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1.
Gene ; 917: 148456, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604507

RESUMO

Various genetic variants have been found to be associated with the clinical onset of premature ovarian insufficiency (POI). However, when measured in vitro, the functional influence of the variants can be difficult to determine. By whole-exome sequencing (WES) of 93 patients with sporadic POI, we found a missense variant c.623G > A;p.R208H in the EIF4ENIF1 gene. In silico prediction of the variant using different algorithms suggested it might be a damaging variant. We compared the property of EIF4ENIF1 R208H and Q842P, a POI-related mutant that we reported previously, with wildtype (WT) protein using 293FT cells in vitro. Surprisingly, a change in subcellular distribution and granule forming ability (Q842P) and nuclear import capacity (R208H) was not observed, despite domain prediction evidences. Since EIF4ENIF1 was reported to inhibit translation, we employed T&T-seq, a translation-transcription dual-omics sequencing method, to profile gene expression upon overexpression of EIF4ENIF1 WT and mutants. EIF4ENIF1 WT overexpression group exhibited significantly (P < 0.0001) lower translation efficiency (TE) than empty vector or GFP overexpression control group. Surprisingly, EIF4ENIF1 Q842P overexpression failed to repress global translation, showing an overall TE significantly higher than WT group. Overexpression R208H significantly (P < 0.0001) lowered the overall TE, whereas exhibiting a reduced translation inhibitory effect on high-TE genes (TE > 2 in GFP control group). Several fertility-associated genes, such as AMH in Q842P group and SERPINE1 and THBS1 in R208H group, was translationally up-regulated in mutant groups versus WT control, suggesting a potential mechanism of mutated EIF4ENIF1 causing POI via impaired translation repression. It is further proposed that T&T-seq can be a sensitive evaluation tool for the measurement of functional alteration by variants in many other translational regulator genes, not only EIF4ENIF1, helping to eliminate misinterpretation of clinical significance of genetic variants.

2.
Endocrinology ; 165(4)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38340326

RESUMO

Ovarian endometriosis (EMs) is a benign, estrogen-dependent gynecological disorder. Estrogen receptor beta (ERß), a nuclear receptor for estradiol, plays an important role in the development of ovarian EMs. Here, we investigated the biological significance of aurora kinase A (AURKA) in ovarian EMs and the mechanism by which it regulates ERß. We used immunohistochemical assays to verify that AURKA and ERß were highly expressed in ectopic endometrial tissues. Cell proliferation and colony formation assays were used to demonstrate that AURKA promoted the proliferation of EMs cells. Wound-healing assay, Transwell migration assay, and Matrigel invasion assay further showed that AURKA enhanced the ability of EMs cells to migrate and invade. In addition, AURKA was shown to stimulate glycolysis in EMs cells by measuring the concentration of glucose and lactate in the cell supernatants. Moreover, the AURKA inhibitor alisertib was found to inhibit the progression of ovarian EMs and glycolysis in a mouse model of EMs by measuring ectopic tissues as well as by testing the peritoneal fluid of mice. Furthermore, coimmunoprecipitation assay showed that AURKA interacted with ERß. The rescue experiments confirmed that AURKA regulated the development and glycolysis of ovarian EMs in an ERß-dependent manner. AURKA contributed to the development of ovarian EMs by upregulating of ERß. AURKA may represent a new target for the treatment of ovarian EMs.


Assuntos
Endometriose , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Aurora Quinase A/genética , Aurora Quinase A/metabolismo , Receptor beta de Estrogênio/metabolismo , Glicólise
3.
ACS Biomater Sci Eng ; 9(6): 3273-3284, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-37134278

