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1.
J Nanobiotechnology ; 22(1): 322, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849858

RESUMO

The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 µm). It was found that scaffolds with a mesh size of 500 µm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration.


Assuntos
Hidrogéis , Nanofibras , Impressão Tridimensional , Medicina Regenerativa , Engenharia Tecidual , Alicerces Teciduais , Nanofibras/química , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Medicina Regenerativa/métodos , Hidrogéis/química , Animais , Camundongos , Macrófagos/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Células RAW 264.7 , Humanos
2.
Cell Signal ; : 111265, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38897527

RESUMO

Despite significant advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) still occurs in some patients. Poor endometrial receptivity and abnormal human endometrial stromal cell (HESC) proliferation and decidualization have been identified as the major causes. Ubiquitin-specific protease 22 (USP22) has been reported to participate in the decidualization of endometrial stromal cells in mice. However, the role of USP22 in HESC function and RIF development remains unknown. In this study, clinical endometrial tissue samples were gathered to investigate the involvement of USP22 in RIF, and HESCs were utilized to examine the molecular mechanisms of USP22 and Forkhead box M1 (FoxM1). The findings indicated a high expression of USP22 in the secretory phase of the endometrium. Knockdown of USP22 led to a notable reduction in the proliferation and decidualization of HESCs, along with a decrease in FoxM1 expression, while overexpression of USP22 yielded opposite results. Furthermore, USP22 was found to deubiquitinate FoxM1 in HESCs. Moreover, both USP22 and FoxM1 were downregulated in the endometria of patients with RIF. In conclusion, these results suggest that USP22 may have a significant impact on HESCs proliferation and decidualization through its interaction with FoxM1, potentially contributing to the underlying mechanisms of RIF pathogenesis.

3.
Biomed Chromatogr ; 38(8): e5905, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38806776

RESUMO

The present study examined the pharmacokinetics of IMM-H012 in rat plasma, utilizing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Internal standard cilostazol was employed, and plasma samples were processed using acetonitrile precipitation. A mobile phase (acetonitrile-0.1% formic acid in water) with gradient elution was used to achieve chromatographic separation using a UPLC BEH C18 column. In multiple reaction monitoring mode, electrospray ionization MS/MS was utilized in positive ionization mode. Based on findings, the lower limit of quantification was 2 ng/mL, and the linearity of IMM-H012 in rat plasma was found to be acceptable within the range of 2-2000 ng/mL (R2 > 0.995). The intra-day and inter-day precision relative standard deviation was less than 14% of IMM-H012 in rat plasma. The matrix effect was within the range of 102%-107%, and the accuracy ranged from 92% to 113%. Pharmacokinetics of IMM-H012 in rats after oral administration were successfully studied using UPLC-MS/MS.


Assuntos
Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Animais , Espectrometria de Massas em Tandem/métodos , Ratos , Cromatografia Líquida de Alta Pressão/métodos , Masculino , Reprodutibilidade dos Testes , Modelos Lineares , Limite de Detecção , Sensibilidade e Especificidade , Administração Oral
4.
Heliyon ; 10(6): e28284, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38533024

RESUMO

The metabolic disorders caused by diabetes can lead to various complications, including male spermatogenesis dysfunction. Exploring effective therapeutics that attenuate diabetes mellitus (DM)-induced male subfertility is of great importance. Pharmaceuticals targeting PPARα activation such as bezafibrate have been regarded as an important strategy for patients with diabetes. In this study, we use streptozocin (STZ) injection to establish a type 1 DM mice model and use bezafibrate to treat DM mice and evaluate the effects of bezafibrate on the spermatogenic function of the DM male mice. Bezafibrate treatment exhibited protective effects on DM-induced spermatogenesis deficiency, as reflected by increased testis weight, improved histological morphology of testis, elevated sperm parameters, increased serum testosterone concentration as well as increased mRNA levels of steroidogenesis enzymes. Meanwhile, testicular cell apoptosis, inflammation accumulation and oxidative stress status were also shown to be alleviated by bezafibrate compared with the DM group. In vivo and in vitro studies, PPARα specific inhibitor and PPARα knockout mice were further used to investigate the role of PPARα in the protective effects of bezafibrate on DM-induced spermatogenesis dysfunction. Our results indicated that the protection of bezafibrate on DM-induced spermatogenesis deficiency was abrogated by PPARα inhibition or deletion. Our study suggested that bezafibrate administration could ameliorate DM-induced spermatogenesis dysfunction and may represent a novel practical strategy for male infertility.

