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Electrical stimulation is an important adjuvant therapy for spinal surgery, but whether receiving electrical stimulation can improve the fusion rate after spinal surgery is still controversial. The purpose of this study was to analyse and evaluate the effect of electrical stimulation on the fusion rate after spinal surgery. We systematically searched for related articles published in the PubMed, Embase and Cochrane Library databases on or before September 30, 2023. The odds ratio (OR) with 95% confidence interval (CI) and the fusion rates of the experimental group and the control group were calculated by a random-effects meta-analysis model. The analysis showed that receiving electrical stimulation significantly increased the probability of successful spinal fusion (OR 2.66 [95% CI 1.79-3.97]), and the average fusion rate of the electrical stimulation group (86.8%) was significantly greater than that of the control group (73.7%). The fusion rate in the direct current (DC) stimulation group was 2.33 times greater than that in the control group (OR 2.33 [95% CI 1.37-3.96]), and that in the pulsed electromagnetic field (PEMF) group was 2.60 times greater than that in the control group (OR 2.60 [95% CI 1.29-5.27]). Similarly, the fusion rate in the capacitive coupling (CC) electrical stimulation group was 3.44 times greater than that in the control group (OR 3.44 [95% CI 1.75-6.75]), indicating that regardless of the type of electrical stimulation, the fusion rate after spinal surgery improved to a certain extent. Electrical stimulation as an adjuvant therapy seems to improve the fusion rate after spinal surgery to a certain extent, but the specific effectiveness of this therapy needs to be further studied.
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Fusión Vertebral , Humanos , Fusión Vertebral/métodos , Terapia por Estimulación Eléctrica/métodos , Estimulación Eléctrica/métodos , Resultado del Tratamiento , Enfermedades de la Columna Vertebral/cirugíaRESUMEN
PURPOSE: Sarcopenia is considered to be an important predictor of adverse outcomes following spinal surgery, but the specific relationship between the two is not clear. The purpose of this meta-analysis is to systematically review all relevant studies to evaluate the impact of sarcopenia on spinal surgery outcomes. METHODS: We systematically searched PubMed, Embase and the Cochrane Library for relevant articles published on or before January 9, 2023. The pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated in a random effects meta-analysis. The main outcome was the risk of adverse outcomes after spinal surgery, including adverse events and mortality. This systematic review and meta-analysis was conducted following the PRISMA guidelines to evaluate the impact of sarcopenia on spinal surgery outcomes. In addition, we also conducted a subgroup analysis and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. RESULTS: Twenty-four cohort studies, with a total of 243,453 participants, met the inclusion criteria. The meta-analysis showed that sarcopenia was significantly associated with adverse events (OR 1.63, 95% CI 1.17-2.27, P < 0.001) but was no significantly associated with mortality (OR 1.17, 95% CI 0.93-1.46, P = 0.180), infection (OR 2.24, 95% CI 0.95-5.26, P < 0.001), 30-day reoperation (OR 1.47, 95% CI 0.92-2.36, P = 0.413), deep vein thrombosis (OR 1.78, 95% CI 0.69-4.61, P = 0.234), postoperative home discharge (OR 0.60, 95% CI 0.26-1.37, P = 0.002) and blood transfusion (OR 3.28, 95% CI 0.74-14.64, P = 0.015). CONCLUSION: The current meta-analysis showed that patients with sarcopenia have an increased risk of adverse events and mortality after spinal surgery. However, these results must be carefully interpreted because the number of studies included is small and the studies are significantly different. These findings may help to increase the clinicians' awareness of the risks concerning patients with sarcopenia to improve their prognosis.
