Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of...Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of melanogenesis-related genes and proteins were analyzed inα-melanocyte-stimulating hormone(α-MSH)-stimulated B16F10 cells.Results:α-MSH treatment significantly increased tyrosinase activity,and extracellular and intracellular melanin content,as well as the expression levels of tyrosinase,microphthalmia-associated transcription factor(MITF),tyrosinase-related protein(TRP)-1,and TRP-2 in B16F10 cells.Treatment with Cyrtomium falcatum crude extract and its solvent fractions reduced tyrosinase activity and extracellular and intracellular melanin content and downregulated the expression levels of tyrosinase,MITF,TRP-1,and TRP-2 in a dose-dependent manner.Conclusions:Cyrtomium falcatum has potential anti-melanogenesis effects and can be used as a potential source material in cosmeceutical industry for the research and development of novel lead molecules with whitening properties.展开更多
Objective： To evaluate the effects of HPV16 E6/E7 siRNAs on cervical cancer SiHa cells. Methods： The expressions of the E6, E7, p53 and Rb genes were assayed by RT-PCR and Western-bloting respectively. The prolifera...Objective： To evaluate the effects of HPV16 E6/E7 siRNAs on cervical cancer SiHa cells. Methods： The expressions of the E6, E7, p53 and Rb genes were assayed by RT-PCR and Western-bloting respectively. The proliferation and apoptosis of the cells were evaluated by MTT and flow cytometry. Results： HPV 16 E6 and E7 oncogenes were selectivly downregulated by HPV 16 E6 and E7 siRNAs, which sustained at least 96 h by single dose siRNA. Furthermore, reduction of E6 and E7 oncogenes expression upregulated the expressions of P53 and RB protein and induced apoptosis in SiHa cells. Conclusion： Introduction of HPV16 E6/E7 siRNA might be a potentially potent and specific approach to inhibit proliferation and induce apoptosis of SiHa cervical cancer cells.展开更多
Objective To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and ...Objective To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis. Methods 16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting. Results NiS-treated cells exhibited overlapping growth. Compared wkh that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases （P〈0.01） and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in pl6 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8. Conclusions The FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.展开更多
干扰素诱导蛋白16(interferonγ-inducible protein 16,IFI16)是人类PYHIN(pyrin and HIN domain-containing protein)家族(也称干扰素诱导蛋白P200家族)成员之一,在人体器官组织中广泛存在,参与细胞周期调控、细胞衰老、细胞凋亡及免...干扰素诱导蛋白16(interferonγ-inducible protein 16,IFI16)是人类PYHIN(pyrin and HIN domain-containing protein)家族(也称干扰素诱导蛋白P200家族)成员之一,在人体器官组织中广泛存在,参与细胞周期调控、细胞衰老、细胞凋亡及免疫反应等多种生物过程。不同生理及病理状态下,IFI16的含量及定位均会发生改变,近年来研究发现,其在抗病毒、肿瘤、炎性疾病及其他多种疾病发生发展过程中可能发挥重要作用。该文对其机制及其在疾病中的研究现状进行综述,以期为深入研究IFI16提供参考。展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a common clinical condition with a poor prognosis and few effective treatment options.Potent anticancer agents for treating HCC must be identified.Epigenetics plays an essent...BACKGROUND Hepatocellular carcinoma(HCC)is a common clinical condition with a poor prognosis and few effective treatment options.Potent anticancer agents for treating HCC must be identified.Epigenetics plays an essential role in HCC tumorigenesis.Suberoylanilide hydroxamic acid(SAHA),the most common histone deacetylase inhibitor agent,triggers many forms of cell death in HCC.However,the underlying mechanism of action remains unclear.Family with sequence similarity 134 member B(FAM134B)-induced reticulophagy,a selective autophagic pathway,participates in the decision of cell fate and exhibits anticancer activity.This study focused on the relationship between FAM134B-induced reticulophagy and SAHA-mediated cell death.AIM To elucidate potential