Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
1.
Front Immunol ; 15: 1415026, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104521

RESUMEN

Introduction: Galactose-deficient IgA1 (GdIgA1) is critical in the formation of immunodeposits in IgA nephropathy (IgAN), whereas the origin of GdIgA1 is unknown. We focused on the immune response to fecal microbiota in patients with IgAN. Methods: By running 16S ribosomal RNA gene sequencing, we compared IgAN samples to the control samples from household-matched or non-related individuals. Levels of plasma GdIgA1 and poly-IgA complexes were measured, and candidate microbes that can either incite IgA-directed antibody response or degrade IgA through specific IgA protease activities were identified. Results: The IgAN group showed a distinct composition of fecal microbiota as compared to healthy controls. Particularly, high abundance of Escherichia-Shigella was associated with the disease group based on analyses using receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738-0.914), principle coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; p < 0.001). Accordingly, the bacterial levels directly correlated with high titers of plasma GdIgA1(r = 0.36, p < 0.001), and patients had higher IgA1 against stx2(2.88 ± 0.46 IU/mL vs. 1.34 ± 0.35 IU/mL, p = 0.03), the main antigen of Escherichia-Shigella. Conversely, the healthy controls showed relatively higher abundance of the commensal bacteria that produce IgA-degrading proteases. Particularly, the abundance of some intestinal bacteria expressing IgA proteases showed an inverse correlation with the levels of plasma GdIgA1 in IgAN. Conclusion: Our data suggest that mucosal IgA production, including those of GdIgA1, is potentially linked to the humoral response to gut Escherichia-Shigella as one of the sources of plasma GdIgA1. Conversely, the IgA protease-producing microbiota in the gut are suppressed in patients with IgAN.


Asunto(s)
Galactosa , Microbioma Gastrointestinal , Glomerulonefritis por IGA , Inmunidad Humoral , Inmunoglobulina A , Glomerulonefritis por IGA/inmunología , Glomerulonefritis por IGA/microbiología , Humanos , Microbioma Gastrointestinal/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/sangre , Masculino , Femenino , Adulto , Heces/microbiología , Persona de Mediana Edad , ARN Ribosómico 16S/genética
2.
Front Endocrinol (Lausanne) ; 15: 1361573, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055062

RESUMEN

Objective: The aim of this study was to evaluate the therapeutic implications of acupuncture on improving ovarian function in women diagnosed with premature ovarian insufficiency (POI) through the implementation of randomized clinical trials (RCTs). Methods: A comprehensive search of eight databases was conducted to identify RCTs up until 5 October 2023. The outcomes included the levels of sex hormones, antral follicle count (AFC), Kupperman score, and total effective rate. The risk of bias (RoB) tool was utilized to evaluate the quality of the included studies. In order to guarantee the robustness and reliability of the findings, subgroup and sensitivity analyses were performed to investigate potential sources of heterogeneity. Results: A total of 13 RCTs comprising 775 patients were included in the study. Acupuncture demonstrated significant efficacy in reducing follicle-stimulating hormone (FSH) [SMD = 0.83, 95% CI (0.27, 1.39), I 2 = 92%, p = 0.004], enhancing estradiol levels (E2) [SMD = 0.50, 95% CI (0.07, 0.93), p = 0.02, I 2 = 87%], and increasing anti-Müllerian hormone (AMH) [SMD = 0.24, 95% CI (0.05, 0.44), p = 0.01, I 2 = 8%], as well as improving the overall effective rate [RR = 1.22, 95% CI (1.10, 1.35), p < 0.01, I 2 = 14%]. Subgroup analysis revealed that compared with non-acupuncture therapy, the acupuncture with Chinese herbal medicine (CHM) and hormone replacement therapy (HRT) group exhibited a substantial reduction in FSH levels [SMD = 1.02, 95% CI (0.52, 1.51), I 2 = 60%, p < 0.01]. Furthermore, the acupuncture with CHM group also exhibited a substantial reduction [SMD = 4.59, 95% CI (1.53, 7.65), I 2 = 98%, p < 0.01]. However, only the acupuncture with CHM and HRT group demonstrated a significant increase in E2 levels [SMD = 0.55, 95% CI (0.23, 0.87), I 2 = 12%, p < 0.01]. Conclusion: Acupuncture has demonstrated superiority over non-acupuncture in diminishing serum FSH levels and increasing serum E2, AMH, and the overall efficacy rate in women diagnosed with POI. These research findings suggest the necessity for broader-scale research with meticulous designs to fully demonstrate the efficacy and safety of acupuncture in the treatment of women with POI. Systematic review registration: https://www.crd.york.ac.uk, identifier CRD42023467751.


