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1.
Magn Reson Imaging ; 112: 1-9, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38844268

RESUMO

BACKGROUND: To compare the value of adipose tissues in abdomen and lumbar vertebra for predicting Crohn's disease (CD) activity based on chemical shift encoded magnetic resonance imaging (CSE-MRI). METHODS: 84 CD patients were divided into remission, mild, and moderate-severely groups based on CD activity index (CDAI). Differences in different adipose parameters [subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), mesenteric fat index (MFI), and bone marrow fat fraction (BMFF)] and blood inflammatory indicators among three groups, as well as the correlation of above parameters and CDAI were analyzed. The areas under the receiver-operating characteristic curves (AUCs) for the parameters selected by multivariate logistic regression analysis for predicting active CD were calculated. RESULTS: There were no significant differences in VAT and MFI among three groups (both P > 0.05). The cross-sectional areas of SAT in moderate-severe group were significantly lower than those in remission group (P = 0.014). BMFF values of remission group were significantly higher than those in the mild and moderate-severe groups (both P < 0.001). BMFF was negatively correlated with CDAI (r = -0.595, P < 0.001). SAT exhibited no significant correlation with CDAI. Erythrocyte sedimentation rate (ESR) and BMFF were the independent predictors of CDAI. Both combined had a higher diagnostic efficacy for active CD with an AUC of 0.895. CONCLUSIONS: BMFF is the best marker for predicting CD activity in fat parameters of abdomen and lumbar vertebra based on CSE-MRI. The model based on BMFF and ESR has a high efficiency in predicting active CD. TRIAL REGISTRATION: No. 22 K164 (Registered 18-07-2022).

2.
Sci Adv ; 10(22): eadl1123, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38809977

RESUMO

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged APP/PS1 mice were rejuvenated through young bone marrow transplantation (BMT). Single-cell RNA sequencing revealed that young BMT restored the expression of aging- and AD-related genes in multiple cell types within blood immune cells. The level of circulating senescence-associated secretory phenotype proteins was decreased following young BMT. Notably, young BMT resulted in a significant reduction in cerebral Aß plaque burden, neuronal degeneration, neuroinflammation, and improvement of behavioral deficits in aged APP/PS1 mice. The ameliorated cerebral amyloidosis was associated with an enhanced Aß clearance of peripheral monocytes. In conclusion, our study provides evidence that immune system rejuvenation represents a promising therapeutic approach for AD.


Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Rejuvenescimento , Animais , Doença de Alzheimer/terapia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/imunologia , Camundongos , Camundongos Transgênicos , Transplante de Medula Óssea , Comportamento Animal , Peptídeos beta-Amiloides/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Placa Amiloide/patologia , Placa Amiloide/metabolismo , Envelhecimento/imunologia , Humanos
3.
Artigo em Inglês | MEDLINE | ID: mdl-38743208

RESUMO

Non-small cell lung cancer (NSCLC) is a common cancer with several accepted treatments, such as chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, and immune checkpoint inhibitors. Nevertheless, NSCLC cells often become insensitive to these treatments, and therapeutic resistance is a major reason NSCLC still has a high mortality rate. The induction of therapeutic resistance in NSCLC often involves hedgehog, and suppression of hedgehog can increase NSCLC cell sensitivity to several conventional therapies. In our previous work, we demonstrated that the marine antimicrobial peptide tilapia piscidin 4 (TP4) exhibits potent anti-NSCLC activity in both EGFR-WT and EGFR-mutant NSCLC cells. Here, we sought to further explore whether hedgehog might influence the sensitivity of NSCLC cells to TP4. Our results showed that hedgehog was activated by TP4 in both WT and EGFR-mutant NSCLC cells and that pharmacological inhibition of hedgehog by vismodegib, a Food and Drug Administration-approved hedgehog inhibitor, potentiated TP4-induced cytotoxicity. Mechanistically, vismodegib acted by enhancing TP4-mediated increases in mitochondrial membrane potential and intracellular reactive oxygen species (ROS). MitoTempo, a specific mitochondrial ROS scavenger, abolished vismodegib/TP4 cytotoxicity. The combination of vismodegib with TP4 also reduced the levels of the antioxidant proteins catalase and superoxide dismutase, and it diminished the levels of chemoresistance-related proteins, Bcl-2 and p21. Thus, we conclude that hedgehog regulates the cytotoxic sensitivity of NSCLC cells to TP4 by protecting against mitochondrial dysfunction and suppressing oxidative stress. These findings suggest that combined treatment of vismodegib and TP4 may be a promising therapeutic strategy for NSCLC.