RESUMO

Inflammatory response in macrophages on account of prostheses-derived wear particles is the leading cause of artificial joint failure. However, the mechanism by which wear particles initiate macrophage inflammation has not been fully elucidated. Previous research studies have identified TANK-binding kinase 1 (TBK1) and stimulator of interferon genes (STING) as potential factors in inflammation and autoimmune diseases. Here, we found that both TBK1 and STING were increased in synovium from aseptic loosening (AL) patients and were activated in titanium particles (TiPs)-stimulated macrophages. Lentivirus-mediated knockdown of TBK or STING significantly inhibited the inflammatory effects of macrophages, while overexpression of TBK or STING exerted opposite results. In concrete, STING/TBK1 promoted the activation of NF-κB and IRF3 pathways and macrophage M1 polarization. For further validation, a mice cranial osteolysis model was constructed for in vivo assays, and we found that STING-overexpressed lentivirus injection exacerbated osteolysis and inflammation, which was counteracted by TBK1-knockdown injection. In conclusion, STING/TBK1 enhanced TiP-induced macrophage inflammation and osteolysis via orchestrating the activation of NF-κB and IRF3 pathways and M1 polarization, which suggested STING/TBK1 as potential therapeutic targets for preventing AL of prostheses.


Assuntos
Osteólise , Titânio , Animais , Camundongos , Titânio/efeitos adversos , Titânio/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Osteólise/induzido quimicamente , Osteólise/metabolismo , Macrófagos/metabolismo , Inflamação/genética , Inflamação/metabolismo
4.
Molecules ; 28(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37049647

RESUMO

Morchella esculenta (L.) Pers., referred to as Morel, is a medicinal and edible homologous fungus, which contains many bioactive substances. In Morel, polysaccharides are the most abundant and have various bioactivities. In the present work, two novel polysaccharides, Se-MPS and MPS, were prepared and purified from selenium-enriched (Se-enriched) and common Morel mycelia, respectively, and their structural and immunomodulatory properties were evaluated. The results show that Se-enriched treatment significantly changed the polysaccharides' chemical composition, molecular weight, and sugar chain configuration. In addition, the Se-enriched treatment also improved the polysaccharides' fragmentation and thermal stability. Importantly, Se-enriched Morel polysaccharide (Se-MPS) could significantly enhance phagocytosis of RAW 264.7 macrophage cells and, remarkably, activate their immune response via activating the TLR4-TRAF6-MAPKs-NF-κB cascade signaling pathway, finally exerting an immunomodulatory function. Based on these findings, selenium-enriched Morel polysaccharide appears to have more potential for development and utilization in functional foods or medicines than ordinary Morel polysaccharide.


Assuntos
Selênio , Selênio/química , Antioxidantes/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Fagocitose
5.
Ying Yong Sheng Tai Xue Bao ; 34(4): 1024-1034, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37078322

RESUMO

As one of the important timber species in China, Cunninghamia lanceolata is widely distributed in southern China. The information of tree individuals and crown plays an important role in accurately monitoring forest resources. Therefore, it is particularly significant to accurately grasp such information of individual C. lanceolata tree. For high-canopy closed forest stands, the key to correctly extract such information is whether the crowns of mutual occlusion and adhesion can be accurately segmented. Taking the Fujian Jiangle State-owned Forest Farm as the research area and using the UAV image as the data source, we developed a method to extract crown information of individual tree based on deep learning method and watershed algorithm. Firstly, the deep learning neural network model U-Net was used to segment the coverage area of the canopy of C. lanceolata, and then the traditional image segmentation algorithm was used to segment the individual tree to obtain the number and crown information of individual tree. Under the condition of maintaining the same training set, validation set and test set, the extraction results of the canopy coverage area by the U-Net model and traditional machine learning methods [random forest (RF) and support vector machine (SVM)] were compared. Then, two individual tree segmentation results were compared, one using the marker-controlled watershed algorithm, and the other using the combination of the U-Net model and marker-controlled watershed algorithm. The results showed that the segmentation accuracy (SA), precision, IoU (intersection over union) and F1-score (harmonic mean of precision and recall) of the U-Net model were higher than those of RF and SVM. Compared with RF, the value of those four indicators increased by 4.6%, 14.9%, 7.6% and 0.05, respectively. Compared with SVM, the four indicators increased by 3.3%, 8.5%, 8.1% and 0.05, respectively. In terms of extracting the number of trees, the overall accuracy (OA) of the U-Net model combined with the marker-controlled watershed algorithm was 3.7% higher than that of the marker-controlled watershed algorithm, with the mean absolute error (MAE) being decreased by 3.1%. In terms of extracting crown area and crown width of individual tree, R2 increased by 0.11 and 0.09, mean squared error decreased by 8.49 m2 and 4.27 m, and MAE decreased by 2.93 m2 and 1.72 m, respectively. The combination of deep learning U-Net model and watershed algorithm could overcome the challenges in accurately extracting the number of trees and the crown information of individual tree of high-density pure C. lanceolata plantations. It was an efficient and low-cost method of extracting tree crown parameters, which could provide a basis for developing intelligent forest resource monitoring.