Asunto(s)
Terapia por Acupuntura , Insuficiencia Ovárica Primaria , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Femenino , Insuficiencia Ovárica Primaria/terapia , Insuficiencia Ovárica Primaria/sangre , Terapia por Acupuntura/métodos , Hormona Folículo Estimulante/sangre , Resultado del Tratamiento , Hormona Antimülleriana/sangre
3.
J Hazard Mater ; 476: 135100, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38972200

RESUMEN

This research proposes a simple and novel strategy for the green detection of antibiotics along with the reduction of microplastic and humic acid (HA) hazards. The entire process is based on a single-step solvent-sieving method to separate HA into insoluble (IHA) and soluble (SHA) components, subsequently recombining and designing the application according to the original characteristics of selected fractions in accordance with the zero-waste principle. IHA was applied as a dispersive solid phase extraction (DSPE) sorbent without chemical modification for the enrichment of trace MACs in complex biological matrices. The recovery of MACs was 74.06-100.84 % in the range of 2.5-1000 µg∙kg-1. Furthermore, SHA could be combined with biodegradable polyvinyl alcohol (PVA) to prepare multifunctional composite films. SHA endows the PVA film with favorable mechanical properties, excellent UV shielding as well as oxidation resistance performance. Compared with pure PVA, the tensile strength, toughness, antioxidant and UV-protection properties were increased to 157.3 Mpa, 258.6 MJ·m-3, 78.6 % and 60 % respectively. This study achieved a green and economically valuable utilization of all components of waste HA, introduced a novel approach for monitoring and controlling harmful substances and reducing white pollution. This has significant implications for promoting sustainable development and recovering valuable resources.


Asunto(s)
Antibacterianos , Sustancias Húmicas , Alcohol Polivinílico , Sustancias Húmicas/análisis , Antibacterianos/química , Antibacterianos/análisis , Alcohol Polivinílico/química , Extracción en Fase Sólida/métodos , Tecnología Química Verde , Resistencia a la Tracción
4.
Complement Ther Med ; 82: 103051, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38761869

RESUMEN

BACKGROUND: Acupuncture stands out as a prominent complementary and alternative medicine therapy employed for functional dyspepsia (FD). We conducted a Bayesian meta-analysis to ascertain both the relative effectiveness and safety of various acupuncture methods in the treatment of functional dyspepsia. METHODS: We systematically searched eight electronic databases, spanning from their inception to April 2023. The eligibility criteria included randomized controlled trials investigating acupuncture treatments for FD. Study appraisal was conducted using the Cochrane risk of bias tool. Pairwise and network meta-analyses were conducted using RevMan 5.3 and ADDIS V.1.16.6 software. Bayesian network meta-analysis was performed to compare and rank the efficacy of different acupuncture therapies for FD symptoms. RESULTS: This study found that combining different acupuncture methods or using acupuncture in conjunction with Western medicine is more effective in improving symptoms of functional dyspepsia compared to using Western medicine alone. According to the comprehensive analysis results, notably, the combination of Western medicine and acupuncture exhibited superior efficacy in alleviating early satiation and postprandial fullness symptoms. For ameliorating epigastric pain, acupuncture combined with moxibustion proved to be the most effective treatment, while moxibustion emerged as the optimal choice for addressing burning sensations. Warming needle was identified as the preferred method for promoting motilin levels. CONCLUSION: The findings of this study demonstrate that acupuncture, both independently and in conjunction with other modalities, emerged as a secure and effective treatment option for patients with functional dyspepsia.


