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1.
FASEB J ; 37(12): e23306, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37934018

RESUMO

Spermatogonial stem cells (SSCs) play a crucial role in mammalian spermatogenesis and maintain the stable inheritance of the germline in livestock. However, stress and bacterial or viral infections can disrupt immune homeostasis of the testes, thereby leading to spermatogenesis destruction and infertility, which severely affects the health and productivity of mammals. This study aimed to explore the effect of ubiquitin C-terminal hydrolase L1 (UCHL1) knockdown (KD) in goat SSCs and mouse testes and investigate the potential anti-inflammatory function of UCHL1 in a poly(I:C)-induced inflammation model to maintain microenvironmental homeostasis. In vitro, the downregulation of UCHL1 (UCHL1 KD) in goat SSCs increased the expression levels of apoptosis and inflammatory factors and inhibited the self-renewal and proliferation of SSCs. In vivo, the structure of seminiferous tubules and spermatogenic cells was disrupted after UCHL1 KD, and the expression levels of apoptosis- and inflammation-related proteins were significantly upregulated. Furthermore, UCHL1 inhibited the TLR3/TBK1/IRF3 pathway to resist poly(I:C)-induced inflammation in SSCs by antagonizing HSPA8 and thus maintaining SSC autoimmune homeostasis. Most importantly, the results of this study showed that UCHL1 maintained immune homeostasis of SSCs and spermatogenesis. UCHL1 KD not only inhibited the self-renewal and proliferation of goat SSCs and spermatogenesis but was also involved in the inflammatory response of goat SSCs. Additionally, UCHL1 has an antiviral function in SSCs by antagonizing HSPA8, which provides an important basis for exploring the specific mechanisms of UCHL1 in goat spermatogenesis.


Assuntos
Cabras , Espermatogônias , Animais , Masculino , Camundongos , Homeostase , Inflamação/metabolismo , Espermatogênese/fisiologia , Espermatogônias/metabolismo , Células-Tronco , Testículo/metabolismo
2.
Environ Res ; 239(Pt 1): 117315, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37805180

RESUMO

Chlorpyrifos (CP) is a pesticide widely used in agricultural production. However, excessive use of CP is risky for human health and the ecological environment. Microbial remediation has become a research hotspot of environmental pollution control. In this study, the effective CP-degrading strain H27 (Bacillus cereus) was screened from farmland soil, and the degradation ratio was more than 80%. Then, the degradation mechanism was discussed in terms of enzymes, pathways, products and genes, and the mechanism was improved in terms of cell motility, secretory transport system and biofilm formation. The key CP-degrading enzymes were mainly intracellular enzymes (IE), and the degradation ratio reached 49.6% within 30 min. The optimal pH for IE was 7.0, and the optimal temperature was 25 °C. Using DFT and HPLC‒MS analysis, it was found that degradation mainly involved oxidation, hydrolysis and other reactions, and 3 degradation pathways and 14 products were identified, among which TCP (3,5,6-trichloro-2-pyridinol) was the main primary degradation product in addition to small molecules such as CO2 and H2O. Finally, the whole genome of strain H27 was sequenced, and the related degrading genes and enzymes were investigated to improve the metabolic pathways. Strain H27 had perfect genes related to flagellar assembly and chemotaxis and tended to tolerate CP. Moreover, it can secrete esterase, phosphatase and other substances, which can form biofilms and degrade CP in the environment. In addition, CP enters the cell under the action of permeases or transporters, and it is metabolized by IE. The degradation mechanism of CP by strain H27 is speculated in this study, which provided a theoretical basis for enriching CP-degrading bacteria resources, improving degradation metabolic pathways and mechanisms, and applying strain H27 to environmental pollution remediation.