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Complicaciones Posoperatorias , Sarcopenia , Columna Vertebral , Humanos , Sarcopenia/complicaciones , Sarcopenia/epidemiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Columna Vertebral/cirugía , IncidenciaRESUMEN
BACKGROUND: Currently, obesity has been recognized to be an independent risk factor for osteoarthritis (OA), and the Metabolic Score for Visceral Fat (METS-VF) has been suggested to be potentially more accurate than body mass index (BMI) in the assessment of obesity. Nevertheless, the correlation of METS-VF with OA has not been obviously revealed yet. Therefore, this study aimed to delve into the potential relationship between METS-VF and OA. METHODS: By examining data from the NHANES (2009-2018), weighted multivariate logistic regression analyses were used for assessing the correlation between METS-VF and OA. Subgroup analyses were then performed to validate the findings. Moreover, the nonlinear relationship between the two was assessed by restricted cubic spline (RCS). Receiver operating characteristic (ROC) curves were plotted to examine the diagnostic accuracy of METS-VF versus previous obesity index for OA. RESULTS: This study involved 7639 participants. According to our results, METS-VF was notably related to an elevated risk of OA, regardless of the METS-VF and the trend of positive association was more pronounced with the elevating METS-VF level (p for trend < 0.05). Subgroup analyses showed that the positive association between METS-VF and prevalence of osteoarthritis persisted in all populations with different characteristics, confirming its validity in all populations. Besides, RCS results showed a significant non-linear relationship between METS-VF and OA (p-non-linear < 0.05). As indicated by the ROC curve analysis results, METS-VF was a superior predictor of OA to BMI and HC. CONCLUSIONS: This study finds a possible nonlinear positive correlation between METS-VF and the risk of OA. In addition, METS-VF may serve as an indicator for the more accurate diagnosis of OA and provide a new way to further evaluate the relationship between visceral fat and OA.
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Grasa Intraabdominal , Encuestas Nutricionales , Osteoartritis , Humanos , Osteoartritis/metabolismo , Osteoartritis/epidemiología , Masculino , Grasa Intraabdominal/metabolismo , Femenino , Estudios Transversales , Persona de Mediana Edad , Factores de Riesgo , Adulto , Anciano , Síndrome Metabólico/epidemiología , Índice de Masa Corporal , Obesidad/epidemiología , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Roxarsone (ROX) is widely used as a feed additive, which is indigestible after ingestion by poultry, and most of it can only be excreted into the natural environment and degraded into highly toxic and carcinogenic inorganic arsenic compounds, which pose a hazard to the ecosystem and human health. However, for roxarsone, traditional detection methods require complex and time-consuming procedures, so it is urgent to find a new fast detection method for detection of ROX. RESULTS: In this work, we developed a novel Raman enhancement material and utilized the Surface-enhanced Raman scattering (SERS) technique to achieve rapid and sensitive detection of roxarsone. Specifically, Mo-doped cobalt layered double hydroxides (Co-LDHs) semiconductor material (abbreviated as CMM-100) was prepared by a simple method of using ion-assisted MOF etching. Under laser excitation at a wavelength of 532 nm, the CMM-100 showed excellent SERS property to various organic dye molecules such as methylene blue (MB), Toluidine Blue(TB), and Crystal Violet (CV). Especially, an enhancement factor (EF) of 1.4 × 106 was achieved for MB. Compared with the traditional method, this work utilized the fast and non-destructive SERS technology, which achieved a rapid detection of ROX. The detection limit was as low as 9.73 × 10-10 M, and the detection range was from 10-9 M to 10-3 M. SIGNIFICANCE: In this work, SERS technology was adopted for the rapid and sensitive detection of ROX. This study provides a Raman-enhanced substrate named CMMs for detection of food additives, pesticides, biomolecules, etc., which also broadens the application areas of SERS materials.
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BACKGROUND: People living with HIV (PLWH) are susceptible to social isolation as a result of stigma and discrimination, which not only diminishes adherence to antiretroviral therapy but also heightens the risks of hospital readmission, depression, and mortality. However, there is currently no systematic review addressing the occurrence and impact of social isolation in individuals with HIV. Therefore, this study undertook a comprehensive systematic review and meta-analysis of existing literature to examine the prevalence and influencing factors associated with social isolation among PLWH. METHODS AND ANALYSIS: PubMed, EMBASE, CINAHL, Cochrane Library, Web of Science, Google Scholar, China Science and Technology Journal Database, The China National Knowledge Infrastructure, WanFang Data and Chinese Biomedicine Literature Database will be searched from the establishment of the database to the latest search date. Literature screening, data extraction and literature quality assessment will be done independently by two researchers and results will be cross-referenced. Data analysis will be performed using stata15.1 software. Risk of publication bias will be assessed using Begg's and Egger's methods. Heterogeneity between studies will then be assessed using the I2 index and its 95% CI and Q statistics. Sources of heterogeneity will be accounted for by subgroup and sensitivity analyses. RESULTS: The results may reveal the prevalence of social isolation among PLWH and provide data support for understanding its etiology and prevention. CONCLUSION: By systematically reviewing the existing literature on social isolation among PLWH, this study aims to provide a comprehensive understanding of the prevalence of social isolation within this population, elucidate the detrimental effects it poses for people affected by HIV, and effectively inform targeted interventions for high-risk groups. Furthermore, these findings offer valuable insights to support evidence-based decision-making in public health policy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42024499044.
