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1.
BMC Genomics ; 25(1): 33, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38177997

RESUMEN

BACKGROUND: The sexual maturity of chickens is an important economic trait, and the breeding of precocious and delayed puberty roosters is an important selection strategy for broilers. The comb serves as an important secondary sexual characteristic of roosters and determines their sexual precocity. Moreover, comb development is closely associated with gonad development in roosters. However, the underlying molecular mechanism regulating the sexual maturity of roosters has not yet been fully explored. RESULTS: In order to identify the genes related to precocious puberty in Qingyuan partridge roosters, and based on the synchrony of testis and combs development, combined with histological observation and RNA-seq method, the developmental status and gene expression profile of combs and testis were obtained. The results showed that during the early growth and development period (77 days of age), the development of combs and testis was significant in the high comb (H) group versus the low comb (L) group (p < 0.05); however, the morphological characteristic of the comb and testicular tissues converged during the late growth and development period (112 days of age) in the H and L groups. Based on these results, RNA-sequencing analysis was performed on the comb and testis tissues of the 77 and 112 days old Qingyuan Partridge roosters with different comb height traits. GO and KEGG analysis enrichment analysis showed that the differentially expressed genes were primarily enriched in MAPK signaling, VEGF signaling, and retinol metabolism pathways. Moreover, weighted correlation network analysis and module co-expression network analysis identified WNT6, AMH, IHH, STT3A, PEX16, KPNA7, CATHL2, ROR2, PAMR1, WISP2, IL17REL, NDRG4, CYP26B1, and CRHBP as the key genes associated with the regulation of precocity and delayed puberty in Qingyuan Partridge roosters. CONCLUSIONS: In summary, we identified the key regulatory genes of sexual precocity in roosters, which provide a theoretical basis for understanding the developmental differences between precocious and delayed puberty in roosters.


Asunto(s)
Pollos , Testículo , Animales , Masculino , Testículo/metabolismo , Pollos/metabolismo , Perfilación de la Expresión Génica , Transcriptoma , Fenotipo
2.
Biotechnol Bioeng ; 121(4): 1384-1393, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38151965

RESUMEN

2,6-diaminopurine (Z), a naturally occurring noncanonical nucleotide base found in bacteriophages, enhances DNA hybridization by forming three hydrogen bonds with thymine (T). These distinct biochemical characteristics make it particularly valuable in applications that rely on the thermodynamics of DNA hybridization. However, the practical use of Z-containing oligos is limited by their high production cost and the challenges associated with their synthesis. Here, we developed an efficient and cost-effective approach to synthesize Z-containing oligos of high quality based on an isothermal strand displacement reaction. These newly synthesized Z-oligos are then employed as toehold-blockers in an isothermal genotyping assay designed to detect rare single nucleotide variations (SNV). When compared with their counterparts containing the standard adenine (A) base, the Z-containing blockers significantly enhance the accuracy of identifying SNV. Overall, our innovative methodology in the synthesis of Z-containing oligos, which can also be used to incorporate other unconventional and unnatural bases into oligonucleotides, is anticipated to be adopted for diverse applications, including genotyping, biosensing, and gene therapy.


Asunto(s)
2-Aminopurina/análogos & derivados , ADN , Nucleótidos , Genotipo , Hibridación de Ácido Nucleico , ADN/química
3.
Eur Radiol ; 34(8): 5066-5076, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38231392

