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1.
Hum Reprod ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237109

RESUMEN

STUDY QUESTION: Can a simplified ovarian hyperstimulation syndrome (OHSS) risk assessment index be developed and validated with sufficient discrimination of moderate/severe OHSS from those without OHSS? SUMMARY ANSWER: This easy-to-use OHSS risk assessment index shows good discriminative power and high calibration accuracy in internal and external validation cohorts. WHAT IS KNOWN ALREADY: An early alert and risk stratification is critical to prevent the occurrence of OHSS. We have previously developed a multi-stage smartphone app-based prediction model to evaluate the risk of OHSS, but app use might not be so convenient in many primary institutions. A simplified OHSS risk assessment index has been required. STUDY DESIGN, SIZE, DURATION: This training and internal validation of an OHSS risk assessment index used retrospective cohort data from January 2016 to December 2020. External validation was performed with a prospective cohort database from January 2021 to May 2022. There were 15 066 cycles in the training cohort, 6502 cycles in the internal validation cohort, and 8097 cycles in the external validation cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was performed in the reproductive medicine center of a tertiary hospital. Infertile women who underwent ovarian stimulation were included. Data were extracted from the local database with detailed medical records. A multi-stage risk assessment index was constructed at multiple stages. The first stage was before the initiation of ovarian stimulation, the second was before the ovulation trigger, the third was after oocyte retrieval, and the last stage was on the embryo transfer day if fresh embryo transfer was scheduled. MAIN RESULTS AND THE ROLE OF CHANCE: We established a simplified multi-stage risk assessment index for moderate/severe OHSS, the performance of which was further evaluated with discrimination and calibration abilities in training and internal and external validation cohorts. The discrimination abilities of the OHSS risk assessment index were determined with C-statistics. C-statistics in training (Stages 1-4: 0.631, 0.692, 0.751, 0.788, respectively) and internal (Stages 1-4: 0.626, 0.642, 0.755, 0.771, respectively) and external validation (Stages 1-4: 0.668, 0.670, 0.754, 0.773, respectively) cohorts were all increased from Stage 1 to 3 with similar trends, and were comparable between Stages 3 and 4. Calibration plots showed high agreement between observed and predicted cases in all three cohorts. Incidences of OHSS based on diverse risk stratification (negligible risk, low risk, medium risk, and high risk) were 0%, 0.6%, 2.7%, and 8.3% in the training cohort, 0%, 0.6%, 3.3%, and 8.5% in the internal validation cohort, and 0.1%, 1.1%, 4.1%, and 7.2% in the external validation cohort. LIMITATIONS, REASONS FOR CAUTION: The influence from clinical interventions including cryopreservation of all embryos cannot be eliminated and thus certain risk factors like estrogen level on trigger day might be assigned with a lower risk score. Another weakness of the study is that several preventive treatments, for instance oral aspirin and letrozole, were not recorded and evaluated in the model. Despite the robust reliability of OHSS assessment index, this tool cannot be used directly for clinical decision-making or as a diagnostic tool. Its value lies in its capacity to evaluate the prognosis of various interventions and to facilitate clinician-patient communication. The combination of this tool and further symptoms and examinations should be all taken into consideration for accurate and personalized management of OHSS. WIDER IMPLICATIONS OF THE FINDINGS: The OHSS risk assessment index can be implemented to facilitate personalized counseling and management of OHSS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by National Key R&D Program of China (2022YFC2702504), Medical Research Fund Guangdong Provincial (A2024003), and Xinjiang Support Rural Science and Technology (Special Correspondent) Program in Guangdong Province (KTPYJ 2023014). All authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

