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1.
EMBO Rep ; 25(7): 2861-2877, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38839944

RESUMO

In developing olfactory bulb (OB), mitral cells (MCs) remodel their dendrites to establish the precise olfactory circuit, and these circuits are critical for individuals to sense odors and elicit behaviors for survival. However, how microtubules (MTs) participate in the process of dendritic remodeling remains elusive. Here, we reveal that calmodulin-regulated spectrin-associated proteins (CAMSAPs), a family of proteins that bind to the minus-end of the noncentrosomal MTs, play a crucial part in the development of MC dendrites. We observed that Camsap2 knockout (KO) males are infertile while the reproductive tract is normal. Further study showed that the infertility was due to the severe defects of mating behavior in male mice. Besides, mice with loss-of-function displayed defects in the sense of smell. Furthermore, we found that the deficiency of CAMSAP2 impairs the classical morphology of MCs, and the CAMSAP2-dependent dendritic remodeling process is responsible for this defect. Thus, our findings demonstrate that CAMSAP2 plays a vital role in regulating the development of MCs.


Assuntos
Dendritos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos , Bulbo Olfatório , Olfato , Animais , Camundongos , Masculino , Olfato/fisiologia , Bulbo Olfatório/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Dendritos/metabolismo , Morfogênese/genética , Microtúbulos/metabolismo , Feminino
2.
Reprod Biol ; 24(2): 100889, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38733657

RESUMO

Mitophagy, the cellular process that removes damaged mitochondria, plays a crucial role in maintaining normal cell functions. It is deeply involved in the entire process of follicle development and is associated with various ovarian diseases. This review aims to provide a comprehensive overview of mitophagy regulation, emphasizing its role at different stages of follicular development. Additionally, the study illuminates the relationship between mitophagy and ovarian diseases, including ovary aging (OA), primary ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS). A detailed understanding of mitophagy could reveal valuable insights and novel strategies for managing female ovarian reproductive health.


Assuntos
Mitofagia , Folículo Ovariano , Mitofagia/fisiologia , Feminino , Folículo Ovariano/fisiologia , Humanos , Animais , Mitocôndrias/fisiologia , Mitocôndrias/metabolismo , Insuficiência Ovariana Primária
3.
Cancer Imaging ; 24(1): 29, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409049

RESUMO

OBJECTIVE: To investigate the diagnostic value of diffusion kurtosis magnetic resonance imaging (DKI) and conventional diffusion-weighted imaging (DWI) for evaluating the response to first-line chemotherapy in unresectable pancreatic cancer. MATERIALS AND METHODS: We retrospectively analyzed 21 patients with clinically and pathologically confirmed unresected pancreatic cancer who received palliative chemotherapy. Three-tesla MRI examinations containing DWI sequences with b values of 0, 100, 700, 1400, and 2100 s/mm2 were performed before and after chemotherapy. Parameters included the apparent diffusion coefficient (ADC), mean diffusion coefficient (MD), and mean diffusional kurtosis (MK). The performances of the DWI and DKI parameters in distinguishing the response to chemotherapy were evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Overall survival (OS) was calculated from the date of first treatment to the date of death or the latest follow-up date. RESULTS: The ADCchange and MDchange were significantly higher in the responding group (PR group) than in the nonresponding group (non-PR group) (ADCchange: 0.21 ± 0.05 vs. 0.11 ± 0.09, P = 0.02; MDchange: 0.37 ± 0.24 vs. 0.10 ± 0.12, P = 0.002). No statistical significance was shown when comparing ADCpre, ADCpost, MKpre, MKpost, MKchange, MDpre, and MDpost between the PR and non-PR groups. The ROC curve analysis indicated that MDchange (AUC = 0.898, cutoff value = 0.7143) performed better than ADCchange (AUC = 0.806, cutoff value = 0.1369) in predicting the response to chemotherapy. CONCLUSION: The ADCchange and MDchange demonstrated strong potential for evaluating the response to chemotherapy in unresectable pancreatic cancer. The MDchange showed higher specificity in the classification of PR and non-PR than the ADCchange. Other parameters, including ADCpre, ADCpost, MKpre, MKpost, MKchange, MDpre, and MDpost, are not suitable for response evaluation. The combined model SUMchange demonstrated superior performance compared to the individual DWI and DKI models. Further experiments are needed to evaluate the potential of DWI and DKI parameters in predicting the prognosis of patients with unresectable pancreatic cancer.