4.
J Cell Biochem ; 125(5): e30563, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38591551

RESUMO

High glucose (HG)-induced endothelial cell (EC) and smooth muscle cell (SMC) dysfunction is critical in diabetes-associated atherosclerosis. However, the roles of heme oxygenase-1 (HO-1), a stress-response protein, in hemodynamic force-generated shear stress and HG-induced metabolic stress remain unclear. This investigation examined the cellular effects and mechanisms of HO-1 under physiologically high shear stress (HSS) in HG-treated ECs and adjacent SMCs. We found that exposure of human aortic ECs to HSS significantly increased HO-1 expression; however, this upregulation appeared to be independent of adenosine monophosphate-activated protein kinase, a regulator of HO-1. Furthermore, HSS inhibited the expression of HG-induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and reactive oxygen species (ROS) production in ECs. In an EC/SMC co-culture, compared with static conditions, subjecting ECs close to SMCs to HSS and HG significantly suppressed SMC proliferation while increasing the expression of physiological contractile phenotype markers, such as α-smooth muscle actin and serum response factor. Moreover, HSS and HG decreased the expression of vimentin, an atherogenic synthetic phenotypic marker, in SMCs. Transfecting ECs with HO-1-specific small interfering (si)RNA reversed HSS inhibition on HG-induced inflammation and ROS production in ECs. Similarly, reversed HSS inhibition on HG-induced proliferation and synthetic phenotype formation were observed in co-cultured SMCs. Our findings provide insights into the mechanisms underlying EC-SMC interplay during HG-induced metabolic stress. Strategies to promote HSS in the vessel wall, such as continuous exercise, or the development of HO-1 analogs and mimics of the HSS effect, could provide an effective approach for preventing and treating diabetes-related atherosclerotic vascular complications.


Assuntos
Células Endoteliais , Glucose , Heme Oxigenase-1 , Miócitos de Músculo Liso , Espécies Reativas de Oxigênio , Estresse Mecânico , Humanos , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Glucose/metabolismo , Glucose/farmacologia , Miócitos de Músculo Liso/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/metabolismo , Células Cultivadas , Proliferação de Células , Técnicas de Cocultura , Ativação Enzimática , Molécula 1 de Adesão de Célula Vascular/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Molécula 1 de Adesão Intercelular/metabolismo
5.
Polymers (Basel) ; 16(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38475371

RESUMO

By integrating fiber-reinforced composites (FRCs) with Three-dimensional (3D) printing, the flexibility of lightweight structures was promoted while eliminating the mold's limitations. The design of the I-beam configuration was performed according to the equal-strength philosophy. Then, a multi-objective optimization analysis was conducted based on the NSGA-II algorithm. 3D printing was utilized to fabricate I-beams in three kinds of configurations and seven distinct materials. The flexural properties of the primitive (P-type), the designed (D-type), and the optimized (O-type) configurations were verified via three-point bending testing at a speed of 2 mm/min. Further, by combining different reinforcements, including continuous carbon fibers (CCFs), short carbon fibers (SCFs), and short glass fibers (SGFs) and distinct matrices, including polyamides (PAs), and polylactides (PLAs), the 3D-printed I-beams were studied experimentally. The results indicate that designed and optimized I-beams exhibit a 14.46% and 30.05% increase in the stiffness-to-mass ratio and a 7.83% and 40.59% increment in the load-to-mass ratio, respectively. The CCFs and SCFs result in an outstanding accretion in the flexural properties of 3D-printed I-beams, while the accretion is 2926% and 1070% in the stiffness-to-mass ratio and 656.7% and 344.4% in the load-to-mass ratio, respectively. For the matrix, PAs are a superior choice compared to PLAs for enhancing the positive impact of reinforcements.