2.
RSC Adv ; 14(39): 28569-28584, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39247503

RESUMEN

Human glucose transporters (GLUTs) facilitate the uptake of hexoses into cells. In cancer, the increased proliferation necessitates higher expression of GLUTs, with particular emphasis on GLUT1 and GLUT3. Thus, inhibiting GLUTs holds promise as an anticancer therapy by starving these cells of fuel. Ganoderic acid A (GAA), a triterpene found in Ganoderma lucidum, has anticancer and antidiabetic properties. Recent studies show that GAA reduces glucose uptake in cancer cells, which indicates that GAA may affect GLUT1/GLUT3 by inhibiting glucose uptake. Therefore, this study aimed to inspect whether GAA could target GLUT1/GLUT3 and play an inhibitory role in changing their endofacial and exofacial conformations. To this end, AlphaFold2 was employed to model the endofacial and exofacial conformations of GLUT3 and GLUT1, respectively. Molecular docking, molecular dynamics simulation, cell viability, cellular thermal shift assays (CETSA), glucose uptake, qPCR, and western blotting were harnessed. In comparison to the endofacial (cytochalasin B) and exofacial (phloretin) GLUT1/3 inhibitors, the computational findings unveiled GAA's capacity to bind and stabilize GLUT1/3 in their two conformational states, with a preference for binding the endofacial conformation. A low, non-cytotoxic dose of GAA thermally stabilized both transporters and inhibited glucose uptake in human lung cancer cells, similar to cytochalasin B and phloretin. In conclusion, this study has unearthed novel functionalities of GAA, suggesting its potential utility in cancer therapy by targeting glucose metabolism.

3.
Anal Chim Acta ; 1326: 343153, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39260919

RESUMEN

BACKGROUND: Wavelength selection is one of the key steps in spectral analysis and plays an irreplaceable role in improving model prediction accuracy and computational efficiency. High-dimensional spectral datasets contain substantial irrelevant information and redundant variables. Whereas, at current stage, such problem can be solved by existing abundant wavelength selection methods. However, it is difficult to achieve the balance between strong wavelength interpretability and prediction accuracy by those methods. As a result, there is an urgent need for a new method that can reach the point of balance. RESULTS: we propose a new framework for wavelength selection based on wavelength importance clustering (WIC) which attempts to establish a hierarchical relationship between wavelength points and attributions of response through a clustering algorithm, consequently, performing combinatorial and filtering to obtain the optimal wavelength combinations. In this paper, a new wavelength selection method (WIC-WRCKF) is constructed based on WIC, and four commonly used wavelength selection methods are selected to be compared with WIC-WRCKF. A large number of experiments are carried out on three publicly available datasets as well, namely, wheat, corn, and tablets. Compared with other methods, WIC-WRCKF has the highest prediction accuracy with high stability on the three datasets, and the number of wavelengths selected is small and highly interpretative, indicating that WIC-WRCKF has a better predictive ability. SIGNIFICANCE: The wavelength selection method can significantly improve the model prediction accuracy, and the WIC architecture can effectively exploit the essence of the spectral data, which has great potential in the application of wavelength selection.

4.
Microbiome ; 12(1): 161, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39223641

RESUMEN

BACKGROUND: Many studies have demonstrated the association between intestinal microbiota and joint diseases. The "gut-joint axis" also has potential roles in chikungunya virus (CHIKV) infection. Pro-inflammatory arthritis after CHIKV infection might disrupt host homeostasis and lead to dysbacteriosis. This study investigated the characteristics of fecal and gut microbiota, intestinal metabolites, and the changes in gene regulation of intestinal tissues after CHIKV infection using multi-omics analysis to explore the involvement of gut microbiota in the pathogenesis of CHIKV infection. RESULTS: CHIKV infection increases the systemic burden of inflammation in the GI system of infected animals. Moreover, infection-induced alterations in GI microbiota and metabolites may be indirectly involved in the modulation of GI and bone inflammation after CHIKV infection, including the modulation of inflammasomes and interleukin-17 inflammatory cytokine levels. CONCLUSION: Our results suggest that the GI tract and its microbes are involved in the modulation of CHIKV infection, which could serve as an indicator for the adjuvant treatment of CHIKV infection. Video Abstract.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Heces , Microbioma Gastrointestinal , Macaca mulatta , Animales , Heces/microbiología , Fiebre Chikungunya/virología , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/aislamiento & purificación , Bacterias/genética , Disbiosis/microbiología , Inflamación , Inflamasomas/metabolismo , Modelos Animales de Enfermedad , Interleucina-17/metabolismo , Tracto Gastrointestinal/microbiología , Citocinas/metabolismo
5.
J Infect Dev Ctries ; 18(8): 1291-1295, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39288379