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Infecciones por VIH , Metaanálisis como Asunto , Aislamiento Social , Revisiones Sistemáticas como Asunto , Humanos , Aislamiento Social/psicología , Infecciones por VIH/psicología , Infecciones por VIH/epidemiología , Infecciones por VIH/tratamiento farmacológico , Incidencia , Síndrome de Inmunodeficiencia Adquirida/psicología , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Estigma SocialRESUMEN
OBJECTIVE: Chronic kidney disease (CKD) and osteoarthritis (OA) represent two frequently seen disorders among the general population, and they share several similar risk factors. The present work focused on assessing the relation of CKD with OA. METHODS: This cohort study included 26,280 eligible participants aged ≥ 20 years who had valid data on CKD and OA from the National Health and Nutrition Examination Survey (NHANES) 2011-2020. The association between CKD and OA was studied by logistic regression, adjusting for demographics, body mass index (BMI), socioeconomic factors, physical activity, ever smoking, alcohol using, diabetes status and hypertension status. RESULTS: Among the participants of this study, 26.69% of OA patients had concurrent CKD, whereas this proportion was only 13.83% among non-OA patients.CKD was related to OA[OR:2.269 (95%CI:2.266-2.271), p < 0.01] and the relation was of significance [OR:1.031 (95%CI:1.030-1.033),p < 0.01] following adjustments. In subgroup analyses based on age, the relation between osteoarthritis and chronic kidney disease remained significant, and in the subgroup analyses based on gender the previously mentioned relation between OA and CKD showed opposite directions in men [OR:0.869(95%CI0.867-0.871), p < 0.01] and women [OR:1.178(95%CI1.177-1.180), p < 0.01]. CONCLUSIONS: In the present 10-year large-scale national-wide survey, OA is closely related to CKD, and women with OA showed a higher risk of developing CKD compared to men. This study suggests that the relationship between OA and CKD deserves further investigation, and we suggest that patients with OA need to pay extra attention to their own kidney health.
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Encuestas Nutricionales , Osteoartritis , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/epidemiología , Masculino , Femenino , Osteoartritis/epidemiología , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto , Anciano , Estudios de Cohortes , Factores de Riesgo , Adulto JovenRESUMEN
The global impact of cancer on human health has raised significant concern. In this context, the tumor microenvironment (TME) plays a pivotal role in the tumorigenesis and malignant progression. In order to enhance the accuracy and efficacy of therapeutic outcomes, there is an imminent requirement for in vitro models that can accurately replicate the intricate characteristics and constituents of TME. Microfluidic devices exhibit notable advantages in investigating the progression and treatment of tumors and have the potential to become a novel methodology for evaluating immune cell activities in TME and assist clinicians in assessing the prognosis of patients. In addition, it shows great advantages compared to traditional cell experiments. Therefore, the review first outlines the applications and advantages of microfluidic chips in facilitating tumor cell culture, constructing TME and investigating immune cell activities. Second, the roles of microfluidic devices in the analysis of circulating tumor cells, tumor prognosis, and drug screening have also been mentioned. Moreover, a forward-looking perspective is discussed, anticipating the widespread clinical adoption of microfluidic devices in the future.
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Soil-based irrigation and the partial substitution of chemical fertilizers with manure are promising practices to improve water and nitrogen (N) use efficiency. We hypothesize that their combination would simultaneously benefit potato production, tuber quality and profitability. A two-year experiment was conducted in semiarid northern China to investigate the combined effects of three water treatments [rainfed (W0), soil-based irrigation (W1), conventional irrigation (W2)] and three N treatments [no N (N0), chemical N (N1), 25% manure substitution (N2)] on these indicators, and to perform a comprehensive evaluation and correlation analysis. The results showed that water and N treatments separately affected all indicators except vitamin C content. Compared to W2, W1 significantly increased water productivity by 12% and irrigation water use efficiency (IWUE) by 30% due to 10% lower evapotranspiration and 21% lower water use. However, W1 and W2 negatively affected crude protein content. Conversely, this was compensated by the combination with N1 and N2. There were slight differences between N1 and N2 for all indicators on average across water treatments, while under W1, N2 significantly increased leaf area index (LAI) and N recovery efficiency (REN) by 18% and 29.4%, respectively, over N1. Also, comprehensive evaluations showed that W1N2 performed best, with the highest tuber yield, profit and acceptable quality. This can be explained by the increase in LAI, IWUE and REN due to the positive correlations with tuber yield and net return. Consequently, soil-based irrigation combined with 25% manure substitution had complementary effects on tuber quality and synergistic effects on potato productivity and profitability.
