RESUMEN
BACKGROUND: Fibrogenesis within ovarian endometrioma (endometrioma), mainly induced by transforming growth factor-ß (TGF-ß), is characterized by myofibroblast over-activation and excessive extracellular matrix (ECM) deposition, contributing to endometrioma-associated symptoms such as infertility by impairing ovarian reserve and oocyte quality. However, the precise molecular mechanisms that underpin the endometrioma- associated fibrosis progression induced by TGF-ß remain poorly understood. METHODS: The expression level of lysine acetyltransferase 14 (KAT14) was validated in endometrium biopsies from patients with endometrioma and healthy controls, and the transcription level of KAT14 was further confirmed by analyzing a published single-cell transcriptome (scRNA-seq) dataset of endometriosis. We used overexpression, knockout, and knockdown approaches in immortalized human endometrial stromal cells (HESCs) or human primary ectopic endometrial stromal cells (EcESCs) to determine the role of KAT14 in TGF-ß-induced fibrosis. Furthermore, an adeno-associated virus (AAV) carrying KAT14-shRNA was used in an endometriosis mice model to assess the role of KAT14 in vivo. RESULTS: KAT14 was upregulated in ectopic lesions from endometrioma patients and predominantly expressed in activated fibroblasts. In vitro studies showed that KAT14 overexpression significantly promoted a TGF-ß-induced profibrotic response in endometrial stromal cells, while KAT14 silencing showed adverse effects that could be rescued by KAT14 re-enhancement. In vivo, Kat14 knockdown ameliorated fibrosis in the ectopic lesions of the endometriosis mouse model. Mechanistically, we showed that KAT14 directly interacted with serum response factor (SRF) to promote the expression of α-smooth muscle actin (α-SMA) by increasing histone H4 acetylation at promoter regions; this is necessary for TGF-ß-induced ECM production and myofibroblast differentiation. In addition, the knockdown or pharmacological inhibition of SRF significantly attenuated KAT14-mediating profibrotic effects under TGF-ß treatment. Notably, the KAT14/SRF complex was abundant in endometrioma samples and positively correlated with α-SMA expression, further supporting the key role of KAT14/SRF complex in the progression of endometrioma-associated fibrogenesis. CONCLUSION: Our results shed light on KAT14 as a key effector of TGF-ß-induced ECM production and myofibroblast differentiation in EcESCs by promoting histone H4 acetylation via co-operating with SRF, representing a potential therapeutic target for endometrioma-associated fibrosis.
Asunto(s)
Endometriosis , Fibrosis , Factor de Respuesta Sérica , Factor de Crecimiento Transformador beta , Adulto , Animales , Femenino , Humanos , Ratones , Endometriosis/patología , Endometriosis/metabolismo , Endometrio/metabolismo , Endometrio/patología , Histona Acetiltransferasas/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patología , Factor de Respuesta Sérica/metabolismo , Células del Estroma/metabolismo , Células del Estroma/patología , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales/metabolismoRESUMEN
Uterine fibroids are a prevalent factor that impacts fertility in women of reproductive age. This study discusses the theoretical foundation and formula principles of Professor MA Kun's clinical treatment for infertility caused by uterine fibroids. The kidney stores essence and is responsible for reproduction, while blood serves as a vital material basis for women's physiological functions. Kidney deficiency is the fundamental pathogenesis of infertility, and imbalances in kidney Qi and essence or deficiencies in kidney Yin and Yang can result in blood stasis. Blood stasis plays a significant role throughout this condition by impeding the flow of blood, which is crucial for nourishing Qi. Therefore, both kidney deficiency and blood stasis are key factors contributing to infertility caused by uterine fibroids. Professor MA Kun treats infertility caused by uterine fibroids using an approach that involves tonifying the kidneys and activating blood circulation based on changes in Qi and blood during the menstrual cycle as well as follicular growth processes. By identifying stage-specific evidence, appropriate treatments can be applied accordingly. During menstruation when the uterus opens and menstrual blood flows out, promoting follicular development through nourishing kidney Yin and activating blood circulation becomes essential. In later stages of menstruation, additional measures are taken to remove blood stasis, alleviate symptoms, disperse knots, attack pathogens while simultaneously replenishing vital energy. During intermenstrual periods when Yin holds greater importance than Yang, tonifying the kidneys and activating blood circulation helps facilitate smooth discharge of eggs by promoting transformation between Yin and Yang energies. Premenstrual period to warm kidney Yang to promote pregnant egg implantation, and at the same time to dredge the liver and regulate Qi, Qi elimination stagnation, complementary in the line, with the symptoms of additional subtractions. Clinical effect is remarkable, for the reference of colleagues.