5.
Am J Pathol ; 194(7): 1197-1217, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38537935

RESUMO

Unexplained recurrent spontaneous abortion (URSA) is a serious reproductive issue that affects women of childbearing age. Studies have shown a close association between disrupted circadian rhythm and impaired epithelial-mesenchymal transition (EMT) in trophoblasts during URSA, although the underlying mechanism is not known. The current study investigated the regulatory relationship between circadian rhythm gene cryptochrome 2 (CRY2) and ferroptosis on the migratory ability of trophoblast cells. Cell proliferation experiments, wound-healing assays, and expression of related markers were conducted to study EMT. Trophoblastic ferroptosis was confirmed by the expressions of malondialdehyde, glutathione, mitochondrial membrane potential, divalent iron ions, and related genes. The results showed significant increased expression of CRY2 and decreased expression of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) in the URSA villous tissues, accompanied by iron-dependent oxidative changes and abnormal expression of ferroptosis-related proteins. CRY2 and BMAL1 were co-localized and functioned as a feedback loop, which regulated the dynamic changes of EMT-related markers in trophoblast cells. CRY2 promoted trophoblastic ferroptosis, whereas BMAL1 had the opposite effect. Particularly, the ferroptosis inhibitor (ferrostatin-1) effectively reversed the trophoblastic ferroptosis and EMT inhibition caused by CRY2 overexpression. Collectively, these results suggest that CRY2 regulates trophoblastic ferroptosis and hinders cellular EMT and migratory ability by suppressing BMAL1 expression.


Assuntos
Criptocromos , Transição Epitelial-Mesenquimal , Ferroptose , Trofoblastos , Ferroptose/fisiologia , Humanos , Feminino , Criptocromos/metabolismo , Criptocromos/genética , Trofoblastos/metabolismo , Trofoblastos/patologia , Gravidez , Adulto , Aborto Habitual/metabolismo , Aborto Habitual/patologia , Proliferação de Células , Movimento Celular , Fatores de Transcrição ARNTL/metabolismo , Fatores de Transcrição ARNTL/genética
6.
Heliyon ; 10(4): e26453, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420431

RESUMO

In order to promote the sustainable economic development, it is critical employ the digital economy to solve the mismatch dilemma of land and marine factors in coastal areas. It analyzed the influencing mechanisms between the digital economy, land and labor factor mismatch and coastal economic sustainable development using network development and new economic growth theories. The intermediary and regulating effect models were used for empirical tests using panel data from 11 Chinese coastal provinces (city or district) between 2009 and 2018. Results found that: (1) Digital economy promoted the sustainable development of land and marine binary economies in coastal areas; (2) Digital economy improved the factor mismatch of land and marine binary economies, which further affected the sustainable economic development; (3) Market integration is conducive to alleviating land and marine factor mismatch and strengthening the optimization effect of the digital economy on the factor mismatch. This research provides a new perspective for clarifying the mechanism of the digital economy on sustainable economic development, as well as a reference for the realization of rational allocation of factor resources and sustainable economic development by taking factor mismatch of land and marine binary economies and market integration as the intermediary variables and regulatory variables.

7.
Int Immunopharmacol ; 125(Pt B): 111201, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37951195

RESUMO

During embryo implantation, trophoblast cells rely on large amounts of energy produced by glycolysis for their rapid growth and invasion. The disorder of trophoblast metabolism may lead to recurrent spontaneous abortion (RSA). Lactate, which is produced by the glycolysis of trophoblast cells during early pregnancy, can promote the polarization of M2 macrophages and maintain an anti-inflammatory environment at the maternal-fetal interface. Our study found that amine oxidase copper-containing 4 pseudogene (AOC4P) was abnormally increased in villi from RSA patients. It inhibited the glycolysis of trophoblast cells and thus hindered the polarization of M2 macrophages. Further studies showed that AOC4P combines with tumor necrosis factor receptor-associated factor 6 (TRAF6) to upregulate TRAF6 expression. TRAF6 acted as an E3 ubiquitin ligase to promote ubiquitination and degradation of zeste homolog 2 (EZH2). These results provided new insights into the important role played by AOC4P at the maternal-fetal interface.