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INTRODUCTION: Hydroxysteroid 17-beta dehydrogenase 4 (HSD17B4) is involved in the progression of hepatocellular carcinoma (HCC). AIMS: This study aimed to investigate the inhibitory effect of gamma-tocotrienol (γ-T3) on the proliferation and growth of HSD17B4-overexpressing HepG2 cells. METHODS: HepG2 cells were transfected with empty or HSD17B4-overexpressing plasmids, followed by vitamin E (VE) or γ-T3 treatment. MTS assay, Western blotting, qRT-PCR, and flow cytometry were employed to assess cell proliferation, protein expression, mRNA levels, and apoptosis. HSD17B4 interaction with γ-T3 was assessed by quantifying γ-T3 in the collected precipitate of HSD17B4 using anti-flag magnetic beads. Tumor xenografts were established in NSG mice, and tumor growth was monitored. RESULTS: HSD17B4 overexpression significantly promoted HepG2 cell proliferation, which was effectively counteracted by VE or γ-T3 treatment in a dose-dependent manner. VE and γ-T3 did not exert their effects through direct regulation of HSD17B4 expression. Instead, γ-T3 was found to interact with HSD17B4, inhibiting its activity in catalyzing the conversion of estradiol (E2) into estrone. Moreover, γ-T3 treatment led to a reduction in cyclin D1 expression and suppressed key proliferation signaling pathways, such as ERK, MEK, AKT, and STAT3. Additionally, γ-T3 promoted apoptosis in HSD17B4-overexpressing HepG2 cells. In an in vivo model, γ-T3 effectively reduced the growth of HepG2 xenograft tumors. CONCLUSION: In conclusion, our study demonstrates that γ-T3 exhibits potent anti-proliferative and anti-tumor effects against HepG2 cells overexpressing HSD17B4. These findings highlight the therapeutic potential of γ-T3 in HCC treatment and suggest its role in targeting HSD17B4-associated pathways to inhibit tumor growth and enhance apoptosis.
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Importance: Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis. Objective: To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed. Interventions: Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90). Main Outcomes and Measures: The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome. Results: A total of 11â¯431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively. Conclusions and Relevance: Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.
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Atorvastatina , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Persona de Mediana Edad , Femenino , Anciano , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Método Doble Ciego , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & control , Atorvastatina/uso terapéutico , Atorvastatina/administración & dosificación , Ataque Isquémico Transitorio/tratamiento farmacológico , Adulto , Isquemia Encefálica/tratamiento farmacológico , Anciano de 80 o más Años , Prevención Secundaria/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/administración & dosificaciónRESUMEN
Bovine viral diarrhea virus (BVDV) is considered to be the most common agent of severe diarrhea in cattle worldwide, causing fever, diarrhea, ulcers, and abortion. Bovine herpesvirus 1 (BoHV-1) is also a major bovine respiratory disease agent that spreads worldwide and causes extensive damage to the livestock industry. Recombinase polymerase amplification (RPA) is a novel nucleic acid amplification method with the advantages of high efficiency, rapidity and sensitivity, which has been widely used in the diagnosis of infectious diseases. A dual RPA assay was developed for the simultaneous detection of BVDV and BoHV-1. The assay was completed at a constant temperature of 37 °C for 30 min. It was highly sensitive and had no cross-reactivity with other common bovine viruses. The detection rate of BVDV RPA in clinical samples (36.67%) was higher than that of PCR (33.33%), the detection rate of BoHV-1 RPA and PCR were equal. Therefore, the established dual RPA assay for BVDV and BoHV-1 could be a potential candidate for use as an immediate diagnostic.