Asunto(s)
Terapia por Acupuntura , Teorema de Bayes , Dispepsia , Humanos , Terapia por Acupuntura/métodos , Dispepsia/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
Int Immunopharmacol ; 133: 112060, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38652970

RESUMEN

Acute respiratory distress syndrome (ARDS) is characterized by lung tissue oedema and inflammatory cell infiltration, with limited therapeutic interventions available. Receptor-interacting protein kinase 1 (RIPK1), a critical regulator of cell death and inflammation implicated in many diseases, is not fully understood in the context of ARDS. In this study, we employed RIP1 kinase-inactivated (Rip1K45A/K45A) mice and two distinct RIPK1 inhibitors to investigate the contributions of RIP1 kinase activity in lipopolysaccharide (LPS)-induced ARDS pathology. Our results indicated that RIPK1 kinase inactivation, achieved through both genetic and chemical approaches, significantly attenuated LPS-induced ARDS pathology, as demonstrated by reduced polymorphonuclear neutrophil percentage (PMN%) in alveolar lavage fluid, expression of inflammatory and fibrosis-related factors in lung tissues, as well as histological examination. Results by tunnel staining and qRT-PCR analysis indicated that RIPK1 kinase activity played a role in regulating cell apoptosis and inflammation induced by LPS administration in lung tissue. In summary, employing both pharmacological and genetic approaches, this study demonstrated that targeted RIPK1 kinase inactivation attenuates the pathological phenotype induced by LPS inhalation in an ARDS mouse model. This study enhances our understanding of the therapeutic potential of RIPK1 kinase modulation in ARDS, providing insights for the pathogenesis of ARDS.


Asunto(s)
Lipopolisacáridos , Inhibidores de Proteínas Quinasas , Proteína Serina-Treonina Quinasas de Interacción con Receptores , Síndrome de Dificultad Respiratoria , Animales , Humanos , Masculino , Ratones , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Neutrófilos/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Síndrome de Dificultad Respiratoria/inducido químicamente , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/inmunología
6.
Cancer ; 130(11): 1991-2002, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38404184

RESUMEN

BACKGROUND: This study investigated the safety and efficacy of an anti-CTLA-4 monoclonal antibody (CS1002) as monotherapy and in combination with an anti-PD-1 monoclonal antibody (CS1003) in patients with advanced/metastatic solid tumors. METHODS: The phase 1 study involved phase 1a monotherapy dose-escalation (part 1) and phase 1b combination therapy dose escalation (part 2) and expansion (part 3). Various dosing schedules of CS1002 (0.3, 1, or 3 mg/kg every 3 weeks, or 3 mg/kg every 9 weeks) were evaluated with 200 mg CS1003 every 3 weeks in part 3. RESULTS: Parts 1, 2, and 3 included a total of 13, 18, and 61 patients, respectively. No dose-limiting toxicities or maximum tolerated doses were observed. Treatment-related adverse events (TRAEs) were reported in 30.8%, 83.3%, and 75.0% of patients in parts 1, 2, and 3, respectively. Grade ≥3 TRAEs were experienced by 15.4%, 50.0%, and 18.3% of patients in each part. Of 61 patients evaluable for efficacy, 23 (37.7%) achieved objective responses in multiple tumor types. Higher objective response rates were observed with conventional and high-dose CS1002 regimens (1 mg/kg every 3 weeks or 3 mg/kg every 9 weeks) compared to low-dose CS1002 (0.3 mg/kg every 3 weeks) in microsatellite instability-high/mismatch repair-deficient tumors, melanoma, and hepatocellular carcinoma (50.0% vs. 58.8%, 14.3% vs. 42.9%, and 0% vs. 16.7%). CONCLUSION: CS1002, as monotherapy, and in combination with CS1003, had a manageable safety profile across a broad dosing range. Promising antitumor activities were observed in patients with immune oncology (IO)-naive and IO-refractory tumors across CS1002 dose levels when combined with CS1003, supporting further evaluation of this treatment combination for solid tumors. PLAIN LANGUAGE SUMMARY: CS1002 is a human immunoglobulin (Ig) G1 monoclonal antibody that blocks the interaction of CTLA-4 with its ligands and increases T-cell activation/proliferation. CS1003, now named nofazinlimab, is a humanized, recombinant IgG4 monoclonal antibody that blocks the interaction between human PD-1 and its ligands. In this original article, we determined the safety profile of CS1002 as monotherapy and in combination with CS1003. Furthermore, we explored the antitumor activity of the combination in anti-programmed cell death protein (ligand)-1 (PD-[L]1)-naive microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) pan tumors, and anti-PD-(L)1-refractory melanoma and hepatocellular carcinoma (HCC). CS1002 in combination with CS1003 had manageable safety profile across a broad dosing range and showed promising antitumor activities across CS1002 dose levels when combined with CS1003. This supports further assessment of CS1002 in combination with CS1003 for the treatment of solid tumors.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Antígeno CTLA-4 , Inhibidores de Puntos de Control Inmunológico , Neoplasias , Receptor de Muerte Celular Programada 1 , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Anciano , Adulto , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Dosis Máxima Tolerada , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
7.
J Nanobiotechnology ; 22(1): 39, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38279115