Assuntos
Cunninghamia , Humanos , Algoritmos , Algoritmo Florestas Aleatórias , China , Redes Neurais de Computação
6.
Reprod Sci ; 30(9): 2692-2702, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37059967

RESUMO

Endometriosis is a common gynecological disorder characterized by the presence of the endometrial glands and the stroma outside the uterine cavity. The disease affects reproductive function and quality of life in women of reproductive age. Endometriosis is similar to tumors in some characteristics, such as glycolysis. PIM2 can promote the development of tumors, but the mechanism of PIM2 in endometriosis is still unclear. Therefore, our goal is to study the mechanism of PIM2 in endometriosis. Through immunohistochemistry, we found PIM2, HK2, PKM2, SMH (smooth muscle myosin heavy chain), Desmin, and α-SMA (α-smooth muscle actin) were strongly expressed in the ovarian endometriosis. In endometriotic cells, PIM2 enhanced glycolysis and fibrosis via upregulating the expression of PKM2. Moreover, the PIM2 inhibitor SMI-4a inhibited the development of endometriosis. And we established a PIM2 knockout mouse model of endometriosis to demonstrate the role of PIM2 in vivo. In summary, our study indicates that PIM2 promotes the development of endometriosis. PIM2 may serve as a promising therapeutic target for endometriosis.


Assuntos
Endometriose , Neoplasias , Humanos , Camundongos , Animais , Feminino , Endometriose/metabolismo , Qualidade de Vida , Glicólise , Fibrose , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo
7.
Plant Foods Hum Nutr ; 78(2): 243-252, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37097509

RESUMO

Inulin is a naturally soluble dietary fiber that is widely distributed and primarily derived from plants. As a reserve biopolysaccharide in plants, inulin is considered an indigestible carbohydrate of fructan because of its unique ß-(2,1)-glycosidic bond structure. Numerous recent animal and human experimental studies have shown that functional inulin possesses multiple bioactivities, including immunomodulatory, antioxidant, antitumor, hepatoprotective, hypoglycemic, and gastrointestinal protective activities. Due to its increasing popularity, people tend to consume foods containing inulin. Moreover, inulin holds promise as a bioactive compound for use in the development of various food products. Therefore, this paper provides a detailed review of the extraction method, physicochemical properties, functional activity, and application development of inulin polysaccharides, to provide a theoretical foundation for further advancements in the fields of preparation and application of functional foods.


Assuntos
Inulina , Polissacarídeos , Animais , Humanos , Inulina/farmacologia , Polissacarídeos/farmacologia , Polissacarídeos/química , Frutanos , Carboidratos , Alimento Funcional
8.
Stem Cells Dev ; 32(13-14): 365-378, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37051687

RESUMO

Articular cartilage injury is common in various conditions, including osteoarthritis, rheumatic diseases, and trauma. Current treatments for cartilage injury fail to completely regenerate the damaged cartilage. Mesenchymal stromal cells (MSCs) have emerged as potential candidates for cartilage regeneration. However, MSCs exhibit hypertrophic differentiation, and their chondrogenic ability is reduced in an inflammatory environment. In recent years, genetic modification has been proposed for optimizing MSC-based therapies, some of which are expected to enter clinical trials. This review summarizes recent research findings and developments in genetic engineering strategies to enhance stem cell-based therapy for cartilage regeneration. We also discuss the mechanisms of biofunctions of MSCs in cartilage regeneration and outline the efficacy and safety of the different genetic modification strategies, including viral and nonviral delivery transduction. Finally, we highlight the major challenges and prospects for clinical translation of genetically modified MSCs.