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Virus de la Diarrea Viral Bovina , Herpesvirus Bovino 1 , Técnicas de Amplificación de Ácido Nucleico , Recombinasas , Animales , Bovinos , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 1/aislamiento & purificación , Técnicas de Amplificación de Ácido Nucleico/métodos , Recombinasas/metabolismo , Virus de la Diarrea Viral Bovina/genética , Virus de la Diarrea Viral Bovina/aislamiento & purificación , Sensibilidad y Especificidad , Diarrea Mucosa Bovina Viral/virología , Diarrea Mucosa Bovina Viral/diagnóstico , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/diagnóstico , ADN Viral/genéticaRESUMEN
Manganese(II)-based contrast agents (MBCAs) are potential candidates for gadolinium-free enhanced magnetic resonance imaging (MRI). In this work, a rigid binuclear MBCA (Mn2-PhDTA2) with a zero-length linker was developed via facile synthetic routes, while the other dimer (Mn2-TPA-PhDTA2) with a longer rigid linker was also synthesized via more complex steps. Although the molecular weight of Mn2-PhDTA2 is lower than that of Mn2-TPA-PhDTA2, their T1 relaxivities are similar, being increased by over 71% compared to the mononuclear Mn-PhDTA. In the presence of serum albumin, the relaxivity of Mn2-PhDTA2 was slightly lower than that of Mn2-TPA-PhDTA2, possibly due to the lower affinity constant. The transmetalation reaction with copper(II) ions confirmed that Mn2-PhDTA2 has an ideal kinetic inertness with a dissociation half-life of approximately 10.4 h under physiological conditions. In the variable-temperature 17O NMR study, both Mn-PhDTA and Mn2-PhDTA2 demonstrated a similar estimated q close to 1, indicating the formation of monohydrated complexes with each manganese(II) ion. In addition, Mn2-PhDTA2 demonstrated a superior contrast enhancement to Mn-PhDTA in in vivo vascular and hepatic MRI and can be rapidly cleared through a dual hepatic and renal excretion pattern. The hepatic uptake mechanism of Mn2-PhDTA2 mediated by SLC39A14 was validated in cellular uptake studies.
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Medios de Contraste , Hígado , Imagen por Resonancia Magnética , Manganeso , Manganeso/química , Hígado/diagnóstico por imagen , Hígado/metabolismo , Imagen por Resonancia Magnética/métodos , Animales , Medios de Contraste/química , Medios de Contraste/síntesis química , Humanos , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/química , Ratones , Complejos de Coordinación/química , Complejos de Coordinación/síntesis químicaRESUMEN
OBJECTIVE: This study aimed to study the correlation between preeclampsia (PE) and lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and to examine the molecular mechanisms behind the development of PE. METHODS: 30 PE and 30 normal pregnant women placental samples were assessed the levels of NEAT1 and miR-217 by quantitative real-time PCR (qRT-PCR). The trophoblast cell line HTR8/SVneo was used for silencing NEAT1 or miR-217 inhibitor in the absence or presence of an inhibitor and H2O2. Cell counting Kit 8 (CCK-8), flow cytometry, and Transwell were used to detect cell proliferation, apoptosis, migration, and invasion. Luciferase reporter gene assay was utilized to verify the binding between miR-217 and Wnt family member 3 (Wnt3), and between the miR-217 and NEAT1. Proteins related to the Wnt/ß-catenin signaling pathway were detected using western blotting. RESULTS: The PE group exhibited a significantly downregulated expression of miR-217 and a significantly upregulated expression of NEAT1. NEAT1 targeted miR-217, and Wnt is a miR-217 target gene. siRNA-NEAT1 inhibited the apoptosis of trophoblast cells, but promoted their invasion, migration, and proliferation. MiR-217 inhibitor could partially reverse the effects of siRNA-NEAT1. The expression of the Wnt/ß-catenin signaling pathway-related proteins, WNT signaling pathway inhibitor 1 (DKK1), cyclin-D1 and ß-catenin, was significantly increased after siRNA-NEAT1. CONCLUSIONS: NEAT1 could reduce trophoblast cell invasion and migration by suppressing miR-217/Wnt signaling pathway, leading to PE.