RESUMEN

BACKGROUND: The design of DNA materials with specific nanostructures for biomedical tissue engineering applications remains a challenge. High-dimensional DNA nanomaterials are difficult to prepare and are unstable; moreover, their synthesis relies on heavy metal ions. Herein, we developed a bimodal DNA self-origami material with good biocompatibility and differing functions using a simple synthesis method. We simulated and characterized this material using a combination of oxDNA, freeze-fracture electron microscopy, and atomic force microscopy. Subsequently, we optimized the synthesis procedure to fix the morphology of this material. RESULTS: Using molecular dynamics simulation, we found that the bimodal DNA self-origami material exhibited properties of spontaneous stretching and curling and could be fixed in a single morphology via synthesis control. The application of different functional nucleic acids enabled the achievement of various biological functions, and the performance of functional nucleic acids was significantly enhanced in the material. Consequently, leveraging the various functional nucleic acids enhanced by this material will facilitate the attainment of diverse biological functions. CONCLUSION: The developed design can comprehensively reveal the morphology and dynamics of DNA materials. We thus report a novel strategy for the construction of high-dimensional DNA materials and the application of functional nucleic acid-enhancing materials.


Asunto(s)
Nanoestructuras , Ácidos Nucleicos , Conformación de Ácido Nucleico , ADN/química , Nanoestructuras/química , Microscopía de Fuerza Atómica , Nanotecnología/métodos
8.
Toxicol Appl Pharmacol ; 482: 116788, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38086441

RESUMEN

Environmental chemicals, such as plasticizers, have been linked to increased rates of obesity, according to epidemiological studies. Acetyl triethyl citrate (ATEC) is a plasticizer that is commonly utilized in pharmaceutical products and food packaging as a non-phthalate alternative. Due to its direct contact with the human body and high leakage rate from the polymers, assessment of the potential risk of ATEC exposure at environmentally relevant low doses to human health is needed. Male C57BL/6 J mice were fed diets containing ATEC at doses of either 0.1 or 10 µg/kg per day in a period of 12 weeks to mimic the real exposure environment. The findings suggest that in C57BL/6 J mice, ATEC exposure resulted in increased body weight gain, body fat percentage, and benign hepatocytes, as well as adipocyte size. Consistent with in vivo models, ATEC treatment obviously stimulated the increase of intracellular lipid load in both mouse and human hepatocytes. Mechanically, ATEC induced the transcriptional expression of genes involved in de novo lipogenesis and lipid uptake. Using both enzyme inhibitor and small interfering RNA (siRNA) transfection, we found that stearoyl-coenzyme A desaturase 1 (SCD1) played a significant role in ATEC-induced intracellular lipid accumulation. This study for the first time provided initial evidence suggesting the obesogenic and fatty liver-inducing effect of ATEC at low doses near human exposure levels, and ATEC might be a potential environmental obesogen and its effect on human health need to be further evaluated.


Asunto(s)
Citratos , Lipogénesis , Plastificantes , Masculino , Ratones , Humanos , Animales , Plastificantes/toxicidad , Ratones Endogámicos C57BL , Obesidad/inducido químicamente , Obesidad/metabolismo , Lípidos , Hígado , Estearoil-CoA Desaturasa/genética , Estearoil-CoA Desaturasa/metabolismo
9.
Infect Med (Beijing) ; 2(1): 11-18, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38013777