RESUMEN

INTRODUCTION: The most common anatomic sites affected by extrapulmonary tuberculosis are lymph nodes, pleura, bones, and joints, urogenital tract, and meninges. Tuberculous arthritis is difficult to diagnose early because of its atypical insidious clinical manifestations and non-specific imaging findings. CASE REPORT: A 59-year-old male presented with progressive swelling in his left knee for over two months. The patient was initially misdiagnosed with pigmented villonodular synovitis (PVNS) and had undergone total knee arthroplasty (TKA) two years ago, however, the TKA did not completely alleviate his symptoms. Comprehensive radiological and laboratory assessments, including X-rays, magnetic resonance imaging and computed tomography scans, and an interferon-γ release assay (IGRA), pointed towards a diagnosis of tuberculous knee arthritis. Definitive diagnosis was established through the detection of Mycobacterium tuberculosis (MTB) DNA in the synovial fluid via polymerase chain reaction (PCR) and a positive IGRA result. CONCLUSIONS: The case underscores the importance of considering MTB infection in the differential diagnosis of chronic unilateral knee arthritis, especially given the atypical clinical manifestations and imaging findings that can mimic other conditions like PVNS.


Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Osteoarticular , Humanos , Masculino , Persona de Mediana Edad , Tuberculosis Osteoarticular/diagnóstico , Tuberculosis Osteoarticular/diagnóstico por imagen , Mycobacterium tuberculosis/aislamiento & purificación , Mycobacterium tuberculosis/genética , Articulación de la Rodilla/patología , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/microbiología , Imagen por Resonancia Magnética , Diagnóstico Diferencial , Líquido Sinovial/microbiología , Ensayos de Liberación de Interferón gamma , Reacción en Cadena de la Polimerasa , Tomografía Computarizada por Rayos X , ADN Bacteriano/genética
6.
Biosens Bioelectron ; 267: 116784, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39288708

RESUMEN

Nanozymes are potential candidates for constructing sensors due to their adjustable activity, high stability, and high cost-effectiveness. However, due to the lack of reasonable means, designing and preparing efficient nanozymes remains challenging. Herein, inspired by the property of natural laccase, we applied the novel and facile low-temperature plasma (LTP) technology to fabricate a series of different base-ligand Cu metal organic framework (MOF) nanozymes (namely, A-Cu, G-Cu, C-Cu and T-Cu nanozymes) with laccase-like activity successfully. Owing to the different catalytic capacities of four types of base-Cu-MOF nanozymes in the response to five common effective bioactive substances, we constructed the nanozyme-encoded array sensor for the identification of different bioactive compounds. As a result, the four-channel colorimetric sensor array was constructed, in which four laccase-like nanozymes were utilized as the sensing units, achieving high-throughput, high-sensitivity and rapid detection/identification of five common bioactive compounds in the concentration range of 1.5-150 µg mL-1 through different color output patterns. It is worth noting that the as-prepared sensor array can successfully distinguish the natural bioactive compounds in a variety of real samples. Furthermore, with the assistance of smartphones, we also designed a portable smart sensing approach for detecting the bioactive compounds effectively in food. This study has therefore not only provided an effective way for preparation highly effectively nanozymes, but also established a new sensing platform for intelligent sensing of bioactive components in food.

7.
J Clin Invest ; 134(18)2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39286971

RESUMEN

Soluble host factors in the upper respiratory tract can serve as the first line of defense against SARS-CoV-2 infection. In this study, we described the identification and function of a human airway trypsin-like protease (HAT), capable of reducing the infectivity of ancestral SARS-CoV-2. Further, in mouse models, HAT analogue expression was upregulated by SARS-CoV-2 infection. The antiviral activity of HAT functioned through the cleavage of the SARS-CoV-2 spike glycoprotein at R682. This cleavage resulted in inhibition of the attachment of ancestral spike proteins to host cells, which inhibited the cell-cell membrane fusion process. Importantly, exogenous addition of HAT notably reduced the infectivity of ancestral SARS-CoV-2 in vivo. However, HAT was ineffective against the Delta variant and most circulating Omicron variants, including the BQ.1.1 and XBB.1.5 subvariants. We demonstrate that the P681R mutation in Delta and P681H mutation in the Omicron variants, adjacent to the R682 cleavage site, contributed to HAT resistance. Our study reports what we believe to be a novel soluble defense factor against SARS-CoV-2 and resistance of its actions in the Delta and Omicron variants.