Assuntos
Aborto Habitual , Aborto Espontâneo , Amina Oxidase (contendo Cobre) , RNA Longo não Codificante , Feminino , Humanos , Gravidez , Aborto Habitual/metabolismo , Aborto Espontâneo/metabolismo , Amina Oxidase (contendo Cobre)/genética , Amina Oxidase (contendo Cobre)/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Macrófagos/metabolismo , Pseudogenes , RNA Longo não Codificante/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Trofoblastos/metabolismo , Ubiquitinação
8.
Int Immunopharmacol ; 124(Pt A): 110840, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37696144

RESUMO

Aberrant polarization and functions of decidual macrophages are closely related to recurrent spontaneous abortion (RSA). C1q/tumor necrosis factor-related protein 6 (CTRP6) is a member of the adiponectin paralog family, and plays indispensable roles in inflammation, glucose uptake and tumor metastasis. However, the regulatory effect of CTRP6 on macrophage polarization and glycolysis in RSA and the underlying mechanisms have not been fully elucidated. In the present study, we first found that CTRP6 expression was positively correlated with the M1 macrophage marker (CD86) in decidual tissues by dual immunofluorescence analysis. In vitro experiments indicated that CTRP6 could facilitate M1 macrophage activation through the PPAR-γ/NF-κB pathway and manipulate the glycolysis of macrophages. Notably, in addition to silencing CTRP6, treatment with a PPAR-γ agonist (GW1929) inhibited M1 macrophage polarization and rescued embryo absorption in vivo. Taken together, these results identify previously unrevealed functions of CTRP6 in macrophage transformation during RSA.

9.
Cardiovasc Toxicol ; 23(11-12): 406-418, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37740139

RESUMO

Salidroside shows an inhibitory effect on myocardial ischemia/reperfusion (I/R) injury; however, the underlying mechanism remains to be explored. The present work analyzes the mechanism that drives salidroside to ameliorate I/R-induced human cardiomyocyte injury. Human cardiomyocytes were subjected to I/R treatment to simulate a myocardial infarction cell model. Cell viability, cell proliferation, and cell apoptosis were analyzed by CCK-8 assay, EdU assay, and flow cytometry analysis, respectively. RNA expression levels of circ_0097682, miR-671-5p, and F-box and ubiquitin-specific peptidase 46 (USP46) were detected by qRT-PCR. Protein expression was measured by Western blotting assay. The levels of IL-6, IL-1ß, and TNF-α in cell supernatant were detected by enzyme-linked immunosorbent assays. Salidroside treatment relieved I/R-induced inhibitory effect on AC16 cell proliferation and promoting effects on cell apoptosis, inflammation, and oxidative stress. Salidroside inhibited circ_0097682 expression in I/R-treated AC16 cells. Salidroside-mediated inhibition of I/R-induced cell injury involved the downregulation of circ_0097682 expression. In addition, circ_0097682 bound to miR-671-5p in AC16 cells, and miR-671-5p inhibitors rescued salidroside pretreatment-mediated effects in I/R-treated AC16 cells. Moreover, miR-671-5p targeted USP46 in AC16 cells, and USP46 introduction partially relieved circ_0097682 depletion or salidroside pretreatment-induced effects in I/R-treated AC16 cells. Salidroside ameliorated I/R-induced AC16 cell injury by inhibiting the circ_0097682/miR-671-5p/USP46 pathway.

10.
Am J Reprod Immunol ; 90(4): e13776, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37766402

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disease, which is an important cause of female infertility worldwide. PCOS patients are in a state of chronic low-grade inflammation, and immune imbalance is considered as a potential cause of its pathogenesis. METHODS: The expression of AOC4P in PCOS and normal ovarian granulosa cells (GCs) was detected by real-time quantitative PCR. KGN cells were induced by dihydrotestosterone at 500 ng/mL to construct the PCOS model. After lentivirus-infected, KGN cells were constructed with AOC4P overexpression cell lines, the proliferation and apoptosis levels of KGN cells in AOC4P and NC groups were detected. Human monocyte cell line (THP-1)-derived macrophages and peripheral blood mononuclear cells (PBMC) were co-cultured with KGN cells for 48 h, respectively, and the differentiation of macrophages and CD4+ T cells were detected by flow cytometry. RESULTS: Decreased AOC4P expression was found in PCOS patients. After constructing the PCOS cell model, we observed that overexpression of AOC4P promoted KGN cell proliferation and inhibited apoptosis. After co-culture with AOC4P overexpressed KGN cells, M1 macrophages decreased, M2 macrophages increased, T helper cells type 1 (Th1)/Th2 ratio increased, and regulatory T cell (Treg) cells increased. Finally, we found that AOC4P inhibited the activation of the nuclear factor κ B (NF-κB) pathway in KGN cells. CONCLUSIONS: In this study, we found that AOC4P regulated the NF-κB signaling pathway by inhibiting the phosphorylation of P65, thereby affecting the proliferation and apoptosis of GCs, altering the differentiation of macrophages and T cells, thus contributing to the pathogenesis of PCOS.