RESUMEN

OBJECTIVE: To build and merge a diagnostic model called multi-input DenseNet fused with clinical features (MI-DenseCFNet) for discriminating between Staphylococcus aureus pneumonia (SAP) and Aspergillus pneumonia (ASP) and to evaluate the significant correlation of each clinical feature in determining these two types of pneumonia using a random forest dichotomous diagnosis model. This will enhance diagnostic accuracy and efficiency in distinguishing between SAP and ASP. METHODS: In this study, 60 patients with clinically confirmed SAP and ASP, who were admitted to four large tertiary hospitals in Kunming, China, were included. Thoracic high-resolution CT lung windows of all patients were extracted from the picture archiving and communication system, and the corresponding clinical data of each patient were collected. RESULTS: The MI-DenseCFNet diagnosis model demonstrates an internal validation set with an area under the curve (AUC) of 0.92. Its external validation set demonstrates an AUC of 0.83. The model requires only 10.24s to generate a categorical diagnosis and produce results from 20 cases of data. Compared with high-, mid-, and low-ranking radiologists, the model achieves accuracies of 78% vs. 75% vs. 60% vs. 40%. Eleven significant clinical features were screened by the random forest dichotomous diagnosis model. CONCLUSION: The MI-DenseCFNet multimodal diagnosis model can effectively diagnose SAP and ASP, and its diagnostic performance significantly exceeds that of junior radiologists. The 11 important clinical features were screened in the constructed random forest dichotomous diagnostic model, providing a reference for clinicians. CLINICAL RELEVANCE STATEMENT: MI-DenseCFNet could provide diagnostic assistance for primary hospitals that do not have advanced radiologists, enabling patients with suspected infections like Staphylococcus aureus pneumonia or Aspergillus pneumonia to receive a quicker diagnosis and cut down on the abuse of antibiotics. KEY POINTS: • MI-DenseCFNet combines deep learning neural networks with crucial clinical features to discern between Staphylococcus aureus pneumonia and Aspergillus pneumonia. • The comprehensive group had an area under the curve of 0.92, surpassing the proficiency of junior radiologists. • This model can enhance a primary radiologist's diagnostic capacity.


Asunto(s)
Aprendizaje Profundo , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Persona de Mediana Edad , Diagnóstico Diferencial , Tomografía Computarizada por Rayos X/métodos , Neumonía Estafilocócica/diagnóstico por imagen , Neumonía Estafilocócica/microbiología , Anciano , Aspergilosis Pulmonar/diagnóstico por imagen , Staphylococcus aureus/aislamiento & purificación , Adulto , Interpretación de Imagen Radiográfica Asistida por Computador/métodos
4.
Soft Matter ; 20(27): 5314-5323, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38712600

RESUMEN

Magnetic hydrogel actuators exhibit promising applications in the fields of soft robotics, bioactuators, and flexible sensors owing to their inherent advantages such as remote control capability, untethered deformation and motion control, as well as easily manipulable behavior. However, it is still a challenge for magnetic hydrogels to achieve adjustable stiffness and shape fixation under magnetic field actuation deformation. Herein, a simple and effective approach is proposed for the design of magnetic shape memory hydrogels to accomplish this objective. The magnetic shape memory hydrogels, consisting of methacrylamide, methacrylic acid, polyvinyl alcohol and Fe3O4 magnetic particles, which crosslinked by hydrogen bonds, are facilely prepared via one-pot polymerization. The dynamic nature of noncovalent bonds offers the magnetic hydrogels with excellent mechanical properties, precisely controlled stiffness, and effective shape fixation. The presence of Fe3O4 particles renders the hydrogels soft when subjected to an alternating current field, facilitating their deformation under the influence of an actuation magnetic field. After the elimination of the alternating current magnetic field, the hydrogels stiffen and attain a fixed actuated shape in the absence of any external magnetic field. Moreover, this remarkable magnetic shape memory hydrogel is effectively employed as an underwater soft gripper for lifting heavy objects. This work provides a novel strategy for fabricating magnetic hydrogels with non-contact reversible actuation deformation, tunable stiffness and shape locking.

5.
BMC Womens Health ; 24(1): 160, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443932

RESUMEN

BACKGROUND: Approximately 30% of post-operative breast cancer patients develop shoulder joint movement disorders affecting routine upper limb movement. This study discusses the impact of a neuromuscular joint facilitation (NJF) method on the physical function of breast cancer patients experiencing shoulder dysfunction during chemotherapy after radical surgery. METHODS: This study included 162 female patients who have unilateral breast cancer in a cancer hospital in China. They developed shoulder joint mobility disorders during chemotherapy within 1-3 months postoperatively. These patients were divided into three groups: NJF, conventional rehabilitation (conventional group), and control groups. The clinical examination included the maximum passive and active range of motion (ROM) of the shoulder (flexion, extension, abduction, adduction, and external and internal rotation). Other evaluations included a pain score using a visual analog scale (VAS), grip strength, and supraspinatus muscle thickness. All tests were evaluated pre-and post-intervention. RESULTS: The NJF group showed a significant increase in all shoulder ROM angles post-intervention. In the conventional group, all other ROM values increased significantly, except passive external rotation ROM. In the control group, all other ROM values increased significantly, except passive and active external rotation ROM. All three groups had decreased VAS scores, increased grip strength, and supraspinatus muscle thickness post-intervention during active abduction. In the control group, the supraspinatus contraction rate decreased significantly at 60° and 90° abduction post-intervention compared to that at pre-intervention. CONCLUSION: This study revealed that NJF during chemotherapy had positive clinical intervention effects, improving shoulder joint mobility disorders, pain, grip strength, and external rotation following radical breast cancer surgery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; https://www.chictr.org.cn/ (ChiCTR2300073170), registered (03/07/2023).


