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1.
J Med Virol ; 96(3): e29496, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38402627

RESUMEN

The detection of high-risk human papillomaviruses (HPVs) is crucial for early screening and preventing cervical cancer. However, the substantial workload in high-level hospitals or the limited resources in primary-level hospitals hinder widespread testing. To address this issue, we explored a sample-to-answer genotyping system and assessed its performance by comparing it with the traditional real-time polymerase chain reaction (PCR) method conducted manually. Samples randomly selected from those undergoing routine real-time PCR detection were re-analyzed using the fully automatic GenPlex® system. This system identifies 24 types of HPV through a combination of ordinary PCR and microarray-based reverse hybridization. Inconsistent results were confirmed by repeated testing with both methods, and the κ concordance test was employed to evaluate differences between the two methods. A total of 365 samples were randomly selected from 7259 women. According to real-time PCR results, 76 were high-risk HPV negative, and 289 were positive. The GenPlex® system achieved a κ value greater than 0.9 (ranging from 0.920 to 1.000, p < 0.0001) for 14 types of high-risk HPV, except HPV 51 (κ = 0.697, p < 0.0001). However, the inconsistent results in high-risk HPV 51 were revealed to be false positive in real-time PCR by other method. When counting by samples without discriminating the high-risk HPV type, the results of both methods were entirely consistent (κ = 1.000, p < 0.0001). Notably, the GenPlex® system identified more positive cases, with 73 having an HPV type not covered by real-time PCR, and 20 potentially due to low DNA concentration undetectable by the latter. Compared with the routinely used real-time PCR assay, the GenPlex® system demonstrated high consistency. Importantly, the system's advantages in automatic operation and a sealed lab-on-chip format respectively reduce manual work and prevent aerosol pollution. For widespread use of GenPlex® system, formal clinical validation following international criteria should be warranted.


Asunto(s)
Alphapapillomavirus , Virus del Papiloma Humano , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Genotipo , Infecciones por Papillomavirus/diagnóstico , Sensibilidad y Especificidad , ADN Viral/genética , Papillomaviridae/genética , Análisis de Secuencia por Matrices de Oligonucleótidos
2.
J Ultrasound Med ; 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38323467

RESUMEN

OBJECTIVES: The coronal plane is the unique display mode of automated breast (AB) ultrasound (US), which has valuable features of showing the entire breast anatomy and providing additional diagnostic value for breast lesions. However, whether adding the coronal plane could improve the diagnostic performance in screening breast cancer remains uncertain. This study aimed to evaluate the value of adding the coronal plane in interpretation for AB US screening. METHODS: In this retrospective study, AB US images from 644 women (396 in the no-finding group, 143 with benign lesions, and 105 with malignant lesions) aged 40-70 years were collected between January 2016 and October 2020. Four novice radiologists (with 1-5 years of experience with breast US) and four experienced radiologists (with >5 years of experience with breast US) were assigned to read all AB US images in the transverse plane plus coronal plane (T + C planes) and transverse plane (T plane) alone in separate reading sessions. Diagnostic performance, lesion conspicuity, and reading time were compared using analysis of variance. RESULTS: The mean reading time of all radiologists was significantly shorter in the T + C planes reading mode than in the T plane alone (115 ± 32 vs 128 ± 31 s, respectively; P < .05), and cancers had a higher conspicuity (odds ratio, 1.76; 95% confidence interval [CI], 1.00-3.08; P = .04). No significant differences were noted in the two reading modes (T + C planes vs T plane) in the sensitivity (82% [95% CI, 74-89%] vs 81% [95% CI, 74-88%], respectively; P = .68) and specificity (68% [95% CI, 62-75%] vs 70% [95% CI, 64-75%], respectively; P = .39) when Breast Imaging-Reporting and Data System (BI-RADS) 3 was set as the threshold. There were also no significant differences in the two reading modes (T + C planes vs T plane) in the sensitivity (70% [95% CI, 64-76%] vs 69% [95% CI, 63-75%], respectively; P = .39) and specificity (91% [95% CI, 87-96%] vs 91% [95% CI, 88-95%], respectively; P = .90) when BI-RADS 4 was set as the threshold. In addition, the mean areas under the receiver operating characteristic curves of all radiologists in the two reading modes (T + C planes vs T plane) were not significantly different (0.84 [95% CI, 0.79-0.89] vs 0.83 [95% CI, 0.78-0.89], respectively; P = .61). CONCLUSIONS: Adding a coronal plane in the AB US screening setting saved the reading time and improved the conspicuity of breast cancers but not the diagnostic performance.