roles and underlying molecular mechanisms of reticulophagy in SAHA-induced HCC cell death.METHODS The viability,apoptosis,cell cycle,migration,and invasion of SAHA-treated Huh7 and MHCC97L cells were measured.Proteins related to the reticulophagy pathway,mitochondria-endoplasmic reticulum(ER)contact sites,intrinsic mitochondrial apoptosis,and histone acetylation were quantified using western blotting.ER and lysosome colocalization,and mitochondrial Ca^(2+)levels were characterized via confocal microscopy.The level of cell death was evaluated through Hoechst 33342 staining and propidium iodide colocalization.Chromatin immunoprecipitation was used to verify histone H4 lysine-16 acetylation in the FAM134B promoter region.RESULTS After SAHA treatment,the proliferation of Huh7 and MHCC97L cells was significantly inhibited,and the migration and invasion abilities were greatly blocked in vitro.This promoted apoptosis and caused G1 phase cells to increase in a concentration-dependent manner.Following treatment with SAHA,ER-phagy was activated,thereby triggering autophagy-mediated cell death of HCC cells in vitro.Western blotting and chromatin immunoprecipitation assays confirmed that SAHA regulated FAM134B expression by enhancing the histone H4 lysine-16 acetylation in the FAM134B promoter region.Further,SAHA disturbed the Ca^(2+)homeostasis and upregulated the level of autocrine motility factor receptor and proteins related to mitochondria-endoplasmic reticulum contact sites in HCC cells.Additionally,SAHA decreased the mitochondrial membrane potential levels,thereby accelerating the activation of the reticulophagy-mediated mitochondrial apoptosis pathway and promoting HCC cell death in vitro.CONCLUSION SAHA stimulates FAM134B-mediated ER-phagy to synergistically enhance the mitochondrial apoptotic pathway,thereby enhancing HCC cell death.展开更多
IL-16 is a ligand and chemotactic factor for CD4+ T cells. IL-16 inhibits the CDS mediated lymphocyte activation and proliferation. The effects of IL-16 on the target cells are dependent on the cell type, the presence...IL-16 is a ligand and chemotactic factor for CD4+ T cells. IL-16 inhibits the CDS mediated lymphocyte activation and proliferation. The effects of IL-16 on the target cells are dependent on the cell type, the presence of co-activators etc. To understand the regulation function and mechanism of IL-16 on target cells, we used a 130 a.a. recombinant IL-16 to study its effects on the growth of Jurkat T leukemia cells in vitro. We found that the rIL-16 stimulated the proliferation of Jurkat cells at low dose (10-9M), but inhibited the growth of the cells at higher concentration (10-5M). Results showed that 10-5 M of rIL-16 treatment induced an enhanced apoptosis in Jurkat cells. The treatment blocked the expression of FasL, but up-regulated the c-myc and Bid expression in the cells. Pre-treatment of PKC inhibitor or MEK1 inhibitor markedly increased or decreased the rIL-16 induced growth-inhibiting effects on Jurkat cells, respectively. The results suggested that the rIL-16 might be a regulator for the growth or apoptosis of Jurkat cells at a dose-dependent manner. The growth-inhibiting effects of rIL-16 might be Fas/FasL independent, but, associated with the activation of PKC, up-regulated expression of c-Myc and Bid, and the participation of the ERK signal pathway in Jurkat cells.展开更多