RESUMEN

Background: Global evidence on the transmission of asymptomatic SARS-CoV-2 infection needs to be synthesized. Methods: A search of 4 electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science databases) as of January 24, 2021 was performed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Studies which reported the transmission rate among close contacts with asymptomatic SARS-CoV-2 cases were included, and transmission activities occurred were considered. The transmission rates were pooled by zero-inflated beta distribution. The risk ratios (RRs) were calculated using random-effects models. Results: Of 4923 records retrieved and reviewed, 15 studies including 3917 close contacts with asymptomatic indexes were eligible. The pooled transmission rates were 1.79 per 100 person-days (or 1.79%, 95% confidence interval [CI] 0.41%-3.16%) by asymptomatic index, which is significantly lower than by presymptomatic (5.02%, 95% CI 2.37%-7.66%; p<0.001), and by symptomatic (5.27%, 95% CI 2.40%-8.15%; p<0.001). Subgroup analyses showed that the household transmission rate of asymptomatic index was (4.22%, 95% CI 0.91%-7.52%), four times significantly higher than non-household transmission (1.03%, 95% CI 0.73%-1.33%; p=0.03), and the asymptomatic transmission rate in China (1.82%, 95% CI 0.11%-3.53%) was lower than in other countries (2.22%, 95% CI 0.67%-3.77%; p=0.01). Conclusions: People with asymptomatic SARS-CoV-2 infection are at risk of transmitting the virus to their close contacts, particularly in household settings. The transmission potential of asymptomatic infection is lower than symptomatic and presymptomatic infections. This meta-analysis provides evidence for predicting the epidemic trend and promulgating vaccination and other control measures. Registered with PROSPERO International Prospective Register of Systematic Reviews, CRD42021269446; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=269446.

10.
Heliyon ; 9(9): e19732, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37810054

RESUMEN

Background: Stress urinary incontinence (SUI), the most prevalent type of urinary incontinence disorder, has aroused increasing attention among societies since it has caused much inconvenience in daily life. In addition to conventional conservative treatments like medication and pelvic floor muscle training, acupuncture is now frequently advised. However, a bibliometric analysis of the trend of SUI therapies is still lacking. Objectives: This article was carried out using CiteSpace (6.3.1) software to research the use of acupuncture therapy on SUI worldwide over the past 30 years (since the database's inception). Methods: All related articles included were retrieved from the Web of Science Core Collection. CiteSpace (6.3.1) software was used to analyze the number of publications, countries and institutions, authors and cited authors, and burst keywords to assess the hotspots and trends over the previous three decades. And Microsoft Office Excel 2019 was also used for sorting data and generating tables. Results: The articles were retrieved on August 31, 2022. A total of 108 records with publication dates ranging from 1992 to 2022 were discovered. The annual number of publications generally increased. In the aspect of publication regions, the USA ranked first in centrality, but China had the largest number of publications. The China Academic of Chinese Medical Sciences, Beijing University of Chinese Medicine, and Shanghai University of Traditional Chinese Medicine were the top 3 institutions, according to the institution map. Liu Z (Liu ZS) was the most productive author, and Chen Y ranked first in the centrality. The article published by Liu Z (Liu ZS) in 2017 was the most cited reference. "Bladder neck suspension", "electrical stimulation" and "acupuncture" were popular therapies mentioned among the top ten hot topics. The keywords "therapy", "postprostatectomy incontinence", "muscle", "cell therapy", and "symptom" ranked in the top five on citation burst. The four frontier topics were "efficacy", "symptom", "cell therapy", and "medical technology". Conclusion: This study illustrated that the application of acupuncture on SUI had an increasing acceptance worldwide. Recent research has concentrated mainly on acupuncture and electroacupuncture, however, there is still not enough literature on these topics. The valuable information was provided for acupuncture researchers to identify prospects including potential collaborators, cooperation institutions, hot themes, and research frontiers.

11.
Nat Methods ; 20(10): 1593-1604, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37770711

RESUMEN

Recent proliferation and integration of tissue-clearing methods and light-sheet fluorescence microscopy has created new opportunities to achieve mesoscale three-dimensional whole-brain connectivity mapping with exceptionally high throughput. With the rapid generation of large, high-quality imaging datasets, downstream analysis is becoming the major technical bottleneck for mesoscale connectomics. Current computational solutions are labor intensive with limited applications because of the exhaustive manual annotation and heavily customized training. Meanwhile, whole-brain data analysis always requires combining multiple packages and secondary development by users. To address these challenges, we developed D-LMBmap, an end-to-end package providing an integrated workflow containing three modules based on deep-learning algorithms for whole-brain connectivity mapping: axon segmentation, brain region segmentation and whole-brain registration. D-LMBmap does not require manual annotation for axon segmentation and achieves quantitative analysis of whole-brain projectome in a single workflow with superior accuracy for multiple cell types in all of the modalities tested.