11.
Medicine (Baltimore) ; 102(22): e33919, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37266636

RESUMO

RATIONALE: Corneal opacity can be caused by various disease. Generally, the opacity gradually increases as the disease progresses. Sudden corneal opacity is mainly caused by corneal trauma, toxic drugs entering the cornea, or acute edema of the keratoconus. However, sudden corneal opacity caused by diabetes has not been reported. PATIENT CONCERNS: A 60-year-old man reported blurred vision and the black eye became white in appearance in the left eye for 5 days. The patient had a history of diabetes which had not been treated. DIAGNOSES: He underwent slit-lamp examination, anterior segment optical coherence tomography, ultrasound bio microscopy, B-mode ultrasound, corneal endothelial examination, random blood glucose testing, and other examinations. The diagnosis of Diabetic Keratopathy was made. INTERVENTIONS: Topical glucocorticoids and dilating eye drops were administered and undergo blood sugar control treatment. OUTCOMES: The corneal of the patient was completely transparent in a few days, and the flocculent exudation in the anterior chamber disappeared. LESSONS: Although diabetes generally causes chronic corneal edema, acute corneal edema may also occur when blood sugar is poorly controlled. Therefore, when we see sudden corneal opacity without obvious incentives, we must consider systemic diseases, especially diabetes.


Assuntos
Doenças do Tecido Conjuntivo , Edema da Córnea , Opacidade da Córnea , Diabetes Mellitus , Ceratocone , Masculino , Humanos , Pessoa de Meia-Idade , Edema da Córnea/etiologia , Glicemia , Opacidade da Córnea/complicações , Ceratocone/complicações , Doenças do Tecido Conjuntivo/complicações , Tomografia de Coerência Óptica/métodos
12.
Biol Reprod ; 109(2): 204-214, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37249558

RESUMO

Trophoblasts are significant components of the placenta and play crucial roles in maternal-fetal crosstalk. Adequate trophoblast migration and invasion are essential for embryo implantation and healthy pregnancy. Ubiquitin-specific protease 7 (USP7), a member of the deubiquitinating enzyme family, regulates the processes of migration and invasion in multiple tumor cells. However, the effects of USP7 on trophoblasts and its possible mechanism in the development of recurrent spontaneous abortion (RSA) are still unclear. In this study, we analyzed the expression of USP7 in villous tissues obtained from RSA patients and healthy controls, and then GNE-6776 (a USP7-specific inhibitor) and USP7 siRNA were used in a trophoblast cell line, HTR-8/SVneo, to further assess the effect of USP7 on the biological function of trophoblasts. Our results provide convincing evidence that USP7 is downregulated in the placental villous tissues of RSA patients. USP7 was found to have a crucial role in the proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) process of trophoblast cells. Further experiments revealed that USP7 directly interacted with the enhancer of zeste homolog 2 (EZH2) and regulated the Wnt/ß-catenin signaling pathway in trophoblasts. Taken together, these findings indicate the vital role of USP7 in regulating trophoblast proliferation, migration and invasion, thus affecting the pathogenesis of RSA, providing new insights into the important role of USP7 in the maternal-fetal interface.