Melanocytes that form stratum basale of skin epidermis express tyrosinase enzyme, which catalyzes initial two rate-limiting steps in the biotransformation of tyrosine into dark pigment called melanin. Even today, Tyro...Melanocytes that form stratum basale of skin epidermis express tyrosinase enzyme, which catalyzes initial two rate-limiting steps in the biotransformation of tyrosine into dark pigment called melanin. Even today, Tyrosinase inhibitors are among the promising candidates in cosmetic industry for skin-lightening formulations. Overexpression of tyrosinase causes excess melanin biosynthesis and deposition resulting in dark skin color. Moreover, localized overexpression of tyrosinase cause variety of hyperpigmentation disorders like melanoma, melasma, chloasma, dark patches, liver patches, etc. There has been a renewed interest in the natural products as main ingredients in the formulation of safe products for skin-whitening and treatment options for hyperpigmentation disorders. In the present communication, the results of our investigations on tyrosinase inhibition, modulation of intracellular tyrosinase and melanin levels in cultured B16F10 melanoma cells by Bacopa monnieri (L.) methanol extract (BME) are presented and discussed as safe option for skin lightening and to treat hyperpigmentation disorders. BME showed 11%, 29%, 54% and 80% inhibition of mushroom tyrosinase activity at an initial 100, 200, 400 and 600 μg of extract. Treatment of α-melanocyte stimulating hormone (α-MSH) stimulated cultured murine melanoma B16F10 cells with 100 μg/ml of the extract showed a decrease in the levels of cellular melanin and cellular tyrosinase content by 22% and 46% respectively. The cytotoxicity studies by MTT assay revealed that the LC50 of the BME is ≥1000 μg/ml in cultured mouse melanoma B16F10 and HEK293 cells.展开更多
BACKGROUND Multinucleated giant cells(MGCs)in bladder carcinomas are poorly studied.AIM To describe the function,morphogenesis,and origin of mononuclear and MGCs in urothelial carcinoma(UC)of the bladder in Bulgarian ...BACKGROUND Multinucleated giant cells(MGCs)in bladder carcinomas are poorly studied.AIM To describe the function,morphogenesis,and origin of mononuclear and MGCs in urothelial carcinoma(UC)of the bladder in Bulgarian and French patients.METHODS Urothelial bladder carcinomas(n=104)from 2016-2020 were analyzed retrospectively using immunohistochemical(IHC)and histochemical stain examination.Giant cells in the bladder stroma were found in 35.6%of cases,more often in highgrades.RESULTS We confirm that MGCs in the mucosa in UC of the bladder were positive for both mesenchymal and myofibroblast markers(vimentin,smooth muscle actin,Desmin,and CD34)and the macrophage marker CD68.Furthermore,IHC studies revealed the following profile of these cells:Positive for p16;negative for epithelial(CK AE1/AE3 and GATA-3),vascular(CD31),neural(PS100 and CKIT),cambial,blastic(CD34-blasts and C-KIT),and immune markers(IG G,immunoglobulin G4,and PD-L1);no proliferative activity,possess no specific immune function,and cannot be used to calculate the Combined Positive Score scale.CONCLUSION In conclusion,the giant stromal cells in non-tumor and tumor bladder can be used as a characteristic and relatively constant,although nonspecific,histological marker for chronic bladder damage,reflecting the chronic irritation or inflammation.Likewise,according to the morphological and IHC of the mono-and multinucleated giant cells in the bladder,they are most likely represent telocytes capable of adapting their morphology to the pathology of the organ.展开更多
In this study, we infected human glioma U251 cells with a replication-defective recombinant adenovirus carrying the p16 gene. This adenovirus constructed was able to transfect exogenous p16 into the human glioma cells...In this study, we infected human glioma U251 cells with a replication-defective recombinant adenovirus carrying the p16 gene. This adenovirus constructed was able to transfect exogenous p16 into the human glioma cells efficiently, and direct a high level of p16 protein expression. Tumor-inhibition experiments demonstrated that treatment with the adenovirus-p16 significantly inhibited the growth of glioma cells in vitro as well as the in vivo development of tumors in nude mice bearing a brain glioma. The combination of adenovirus-p16 gene treatment and X-ray irradiation resulted in a greater inhibition of tumor growth. Adenovirus-mediated p16 gene therapy conferred a significant antitumor effect against human glioma cells both in vitro and in vivo, and that there was a synergistic effect when X-ray irradiation was also used.展开更多