6.
Elife ; 122023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099574

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA sequencing (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC, and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors along AK to cSCC progression. Immunohistochemistry (IHC)/immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration, and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.


Assuntos
Carcinoma de Células Escamosas , Ceratose Actínica , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/metabolismo , Ceratose Actínica/genética , Ceratose Actínica/metabolismo , Ceratose Actínica/patologia , Neoplasias Cutâneas/patologia , Queratinócitos/metabolismo , Transcriptoma , Microambiente Tumoral/genética
7.
J Cell Physiol ; 238(12): 2751-2764, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37795566

RESUMO

Skin and its cell components continuously subject to extrinsic and intrinsic mechanical forces and are mechanical sensitive. Disturbed mechanical homeostasis may lead to changes in skin functions. Gravity is the integral mechanical force on the earth, however, how gravity contributes to the maintenance of skin function and how microgravity in space affects the wound healing are poorly understood. Here, using microgravity analogs, we show that simulated microgravity (SMG) inhibits the healing of cutaneous wound and the accumulation of dermal fibroblasts in the wound bed. In vitro, SMG inhibits the migration of human foreskin fibroblast cells (HFF-1), and decreases the F-actin polymerization and YAP (yes-associated protein) activity. The SMG-inhibited migration can be recovered by activating YAP or F-actin polymerization using lysophosphatidic acid (LPA) or jasplakinolide (Jasp), suggesting the involvement of F-actin/YAP signaling pathway in this process. In SMG rats, LPA treatment improves the cutaneous healing with increased dermal fibroblasts in the wound bed. Together, our results demonstrate that SMG attenuates the cutaneous wound healing by inhibiting dermal fibroblast migration, and propose the crucial role of F-actin/YAP mechano-transduction in the maintenance of skin homeostasis under normal gravity, and YAP as a possible therapeutic target for the skin care of astronauts in space.


Assuntos
Actinas , Ausência de Peso , Animais , Humanos , Ratos , Actinas/metabolismo , Fibroblastos/metabolismo , Transdução de Sinais , Pele/metabolismo , Cicatrização , Feminino , Ratos Sprague-Dawley , Linhagem Celular
8.
Front Vet Sci ; 10: 1179374, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275607

RESUMO

Introduction: Copper (Cu) is an essential trace element for the growth of rabbits. This study aimed to investigate the effects of different Cu sources on intestinal microorganisms and short-chain fatty acids (SCFAs) in growing rabbits. Methods: The experimental animals were randomly divided into four experimental groups, each group comprised eight replicates, with six rabbits (half male and half female) per replicate. And they were fed diets was composed by mixing the basal diet with 20 mg/kg Cu from one of the two inorganic Cu (cupric sulfate and dicopper chloride trihydroxide) or two organic Cu (cupric citrate and copper glycinate). Cecal contents of four rabbits were collected from four experimental groups for 16S rDNA gene amplification sequencing and gas chromatography analysis. Results: Our results indicate that the organic Cu groups were less variable than the inorganic Cu groups. Compared with the inorganic Cu groups, the CuCit group had a significantly higher relative abundance of Rikenella Tissierella, Lachnospiraceae_NK3A20_group, Enterococcus, and Paeniclostridium, while the relative abundance of Novosphingobium and Ruminococcus were significantly lower (p < 0.05). The SCFAs level decreased in the organic Cu groups than in the inorganic Cu groups. Among the SCFAs, the butyric acid level significantly decreased in the CuCit group than in the CuSO4 and CuCl2 groups. The relative abundance of Rikenella and Turicibacter genera was significantly negatively correlated with the butyric acid level in the CuCit group compared with both inorganic Cu groups. These results revealed that the organic Cu (CuCit) group had an increased abundance of Rikenella, Enterococcus, Lachnospiraceae_NK3A20_group, and Turicibacter genera in the rabbit cecum. Discussion: In summary, this study found that organic Cu and inorganic Cu sources had different effects on cecal microbiota composition and SCFAs in rabbits. The CuCit group had the unique higher relative abundance of genera Rikenella and Lachnospiraceae_NK3A20_group, which might be beneficial to the lower incidence of diarrhea in rabbits.