Assuntos
Cartilagem Articular , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Osteoartrite , Humanos , Diferenciação Celular/genética , Condrogênese/genética
9.
J Inorg Biochem ; 243: 112190, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36965431

RESUMO

Antibiotics overuse and misuse increase the emergence of multidrug-resistant bacterial strains, which often leads to the failure of conventional antibiotic therapies. Even worse, the tendency of bacteria to form biofilms further increases the therapeutic difficulty, because the extracellular matrix prevents the penetration of antibiotics and triggers bacterial tolerance. Therefore, developing novel antibacterial agents or therapeutic strategies with diverse antibacterial mechanisms and destruction of bacteria biofilm is a promising way to combat bacterial infections. In the present study, the combination of quaternary ammonium compound poly(diallyl dimethyl ammonium chloride) (PDDA) with Cu2+ was screened out to fight common pathogenic Staphylococcus aureus (S. aureus) through multi-mechanisms. This combination appeared strong synergistic antibacterial activity, and the fractional inhibitory concentration index was as low as 0.032. The synergistic antibacterial mechanism involved the destruction of the membrane function, generation of intracellular reactive oxygen, and promotion more Cu2+ into the cytoplasm. Further, the combination of PDDA and Cu2+ reduced the extracellular polysaccharide matrix, meanwhile killing the bacteria embedded in the biofilm. The biocompatibility study in vitro revealed this combination exhibited low cytotoxicity and hemolysis ratio even at 8 times of minimum bactericidal concentration. This work provides a novel antibacterial agents combination with higher efficiency to fight planktonic and biofilm conditions of S. aureus.


Assuntos
Cobre , Staphylococcus aureus Resistente à Meticilina , Cobre/farmacologia , Staphylococcus aureus , Compostos de Amônio Quaternário/farmacologia , Antibacterianos/farmacologia , Bactérias , Biofilmes , Testes de Sensibilidade Microbiana
11.
Sci Total Environ ; 871: 162077, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36764534

RESUMO

This work aims to resolve residual film pollution in farmlands and improve tomato quality. The mechanical properties and degradation of PBAT/PLA lignin (MZS) and PBAT/PLA humic acid (FZS) composite biodegradable film were analyzed, and its effect on soil temperature and humidity, soil microorganisms, soil physical and chemical properties, tomato yield, and quality was studied. Polyethylene film (PE) was used as a control. The results demonstrate a higher degradation degree of FZS film than of MZS film. The degradation degree of FZS and MZS films reached level 2 and level 1, respectively, after 131 days of film covering. The weight loss rate of FZS and MZS films reached 52.74 % and 57.82 %, respectively, when buried for 160 days. Compared to the coverings of PE and MZS films, FZS film could significantly increase the soil's electric conductivity and organic matter content (p < 0.05). The relative abundance of soil fungi Chaetomium also increased. The yield, soluble solids, vitamin C (Vc), soluble sugar, and lycopene of tomato plants covered with FZS film significantly increased by 6.74 %, 8.75 %, 15.41 %, 8.30 %, and 27.27 % compared to plants covered with PE film, and the total acid and hardness significantly decreased by 24.95 % and 8.46 %, respectively (p < 0.05). Using 10 µm PBAT/PLA humic acid biodegradable film for tomato cultivation in autumn and winter increased the lycopene and decreased the total acid content by changing the soil's physical and chemical characteristics and increasing the content of Chaetomium soil.


Assuntos
Substâncias Húmicas , Solanum lycopersicum , Licopeno , Solo , Poliésteres/química
12.
Asian J Psychiatr ; 79: 103400, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36521406