Assuntos
Bacillus , Clorpirifos , Humanos , Biodegradação Ambiental , Monoéster Fosfórico Hidrolases , Sequenciamento Completo do Genoma
3.
J Cell Physiol ; 236(5): 3536-3551, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32996162

RESUMO

Orchitis is one of the leading causes of male animal infertility and is associated with inflammatory reactions caused by the bacterium. It has been reported that there is a mutual coupling effect between endoplasmic reticulum stress (ERS) and inflammatory response. Our studies showed that lipopolysaccharide (LPS) could cause testicular damages, apoptosis, ERS, and inflammatory responses in spermatogonial stem cells (SSCs); ERS-related apoptosis proteins were activated and the expression of ERS genes was significantly upregulated; meanwhile, the expression of Toll-like receptor 4 and inflammation factors was apparently increased with LPS treatment. Moreover, melatonin (MEL) could rescue testicular damage, and significantly inhibited the expression of ERS-related apoptosis genes, ERS markers, and inflammatory factors in SSCs and MEL played repairing and anti-infection roles in LPS-induced testicular damage. Therefore, MEL may be used as a drug to prevent and control bacterial infections in male reproductive systems. However, the specific molecular mechanism of MEL to resist ERS and inflammatory response remains to be further studied.


Assuntos
Células-Tronco Germinativas Adultas/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Inflamação/patologia , Melatonina/farmacologia , Células-Tronco Germinativas Adultas/efeitos dos fármacos , Células-Tronco Germinativas Adultas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lipopolissacarídeos , Masculino , Camundongos , Modelos Biológicos , Receptores de Melatonina/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia
4.
J Cell Physiol ; 236(2): 1481-1493, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32692417

RESUMO

Spermatogenesis is a complex process that originates from and depends on the spermatogonial stem cells (SSCs). The number of SSCs is rare, which makes the separation and enrichment of SSCs difficult and inefficient. The transcription factor PAX7 maintains fertility in normal spermatogenesis in mice. However, for large animals, much less is known about the SSCs' self-renewal regulation, especially in dairy goats. We isolated and enriched the CD49f-positive and negative dairy goat testicular cells by magnetic-activated cell sorting strategies. The RNA- sequencing and experimental data revealed that cells with a high CD49f and PAX7 expression are undifferentiated spermatogonia in goat testis. Our findings indicated that ZBTB16 (PLZF), PAX7, LIN28A, BMPR1B, FGFR1, and FOXO1 were expressed higher in CD49f-positive cells as compared to negative cells and goat fibroblasts cells. The expression and distribution of PAX7 in dairy goat also have been detected, which gradually decreased in testis tissue along with the increasing age. When the PAX7 gene was overexpressed in dairy goat immortal mGSCs-I-SB germ cell lines, the expression of PLZF, GFRα1, ID4, and OCT4 was upregulated. Together, our data demonstrated that there is a subset of spermatogonial stem cells with a high expression of PAX7 among the CD49f+ spermatogonia, and PAX7 can maintain the self-renewal of CD49f-positive SSCs.


Assuntos
Integrina alfa6/genética , Fator de Transcrição PAX7/genética , Espermatogênese/genética , Testículo/crescimento & desenvolvimento , Animais , Diferenciação Celular/genética , Proliferação de Células/genética , Autorrenovação Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Cabras/genética , Cabras/crescimento & desenvolvimento , Masculino , MicroRNAs/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Espermatogônias/crescimento & desenvolvimento , Células-Tronco/citologia , Células-Tronco/metabolismo , Testículo/metabolismo
5.
Mol Cell Biochem ; 476(2): 1123-1134, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33200378

RESUMO

Double sex and mab-3 related transcription factor 1 (DMRT1) encodes a double sex/mab-3 (DM) domain, which is the most conserved structure that involved in sex determination both in vertebrates and invertebrates. This study revealed important roles of DMRT1 in maintaining self-renewal of male germline stem cells (mGSCs). Our results showed that insufficient expression of DMRT1 in mice testes resulted in decreased number of spermatogonial cells and collapse of testicular niche in vivo. Self-renewal and proliferation of mGSCs were inhibited. Based on the bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (co-IP) assay, it was finally revealed that the interaction between DMRT1 and promyelocytic leukemia zinc finger (PLZF) protein was essential for maintaining self-renewal of mGSCs. Moreover, BTB domain of PLZF, DM and DMRT1 domain of DMRT1 were indispensable in mGSC, which were responsible for preserving the quantity of germ cells. Our research provided a new scientific basis for studying the mechanism of self-renewal and spermatogenesis in goat mGSCs.