Asunto(s)
Neoplasias de la Mama , Entrenamiento de Fuerza , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Mama , Pueblo Asiatico , Dolor
6.
Neurosurg Rev ; 47(1): 328, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39004661

RESUMEN

STUDY DESIGN: Retrospective cohort analysis. OBJECTIVE: The purpose of this study is to investigate whether the removal of the posterior longitudinal ligament (PLL) affects the mid-term outcome of anterior cervical fusion for cervical spondylosis with sympathetic symptoms(CSSS). METHODS: From January 2012 to July 2013, 66 patients who were diagnosed with CSSS with ≥ 10-year follow-up at our institution were assessed. All patients were divided into two groups: Group A (36 cases) in which patients underwent anterior cervical fusion with PLL resection and Group B (30 cases) in which patients underwent anterior cervical fusion without PLL resection. The sympathetic symptom 20-point system was used to evaluate the sympathetic symptoms, such as tinnitus, headache and vertigo, etc. And the neurological status was assessed by the Japanese Orthopedic Association (JOA) scores. Clinical and radiologic data were evaluated preoperatively, 9 days, 3 months, 6 months, 12 months, 24 months, 60 months, and 120 months postoperatively. Data collected included all perioperative complications as morbidities that occurred during the period of follow-up. RESULTS: The postoperative JOA scores and 20-point score can be significantly improved compared with preoperative whether the PLL is removed in both groups. However, the postoperative 20-point score of patients in group A was significantly different from that in group B. No loosening and displacement of prosthesis occurred. CONCLUSION: A better clinical effect could be attained when resecting the PLL in the operation. The PLL may play an important role in CSSS. The mid-term outcomes of anterior cervical fusion with PLL resection were satisfied in treating CSSS.


Asunto(s)
Vértebras Cervicales , Ligamentos Longitudinales , Fusión Vertebral , Espondilosis , Humanos , Masculino , Femenino , Espondilosis/cirugía , Espondilosis/complicaciones , Persona de Mediana Edad , Fusión Vertebral/métodos , Estudios Retrospectivos , Vértebras Cervicales/cirugía , Resultado del Tratamiento , Anciano , Ligamentos Longitudinales/cirugía , Adulto , Estudios de Cohortes , Estudios de Seguimiento
7.
Eur Spine J ; 33(7): 2569-2576, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38764090

RESUMEN

BACKGROUND: Understanding spinal sagittal balance is crucial for assessing and treating spinal deformities in pediatric populations. OBJECTIVE: The aim of the present observational study is to examine the parameters of sagittal alignment of the regional spine and spinopelvic region in asymptomatic pediatric populations and the characteristics of these parameters with age and sex. METHODS: We enrolled 217 participants, consisting of 112 males (51.6%) and 105 females (48.4%), aged between 4 and 15 years, with an average age of 12.19 years. Pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis, T1 slope, C7 slope, cervical sagittal vertical axis, and C2-7 Cobb angle were measured. Three spine surgeons conducted radiographic measurements utilizing the PACS software. The measurement reliability was assessed through ICCs. RESULTS: Our results show significant age-related changes in pelvic tilt and cervical sagittal vertical axis, with notable gender differences in pelvic tilt, lumbar lordosis, and thoracic kyphosis. Girls have larger PT, boys have larger cSVA. PI, PT, and cSVA also differ among different age groups. Correlation analysis shows that a series of relationships that align with adult population patterns between pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, and thoracic kyphosis. CONCLUSION: Significant variations in PT and cSVA across diverse age cohorts highlights notable disparities in the distribution of PT and cSVA values within the pediatric population. Gender-based differences in PT, LL, and TK and correlation in spinopelvic parameter could enhances our understanding of compensatory mechanisms.