Asunto(s)
Medicamentos Herbarios Chinos , Infertilidad Femenina , Riñón , Leiomioma , Humanos , Femenino , Riñón/fisiopatología , Infertilidad Femenina/etiología , Infertilidad Femenina/terapia , Infertilidad Femenina/fisiopatología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Global warming has contributed to shifts in precipitation patterns and increased plant productivity, resulting in a significant increase in litter input into the soils. The enhanced litter input, combined with higher levels of precipitation, may potentially affect soil microbial communities. This study aims to investigate the effects of litter input and increased precipitation on soil microbial biomass, community structure, and diversity in a temperate meadow steppe in northeastern China. Different levels of litter input (0%, +30%, +60%) and increased precipitation (0%, +15%, +30%) were applied over a three-year period (2015-2017). The results showed that litter input significantly increased the biomass of bacteria and fungi without altering their diversity, as well as the ratio of bacterial to fungal biomass. Increased precipitation did not have a notable effect on the biomass and diversity of bacteria and fungi, but it did increase the fungal-to-bacterial biomass ratio. However, when litter input and increased precipitation interacted, bacterial diversity significantly increased while the fungal-to-bacterial biomass ratio remained unchanged. These findings indicate that the projected increases in litter and precipitation would have a substantial impact on soil microbial communities. In energy-and water-limited temperate grasslands, the additional litter inputs and increased precipitation contribute to enhanced nutrient and water availability, which in turn promotes microbial growth and leads to shifts in community structure and diversity.
RESUMEN
BACKGROUND: The COVID-19 pandemic is an unprecedented health crisis that has affected in vitro fertilization practices globally. Previous studies have shown that SARS-CoV-2 impacts the quality of embryos by inducing an immunological response in infertile patients. In this study, the early embryonic development of SARS-CoV-2-infected infertile patients was investigated. METHODS: Sixty-five SARS-CoV-2 infected infertile patients and 258 controls were involved in this study. The major outcome parameters for the cycle were analyzed, including the number of oocytes, maturation oocytes, available embryos per cycle, and embryo morpho kinetic characteristics. RESULTS: From SARS-CoV-2 infection until oocyte retrieval, it took an average of 6.63 days. The results revealed that the number of oocytes and high-quality embryos on day 3 dramatically reduced in SARS-CoV-2-infected infertile patients. SARS-CoV-2 was detected in the follicular fluid of three infertile patients. SARS-CoV-2 infection had negatively impacted the number of oocytes in multivariate linear regression models. The early embryonic development in the SARS-CoV-2 infection group had a noticeable delay from the six-cell stage to blastocyst stage. CONCLUSIONS: SARS-CoV-2 infection reduced the number of oocytes and high-quality embryos on day 3. It delays the early embryonic development from the six-cell stage to blastocyst stage and has a negative impact on the quality of embryos.
Asunto(s)
COVID-19 , Infertilidad , Femenino , Embarazo , Humanos , SARS-CoV-2 , Pandemias , Oocitos , Desarrollo EmbrionarioRESUMEN
Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women's reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.
Asunto(s)
Infertilidad , Ovulación , Femenino , Humanos , Atrofia/metabolismo , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Infertilidad/metabolismo , Folículo OváricoRESUMEN
Biodiversity plays a crucial role in driving multiple ecosystem functions in temperate grasslands. However, our understanding of how biodiversity regulates the impacts of desertification processes on ecosystem multifunctionality (EMF) remains limited. In this study, we investigate plant diversity, soil microbial diversity (fungal, bacterial, archaeal, and arbuscular mycorrhizal fungal (AMF) diversity), soil properties (soil water content, pH, and soil clay content), and multiple ecosystem functions (soil N mineralization, soil phosphatase activity, AMF infection rate, microbial biomass, plant biomass, and soil C and nutrients (N, P, K, Ca, Fe, Na, Cu, Mg, and Mn)) at six different grassland desertification intensities. The random forest model was conducted to assess the importance of soil properties, plant diversity, and soil microbial diversity in driving EMF. Furthermore, a structural equation model (SEM) was employed to analyze the indirect and direct impacts of these predictors on EMF. Our study showed that plant, soil bacterial, fungal, and archaeal diversity gradually decreased with increasing desertification intensity. However, only AMF diversity was found to be less sensitive to desertification. Similarly, EMF also showed a significant decline with increasing desertification. Importantly, both plant and soil microbial diversity were positively associated with EMF during desertification processes. The random forest model and SEM revealed that both plant and soil microbial diversity were identified as important and direct predictors of EMF during desertification processes. This highlights the primary influence of above- and below-ground biodiversity in co-regulating the response of EMF to grassland desertification. These findings have important implications for planned ecosystem restoration and sustainable grassland management.