Assuntos
Autorrenovação Celular , Proteína com Dedos de Zinco da Leucemia Promielocítica/metabolismo , Domínios e Motivos de Interação entre Proteínas , Espermatogênese , Células-Tronco/citologia , Testículo/citologia , Fatores de Transcrição/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Cabras , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Modelos Animais , Células-Tronco/metabolismo , Testículo/metabolismo
6.
Int J Med Sci ; 17(12): 1751-1762, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714078

RESUMO

Bisphenol A (BPA) is widely used in industrial production. It is closely related to the growth and development of the nervous system, and can enter the fetal circulation through the placental barrier, and can be secreted through breast milk. The development of nervous system is very important in fetus and neonatal period. The purpose of this study is to investigate the effects of different doses of BPA on learning and memory function of nervous system in rats. Pregnant rats were randomly divided into three treatment groups (control group, 5 mg/kg/d, 50 mg/kg/d). All animals received BPA from the discovery of pregnancy to 21 days after birth. Results had shown that after high concentration BPA exposure, the increase of PS amplitude and f-EPSP slope in hippocampal CA1 area of male offspring was lower than that of control group. High concentration of BPA could inhibit Nestin, Cyclin D1, bcl-2 and Rac1 in male offspring rats and the expression of bax and RhoA was promoted by BPA. In summary, our study indicated that BPA exposure during pregnancy and lactation could impair the hippocampal function of male offspring by affecting the growth and apoptosis of hippocampal neurons, which might be due to the abnormal regulation of RhoA and Rac1.


Assuntos
Compostos Benzidrílicos/farmacologia , Ciclina D1/genética , Nestina/genética , Fenóis/farmacologia , Efeitos Tardios da Exposição Pré-Natal/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Hipocampo/patologia , Lactação/efeitos dos fármacos , Lactação/genética , Masculino , Fenóis/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , Ratos , Proteínas rac1 de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/genética
7.
J Cell Physiol ; 234(6): 8113-8121, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30317605

RESUMO

LIN28A serves as a crucial marker of dairy goat male germline stem cells (GmGSCs). In our previous study, we demonstrated that LIN28A promotes proliferation, self-renewal, and maintains the stemness of GmGSCs. Here, we found that LIN28A could activate the transcription of NANOG in a let-7g independent manner. We cloned the 5' upstream of two NANOG genes which were located on chromosome 15 ( NANOG-ch15) and chromosome 5 ( NANOG-ch5), respectively, and then examined their promoter activities and promoter methylation levels. Results showed that NANOG-ch15 is a pseudogene whereas NANOG-ch5 is active in Capra hircus. Bioinformatics analysis indicated that the 5' upstream region of NANOG-ch5 does not have typical CpG islands but contains several CG enrichment regions and several LIN28A binding sites. Deletion analysis suggested that NANOG-ch5 promoter can be activated by LIN28A directly binding to the site -210 but not by the indirect effect from the inhibition of let-7g, which is known to be downregulated by LIN28A. Mechanistically, LIN28A recruits and interacts with 5-methylcytosine-dioxygenase Ten-Eleven translocation 1 (TET1) to NANOG-ch5 gene promoter binding sites to orchestrate 5-methylcytosine and 5-hydroxymethylcytosine dynamics. These results revealed the role of LIN28A in NANOG transcriptional regulation via epigenetic DNA modifications to maintain the stemness of GmGSC.


Assuntos
Células Germinativas/metabolismo , Cabras/genética , Proteína Homeobox Nanog/genética , Proteínas de Ligação a RNA/genética , Animais , Diferenciação Celular/genética , Metilação de DNA/genética , Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Células Germinativas/crescimento & desenvolvimento , Cabras/crescimento & desenvolvimento , Masculino , Células-Tronco/metabolismo , Ativação Transcricional/genética
8.
BMC Plant Biol ; 19(1): 554, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842763