3.
Adv Sci (Weinh) ; 11(17): e2306622, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38353402

RESUMEN

Hydrocephalus is one of the most common brain disorders and a life-long incurable condition. An empirical "one-size-fits-all" approach of cerebrospinal fluid (CSF) shunting remains the mainstay of hydrocephalus treatment and effective pharmacotherapy options are currently lacking. Macrophage-mediated ChP inflammation and CSF hypersecretion have recently been identified as a significant discovery in the pathogenesis of hydrocephalus. In this study, a pioneering DNA nano-drug (TSOs) is developed by modifying S2 ssDNA and S4 ssDNA with SPAK ASO and OSR1 ASO in tetrahedral framework nucleic acids (tFNAs) and synthesis via a one-pot annealing procedure. This construct can significantly knockdown the expression of SPAK and OSR1, along with their downstream ion channel proteins in ChP epithelial cells, thereby leading to a decrease in CSF secretion. Moreover, these findings indicate that TSOs effectively inhibit the M0 to M1 phenotypic switch of ChP macrophages via the MAPK pathways, thus mitigating the cytokine storm. In in vivo post-hemorrhagic hydrocephalus (PHH) models, TSOs significantly reduce CSF secretion rates, alleviate ChP inflammation, and prevent the onset of hydrocephalus. These compelling results highlight the potential of TSOs as a promising therapeutic option for managing hydrocephalus, with significant applications in the future.


Asunto(s)
Modelos Animales de Enfermedad , Hidrocefalia , Proteínas Serina-Treonina Quinasas , Animales , Hidrocefalia/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Ratones , Ácidos Nucleicos/genética , Ácidos Nucleicos/metabolismo , Masculino , Macrófagos/metabolismo , Líquido Cefalorraquídeo/metabolismo
4.
BMC Geriatr ; 24(1): 19, 2024 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178005

RESUMEN

BACKGROUND: Malnutrition is a prevalent and major challenge among senior citizens, possibly due to the continual low-grade inflammatory state of the body. A novel inflammatory parameter, the systemic immune-inflammation index (SII), is highly valuable in evaluating and predicting the prognosis of a wide range of diseases. This study aims to explore the significance of the SII in assessing malnutrition in older inpatients. METHODS: This retrospective study included 500 senior hospitalized patients who met the inclusion and exclusion criteria from the Comprehensive Geriatric Assessment database of the First Hospital of Jilin University. The Mini-Nutritional Assessment (MNA) questionnaire was used to evaluate the nutritional status of patients. The SII was calculated using complete blood counts, and we performed natural logarithm transformation of the SII [ln(SII)]. Multivariable logistic regression analysis was used to identify the association between ln(SII) and malnutrition. To ensure the stability of the findings, a sensitivity analysis was conducted. RESULTS: The 500 patients had a mean age of 77.29 ± 9.85 years, and 68.6% were male. In accordance with the MNA, 30.4% of the patients were malnourished or at risk of malnutrition, and patients in this group had considerably greater levels of ln(SII) than patients with adequate nutrition (P < 0.001). The optimum ln(SII) cutoff value for patients with malnutrition or at risk of malnutrition was 6.46 (SII = 635.87) with 46.7% sensitivity and 80.2% specificity [95% CI: 0.613-0.721, AUC: 0.667, P < 0.001]. Multivariable logistic regression demonstrated that ln(SII) was an independent risk factor for the risk of malnutrition or malnutrition in older individuals (OR 3.984, 95% CI: 2.426-6.543, P < 0.001). Other metrics from the geriatric comprehensive assessment, including body mass index, calf circumference, fat ratio, activities of daily living and instrumental activities of daily living, and geriatric depression scale scores, were also independently correlated with nutritional status. CONCLUSIONS: According to our research, a high SII is an independent predictor of older inpatient malnutrition, and the SII aids in screening for malnutrition and may be a potential target for intervention. Comprehensive geriatric assessment parameters such as BMI, calf circumference, fat ratio, activities of daily living and depression were also linked to malnutrition.