Assuntos
Imagem de Tensor de Difusão , Neoplasias Pancreáticas , Humanos , Sensibilidade e Especificidade , Estudos Retrospectivos , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico
4.
Eur J Radiol ; 173: 111327, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38330535

RESUMO

PURPOSE: To predict histopathological differentiation grades in patients with pancreatic ductal adenocarcinoma (PDAC) before surgery with quantitative and qualitative variables obtained from dual-layer spectral detector CT (DLCT). METHODS: Totally 128 patients with histopathologically confirmed PDAC and preoperative DLCT were retrospectively enrolled and categorized into the low-grade (LG) (well and moderately differentiated, n = 82) and high-grade (HG) (poorly differentiated, n = 46) subgroups. Both conventional and spectral variables for PDAC were measured. The ratio of iodine concentration (IC) values in arterial phase(AP) and venous phase (VP) was defined as iodine enhancement fraction_AP/VP (IEF_AP/VP). Necrosis was visually assessed on both conventional CT images (necrosis_con) and virtual mono-energetic images (VMIs) at 40 keV (necrosis_40keV). Forward stepwise logistic regression method was conducted to perform univariable and multivariable analysis. Receiver operating characteristic (ROC) curves and the DeLong method were used to evaluate and compare the efficiencies of variables in predicting tumor grade. RESULTS: Necrosis_con (odds ratio [OR] = 2.84, 95% confidence interval [CI]: 1.13-7.13; p < 0.001) was an independent predictor among conventional variables, and necrosis_40keV (OR = 5.82, 95% CI: 1.98-17.11; p = 0.001) and IEF_AP/VP (OR = 1.12, 95% CI:1.07-1.17; p < 0.001) were independent predictors among spectral variables for distinguishing LG PDAC from HG PDAC. IEF_AP/VP (AUC = 0.754, p = 0.016) and combination model (AUC = 0.812, p < 0.001) had better predictive performances than necrosis_con (AUC = 0.580). The combination model yielded the highest sensitivity (72%) and accuracy (79%), while IEF_AP/VP exhibited the highest specificity (89%). CONCLUSION: Variables derived from DLCT have the potential to preoperatively evaluate PDAC tumor grade. Furthermore, spectral variables and their combination exhibited superior predictive performances than conventional CT variables.


Assuntos
Carcinoma Ductal Pancreático , Iodo , Neoplasias Pancreáticas , Humanos , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Necrose
5.
Development ; 150(22)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37882745

RESUMO

Primitive erythropoiesis serves a vital role in embryonic development, generating primitive red blood cells responsible for transportation of oxygen throughout the body. Although diverse niche factors are known to function in definitive hematopoiesis, the microenvironment contributing to primitive hematopoiesis remains largely elusive. Here, we report that platelet-derived growth factor (PDGF) signaling is required for erythroid progenitor differentiation in zebrafish. Ablating pdgfαa (also known as pdgfaa) and pdgfαb (also known as pdgfab) or blocking PDGF signaling with an inhibitor impairs erythroid progenitor differentiation, thus resulting in a significant decrease in the number of erythrocytes. We reveal that pdgfαb is expressed in sclerotomal cells, and that its receptor genes, pdgfra and pdgfrb, are expressed in the adjacent erythroid progenitor cells. Sclerotome-specific overexpression of pdgfαb effectively restores primitive erythropoiesis in pdgfαa-/-;pdgfαb-/- mutant embryos. In addition, we have defined ERK1/2 signaling as a downstream pathway of PDGF signaling during embryonic erythropoiesis. Taken together, our findings indicate that PDGF signaling derived from sclerotome functions as a niche cue for primitive erythropoiesis.