RESUMO

BACKGROUND: Gametogenesis is a key step in the production of ovules or pollen in higher plants. The sex-determination aspects of gametogenesis have been well characterized in the model plant Arabidopsis. However, little is known about this process in androdioecious plants. Tapiscia sinensis Oliv. is a functionally androdioecious tree, with both male and hermaphroditic individuals. Hermaphroditic flowers (HFs) are female-fertile flowers that can produce functional pollen and set fruits. However, compared with male flowers (MFs), the pollen viability and number of pollen grains per flower are markedly reduced in HFs. MFs are female-sterile flowers that fail to set fruit and that eventually drop. RESULTS: Compared with HF, a notable cause of MF female sterility in T. sinensis is when the early gynoecium meristem is disrupted. During the early stage of HF development (stage 6), the ring meristem begins to form as a ridge around the center of the flower. At this stage, the internal fourth-whorl organ is stem-like rather than carpelloid in MF. A total of 52,945 unigenes were identified as transcribed in MF and HF. A number of differentially expressed genes (DEGs) and metabolic pathways were detected as involved in the development of the gynoecium, especially the ovule, carpel and style. At the early gynoecium development stage, DEGs were shown to function in the metabolic pathways regulating ethylene biosynthesis and signal transduction (upstream regulator), auxin, cytokinin transport and signalling, and sex determination (or flower meristem identity). CONCLUSIONS: Pathways for the female sterility model were initially proposed to shed light on the molecular mechanisms of gynoecium development at early stages in T. sinensis.


Assuntos
Flores/crescimento & desenvolvimento , Genes de Plantas , Magnoliopsida/crescimento & desenvolvimento , Árvores/crescimento & desenvolvimento , Flores/genética , Magnoliopsida/anatomia & histologia , Magnoliopsida/genética , RNA-Seq , Análise de Sequência de RNA , Diferenciação Sexual/genética , Árvores/anatomia & histologia , Árvores/genética
9.
J Virol ; 91(10)2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28275186

RESUMO

Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine-enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross talk between TLR and Notch signaling pathways results in fine-tuning of TLR-triggered innate inflammatory responses. We evaluated the impact of TLR and Notch signaling on ERD in a murine model by administering CpG, an agonist of TLR9, in combination with L685,458, an inhibitor of Notch signaling during FI-RSV immunization. Activation with CpG or deficiency of MyD88-dependent TLR signaling did not alleviate airway inflammation in FI-RSV-immunized mice. Activation or inhibition of Notch signaling with Dll4, one of the Notch ligands, or L685,458 did not suppress FI-RSV-enhanced airway inflammation either. However, the CpG together with L685,458 markedly inhibited FI-RSV-enhanced airway hyperresponsiveness, weight loss, and lung inflammation. Interestingly, CpG plus L685,458 completely inhibited FI-RSV-associated Th17 and Th17-associated proinflammatory chemokine responses in lungs following RSV challenge but not Th1 or Th2, memory responses. In addition, FI-RSV plus CpG plus L685,458 promoted protective CD8+ lung tissue-resident memory (TRM) cells. These results indicate that activation of TLR signaling combined with inhibition of Notch signaling prevent FI-RSV ERD, and the mechanism appears to involve suppressing proinflammatory Th17 memory responses and promoting protective TRM in lungs.IMPORTANCE RSV is the most important cause of lower respiratory tract infections in infants. The FI-RSV-enhanced respiratory disease (ERD) is a major impediment to the development of a safe and effective killed RSV vaccine. Using adjuvants to regulate innate and adaptive immune responses could be an effective method to prevent ERD. We evaluated the impact of TLR and Notch signaling on ERD by administering CpG, an agonist of TLR9, in combination with L685,458, an inhibitor of Notch signaling, during FI-RSV immunization. The data showed that treatment of TLR or Notch signaling alone did not suppress FI-RSV-enhanced airway inflammation, while CpG plus L685,458 markedly inhibited ERD. The mechanism appears to involve suppressing Th17 memory responses and promoting tissue-resident memory cells. Moreover, these results suggest that regulation of lung immune memory with adjuvant compounds containing more than one immune-stimulatory molecule may be a good strategy to prevent FI-RSV ERD.