Asunto(s)
Columna Vertebral , Humanos , Masculino , Femenino , Niño , Adolescente , Preescolar , Columna Vertebral/diagnóstico por imagen , Pelvis/diagnóstico por imagen , Lordosis/diagnóstico por imagen , Cifosis/diagnóstico por imagen , Cifosis/epidemiología , Huesos Pélvicos/diagnóstico por imagen , Radiografía/métodos
8.
Environ Toxicol ; 39(7): 3883-3896, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38563506

RESUMEN

Excessive exposure to manganese (Mn) through drinking water and food during pregnancy significantly heightens the likelihood of neurodevelopmental damage in offspring. Multiple studies have indicated that melatonin (Mel) may help to relieve neurodevelopmental disorders caused by Mn, but potential mechanisms underlying this effect require further exploration. Here, we utilized primary neural stem cells (NSCs) as a model to elucidate the molecular mechanism underlying the protective function of Mel on Mn-induced cell proliferation dysfunction and cycle arrest. Our results showed that Mn disrupted the cell cycle in NSCs by suppressing positive regulatory proteins (CDK2, Cyclin A, Cyclin D1, and E2F1) and enhancing negative ones (p27KIP1 and p57KIP2), leading to cell proliferation dysfunction. Mel inhibited the Mn-dependent changes to these proteins and the cell cycle through nuclear receptor-related protein 1 (Nurr1), thus alleviating the proliferation dysfunction. Knockdown of Nurr1 using lentivirus-expressed shRNA in NSCs resulted in a diminished protective effect of Mel. We concluded that Mel mitigated Mn-induced proliferation dysfunction and cycle arrest in NSCs through Nurr1.


Asunto(s)
Ciclo Celular , Proliferación Celular , Manganeso , Melatonina , Células-Madre Neurales , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Melatonina/farmacología , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Animales , Proliferación Celular/efectos de los fármacos , Manganeso/toxicidad , Ciclo Celular/efectos de los fármacos , Células Cultivadas , Ratones
9.
Angew Chem Int Ed Engl ; 63(7): e202317935, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38117662

RESUMEN

An emerging class of C-C coupling transformations that furnish drug-like building blocks involves catalytic hydrocarbonation of alkenes. However, despite notable advances in the field, hydrocarbon addition to gem-difluoroalkenes without additional electronic activation remains largely unsuccessful. This owes partly to poor reactivity and the propensity of difluoroalkenes to undergo defluorinative side reactions. Here, we report a nickel catalytic system that promotes efficient 1,2-selective hydroarylation and hydroalkenylation, suppressing defluorination and providing straightforward access to a diverse assortment of prized organofluorides bearing difluoromethyl-substituted carbon centers. In contrast to radical-based pathways and reactions triggered by hydrometallation via a nickel-hydride complex, our experimental and computational studies support a mechanism in which a catalytically active nickel-bromide species promotes selective carbonickelation with difluoroalkenes followed by alkoxide exchange and hydride transfer, effectively overcoming the difluoroalkene's intrinsic electronic bias.

11.
Anal Chim Acta ; 1312: 342742, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38834261

RESUMEN

Hyperuricemia (HUA) has gradually become a public health burden as an independent risk factor for a variety of chronic diseases. Herein, a user-friendly point-of-care (POC) detection system (namely "Smart-HUA-Monitor") based on smartphone-assisted paper-based microfluidic is proposed for colorimetric quantification of HUA urinary markers, including uric acid (UA), creatinine (CR) and pH. The detection limits of UA and CR were 0.0178 and 0.5983 mM, respectively, and the sensitivity of pH were 0.1. The method was successfully validated in artificial urine samples and 100 clinical samples. Bland-Altman plots showed a high consistency between µPAD and the testing instruments (HITACHI 7600 Automatic Analyzer, URIT-500B Urine Analyzer and AU5800B automatic biochemical analyzer) in hospital. Smart-HUA-Monitor provides an accurate quantitative, rapid, low-cost and reliable tool for the monitoring and early diagnosis of HUA urine indicators.


Asunto(s)
Colorimetría , Hiperuricemia , Papel , Polímeros , Ácido Úrico , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/orina , Polímeros/química , Ácido Úrico/orina , Colorimetría/instrumentación , Dispositivos Laboratorio en un Chip , Teléfono Inteligente , Creatinina/orina , Técnicas Analíticas Microfluídicas/instrumentación , Límite de Detección , Biomarcadores/orina , Concentración de Iones de Hidrógeno
12.
J Agric Food Chem ; 72(20): 11733-11745, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38725145