Asunto(s)
COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , SARS-CoV-2/metabolismo , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , COVID-19/virología , COVID-19/metabolismo , COVID-19/genética , Animales , Ratones , Serina Endopeptidasas/metabolismo , Serina Endopeptidasas/genética , Células HEK293 , Mutación , Mutación Missense , Chlorocebus aethiops
8.
SLAS Technol ; : 100189, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39303920

RESUMEN

Thyroid nodule is a common thyroid disease, but the study of its pathology and pathogenesis is still limited. As a non-invasive diagnostic method, medical image examination is of great value to study the pathological correlation of thyroid nodules. The purpose of this study was to investigate the expression of eosinophils in medical image examination and the pathological correlation between eosinophils and thyroid nodules. The study analyzed the pathological reports of a group of patients with thyroid nodules examined by medical images and performed corresponding imaging scans or examinations. The imaging data is processed, including image reconstruction, data transmission and other steps, to generate images that can be diagnosed by doctors. Thyroid function and parameters of leukocyte were collected and compared.The serum levels of TT4 and fT4 were observed lower in G2 group, while thyroid stimulating hormone (TSH) was higher compared to G1 group before surgery. Compared to G2 group, eosinophils count and percentage were lower in G1group (p<0.05) post-surgery and lower ratio of eosinophils count with lymphocyte count (ELR) were observed in G1 group patients (p<0.05).Elevated TSH is closely related to malignant TN per surgery, while lower ELR suggesting that TN removed thoroughly. Relevant cut-off values required further study to guide the diagnosis, treatment and follow-up of TN.

9.
Talanta ; 281: 126897, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39293246

RESUMEN

The development of electrochemical glucose sensors with high sensitivity, specificity, and stability, enabling real-time continuous monitoring, has posed a significant challenge. However, an opportunity exists to fabricate electrochemical glucose biosensors with optimal performance through innovative device structures and surface modification materials. This paper provides a comprehensive review of recent advances in electrochemical glucose sensors. Novel classes of nanomaterials-including metal nanoparticles, carbon-based nanomaterials, and metal-organic frameworks-with excellent electronic conductivity and high specific surface areas, have increased the availability of reactive sites to improved contact with glucose molecules. Furthermore, in line with the trend in electrochemical glucose sensor development, research progress concerning their utilisation with sweat, tears, saliva, and interstitial fluid is described. To facilitate the commercialisation of these sensors, further enhancements in biocompatibility and stability are required. Finally, the characteristics of the ideal electrochemical glucose sensor are described and the developmental trends in this field are outlines.

10.
BMC Genomics ; 25(1): 851, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261781

RESUMEN

BACKGROUND: The WD40 domain, one of the most abundant in eukaryotic genomes, is widely involved in plant growth and development, secondary metabolic biosynthesis, and mediating responses to biotic and abiotic stresses. WD40 repeat (WD40) protein has been systematically studied in several model plants but has not been reported in the Capsicum annuum (pepper) genome. RESULTS: Herein, 269, 237, and 257 CaWD40 genes were identified in the Zunla, CM334, and Zhangshugang genomes, respectively. CaWD40 sequences from the Zunla genome were selected for subsequent analysis, including chromosomal localization, phylogenetic relationships, sequence characteristics, motif compositions, and expression profiling. CaWD40 proteins were unevenly distributed on 12 chromosomes, encompassing 19 tandem duplicate gene pairs. The 269 CaWD40s were divided into six main branches (A to F) with 17 different types of domain distribution. The CaWD40 gene family exhibited diverse expression patterns, and several genes were specifically expressed in flowers and seeds. Yeast two-hybrid (Y2H) and dual-luciferase assay indicated that CaWD40-91 could interact with CaAN1 and CaDYT1, suggesting its involvement in anthocyanin biosynthesis and male sterility in pepper. CONCLUSIONS: In summary, we systematically characterized the phylogeny, classification, structure, and expression of the CaWD40 gene family in pepper. Our findings provide a valuable foundation for further functional investigations on WD40 genes in pepper.