RESUMEN
OBJECTIVE: This study assessed the impacts of in vitro culture times of cleavage embryos on clinical pregnancy outcomes. METHODS: This retrospective cohort study was performed at the Reproductive Medicine Department of Hainan Modern Women and Children's Hospital in China between January 2018 and December 2022. Patients who first underwent frozen embryo transfer with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles on day 3 were included. According to the time of embryo culture after thawing, the embryos were divided into long-term culture group(18-20 h) and short-term culture group (2-4 h). The clinical pregnancy rate was regarded as he primary outcome. To minimize confounding factors and reduce selection bias, the propensity score matching was used to balance the effects of known confounding factors and to reduce selection bias. Stratified analyses and multiple logistic regression analyses were used to evaluate the risk factors affecting the clinical pregnancy outcomes after matching. RESULTS: General characteristics between two groups were comparable after matching. In the long-term culture group, 266/381 (69.81%) embryos had more than 10 blastomeres, and 75/381 (19.68%) reached the morula stage. After overnight culture, the implantation rate (27.97% vs. 14.28%, P = 0.018) and clinical pregnancy rate (38.46% vs. 22.5%, P = 0.05) were increased in the group with proliferating blastomeres. The long-term culture group trended to have a higher clinical pregnancy rate compared with the short-term culture group (35.74% vs. 29.79%). No statistical differences in clinical pregnancy outcomes between the two groups were observed after matching, including the rates of implantation (25.46% vs23.98%), miscarriages (25% vs. 22.85%), ongoing pregnancy rate (76.2% vs. 77.15%) and live birth rate (26.8% vs. 22.98%). Stratified analyses were performed according to the age of the patients. After matching, there were no significant differences in the clinical pregnancy, implantation and miscarriage rates between the two groups for patients > 35 or ≤ 35 years of age. Subgroup analyses were performed according to the quality of the transferred embryos. There were no significant differences in the clinical outcomes, between two groups after embryos transferred with the same quality. Multivariate Logistic regression analysis was used to evaluate the influencing factors of clinical pregnancy outcomes after matching. Culture time was not found to be an independent predictor for clinical pregnancy [OR 0.742, 95%CI 0.487 ~ 1.13; P = 0.165]. The age of oocyte retrieval [OR 0.906, 95%CI 0.865 ~ 0.949; P <0.001] and the number of high-quality embryos transferred [OR 1.787, 95%CI 1.256 ~ 2.543; P = 0.001] were independent factors affecting clinical pregnancy outcomes. CONCLUSIONS: In vitro 18-20 h culture of embryos with either good-or non-good-quality will not adversely affect the clinical pregnancy.