Assuntos
Aborto Habitual , Trofoblastos , Gravidez , Humanos , Feminino , Trofoblastos/metabolismo , Placenta/metabolismo , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Peptidase 7 Específica de Ubiquitina/metabolismo , Aborto Habitual/metabolismo , Apoptose , Proliferação de Células , Movimento Celular
13.
PLoS One ; 18(3): e0283843, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37000894

RESUMO

A theoretical mechanism was analyzed from the micro perspective of the enterprise to explore how information accessibility moderates the effect of accounting manipulation on the sustainable development of digital enterprises. Using data from 1200 listing digital enterprises in China and the DEA-Malmquist index method, the efficiency value of digital enterprises in 2007-2021 was estimated to represent the index of sustainable development of digital enterprises. The accounting manipulation was detected using the panel PSM-DID method based on the Administrative Measures for the Recognition of High-tech Enterprise's policy. The information accessibility value was estimated based on the MDA method. Empirical studies were conducted using text analysis, the panel PSM-DID method, and the double moderating effect model. The results showed that: (1) Accounting manipulation had a negative impact on the sustainable development of "true" digital enterprises and the "fake" digital enterprises. (2) Information accessibility directly and positively enhanced the technological progress and scale efficiency of digital enterprises, and its moderating effect was heterogeneous, with a significant moderating effect on the "true" digital enterprises and a negative effect on the "fake" ones.


Assuntos
Políticas , Desenvolvimento Sustentável , China , Pesquisa Empírica , Reconhecimento Psicológico
14.
Immunol Invest ; 52(4): 467-481, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36989080

RESUMO

Aplastic anemia (AA) is a T cell immune mediated autoimmune disease in which cytokines, particularly IFN-γ are pathogenesis factors. Glucose metabolism is closely related to effector functions of activated T cells, such as IFN-γ production. The characteristics of glucose metabolism and whether interfering with glucose metabolism could affect T cells produce IFN-γ ability in AA patients remains unknown. In this study, we examined the characteristics of glucose metabolism in T cells from AA patients and the effects of the glucose metabolism inhibitor 2-deoxy-D-glucose (2-DG) on the ability of T cell production IFN-γ. Our data demonstrated abnormal glucose metabolism in stimulated T cells from AA patients, mainly reflected by increased glucose uptake and lactate secretion. In addition, EM and TEMRA cells exhibit higher glucose uptake in patients with AA compared with healthy individuals. Moreover, the frequency of IFN-γ+ was reduced by 2-DG in T cell from AA patients. Unexpectedly, 2-DG re-normalized the frequency of IFN-γ+ in other T cell subsets, except for in the TEMRA. In conclusion, our study reveals for the first time the existence of enhanced aerobic glycolysis in T cells from AA patients, and different T cell subsets exhibit different extent glucose uptake requirements. Aerobic glycolysis regulation may be a potential therapeutic strategy for aberrant T cell immunity. Moreover, TEMRA may have specific metabolic abnormalities, which should receive more attention in future targeted immune metabolism research.


Assuntos
Anemia Aplástica , Humanos , Subpopulações de Linfócitos T , Interferon gama , Citocinas
15.
Int J Biol Macromol ; 225: 625-633, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36402389

RESUMO

Tetrahydrobiopterin (BH4) is a vital coenzyme for several enzymes involved in diverse enzymatic reactions in animals. BH4 deficiency can lead to metabolic and neurological disorders due to dysfunction in its metabolism. Sepiapterin reductase (SPR) and dihydrofolate reductase (DHFR) are crucial enzymes in the BH4 de novo synthesis pathway and salvage pathway, respectively. Dihydrobiopterin (BH2) is an oxidized product of BH4 metabolism. The ratio of BH4/BH2 is a key indicator of the stability of BH4 levels. The de novo pathway of BH4 synthesis is well-defined; however, little is known about the mechanisms of the salvage pathway in insects. Herein, we used the natural BmSPR mutant silkworm (lem) as a resource material. Our results reveal that the BmDHFR expression and the BH4/BH2 ratio were remarkably higher in lem as compared to the wild-type silkworm. In BmN cells, knockdown of BmSpr showed increased BmDHFR expression, while the BH4/BH2 ratio decreased after BmDhfr knockdown by RNAi. Furthermore, simultaneous RNAi of BmSpr and BmDhfr showed a further decrease in the BH4/BH2 ratio. These manifest that the expression of BmDHFR is up-regulated to trigger an increase in the BH4/BH2 ratio when the de novo synthesis of BH4 is blocked in silkworm. Additionally, the knockdown of BmSpr in wild-type silkworms also showed an increased BmDHFR level and BH4/BH2 ratio. Taken together, when the silkworm BH4 de novo synthesis pathway is blocked, the salvage pathway is activated, and BmDHFR plays an important role in maintaining the metabolic balance of silkworm BH4. This study enriches our understanding of the molecular mechanism of the BH4 salvage pathway and lays a good foundation for further studies on BH4 using the silkworm as a model insect.