Asunto(s)
Antocianinas , Capsicum , Filogenia , Proteínas de Plantas , Capsicum/genética , Capsicum/metabolismo , Antocianinas/biosíntesis , Antocianinas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Regulación de la Expresión Génica de las Plantas , Infertilidad Vegetal/genética , Repeticiones WD40/genética , Familia de Multigenes , Perfilación de la Expresión Génica , Cromosomas de las Plantas/genética
11.
J Hazard Mater ; 480: 135895, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39312844

RESUMEN

Polyethylene terephthalate (PET) is one of the most widely used plastics, but its fragmentation into microplastics poses significant environmental challenges. The recycling of PET microplastics is hindered by their low solubility and widespread dispersion in the environment, making microbial in-situ degradation a promising solution. However, existing PET-degrading strains exhibited the limited effectiveness, primarily due to the diffusion of secreted hydrolases away from the PET surface. In this study, Stenotrophomonas pavanii JWG-G1 was engineered to achieve the targeted aggregation of PET hydrolase PETase on the cell surface by fusing it with an endogenous anchor protein. This approach aims to maximise the local concentration of PETase around PET, thereby increasing the overall rate of PET degradation. The PETase surface-aggregated system, S. pavanii/PaL-PETase, demonstrated the highest degradation efficiency, achieving 63.3 % degradation of low-crystallinity PET (lcPET) and 27.3 % degradation of high-crystallinity PET bottles (hcPET) at 30 °C. This represents the highest degradation rate reported for a displayed whole-cell system at ambient temperature. Furthermore, this system exhibited broad-spectrum degradation activity against various polyesters. These findings suggest that this system offers a promising, eco-friendly solution to PET and other polyester pollution, with potential implications for environmental bioremediation strategies.

12.
J Colloid Interface Sci ; 677(Pt A): 1005-1015, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39128284

RESUMEN

Heterostructures endow electrochemical hybrids with promising energy storage properties owing to synergistic effects and interfacial interaction. However, developing a facile but effective approach to maximize interface effects is crucial but challenging. Herein, a bimetallic sulfide/carbon heterostructure is realized in a confined carbon network via a high-throughput template-assisted strategy to induce highly active and stable electrode architecture. The designed heterostructures not only yield abundant interconnected Co9S8/MoS2/N-doped carbon (Co9S8/MoS2/NC) heterojunctions with continuous channels for ion/electron transfer but maintain excellent conversion reversibility. Serving as anode for sodium storage, the Co9S8/MoS2/NC framework displayed excellent sodium storage properties (reversible capacity of 480 mAh/g after 100 cycles at 0.2 A/g and 286.2 mAh/g after 500 cycles at 2 A/g). Given this, this study can guide future design protocols for interface engineering by forming dynamic channels of conversion reaction kinetics for potential applications in high-performance electrodes.

13.
Ren Fail ; 46(2): 2387205, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39120130

RESUMEN

BACKGROUND: To compare the impact of tunneled cuffed catheters (TCCs) and arteriovenous fistulas (AVFs) on outcomes in elderly hemodialysis (HD) patients. METHODS: A retrospective matched cohort study was performed. Propensity score matching (PSM) was applied to balance the baseline conditions, and we compared all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCEs), hospitalization, and infection rates between AVF and TCC patients ≥70 years old. Cox survival analysis was used to analyze the risk factors for death. RESULTS: There were 2119 patients from our center in the Chinese National Renal Data System (CNRDS) between 1 January 2010 and 10 October 2023. Among these patients, 77 TCC patients were matched with 77 AVF patients. There was no significant difference in all-cause mortality between the TCC and AVF groups (30.1/100 vs. 33.3/100 patient-years, p = 0.124). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank p = 0.242). The TCC group had higher rates of MACCEs, hospitalization, and infection than the AVF group (33.7/100 vs. 29.5/100 patient-years, 101.2/100 vs. 79.5/100 patient-years, and 30.1/100 vs. 14.1/100 patient-years, respectively). Multivariate analysis showed that high Charlson comorbidity index (CCI) score was a risk factor for death. CONCLUSIONS: There was no significant difference in all-cause mortality between elderly HD patients receiving TCCs and AVFs. Compared with those with a TCC, elderly HD patients with an AVF have a lower risk of MACCEs, hospitalization, and infection.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Fallo Renal Crónico , Puntaje de Propensión , Diálisis Renal , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Fallo Renal Crónico/terapia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/mortalidad , Factores de Riesgo , Derivación Arteriovenosa Quirúrgica/efectos adversos , Anciano de 80 o más Años , Hospitalización/estadística & datos numéricos , China/epidemiología , Pronóstico , Estimación de Kaplan-Meier
14.
J Exp Clin Cancer Res ; 43(1): 225, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39135122