Assuntos
Adjuvantes Imunológicos/química , Memória Imunológica , Pulmão/imunologia , Oligodesoxirribonucleotídeos/farmacologia , Receptores Notch/metabolismo , Células Th17/imunologia , Animais , Hiper-Reatividade Brônquica/induzido quimicamente , Linfócitos T CD8-Positivos/imunologia , Carbamatos/farmacologia , Dipeptídeos/farmacologia , Formaldeído , Humanos , Inflamação , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Vírus Respiratório Sincicial/imunologia , Vacinas contra Vírus Sincicial Respiratório/imunologia , Vírus Sincicial Respiratório Humano/imunologia , Transdução de Sinais , Receptor 1 Toll-Like/imunologia , Receptor 1 Toll-Like/metabolismo , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia
10.
Fungal Genet Biol ; 63: 24-41, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24291007

RESUMO

Trehalose 6-phosphate synthase (TPS1) and trehalose 6-phosphate phosphatase (TPS2) are required for trehalose biosynthesis in yeast and filamentous fungi, including Fusarium graminearum. Three null mutants Δtps1, Δtps2 and Δtps1-Δtps2, each carrying either a single deletion of TPS1 or TPS2 or a double deletion of TPS1-TPS2, were generated from a toxigenic F. graminearum strain and were not able to synthesize trehalose. In contrast to its reported function in yeasts and filamentous fungi, TPS1 appeared dispensable for development and virulence. However, deletion of TPS2 abolished sporulation and sexual reproduction; it also altered cell polarity and ultrastructure of the cell wall in association with reduced chitin biosynthesis. The cell polarity alteration was exhibited as reduced apical growth and increased lateral growth and branching with increased hyphal and cell wall widths. Moreover, the TPS2-deficient strain displayed abnormal septum development and nucleus distribution in its conidia and vegetative hyphae. The Δtps2 mutant also had 62% lower mycelial growth on potato dextrose agar and 99% lower virulence on wheat compared with the wild-type. The Δtps1, Δtps2 and Δtps1-Δtps2 mutants synthesized over 3.08-, 7.09- and 2.47-fold less mycotoxins, respectively, on rice culture compared with the wild-type. Comparative transcriptome analysis revealed that the Δtps1, Δtps2 and Δtps1-Δtps2 mutants had 486, 1885 and 146 genotype-specific genes, respectively, with significantly changed expression profiles compared with the wild-type. Further dissection of this pathway will provide new insights into regulation of fungal development, virulence and trichothecene biosynthesis.


Assuntos
Proteínas Fúngicas/genética , Fusarium/patogenicidade , Glucosiltransferases/metabolismo , Micotoxinas/biossíntese , Monoéster Fosfórico Hidrolases/metabolismo , Trealose/biossíntese , Parede Celular/genética , Parede Celular/metabolismo , Proteínas Fúngicas/metabolismo , Fusarium/genética , Fusarium/metabolismo , Regulação Fúngica da Expressão Gênica , Glucosiltransferases/genética , Hifas/genética , Hifas/metabolismo , Hifas/patogenicidade , Mutação , Micotoxinas/genética , Monoéster Fosfórico Hidrolases/genética , Esporos Fúngicos/genética , Esporos Fúngicos/metabolismo , Trealose/genética , Triticum/microbiologia
11.
Front Psychol ; 15: 1278996, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524295

RESUMO

With the intensification of competition in the business environment, organizational creativity is increasingly becoming crucial for organizations to build competitive advantages and promote organizational development. For innovative enterprises, their entrepreneurs largely determine the development orientation of the enterprise. They are one of the most critical factors determining the level of corporate innovation, but there need to be more effective creativity transformation path to pursue innovation development. The findings in this study show that entrepreneurial individual creativity has a significant positive effect on organizational creativity, platform leadership mediates the path of creativity transformation across hierarchical levels, and organizational culture has positive moderating effect between platform leadership and organizational creativity. The study results explain the transformation mechanism of creativity from the entrepreneur's perspective, expand the potential transformation path of organizational creativity, and are instructive for enhancing organizational creativity.

12.
Stress Biol ; 4(1): 9, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300431

RESUMO

The male reproductive system has a standard immune response regulatory mechanism, However, a variety of external stimuli, including viruses, bacteria, heat, and medications can damage the testicles and cause orchitis and epididymitis. It has been shown that various RNA viruses are more likely to infect the testis than DNA viruses, inducing orchitis and impairing testicular function. It was found that local injection of the viral RNA analog poly(I:C) into the testes markedly disrupted the structure of the seminiferous tubules, accompanied by apoptosis and inflammation. Poly(I:C) mainly inhibited the expression of testosterone synthesis-associated proteins, STAR and MGARP, and affected the synthesis and metabolism of amino acids and lipids in the testis. This led to the disruption of the metabolite levels in the testis of mice, thus affecting the normal spermatogenesis process. The present study analyzed the acute inflammatory response of the testis to viral infection using a multi-omics approach. It provides insights into how RNA virus infection impairs testicular function and offers a theoretical basis for future studies on immune homeostasis and responses under stress conditions in male reproduction.