9.
Neurosci Bull ; 39(12): 1775-1788, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37316674

RESUMO

Deficiencies in the clearance of peripheral amyloid ß (Aß) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aß is decreased in AD. However, the exact mechanism of Aß clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aß. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aß in vivo and in vitro. Moreover, enhancing blood monocyte Aß phagocytosis by improving energy metabolism alleviated brain Aß deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aß phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Peptídeos beta-Amiloides , Monócitos , Cognição , Metabolismo Energético , Fagocitose
10.
Jpn J Radiol ; 41(10): 1148-1156, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37266825

RESUMO

PURPOSE: The aim of this study was to evaluate the utility of RAI therapy after reoperation for patients with LN relapse. MATERIALS AND METHODS: We retrospectively evaluated PTC patients who had undergone reoperation due to cervical LN recurrence. We used the chi-square test, Fisher's exact test, Student's t test and the Mann-Whitney U test to compare characteristics between patients retreated with RAI and those who did not receive RAI after reoperation. A multivariate logistic regression model was used to determine the association between RAI and biochemical response. By means of the Kaplan-Meier estimator and a multivariate Cox proportional hazard model, we assessed whether administration of RAI after reoperation is associated with improved prognosis. RESULTS: RAI therapy was closely associated with a superior biochemical response in all selected patients according to both univariate (p = 0.012) and multivariate analyses (p = 0.020). Thirteen of 97 patients developed a second recurrence or progression of structural disease during follow-up. A Kaplan-Meier progression-free survival (PFS) curve showed that high post-retreatment thyroglobulin (Tg) levels (≥ 1 ng/mL) were associated with unfavourable prognosis (p = 0.0172). In the subgroup analysis, univariate analysis revealed that only patients without extranodal invasion who received adjuvant RAI therapy achieved better PFS than those who did not receive RAI therapy (p = 0.0203). Multivariate analysis showed that RAI (p = 0.045) also improved PFS in patients without extranodal invasion. CONCLUSIONS: Adjuvant RAI after reoperation for PTC recurrence/persistence was associated with a favourable biochemical response and tended to increase PFS. Specifically, it was significantly associated with improved PFS only in patients without extranodal extension.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/radioterapia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Reoperação , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Tireoidectomia , Recidiva Local de Neoplasia/radioterapia , Linfonodos/patologia
11.
Antioxidants (Basel) ; 12(5)2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37237856

RESUMO

Weightlessness in space leads to bone loss, muscle atrophy, and impaired immune defense in astronauts. Mesenchymal stem cells (MSCs) play crucial roles in maintaining the homeostasis and function of the tissue. However, how microgravity affects the characteristics MSCs and the related roles in the pathophysiological changes in astronauts remain barely known. Here we used a 2D-clinostat device to simulate microgravity. Senescence-associated-ß-galactosidase (SA-ß-gal) staining and the expression of senescent markers p16, p21, and p53 were used to evaluate the senescence of MSCs. Mitochondrial membrane potential (mΔΨm), reactive oxygen species (ROS) production, and ATP production were used to evaluate mitochondrial function. Western blot and immunofluorescence staining were used to investigate the expression and localization of Yes-associated protein (YAP). We found that simulated microgravity (SMG) induced MSC senescence and mitochondrial dysfunction. Mito-TEMPO (MT), a mitochondrial antioxidant, restored mitochondrial function and reversed MSC senescence induced by SMG, suggesting that mitochondrial dysfunction mediates SMG-induced MSC senescence. Further, it was found that SMG promoted YAP expression and its nuclear translocation in MSCs. Verteporfin (VP), an inhibitor of YAP, restored SMG-induced mitochondrial dysfunction and senescence in MSCs by inhibiting YAP expression and nuclear localization. These findings suggest that YAP inhibition alleviates SMG-induced MSC senescence via targeting mitochondrial dysfunction, and YAP may be a potential therapeutic target for the treatment of weightlessness-related cell senescence and aging.