RESUMO

BACKGROUND: Oxidative stress (OS) and neuroinflammatory pathways play an important role in the pathophysiology of schizophrenia. The present study investigated the relationship between OS, inflammatory cytokines, and clinical features in male patients with treatment-resistant schizophrenia (TRS). METHOD: We measured plasma OS parameters, including manganese-superoxide dismutase (Mn-SOD), copper/zinc-containing SOD (CuZn-SOD), total-SOD (T-SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px); and serum inflammatory cytokines, including interleukin (IL)- 1α, IL-6, tumor necrosis factor-alpha (TNF-α), and interferon (IFN)-γ, from 80 male patients with chronic schizophrenia (31 had TRS and 49 had chronic stable schizophrenia (CSS)), and 42 healthy controls. The severity of psychotic symptoms was evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Compared with healthy controls, plasma Mn-SOD, CuZn-SOD, T-SOD, GSH-Px, and MDA levels were significantly lower, while CAT and serum IL-6 levels were higher in both TRS and CSS male patients (all P < 0.05). Significant differences in the activities of CAT (F = 6.068, P = 0.016) and IL-6 levels (F = 6.876, P = 0.011) were observed between TRS and CSS male patients after analysis of covariance. Moreover, a significant positive correlation was found between IL-6 levels and PANSS general psychopathology subscores (r = 0.485, P = 0.006) and between CAT activity and PANSS total scores (r = 0.409, P = 0.022) in TRS male patients. CAT and IL-6 levels were predictors for TRS. Additionally, in chronic schizophrenia patients, a significant positive correlation was observed between IL-6 and GSH-Px (r = 0.292, P = 0.012), and the interaction effect of IL-6 and GSH-Px was positively associated with PANSS general psychopathology scores (r = 0.287, P = 0.014). CONCLUSION: This preliminary study indicated that variations in OS and inflammatory cytokines may be involved in psychopathology for patients with chronic schizophrenia, especially in male patients with TRS.


Assuntos
Catalase , Interleucina-6 , Esquizofrenia , Humanos , Masculino , Catalase/sangue , Catalase/química , Citocinas/sangue , Citocinas/química , Interleucina-6/sangue , Interleucina-6/química , Estresse Oxidativo/fisiologia , Esquizofrenia/diagnóstico , Esquizofrenia/metabolismo , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo
13.
Cytometry A ; 103(1): 27-38, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35869932

RESUMO

In the recent decade, chimeric antigen receptor (CAR)-T cell therapy has revolutionized strategies for cancer treatments due to its highly effective clinical efficacy and response for B cell malignancies. The success of CAR-T cell therapy has stimulated the increase in the research and development of various CAR constructs to target different tumor types. Therefore, a robust and efficient in vitro potency assay is needed to quickly identify potential CAR gene design from a library of construct candidates. Image cytometry methodologies have been utilized for various CAR-T cell-mediated cytotoxicity assay using different fluorescent labeling methods, mainly due to their ease-of-use, ability to capture cell images for verification, and higher throughput performance. In this work, we employed the Celigo Image Cytometer to evaluate and compare two CAR-T cell-mediated cytotoxicity assays using GFP-expressing or fluorescent dye-labeled myeloma and plasmacytoma cells. The GFP-based method demonstrated higher sensitivity in detecting CAR-T cell-mediated cytotoxicity when compared to the CMFDA/DAPI viability method. We have established the criteria and considerations for the selection of cytotoxicity assays that are fit-for-purpose to ensure the results produced are meaningful for the specific testing conditions.


Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T , Linhagem Celular Tumoral , Imunoterapia Adotiva/métodos
14.
Cell Mol Life Sci ; 80(1): 13, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36536161

RESUMO

Ovarian endometriosis is a common gynecological condition that can cause infertility in women of childbearing age. However, the pathogenesis is still unknown. We demonstrate that the carboxyl terminus of Hsc70-interacting protein (CHIP) is a negative regulator in the development of endometriosis and reduces HMGB1 expression in endometriotic cells. Meanwhile, CHIP interacts with HMGB1 and promotes its ubiquitinated degradation, thereby inhibiting aerobic glycolysis and the progression of endometriosis. Furthermore, the CHIP agonist YL-109 effectively suppresses the growth of ectopic endometrium in endometriosis mouse model, which could be a potential therapeutic approach for endometriosis. In conclusion, our data suggest that CHIP may inhibit the development of endometriosis by suppressing the HMGB1-related glycolysis.


Assuntos
Endometriose , Proteína HMGB1 , Ubiquitina-Proteína Ligases , Animais , Feminino , Humanos , Camundongos , Endometriose/patologia , Glicólise , Proteína HMGB1/metabolismo , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismo
15.
iScience ; 25(11): 105363, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36339263

RESUMO

Endometriosis is a common chronic condition characterized by abnormal growth of the endometrium outside the uterus. Heat shock transcription factor 1 (HSF1) is a significant regulator of the proteotoxic stress response and plays an essential role in developing endometriosis. However, the mechanisms regulating HSF1 protein stability in endometriosis remain unclear. Here, we demonstrate that OTUB1 interacts with HSF1 and promotes HSF1 protein stability through deubiquitination. In addition, OTUB1 enhances glycolysis and epithelial-mesenchymal transition of endometriosis cells, leading to promote proliferation, migration, and invasion of endometriosis cells. The progression of endometriosis is inhibited in an OTUB1-knockout mouse model. In summary, OTUB1 promotes the development of endometriosis by up-regulating HSF1. OTUB1/HSF1 axis may become a new therapeutic target for endometriosis.