Assuntos
Eritropoese , Fator de Crescimento Derivado de Plaquetas , Animais , Eritropoese/genética , Peixe-Zebra , Sinais (Psicologia) , Diferenciação Celular/genética , Desenvolvimento Embrionário
6.
Proc Natl Acad Sci U S A ; 120(45): e2313787120, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37903275

RESUMO

The manchette is a crucial transient structure involved in sperm development, with its composition and regulation still not fully understood. This study focused on investigating the roles of CAMSAP1 and CAMSAP2, microtubule (MT) minus-end binding proteins, in regulating manchette MTs, spermiogenesis, and male fertility. The loss of CAMSAP1, but not CAMSAP2, disrupts the well-orchestrated process of spermiogenesis, leading to abnormal manchette elongation and delayed removal, resulting in deformed sperm nuclei and tails resembling oligoasthenozoospermia symptoms. We investigated the underlying molecular mechanisms by purifying manchette assemblies and comparing them through proteomic analysis, and results showed that the absence of CAMSAP1 disrupted the proper localization of key proteins (CEP170 and KIF2A) at the manchette minus end, compromising its structural integrity and hindering MT depolymerization. These findings highlight the significance of maintaining homeostasis in manchette MT minus-ends for shaping manchette morphology during late spermiogenesis, offering insights into the molecular mechanisms underlying infertility and sperm abnormalities.


Assuntos
Proteômica , Sêmen , Humanos , Masculino , Espermatogênese/fisiologia , Microtúbulos/metabolismo , Fertilidade
8.
J Mol Cell Biol ; 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37567766

RESUMO

Microtubule networks support many cellular processes and have a highly ordered architecture. However, due to the limited axial resolution of conventional light microscopy, the structural features of these networks cannot be resolved in three-dimensional (3D) space. Here, we use customized ultra-high resolution interferometric single-molecule localization microscopy to characterize the microtubule networks in Caco2 cells. We find that the microtubule minus-ends associated protein CAMSAPs localize at a portion of microtubule intersections. Further investigation shows that depletion of CAMSAP2 and CAMSAP3 leads to the narrowing of the inter-microtubule distance. We find that CAMSAPs recognize microtubule defects, which are often associated with microtubule intersections, and then recruit katanin to remove the damaged microtubules. Therefore, the CAMSAP-katanin complex is a regulating module for the distance between microtubules. Taken together, our results characterize the architecture of the cellular microtubule networks in high resolution and provide molecular insights into how the 3D structure of microtubule networks is controlled.

9.
Eur Radiol ; 33(11): 7782-7793, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37624415

RESUMO

OBJECTIVES: To identify prognostic CT features that predict recurrence in patients with resectable pancreatic body/tail adenocarcinoma (PBTA) and construct a CT-based nomogram for preoperative risk stratification. METHODS: A total of 258 patients with resectable PBTA who underwent upfront surgery were retrospectively enrolled (development cohort, n = 172; validation cohort, n = 86), and their clinical and CT features were analyzed. Stepwise Cox proportional hazard analysis was performed to identify prognostic features and construct a predictive nomogram for recurrence-free survival (RFS). The prognostic performance of the CT-based nomogram was validated and compared to the 8th American Joint Committee on Cancer (AJCC) pathological staging system. RESULTS: In the development cohort, the following five CT features for predicting recurrence were identified to construct the nomogram: tumor density in the venous phase, tumor necrosis, adjacent organ invasion, splenic vein invasion, and superior mesenteric vein/portal vein abutment. In the validation cohort, the CT-based nomogram showed a concordance index of 0.65 (95% confidence interval: 0.58-0.73), which was higher than the 8th AJCC staging system. The area under the curves of the nomogram for predicting recurrence at 0.5, 1, and 2 years were 0.66, 0.71, and 0.72, respectively. Patients were categorized into high- and low-risk groups with 1-year recurrence probabilities of 0.73 and 0.43, respectively. CONCLUSIONS: The proposed nomogram provided accurate recurrence risk stratification for patients with resectable PBTA in a preoperative setting and may be used to facilitate clinical decision-making. CLINICAL RELEVANCE STATEMENT: The proposed CT-based nomogram, based on easily available CT features, may serve as an effective and convenient tool for stratifying further the recurrence risk of patients with pancreatic body/tail adenocarcinoma. KEY POINTS: • The CT-based nomogram, incorporating five commonly used CT features, successfully preoperatively stratified patients with resectable PBTA into distinct prognosis groups. • Tumor density in the venous phase, tumor necrosis, splenic vein invasion, adjacent organ invasion, and superior mesenteric vein/portal vein abutment were associated with RFS in patients with resectable PBTA. • The CT-based nomogram exhibited better predictive performance for recurrence than the 8th AJCC staging system.