12.
Eur J Neurol ; 30(9): 2620-2628, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37203242

RESUMO

BACKGROUND AND PURPOSE: This study was undertaken to investigate the longitudinal impact of type 2 diabetes mellitus (T2DM) on the prodromal and dementia stages of Alzheimer disease (AD), focusing on diabetes duration and other comorbidities. METHODS: A total of 1395 dementia-free individuals aged 55-90 years with maximum 15-year follow-up data were enrolled from the Alzheimer's Disease Neuroimaging Initiative database. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of the incidence of prodromal or dementia stages of AD. RESULTS: Longer T2DM duration (≥5 years; multiadjusted HR = 2.19, 95% confidence interval [CI] = 1.05-4.58), but not shorter T2DM duration (<5 years), was associated with a significantly increased risk of incident prodromal AD over a mean follow-up of 4.8 years. APOE ε4 allele (HR = 3.32, 95% CI = 1.41-7.79) and comorbid coronary artery disease (CAD; HR = 3.20, 95% CI = 1.29-7.95) further increased the risk of incident prodromal AD in patients with T2DM. No significant association was observed between T2DM and the risk of progression from prodromal AD to AD dementia. CONCLUSIONS: T2DM, which is characterized by a longer duration, increases the incidence risk of prodromal AD but not AD dementia. APOE ε4 allele and comorbid CAD strengthen the relationship between T2DM and prodromal AD. These findings highlight T2DM characteristics and its comorbidities as predictors for accurate prediction of AD and screening of at-risk populations.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Humanos , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Doença de Alzheimer/complicações , Estudos Longitudinais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Apolipoproteína E4/genética , Genótipo , Fatores de Risco
13.
J Prosthet Dent ; 129(6): 887.e1-887.e10, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37100651

RESUMO

STATEMENT OF PROBLEM: Previous studies have classified the sagittal root position of the maxillary anterior teeth and measured buccal plate thickness to aid treatment planning. A thin labial wall and buccal concavity may cause buccal perforation, dehiscence, or both in maxillary premolars. However, data on the restoration-driven principle to classify the maxillary premolar region are lacking. PURPOSE: The purpose of this clinical study was to investigate the occurrence of labial bone perforation and implantation into the maxillary sinus between various tooth-alveolar classifications with respect to the crown axis in maxillary premolars. MATERIAL AND METHODS: Cone beam computed tomography images of 399 participants (1596 teeth) were analyzed to determine the probability of labial bone perforation and implantation into the maxillary sinus when associated with variables that included tooth position and tooth-alveolar classification. RESULTS: The morphology in the maxillary premolars was classified as straight, oblique, or boot-shaped. The first premolars were 62.3% straight, 37.0% oblique, and 0.8% boot-shaped, and labial bone perforation occurred in 4.2% (21 of 497) of the straight, 54.2% (160 of 295) of the oblique, and 83.3% (5 of 6) of the boot-shaped first premolars when the virtual implant was 3.5×10 mm. When the virtual tapered implant was 4.3×10 mm, labial bone perforation occurred in 8.5% (42 of 497) of the straight, 68.5% (202 of 295) of the oblique, and 83.3% (5 of 6) of the boot-shaped first premolars. The second premolars were 92.4% straight, 7.5% oblique, and 0.1% boot-shaped, and labial bone perforation occurred in 0.5% (4 of 737) of the straight, 33.3% (20 of 60) of the oblique, and 0% (0 of 1) of the boot-shaped, respectively, when the virtual tapered implant was 3.5×10 mm; and labial bone perforation occurred in 1.3% (10/737) of the straight, 53.3% (32/60) of the oblique, and 100% (1/1) of the boot-shaped second premolars when the virtual tapered implant was 4.3×10 mm. CONCLUSIONS: When an implant is placed in the long axis of a maxillary premolar, the tooth position and tooth-alveolar classification should be considered when assessing the risk of labial bone perforation. Attention should be paid to the implant direction, diameter, and length in the oblique and boot-shaped maxillary premolars.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Seio Maxilar , Humanos , Dente Pré-Molar/diagnóstico por imagem , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Maxila/diagnóstico por imagem , Maxila/anatomia & histologia , Raiz Dentária/diagnóstico por imagem
14.
J Dairy Sci ; 106(6): 4366-4379, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37059660