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Apoptosis , Movimiento Celular , Proliferación Celular , MicroARNs , Preeclampsia , ARN Largo no Codificante , Trofoblastos , Vía de Señalización Wnt , Humanos , MicroARNs/genética , ARN Largo no Codificante/genética , Femenino , Trofoblastos/metabolismo , Trofoblastos/patología , Vía de Señalización Wnt/genética , Movimiento Celular/genética , Embarazo , Proliferación Celular/genética , Preeclampsia/genética , Preeclampsia/patología , Preeclampsia/metabolismo , Apoptosis/genética , Adulto , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
Introduction: Rheumatoid arthritis (RA) is an inflammatory immune-mediated disease that involves synovitis, cartilage destruction, and even joint damage. Traditional agents used for RA therapy remain unsatisfactory because of their low efficiency and obvious adverse effects. Therefore, we here established RA microenvironment-responsive targeted micelles that can respond to the increase in reactive oxygen species (ROS) levels in the joint and improve macrophage-specific targeting of loaded drugs. Methods: We here prepared ROS-responsive folate-modified curcumin micelles (TK-FA-Cur-Ms) in which thioketal (TK) was used as a ROS-responsive linker for modifying polyethylene glycol 5000 (PEG5000) on the micellar surface. When micelles were in the ROS-overexpressing inflammatory microenvironment, the PEG5000 hydration layer was shed, and the targeting ligand FA was exposed, thereby enhancing cellular uptake by macrophages through active targeting. The targeting, ROS sensitivity and anti-inflammatory properties of the micelles were assessed in vitro. Collagen-induced arthritis (CIA) rats model was utilized to investigate the targeting, expression of serum inflammatory factors and histology change of the articular cartilage by micelles in vivo. Results: TK-FA-Cur-Ms had a particle size of 90.07 ± 3.44 nm, which decreased to 78.87 ± 2.41 nm after incubation with H2O2. The micelles exhibited in vitro targeting of RAW264.7 cells and significantly inhibited inflammatory cytokine levels. Pharmacodynamic studies have revealed that TK-FA-Cur-Ms prolonged the drug circulation and exhibited augmented cartilage-protective and anti-inflammatory effects in vivo. Conclusion: The unique ROS-responsive targeted micelles with targeting, ROS sensitivity and anti-inflammatory properties were successfully prepared and may offer an effective therapeutic strategy against RA.
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Artritis Reumatoide , Curcumina , Receptores de Folato Anclados a GPI , Micelas , Especies Reactivas de Oxígeno , Animales , Masculino , Ratones , Ratas , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacocinética , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Curcumina/administración & dosificación , Curcumina/química , Curcumina/farmacología , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Receptores de Folato Anclados a GPI/metabolismo , Ácido Fólico/química , Ácido Fólico/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Tamaño de la Partícula , Polietilenglicoles/química , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos , Inmunoterapia , Neoplasias Pulmonares , Terapia Molecular Dirigida , Microambiente Tumoral , Humanos , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/inmunología , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Animales , Biomarcadores de TumorRESUMEN
Background: Leukemia patients undergoing cryopreserved ovarian tissue transplantation (OTT) may carry a high risk of disease induction. Measurable residual disease (MRD) in bone marrow is linked to an elevated risk of relapse. It is controversial whether leukemia patients must be allowed to achieve measurable residual disease negative (MRD-negative) status instead of measurable residual disease positive (MRD-positive) status before ovarian tissue cryopreservation (OTC). Objective: To explore the safety and efficacy of OTT in acute leukemia patients with different MRD status by using xenotransplantation. Method: Cryopreserved ovarian tissue from 19 leukemia patients was thawed and xenotransplanted to ovariectomized BALB/C nude mice (n=36). The mice were divided into 2 groups based on the patient's MRD status before OTC: MRD-negative group (n=18) and MRD-positive group (n=18), additionally, a control group consisted of ovariectomized mice (n=9). Body weight was measured weekly and mortality, emaciation, and other abnormalities were recorded. Twenty-six weeks post-surgery, livers, spleens, uteruses, and ovarian grafts were removed for macroscopic and histological examinations to evaluate the efficacy of xenotransplantation and assess malignant cell contamination in mice. Results: Follicle growth was visible in the ovarian grafts of the MRD-negative and MRD-positive groups. Compared with the ovariectomized group, a significant decrease in body weight (p<0.01) was noted, the uterine volume was notably larger, estradiol (E2) levels were significantly higher (p<0.01), and follicle-stimulating hormone (FSH) levels were significantly lower (p<0.001) in the other two groups. Mice in the MRD-positive group showed a significantly higher incidence of death (p<0.001) and emaciation (p<0.01), compared to the MRD-negative group. Histological observation revealed the presence of malignant cells in the grafts, livers, and spleens of 3 mice in the MRD-positive group. No abnormalities were observed in the mice from the MRD-negative group in both macroscopic and histological observations except one mouse was sacrificed for ascites unrelated to leukemia relapse. Conclusion: For leukemia patients having ovarian tissue preserved in the first and only centralized human ovarian tissue cryobank in China, immunodeficient mice xenotransplantation can be a method to evaluate the safety and efficacy of OTT; the risk of malignant cell reimplantation due to OTT is higher in leukemia patients with MRD-positive status than those with MRD-negative status before OTC.
