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1.
Acad Radiol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38658211

RESUMO

RATIONALE AND OBJECTIVES: The aim of this study was to develop a deep learning radiomics nomogram (DLRN) based on B-mode ultrasound (BMUS) and color doppler flow imaging (CDFI) images for preoperative assessment of lymphovascular invasion (LVI) status in invasive breast cancer (IBC). MATERIALS AND METHODS: In this multicenter, retrospective study, 832 pathologically confirmed IBC patients were recruited from eight hospitals. The samples were divided into training, internal test, and external test sets. Deep learning and handcrafted radiomics features reflecting tumor phenotypes on BMUS and CDFI images were extracted. The BMUS score and CDFI score were calculated after radiomics feature selection. Subsequently, a DLRN was developed based on the scores and independent clinic-ultrasonic risk variables. The performance of the DLRN was evaluated for calibration, discrimination, and clinical usefulness. RESULTS: The DLRN predicted the LVI with accuracy, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI 0.90-0.95), 0.91 (95% CI 0.87-0.95), and 0.91 (95% CI 0.86-0.94) in the training, internal test, and external test sets, respectively, with good calibration. The DLRN demonstrated superior performance compared to the clinical model and single scores across all three sets (p < 0.05). Decision curve analysis and clinical impact curve confirmed the clinical utility of the model. Furthermore, significant enhancements in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indicated that the two scores could serve as highly valuable biomarkers for assessing LVI. CONCLUSION: The DLRN exhibited strong predictive value for LVI in IBC, providing valuable information for individualized treatment decisions.

2.
Cell Rep ; 43(4): 114088, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38602878

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) features an immunosuppressive tumor microenvironment (TME) that resists immunotherapy. Tumor-associated macrophages, abundant in the TME, modulate T cell responses. Bone marrow stromal antigen 2-positive (BST2+) macrophages increase in KrasG12D/+; Trp53R172H/+; Pdx1-Cre mouse models during PDAC progression. However, their role in PDAC remains elusive. Our findings reveal a negative correlation between BST2+ macrophage levels and PDAC patient prognosis. Moreover, an increased ratio of exhausted CD8+ T cells is observed in tumors with up-regulated BST2+ macrophages. Mechanistically, BST2+ macrophages secrete CXCL7 through the ERK pathway and bind with CXCR2 to activate the AKT/mTOR pathway, promoting CD8+ T cell exhaustion. The combined blockade of CXCL7 and programmed death-ligand 1 successfully decelerates tumor growth. Additionally, cGAS-STING pathway activation in macrophages induces interferon (IFN)α synthesis leading to BST2 overexpression in the PDAC TME. This study provides insights into IFNα-induced BST2+ macrophages driving an immune-suppressive TME through ERK-CXCL7 signaling to regulate CD8+ T cell exhaustion in PDAC.


Assuntos
Antígeno 2 do Estroma da Médula Óssea , Proteínas Ligadas por GPI , Interferon-alfa , Neoplasias Pancreáticas , Macrófagos Associados a Tumor , Animais , Feminino , Humanos , Camundongos , Antígenos CD/metabolismo , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Proteínas Ligadas por GPI/metabolismo , Tolerância Imunológica , Interferon-alfa/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/metabolismo , Transdução de Sinais , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/patologia
3.
Sci Rep ; 14(1): 5228, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433277

RESUMO

BAZ2A, an epigenetic regulatory factor that affects ribosomal RNA transcription, has been shown to be highly expressed in several cancers and promotes tumor cell migration. This study explored the expression and mechanism of BAZ2A in tumorigenesis at the pan-cancer level. The Cancer Genome Atlas, Gene Expression Omnibus databases and TIMER2.0, cBioPortal and other tools were used to analyze the level of expression of BAZ2A in various tumor tissues and to examine the relationship between BAZ2A and survival, prognosis, mutation and immune invasion. In vitro experiments were performed to assess the function of BAZ2A in cancer cells. Using combined transcriptome and proteome analysis, we examined the possible mechanism of BAZ2A in tumors. BAZ2A exhibited high expression levels in multiple tumor tissues and displayed a significant association with cancer patient prognosis. The main type of BAZ2A genetic variation in cancer is gene mutation. Downregulation of BAZ2A inhibited proliferation, migration, and invasion and promoted apoptosis in LM6 liver cancer cell. The mechanism of BAZ2A in cancer development may involve lipid metabolism. These results help expand our understanding of BAZ2A in tumorigenesis and development and suggest BAZ2A may serve as a prognostic and diagnostic factor in several cancers.