RESUMO

Misregulation of spermatogenesis transcription factors (TF) in hybrids can lead to misexpression, which is a mechanism for hybrid male sterility (HMS). We used dzo (male offspring of Bos taurus ♂ × Bos grunniens ♀) in bovines to investigate the relationship of the key TF with HMS via RNA sequencing and assay for transposase-accessible chromatin with high-throughput sequencing analyses. RNA sequencing showed that the widespread misexpression in dzo was associated with spermatogenesis-related genes and somatic or progenitor genes. The transition from leptotene or zygotene spermatocytes to pachytene spermatocytes may be the key stage for meiosis arrest in dzo. The analysis of TF-binding motif enrichment revealed that the male meiosis-specific master TF MYB proto-oncogene like 1 (MYBL1, known as A-MYB) motif was enriched on the promoters of downregulated pachytene spermatocyte genes in dzo. Assay for transposase-accessible chromatin with high-throughput sequencing revealed that TF-binding sites for MYBL1, nuclear transcription factor Y, and regulatory factor X were enriched in the low-chromatin accessibility region of dzo. The target genes of the MYBL1-binding motif were associated with meiosis-specific genes and significantly downregulated in dzo testis. The transcription factor MYBL1 may be the candidate master regulator for pachytene spermatocyte genes dysregulated in interspecific HMS dzo. This study reported that a few upstream TF regulation changes might exert a cascading effect downstream in a regulatory network as a mechanism for HMS.


Assuntos
Espermatócitos , Fatores de Transcrição , Bovinos , Masculino , Animais , Espermatócitos/fisiologia , Fatores de Transcrição/genética , Espermatogênese , Testículo , Cromatina
15.
Funct Plant Biol ; 50(5): 363-377, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36949582

RESUMO

Mesembryanthemum crystallinum L. (ice plant) develops salt tolerance during the transition from the juvenile to the adult stage through progressive morphological, physiological, biochemical, and molecular changes. Myo -inositol is the precursor for the synthesis of compatible solute D-pinitol and promotes Na+ transport in ice plants. We previously showed that supplying myo -inositol to 9-day-old seedlings alleviates salt damage by coordinating the expression of genes involved in inositol synthesis and transport, affecting osmotic adjustment and the Na/K balance. In this study, we examined the effects of myo -inositol on physiological parameters and inositol-related gene expression in early- and late-stage juvenile plants. The addition of myo -inositol to salt-treated, hydroponically grown late juvenile plants had no significant effects on growth or photosynthesis. In contrast, supplying exogenous myo -inositol to salt-treated early juvenile plants increased leaf biomass, relative water content, and chlorophyll content and improved PSII activity and CO2 assimilation. The treatment combining high salt and myo -inositol synergistically induced the expression of myo -inositol phosphate synthase (INPS ), myo -inositol O -methyltransferase (IMT ), and inositol transporters (INTs ), which modulated root-to-shoot Na/K ratio and increased leaf D-pinitol content. The results indicate that sufficient myo -inositol is a prerequisite for high salt tolerance in ice plant.


Assuntos
Mesembryanthemum , Plantas Tolerantes a Sal , Plantas Tolerantes a Sal/metabolismo , Mesembryanthemum/genética , Mesembryanthemum/metabolismo , Tolerância ao Sal , Inositol/metabolismo
16.
BMC Musculoskelet Disord ; 24(1): 125, 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36788513