16.
Polymers (Basel) ; 14(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36298031

RESUMO

Edible fungi, commonly known as mushrooms, are precious medicinal and edible homologous gifts from nature to us. Because of their distinctive flavor and exceptional nutritional and medicinal value, they have been a frequent visitor to people's dining tables and have become a hot star in the healthcare, pharmaceutical, and cosmetics industries. Edible fungal polysaccharides (EFPs) are an essential nutrient for edible fungi to exert bioactivity. They have attracted much attention because of their antioxidant, immunomodulatory, antitumor, hypoglycemic, and hypolipidemic bioactivities. As a result, EFPs have demonstrated outstanding potential over the past few decades in various disciplines, including molecular biology, immunology, biotechnology, and pharmaceutical chemistry. However, the complexity of EFPs and the significant impact of mushroom variety and extraction techniques on their bioactivities prevents a complete investigation of their biological features. Therefore, the authors of this paper thoroughly reviewed the comparison of different extraction methods of EFPs and their advantages and disadvantages. In addition, the molecular weight, monosaccharide composition, and glycosidic bond type and backbone structure of EFPs are described in detail. Moreover, the in vitro and in vivo bioactivities of EFPs extracted by different methods and their potential regulatory mechanisms are summarized. These provide a valuable reference for improving the extraction process of EFPs and their production and development in the pharmaceutical field.

17.
Cell Death Dis ; 13(9): 790, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109523

RESUMO

Endometriosis (EM) is one of the vanquished wonted causes of chronic pelvic sting in women and is closely associated with infertility. The long-term, complex, systemic, and post-treatment recurrence of EM wreaks havoc on women's quality of life. Extensive metabolic reprogramming (aerobic glycolysis, glucose overweening intake, and high lactate production) and cancer-like changes have been found in EM, which bears striking similarities to tumorigenesis. The key glycolysis regulator PFKFB4 is overexpressed in EM. However, the mechanism of PFKFB4 in EM remains unknown. We found that PFKFB4 was upregulated and was closely related to the progression of EM. We identified focus PIM2 as a new pioneering adjoin protein of PFKFB4. Vigorous biochemical methods were used to confirm that PIM2 phosphorylated site Thr140 of PFKFB4. PIM2 also could enhance PFKFB4 protein expression through the ubiquitin-proteasome pathway. Moreover, PIM2 expression was really corresponding prevalent with PFKFB4 in endometriosis in vivo. Importantly, phosphorylation of PFKFB4 on Thr140 by PIM2 promoted EM glycolysis and cell growth. Our study demonstrates that PIM2 mediates PFKFB4 Thr140 phosphorylation thus regulating glycolysis and EM progression. We illustrated a new mechanism that PIM2 simulated a central upstream partnership in the regulation of PFKFB4, and reveal a novel means of PIM2-PFKFB4 setting EM growth. Our research provided new theoretical support for further clarifying the reprogramming of EM glucose metabolism, and provided new clues for exploring non-contraceptive treatments for EM.


Assuntos
Endometriose , Fosfofrutoquinase-2 , Anaerobiose , Proliferação de Células/genética , Endometriose/genética , Feminino , Glucose/metabolismo , Glicólise/genética , Humanos , Lactatos , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Fosforilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas/metabolismo , Qualidade de Vida , Ubiquitinas/metabolismo
18.
Reprod Biol ; 22(4): 100698, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36162310