Objective:Study on the mechanism of HPV16 E6 gene mutation promoting the proliferation of cervical cancer cells by influencing the expression of BDNF/TrkB.Methods:The expression levels of HPV16 E6 T350G,BDNF,TrkB and ...Objective:Study on the mechanism of HPV16 E6 gene mutation promoting the proliferation of cervical cancer cells by influencing the expression of BDNF/TrkB.Methods:The expression levels of HPV16 E6 T350G,BDNF,TrkB and p53 mRNA in cervical cancer tissue samples and CINII cervical tissues were detected by Real-time PCR.HPV16 E6 T350G lentivirus(pLV5-HPV16 E6 T350G)and empty vector(pLV5-vector)were designed and constructed,and transfected with HCerEpiC cells,the expression levels of HPV16 E6 T350G,BDNF,TrKB and p53 mRNA were detected by Real-time PCR,and the expression levels of BDNF,TrKB,PI3K,pPI3K,AKT and pAKT protein were detected by western blot;cell proliferation was detected by MTT experiments.Results:Compared with cinii cervical tissue,HPV16 E6 T350G,BDNF and TrkB mRNA expression levels were all positive,while p53 mRNA expression was negative.After overexpression of HPV16 E6 T350G in HCerEpiC cells,it can up-regulate the expression levels of BDNF and TrKB protein and mRNA,and activate the PI3K/AKT signaling pathway which is the downstream of BDNF/TrKB,and reduce p53 protein expression levels;HPV16 E6 T350G overexpression can enhance the proliferation capacity of HCerEpiC cells.Conclusion:Overexpression of HPV16 E6 T350G can promote the proliferation of cervical cancer cells,which may be related to the upregulation of BDNF/TrKB expression,the activation of PI3K/AKT signaling pathway,and the decrease of p53 expression.展开更多
基金This work was supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.2023R1A2C1006268 and RS-2023-00212560).
文摘Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of melanogenesis-related genes and proteins were analyzed inα-melanocyte-stimulating hormone(α-MSH)-stimulated B16F10 cells.Results:α-MSH treatment significantly increased tyrosinase activity,and extracellular and intracellular melanin content,as well as the expression levels of tyrosinase,microphthalmia-associated transcription factor(MITF),tyrosinase-related protein(TRP)-1,and TRP-2 in B16F10 cells.Treatment with Cyrtomium falcatum crude extract and its solvent fractions reduced tyrosinase activity and extracellular and intracellular melanin content and downregulated the expression levels of tyrosinase,MITF,TRP-1,and TRP-2 in a dose-dependent manner.Conclusions:Cyrtomium falcatum has potential anti-melanogenesis effects and can be used as a potential source material in cosmeceutical industry for the research and development of novel lead molecules with whitening properties.
基金supported by the grants from the National Natural Science Foundation of China(No.30660192)the Key Project of Education Committee of Jiangxi Province(No.2005-179).
文摘Objective： To evaluate the effects of HPV16 E6/E7 siRNAs on cervical cancer SiHa cells. Methods： The expressions of the E6, E7, p53 and Rb genes were assayed by RT-PCR and Western-bloting respectively. The proliferation and apoptosis of the cells were evaluated by MTT and flow cytometry. Results： HPV 16 E6 and E7 oncogenes were selectivly downregulated by HPV 16 E6 and E7 siRNAs, which sustained at least 96 h by single dose siRNA. Furthermore, reduction of E6 and E7 oncogenes expression upregulated the expressions of P53 and RB protein and induced apoptosis in SiHa cells. Conclusion： Introduction of HPV16 E6/E7 siRNA might be a potentially potent and specific approach to inhibit proliferation and induce apoptosis of SiHa cervical cancer cells.
基金This work was supported by a grant (No. 39170651 and 30200235) from National Natural Science Foundation of China.