RESUMO

BACKGROUND: To investigate the diagnostic efficacy of mDIXON-Quant technique for prediction of bone loss in male adults. METHODS: One hundred thirty-eight male adults were divided into normal, osteopenia, and osteoporosis groups based on DXA and QCT for the lumbar spine. Differences in mDIXON-Quant parameters [fat fraction (FF) and T2* value] among three groups, as well as the correlation of mDIXON-Quant parameters and bone mineral density (BMD) were analyzed. The areas under the curves (AUCs) for mDIXON-Quant parameters for prediction of low bone mass were calculated. RESULTS: According to DXA standard, FF and T2* value were significantly increased in osteoporosis group compared with normal group (P = 0.012 and P < 0.001). According to QCT standard, FF was significantly increased in osteopenia and osteoporosis groups compared with normal group (both P < 0.001). T2* values were significantly different among three groups (all P < 0.05). After correction for age and body mass index, FF was negatively correlated with areal BMD and volumetric BMD (r = -0.205 and -0.604, respectively; both P < 0.05), and so was T2* value (r = -0.324 and -0.444, respectively; both P < 0.05). The AUCs for predicting low bone mass according to DXA and QCT standards were 0.642 and 0.898 for FF, 0.648 and 0.740 for T2* value, and 0.677 and 0.920 for both combined, respectively. CONCLUSIONS: FF combined with T2* value has a better diagnostic efficacy than FF or T2* value alone in prediction of low bone mass in male adults, which is expected to be a promising MRI method for the screening of bone quality. TRIAL REGISTRATION: ChiCTR1900024511 (Registered 13-07-2019).


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Adulto , Humanos , Masculino , Densidade Óssea , Osteoporose/diagnóstico por imagem , Doenças Ósseas Metabólicas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Vértebras Lombares/diagnóstico por imagem , Absorciometria de Fóton
17.
BMC Musculoskelet Disord ; 24(1): 136, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36810003

RESUMO

BACKGROUND: With the wide application of QCT in the clinical assessment of osteoporosis and sarcopenia, the characteristics of musculoskeletal degeneration in middle-aged and elderly people need to be further revealed. We aimed to investigate the degenerate characteristics of lumbar and abdominal muscles in middle-aged and elderly people with varying bone mass. METHODS: A total of 430 patients aged 40-88 years were divided into normal, osteopenia, and osteoporosis groups according to quantitative computed tomography (QCT) criteria. The skeletal muscular mass indexes (SMIs) of five muscles [abdominal wall muscles (AWM), rectus abdominis (RA), psoas major muscle (PMM), posterior vertebral muscles (PVM), and paravertebral muscles (PM)] included in lumbar and abdominal muscles were measured by QCT. Differences in SMIs among three groups, as well as the correlation between SMIs and volumetric bone mineral density (vBMD) were analyzed. The areas under the curves (AUCs) for SMIs for prediction of low bone mass and osteoporosis were calculated. RESULTS: In male group, SMIs of RA and PM in osteopenia group were significantly lower than those in the normal group (P = 0.001 and 0.023, respectively). In female group, only SMI of RA in osteopenia group was significantly lower than that in the normal group (P = 0.007). SMI of RA was positively correlated with vBMD with the highest coefficients in male and female groups (r = 0.309 and 0.444, respectively). SMIs of AWM and RA had higher AUCs varying from 0.613 to 0.737 for prediction of low bone mass and osteoporosis in both genders. CONCLUSIONS: The changes of SMIs of the lumbar and abdominal muscles in patients with varying bone mass are asynchronous. SMI of RA is expected to be a promising imaging marker for predicting abnormal bone mass. TRIAL REGISTRATION: ChiCTR1900024511 (Registered 13-07-2019).


Assuntos
Músculos do Dorso , Doenças Ósseas Metabólicas , Osteoporose , Idoso , Pessoa de Meia-Idade , Humanos , Feminino , Masculino , Densidade Óssea/fisiologia , Vértebras Lombares , Músculos Abdominais
18.
Comput Inform Nurs ; 40(12): 814-824, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36516032