RESUMO

Recurrent implantation failure (RIF) is characterized by the absence of implantation after high-grade embryos are transferred to the endometrium by at least three in vitro fertilization cycles. It is one of the most important factors contributing to reproductive failure. After numerous barriers have been overcome to obtain good-quality embryos, RIF causes extreme distress and frustration in women and couples. In recent years, significant progress has been made in understanding how inflammatory factors, which include pro-inflammatory factors, anti-inflammatory factors, chemokines, and other molecules, contribute to RIF. Immunological abnormalities, hypercoagulability, and reproductive diseases are considered potential causes of RIF. In alloimmune disorders, inflammatory factors can affect the success rate of embryo implantation by altering T helper (Th)1/Th2 and Th17/regulatory T cell ratios and causing imbalances of uterine natural killer cells and macrophages. Autoimmune disorders can also lead to RIF. Inflammatory factors also play key roles in RIF-related disorders such as hypercoagulability, chronic endometritis, adenomyosis, hydrosalpinx, and endometriosis. This review focuses on the roles of inflammatory factors in RIF, including immune factors, blood hypercoagulable states, and reproductive diseases such as chronic endometritis, adenomyosis, hydrosalpinx, and endometriosis. It also summarizes the different treatments according to the causes of RIF and discusses the efficacy of sirolimus, peripheral blood mononuclear cells, low-dose aspirin combined with low-molecular-weight heparin, blocking interleukin-22, and gonadotropin-releasing hormone agonists in the treatment of RIF.


Assuntos
Adenomiose , Endometriose , Endometrite , Trombofilia , Feminino , Humanos , Leucócitos Mononucleares , Implantação do Embrião , Fertilização in vitro , Endométrio
19.
Front Plant Sci ; 13: 945105, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968120

RESUMO

Photoperiod- and thermosensitive genic male sterility (PTGMS) rice is a vital germplasm resource consisting of two-line hybrid rice in which light and temperature strictly control their fertility changes. Variable environmental conditions present huge risks to the two-lines hybrid seed production. Explaining the regulatory mechanism of male fertility in rice PTGMS lines is an essential prerequisite to ensuring food security production. A group of near-isogenic lines (NILs) of a rice PTGMS line unique to this research group was used for this study. These lines have the same genetic background and regulate male fertility by responding to different temperature changes. Transcriptomic analysis revealed that 315 upregulated genes and 391 regulated genes regulated male fertility in response to temperature changes, and differentially expressed genes (DEGs) were mainly characterized in enrichment analysis as having roles in the metabolic pathways of sugar, lipid and phenylpropanoid. Electron microscopy analysis revealed that a lack of starch accumulation in sterile pollen grains induced by high temperature, with an abnormal exine development and a lack of inner pollen grains. Defective processes for sporopollenin synthesis, sporopollenin transport and pollen wall formation in sterile anthers were verified using qPCR. Targeted metabolomics analysis revealed that most lipids (phospholipids, sphingolipids and fatty acids) and flavonoids (flavones and flavanones) were upregulated in fertile anthers and involved in pollen wall development and male fertility formation, while lignin G units and C-type lignin were the major contributors to pollen wall development. The coding genes for trehalose 6-phosphate phosphatase, beta-1,3-glucanase, phospholipase D and 4-coumarate-CoA ligase are considered essential regulators in the process of male fertility formation. In conclusion, our results indicated that the expression of critical genes and accumulation of metabolites in the metabolism of sugar, lipid, and phenylpropanoid are essential for male fertility formation. The results provide new insights for addressing the negative effects of environmental variation on two-line hybrid rice production.

20.
Front Mol Biosci ; 9: 921298, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35775079

RESUMO

Ferroptosis is a new type of cell death different from apoptosis and necrosis, which can regulate the accumulation of lipid peroxidation through different pathways, ultimately leading to cell death. An increasing number of studies have revealed that the relationship between ferroptosis and cancer is extremely complex, which holds promise as a new treatment. In gynecological malignancies, ferroptosis has been found to have excellent antitumor activity, which can regulate the proliferation, metastasis and radiochemotherapy resistance. With the continuous progress of research, nanodrugs, gene therapy and other new therapeutic techniques for inducing ferroptosis have been proposed. However, the study of ferroptosis in gynecological malignancies is still in its infancy, and further research is needed to design safe and effective cancer therapies based on ferroptosis. This article reviews the mechanism of ferroptosis and the latest research progress and prospects in gynecological malignancies.

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