Asunto(s)
Pacientes Internos , Desnutrición , Humanos , Masculino , Anciano , Anciano de 80 o más Años , Femenino , Actividades Cotidianas , Evaluación Geriátrica , Estudios Retrospectivos , Desnutrición/diagnóstico , Desnutrición/epidemiología , Estado Nutricional , Evaluación Nutricional , Inflamación/diagnóstico , Inflamación/epidemiología
5.
Nat Commun ; 15(1): 298, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38182560

RESUMEN

The inherent structural flexibility and reversibility of non-covalent organic frameworks have enabled them to exhibit switchable multistate structures under external stimuli, providing great potential in the field of resistive switching (RS), but not well explored yet. Herein, we report the 0D+1D hydrogen-bonded polycatenation non-covalent organic framework (HOF-FJU-52), exhibiting diverse and reversible RS behaviors with the high performance. Triggered by the external stimulus of electrical field E at room temperature, HOF-FJU-52 has excellent resistive random-access memory (RRAM) behaviors, comparable to the state-of-the-art materials. When cooling down below 200 K, it was transferred to write-once-read-many-times memory (WORM) behaviors. The two memory behaviors exhibit reversibility on a single crystal device through the temperature changes. The RS mechanism of this non-covalent organic framework has been deciphered at the atomic level by the detailed single-crystal X-ray diffraction analyses, demonstrating that the structural dual-flexibility both in the asymmetric hydrogen bonded dimers within the 0D loops and in the infinite π-π stacking column between the loops and chains contribute to reversible structure transformations between multi-states and thus to its dual RS behaviors.

7.
J Neurosci Res ; 102(1): e25254, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37814994

RESUMEN

Ivermectin (IVM), a semi-synthetic macrolide parasiticide, has demonstrated considerable effectiveness in combating internal and external parasites, particularly nematodes and arthropods. Its remarkable ability to control parasites has earned it significant recognition, culminating in Satoshi Omura and William C. Campbell's receipt of the 2015 Nobel Prize in Physiology or Medicine for their contributions to the development of IVM. In recent years, investigations have revealed that IVM possesses antitumor properties. It can suppress the growth of various cancer cells, including glioma, through a multitude of mechanisms such as selective targeting of tumor-specific proteins, inducing programmed cell death, and modulation of tumor-related signaling pathways. Hence, IVM holds tremendous potential as a novel anticancer drug. This review seeks to provide an overview of the underlying mechanisms that enable IVM's capacity to suppress glioma. Furthermore, it aims to elucidate the challenges and prospects associated with utilizing IVM as a new anticancer agent.


Asunto(s)
Antineoplásicos , Glioma , Humanos , Ivermectina/farmacología , Ivermectina/uso terapéutico , Ivermectina/historia , Glioma/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Premio Nobel , Apoptosis
8.
J Agric Food Chem ; 71(41): 15145-15155, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37800321

RESUMEN

Abrus mollis Hance is a characteristic medicinal herb which is used in Guangdong and Guangxi provinces of China for making soup, medicinal meals, and herbal tea to treat dampheat jaundice and rib discomfort. Current phytochemical study on A. mollis led to the isolation of four new flavones, mollisone A-D (1-4), and thirty two known compounds (5-36). Their structures were characterized by an extensive analysis of spectroscopic data including IR, UV, HR-ESI-MS, and 1D and 2D NMR, as well as electronic circular dichroism calculation. In addition, in order to initially understand their biological activities for traditional applications, in vitro antioxidant and hepatoprotective tests were carried out, whose results illustrated that 25 compounds had significant free radical scavenging ability, and compounds 13 and 16 exhibited protective activities on D-GalN-induced LO2 cell damage than the positive control. Moreover, network pharmacological analysis revealed that the hepatoprotective activity of A. mollis involved multitargets and multipathways such as PI3K/Akt, MAPK, and JAK-STAT pathways and various biological processes such as positive regulation of phosphorylation and regulation of kinase activity. These results suggested that this species could serve as a potential hepatoprotective agent for functional food or medicinal use.