RESUMO

The present study referred to the technology-based learning model to conduct a systematic review of the dimensions of nursing activities, research samples, research methods, roles of artificial intelligence, applied artificial intelligence algorithms, evaluation measure of algorithms, and research foci. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses procedure, this study obtained and analyzed a total of 102 high-quality artificial intelligence-associated nursing activities studies published from 2001 to 2020 in the Web of Science database. The results showed: (1) In terms of nursing activities, nursing management was explored the most, followed by nursing assessment; (2) quantitative methods were most frequently adopted in artificial intelligence-associated nursing activities studies to investigate issues related to patients, followed by nursing staff; (3) the most adopted roles of artificial intelligence in artificial intelligence-associated nursing activities studies were profiling and prediction, followed by assessment and evaluation; (4) artificial intelligence-associated nursing activities studies frequently mixed applied artificial intelligence algorithms and evaluation measure of algorithms; (5) in the dimension of research foci, most studies mainly paid attention to the design or evaluation of the artificial intelligence systems/instruments, followed by investigating the correlation and affect issues. Based on the findings, several recommendations are raised as a reference for future researchers, educators, and policy makers.


Assuntos
Algoritmos , Inteligência Artificial , Humanos , Bases de Dados Factuais , Publicações
19.
Int J Ophthalmol ; 15(11): 1765-1771, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36404979

RESUMO

AIM: To evaluate the outcome of endoscopic dacryocystorhinostomy (En-DCR) with mucosal anastomosis in chronic dacryocystitis patients, with various categories of ethmoid sinuses. METHODS: Between July 2015 and September 2019, 1439 adult patients, representing 1623 affected eyes, presented with chronic dacryocystitis and were scheduled for En-DCR. The categories of ethmoid sinuses were preoperatively determined, using computed tomography-dacryocystography (CT-DCG), and were classified as category 1 (C1), category 2 (C2), and category 3 (C3). No sinuses anterior to the posterior lacrimal crest defined as C1. Sinuses found between the anterior edge of the lacrimal bone and the posterior lacrimal crest defined as C2. Sinuses found anterior to the lacrimal bone suture defined as C3. At the end of surgery, the dacryocyst and nasal mucosa were anastomosed in C1, and the dacryocyst mucosa and anterior ethmoid sinus were anastomosed in C2 and C3 ethmoid sinus patients. The surgical success rate and related complications, in patients with 3 categories of ethmoid cells, were monitored and documented. RESULTS: Postoperative data was obtained for 179 C1 affected eyes, 878 C2 affected eyes, and 432 C3 affected eyes. The overall success rate of En-DCR was 93.0% (1385/1489). Additionally, the success rates were comparable among the different ethmoid categories at 12mo post operation. We demonstrated that the major reason for surgical failure was intranasal ostial closure, due to granulation or scar tissue. CONCLUSION: En-DCR is a feasible and highly effective primary treatment for chronic dacryocystitis. To ensure surgical success, the surgery protocol must be designed in accordance with the category of ethmoid sinuses present in individual patient.

20.
Front Genet ; 13: 1008649, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186474

RESUMO

MicroRNAs (miRNAs) might play critical roles in skeletal myofiber specification. In a previous study, we found that chicken miR-499-5p is specifically expressed in slow-twitch muscle and that its potential target gene is SOX6. In this study, we performed RNA sequencing to investigate the effects of SOX6 and miR-499-5p on the modulation and regulation of chicken muscle fiber type and its regulatory mechanism. The expression levels of miR-499-5p and SOX6 demonstrated opposing trends in different skeletal muscles and were associated with muscle fiber type composition. Differential expression analysis revealed that miR-499-5p overexpression led to significant changes in the expression of 297 genes in chicken primary myoblasts (CPMs). Myofiber type-related genes, including MYH7B and CSRP3, showed expression patterns similar to those in slow-twitch muscle. According to functional enrichment analysis, differentially expressed genes were mostly associated with muscle development and muscle fiber-related processes. SOX6 was identified as the target gene of miR-499-5p in CPM using target gene mining and luciferase reporter assays. SOX6 knockdown resulted in upregulation of the slow myosin genes and downregulation of fast myosin genes. Furthermore, protein-protein interaction network analysis revealed that MYH7B and RUNX2 may be the direct targets of SOX6. These results indicated that chicken miR-499-5p may promote slow-twitch muscle fiber formation by repressing SOX6 expression. Our study provides a dataset that can be used as a reference for animal meat quality and human muscle disease studies.

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