Assuntos
Bombyx , Animais , Bombyx/genética , Insetos
16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-974755

RESUMO

@#Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa. The pathogenesis of OLP is still unclear. Immune abnormalities mediated by T cells and related cytokines play a crucial role in the pathogenesis of OLP. In recent years, glycolytic metabolism-related transporters, enzymes and regulators, such as glucose transporter-1 (Glut1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase A (LDHA), mammalian target of rapamycin (mTOR) and hypoxia inducible factor-1α (HIF-1a), have attracted an increasing amount of attention in OLP by regulating the proliferation and differentiation of T cells and the secretion of inflammatory factors. It has been shown that 2-deoxy-D-glucose (2-DG) or rapamycin (RAPA) inhibits the glycolytic metabolism of T cells and then inhibits OLP. This article reviews the research progress of glycolytic metabolism-related transporters, enzymes and regulatory factors in OLP in recent years.

17.
Reprod Biol ; 22(3): 100679, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35961097

RESUMO

It has been reported that oxidative stress and chronic inflammation may be involved in the pathogenesis of polycystic ovary syndrome (PCOS). 8-oxoguanine DNA glycosylase (OGG1) is the main glycosylase that catalyzes the excision of DNA oxidation products. In this study, we investigated the role and potential mechanisms of OGG1 in the development of PCOS. We first analyzed OGG1 levels in serum and follicular fluid (FF) of PCOS patients, and significantly elevated OGG1 levels were noted in PCOS patients. We similarly observed a significant upregulation of OGG1 expression levels in ovarian tissue of the dehydroepiandrosterone (DHEA)-induced PCOS rat model. In addition, increased apoptosis and increased production of reactive oxygen species (ROS) were observed after the addition of OGG1-specific inhibitor (TH5487) in human granulosa-like tumor cell line (KGN) cells following a concentration gradient, along with a significant decrease in mRNA levels of inflammatory factors such as CXCL2, IL-6, MCP1, IL-1ß, and IL-18. Significant decreases in protein phosphorylation levels of P65 and IκBα were also observed in cells. In addition, we found a significant positive correlation between OGG1 and IL-6 expression levels in human and DHEA-induced PCOS rat models. In conclusion, our results suggest that OGG1 might be involved in the pathogenesis of PCOS by regulating the secretion of IL-6 through NF-κB signaling pathway, and there might be a balance between the inhibition of oxidative stress and the promotion of chronic inflammation by OGG1 on KGN cells.


Assuntos
DNA Glicosilases , Síndrome do Ovário Policístico , Animais , Benzimidazóis , Desidroepiandrosterona , Feminino , Guanina/análogos & derivados , Humanos , Inflamação , Interleucina-6 , NF-kappa B , Piperidinas , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Ratos , Transdução de Sinais
18.
J Reprod Immunol ; 152: 103647, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35667342

RESUMO

The purpose of this study was to determine the regulation of the miR-410-5p /ITGA6 axis on the biological functions of trophoblast cells and the mechanism involved in recurrent spontaneous abortion(RSA). We used qRT-PCR and Western blotting to quantify the expression levels of Mir-410-5p and ITGA6 in placenta of RSA and normal, and found that compared with normal placenta, the placenta of RSA patients showed higher miR-410-5p and lower ITGA6 expression. Dual luciferase reporter gene assay confirmed the binding of miR-410-5p to ITGA6. The expression of miR-410-5p and ITGA6, and proliferation, apoptosis, invasion and migration of trophoblast cells and the effect on the polarization of M2 macrophages were detected in the trophoblast derived cell lines HTR8/Svneo transfected with miR-410-5p mimic, sh-miR-410-5p and si-ITGA6 respectively. Meanwhile, the molecular mechanism of ITGA6 regulation on trophoblast cells was explored. Transfection with miR-410-5p mimic or si-ITGA6 attenuated the proliferation, migration and invasion and induced apoptosis of HTR-8/SVneo cells. Transfection of sh-miR-410-5p promoted proliferation, migration and invasion, and weakened apoptosis of HTR-8/SVneo cells. In addition, overexpression of miR-410-5p in trophoblast cells inhibited the polarization of M2 macrophages, while knockdown of miR-410-5p was beneficial to recruitment of trophoblast cell and promoted the polarization of M2 macrophages. ITGA6 may affect the biological functions of trophoblast cells by regulating PI3K/AKT and MAPK signaling pathways. In conclusion, miR-410-5p mediates trophoblast cell proliferation, apoptosis, invasion and migration through regulating ITGA6 expression.