13.
Theriogenology ; 215: 321-333, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128225

RESUMO

The transcription factor promyelocytic leukemia zinc finger (PLZF, also known as ZBTB16) is critical for the self-renewal of spermatogonial stem cells (SSCs). However, the function of PLZF in SSCs is not clear. Here, we found that PLZF acted as an epigenetic regulator of stem cell maintenance and self-renewal of germ cells. The PLZF protein interacts with the ten-eleven translocation 1 (TET1) protein and subsequently acts as a modulator to regulate the expression of self-renewal-related genes. Furthermore, Transcription Factor 7-like 2 (TCF7L2) is promoted by the coordination of PLZF and Tri-methylation of lysine 4 on histone H3 (H3K4me3). In addition, testicular single-cell sequencing indicated that TCF7L2 is commonly expressed in the PLZF cluster. We demonstrated that PLZF directly targets TCF7L2 and alters the landscape of histone methylation in the SSCs nucleus. Meanwhile, the RD domain and Zn finger domain of PLZF synergize with H3K4me3 and directly upregulate TCF7L2 expression at the transcriptional level. Additionally, we identified a new association between PLZF and the histone methyltransferase EZH2 at the genomic level. Our study identified a new association between PLZF and H3K4me3, established the novel PLZF&TET1-H3K4me3-TCF7L2 axis at the genomic level which regulates undifferentiated spermatogonia, and provided a platform for studying germ cell development in male domestic animals.


Assuntos
Fatores de Transcrição Kruppel-Like , Espermatogônias , Masculino , Animais , Espermatogônias/metabolismo , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Testículo/metabolismo , Fatores de Transcrição/metabolismo
14.
Theriogenology ; 211: 65-75, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37586163

RESUMO

Eif2s3y (eukaryotic translation initiation factor 2, subunit 3, structural gene Y-linked, Eif2s3y) is an essential gene for spermatogenesis. Early studies have shown that Eif2s3y can promote the proliferation of spermatogonial stem cells (SSCs) and can replace the Y chromosome together with sex-determining region Y (Sry) to transform SSCs into round spermatozoa. We injected lentiviral particles into the seminiferous tubules of mouse testes by sterile surgery surgically to establish overexpressing Eif2s3y testes. And then the mice were intraperitoneally injected with LPS to established the model of testis inflammation. Through RNA sequencing, qRT-PCR analysis, Western blot, co-culture etc., we found that Eif2s3y alleviated LPS-induced damage in mouse testes and maintained spermatogenesis. In testes with Eif2s3y overexpression, the seminiferous tubules were more regularly organized after exposure to LPS compared with the control. Eif2s3y performs its function by negatively regulating Adamts5 (a disintegrin and metalloproteinase containing a thrombospondin-1 motif), an extracellular matrix-degrading enzyme. ADAMTS5 shows a disruptive effect when the testis is exposed to LPS. Overexpression of Eif2s3y inhibited the TLR4/NFκB signaling pathway in the testis in response to LPS. Generally, our research shows that Eif2s3y protects the testis from LPS and maintains spermatogenesis by negatively regulating Adamts5.


Assuntos
Lipopolissacarídeos , Testículo , Masculino , Camundongos , Animais , Testículo/metabolismo , Lipopolissacarídeos/toxicidade , Espermatogênese/fisiologia , Espermatozoides/metabolismo , Túbulos Seminíferos , Espermatogônias , Proteína ADAMTS5 , Fatores de Transcrição/metabolismo
15.
Zool Res ; 44(3): 505-521, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37070575

RESUMO

Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.