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Médula Ósea , Leucemia , Femenino , Humanos , Animales , Ratones , Trasplante Heterólogo , Ratones Desnudos , Emaciación , Ratones Endogámicos BALB C , Criopreservación , RecurrenciaRESUMEN
Effective vascular and hepatic enhancement and better safety are the key drivers for exploring gadolinium-free hepatobiliary contrast agents. Herein, a facile strategy proposes that the high lipophilicity may be favorable to enhancing sequentially vascular and hepatobiliary signal intensity based on the structure-activity relationship that both hepatic uptake and interaction with serum albumins partly depend on lipophilicity. Therefore, 11 newly synthesized derivatives of manganese o-phenylenediamine-N,N,N',N'-tetraacetic acid (MnLs) were evaluated as vascular and hepatobiliary agents. The maximum signal intensities of the heart, liver, and kidneys were strongly correlated with log P, a key indicator of lipophilicity. The most lipophilic agent, MnL6, showed favorable relaxivity when binding with serum albumin, good vascular enhancement, rapid excretion, and reliable hepatobiliary phases comparable to a classic hepatobiliary agent, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for in vivo liver tumor imaging. Inhibition experiments confirmed the hepatic targeting of MnL6 is mediated by organic anion-transporting polypeptides.
Asunto(s)
Medios de Contraste , Neoplasias Hepáticas , Humanos , Medios de Contraste/metabolismo , Manganeso , Gadolinio DTPA/metabolismo , Hígado/metabolismo , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodosRESUMEN
Due to the physiological alteration during pregnancy, maternal gut microbiota changes following the metabolic processes. Recent studies have revealed that maternal gut microbiota is closely associated with the immune microenvironment in utero during pregnancy and plays a vital role in specific pregnancy complications, including preeclampsia, gestational diabetes, preterm birth and recurrent miscarriages. Some other evidence has also shown that aberrant maternal gut microbiota increases the risk of various diseases in the offspring, such as allergic and neurodevelopmental disorders, through the immune alignment between mother and fetus and the possible intrauterine microbiota. Probiotics and the high-fiber diet are effective inventions to prevent mothers and fetuses from diseases. In this review, we summarize the role of maternal gut microbiota in the development of pregnancy complications and the health condition of future generations from the perspective of immunology, which may provide new therapeutic strategies for the health management of mothers and offspring.
Asunto(s)
Microbioma Gastrointestinal , Microbiota , Complicaciones del Embarazo , Nacimiento Prematuro , Embarazo , Femenino , Humanos , Recién Nacido , Madres , Complicaciones del Embarazo/metabolismoRESUMEN
Coronary atherosclerosis leading to ischemic artery disease is one of the etiological factors to develop heart failure (HF). This study aimed to investigate potential biomarkers for discriminating HF in atherosclerotic patients. This study included 40 consecutive atherosclerotic patients who underwent angiography. Concentrations of B-type natriuretic peptide (BNP), fibronectin type III domain containing 5 (FNDC5), and Phosphodiesterase 9A (PDE9A) were measured in 20 atherosclerotic patients with HF symptoms/signs and 20 without HF symptoms/signs. Circulating BNP levels were elevated, while FNDC5 levels were reduced in atherosclerotic patients with HF symptoms/signs compared to those without HF symptoms/signs. Pearson correlation analysis showed a significant correlation between FNDC5 and BNP. Receiver Operating Characteristics analysis indicated that both FNDC5 and BNP were able to discriminate HF in atherosclerotic patients. Our findings suggest that FNDC5, along with BNP, has independent value as a biomarker for discriminating HF in patients with coronary atherosclerosis.