Asunto(s)
Abrus , Abrus/química , Extractos Vegetales/química , Fosfatidilinositol 3-Quinasas/metabolismo , China , Hígado/metabolismo , Té/metabolismo
9.
Brain Sci ; 13(10)2023 Oct 19.
Artículo en Inglés | MEDLINE | ID: mdl-37891850

RESUMEN

BACKGROUND: The prognosis of diffuse midline glioma (DMG) patients with H3K27M (H3K27M-DMG) alterations is poor; however, a model that encourages accurate prediction of prognosis for such lesions on an individual basis remains elusive. We aimed to construct an H3K27M-DMG survival model based on DeepSurv to predict patient prognosis. METHODS: Patients recruited from a single center were used for model training, and patients recruited from another center were used for external validation. Univariate and multivariate Cox regression analyses were used to select features. Four machine learning models were constructed, and the consistency index (C-index) and integrated Brier score (IBS) were calculated. We used the receiver operating characteristic curve (ROC) and area under the receiver operating characteristic (AUC) curve to assess the accuracy of predicting 6-month, 12-month, 18-month and 24-month survival rates. A heatmap of feature importance was used to explain the results of the four models. RESULTS: We recruited 113 patients in the training set and 23 patients in the test set. We included tumor size, tumor location, Karnofsky Performance Scale (KPS) score, enhancement, radiotherapy, and chemotherapy for model training. The accuracy of DeepSurv prediction is highest among the four models, with C-indexes of 0.862 and 0.811 in the training and external test sets, respectively. The DeepSurv model had the highest AUC values at 6 months, 12 months, 18 months and 24 months, which were 0.970 (0.919-1), 0.950 (0.877-1), 0.939 (0.845-1), and 0.875 (0.690-1), respectively. We designed an interactive interface to more intuitively display the survival probability prediction results provided by the DeepSurv model. CONCLUSION: The DeepSurv model outperforms traditional machine learning models in terms of prediction accuracy and robustness, and it can also provide personalized treatment recommendations for patients. The DeepSurv model may provide decision-making assistance for patients in formulating treatment plans in the future.

10.
Foods ; 12(18)2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37761080

RESUMEN

The basic physical and chemical qualities, nutrition, aroma components, and sensory evaluation of 17 varieties of table grapes were studied. The quality evaluation system of different table grape varieties was preliminarily determined. Our results show that the soluble solid content in Ruby Seedless was 21.17%, which was higher than that of other varieties. The black varieties Aishenmeigui and Sweet Sapphire had the highest total phenol content. Aishenmeigui had high levels of tannin and vitamin C. In addition, the aroma contents in Meixiangbao, Ruby Seedless, and Shine-Muscat were higher than those in other varieties. Manicure Finger and Ruby Seedless had higher levels of C6 compounds. Moreover, the "Kyoho" series of grape Meixiangbao, Sunmmer Black, Jumeigui, Hutai 8 hao, and Black Beet were high in ester content, while Muscat varieties, including Zaoheibao, Aishenmeigui, Jumeigui, and Shine-Muscat were rich in terpene substances. Ruby Seedless, Shine-Muscat, and Heibaladuo had higher comprehensive scores in sensory evaluation. Hence, the comprehensive quality of Shine-Muscat, Ruby Seedless, and Aishenmeigui was better. These results may serve as references for determining the quality differences between table grape varieties.

11.
Hematology ; 28(1): 2241226, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37548329

RESUMEN

BACKGROUND: In China, conventional genetic testing methods can only detect common thalassemia variants. Accurate detection of rare thalassemia is crucial for clinical diagnosis, especially for children that need long-term blood transfusion. This study aims to explore the application value of third-generation sequencing (TGS) in the diagnosis of rare thalassemia in children with anemia. METHODS: We enrolled 20 children with anemia, excluding from iron deficiency anemia (IDA). TGS was employed to identify both known and novel thalassemia genotypes, while sanger sequencing was used to confirm the novel mutation detected. RESULTS: Among the 20 samples, we identified 5 cases of rare thalassemia. These included ß-4.9 (hg38,Chr11:5226187-5231089) at HBB gene, α-91(HBA2:c.*91delT), αCD30(HBA2:c.91-93delGAG), Chinese Gγ+(Aγδß)0(NG_000007.3: g .48795-127698 del 78904) and delta - 77(T > C)(HBD:c.-127T>C). Notably, the -SEA/α-91α genotype associated with severe non-deletional hemoglobin H disease (HbH disease) has not been previously reported. Patients with genotypes ß654/ß-4.9 and -SEA/α-91α necessitate long-term blood transfusions, and those with the -SEA/αCD30α, Chinese Gγ+(Aγδß)0 and delta thalassemia demonstrate mild anemia. CONCLUSIONS: TGS demonstrates promising potential as a diagnostic tool for suspected cases of rare thalassemia in children, especially those suspected to have transfusion-dependent thalassemia (TDT).