RESUMEN

BACKGROUND: Long non-coding RNAs (LncRNAs) have been implicated as critical regulators of cancer tumorigenesis and progression. However, their functions and molecular mechanisms in colorectal cancer (CRC) still remain to be further elucidated. METHODS: LINC00460 was identified by differential analysis between human CRC and normal tissues and verified by in situ hybridization (ISH) and qRT-PCR. We investigated the biological functions of LINC00460 in CRC by in vitro and in vivo experiments. We predicted the mechanism and downstream functional molecules of LINC00460 by bioinformatics analysis, and confirmed them by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP), RNA pull-down, etc. RESULTS: LINC00460 was found to be significantly overexpressed in CRC and associated with poor prognosis. Overexpression of LINC00460 promoted CRC cell immune escape and remodeled a suppressive tumor immune microenvironment, thereby promoting CRC proliferation and metastasis. Mechanistic studies showed that LINC00460 served as a molecular sponge for miR-186-3p, and then promoted the expressions of MYC, CD47 and PD-L1 to facilitate CRC cell immune escape. We also demonstrated that MYC upregulated LINC00460 expression at the transcriptional level and formed a positive feedback loop. CONCLUSIONS: The LINC00460/miR-186-3p/MYC feedback loop promotes CRC cell immune escape and subsequently facilitates CRC proliferation and metastasis. Our findings provide novel insight into LINC00460 as a CRC immune regulator, and provide a potential therapeutic target for CRC patients.


Asunto(s)
Antígeno B7-H1 , Antígeno CD47 , Neoplasias Colorrectales , MicroARNs , ARN Largo no Codificante , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/inmunología , MicroARNs/genética , Antígeno CD47/metabolismo , Antígeno CD47/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ratones , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Animales , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Escape del Tumor/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/genética , Masculino , Femenino , Proliferación Celular , Retroalimentación Fisiológica , Pronóstico , Ratones Desnudos
16.
Mol Biomed ; 5(1): 30, 2024 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-39095588

RESUMEN

Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/ß and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.


Asunto(s)
Citocinas , Modelos Animales de Enfermedad , Huésped Inmunocomprometido , Replicación Viral , Infección por el Virus Zika , Virus Zika , Animales , Virus Zika/inmunología , Virus Zika/patogenicidad , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/virología , Replicación Viral/efectos de los fármacos , Ratones , Citocinas/metabolismo , Tasa de Supervivencia , Receptor de Interferón alfa y beta/genética , Antivirales/farmacología , Antivirales/uso terapéutico , Receptores de Interferón/deficiencia , Receptores de Interferón/genética , Receptores de Interferón/metabolismo , Receptor de Interferón gamma , Células Vero
17.
Nat Mater ; 23(8): 1017-1018, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39090396
18.
Bioorg Med Chem Lett ; 111: 129880, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38996941

RESUMEN

Viral infectivity factor (Vif) has been recognized as a new therapeutic target for human immunodeficiency virus-1 (HIV-1) infected patients. In our previous work, we have synthesized a novel class of Vif inhibitors with 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold, which show obvious activity in HIV-1 infected cells and are also effective against drug-resistant strains. Proteolytic targeting chimera (PROTAC) utilizes the ubiquitin-proteasome system to degrade target proteins, which is well established in the field of cancer, but the antiviral PROTAC molecules are rarely reported. In order to explore the effectiveness of PROTAC in the antiviral area, we designed and synthesized a series of degrader of HIV-1 Vif based on 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold. Among them, L15 can degrade Vif protein obviously in a dose-dependent manner and shows certain antivirus activity. Meanwhile, molecular dynamics simulation indicated that the ternary complex formed by L15, Vif, and E3 ligase adopted a reasonable binding mode and maintained a stable interaction. This provided a molecular basis and prerequisite for the selective degradation of the Vif protein by L15. This study reports the HIV-1 Vif PROTAC for the first time and represents the proof-of-concept of PROTACs-based antiviral drug discovery in the field of HIV/ acquired immune deficiency syndrome (AIDS).