Assuntos
Neoplasias Hepáticas , Multiômica , Humanos , Prognóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Carcinogênese , Transformação Celular Neoplásica , Proteínas que Contêm Bromodomínio , Proteínas Cromossômicas não Histona
4.
Biochem Biophys Res Commun ; 708: 149810, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38531222

RESUMO

At present, the physiological roles of various hormones in fish glucose metabolism have been elucidated. Spexin, a 14-amino acids polypeptide, is highly conserved in many species and has functions such as reducing body weight and improving insulin resistance. In this paper, the open reading frame (ORF) of spx21 in grass carp (Ctenopharyngodon idella) was cloned, and the tissue distribution of spx1 and spx2, their direct and indirect regulatory effects on glucose metabolism of grass carp were investigated. The ORF of spx2 gene in grass carp was 279 bp in length. Moreover, spx1 was highly expressed in the adipose tissue, while spx2 was highly expressed in the brain. In vitro, SPX1 and SPX2 showed opposite effects on the glycolytic pathway in the primary hepatocytes. In vivo, intraperitoneal injection of SPX1 and SPX2 significantly reduced serum glucose levels and increased hepatopancreas glycogen contents. Meanwhile, SPX1 and SPX2 promoted the expression of key genes of glycolysis (pk) and glycogen synthesis (gys) in the hepatopancreas at 3 h post injection. As for indirect effects, 1000 nM SPX1 and SPX2 significantly increased insulin-mediated liver type phosphofructokinase (pfkla) mRNA expression and enhanced the inhibitory effects of insulin on glucose-6-phosphatase (g6pase), phosphoenolpyruvate carboxykinase (pepck), glycogen phosphorylase L (pygl) mRNA expression. Our results show that SPX1 and SPX2 have similar indirect effects on the regulation of glucose metabolism that enhance insulin activity, but they exhibit opposite roles in terms of direct effects.


Assuntos
Carpas , Glucose , Animais , Glucose/metabolismo , Carpas/metabolismo , Insulina , RNA Mensageiro/genética , Glicogênio , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo
5.
Nature ; 627(8005): 847-853, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38480885

RESUMO

Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain mediate recognition of strain-specific pathogen effectors, typically via their C-terminal ligand-sensing domains1. Effector binding enables TIR-encoded enzymatic activities that are required for TIR-NLR (TNL)-mediated immunity2,3. Many truncated TNL proteins lack effector-sensing domains but retain similar enzymatic and immune activities4,5. The mechanism underlying the activation of these TIR domain proteins remain unclear. Here we show that binding of the TIR substrates NAD+ and ATP induces phase separation of TIR domain proteins in vitro. A similar condensation occurs with a TIR domain protein expressed via its native promoter in response to pathogen inoculation in planta. The formation of TIR condensates is mediated by conserved self-association interfaces and a predicted intrinsically disordered loop region of TIRs. Mutations that disrupt TIR condensates impair the cell death activity of TIR domain proteins. Our data reveal phase separation as a mechanism for the activation of TIR domain proteins and provide insight into substrate-induced autonomous activation of TIR signalling to confer plant immunity.


Assuntos
Trifosfato de Adenosina , Arabidopsis , NAD , Nicotiana , Separação de Fases , Proteínas de Plantas , Domínios Proteicos , Trifosfato de Adenosina/metabolismo , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/imunologia , Proteínas de Arabidopsis/metabolismo , Morte Celular , Mutação , NAD/metabolismo , Nicotiana/genética , Nicotiana/imunologia , Nicotiana/metabolismo , Proteínas NLR/química , Proteínas NLR/genética , Proteínas NLR/imunologia , Proteínas NLR/metabolismo , Doenças das Plantas/imunologia , Imunidade Vegetal/genética , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/imunologia , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas , Domínios Proteicos/genética , Receptores Imunológicos/química , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Receptores Imunológicos/metabolismo , Transdução de Sinais , Receptores Toll-Like/química , Receptores de Interleucina-1/química
6.
Pancreas ; 53(3): e288-e297, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38277420