RESUMEN

Amino acids are essential for the activation of the mechanistic target of rapamycin (mTOR), but the corresponding molecular mechanism is not yet fully understood. We previously found that Met stimulated eukaryotic elongation factor α (eEF1Bα) nuclear localization in bovine mammary epithelial cells (MECs). Herein, we explored the role and molecular mechanism of eEF1Bα in methionine (Met)- and leucine (Leu)-stimulated mTOR gene transcription and milk synthesis in MECs. eEF1Bα knockdown decreased milk protein and fat synthesis, cell proliferation, and mTOR mRNA expression and phosphorylation, whereas eEF1Bα overexpression had the opposite effects. QE-MS analysis detected that eEF1Bα was phosphorylated at Ser106 in the nucleus and Met and Leu stimulated p-eEF1Bα nuclear localization. eEF1Bα knockdown abrogated the stimulation of Met and Leu by mTOR mRNA expression and phosphorylation, and this regulatory role was dependent on its phosphorylation. Akt knockdown blocked the stimulation of Met and Leu by eEF1Bα and p-eEF1Bα expression. ChIP-PCR detected that p-eEF1Bα bound only to the -548 to -793 nt site in the mTOR promoter, and ChIP-qPCR further detected that Met and Leu stimulated this binding. eEF1Bα mediated Met and Leu' stimulation on mTOR mRNA expression and phosphorylation through inducing AT-rich interaction domain 1A (ARID1A) ubiquitination degradation, and this process depended on eEF1Bα phosphorylation. p-eEF1Bα interacted with ARID1A and ubiquitin protein ligase E3 module N-recognition 5 (UBR5), and UBR5 knockdown rescued the decrease of the ARID1A protein level by eEF1Bα overexpression. Both eEF1Bα and p-eEF1Bα were highly expressed in mouse mammary gland tissues during the lactating period. In summary, we reveal that Met and Leu stimulate mTOR transcriptional activation and milk protein and fat synthesis in MECs through eEF1Bα-UBR5-ARID1A signaling.


Asunto(s)
Células Epiteliales , Leucina , Metionina , Leche , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Bovinos , Femenino , Ratones , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Leucina/farmacología , Leucina/metabolismo , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/citología , Metionina/metabolismo , Metionina/farmacología , Leche/química , Leche/metabolismo , Factor 1 de Elongación Peptídica/genética , Factor 1 de Elongación Peptídica/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcripción Genética/efectos de los fármacos , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
13.
Comput Struct Biotechnol J ; 23: 1429-1438, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38616961

RESUMEN

The development of an innovative drug is complex and time-consuming, and the drug target identification is one of the critical steps in drug discovery process. Effective and accurate identification of drug targets can accelerate the drug development process. According to previous research, evolutionary and genetic information of genes has been found to facilitate the identification of approved drug targets. In addition, allosteric proteins have great potential as targets due to their structural diversity. However, this information that could facilitate target identification has not been collated in existing drug target databases. Here, we construct a comprehensive drug target database named Genetic and Evolutionary features of drug Targets database (GETdb, http://zhanglab.hzau.edu.cn/GETdb/page/index.jsp). This database not only integrates and standardizes data from dozens of commonly used drug and target databases, but also innovatively includes the genetic and evolutionary information of targets. Moreover, this database features an effective allosteric protein prediction model. GETdb contains approximately 4000 targets and over 29,000 drugs, and is a user-friendly database for searching, browsing and downloading data to facilitate the development of novel targets.

14.
Adv Sci (Weinh) ; 11(25): e2400207, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38655847

RESUMEN

Wearable sensors hold immense potential for real-time and non-destructive sensing of volatile organic compounds (VOCs), requiring both efficient sensing performance and robust mechanical properties. However, conventional colorimetric sensor arrays, acting as artificial olfactory systems for highly selective VOC profiling, often fail to meet these requirements simultaneously. Here, a high-performance wearable sensor array for VOC visual detection is proposed by extrusion printing of hybrid inks containing surface-functionalized sensing materials. Surface-modified hydrophobic polydimethylsiloxane (PDMS) improves the humidity resistance and VOC sensitivity of PDMS-coated dye/metal-organic frameworks (MOFs) composites. It also enhances their dispersion within liquid PDMS matrix, thereby promoting the hybrid liquid as high-quality extrusion-printing inks. The inks enable direct and precise printing on diverse substrates, forming a uniform and high particle-loading (70 wt%) film. The printed film on a flexible PDMS substrate demonstrates satisfactory flexibility and stretchability while retaining excellent sensing performance from dye/MOFs@PDMS particles. Further, the printed sensor array exhibits enhanced sensitivity to sub-ppm VOC levels, remarkable resistance to high relative humidity (RH) of 90%, and the differentiation ability for eight distinct VOCs. Finally, the wearable sensor proves practical by in situ monitoring of wheat scab-related VOC biomarkers. This study presents a versatile strategy for designing effective wearable gas sensors with widespread applications.