Assuntos
Fertilidade , Homeostase , NF-kappa B , Testículo , NF-kappa B/metabolismo , Fertilidade/genética , Fertilidade/imunologia , Humanos , Masculino , Testículo/imunologia , Testículo/metabolismo , Homeostase/imunologia , Animais , Camundongos , Células HEK293 , Espermatogênese , Inflamação , Regiões Promotoras Genéticas/genética , Ativação Transcricional , Técnicas de Silenciamento de Genes
16.
Artigo em Inglês | MEDLINE | ID: mdl-36429896

RESUMO

Due to the mountainous terrain in the urban areas of southwest China, there are a large number of barren slopes in the community unsuitable for construction. These areas, alongside other unusable space which is often cultivated by residents to create informal community vegetable gardens and fruit growing areas, have become a "gray area" for urban management. This paper attempts to study the characteristics of informal community growing, the composition of growers, the motivation for growing, and the satisfaction of residents in urban areas in mountainous southwest China to explore its relative value. The sample area for the study was Yongchuan, Chongqing, Southwest China. Through a field survey, a semantic differential questionnaire, and data analysis, we found that: (1) growers use traditional cultivation methods to grow diverse fruits and vegetables according to the size of the slope, and the scale is so large that it serves as a local food supply; (2) growers are mainly vulnerable groups who use the land for economic gain and green food acquisition; and (3) growers and non-growers are more satisfied with the food supply and economic benefits generated by cultivation, while they are dissatisfied with the environmental and social benefits and the planting process. Satisfaction also varies with age, occupation, income, education, household registration, and farming experience. Based on the findings, this paper presents recommendations for the future transformation and development of informal community cultivation in mountainous areas. The study has implications for the construction of community gardens and urban agriculture in the mountains.


Assuntos
Jardinagem , Jardins , China , Verduras , Agricultura
17.
Stem Cell Res Ther ; 13(1): 164, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35414044

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSC therapy. This study investigated whether the combination of melatonin and human umbilical cord mesenchymal stem cells (hUC-MSCs) was superior to hUC-MSCs alone in ameliorating high-fat diet and streptozocin (STZ)-induced type II diabetes mellitus (T2DM) in a mouse model. METHODS: Mice were divided into four groups: normal control (NC) group; T2DM group; hUC-MSCs treatment alone (UCMSC) group and pretreatment of hUC-MSCs with melatonin (UCMSC/Mel) group. RESULTS: RNA sequence analysis showed that certain pathways, including the signaling pathway involved in the regulation of cell proliferation signaling pathway, were regulated by melatonin. The blood glucose levels of the mice in the UCMSC and UCMSC/Mel treatment groups were significantly reduced compared with the T2DM group without treatment (P < 0.05). Furthermore, hUC-MSCs enhance the key factor in the activation of the PI3K/Akt pathway in T2DM mouse hepatocytes. CONCLUSION: The pretreatment of hUC-MSCs with melatonin partly boosted cell efficiency and thereby alleviated impaired glycemic control and insulin resistance. This study provides a practical strategy to improve the application of hUC-MSCs in diabetes mellitus and cytotherapy. Overview of the PI3K/AKT signaling pathway. (A) Underlying mechanism of UCMSC/Mel inhibition of hyperglycemia and insulin resistance T2DM mice via regulation of PI3K/AKT pathway. hUC-MSCs stimulates glucose uptake and improves insulin action thus should inhibition the clinical signs of T2DM, through activation of the p-PI3K/Akt signaling pathway and then regulates glucose transport through activating AS160. UCMSC/Mel increases p53-dependent expression of BCL2, and inhibit BAX and Capase3 protein activation. Leading to the decrease in apoptosis. (B) Melatonin modulated PI3K/AKT signaling pathway. Melatonin activated PI3K/AKT response pathway through binding to MT1and MT2 receptor. Leading to the increase in hUC-MSCs proliferation, migration and differentiation. → (Direct stimulatory modification); ┴ ( Direct Inhibitory modification); → ┤ (Multistep inhibitory modification); ↑ (Up regulate); ↓ (Down regulate); PI3K (Phosphoinositide 3-Kinase); AKT ( protein kinase B); PDK1 (Phosphoinositide-dependent protein kinase 1); IR, insulin receptor; GLUT4 ( glucose transporter type 4); ROS (reactive oxygen species); BCL-2 (B-cell lymphoma-2); PDK1 (phosphoinositide-dependent kinase 1) BAX (B-cell lymphoma-2-associated X protein); PCNA (Proliferating cell nuclear antigen); Cell cycle-associated proteins (KI67, cyclin A, cyclin E).