Asunto(s)
Anemia , Hemoglobinas , Secuenciación de Nucleótidos de Alto Rendimiento , Talasemia , Niño , Humanos , Talasemia alfa/diagnóstico , Talasemia alfa/genética , Anemia/etiología , Anemia/genética , Pueblo Asiatico , Talasemia beta/diagnóstico , Talasemia beta/genética , China , Genotipo , Hemoglobinas/genética , Mutación , Enfermedades Raras/diagnóstico , Enfermedades Raras/genética , Talasemia/diagnóstico , Talasemia/genética , Talasemia/terapia , Transfusión Sanguínea
12.
Angew Chem Int Ed Engl ; 62(34): e202308418, 2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37401627

RESUMEN

Rational design of crystalline porous materials with coupled proton-electron transfer has not yet been reported to date. Herein, we report a donor-acceptor (D-A) π-π stacking hydrogen-bonded organic framework (HOF; HOF-FJU-36) with zwitterionic 1,1'-bis(3-carboxybenzyl)-4,4'-bipyridinium (H2 L2+ ) as acceptor and 2,7-naphthalene disulfonate (NDS2- ) as donor to form a two-dimensional (2D) layer. Three water molecules were situated in the channels to connect with acidic species through hydrogen bonding interactions to give a 3D framework. The continuous π-π interactions along the a axis and the smooth H-bonding chain along the b axis provide the electron and proton transfer pathways, respectively. After 405 nm light irradiation, the photogenerated radicals could simultaneously endow HOF-FJU-36 with photoswitchable electron and proton conductivity due to coupled electron-proton transfer. By single-crystal X-ray diffraction (SCXRD) analyses, X-ray photoelectron spectroscopy (XPS), transient absorption spectra and density functional theory (DFT) calculations, the mechanism of the switchable conductivity upon irradiation has been demonstrated.

13.
Cancer Med ; 12(16): 17139-17148, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37461358

RESUMEN

BACKGROUND: H3K27M mutation status significantly affects the prognosis of patients with diffuse midline gliomas (DMGs), but this tumor presents a high risk of pathological acquisition. We aimed to construct a fully automated model for predicting the H3K27M alteration status of DMGs based on deep learning using whole-brain MRI. METHODS: DMG patients from West China Hospital of Sichuan University (WCHSU; n = 200) and Chengdu Shangjin Nanfu Hospital (CSNH; n = 35) who met the inclusion and exclusion criteria from February 2016 to April 2022 were enrolled as the training and external test sets, respectively. To adapt the model to the human head MRI scene, we use normal human head MR images to pretrain the model. The classification and tumor segmentation tasks are naturally related, so we conducted cotraining for the two tasks to enable information interaction between them and improve the accuracy of the classification task. RESULTS: The average classification accuracies of our model on the training and external test sets was 90.5% and 85.1%, respectively. Ablation experiments showed that pretraining and cotraining could improve the prediction accuracy and generalization performance of the model. In the training and external test sets, the average areas under the receiver operating characteristic curve (AUROCs) were 94.18% and 87.64%, and the average areas under the precision-recall curve (AUPRC) were 93.26% and 85.4%. CONCLUSIONS: The developed model achieved excellent performance in predicting the H3K27M alteration status in DMGs, and its good reproducibility and generalization were verified in the external dataset.


Asunto(s)
Aprendizaje Profundo , Glioma , Humanos , Reproducibilidad de los Resultados , Imagen por Resonancia Magnética , Encéfalo , Glioma/diagnóstico por imagen , Glioma/genética
14.
Chem Biodivers ; 20(7): e202300696, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37269051

RESUMEN

Through a phytochemical investigation of Abrus mollis Hance, a folk medicinal plant in China, we isolated and identified three undescribed compounds, including two flavonoids and one amides alkaloid, along with nine known from this plant. Their structures were elucidated by analyses of 1D, 2D NMR, HR-ESI-MS, ECD, and DP4+ analysis. Furthermore, we evaluated the hepatoprotective effects of all twelve compounds on D-GalN-induced Brl-3 A cells. According to the results, at a concentration of 25 µM, the cell survival rates were observed to be 71.92±0.34 %, 70.03±1.29 %, and 69.11±1.90 % for compound 2, 4, and 11, respectively. Further experimental studies showed that compound 2 (EC50 5.76±0.37 µM) showed more significant protective activity than the bicyclol.