Assuntos
Adenocarcinoma , Nomogramas , Humanos , Estudos Retrospectivos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Prognóstico , Veia Porta/patologia , Medição de Risco , Tomografia Computadorizada por Raios X , Necrose/patologia , Neoplasias Pancreáticas
10.
ACS Appl Mater Interfaces ; 15(20): 24880-24891, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37184365

RESUMO

The enhancement of the heat-dissipation property of polymer-based composites is of great practical interest in modern electronics. Recently, the construction of a three-dimensional (3D) thermal pathway network structure for composites has become an attractive way. However, for most reported high thermal conductive composites, excellent properties are achieved at a high filler loading and the building of a 3D network structure usually requires complex steps, which greatly restrict the large-scale preparation and application of high thermal conductive polymer-based materials. Herein, utilizing the framework-forming characteristic of polymerization-induced para-aramid nanofibers (PANF) and the high thermal conductivity of hexagonal boron nitride nanosheets (BNNS), a 3D-laminated PANF-supported BNNS aerogel was successfully prepared via a simple vacuum-assisted self-stacking method, which could be used as a thermal conductive skeleton for epoxy resin (EP). The obtained PANF-BNNS/EP nanocomposite exhibits a high thermal conductivity of 3.66 W m-1 K-1 at only 13.2 vol % BNNS loading. The effectiveness of the heat conduction path was proved by finite element analysis. The PANF-BNNS/EP nanocomposite shows outstanding practical thermal management capability, excellent thermal stability, low dielectric constant, and dielectric loss, making it a reliable material for electronic packaging applications. This work also offers a potential and promotable strategy for the easy manufacture of 3D anisotropic high-efficiency thermal conductive network structures.

11.
Curr Res Food Sci ; 5: 1403-1411, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105890

RESUMO

Nicotinamide mononucleotide (NMN) exerts physiological effects in mammals through its conversion to nicotinamide adenine dinucleotide (NAD+). In this study, we established experimental models of colitis by mixing drinking water of C57BL/6J mice with dextran sodium sulphate (DSS), and then fed them with the same concentration of NMN or at the same time. After NMN treatment, we observed improved morphology of inflamed intestines, slightly restored length of colon, improved barrier function and reduced proinflammatory factors expression in serum. Also, significant alterations in the composition and abundance of intestinal flora in IBD mice were found. The abundance of Firmicutes, Verrucomicrobia, Akkermansia and Lactobacillus, considered as beneficial bacteria, increased, while Bacteroidetes and Muribaculaceae unclassifiably decreased. Taken together, these results suggest that NMN may improve intestinal inflammation, reduce intestinal mucosal permeability and repair gut flora dysbiosis in IBD.

12.
Medicine (Baltimore) ; 101(34): e30222, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36042628

RESUMO

Aldolase A (A-2) (ALD), Kelch-like-ECH associated protein-1 (Keap-1), and Forkhead box O4 (FoxO4) are key regulatory proteins, which have been proven to be involved in tumor development. However, the clinicopathological significance of ALD, Keap-1, and FoxO4 expressions in colorectal (colon) carcinoma (CRC) is not clearly known. We sought to explore the clinicopathological significance of ALD, Keap-1, and FoxO4 in CRC to provide evidences for potential monitoring index of CRC. Cases of 199 CRC patients were analyzed retrospectively. Evaluation of ALD, cAMP response element-binding protein-2, cyclo-oxygenase 2, FoxO4, Keap-1, and p53 expressions in CRC patients was accomplished with immunohistochemical technique. The patients were divided into negative and positive groups in accordance with immunohistochemical result. We compared the clinicopathological characteristics of the patients in the 2 groups, coupled with analysis of the relationship between 6 aforesaid proteins and clinicopathological characteristics. Herein, we confirmed the association of tumor location with the expression of ALD, Keap-1, and FoxO4. Also, tumor differentiation was observed to associate significantly with the expression of Keap-1, FoxO4, and Cox-2. The data also revealed that there was a correlation between smoking and expression of ALD, Keap-1, FoxO4, p53, and Cox-2. Nevertheless, insignificant difference was observed when clinicopathological characteristics were compared with cAMP response element-binding protein-2 expression. These findings suggest that ALD, Keap-1, and FoxO4 reinvolved in CRC development, and thus may be considered as potential monitoring protein for CRC.