Asunto(s)
Tinta , Estructuras Metalorgánicas , Compuestos Orgánicos Volátiles , Dispositivos Electrónicos Vestibles , Compuestos Orgánicos Volátiles/análisis , Estructuras Metalorgánicas/química , Impresión/métodos , Humanos , Dimetilpolisiloxanos/química
15.
Int J Nanomedicine ; 19: 6845-6855, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39005957

RESUMEN

Objective: Collagen, a widely used natural biomaterial polymer in skin tissue engineering, can be innovatively processed into nanocollagen through cryogenic milling to potentially enhance skin tissue healing. Although various methods for fabricating nanocollagen have been documented, there is no existing study on the fabrication of nanocollagen via cryogenic milling, specifically employing graphene oxide as separators to prevent agglomeration. Methods: In this study, three research groups were created using cryogenic milling: pure nanocollagen (Pure NC), nanocollagen with 0.005% graphene oxide (NC + 0.005% GO), and nanocollagen with 0.01% graphene oxide (NC+0.01% GO). Characterization analyses included transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, x-ray diffraction (XRD), zeta potential (ZP), and polydispersity index (PDI). Results: TEM and SEM analysis revealed that nanocollagen groups alone exhibited particle sizes of less than 100 nm. FTIR spectroscopic investigations indicated the presence of amide A, B, and I, II, and III (1800 to 800 cm-1) in all nanocollagen study groups, with the characteristic C-O-C stretching suggesting the incorporation of graphene oxide (GO). XRD data exhibited broadening of the major peak as the proportion of GO increased from pure NC to the nanocollagen groups with GO. Zeta potential measurements indicated electrostatic attraction of the samples to negatively charged surfaces, accompanied by sample instability. PDI results depicted size diameters ranging from 800 to 1800 nm, indicating strong polydispersity with multiple size populations. Conclusion: This research demonstrated that collagen can be successfully fabricated into nanoparticles with sizes smaller than 100 nm.


Asunto(s)
Colágeno , Grafito , Tamaño de la Partícula , Grafito/química , Colágeno/química , Espectroscopía Infrarroja por Transformada de Fourier , Materiales Biocompatibles/química , Difracción de Rayos X , Ingeniería de Tejidos/métodos , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión
16.
Mol Med Rep ; 30(2)2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38818814

RESUMEN

C1q/tumor necrosis factor­related protein 3 (CTRP3) expression is markedly reduced in the serum of patients with osteoporosis. The present study aimed to investigate whether CTRP3 reduces bone loss in oophorectomy (OVX)­induced mice via the AMP­activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/nuclear factor E2­related factor 2 (Nrf2) signaling pathway. Female C57BL/6J mice and MC3T3­E1 cells were used to construct in vivo and in vitro models of osteoporosis, respectively. The left femurs of mice were examined using micro­computed tomography scans and bone­related quantitative morphological evaluation was performed. Pathological changes and the number of osteoclasts in the left femurs of mice were detected using hematoxylin and eosin, and tartrate­resistant acid phosphatase (TRAP) staining. Runt­related transcription factor­2 (RUNX2) expression in the left femurs was detected using immunofluorescence analysis, and the serum levels of bone resorption markers (C­telopeptide of type I collagen and TRAP) and bone formation markers [osteocalcin (OCN) and procollagen type 1 N­terminal propeptide] were detected. In addition, osteoblast differentiation and calcium deposits were examined in MC3T3­E1 cells using alkaline phosphatase (ALP) and Alizarin red staining, respectively. Moreover, RUNX2, ALP and OCN expression levels were detected using reverse transcription­quantitative PCR, and the expression levels of proteins associated with the AMPK/SIRT1/Nrf2 signaling pathway were detected using western blot analysis. The results revealed that globular CTRP3 (gCTRP3) alleviated bone loss and promoted bone formation in OVX­induced mice. gCTRP3 also facilitated the osteogenic differentiation of MC3T3­E1 cells through the AMPK/SIRT1/Nrf2 signaling pathway. The addition of an AMPK inhibitor (Compound C), SIRT1 inhibitor (EX527) or Nrf2 inhibitor (ML385) reduced the osteogenic differentiation of MC3T3­E1 cells via inhibition of gCTRP3. In conclusion, gCTRP3 inhibits OVX­induced osteoporosis by activating the AMPK/SIRT1/Nrf2 signaling pathway.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Factor 2 Relacionado con NF-E2 , Osteoporosis , Ovariectomía , Transducción de Señal , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Sirtuina 1/genética , Femenino , Ratones , Osteoporosis/metabolismo , Osteoporosis/etiología , Osteoporosis/patología , Factor 2 Relacionado con NF-E2/metabolismo , Ovariectomía/efectos adversos , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones Endogámicos C57BL , Osteoblastos/metabolismo , Línea Celular , Osteoclastos/metabolismo , Modelos Animales de Enfermedad , Fémur/metabolismo , Fémur/patología , Fémur/diagnóstico por imagen , Osteogénesis/efectos de los fármacos
17.
Int Immunopharmacol ; 130: 111746, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38442575