Asunto(s)
Abrus , Alcaloides , Flavonoides/química , Extractos Vegetales/química , Abrus/química , Amidas/farmacología , Alcaloides/farmacología
15.
Biochem Pharmacol ; 213: 115616, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37211173

RESUMEN

Cancer stem cells (CSCs) are the leading cause of recurrence and poor prognosis in non-small cell lung cancer (NSCLC). Eukaryotic translation initiation factor 3a (eIF3a) participates in many tumor development processes, such as metastasis, therapy resistance, and glycolysis, all of which are closely associated with the presence of CSCs. However, whether eIF3a maintains NSCLC-CSC-like properties remains to be elucidated. In this study, eIF3a was highly expressed in lung cancer tissues and was linked to poor prognosis. eIF3a was also highly expressed in CSC-enriched spheres compared with adherent monolayer cells. Moreover, eIF3a is required for NSCLC stem cell-like traits maintenance in vitro and in vivo. Mechanistically, eIF3a activates the Wnt/ß-catenin signaling pathway, promoting the transcription of cancer stem cell markers. Specifically, eIF3a promotes the transcriptional activation of ß-catenin and mediates its nuclear accumulation to form a complex with T cell factor 4 (TCF4). However, eIF3a has no significant effect on protein stability and translation. Proteomics analysis revealed that the candidate transcription factor, Yin Yang 1 (YY1), mediates the activated effect of eIF3a on ß-catenin. Overall, the findings of this study implied that eIF3a contributes to the maintenance of NSCLC stem cell-like characteristics through the Wnt/ß-catenin pathway. eIF3a is a potential target for the treatment and prognosis of NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias Pulmonares/metabolismo , Células Madre Neoplásicas , Activación Transcripcional , Vía de Señalización Wnt , Factor de Transcripción YY1/metabolismo
16.
Intractable Rare Dis Res ; 12(1): 58-61, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36873675

RESUMEN

The Wnt signaling pathway is vital in encouraging bone growth. WNT1 gene mutations have been identified as the major cause of type XV osteogenesis imperfecta (OI). Described here is a case of complex heterozygous WNT1 c.620G>A (p.R207H) and c.677C >T (p.S226L) OI caused by a novel mutation at locus c.620G >A (p.R207H). The female patient had type XV OI, distinguished by poor bone density, frequent fractures, a small stature, skull softening, lack of dentine hypoplasia, a brain malformation, and obvious blue sclera. A CT scan of the temporal bone revealed abnormalities of the inner ear, necessitating a hearing aid 8 months after birth. There was no family history of such disorders in the proband's parents. The proband inherited complex heterozygous WNT1 gene variants c.677C>T (p.S226L) and c.620G>A (p.R207H) from her father and mother, respectively. Presented here is a case of OI with inner ear deformation caused by c.620G>A (p.R207H), which is a novel WNT1 site mutation. This case broadens the genetic spectrum of OI and it provides a rationale for genetic testing of mothers and a medical consultation to estimate the risk of fetal illness.

17.
Front Pharmacol ; 14: 1137151, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36909172

RESUMEN

Poly (ADP-ribose) polymerase 1 (PARP1) is a key DNA damage sensor that is recruited to damaged sites after DNA strand breaks to initiate DNA repair. This is achieved by catalyzing attachment of ADP-ribose moieties, which are donated from NAD+, on the amino acid residues of itself or other acceptor proteins. PARP inhibitors (PARPi) that inhibit PARP catalytic activity and induce PARP trapping are commonly used for treating BRCA1/2-deficient breast and ovarian cancers through synergistic lethality. Unfortunately, resistance to PARPi frequently occurs. In this review, we present the novel substrates and regulators of the PARP1-catalyzed poly (ADP-ribosyl)ation (PARylatison) that have been identified in the last 3 years. The overall aim is the presentation of protein interactions of potential therapeutic intervention for overcoming the resistance to PARPi.