Assuntos
Aborto Habitual , Integrina alfa6 , MicroRNAs , Pré-Eclâmpsia , Trofoblastos , Aborto Habitual/metabolismo , Aborto Habitual/patologia , Movimento Celular , Proliferação de Células/fisiologia , Feminino , Humanos , Integrina alfa6/genética , Integrina alfa6/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Placenta/metabolismo , Placenta/patologia , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Transdução de Sinais , Trofoblastos/metabolismo , Trofoblastos/patologia
19.
Foods ; 11(3)2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35159545

RESUMO

Food-derived hypotensive peptides have attracted attention in the field of active peptide research in recent years. In this study, based on ACE inhibition rate and using the Box-Behnken central combination design principle to optimise the process of ACE inhibitor peptides prepared by double-enzyme hydrolysis. The amino acid sequences of ACE inhibitor peptides were determined by liquid chromatography mass spectrometry (LC-MS/MS), and their binding to ACE was studied by molecular docking. The optimal processing conditions were 1:1 alkaline protease: compound protease, pH was 8.43, enzymolysis temperature was 44.32 °C, and enzymolysis time was 3.52 h. Under these conditions, the ACE inhibition rate reached 65.12%, and the inhibition rate after separation and purification was 80.68% (IC50 = 0.9 mg/mL). Three novel peptides with ACE inhibitory activity were detected by LC-MS/MS, with sequences LVYP (Leu-Val-Tyr-Pro), VYPW(Val-Tyr-Pro-Trp) and YPWT(Tyr-Pro-Trp-Thr). Molecular docking revealed that the three novel peptides all established hydrogen bonds with the S1(Tyr523, Glu384, Ala354) and S2 (His353) pockets of ACE. Among them, LVYP, VYPW and YPWT, respectively, formed eleven hydrogen bonds, six hydrogen bonds and nine hydrogen bonds with ACE. The study revealed that these peptides have the potential for the development of novel ACE inhibitor drugs and provide a new avenue for high-value utilisation of mushrooms scraps.

20.
Reprod Sci ; 29(10): 2820-2828, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34820775

RESUMO

Macrophages are known to be pivotal for ensuring the establishment of the immune tolerance microenvironment at the maternal-fetal interface. In particular, trophoblasts stay in close contact with decidual macrophages (DMs), which have been reported to play an active role in the modulation of the polarization of DMs. Thus, any dysfunction of trophoblasts might be associated with certain pregnancy-related complications, such as recurrent spontaneous abortion (RSA). Enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulatory gene that has been previously shown to be related to immune regulation. The present study assessed the expression of EZH2 in villi tissue obtained from healthy controls and RSA patients. Trophoblasts conditioned medium was collected to incubate macrophages differentiated from the THP-1 cell line. The expression and function of EZH2 in trophoblasts were knocked down either by the use of siRNA or GSK126 as an inhibitor. Our results show a significant decrease in the expression of EZH2 in villi tissue from RSA patients as compared to healthy controls. Further, the inhibition of expression or function of EZH2 in trophoblasts promoted M1 macrophage polarization, which might be involved in the pathogenesis of RSA. Moreover, the suppression of EZH2 was found to affect the secretion of immune and inflammatory cytokines in trophoblasts. Altogether, these results indicated the importance of EZH2 in the regulation of immune functions of trophoblasts and thus highlighted its potential to be explored as a therapeutic target to prevent and treat pregnancy loss.


Assuntos
Aborto Habitual , Aborto Espontâneo , Aborto Espontâneo/metabolismo , Meios de Cultivo Condicionados , Citocinas/metabolismo , Decídua/metabolismo , Regulação para Baixo , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Humanos , Macrófagos/metabolismo , Gravidez , RNA Interferente Pequeno/metabolismo , Trofoblastos/metabolismo
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