Asunto(s)
Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador , Procesamiento de Imagen Asistido por Computador/métodos , Encéfalo , Algoritmos , Mapeo Encefálico
12.
Br J Cancer ; 129(10): 1608-1618, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37731023

RESUMEN

BACKGROUND: We assessed nofazinlimab, an anti-PD-1 antibody, in solid tumors and combined with regorafenib in metastatic colorectal cancer (mCRC). METHODS: This phase 1 study comprised nofazinlimab dose escalation (phase 1a) and expansion (phase 1b), and regorafenib dose escalation (80 or 120 mg QD, days 1-21 of 28-day cycles) combined with 300-mg nofazinlimab Q4W (part 2a) to determine safety, efficacy, and RP2D. RESULTS: In phase 1a (N = 21), no dose-limiting toxicity occurred from 1 to 10 mg/kg Q3W, with 200 mg Q3W determined as the monotherapy RP2D. In phase 1b (N = 87), 400-mg Q6W and 200-mg Q3W regimens were found comparable. In part 2a (N = 14), both regimens were deemed plausible RP2Ds. Fatigue was the most frequent treatment-emergent adverse event (AE) in this study. Any-grade and grade 3/4 nofazinlimab-related AEs were 71.4% and 14.3%, 56.3% and 5.7%, and 57.1% and 21.4% in phases 1a, 1b, and part 2a, respectively. ORRs were 14.3% and 25.3% in phases 1a and 1b, respectively. In part 2a, no patients had radiological responses. CONCLUSIONS: Nofazinlimab monotherapy was well tolerated and demonstrated preliminary anti-tumor activity in multiple tumor types. Regorafenib plus nofazinlimab had a manageable safety profile but was not associated with any response in mCRC. CLINICAL TRIAL REGISTR ATION: Clinicaltrials.gov (NCT03475251).


Asunto(s)
Neoplasias del Colon , Neoplasias del Recto , Humanos , Piridinas , Compuestos de Fenilurea , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Recto/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
13.
J Nanobiotechnology ; 21(1): 269, 2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37574546

RESUMEN

Successful biomaterial implantation requires appropriate immune responses. Macrophages are key mediators involved in this process. Currently, exploitation of the intrinsic properties of biomaterials to modulate macrophages and immune responses is appealing. In this study, we prepared hydrophilic nanofibers with an aligned topography by incorporating polyethylene glycol and polycaprolactone using axial electrospinning. We investigated the effect of the nanofibers on macrophage behavior and the underlying mechanisms. With the increase of hydrophilicity of aligned nanofibers, the inflammatory gene expression of macrophages adhering to them was downregulated, and M2 polarization was induced. We further presented clear evidence that the inflammasome NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was the cellular sensor by which macrophages sense the biomaterials, and it acted as a regulator of the macrophage-mediated response to foreign bodies and implant integration. In vivo, we showed that the fibers shaped the implant-related immune microenvironment and ameliorated peritendinous adhesions. In conclusion, our study demonstrated that hydrophilic aligned nanofibers exhibited better biocompatibility and immunological properties.


Asunto(s)
Inflamasomas , Nanofibras , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Macrófagos/metabolismo , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas
14.
Foods ; 12(14)2023 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-37509751

RESUMEN

Five volatile thiol compounds (methanethiol, ethanethiol, 2-mercapto-1-ethanol, 2-furfurylthiol, and 2-methyl-3-furanethiol) in fermented grains of sauce-aroma baijiu were determined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The samples were pre-treated using a modified QuEChERS method. 4,4'-Dithiodipyridine (DTDP) derivatization reaction improved the detectability and stability of volatile thiol compounds. From the end of the first round to the end of the seventh round of fermentation and different fermentation states from the fifth round of fermented grains of the sauce-aroma baijiu production process were analyzed. The results showed that the concentrations of methanethiol (67.64-205.37 µg/kg), ethanethiol (1.22-1.76 µg/kg), 2-furfurylthiol (0.51-3.03 µg/kg), and 2-methyl-3-furanthiol (1.70-12.74 µg/kg) were increased with the number of fermentation rounds. Methanethiol, 2-furfurylthiol, and 2-methyl-3-furanthiol increased during fermentation and distillation in the fifth round. Fermentation and distillation were important stages for their widespread production. After distillation, there were still a large number of volatile thiol compounds in the fermented grains. The thermal reaction was of great significance in the formation of these thiols.