文摘Objective To study the alterations of FHIT gene and P16 gene in malignant transformed human bronchial epithelial cells induced by crystalline nickel sulfide using an immortal human bronchial epithelial cell line, and to explore the molecular mechanism of nickel carcinogenesis. Methods 16HBE cells were treated 6 times with different concentrations of NiS in vitro, and the degree of malignant transformation was determined by assaying the anchorage-independent growth and tumorigenicity. Malignant transformed cells and tumorigenic cells were examined for alterations of FHIT gene and P16 gene using RT-PCR, DNA sequencing, silver staining PCR-SSCP and Western blotting. Results NiS-treated cells exhibited overlapping growth. Compared wkh that of negative control cells, soft agar colony formation efficiency of NiS-treated cells showed significant increases （P〈0.01） and dose-dependent effects. NiS-treated cells could form tumors in nude mice, and a squamous cell carcinoma was confirmed by histopathological examination. No mutation of exon 2 and exons 2-3, no abnormal expression in pl6 gene and mutation of FHIT exons 5-8 and exons 1-4 or exons 5-9 were observed in transformed cells and tumorigenic cells. However, aberrant transcripts or loss of expression of the FHIT gene and Fhit protein was observed in transformed cells and tumorigenic cells. One of the aberrant transcripts in the FHIT gene was confirmed to have a deletion of exon 6, exon 7, exon 8, and an insertion of a 36 bp sequence replacing exon 6-8. Conclusions The FHIT gene rather than the P16 gene, plays a definite role in nickel carcinogenesis. Alterations of the FHIT gene induced by crystalline NiS may be a molecular event associated with carcinogen, chromosome fragile site instability and cell malignant transformation. FHIT may be an important target gene activated by nickel and other exotic carcinogens.
文摘干扰素诱导蛋白16(interferonγ-inducible protein 16,IFI16)是人类PYHIN(pyrin and HIN domain-containing protein)家族(也称干扰素诱导蛋白P200家族)成员之一,在人体器官组织中广泛存在,参与细胞周期调控、细胞衰老、细胞凋亡及免疫反应等多种生物过程。不同生理及病理状态下,IFI16的含量及定位均会发生改变,近年来研究发现,其在抗病毒、肿瘤、炎性疾病及其他多种疾病发生发展过程中可能发挥重要作用。该文对其机制及其在疾病中的研究现状进行综述,以期为深入研究IFI16提供参考。
基金the National Natural Science Foundation of China,No.82260127Guizhou Provincial Science and Technology Projects,No.Qiankehe Jichu-ZK[2021]365 and Qiankehe Jichu-ZK[2021]364+2 种基金National Natural Science Foundation Cultivation Project of Guizhou Medical University,No.20NSP016Guizhou Provincial Natural Science Foundation,No.[2021]4029 and[2022]4017Science and Technology Foundation of Guizhou Provincial Health Commission,No.gzwjkj2019-1-102.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a common clinical condition with a poor prognosis and few effective treatment options.Potent anticancer agents for treating HCC must be identified.Epigenetics plays an essential role in HCC tumorigenesis.Suberoylanilide hydroxamic acid(SAHA),the most common histone deacetylase inhibitor agent,triggers many forms of cell death in HCC.However,the underlying mechanism of action remains unclear.Family with sequence similarity 134 member B(FAM134B)-induced reticulophagy,a selective autophagic pathway,participates in the decision of cell fate and exhibits anticancer activity.This study focused on the relationship between FAM134B-induced reticulophagy and SAHA-mediated cell death.AIM To elucidate potential roles and underlying molecular mechanisms of reticulophagy in SAHA-induced HCC cell death.METHODS The viability,apoptosis,cell cycle,migration,and invasion of SAHA-treated Huh7 and MHCC97L cells were measured.Proteins related to the reticulophagy pathway,mitochondria-endoplasmic reticulum(ER)contact sites,intrinsic mitochondrial apoptosis,and histone acetylation were quantified using western blotting.ER and lysosome colocalization,and mitochondrial Ca^(2+)levels were characterized via confocal microscopy.The level of cell death was evaluated through Hoechst 33342 staining and propidium iodide colocalization.Chromatin immunoprecipitation was used to verify histone H4 lysine-16 acetylation in the FAM134B promoter region.RESULTS After SAHA treatment,the proliferation of Huh7 and MHCC97L cells was significantly inhibited,and the migration and invasion abilities were greatly blocked in vitro.This promoted apoptosis and caused G1 phase cells to increase in a concentration-dependent manner.Following treatment with SAHA,ER-phagy was activated,thereby triggering autophagy-mediated cell death of HCC cells in vitro.Western blotting and chromatin immunoprecipitation assays confirmed that SAHA regulated FAM134B expression by enhancing the histone H4 lysine-16 acetylation in the FAM134B promoter region.Further,SAHA disturbed the Ca^(2+)homeostasis and upregulated the level of autocrine motility factor receptor and proteins related to mitochondria-endoplasmic reticulum contact sites in HCC cells.Additionally,SAHA decreased the mitochondrial membrane potential levels,thereby accelerating the activation of the reticulophagy-mediated mitochondrial apoptosis pathway and promoting HCC cell death in vitro.CONCLUSION SAHA stimulates FAM134B-mediated ER-phagy to synergistically enhance the mitochondrial apoptotic pathway,thereby enhancing HCC cell death.