Asunto(s)
Fármacos Anti-VIH , VIH-1 , Productos del Gen vif del Virus de la Inmunodeficiencia Humana , VIH-1/efectos de los fármacos , Productos del Gen vif del Virus de la Inmunodeficiencia Humana/antagonistas & inhibidores , Productos del Gen vif del Virus de la Inmunodeficiencia Humana/metabolismo , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/química , Humanos , Relación Estructura-Actividad , Estructura Molecular , Benzamidas/farmacología , Benzamidas/química , Benzamidas/síntesis química , Descubrimiento de Drogas , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Proteolisis/efectos de los fármacos , Simulación de Dinámica Molecular
19.
J Sci Food Agric ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39011979

RESUMEN

BACKGROUND: The supplemental effect of zinc depends not only on adequate intake, but also on how efficiently it is absorbed in the small intestine. In the present study, weak hydrophobic peptides (WHP), strong hydrophobic peptides (SHP), positively charged peptides (PCP) and negatively charged peptides (NCP) were isolated from soybean peptides (SP). The peptide-Zn complexes (PCP-Zn, NCP-Zn, WHP-Zn, SHP-Zn and SP-Zn) were prepared to compare their promotion zinc absorption capacity in the Caco-2 cells monolayers model. RESULTS: We found that the carboxyl, carbonyl and amino groups in peptide were the primary binding sites of Zn. Compared with zinc sulfate, the peptide-Zn complexes with different charge and hydrophobic peptides could improve zinc solubility at different pH. NCP-Zn had a lower Zn-binding capacity but a higher zinc absorption capacity compared to that of PCP-Zn in Caco-2 cells. In addition, the capacity of PCP-Zn to promote zinc absorption was lower than the control group (SP-Zn). There were no significant differences in transport rates, retention rates and uptake rates of WHP-Zn, SHP-Zn and SP-Zn. NCP-Zn could improve the activity of Zn-related enzymes, and the expression levels of PepT1 and ZnT1 were higher than other peptide-Zn complexes. CONCLUSION: The promotion zinc absorption capacity of peptide-Zn complexes was not completely dependent on the Zn-binding capacity, but also depended on the charge and hydrophobicity of peptides. © 2024 Society of Chemical Industry.

20.
Hum Vaccin Immunother ; 20(1): 2371664, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38961667

RESUMEN

Recently, CAR-T cell therapy in hematological malignancies has received extensive attention. The objective of this study is to gain a comprehensive understanding of the current research status, development trends, research hotspots, and emerging topics pertaining to CAR-T cells in the treatment of hematological malignancies. Articles pertaining to CAR-T cell therapy for hematological malignancies from the years 2012 to 2023 were obtained and assessed from the Web of Science Core Collection (WoSCC). A bibliometric approach was employed to conduct a scientific, comprehensive, and objective quantitative analysis, as well as a visual analysis, of this particular research domain. A comprehensive analysis was conducted on a corpus of 3643 articles, which were collaboratively authored by 72 countries and various research institutions. CAR-T cell research in treating hematological malignancies shows an increasing trend each year. Notably, the study identified the countries and institutions displaying the highest level of activity, the journals with the most citations and output, as well as the authors who garnered the highest frequency of citations and co-citations. Furthermore, the analysis successfully identified the research hotspots and highlighted six emerging topics within this domain. This study conducted a comprehensive exploration and analysis of the research status, development trends, research hotspots, and emerging topics about CAR-T cells in the treatment of hematological malignancies from 2012 to 2023. The findings of this study will serve as a valuable reference and guide for researchers seeking to delve deeper into this field and determine the future direction of their research.


Asunto(s)
Bibliometría , Neoplasias Hematológicas , Inmunoterapia Adoptiva , Neoplasias Hematológicas/terapia , Humanos , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunología
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