RESUMEN

BACKGROUND: In clear cell renal cell carcinoma (ccRCC), the role of Regulatory T cells (Treg cells) as prognostic and immunotherapy response predictors is not fully explored. METHODS: Analyzing renal clear cell carcinoma datasets from TISCH, TCGA, and GEO, we focused on 8 prognostic Treg genes to study patient subtypes in ccRCC. We assessed Treg subtypes in relation to patient prognosis, tumor microenvironment, metabolism. Using Cox regression and principal component analysis, we devised Treg scores for individual patient characterization and explored the molecular role of C1QL1, a critical gene in the Treg model, through in vivo and in vitro studies. RESULTS: Eight Treg-associated prognostic genes were identified, classifying ccRCC patients into cluster A and B. Cluster A patients showed poorer prognosis with distinct clinical and molecular profiles, potentially benefiting more from immunotherapy. Low Treg scores correlated with worse outcomes and clinical progression. Low scores also suggested that patients might respond better to immunotherapy and targeted therapies. In ccRCC, C1QL1 knockdown reduced tumor proliferation and invasion via NF-kb-EMT pathways and decreased Treg cell infiltration, enhancing immune efficacy. CONCLUSIONS: The molecular subtype and Treg score in ccRCC, based on Treg cell marker genes, are crucial in personalizing ccRCC treatment and underscore C1QL1's potential as a tumor biomarker and target for immunotherapy.


Asunto(s)
Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Pronóstico , Linfocitos T Reguladores , Transcriptoma , Análisis de Secuencia de ARN , Neoplasias Renales/genética , Microambiente Tumoral/genética
18.
J Orthop Surg Res ; 19(1): 264, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664852

RESUMEN

OBJECTIVE: This study aimed to evaluate the influence of herniation of cartilaginous endplates on postoperative pain and functional recovery in patients undergoing percutaneous endoscopic lumbar discectomy (PELD) for lumbar disc herniation (LDH). METHODS: A retrospective analysis was conducted on 126 patients with LDH treated with PELD at the Third Hospital of Hebei Medical University from January 2021 to January 2022. Whether cartilaginous endplates had herniated was identified by analyzing these specific findings from MRI scans: posterior marginal nodes, posterior osteophytes, mid endplate irregularities, heterogeneous low signal intensity of extruded material, and Modic changes in posterior corners and mid endplates. Patients were assessed for postoperative pain using the Visual Analogue Scale (VAS) and functional recovery using the Oswestry Disability Index (ODI) and Modified MacNab criteria. Statistical analyses compared outcomes based on the presence of herniation of cartilaginous endplates. RESULTS: Patients with herniation of cartilaginous endplates experienced higher pain scores early postoperatively but showed significant improvement in pain and functional status over the long term. The back pain VAS scores showed significant differences between the groups with and without herniation of cartilaginous endplates on postoperative day 1 and 1 month (P < 0.05). Leg pain VAS scores showed significant differences on postoperative day 1 (P < 0.05). Modic changes were significantly associated with variations in postoperative recovery, highlighting their importance in predicting patient outcomes. In patients with herniation of cartilaginous endplates, there were statistically significant differences in the back pain VAS scores at 1 month postoperatively and the ODI functional scores on postoperative day 1 between the groups with and without Modic changes (P < 0.05). There were no significant differences in the surgical outcomes between patients with and without these conditions regarding the Modified MacNab criteria (P > 0.05). CONCLUSION: Herniation of cartilaginous endplates significantly affect early postoperative pain and functional recovery in LDH patients undergoing PELD. These findings emphasize the need for clinical consideration of these imaging features in the preoperative planning and postoperative management to enhance patient outcomes and satisfaction.