文摘IL-16 is a ligand and chemotactic factor for CD4+ T cells. IL-16 inhibits the CDS mediated lymphocyte activation and proliferation. The effects of IL-16 on the target cells are dependent on the cell type, the presence of co-activators etc. To understand the regulation function and mechanism of IL-16 on target cells, we used a 130 a.a. recombinant IL-16 to study its effects on the growth of Jurkat T leukemia cells in vitro. We found that the rIL-16 stimulated the proliferation of Jurkat cells at low dose (10-9M), but inhibited the growth of the cells at higher concentration (10-5M). Results showed that 10-5 M of rIL-16 treatment induced an enhanced apoptosis in Jurkat cells. The treatment blocked the expression of FasL, but up-regulated the c-myc and Bid expression in the cells. Pre-treatment of PKC inhibitor or MEK1 inhibitor markedly increased or decreased the rIL-16 induced growth-inhibiting effects on Jurkat cells, respectively. The results suggested that the rIL-16 might be a regulator for the growth or apoptosis of Jurkat cells at a dose-dependent manner. The growth-inhibiting effects of rIL-16 might be Fas/FasL independent, but, associated with the activation of PKC, up-regulated expression of c-Myc and Bid, and the participation of the ERK signal pathway in Jurkat cells.
文摘Melanocytes that form stratum basale of skin epidermis express tyrosinase enzyme, which catalyzes initial two rate-limiting steps in the biotransformation of tyrosine into dark pigment called melanin. Even today, Tyrosinase inhibitors are among the promising candidates in cosmetic industry for skin-lightening formulations. Overexpression of tyrosinase causes excess melanin biosynthesis and deposition resulting in dark skin color. Moreover, localized overexpression of tyrosinase cause variety of hyperpigmentation disorders like melanoma, melasma, chloasma, dark patches, liver patches, etc. There has been a renewed interest in the natural products as main ingredients in the formulation of safe products for skin-whitening and treatment options for hyperpigmentation disorders. In the present communication, the results of our investigations on tyrosinase inhibition, modulation of intracellular tyrosinase and melanin levels in cultured B16F10 melanoma cells by Bacopa monnieri (L.) methanol extract (BME) are presented and discussed as safe option for skin lightening and to treat hyperpigmentation disorders. BME showed 11%, 29%, 54% and 80% inhibition of mushroom tyrosinase activity at an initial 100, 200, 400 and 600 μg of extract. Treatment of α-melanocyte stimulating hormone (α-MSH) stimulated cultured murine melanoma B16F10 cells with 100 μg/ml of the extract showed a decrease in the levels of cellular melanin and cellular tyrosinase content by 22% and 46% respectively. The cytotoxicity studies by MTT assay revealed that the LC50 of the BME is ≥1000 μg/ml in cultured mouse melanoma B16F10 and HEK293 cells.
基金the European Union-NextGenerationEU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008.