Assuntos
Neoplasias Colorretais , Fatores de Transcrição Forkhead , Frutose-Bifosfato Aldolase , Proteína 1 Associada a ECH Semelhante a Kelch , Biomarcadores Tumorais/análise , Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorretais/patologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Ciclo-Oxigenase 2 , Fatores de Transcrição Forkhead/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Estudos Retrospectivos , Proteína Supressora de Tumor p53
13.
J Integr Neurosci ; 21(4): 109, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35864761

RESUMO

BACKGROUND: Peripheral nerve regeneration is a coordinated process of Schwann cell (SC) reprogramming and intrinsic neuronal growth program activation. Panaxydol (PND) is a strong biologically active traditional Chinese medicine monomer extracted from Panax notoginseng rhizomes. In vitro, PND protects neurons and SCs from injury and stimulates the expression and secretion of neurotrophic factors (NTFs) by SCs. We hypothesized that PND may also promote peripheral nerve regeneration in adult animals. METHODS: PND (10 mg/kg body weight) was injected intraperitoneally into the Sprague-Dawley (SD) rats for two consecutive weeks after sciatic nerve transection. The morphology of the repaired sciatic nerve was evaluated after 16 weeks, and sensory and motor function recovery was evaluated using functional and behavioral techniques. RESULTS: PND was biologically safe at an injection dose of 10 mg/kg/day. After 14 days, it significantly increased the myelination of regenerated nerve fibers, and promoted sensory and motor function recovery. In the early stage of injury, PND significantly upregulated the mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptors in distal injured nerves, which may represent a possible mechanism by which PND promotes nerve regeneration in vivo. CONCLUSIONS: Our study demonstrated that PND leads to sensory and motor recovery in a sciatic nerve transection model rat. Furthermore, we showed that BDNF mRNA level was significantly increased in the injured distal nerve, potentially contributing to the functional recovery. Further research is warrantied to examine whether direct injection is a more efficient method to increase BDNF expression compared to an exogenous BDNF administration.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Panax notoginseng , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Di-Inos , Álcoois Graxos , Regeneração Nervosa/fisiologia , Panax notoginseng/genética , Panax notoginseng/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Células de Schwann/metabolismo , Nervo Isquiático/lesões
14.
Breast Cancer Res ; 24(1): 20, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35292076

RESUMO

BACKGROUND: This study investigated the efficacy of radiomics to predict survival outcome for locally advanced breast cancer (LABC) patients and the association of radiomics with tumor heterogeneity and microenvironment. METHODS: Patients with LABC from 2010 to 2015 were retrospectively reviewed. Radiomics features were extracted from enhanced MRI. We constructed the radiomics score using lasso and assessed its prognostic value. An external validation cohort from The Cancer Imaging Archive was used to assess phenotype reproducibility. Sequencing data from TCGA and our center were applied to reveal genomic landscape of different radiomics score groups. Tumor infiltrating lymphocytes map and bioinformatics methods were applied to evaluate the heterogeneity of tumor microenvironment. Computational histopathology was also applied. RESULTS: A total of 278 patients were divided into training cohort and validation cohort. Radiomics score was constructed and significantly associated with disease-free survival (DFS) of the patients in training cohort, validation cohort and external validation cohort (p < 0.001, p = 0.014 and p = 0.041, respectively). The radiomics-based nomogram showed better predictive performance of DFS compared with TNM model. Distinct gene expression patterns were identified. Immunophenotype and immune cell composition was different in each radiomics score group. The link between radiomics and computational histopathology was revealed. CONCLUSIONS: The radiomics score could effectively predict prognosis of LABC after neoadjuvant chemotherapy and radiotherapy. Radiomics revealed heterogeneity of tumor cell and tumor microenvironment and holds great potential to facilitate individualized DFS estimation and guide personalized care.


Assuntos
Neoplasias da Mama , Microambiente Tumoral , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Humanos , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos
15.
Neuroscience ; 498: 19-30, 2022 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-35121079

RESUMO

Resting gamma-band brain networks are known as an inhibitory component in functional brain networks. Although autism spectrum disorder (ASD) is considered as with imbalanced brain networks, the inhibitory component remains not fully explored. The study reported 10 children with ASD and 10 typically-developing (TD) controls. The power spectral density analysis of the gamma-band signal in the cerebral cortex was performed at the source level. The normalized phase transfer entropy values (nPTEs) were calculated to construct brain connectivity. Gamma-band activity of the ASD group was lower than the TD children. The significantly inhibited brain regions were mainly distributed in the bilateral frontal and temporal lobes. Connectivity analysis showed alterations in the connections from key nodes of the social brain network. The behavior assessments in the ASD group revealed a significantly positive correlation between the total score of Childhood Autism Rating Scale and the regional nPTEs of the right transverse temporal gyrus. Our results provide strong evidence that the gamma-band brain networks of ASD children have a lower level of brain activities and different distribution of information flows. Clinical meanings of such imbalances of both activity and connectivity were also worthy of further explorations.