15.
Adv Sci (Weinh) ; 10(27): e2207715, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37518822

RESUMEN

The microenvironment and stem cell fate guidance of post-traumatic articular cartilage regeneration is primarily the focus of cartilage tissue engineering. In articular cartilage, stem cells are characterized by overlapping lineages and uneven effectiveness. Within the first 12 weeks after trauma, the articular inflammatory microenvironment (AIME) plays a decisive role in determining the fate of stem cells and cartilage. The development of fibrocartilage and osteophyte hyperplasia is an adverse outcome of chronic inflammation, which results from an imbalance in the AIME during the cartilage tissue repair process. In this review, the sources for the different types of stem cells and their fate are summarized. The main pathophysiological events that occur within the AIME as well as their protagonists are also discussed. Additionally, regulatory strategies that may guide the fate of stem cells within the AIME are proposed. Finally, strategies that provide insight into AIME pathophysiology are discussed and the design of new materials that match the post-traumatic progress of AIME pathophysiology in a spatial and temporal manner is guided. Thus, by regulating an appropriately modified inflammatory microenvironment, efficient stem cell-mediated tissue repair may be achieved.


Asunto(s)
Artritis , Cartílago Articular , Humanos , Regeneración/fisiología , Ingeniería de Tejidos/métodos , Células Madre , Cartílago Articular/lesiones , Cartílago Articular/fisiología , Cicatrización de Heridas
16.
J Hazard Mater ; 451: 131064, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-36871461

RESUMEN

Frequent crude oil spills and illegal discharges of industrial organic pollutants cause serious damage to the ecological environment and considerable loss of valuable resources. Therefore, there is an urgent need to develop efficient strategies to separate and recover oils or reagents from sewage. Herein, a green, facile and rapid one-step hydration method was applied to obtain the composite sponge (ZIF-8-PDA@MS) that monodispersed zeolitic imidazolate framework-8 nanoparticles with high porosity and large specific surface area were firmly loaded onto the melamine sponge by ligand exchange and the self-assembly of dopamine. The water contact angle of ZIF-8-PDA@MS with multiscale hierarchical porous structure could reach 162°, which remained stable over a long period of time and a wide pH range. ZIF-8-PDA@MS displayed excellent adsorption capacities (up to 85.45-168.95 g⋅g-1), and could be reused at least 40 times. Besides, ZIF-8-PDA@MS exhibited remarkable photothermal effect. Simultaneously, Silver nanoparticle-immobilized composite sponges were also prepared via in-situ reduction of silver ions to inhibit bacterial contamination. The composite sponge developed in this work can be used not only for the treatment of industrial sewage, but also for the emergency response of large-scale marine oil spill accidents, which has inestimable practical value for water decontamination.

17.
Environ Toxicol ; 38(6): 1395-1404, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36896678

RESUMEN

Diisobutyl adipate (DIBA), as a novel non-phthalate plasticizer, is widely used in various products. However, little effort has been made to investigate whether DIBA might have adverse effects on human health. In this study, we integrated an in silico and in vitro strategy to assess the impact of DIBA on cellular homeostasis. Since numerous plasticizers could activate peroxisome proliferator-activated receptor γ (PPARγ) pathway to interrupt metabolism systems, we first utilized molecular docking to analyze interaction between DIBA and PPARγ. Results indicated that DIBA had strong affinity with the ligand-binding domain of PPARγ (PPARγ-LBD) at Histidine 499. Afterwards, we used cellular models to investigate in vitro effects of DIBA. Results demonstrated that DIBA exposure increased intracellular lipid content in murine and human hepatocytes, and altered transcriptional expression of genes related to PPARγ signaling and lipid metabolism pathways. At last, target genes regulated by DIBA were predicted and enriched for Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Protein-protein interaction (PPI) network and transcriptional factors (TFs)-genes network were established accordingly. Target genes were enriched in Phospholipase D signaling pathway, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and Epidermal growth factor receptor (EGFR) signaling pathway which were related to lipid metabolism. These findings suggested that DIBA exposure might disturb intracellular lipid metabolism homeostasis via targeting PPARγ. This study also demonstrated that this integrated in silico and in vitro methodology could be utilized as a high throughput, cost-saving and effective tool to assess the potential risk of various environmental chemicals on human health.


