Pear(Pyrus bretschneideri)fruit stone cells are primarily composed of lignin and have strongly lignified cell walls.The presence of stone cells has a negative influence on fruit texture and taste,and thus the reductio...Pear(Pyrus bretschneideri)fruit stone cells are primarily composed of lignin and have strongly lignified cell walls.The presence of stone cells has a negative influence on fruit texture and taste,and thus the reduction of stone cell content in pear fruit is a key goal of breeding efforts.However,research into the key transcription factors and regulatory networks associated with pear fruit stone cell formation have been limited.We here used a combination of co-expression network and expression quantitative trait locus(eQTL)analyses in 206 pear cultivars with different stone cell contents to identify relevant genes;these analyses uncovered the gene PbrMYB4,a R2R3 MYB transcription factor gene.There was a strong positive correlation between relative PbrMYB4 expression levels in the fruit flesh and stone cell/lignin contents.Overexpression of PbrMYB4 significantly increased the lignin contents,whereas silencing of PbrMYB4 had the opposite effect,decreasing the contents of lignin.PbrMYB4 overexpression in pear calli significantly promoted lignin biosynthesis.In Arabidopsis thaliana,PbrMYB4 overexpression resulted in increasing lignin deposition,cell wall thickness of vessels and xylary fiber,and accelerating expression level of lignin biosynthetic genes.PbrMYB4 was found to activate 4-Coumarate:Coenzyme A Ligase(Pbr4CL1)by binding to AC-I elements in the promoter regions,as demonstrated with dual-luciferase reporter assays and a yeast one-hybrid assay.These results demonstrated that PbrMYB4 positively regulated lignin biosynthesis in pear fruit stone cells by activating lignin biosynthesis genes.This study improves our understanding of the gene regulatory networks associated with stone cell formation in pear fruit,providing guidance for molecular breeding of pear varieties with low stone cell content.展开更多
Noise-induced hearing loss(NIHL)is primarily driven by inflammatory processes within the cochlea,where noise exposure triggers the activation of the NOD-like receptor protein 3(NLRP3)inflammasome,leading to an inflamm...Noise-induced hearing loss(NIHL)is primarily driven by inflammatory processes within the cochlea,where noise exposure triggers the activation of the NOD-like receptor protein 3(NLRP3)inflammasome,leading to an inflammatory cascade.The interaction between increased NLRP3 expression and NF-κB activity can further amplify cochlear inflammation.Our findings reveal that(R)-PFI-2 hydrochloride,a selective inhibitor of the SETD7 enzyme,effectively inhibits the activation of the cochlear NF-κB pathway,suppresses the release of proinflammatory factors,and prevents inflammasome assembly.This intervention disrupts the perpetuating cycle of inflammation,thereby alleviating damage to cochlear hair cells attributed to acoustic trauma.Consequently,(R)-PFI-2 hydrochloride emerges as a promising pharmacological candidate for NIHL,targeting and moderating the excessive immune and inflammatory responses implicated in the pathology of hearing loss.展开更多
Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(...Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.展开更多
AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained fr...AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.展开更多
Allergic rhinitis (AR) is the inflammation of nasal mucosa due to the type 1 hypersensitivity reactions mediated by immunoglobulin E (IgE) and triggered by certain allergens. The latest concept in allergic disease is ...Allergic rhinitis (AR) is the inflammation of nasal mucosa due to the type 1 hypersensitivity reactions mediated by immunoglobulin E (IgE) and triggered by certain allergens. The latest concept in allergic disease is the role of regulatory T cells (Treg). Interleukin-2 enhances the function and survival of Treg to perform its function as a controller of effector for forming a tolerant system by suppressing and regulating the homeostasis system. Treg has a transcription factor FoxP3 which plays a role in developing major function of Treg and progression to produce IL-10 and TGF-?. The atopic diseases are caused by a deficiency of Treg. The new perspective is low-dose IL-2 therapy towards autoimmune disease and allergic inflammation. Low-dose IL-2 therapy requires further clinical studies to optimize the dose, time, and the schedule of the IL-2 treatment. FoxP3 has the potential to assist in evaluating the active process of immunological process, which cannot be evaluated by Th1 and Th2 markers, and FoxP3 can be a successful immunotherapy marker.展开更多
基金funded by the Science Foundation of China(Grant No.32230097)Earmarked Fund for China Agriculture Research System(Grant No.CARS-28)+2 种基金the Earmarked Fund for Jiangsu Agricultural Industry Technology System(Grant No.JATS[2023]412)Natural Science Foundation of Jiangsu Province for Young Scholar(Grant No.BK20221010)supported by the high-performance computing platform of Bioinformatics Center,Nanjing Agricultural University。
文摘Pear(Pyrus bretschneideri)fruit stone cells are primarily composed of lignin and have strongly lignified cell walls.The presence of stone cells has a negative influence on fruit texture and taste,and thus the reduction of stone cell content in pear fruit is a key goal of breeding efforts.However,research into the key transcription factors and regulatory networks associated with pear fruit stone cell formation have been limited.We here used a combination of co-expression network and expression quantitative trait locus(eQTL)analyses in 206 pear cultivars with different stone cell contents to identify relevant genes;these analyses uncovered the gene PbrMYB4,a R2R3 MYB transcription factor gene.There was a strong positive correlation between relative PbrMYB4 expression levels in the fruit flesh and stone cell/lignin contents.Overexpression of PbrMYB4 significantly increased the lignin contents,whereas silencing of PbrMYB4 had the opposite effect,decreasing the contents of lignin.PbrMYB4 overexpression in pear calli significantly promoted lignin biosynthesis.In Arabidopsis thaliana,PbrMYB4 overexpression resulted in increasing lignin deposition,cell wall thickness of vessels and xylary fiber,and accelerating expression level of lignin biosynthetic genes.PbrMYB4 was found to activate 4-Coumarate:Coenzyme A Ligase(Pbr4CL1)by binding to AC-I elements in the promoter regions,as demonstrated with dual-luciferase reporter assays and a yeast one-hybrid assay.These results demonstrated that PbrMYB4 positively regulated lignin biosynthesis in pear fruit stone cells by activating lignin biosynthesis genes.This study improves our understanding of the gene regulatory networks associated with stone cell formation in pear fruit,providing guidance for molecular breeding of pear varieties with low stone cell content.
基金supported by the Science and Technology Development Project of Xuzhou Science and Technology Bureau(KC21249)Science and Technology Development Project of Chongqing(CSTB2022NSCQ-M SX1598)+2 种基金Science and Technology Development Project of Xiaogan(XGKJ2023010010)Scientific Research Startup Foundation of Hainan UniversityScience and Technology Development Project of Hainan.
文摘Noise-induced hearing loss(NIHL)is primarily driven by inflammatory processes within the cochlea,where noise exposure triggers the activation of the NOD-like receptor protein 3(NLRP3)inflammasome,leading to an inflammatory cascade.The interaction between increased NLRP3 expression and NF-κB activity can further amplify cochlear inflammation.Our findings reveal that(R)-PFI-2 hydrochloride,a selective inhibitor of the SETD7 enzyme,effectively inhibits the activation of the cochlear NF-κB pathway,suppresses the release of proinflammatory factors,and prevents inflammasome assembly.This intervention disrupts the perpetuating cycle of inflammation,thereby alleviating damage to cochlear hair cells attributed to acoustic trauma.Consequently,(R)-PFI-2 hydrochloride emerges as a promising pharmacological candidate for NIHL,targeting and moderating the excessive immune and inflammatory responses implicated in the pathology of hearing loss.
基金The Sixth Batch of Special Support Plans in Anhui Province(No.dlPtzjh20200050)Key Natural Science Research Project of Higher Education Institutions in Anhui Province(No.KJ2020A0426)。
文摘Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.
基金Supported by National Natural Science Foundation of China,No.81072692Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.10KJB320007
文摘AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.
文摘Allergic rhinitis (AR) is the inflammation of nasal mucosa due to the type 1 hypersensitivity reactions mediated by immunoglobulin E (IgE) and triggered by certain allergens. The latest concept in allergic disease is the role of regulatory T cells (Treg). Interleukin-2 enhances the function and survival of Treg to perform its function as a controller of effector for forming a tolerant system by suppressing and regulating the homeostasis system. Treg has a transcription factor FoxP3 which plays a role in developing major function of Treg and progression to produce IL-10 and TGF-?. The atopic diseases are caused by a deficiency of Treg. The new perspective is low-dose IL-2 therapy towards autoimmune disease and allergic inflammation. Low-dose IL-2 therapy requires further clinical studies to optimize the dose, time, and the schedule of the IL-2 treatment. FoxP3 has the potential to assist in evaluating the active process of immunological process, which cannot be evaluated by Th1 and Th2 markers, and FoxP3 can be a successful immunotherapy marker.