Asunto(s)
Discectomía Percutánea , Endoscopía , Desplazamiento del Disco Intervertebral , Vértebras Lumbares , Recuperación de la Función , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Masculino , Femenino , Discectomía Percutánea/métodos , Estudios Retrospectivos , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen , Persona de Mediana Edad , Adulto , Endoscopía/métodos , Dolor Postoperatorio/etiología , Resultado del Tratamiento , Dimensión del Dolor , Cartílago/diagnóstico por imagen , Anciano , Imagen por Resonancia Magnética
19.
ACS Appl Mater Interfaces ; 16(8): 9787-9798, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38350068

RESUMEN

The controlled peptide self-assembly and disassembly are not only implicated in many cellular processes but also possess huge application potential in a wide range of biotechnology and biomedicine. ß-sheet peptide assemblies possess high kinetic stability, so it is usually hard to disassemble them rapidly. Here, we reported that both the self-assembly and disassembly of a designed short ß-sheet peptide IIIGGHK could be well harnessed through the variations of concentration, pH, and mechanical stirring. Microscopic imaging, neutron scattering, and infrared spectroscopy were used to track the assembly and disassembly processes upon these stimuli, especially the interconversion between thin, left-handed protofibrils and higher-order nanotubes with superstructural right-handedness. The underlying rationale for these controlled disassembly processes mainly lies in the fact that the specific His-His interactions between protofibrils were responsive to these stimuli. By taking advantage of the peptide self-assembly and disassembly, the encapsulation of the hydrophobic drug curcumin and its rapid release upon stimuli were achieved. Additionally, the peptide hydrogels facilitated the differentiation of neural cells while maintaining low cell cytotoxicity. We believe that such dynamic and reversible structural transformation in this work provides a distinctive paradigm for controlling the peptide self-assembly and disassembly, thus laying a foundation for practical applications of peptide assemblies.


Asunto(s)
Nanotubos de Péptidos , Nanotubos , Nanotubos de Péptidos/química , Péptidos/farmacología , Péptidos/química , Conformación Proteica en Lámina beta
20.
J Mol Neurosci ; 74(3): 60, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904846

RESUMEN

Our former studies have identified the alleviating effect of Calycosin (CA) on spinal cord injury (SCI). In this study, our purpose is to explore the influence of CA on SCI from the perspective of promoting axon growth. The SCI animal model was constructed by spinal cord compression, wherein rat primary cortex neuronal isolation was performed, and the axonal growth restriction cell model was established via chondroitin sulfate proteoglycan (CSPG) treatment. The expressions of axon regeneration markers were measured via immunofluorescent staining and western blot, and the direct target of CA was examined using silver staining. Finally, the expression of the protein tyrosine phosphatase receptor type S (PTPRS) was assessed using western blot. CA treatment increased neuronal process outgrowth and the expressions of axon regeneration markers, such as neurofilament H (NF-H), vesicular glutamate transporter 1 (vGlut1), and synaptophysin (Syn) in both SCI model rats and CSPG-treated primary cortical neurons, and PTPRS levels were elevated after SCI induction. In addition, PTPRS was the direct target of CA, and according to in vivo findings, exposure to CA reduced the PTPRS content. Furthermore, PTPRS overexpression inhibited CA's enhancement of axon regeneration marker content and neuronal axon lengths. CA improves SCI by increasing axon development through regulating PTPRS expression.


Asunto(s)
Axones , Isoflavonas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal , Sinaptofisina , Animales , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Ratas , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Axones/efectos de los fármacos , Axones/metabolismo , Células Cultivadas , Sinaptofisina/metabolismo , Sinaptofisina/genética , Proteínas de Neurofilamentos/metabolismo , Proteína 1 de Transporte Vesicular de Glutamato/metabolismo , Proteína 1 de Transporte Vesicular de Glutamato/genética , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/citología , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/metabolismo , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/genética , Masculino , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Proyección Neuronal/efectos de los fármacos , Femenino , Proteína 2 de Transporte Vesicular de Glutamato
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