Assuntos
Córtex Auditivo , Transtorno do Espectro Autista , Encéfalo , Mapeamento Encefálico , Criança , Humanos , Imageamento por Ressonância Magnética , Vias Neurais
16.
J Nutr Biochem ; 101: 108911, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34801690

RESUMO

Ovarian aging affects the reproductive health of elderly women due to decline in oocyte quality, which is closely related to mitochondrial dysfunction. Nicotinamide mononucleotide (NMN), as a precursor of NAD+, effectively regulate mitochondria metabolism in mice. However, roles of NMN in improving age-related diminished ovary reserve remain to be determined. In present study, 4, 8, 12, 24, 40-week old female ICR mice were collected and a 20-week-long administration of NMN was conducted to 40-week-old mice (60WN), meanwhile the control group is given water (60WC). First, we found that 20-week-long administration of NMN to 40-week-old mice exhibited anti-aging and anti-inflammatory effects on organ structures, along with the improvement of estrus cycle condition and endocrine function. The number of primordial, primary, secondary, antral follicles and corpora luteum of ovaries in 60WN group was significantly increased compared with those in 60WC group. Additionally, the protein and gene expressions of P16 of ovaries were significantly reduced in 60WN group than in 60WC group. the mitochondria biogenesis, autophagy level, and proteases activity enhanced in granulosa cells after 20-week-administration of NMN. Present results indicate that NMN has the potential to save diminished ovary reserve by long-term treatment, providing a basis for exploring the role of NMN in anti-ovarian aging by enhancing the mitophagy level of granulosa cells.


Assuntos
Envelhecimento , Células da Granulosa/fisiologia , Mitofagia/efeitos dos fármacos , Mononucleotídeo de Nicotinamida/administração & dosagem , Reserva Ovariana/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Catepsina D/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Endopeptidase Clp/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Células da Granulosa/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Biogênese de Organelas , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/fisiologia , Ovário/efeitos dos fármacos , Ovário/metabolismo
17.
J Digit Imaging ; 34(5): 1146-1155, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34545474

RESUMO

Machine learning has been widely used in the characterization of tumors recently. This article aims to explore the feasibility of the whole tumor fat-suppressed (FS) T2WI and ADC features-based least absolute shrinkage and selection operator (LASSO)-logistic predictive models in the differentiation of soft tissue neoplasms (STN). The clinical and MR findings of 160 cases with 161 histologically proven STN were reviewed, retrospectively, 75 with diffusion-weighted imaging (DWI with b values of 50, 400, and 800 s/mm2). They were divided into benign and malignant groups and further divided into training (70%) and validation (30%) cohorts. The MR FS T2WI and ADC features-based LASSO-logistic models were built and compared. The AUC of the FS T2WI features-based LASSO-logistic regression model for benign and malignant prediction was 0.65 and 0.75 for the training and validation cohorts. The model's sensitivity, specificity, and accuracy of the validation cohort were 55%, 96%, and 76.6%. While the AUC of the ADC features-based model was 0.932 and 0.955 for the training and validation cohorts. The model's sensitivity, specificity, and accuracy were 83.3%, 100%, and 91.7%. The performances of these models were also validated by decision curve analysis (DCA). The AUC of the whole tumor ADC features-based LASSO-logistic regression predictive model was larger than that of FS T2WI features (p = 0.017). The whole tumor fat-suppressed T2WI and ADC features-based LASSO-logistic predictive models both can serve as useful tools in the differentiation of STN. ADC features-based LASSO-logistic regression predictive model did better than that of FS T2WI features.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias de Tecidos Moles , Estudos de Coortes , Humanos , Aprendizado de Máquina , Estudos Retrospectivos , Neoplasias de Tecidos Moles/diagnóstico por imagem
18.
Front Nutr ; 8: 714604, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395502