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Melatonina , Transplante de Células-Tronco Mesenquimais , Animais , Diabetes Mellitus Tipo 2/terapia , Humanos , Melatonina/farmacologia , Melatonina/uso terapêutico , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositóis/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Cordão Umbilical , Proteína X Associada a bcl-2
18.
J Healthc Eng ; 2021: 6698122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33505644

RESUMO

This study aims to explore the application of blockchain technology in smart healthcare, establish a hierarchical theoretical framework of smart healthcare, reveal the impact of blockchain on smart healthcare, and finally, construct a development application system of smart healthcare under the blockchain based on stakeholder theory. However, such a hierarchical theoretical framework should consider not only the necessary attributes and the interrelationship among various aspects and attributes but also the role of multiple stakeholders. Therefore, the paper uses fuzzy set theory to filter unnecessary attributes, proposes a decision-making and experimental evaluation laboratory (DEMATEL) to manage the complex interrelationships between various aspects and attributes, and uses Interpretive Structure Modeling (ISM) to divide the hierarchy and construct a hierarchical theoretical framework. The results show that (1) the top-level design, the medical record management, and the doctor management are the root causes of system. (2) The specific application of blockchain in the field of smart healthcare is mainly carried out around the intelligent contract, which relies on the medical record management and is constrained by the system, and optimization of application is the key to system upgrading. (3) The internal and external regulation, the medical insurance, and the environmental governance play a guaranteed role for the development of the system and effectively safeguard the interests of stakeholders. (4) The application system of smart healthcare under the blockchain needs to be built based on three layers: the transaction layer, information layer, and stakeholder layer. The theoretical hierarchical framework is intended to guide smart healthcare towards blockchain applications, and stakeholders are suggested to participate in the development application systems.


Assuntos
Blockchain , Conservação dos Recursos Naturais , Atenção à Saúde , Política Ambiental , Humanos , Tecnologia
19.
Front Psychol ; 12: 651817, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33889118

RESUMO

Individual creativity has been the focus of long-term research in creative industries. However, few studies have explored the impact on individual creativity from social factors. At the same time, the influence of individual creativity on the existence of subsequent factors in the creative industry is also worthy of further investigation. From a social standpoint, this research aims to explore how social norms affect individual creativity, and how individual creativity affects subsequent leadership. The present research takes creative entrepreneurs in creative enterprises as the research objects, and the structural equation model is used to analyze the data obtained from 202 valid questionnaires. Besides, the mediating effect of individual creativity between social norms and individual leadership is verified. The results show that social norms can effectively promote the generation of individual creativity that has a positive impact on both transactional or transformational leadership. It is revealed that social norms are effective tools for enhancing creativity, answering the question of how creative ideas are transformed into creative work and leadership. Individual creativity plays a mediating role between social norms and individual leadership.

20.
Stem Cells Int ; 2021: 6668658, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603791

RESUMO

The future fertility of males with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Spermatogonial stem cell transplantation is believed to be a way to restore fertility in men. However, the survival efficiency of transplanted cells is still low. Eukaryotic translation initiation factor 2 subunit 3 and structural gene Y-linked (Eif2s3y) located on the Y chromosome of male animals is a coding gene of eIF2γ which mainly functions in translation initiation. Recently, the emerging role of Eif2s3y in spermatogenesis has been emphasized in several studies. However, the underlying mechanism is still unclear. In addition, how Eif2s3y functions in large animals remains largely unknown. In this study, we obtained the CDS sequence of the Eif2s3y gene from the testis of dairy goats and found that this gene was highly expressed in the testis and was evolutionarily conserved among different species. Interestingly, overexpression of Eif2s3y promoted the proliferation of spermatogonial stem cells of dairy goats by activating the ERK signaling pathway. In animal experiments, overexpressing Eif2s3y promoted transplanted goat spermatogonial stem cells and produced more colonies after microinjection into the seminiferous tubules of infertile mice. In conclusion, our study highlights an undiscovered role of Eif2s3y in dairy goat reproduction. This finding may provide an important basis for future works regarding male spermatogenic cell restoration and represent a major advance toward surrogate sires becoming a tool for disseminating and regenerating germplasm in all mammals.

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