18.
Am J Transl Res ; 15(2): 1254-1258, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36915721

RESUMEN

BACKGROUND: Hemangiopericytoma (HPC) is a tumor originating from pericytes surrounding the capillary walls. Most HPCs grow slowly, but some display aggressive growth. Treatment for HPC is total resection or resection plus adjuvant radiation. CASE PRESENTATION: A 14-year-old girl presented with a blood vessel-rich tumor with a smooth surface located on the left side of the parietal bone, attached to the inner surface of the skull. The dura was completely intact. The final diagnosis was HPC based on the histopathologic and immunohistochemical findings. The patient underwent total resection of the tumor and cranioplasty. The dura was not incised because of the lack of invasive growth. Within the 2-year follow-up, the patient showed an excellent prognosis without any local recurrence or positive radiologic features. CONCLUSION: The patient presented with common intracranial hypertension symptoms. A blood vessel-rich tumor with a smooth surface was attached to the inner surface of the skull with the dura completely intact. Simple surgical resection without radiotherapy offered an excellent prognosis during 2 years of follow-up.

19.
Adv Healthc Mater ; 12(20): e2300303, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36964976

RESUMEN

Treatment of infected bone defects is a major clinical challenge; bioactive materials combining sufficient antimicrobial activity and favorable osteogenic ability are urgently needed. In this study, through a facile one-pot hydrothermal reaction of zinc acetate in the presence of tannic acid (TA), with or without silver nitrate (AgNO3 ), is used to synthesize a TA or TA and silver nanoparticles (Ag NPs) bulk-modified zinc oxide (ZnO) (ZnO-TA or ZnO-TA-Ag), which is further composited with zein to fabricate porous microparticulate scaffolds for infected bone defect repair. Bulk TA modification significantly improves the release rate of antibacterial metal ions (Zn2+ release rate is >100 times that of ZnO). Fast and long-lasting (>35 d) Zn2+ and Ag+ release guaranteed sufficient antibacterial capability and excellent osteogenic properties in promoting the osteogenic differentiation of bone marrow mesenchymal stem cells and endogenous citric acid production and mineralization and providing considerable immunomodulatory activity in promoting M2 polarization of macrophages. At the same time, synchronously-released TA could scavenge endogenous reactive oxygen species (ROS) and ROS produced by antibacterial metal ions, effectively balancing antibacterial activity and osteogenesis to sufficiently control infection while protecting the surrounding tissue from damage, thus effectively promoting infected bone defect repair.


Asunto(s)
Antiinfecciosos , Nanopartículas del Metal , Óxido de Zinc , Osteogénesis , Zinc/farmacología , Óxido de Zinc/farmacología , Especies Reactivas de Oxígeno , Taninos/farmacología , Plata/farmacología , Antibacterianos/farmacología , Iones/farmacología , Antiinfecciosos/farmacología , Andamios del Tejido
20.
Ying Yong Sheng Tai Xue Bao ; 34(1): 203-212, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36799395

RESUMEN

Soil microorganisms play an important role in the biogeochemical cycles of terrestrial ecosystems. How-ever, it is still unclear how the amount and duration of nitrogen (N) addition affect soil microbial community structure and whether there is a correlation between the changes in microbial community structure and their nutrient limi-tation status. In this study, we conducted an N addition experiment in a subtropical Pinus taiwanensis forest to simulate N deposition with three treatments: control (CK, 0 kg N·hm-2·a-1), low N (LN, 40 kg N·hm-2·a-1), and high N (HN, 80 kg N·hm-2·a-1). Basic soil physicochemical properties, phospholipid fatty acids content, and carbon (C), N and phosphorus (P) acquisition enzyme activities were measured after one and three years of N addition. The relative nutrient limitation status of soil microorganisms was analyzed using ecological enzyme stoichiometry. The results showed that one-year N addition did not affect soil microbial community structure. Three-year LN treatment significantly increased the contents of Gram-positive bacteria (G+), Gram-negative bacteria (G-), actinomycetes (ACT), and total phospholipid fatty acids (TPLFA), whereas three-year HN treatment did not significantly affect soil microbial community, indicating that bacteria and ACT might be more sensitive to N addition. Nitrogen addition exacerbated soil C and P limitation. Phosphorus limitation was the optimal explanatory factor for the changes in soil microbial community structure. It suggested that P limitation induced by N addition might be more beneficial for the growth of certain oligotrophic bacteria (e.g. G+) and the microorganisms participating in the P cycling (e.g. ACT), with consequences on soil microbial community structure of subtropical Pinus taiwanensis forest.


Asunto(s)
Microbiota , Pinus , Fósforo , Nitrógeno/análisis , Suelo/química , Biomasa , Microbiología del Suelo , Bosques , Fosfolípidos , Ácidos Grasos , Bacterias , Carbono , China
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