RESUMO

The aim of this study was to determine the effects of long-term Nicotinamide mononucleotide (NMN) treatment on modulating gut microbiota diversity and composition, as well as its association with intestinal barrier function. In this study, C57BL/6J mice were fed different concentrations of NMN, and their feces were collected for detection of 16S rDNA and non-targeted metabolites to explore the effects of NMN on intestinal microbiota and metabolites. The results revealed that NMN increased the abundance of butyric acid-producing bacteria (Ruminococcae_UCG-014 and Prevotellaceae_NK3B31_group) and other probiotics (Akkermansia muciniphila), while the abundance of several harmful bacteria (Bilophila and Oscillibacter) were decreased after NMN treatment. Meanwhile, the level of bile acid-related metabolites in feces from the G1 group (0.1 mg/ml) was significantly increased compared to the control group, including cholic acid, taurodeoxycholic acid, taurocholic acid, glycocholic acid, and tauro-ß-muricholic acid. In addition, long-term NMN treatment affected the permeability of the intestinal mucosa. The number of goblet cells and mucus thickness increased, as well as expression of tight junction protein. These results demonstrate that NMN reduced intestinal mucosal permeability and exerts a protective effect on the intestinal tract. This study lays the foundation for exploring NMN's utility in clinical research.

19.
Front Oncol ; 11: 621520, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178619

RESUMO

OBJECTIVES: To investigate the value of CT-based radiomics analysis in preoperatively discriminating pancreatic mucinous cystic neoplasms (MCN) and atypical serous cystadenomas (ASCN). METHODS: A total of 103 MCN and 113 ASCN patients who underwent surgery were retrospectively enrolled. A total of 764 radiomics features were extracted from preoperative CT images. The optimal features were selected by Mann-Whitney U test and minimum redundancy and maximum relevance method. The radiomics score (Rad-score) was then built using random forest algorithm. Radiological/clinical features were also assessed for each patient. Multivariable logistic regression was used to construct a radiological model. The performance of the Rad-score and the radiological model was evaluated using 10-fold cross-validation for area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. RESULTS: Ten screened optimal features were identified and the Rad-score was then built based on them. The radiological model was built based on four radiological/clinical factors. In the 10-fold cross-validation, the Rad-score was proved to be robust and reliable (average AUC: 0.784, sensitivity: 0.847, specificity: 0.745, PPV: 0.767, NPV: 0.849, accuracy: 0.793). The radiological model performed slightly less well in classification (average AUC: average AUC: 0.734 sensitivity: 0.748, specificity: 0.705, PPV: 0.732, NPV: 0.798, accuracy: 0.728. CONCLUSIONS: The CT-based radiomics analysis provided promising performance for preoperatively discriminating MCN from ASCN and showed good potential in improving diagnostic power, which may serve as a novel tool for guiding clinical decision-making for these patients.

20.
J Nanosci Nanotechnol ; 21(9): 4565-4572, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33691834

RESUMO

The objective of this study was to prepare doxorubicin-loaded EGF modified PEG-nanoparticles and evaluate its targeting capability and therapeutic effects with EGFR-expressing hepatocellular carcinoma cells. The morphology, particle size distribution, and doxorubicin content of the nanoparticles were measured, and the drug loading and encapsulation efficiency were calculated. The doxorubicin nanoparticles prepared were regular circular, with good dispersibility, no adhesion, and the average particle size was (136.7±9.3) nm. The average encapsulation efficiency was (76.67±8.63)%, the average drug loading was (3.86±0.55)%; the drug release rate of doxorubicin was 100% for 12 h, and the doxorubicin nanometer was loaded. The drug release rate of the granules was 52.9% at 24 h and 81.2% at 144 h. The inhibition rate of the proliferation of hepatocarcinoma cells by the doxorubicin-containing nanoparticles was slower than that of doxorubicin, and the IC50 of the two cells was 1.844 and 0.345 µg/mL, respectively. At the same time, apoptosis and cycle analysis showed that the doxorubicin nanoparticles could significantly inhibit the cell cycle of hepatoma cells and promote the apoptosis of hepatoma cells. This study successfully produced nanoparticles loaded with doxorubicin targeting EGFR, which has a good sustained release effect, and its antitumor effect is stronger than free doxorubicin.


Assuntos
Neoplasias Hepáticas , Nanopartículas , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Portadores de Fármacos/uso terapêutico , Fator de Crescimento Epidérmico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Tamanho da Partícula
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