RESUMO

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal diseases globally, boasting a grim 5-year survival prognosis. The origin cell and the molecular signaling pathways that drive PDAC progression are not entirely understood. This review comprehensively outlines the categorization of PDAC and its precursor lesions, expounds on the creation and utility of genetically engineered mouse models used in PDAC research, compiles a roster of commonly used markers for pancreatic progenitors, duct cells, and acinar cells, and briefly addresses the mechanisms involved in the progression of PDAC. We acknowledge the value of precise markers and suitable tracing tools to discern the cell of origin, as it can facilitate the creation of more effective models for PDAC exploration. These conclusions shed light on our existing understanding of foundational genetically engineered mouse models and focus on the origin and development of PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Camundongos , Animais , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Células Acinares/metabolismo , Ductos Pancreáticos/patologia
7.
Dalton Trans ; 53(7): 3027-3038, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38269582

RESUMO

Tin dioxide (SnO2)-based electronic materials and gas sensors have attracted extensive attention from academia and industry. Herein we report the preparation of two-dimensional (2D) porous SnO2 flakes by thermal oxidation of 2D SnS flakes that serve as a self-sacrificial template. An oxidation-enabled, temperature-dependent matter conversion from SnS through three-phase SnS-SnS2-SnO2 (400 °C) and two-phase SnS2-SnO2 (600 °C) to pure-phase SnO2 (≥800 °C) is disclosed by means of combined XRD, TG-DSC and XPS studies. Meanwhile, the associated chemical reactions and the mass and heat changes during this solid-state conversion process are clarified. The as-prepared 2D SnO2 flakes exhibit structural porosity with tunable pore sizes and crystallite sizes/crystallinity, resulting in superior potential for NO2 sensing. At the optimized operating temperature of 200 °C, the prototype gas sensors made of porous SnO2 flakes show competitive sensing parameters in a broad NO2 concentration range of 50 ppb-10 ppm in terms of high response, faster response/recovery speeds, and good selectivity and stability. A sensing mechanism involving the adsorption and desorption of NO2/O2 molecules and the possible surface reactions is further rationalized for the SnO2 NO2 gas sensors.

9.
Sci Total Environ ; 915: 170128, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38242464

RESUMO

Studies have revealed neurotoxicity, hepatotoxicity, and developmental and reproductive toxicity in mice exposed to aluminum. However, relatively few studies have been conducted to clarify the mechanism underlying the impact of embryonic exposure to aluminum on the development of the male reproductive system in offspring. Pregnant mice were administered aluminum chloride (AlCl3) by gavage from day 12.5 of gestation until birth. Our findings demonstrated that embryonic exposure to AlCl3 disrupted testicular development and spermatogenesis by impairing testicular architecture, reducing sperm count, and upregulating the expression of tight junction (TJ) protein between Sertoli cells (SCs). Further in vitro studies revealed that treatment with AlCl3 stabilized TJ proteins Occludin and ZO-1 expression by inhibiting ERK signaling pathway activation, thereby upregulating Slc25a5 expression which induced ATP production leading to disruption of cytoskeletal protein homeostasis. Therefore, the study provided a new mechanistic insight into how AlCl3 exposure interfered with testicular development and spermatogenesis while suggesting that Slc25a5 might be a target affected by AlCl3 influencing cell metabolism.


Assuntos
Alumínio , Junções Íntimas , Gravidez , Feminino , Masculino , Camundongos , Animais , Cloreto de Alumínio , Alumínio/metabolismo , Junções Íntimas/metabolismo , Sêmen , Testículo/metabolismo , Espermatogênese , Proteínas de Junções Íntimas/metabolismo
10.
Acad Radiol ; 31(1): 93-103, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37544789

RESUMO

RATIONALE AND OBJECTIVES: This study aimed to create and verify a nomogram for preoperative prediction of Ki-67 expression in breast malignancy to assist in the development of personalized treatment strategies. MATERIALS AND METHODS: This retrospective study received approval from the institutional review board and included a cohort of 197 patients with breast malignancy who were admitted to our hospital. Ki-67 expression was divided into two groups based on a 14% threshold: low and high. A radiomics signature was built utilizing 1702 radiomics features based on an intra- and peritumoral (10 mm) regions of interest. Using multivariate logistic regression, radiomics signature, and ultrasound (US) characteristics, the nomogram was developed. To evaluate the model's calibration, clinical application, and predictive ability, decision curve analysis (DCA), the calibration curve, and the receiver operating characteristic curve were used, respectively. RESULTS: The final nomogram included three independent predictors: tumor size (P = .037), radiomics signature (P < .001), and US-reported lymph node status (P = .018). The nomogram exhibited satisfactory performance in the training cohort, demonstrating a specificity of 0.944, a sensitivity of 0.745, and an area under the curve (AUC) of 0.905. The validation cohort recorded a specificity of 0.909, a sensitivity of 0.727, and an AUC of 0.882. The DCA showed the nomogram's clinical utility, and the calibration curve revealed a high consistency among the expected and detected values. CONCLUSION: The nomogram used in this investigation can accurately predict Ki-67 expression in people with malignant breast tumors, helping to develop personalized treatment approaches.


Assuntos
Neoplasias da Mama , Nomogramas , Humanos , Feminino , Antígeno Ki-67 , Radiômica , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia
11.
J Environ Sci (China) ; 139: 308-319, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38105057

RESUMO

Aluminum (Al) can lead to an exposure of creature in varieties ways for its universality, and it could disturb normal physiological metabolism, with the damage to multisystem including reproduction. Since the oocyte quality is critical for female reproduction, we inspected the toxicity of Al on mouse oocyte maturation. We constructed in vitro exposure mouse model, and we found that 5 mmol/L Al had adverse effects on oocyte maturation by impairing organelle and cytoskeleton. Aberrant spindle and misaligned chromosomes which might be considered to be caused by elevated levels of acetylation, as well as abnormal distribution of actin dynamics could hinder normal meiosis of oocytes. Organelle dysfunction indicated that Al affected proteins synthesis, transport and digestion, which would further damage oocyte maturation. In order to explore the mechanism of Al toxicity, our further investigation demonstrated that Al caused mitochondrial dysfunction and imbalance calcium homeostasis, resulting in limited energy supply. Moreover, high level of reactive oxygen species, DNA damage and apoptosis caused by oxidative stress were also the manifestation of Al toxicity on oocytes. In conclusion, our study provided the evidence that Al exposure affected oocyte quality through its effects on spindle organization, actin dynamics, organelle function and the induction of DNA damage-related apoptosis with mouse model.


Assuntos
Actinas , Alumínio , Feminino , Camundongos , Animais , Alumínio/toxicidade , Actinas/metabolismo , Oócitos/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Dano ao DNA , Apoptose
12.
Cancer Med ; 12(24): 22381-22394, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087815

RESUMO

BACKGROUND: Cornichon homolog 4 (CNIH4) belongs to the CNIH family. It functions as an oncogene in many tumors. However, CNIH4's significance in the immune landscape and its predictive potential in cervical cancer (CESC) is unexplored. METHODS: CNIH4 levels and its effect on the survival of patients with CESC were evaluated using data retrieved from The Cancer Genome Atlas (TCGA). The oncogenic effect of CNIH4 in CESC was determined using small interfering RNA-mediated transfected cell lines and tumorigenesis experiments in animal models. RESULTS: Higher expression of CNIH4 was found in advanced tumor and pathological stages, as well as lymph node metastasis. CNIH4 expression correlated positively with the infiltration of macrophages M2 and resting dendritic cells into the affected tissue. Additionally, functional enrichment of RNA-sequencing of CNIH4-knocked down CESC cell lines showed the association of CNIH4 to the PI3K-Akt signaling pathway. Single-sample gene set enrichment analysis highlighted several immune pathways that were elevated in the CESC samples with enhanced levels of CNIH4, including Type-I and Type-II IFN-response pathways. The impact of CNIH4 on drug sensitivity was further assessed using the GDSC database. As CNIH4 is linked to the immune landscape in CESC, this study determined a four-gene risk prediction signature utilizing CNIH4-related immunomodulators. The risk score quantified from the prediction signature was an independent predictive indicator in CESC. Receiver operating characteristic curve analysis verified the good predictive ability of the four-gene signature in TCGA-CESC cohort. Thus, the CNIH4-related model showed potential as an auxiliary TNM staging system tool. CONCLUSION: CNIH4 may be an effective predictive biomarker for patients with cervical cancer, thus providing new ideas and research directions for CESC.


Assuntos
Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Fosfatidilinositol 3-Quinases , Prognóstico , Oncogenes , Adjuvantes Imunológicos , Receptores Citoplasmáticos e Nucleares
13.
Sci Rep ; 13(1): 21603, 2023 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062233

RESUMO

Endometriosis (EMT) is an aggressive disease of the reproductive system, also called "benign cancer". However, effective treatments for EMT are still lacking in clinical practice. Interestingly, immune infiltration is significantly involved in EMT pathogenesis. Currently, no studies have shown the involvement of cuproptosis-related genes (CRGs) in regulating immune infiltration in EMT. This study identified three CRGs such as GLS, NFE2L2, and PDHA1, associated with EMT using machine learning algorithms. These three CRGs were upregulated in the endometrium of patients with moderate/severe EMT and downregulated in patients with infertility. Single sample genomic enrichment analysis (ssGSEA) revealed that these CRGs were closely correlated with autoimmune diseases such as systemic lupus erythematosus. Furthermore, these CRGs were correlated with immune cells such as eosinophils, natural killer cells, and macrophages. Therefore, profiling patients based on these genes aid in a more accurate diagnosis of EMT progression. The mRNA and protein expression levels of GLS, NFE2L2 and PDHA1 were validated by qRT-PCR and WB studies in EMT samples. These findings provide a new idea for the pathology and treatment of endometriosis, suggesting that CRGs such as GLS, NFE2L2 and PDHA1 may play a key role in the occurrence and development of endometriosis.


Assuntos
Doenças Autoimunes , Endometriose , Feminino , Humanos , Endometriose/diagnóstico , Endometriose/genética , Agressão , Algoritmos , Aprendizado de Máquina
14.
Artigo em Inglês | MEDLINE | ID: mdl-37944954

RESUMO

Objective: Hysteroscopy has a positive role in the treatment of abnormal pregnancy, with less damage to the patient, good surgical effect, rapid postoperative recovery, and positive clinical value. This work aimed to explore the role and value of hysteroscopy in preserving the fertility of women with abnormal pregnancies. Methods: 60 patients with abnormal pregnancies in Maanshan Maternal and Child Health Care Hospital were enrolled from December 1, 2021 to December 31, 2022. They were grouped Based on treatment methods: controls (30 cases) and observation groups (30 cases). The average age of the control group was 30.66 ± 5.32 years, with a BMI of 23.36 ± 2.15 kg/m2, and an educational duration of 12.24 ± 3.61 years. The observation group had an average age of 30.18 ± 5.71 years, a BMI of 23.23 ± 2.53 kg/m2, and an educational duration of 12.33 ± 3.28 years. Controls adopted the traditional method (laparoscopic surgery), and an observation group was given with hysteroscopic localization and removal of pregnancy products. The surgical conditions, postoperative recovery, cure rate, complications, preoperative and postoperative blood human chorionic gonadotropin (HCG) level and 36-Item Short Form Health Survey (SF-36) score were compared between the two groups. Results: The observation group had a significantly shorter surgical time of 10.22 minutes, a postoperative hemostasis time of 7.32 days, a menstrual recovery time of 25.73 days, and a time for blood HCG turning negative of 10.76 days compared to the control group (P < .05). The observation group also experienced significantly less intraoperative bleeding, with 6.22 ml compared to 11.69 ml in the control group (P < .05). The cure rate of controls was 83.33%, and that of the observation group was 100.00%. The cure rate of the observation group was obviously higher as against controls. The incidence of complications in the observation group was 6.67%, and that in controls was 26.67%. The incidence of complications in the observation group was clearly lower as against controls. Through operation, the serum HCG levels of two groups were clearly decreased, the SF-36 scores were clearly increased, and the changes in the observation group were more obvious (P < .05). Conclusion: Compared to traditional surgery, hysteroscopy examination demonstrates multiple advantages in the management of abnormal pregnancies, primarily attributed to its minimally invasive nature, high precision, minimal tissue trauma, and quick recovery. This contributes to providing a safer and more effective treatment, increasing patient satisfaction, and reducing healthcare costs, with a positive impact on patient care and clinical practice. However, this work had a relatively small sample size, a single source of patients, and a short duration, which necessitates future validation through the expansion of the sample size and multicenter research. A more comprehensive assessment of long-term postoperative effects is required to confirm the long-term advantages of this treatment method.

15.
Biol Trace Elem Res ; 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37851298

RESUMO

This study aimed to investigate the protective effect of nicotinamide mononucleotide (NMN) on testicular spermatogenesis in aluminum chloride (AlCl3)-exposed rats and to elucidate the potential underlying mechanism. The results indicated that AlCl3-induced testicular damage, leading to reduced sperm quality, increased apoptosis, decreased cell proliferation, and impaired Sertoli cell function in rats. Additionally, glycolytic metabolism was observed to be hindered. However, after NMN treatment, there was a noticeable improvement in testicular damage among the rats, marked by increased sperm quality, reduced apoptosis, enhanced cell proliferation, improved Sertoli cell function, and an activated glycolytic metabolism. The findings of this study suggest that NMN alleviates testicular spermatogenesis impairment induced by AlCl3 exposure through the inhibition of spermatogenic cell apoptosis, promotion of spermatogenic cell proliferation, and activation of glycolytic pathways. The study contributes an experimental foundation for potential future clinical applications of NMN in cases of AlCl3-exposed spermatogenic dysfunction.

16.
Microsc Microanal ; 29(2): 754-761, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-37749726

RESUMO

Deoxynivalenol is a mycotoxin, produced by Fusarium from contaminated corn, wheat, and other grains, that induces multiple effects in humans and animals, including cytotoxic, genotoxic, immunotoxic, and carcinogenic effects. Recent studies show that deoxynivalenol also affects the reproductive system of mammals, including oocyte quality. However, the effects of deoxynivalenol on early embryonic development have not been reported. In this study, fluorescence intensity analysis was used to show that deoxynivalenol disrupted the first cleavage of the zygote. The high deoxynivalenol dose disturbed the movement of the pronucleus after fertilization, while the low deoxynivalenol dose caused aberrant spindle morphology during the metaphase of the first cleavage. Further analysis showed that the reactive oxygen species level increased in the deoxynivalenol-exposed two-cell embryos, indicating oxidative stress. Moreover, deoxynivalenol caused DNA damage in the embryos, as positive γH2A.X signals were detected in the nucleus. These events led to the early apoptosis of mouse embryos, which was confirmed by autophagy. Taken together, our study provides evidence for the toxicity of deoxynivalenol during early embryonic development in the mouse model.


Assuntos
Apoptose , Micotoxinas , Feminino , Gravidez , Humanos , Animais , Camundongos , Autofagia , Núcleo Celular , Micotoxinas/toxicidade , Mamíferos
17.
Acta Otolaryngol ; 143(8): 669-674, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37702578

RESUMO

BACKGROUND: ABO blood type associated with differentiated onset of infectious diseases. AIMS/OBJECTIVE: To investigate whether people with different blood types were vulnerable in developing chronic otitis media (CSOM) and if the risk and protective factors varied among them. MATERIAL AND METHODS: The study was a case-control study that included 206 participants in the case group and 210 in the control group. Stratified analysis for blood type was adopted. RESULTS: Patients with different blood types were insignificantly different in the incidence of CSOM. Upper respiratory tract infection (URTI, OR = 21.81, 95% CI: 4.80-99.06), socioeconomic status (OR = 3.02, 95% CI: 1.35-6.74), and were risk factors in blood type A. In blood type B, smoking and urban residence were risk factors. The OR (95% CI) were 11.42 (2.77-47.08), and 0.14 (0.03-0.65). Urban residence, BMI and blood calcium increase, male gender were protective factors for different blood types. CONCLUSIONS AND SIGNIFICANCE: Our study identified the risk and protective factors for CSOM among different blood types. The findings might provide new insights into taking precautions against CSOM in people of different blood types.