Asunto(s)
Aborto Espontáneo , Resultado del Embarazo , Embarazo , Niño , Humanos , Masculino , Femenino , Resultado del Embarazo/epidemiología , Estudios Retrospectivos , Semen , Fertilización In Vitro , Transferencia de Embrión/efectos adversos , Índice de Embarazo , Aborto Espontáneo/etiologíaRESUMEN
BACKGROUND: Dysregulated epithelial-mesenchymal transition (EMT) is involved in cervical cancer metastasis and associated with histone acetylation. However, the underlying molecular mechanisms of histone acetylation in cervical cancer EMT and metastasis are still elusive. METHODS: We systematically investigated the expression patterns of histone acetylation genes and their correlations with the EMT pathway in cervical cancer. The expression of CSRP2BP among cervical cancer tissues and cell lines was detected using Western blotting and immunohistochemistry analyses. The effects of CSRP2BP on cervical cancer cell proliferation and tumorigenicity were examined by cell growth curve, EdU assay, flow cytometry and xenotransplantation assays. Wound healing assays, transwell migration assays and pulmonary metastasis model were used to evaluate the effects of CSRP2BP on cell invasion and metastasis of cervical cancer cells in vivo and in vitro. RNA-seq, chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP) and luciferase reporter assays were used to uncover the molecular mechanisms of CSRP2BP in promoting cervical cancer EMT and metastasis. RESULTS: We prioritized a top candidate histone acetyltransferase, CSRP2BP, as a key player in cervical cancer EMT and metastasis. The expression of CSRP2BP was significantly increased in cervical cancer tissues and high CSRP2BP expression was associated with poor prognosis. Overexpression of CSRP2BP promoted cervical cancer cell proliferation and metastasis both in vitro and in vivo, while knockdown of CSRP2BP obtained the opposite effects. In addition, CSRP2BP promoted resistance to cisplatin chemotherapy. Mechanistically, CSRP2BP mediated histone 4 acetylation at lysine sites 5 and 12, cooperated with the transcription factor SMAD4 to bind to the SEB2 sequence in the N-cadherin gene promotor and upregulated N-cadherin transcription. Consequently, CSRP2BP promoted cervical cancer cell EMT and metastasis through activating N-cadherin. CONCLUSIONS: This study demonstrates that the histone acetyltransferase CSRP2BP promotes cervical cancer metastasis partially through increasing the EMT and suggests that CSRP2BP could be a prognostic marker and a potential therapeutic target for combating cervical cancer metastasis.
Asunto(s)
Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Cadherinas/genética , Cadherinas/metabolismo , Transición Epitelial-Mesenquimal/genética , Histonas/metabolismo , Movimiento Celular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proliferación Celular , Metástasis de la NeoplasiaRESUMEN
Diffuse alveolar epithelial cell (AEC) death occurs extensively during acute lung injury (ALI). Due to the limited proliferative capacity of alveolar type 1 epithelial (AT1) cells, the differentiation and regenerative capacity of alveolar type 2 epithelial (AT2) cells are required to restore the barrier function of AECs. However, during lung injury, AT1 cells are particularly susceptible to injury, and ATII cells die in the presence of severe or certain types of injury. This disruption ultimately results in a hindrance to the ability of AT2 cells to proliferate and differentiate into AT1 cells in time to repair the extensively damaged AECs. Therefore, understanding the mechanism of injury death of AT2 cells may be beneficial to reverse the above situation. This article reviews the main death modes of AT2 cells, including apoptosis, necrosis, necroptosis, pyroptosis, autophagic cell death, and ferroptosis. It compares the various forms of death, showing that various cell injury death modes have unique action mechanisms and partially overlapping pathways. Studying the mechanism of AT2 cell death is helpful in screening and analyzing the target pathway of AEC barrier function recovery. It opens up new ideas and strategies for preventing and treating ALI.
Asunto(s)
Lesión Pulmonar Aguda , Células Epiteliales Alveolares , Humanos , Células Epiteliales Alveolares/metabolismo , Lesión Pulmonar Aguda/metabolismo , Diferenciación Celular/fisiología , Células Cultivadas , Apoptosis/fisiología , PulmónRESUMEN
Healthy birth and child development are the prerequisite for improving the overall quality of the population. However, premature ovarian failure(POF) threatens the reproductive health of women. The incidence of this disease has been on the rise, and it tends to occur in the young. The causes are complex, involving genetics, autoimmune, infectious and iatrogenic factors, but most of the causes remain unclear. At the moment, hormone replacement therapy and assisted reproductive technology are the main clinical approaches. According to traditional Chinese medicine(TCM), kidney deficiency and blood stasis are one of the major causes of POF, and TCM with the effects of tonifying kidney and activating blood has a definite effect. Through clinical trials, TCM prescriptions for POF have excellent therapeutic effect as a result of multi-target regulation and slight toxicity. In particular, they have no obvious side effects. A large number of studies have shown that the kidney-tonifying and blood-activating TCM can regulate the neuroendocrine function of hypothalamic-pituitary-ovarian axis, improve ovarian hemodynamics and microcirculation, reduce the apoptosis of granulosa cells, alleviate oxidative stress injury, and modulate immunologic balance. The mechanism is that it regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt), vascular endothelial growth factor(VEGF), transforming growth factor(TGF)-ß/Smads, nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE), and nuclear factor-kappa B(NF-κB) signaling pathways. This article summarized the pathological mechanisms of tonifying kidney and activating blood TCM in the prevention and treatment of POF and explored the biological basis of its multi-pathway and multi-target characteristics in the treatment of this disease. As a result, this study is expected to serve as a reference for the treatment of POF with the tonifying kidney and activating blood therapy.
Asunto(s)
Insuficiencia Ovárica Primaria , Niño , Humanos , Femenino , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Factor A de Crecimiento Endotelial Vascular , Medicina Tradicional China , FN-kappa B , RiñónRESUMEN
Ecosystem functioning plays a crucial role in maintaining human welfare. Terrestrial ecosystems provide multiple ecosystem services simultaneously, such as carbon sequestration, nutrient cycling, water purification, and biodiversity conservation, known as ecosystem multifunctionality (EMF). However, the mechanisms by which biotic and abiotic factors, and their interactions regulate EMF in grasslands are unclear. We conducted a transect survey to illustrate the single and combined effects of biotic factors (including plant species diversity, trait-based functional diversity, community-weighted mean (CWM) of traits, and soil microbial diversity) and abiotic factors (including climate and soil) on EMF. Eight functions were investigated, including aboveground living biomass and litter biomass, soil bacterial biomass, fungal biomass, arbuscular mycorrhizal fungi biomass, and soil organic carbon storage, total carbon storage and total nitrogen storage. We detected a significant interactive effect between plant species diversity and soil microbial diversity on the EMF; Structural equation model showed that soil microbial diversity indirectly affected EMF by regulating plant species diversity. These findings highlight the importance of the interaction effect of above- and below-ground diversity on EMF. Both plant species diversity and functional diversity had similar explanatory power for the variation in EMF, implying that niche differentiation and multifunctional complementarity among plant species and traits are essential in regulating the EMF. Furthermore, the effects of abiotic factors on EMF were stronger than those of biotic factors via direct and indirect pathways affecting above- and below-ground biodiversity. As a dominant regulator, the soil sand content was negatively correlated with EMF. These findings indicate the vital role of abiotic mechanisms in affecting EMF, and deepen our understanding of the single and combined effects of biotic and abiotic factors on EMF. We conclude that soil texture and plant diversity, representing crucial abiotic and biotic factors, respectively, are important determinants of the EMF of grasslands.
Asunto(s)
Ecosistema , Pradera , Humanos , Carbono , Suelo/química , Biodiversidad , China , Biomasa , PlantasRESUMEN
Plants have evolved two layers of protection against biotic stress: PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI). The primary mechanism of ETI involves nucleotide-binding leucine-rich repeat immune receptors (NLRs). Although NLR genes have been studied in several plant species, a comprehensive database of NLRs across a diverse array of species is still lacking. Here, we present a thorough analysis of NLR genes across 100 high-quality plant genomes (PlantNLRatlas). The PlantNLRatlas includes a total of 68,452 NLRs, of which 3,689 are full-length and 64,763 are partial-length NLRs. The majority of NLR groups were phyletically clustered. In addition, the domain sequences were found to be highly conserved within each NLR group. Our PlantNLRatlas dataset is complementary to RefPlantNLR, a collection of NLR genes which have been experimentally confirmed. The PlantNLRatlas should prove helpful for comparative investigations of NLRs across a range of plant groups, including understudied taxa. Finally, the PlantNLRatlas resource is intended to help the field move past a monolithic understanding of NLR structure and function.
RESUMEN
Soil microbes play crucial roles in grassland ecosystem functions, such as soil carbon (C) pool and nutrient cycle. Soil microbes in grasslands are susceptible to the degradation mediated by climate change and anthropogenic disturbance. However, research on how the degradation influences the diversity and community structure of different soil microbial taxa is relatively scarce. We conducted a large-scale field survey to describe the effects of four degradation levels (PD: potential degradation, LD: light degradation, MD: moderate degradation, and SD: severe degradation) on soil bacterial and fungal community in the semi-arid grasslands of northern China. We found that soil moisture, nutrients, and clay content decreased, but soil sand content increased along the increasing degradation gradient. However, the degradation had no effects on soil pH and the C:N ratio. Grassland degradation had non-significant effect on soil bacterial diversity, but it significantly affected soil bacterial community structure. The degradation decreased soil fungal diversity and had a relatively larger influence on the community structure of soil fungi than that of bacteria. The community composition and structure of soil fungi were mainly affected by soil nutrients and texture, while those of soil bacteria were mainly affected by soil pH. These results indicate that changes in soil properties induced by grassland degradation mainly drive the variation in the soil fungal community and have less effect on the soil bacterial community. This study reveals the sensitivity of soil fungal community to grassland degradation, highlighting the priority of soil fungal community for the management and restoration of degraded grasslands.
RESUMEN
MEME (Multiple Em for Motif Elicitation) is the most commonly used tool to identify motifs within deoxyribonucleic acid (DNA) or protein sequences. However, the results generated by the MEMEare saved using file formats .xml and .txt, which are difficult to read, visualize, or integrate with other widely used phylogenetic tree packages, such as ggtree. To overcome this problem, we developed the ggmotif R package, which provides two easy-to-use functions that can facilitate the extraction and visualization of motifs from the results files generated by the MEME. ggmotif can extract the information of the location of motif(s) on the corresponding sequence(s) from the .xml format file and visualize it. Additionally, the data extracted by ggmotif can be easily integrated with the phylogenetic data. On the other hand, ggmotif can obtain the sequence of each motif from the .txt format file and draw the sequence logo with the function ggseqlogo from the ggseqlogo R package. The ggmotif R package is freely available (including examples and vignettes) from GitHub at https://github.com/lixiang117423/ggmotif or from CRAN at https://CRAN.R-project.org/package=ggmotif.
Asunto(s)
Programas Informáticos , Filogenia , Posición Específica de Matrices de Puntuación , Secuencia de AminoácidosRESUMEN
BACKGROUND: Gastric cancer has a high incidence and mortality rate. Angiogenesis is necessary for tumor infiltration and metastasis and affects patient prognosis. YKL-39 has monocyte chemotactic activity and pro-angiogenic activity in some tumors. In this study, we investigated the relationship between YKL-39 and tumor-associated macrophages and microangiogenesis in gastric cancer to determine its potential as a prognostic biomarker. MATERIALS AND METHODS: A total of 119 patients with gastric cancer who had undergone gastrectomy at the 940th Hospital of the Joint Security Force between 2014 and 2018 were included in this study. We assayed the protein expression of YKL-39, CD68, and CD34 by immunohistochemistry in tissues of 119 patients with gastric cancer, as well as the intracellular expression of YKL-39 and CD68 by immunofluorescence. Data were analyzed with SPSS Statistics 25.0 to explore the impact of expression of YKL-39, CD68, and CD34 in gastric cancer patients and the relationship among them. RESULTS: Our results show that YKL-39 was expressed in both the nucleus and cytoplasm of gastric cancer cells and tumor mesenchyme. YKL-39 protein expression was associated with the depth of tumor infiltration, lymph node metastasis, and TNM stage; CD68 protein expression was associated with lymph node metastasis and TNM stage; CD34 protein expression was not associated with clinicopathological characteristics. Expression of YKL-39 was positively correlated with CD68 and CD34 (p < 0.001), and high expression of YKL-39 was associated with poor prognosis (p < 0.05). CONCLUSION: In gastric cancer, YKL-39 expression is positively correlated with the degree of tumor-associated macrophage infiltration and angiogenesis, and is a potential prognostic marker for gastric cancer.
Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Pronóstico , Macrófagos Asociados a Tumores , Metástasis Linfática , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Neovascularización Patológica/patología , Biomarcadores de Tumor/metabolismo , Estadificación de NeoplasiasRESUMEN
IL-38, an anti-inflammatory cytokine, is a key regulator of homeostasis in host immunity. Intestinal immunity plays a critical role in defence against pathogenic invasion, as it is the largest surface organ and the most common entry point for micro-organisms. Dysregulated IL-38 activity is observed in several autoimmune diseases including systemic lupus erythematosus and atherosclerosis. The protective role of IL-38 is well illustrated in experimental colitis models, showing significantly worse colitis in IL-38 deficient mice, compared to wildtype mice. Moreover, exogenous IL-38 has been shown to ameliorate experimental colitis. Surprisingly, upregulated IL-38 is detected in inflamed tissue from inflammatory bowel disease patients, consistent with increased circulating cytokine levels, demonstrating the complex nature of host immunity in vivo. However, colonic IL-38 is significantly reduced in malignant tissues from patients with colorectal cancer (CRC), compared to adjacent non-cancerous tissue. Additionally, IL-38 expression in CRC correlates with 5-year survival, tumour size and differentiation, suggesting IL-38 plays a protective role during the development of CRC. IL-38 is also an independent biomarker for the prognosis of CRC, offering useful information in the management of CRC. Taken together, these data demonstrate the role of IL-38 in the maintenance of normal intestinal mucosal homeostasis, but that dysregulation of IL-38 contributes to initiation of chronic inflammatory bowel disease (resulting from persistent local inflammation), and that IL-38 provides protection during the development of colorectal cancer. Such data provide useful information for the development of novel therapeutic targets in the management of intestinal diseases for more precise medicine.
Asunto(s)
Colitis , Neoplasias Colorrectales , Enfermedades Inflamatorias del Intestino , Ratones , Animales , Citocinas , Neoplasias Colorrectales/patologíaRESUMEN
Growing evidence indicates that testosterone is a conspicuous marker for assessing male bone mineral density (BMD). However, research regarding testosterone levels and BMD is sparse and controversial for females. Hence, we aimed to investigate the association between testosterone levels and BMD among adult females aged 40-60 years in the United States. In this cross-sectional study, all participants were part of the National Health and Nutrition Examination Survey (2011-2016). A weighted general linear model was used to estimate the association between testosterone levels and lumbar BMD. Age, race, income level, education level, body mass index (BMI), blood urea nitrogen (BUN) level, serum uric acid (UA) level, serum calcium (Ca) level, serum phosphorus (P) level, the use of oral contraceptive pills, the use of hormone replacement therapy (HRT), smoking status, drinking status, and the use of corticosteroids were adjusted using a weighted multiple regression model. Subgroup analyses were performed using the same regression model. We included 2198 female participants in the study, and testosterone levels were positively associated with lumbar BMD after adjusting for all the covariates (ß = 1.12, 95% CI 0.31, 1.93). In subgroup analyses, the associations in the fourth quartile of testosterone levels were stronger for the participants aged 40-50 years old (quartile 4, ß = 42.92, 95% CI 7.53, 78.30 vs. quartile 1) and 50 to 60-year-old (quartile 4, ß = 32.41, 95% CI 0.14, 64.69 vs. quartile 1). Similar results were found in other subgroups, including subgroups for race (Non-Hispanic Black, Other), income level (income ≤ 1.3, income > 3.5), education level (college or higher), BMI > 25 kg/m2, BUN levels ≤ 20 mg/dL, UA levels ≤ 6 mg/dL, Ca levels ≤ 10.1 mg/dL, P levels ≤ 5 mg/dL, drinking status, never smoker, never taking birth control pills, and HRT user. There was no interaction among the covariates in the association between lumbar BMD and testosterone levels (P for interaction > 0.05). In US adult females aged 40-60 years, the testosterone level was a positive predictor of the lumbar BMD after adjusting for covariates.