文摘BACKGROUND Multinucleated giant cells(MGCs)in bladder carcinomas are poorly studied.AIM To describe the function,morphogenesis,and origin of mononuclear and MGCs in urothelial carcinoma(UC)of the bladder in Bulgarian and French patients.METHODS Urothelial bladder carcinomas(n=104)from 2016-2020 were analyzed retrospectively using immunohistochemical(IHC)and histochemical stain examination.Giant cells in the bladder stroma were found in 35.6%of cases,more often in highgrades.RESULTS We confirm that MGCs in the mucosa in UC of the bladder were positive for both mesenchymal and myofibroblast markers(vimentin,smooth muscle actin,Desmin,and CD34)and the macrophage marker CD68.Furthermore,IHC studies revealed the following profile of these cells:Positive for p16;negative for epithelial(CK AE1/AE3 and GATA-3),vascular(CD31),neural(PS100 and CKIT),cambial,blastic(CD34-blasts and C-KIT),and immune markers(IG G,immunoglobulin G4,and PD-L1);no proliferative activity,possess no specific immune function,and cannot be used to calculate the Combined Positive Score scale.CONCLUSION In conclusion,the giant stromal cells in non-tumor and tumor bladder can be used as a characteristic and relatively constant,although nonspecific,histological marker for chronic bladder damage,reflecting the chronic irritation or inflammation.Likewise,according to the morphological and IHC of the mono-and multinucleated giant cells in the bladder,they are most likely represent telocytes capable of adapting their morphology to the pathology of the organ.
基金Science and Technology Fund Program of Shaanxi Province, No. 2002K10-G3Xi'an Jiaotong University Innovation Fund, No. 0203207
文摘In this study, we infected human glioma U251 cells with a replication-defective recombinant adenovirus carrying the p16 gene. This adenovirus constructed was able to transfect exogenous p16 into the human glioma cells efficiently, and direct a high level of p16 protein expression. Tumor-inhibition experiments demonstrated that treatment with the adenovirus-p16 significantly inhibited the growth of glioma cells in vitro as well as the in vivo development of tumors in nude mice bearing a brain glioma. The combination of adenovirus-p16 gene treatment and X-ray irradiation resulted in a greater inhibition of tumor growth. Adenovirus-mediated p16 gene therapy conferred a significant antitumor effect against human glioma cells both in vitro and in vivo, and that there was a synergistic effect when X-ray irradiation was also used.
基金Science and technology development fund of Shanghai Pudong New Area(No.PKJ2017-Y34)。
文摘Objective:Study on the mechanism of HPV16 E6 gene mutation promoting the proliferation of cervical cancer cells by influencing the expression of BDNF/TrkB.Methods:The expression levels of HPV16 E6 T350G,BDNF,TrkB and p53 mRNA in cervical cancer tissue samples and CINII cervical tissues were detected by Real-time PCR.HPV16 E6 T350G lentivirus(pLV5-HPV16 E6 T350G)and empty vector(pLV5-vector)were designed and constructed,and transfected with HCerEpiC cells,the expression levels of HPV16 E6 T350G,BDNF,TrKB and p53 mRNA were detected by Real-time PCR,and the expression levels of BDNF,TrKB,PI3K,pPI3K,AKT and pAKT protein were detected by western blot;cell proliferation was detected by MTT experiments.Results:Compared with cinii cervical tissue,HPV16 E6 T350G,BDNF and TrkB mRNA expression levels were all positive,while p53 mRNA expression was negative.After overexpression of HPV16 E6 T350G in HCerEpiC cells,it can up-regulate the expression levels of BDNF and TrKB protein and mRNA,and activate the PI3K/AKT signaling pathway which is the downstream of BDNF/TrKB,and reduce p53 protein expression levels;HPV16 E6 T350G overexpression can enhance the proliferation capacity of HCerEpiC cells.Conclusion:Overexpression of HPV16 E6 T350G can promote the proliferation of cervical cancer cells,which may be related to the upregulation of BDNF/TrKB expression,the activation of PI3K/AKT signaling pathway,and the decrease of p53 expression.
