开更多
文摘BACKGROUND Ependymoma with lipomatous differentiation is a rare type of ependymoma.The ZFTA fusion-positive supratentorial ependymoma is a novel tumor type in the 2021 World Health Organization classification of central nervous system tumors.ZFTA fusion-positive lipomatous ependymoma has not been reported to date.CASE SUMMARY We reported a case of a 15-year-old Chinese male who had a sudden convulsion lasting approximately six minutes.Magnetic resonance imaging showed a round cystic shadow of approximately 1.9 cm×1.5 cm×1.9 cm under the right parieto-occipital cortex.Microscopic examination showed characteristic perivascular pseudorosettes and adipose differentiation in the cytoplasm.Immunohisto-chemical staining showed that the tumor cells were negative for cytokeratin,NeuN,Syn and p53,but positive for GFAP,vimentin and S-100 protein.Signi-ficant punctate intracytoplasmic EMA immunoreactivity was observed.The level of Ki-67 was about 5%.Genetic analysis revealed ZFTA:RELA fusion.A cranio-tomy with total excision of the tumor was performed.The follow-up time was 36 months,no evidence of disease recurrence was found in magnetic resonance imaging.CONCLUSION Based on these findings,the patient was diagnosed as a ependymoma with ZFTA fusion and lipomatous differentiation.This case report provides information on the microscopic morphological features of ependymoma with ZFTA fusion and lipomatous differentiation,which can help pathologists to make a definitive diagnosis of this tumor.
基金Supported by Natural Science Foundation of Guangdong Province(2025A1515011061)Outstanding Graduate Entering Laboratory Project of College of Fisheries,Guangdong Ocean University+1 种基金Undergraduate Innovation and Entrepreneurship Training Program of Guangdong Ocean University(CXXL2024007)Undergraduate Innovation Team of Guangdong Ocean University(CCTD201802).
文摘[Objectives]To develop a pair of specific primers for the PCR amplification of the full-length relA gene from Vibrio alginolyticus strain HY9901,as well as to conduct bioinformatics analysis.[Methods]The relA gene was amplified through PCR,and the resulting gene sequence was subsequently analyzed using bioinformatics tools,including amino acid sequence prediction,functional site analysis,subcellular localization prediction,and homology comparison.[Results]The relA gene had a total length of 2220 bp and encoded 739 amino acid residues.The molecular weight was approximately 84.1261 kDa,and its isoelectric point was 5.95.The protein lacked a signal peptide and transmembrane regions,while exhibiting multiple phosphorylation sites.Predictions regarding its subcellular localization suggested that it was predominantly situated in the cytoplasm.The amino acid sequence demonstrated a homology of 97%to 99%with other species within the genus Vibrio,and it clustered within the same subfamily as V.antiquarius and V.diabolicus.In the prediction of secondary structure,the proportions ofα-helix,extended strand,random coil,andβ-sheet were 54.13%,12.04%,28.15%and 5.68%,respectively.The similarity between the tertiary structure model and template 5kpw.1.w was 66%.[Conclusions]In this study,the relA gene of V.alginolyticus strain HY9901 has been successfully amplified and analyzed.The structural characteristics and potential functions of the encoded protein have been elucidated,thereby providing foundational data for understanding the role of this gene in V.alginolyticus.
文摘BACKGROUND Cellular myofibroma is a rare subtype of myofibroma that was first described in 2017.Its diagnosis is often challenging because of its relative rarity,lack of known genetic abnormalities,and expression of muscle markers that can be confused with sarcomas that have myogenic differentiation.Currently,scholars have limited knowledge of this disease,and published cases are few.Further accumulation of diagnostic and treatment experiences is required.CASE SUMMARY A 16-year-old girl experienced left upper limb swelling for 3 years.She sought medical attention at a local hospital 10 months ago,where magnetic resonance imaging revealed a 5-cm soft tissue mass.Needle biopsy performed at a local hospital resulted in the diagnosis of a spindle cell soft tissue sarcoma.The patient was referred to our hospital for limb salvage surgery with endoprosthetic replacement.She was initially diagnosed with a synovial sarcoma.Consequently,clinical management with chemotherapy was continued for the malignant sarcoma.Our pathology department also performed fluorescence in situ hybridization for result validation,which returned negative for SS18 gene breaks,indicating that it was not a synovial sarcoma.Next-generation sequencing was used to identify the SRF-RELA rearrangement.The final pathological diagnosis was a cellular/myofibroblastic neoplasm with an SRF-RELA gene fusion.The patient had initially received two courses of chemotherapy;however,chemotherapy was discontinued after the final diagnosis.CONCLUSION This case was misdiagnosed because of its rare occurrence,benign biological behavior,and pathological similarity to soft tissue sarcoma.
基金funded by Suzhou Science and Technology Council(SNG201907)Universities Natural Science Foundation of Jiangsu Province(20KJB330002)+6 种基金General Program of China Postdoctoral Science Foundation(2022M711369)the Startup Funding of Soochow University,Jiangsu Province-Suzhou Science and Technology Planning Project(SL T201917)National Natural Science Foundation of China(32172922,31972741)Natural Science Foundation of Jiangsu Province of China(BK20211216,BK20221091)the Startup Funding of Hefei University of Technology(1302003712022058)China-CEEC Joint University Education Project(202010)the Excellence Project PrF UHK(2217/2022-2023)。
文摘Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.
文摘Ependymoma is a rare and chemotherapy-resistant brain tumor, which has resulted in a delay in the development of drugs to treat it. A subclass of supratentorial ependymomas (ST-EPN), designated ST-EPN-zinc finger-translocation-associated (ZFTA, ST-EPN-ZFTA), exhibits the expression of a fusion protein comprising ZFTA and v-rel reticuloendotheliosis viral oncogene homolog A (RELA), an effector transcription factor of the nuclear factor-kappa B (NF-κB) pathway (ZFTA-RELA). The expression of ZFTA-RELA results in the hyperactivation of the oncogenic NF-κB signaling pathway, which ultimately leads to the development of ST-EPN-ZFTA. To identify inhibitors of the NF-κB signaling pathway activated by the expression of ZFTA-RELA, we used a doxycycline-inducible ZFTA-RELA-expressing NF-κB reporter cell line and found that extracts of the fungus Neosartorya spinosa IFM 47025 exhibited NF-κB inhibitory activity. We identified eight compounds [aszonapyrone A (2), sartorypyrone A (3), epiheveadride (4), acetylaszonalenin (5), (R)-benzodiazepinedione (6), aszonalenin (7), sartorypyrone E (8) and (Z, Z)-N,N’-(1,2-bis[(4-methoxyphenyl)methylene]-1,2-ethanediyl)bis-formamide (9)] from N. spinosa IFM 47025 culture extract using a variety of chromatographic techniques. The structures of these compounds were identified through the analysis of various instrumental data (1D, 2D-NMR, MS, and optical rotation). The NF-κB responsive reporter assay indicated that compounds 2, 3, 5, 7, and 9 exhibited inhibitory activity. We further evaluated the inhibitory activity of these compounds against the expression of endogenous NF-κB responsive genes (CCND1, L1CAM, ICAM1, and TNF) and found that compound 2 showed significant inhibitory activity. Further studies are required to elucidate the mechanism of action of compound 2, which may serve as a lead compound for the development of a novel therapy for ST-EPN-ZFTA.