Asunto(s)
Densidad Ósea , Ácido Úrico , Absorciometría de Fotón/métodos , Adulto , Calcio , Anticonceptivos Orales , Estudios Transversales , Femenino , Humanos , Vértebras Lumbares , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Fósforo , Testosterona , Estados UnidosRESUMEN
BACKGROUND: Studies have shown that abnormalities in the decidualization process were closely related to recurrent implantation failure (RIF). Prokineticin 2 (PK2) is a secreted protein with angiogenic and tissue remodeling functions but its role in the endometrium is unknown. METHODS: PK2 levels and its receptor PKR1 mRNA and protein levels in mid-secretory endometrium from normal and RIF women were examined by real-time PCR and western blotting, respectively. The effects of PK2 were evaluated by overexpressed PK2 in immortalized endometrial T-HESC cells using lentivirus vector and found different expression of Matrix metalloproteinase 9(MMP9) and lncRNA LUCAT1 by RNA-sequencing. The ability of PK2 to regulate LUCAT1 and MMP9 was verified in endometrial cells by real-time PCR and western blotting. RESULTS: Using endometrial biopsies from normal and RIF patients, we found increased expression of PK2, together with its receptor PKR1 in RIF patients. We then overexpressed PK2 in immortalized endometrial T-HESC cells using lentivirus vector and found decreased expression of Matrix metalloproteinase 9(MMP9), and increased expression of lncRNA LUCAT1. We verified the ability of PK2 to stimulate LUCAT1 and decrease MMP9 in endometrial cells. We further demonstrated that increased expression of a long noncoding RNA LUCAT1 and decreased expression of MMP9 in endometrial biopsies of patients with RIF. Thus, we highlighted the important role of PK2 and its receptor PKR1 in decidualization and RIF. CONCLUSION: Prokineticin 2 and its receptor are important in endometrium decidualization. PK2 may affect endometrial decidualization through the LUCAT1- MMP9 pathway, thereby affecting embryo implantation.
Asunto(s)
Metaloproteinasa 9 de la Matriz , ARN Largo no Codificante , Implantación del Embrión/genética , Endometrio/metabolismo , Femenino , Humanos , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , ARN Largo no Codificante/genética , ARN Mensajero/metabolismoRESUMEN
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in women of childbearing age. Recent studies suggest important roles for lncRNAs in PCOS development. Based on the hypothesis that lncRNAs are able to regulate mRNA functions by competitive binding to shared miRNAs, the present work sought to construct a PCOS-related lncRNA-mRNA network (PCLMN) to identify key lncRNAs with dysregulated expression and potential prognostic and therapeutic relevance. A global background network was constructed after retrieving lncRNA-miRNA and miRNA-mRNA pairs from the lncRNASNP2, miRTarBase and StarBase databases. Based on gene expression profiles from ovarian granulosa cells from PCOS patients and controls in the GEO's GSE95728 dataset, the PCLMN was then constructed by applying hypergeometric testing. Using topological analysis, we identified 3 lncRNAs (LINC00667, AC073172.1 and H19) ranking within the top-ten gene lists for all three centrality measures. We then explored their subcellular localization, performed functional module analyses, and identified 4 sex hormone-related transcription factors as potential regulators of their expression. Significant associations with inflammation, oxidative stress, and apoptosis-related processes and pathways were revealed for the key lncRNAs in our PCMLN. Further studies verifying the mRNA/lncRNA relationships identified herein are needed to clarify their clinical significance.
Asunto(s)
Regulación de la Expresión Génica/genética , Redes Reguladoras de Genes/genética , Síndrome del Ovario Poliquístico/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , Femenino , HumanosRESUMEN
OBJECTIVE: To study the association between hyperandrogenism (HA) and adverse pregnancy outcomes in patients with different polycystic ovary syndrome phenotypes undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). METHODS: We reviewed all eligible articles published up to October 2020 after searching in PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, and CNKI databases. The primary outcomes were the clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR), whereas the secondary outcomes were the number of retrieved oocytes and endometrial thickness. Risk ratios (RRs) or mean differences with 95% confidence intervals (CIs) were calculated to estimate the HA impact on IVF/ICSI outcomes in patients with polycystic ovary syndrome (PCOS) phenotypes. RESULTS: Of the 789 trials identified, nine retrospective studies involving 3037 patients with PCOS were included. Compared to the PCOS group with normal androgen levels, the PCOS group with HA exhibited increased MR (RR: 1.56, 95% CI: 1.13, 2.16); the CPR (RR: 0.88, 95% CI: 0.77, 1.01) and LBR (RR: 0.79, 95% CI: 0.55, 1.11) were not significantly different between these groups. Subgroup analysis revealed that the CPR was lower in the polycystic ovarian (PCO)-morphology + HA + oligo-anovulation (AO) group than in the PCO + AO group (RR: 0.81, 95% CI: 0.67, 0.99). Among Asians, the PCOS/HA group had increased MR (RR: 1.56, 95% CI: 1.06, 2.31) and showed thinner endometrial thickness. However, among Caucasians, no differences were observed between the two groups. CONCLUSIONS: HA may have adverse effects on clinical pregnancy and miscarriage outcomes in different PCOS phenotypes, particularly among Asians.