Assuntos
Otite Média Supurativa , Humanos , Masculino , Otite Média Supurativa/epidemiologia , Fatores de Proteção , Estudos de Casos e Controles , Fatores de Risco , Fumar
18.
Front Nutr ; 10: 1170084, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37701374

RESUMO

Introduction: Food-components-target-function (FCTF) is an evaluation and prediction model based on association rule mining (ARM) and network interaction analysis, which is an innovative exploration of interdisciplinary integration in the food field. Methods: Using the components as the basis, the targets and functions are comprehensively explored in various databases and platforms under the guidance of the ARM concept. The focused active components, key targets and preferred efficacy are then analyzed by different interaction calculations. The FCTF model is particularly suitable for preliminary studies of medicinal plants in remote and poor areas. Results: The FCTF model of the local medicinal food Laoxianghuang focuses on the efficacy of digestive system cancers and neurological diseases, with key targets ACE, PTGS2, CYP2C19 and corresponding active components citronellal, trans-nerolidol, linalool, geraniol, α-terpineol, cadinene and α-pinene. Discussion: Centuries of traditional experience point to the efficacy of Laoxianghuang in alleviating digestive disorders, and our established FCTF model of Laoxianghuang not only demonstrates this but also extends to its possible adjunctive efficacy in neurological diseases, which deserves later exploration. The FCTF model is based on the main line of components to target and efficacy and optimizes the research level from different dimensions and aspects of interaction analysis, hoping to make some contribution to the future development of the food discipline.

19.
Biochem Genet ; 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658254

RESUMO

Metabolites are important indicators of cancer and mutations in genes involved in amino acid metabolism may influence tumorigenesis. Immunotherapy is an effective cancer treatment option; however, its relationship with amino acid metabolism has not been reported. In this study, RNA-seq data for 371 liver cancer patients were acquired from TCGA and used as the training set. Data for 231 liver cancer patients were obtained from ICGC and used as the validation set to establish a gene signature for predicting liver cancer overall survival outcomes and immunotherapeutic responses. Four reliable groups based on 132 amino acid metabolism-related DEGs were obtained by consistent clustering of 371 HCC patients and a four-gene signature for prediction of liver cancer survival outcomes was developed. Our data show that in different clinical groups, the overall survival outcomes in the high-risk group were markedly low relative to the low-risk group. Univariate and multivariate analyses revealed that the characteristics of the 4-gene signature were independent prognostic factors for liver cancer. The ROC curve revealed that the risk characteristic is an efficient predictor for 1-, 2-, and 3-year HCC survival outcomes. The GSVA and KEGG pathway analyses revealed that high-risk score tumors were associated with all aspects of the degree of malignancy in liver cancer. There were more mutant genes and greater immune infiltrations in the high-risk groups. Assessment of the three immunotherapeutic cohorts established that low-risk score patients significantly benefited from immunotherapy. Then, we established a prognostic nomogram based on the TCGA cohort. In conclusion, the 4-gene signature is a reliable diagnostic marker and predictor for immunotherapeutic efficacy.

20.
Radiol Med ; 128(10): 1206-1216, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37597127

RESUMO

PURPOSE: To construct a nomogram based on sonogram features and radiomics features to differentiate granulomatous lobular mastitis (GLM) from invasive breast cancer (IBC). MATERIALS AND METHODS: A retrospective collection of 213 GLMs and 472 IBCs from three centers was divided into a training set, an internal validation set, and an external validation set. A radiomics model was built based on radiomics features, and the RAD score of the lesion was calculated. The sonogram radiomics model was constructed using ultrasound features and RAD scores. Finally, the diagnostic efficacy of the three sonographers with different levels of experience before and after combining the RAD score was assessed in the external validation set. RESULTS: The RAD score, lesion diameter, orientation, echogenicity, and tubular extension showed significant differences in GLM and IBC (p < 0.05). The sonogram radiomics model based on these factors achieved optimal performance, and its area under the curve (AUC) was 0.907, 0.872, and 0.888 in the training, internal, and external validation sets, respectively. The AUCs before and after combining the RAD scores were 0.714, 0.750, and 0.830 and 0.834, 0.853, and 0.878, respectively, for sonographers with different levels of experience. The diagnostic efficacy was comparable for all sonographers when combined with the RAD score (p > 0.05). CONCLUSION: Radiomics features effectively enhance the ability of sonographers to discriminate between GLM and IBC and reduce interobserver variation. The nomogram combining ultrasound features and radiomics features show promising diagnostic efficacy and can be used to identify GLM and IBC in a noninvasive approach.


Assuntos
Neoplasias da Mama , Mastite , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Estudos Retrospectivos , Área Sob a Curva , Ultrassonografia
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