Asunto(s)
PPAR gamma , Plastificantes , Ratones , Humanos , Animales , Plastificantes/toxicidad , PPAR gamma/metabolismo , Metabolismo de los Lípidos , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas/metabolismo , Adipatos
18.
Adv Biol (Weinh) ; 7(10): e2200304, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36808899

RESUMEN

This study aims to evaluate the comparative efficacy of electroacupuncture (EA) and analgesics in treating knee osteoarthritis (KOA) and provide evidence-based medical support for EA for the treatment of KOA. Randomized controlled trials from January 2012 to December 2021 are included in electronic databases. The Cochrane risk of bias tool for randomized trials is used to assess the risk of bias in the included studies, while the Grading of Recommendations, Assessment, Development and Evaluation is used to assess the quality of evidence. Statistical analyses are performed using Review Manager V5.4. There are 1616 patients from 20 clinical studies, including 849 patients in the treatment group and 767 patients in the control group. The effective rate in the treatment group is significantly higher than in the control group (p < 0.00001). In the treatment group, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) stiffness scores are significantly improved as compared to the control group (p < 0.0001). However, EA is similar to analgesics in improving visual analog scale scores and WOMAC subitems such as pain and joint function. EA is effective in treating KOA because it can significantly improve clinical symptoms and quality of life in KOA patients.

19.
Small ; 19(20): e2207234, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36703519

RESUMEN

The current solar-chemical-industry based on semiconductor photocatalyst is impractical. Metal catalysts are extensively employed in thermal- and electro-catalysis industries, but unsuitable for direct-driven photocatalysis. Herein, silver quantum dots (Ag-QDs) are synthesized on support via an in situ photoreduction method, and in situ photocatalysis temperature programmed dynamics chemisorption desorption analyses are designed to demonstrate that Ag-QDs should be the actual photocatalytic sites. The surface plasmon resonance of Ag-QDs could harvests entire visible solar, and the plasmon-driven charge-transfer exhibits opposite directions at the interface when supports are different. Consequently, Ag-QDs could be alternatively regulated as oxidation or reduction active centers. Furthermore, Ag-QDs excite electron tunneling transfer with adsorbate, which does not generate high-energy free-radical intermediates. As a result, the efficiencies of hydrocarbon photooxidation and CO2 photoreduction are improved in several orders of magnitude. Evidently, the Ag-QDs direct photocatalytic technology greatly promotes solar-chemical-industry applications.

20.
Animals (Basel) ; 13(1)2023 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-36611783

RESUMEN

Although broiler ascites syndrome (AS) has been extensively studied, its pathogenesis remains unclear. The lack of cardiopulmonary function in broilers causes relative hypoxia in the body; hence, the lung is the main target organ of AS. However, the transcriptome of AS lung tissue in broilers has not been studied. In this study, an AS model was successfully constructed, and lung tissues of three AS broilers and three healthy broilers were obtained for RNA sequencing (RNA-seq) and pathological observation. The results showed that 614 genes were up-regulated and 828 genes were down-regulated in the AS group compared with the normal group. Gene Ontology (GO) functional annotation revealed the following up-regulated genes: FABP4, APLN, EIF2AK4, HMOX1, MMP9, THBS1, TLR4, BCL2; and down-regulated genes: APELA, FGF7, WNT5A, CDK6, IL7, IL7R, APLNR. These genes have attracted much attention in cardiovascular diseases such as pulmonary hypertension. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that multiple metabolic processes were enriched, indicating abnormal lung metabolism of AS in broilers. These findings elucidate the potential genes and signal pathways in the lungs of broilers with AS and provide a potential target for studying the pathogenesis and preventing AS.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA