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1.
BMC Musculoskelet Disord ; 24(1): 40, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36650473

RESUMEN

BACKGROUND: This study was aimed to investigate whether the application of platelet-rich plasma (PRP) combined with ß-tri-calcium phosphate (ß-TCP) grafts after core decompression (CD) could improve the clinical outcomes of early stage of avascular necrosis of femoral head. METHODS: Forty-five (54 hips) patients with Ficat-Arlet classification stage I-II treated by CD with ß-TCP grafts with or without the application of PRP from July 2015 to October 2020 were reviewed. Group A (CD + ß-TCP grafts) included 24 patients (29 hips), while group B (CD + ß-TCP grafts + PRP) included 21 patients (25 hips). Visual analogue scale (VAS) score, Harris hip score (HHS), change in modified Kerboul angle and the hip joint survival were evaluated and compared between the groups. Patients had a mean follow-up period of 62.1 ± 17.2 months and 59.3 ± 14.8 months in group A and group B, respectively. RESULTS: The mean VAS scores in group A was significantly higher than group B at the 6 months (2.9 ± 0.7 vs 1.9 ± 0.6, p < 0.01) and final follow up postoperative (2.8 ± 1.2 vs 2.2 ± 0.7, p = 0.04). The mean HHS in group A was significantly lower than group B at the 6 months (80.5 ± 13.8 vs 89.8 ± 12.8, p = 0.02). However, at the final follow up, there is no significant difference between the groups (77.0 ± 12.4 vs 83.1 ± 9.3, p = 0.07). The mean change in modified Kerboul angle was -7.4 ± 10.6 in group A and -19.9 ± 13.9 in group B which is statistically significant (p < 0.01). Survivorship from total hip arthroplasty were 86.2%/84% (p = 0.86) at the final follow up, which was not statistically significant. No serious complications were found in both groups. CONCLUSIONS: A single dose of PRP combined with CD and ß-TCP grafts provided significant pain relief, better functional outcomes, and delayed progression in the short term compared to CD combined with ß-TCP grafts. However, the prognosis of the femoral head did not improve significantly in the long term. In the future, designing new implants to achieve multiple PRP injections may improve the hip preservation rate.


Asunto(s)
Necrosis de la Cabeza Femoral , Plasma Rico en Plaquetas , Humanos , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Necrosis de la Cabeza Femoral/cirugía , Resultado del Tratamiento , Cabeza Femoral/diagnóstico por imagen , Cabeza Femoral/cirugía , Descompresión Quirúrgica/efectos adversos , Fosfatos de Calcio/uso terapéutico , Trasplante Óseo/efectos adversos
2.
BMC Musculoskelet Disord ; 24(1): 123, 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36782133

RESUMEN

BACKGROUND: The purpose of this study is to investigate the microbial patterns of periprosthetic joint infection (PJI) and fracture-related infection (FRI), and guide for the formulation of more accurate empirical antimicrobial regimens based on the differences in pathogen distribution. METHODS: A comparative analysis of pathogen distribution was conducted between 153 patients (76 with PJI and 77 with FRI). Predicted analyses against isolated pathogens from two cohorts were conducted to evaluate the best expected efficacy of empirical antimicrobial regimens (imipenem + vancomycin, ciprofloxacin + vancomycin, and piperacillin/tazobactam + vancomycin). RESULTS: Our study found significant differences in pathogen distribution between the PJI and FRI cohorts. Staphylococci (61.3% vs. 31.9%, p = 0.001) and Gram-negative bacilli (GNB, 26.7% vs. 56.4%, p < 0.001) were responsible for the majority of infections both in the PJI and FRI cohorts, and their distribution in the two cohorts showed a significant difference (p < 0.001). Multi-drug resistant organisms (MDRO) were more frequently detected in the FRI cohort (29.3% vs. 44.7%, p = 0.041), while methicillin-resistant coagulase-negative Staphylococci (MRCoNS, 26.7% vs. 8.5%, p = 0.002) and Canidia albicans (8.0% vs. 1.1%, p = 0.045) were more frequently detected in the PJI cohort. Enterobacter spp. and Acinetobacter baumannii were detected only in the FRI cohort (11.7% and 8.5%, respectively). CONCLUSIONS: Staphylococci and GNB were responsible for the majority of infections in both PJI and FRI. Empirical antimicrobial therapy should focus on the coverage of Staphylococci in PJI and GNB in FRI, and infections caused by MDROs should be more vigilant in FRI, while the high incidence of MRCoNS in PJI should be noted, which could guide for the formulation of more accurate empirical antimicrobial regimens. Targeted therapy for FRI caused by A. baumannii and PJI caused by C. albicans needs to be further investigated. Our study reports significant differences in pathogen distribution between the two infections and provides clinical evidence for studies on the mechanism of implant-associated infection.


Asunto(s)
Antiinfecciosos , Artritis Infecciosa , Infecciones Relacionadas con Prótesis , Humanos , Vancomicina , Antibacterianos/uso terapéutico , Estudios Retrospectivos , Infecciones Relacionadas con Prótesis/epidemiología , Staphylococcus , Antiinfecciosos/uso terapéutico , Combinación Piperacilina y Tazobactam/uso terapéutico
3.
Small ; 17(38): e2102545, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34363305

RESUMEN

Nanocellulose including cellulose nanocrystal (CNC) and cellulose nanofiber (CNF) has attracted much attention due to its exceptional mechanical, chemical, and rheological properties. Although considered biocompatible, recent reports have demonstrated nanocellulose can be hazardous, including serving as drug carriers that accumulate in the liver. However, the nanocellulose effects on liver cells, including Kupffer cells (KCs) and hepatocytes are unclear. Here, the toxicity of nanocellulose with different lengths is compared, including the shorter CNCs (CNC-1, CNC-2, and CNC-3) and longer CNF (CNF-1 and CNF-2), to liver cells. While all CNCs triggered significant cytotoxicity in KCs and only CNC-2 induced toxicity to hepatocytes, CNFs failed to induce significant cytotoxicity due to their minimal cellular uptake. The phagocytosis of CNCs by KCs induced mitochondria ROS generation, caspase-3/7 activation, and apoptotic cell death as well as lysosomal damage, cathepsin B release, NLRP3 inflammasome and caspase-1 activation, and IL-1ß production. The cellular uptake of CNC-2 by hepatocytes is through clathrin-mediated endocytosis, and it induced the caspase-3/7-mediated apoptosis. CNC-2 shows the highest levels of uptake and cytotoxicity among CNCs. These results demonstrate the length-dependent mechanisms of toxicity on liver cells in a cell type-dependent fashion, providing information to safely use nanocellulose for biomedical applications.


Asunto(s)
Hepatocitos , Macrófagos del Hígado , Inflamasomas , Hígado , Macrófagos
4.
Small ; 17(25): e2101084, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34032006

RESUMEN

2D boron nitride (BN) and molybdenum disulfide (MoS2 ) materials are increasingly being used for applications due to novel chemical, electronic, and optical properties. Although generally considered biocompatible, recent data have shown that BN and MoS2 could potentially be hazardous under some biological conditions, for example, during, biodistribution of drug carriers or imaging agents to the liver. However, the effects of these 2D materials on liver cells such as Kupffer cells (KCs), liver sinusoidal endothelial cells, and hepatocytes, are unknown. Here, the toxicity of BN and MoS2 , dispersed in Pluronic F87 (designated BN-PF and MoS2 -PF) is compared with aggregated forms of these materials (BN-Agg and MoS2 -Agg) in liver cells. MoS2 induces dose-dependent cytotoxicity in KCs, but not other cell types, while the BN derivatives are non-toxic. The effect of MoS2 could be ascribed to nanosheet dissolution and the release of hexavalent Mo, capable of inducing mitochondrial reactive oxygen species generation and caspases 3/7-mediated apoptosis in KUP5 cells. In addition, the phagocytosis of MoS2 -Agg triggers an independent response pathway involving lysosomal damage, NLRP3 inflammasome activation, caspase-1 activation, IL-1ß, and IL-18 production. These findings demonstrate the importance of Mo release and the state of dispersion of MoS2 in impacting KC viability.


Asunto(s)
Células Endoteliales , Molibdeno , Compuestos de Boro , Disulfuros , Hepatocitos , Hígado , Molibdeno/toxicidad , Solubilidad , Distribución Tisular
5.
Arch Toxicol ; 95(1): 195-205, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33159582

RESUMEN

Electronic cigarette (e-cigarette) use has been linked to recent acute lung injury case clusters in over 2000 patients and dozens of deaths in the United States, however, the mechanism leading to lung injury is not certain although ultrafine particles, heavy metals, volatile organic compounds, and other harmful ingredients have been implicated. To systematically evaluate e-cigarette toxicity, we generated e-cigarette aerosols by varying the puff numbers (20-480), nicotine contents (0-24 mg/mL), and collected e-cigarette samples through an impinger system for biological assays. The calculated samples' concentration ranged from 1.96 to 47.06 mg/mL. THP-1 monocyte-differentiated macrophages, BEAS-2B bronchial epithelial cells, wild-type C57BL/6 mice, and NF-κB-luc transgenic mice were used to test the effects of these samples. E-cigarette samples showed cytotoxicity to THP-1 cells and BEAS-2B in vitro, leading to increased oxidative stress, inflammatory cytokine production with or without nicotine, and cell death. Furthermore, aerosol generated from PG is more toxic than VG. The toxicity of e-cigarette samples is at least partially due to the reactive oxygen species and aldehydes, which are generated during the aerosolization processes by the e-cigarette device. After NF-κB-luc mice exposed with e-cigarette samples by oropharyngeal aspiration, NF-κB expressions were observed in a dose-response fashion with or without nicotine. In addition, the e-cigarette samples induced neutrophil infiltration, IL-1ß production, oxidative stress marker heme oxygenase-1 expression in wild-type C57BL/6 mice. These results suggested that oxidative stress, pro-inflammatory NF-κB pathway activation, and cell death are involved in e-cigarette aerosol-induced acute lung inflammation.


Asunto(s)
Cigarrillo Electrónico a Vapor/toxicidad , Pulmón/efectos de los fármacos , FN-kappa B/metabolismo , Estrés Oxidativo/efectos de los fármacos , Neumonía/inducido químicamente , Aerosoles , Aldehídos/metabolismo , Animales , Muerte Celular/efectos de los fármacos , Citocinas/metabolismo , Humanos , Exposición por Inhalación , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , FN-kappa B/genética , Infiltración Neutrófila/efectos de los fármacos , Neumonía/inmunología , Neumonía/metabolismo , Neumonía/patología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Células THP-1
6.
J Org Chem ; 84(11): 6798-6806, 2019 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-31095379

RESUMEN

A novel visible-light photoredox-catalyzed phosphinyloxy radical addition/cyclization cascade of arylphosphinic acids or arylphosphonic acid monoesters with alkynes has been developed, which provides an efficient and practical access to various phosphaisocoumarins by using a dual catalytic system containing an acridinium photosensitizer and a cobaloxime proton-reducing catalyst [Co(dmgH)2]PyCl at ambient temperature. This method has advantages of a broad substrate scope, mild condition, as well as no sacrificial oxidant.

7.
Angew Chem Int Ed Engl ; 58(32): 11088-11096, 2019 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-31131511

RESUMEN

Exogenous FeIII can be used for cancer magnetic resonance (MR) imaging and potentially for cancer treatment by a ferroptosis pathway or photothermal ablation. To achieve this, effective and accurate delivery of FeIII to cancerous sites is critical, requiring a balance of release kinetics of Fe3+ in tumorous and normal tissues. A nanoprobe is described consisting of upconversion luminescence (UCL) nanoparticles as a core and a coordinatively unsaturated FeIII -containing Fe3+ /gallic acid complex as a shell. Owing to the introduction of an unsaturated coordination structure, FeIII in the nanoprobe can be released only in the tumor microenvironment in response to the lightly acidic pH. The multiple UCLs are used for quantitatively visualizing the release of Fe3+ in vivo, whilst the release resultant serves as a photothermal agent. This nanoprobe exhibited ligand-free tumor targeting ability, activatable MR imaging performance, and efficacious therapeutic effects against tumors in vivo.


Asunto(s)
Antineoplásicos/farmacología , Compuestos Férricos/farmacología , Colorantes Fluorescentes/farmacología , Imagen por Resonancia Magnética , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Imagen Óptica , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Compuestos Férricos/química , Colorantes Fluorescentes/química , Humanos , Concentración de Iones de Hidrógeno , Nanopartículas/química , Tamaño de la Partícula , Propiedades de Superficie
8.
J Am Chem Soc ; 140(1): 211-218, 2018 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-29237264

RESUMEN

The abnormal expression of tumor-associated proteases and lowered extracellular pH are important signatures strongly associated with cancer invasion, progression, and metastasis. However, their malignant effects were mainly identified using cell and tissue studies. To noninvasively visualize the heterogeneous distribution of these abnormal indicators in vivo and further disclose their collective behaviors, a target-triggered fluorescent nanoprobe composed of a ratiometric pH-sensitive dye, a near-infrared dye (Cy5.5), and biocompatible Fe3O4 nanoparticles was constructed. The pH-sensitive dye was linked through a peptide substrate of matrix metalloprotease-9 (MMP-9) with Fe3O4 nanoparticles to establish a Förster resonance energy transfer (FRET) system for sensing the pH of the tumor microenvironment. Cy5.5 served as an internal reference for forming a secondary ratiometric fluorescent system together with the activated pH dye to enable the visualization of protease activities in vivo. Extensive imaging studies using a mouse model of human colon cancer revealed that the overexpression of MMP-9 and abnormal microenvironmental pH quantitatively visualized by this dual-ratiometric probe are spatially heterogeneous and synergistically guide the tumor invasion in vivo.


Asunto(s)
Carbocianinas/química , Colorantes Fluorescentes/química , Metaloproteinasa 9 de la Matriz/metabolismo , Microambiente Tumoral , Animales , Materiales Biocompatibles/química , Transferencia Resonante de Energía de Fluorescencia , Concentración de Iones de Hidrógeno , Nanopartículas de Magnetita/química , Ratones , Estructura Molecular , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/metabolismo , Imagen Óptica , Tamaño de la Partícula , Espectrometría de Fluorescencia
9.
Small ; 14(23): e1800573, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29665290

RESUMEN

Ischemic stroke is one of the major leading causes for long-term disability and mortality. Collateral vessels provide an alternative pathway to protect the brain against ischemic injury after arterial occlusion. Aiming at visualizing the collaterals occurring during acute ischemic stroke, an integrin αv ß3 -specific Fe3 O4 -Arg-Gly-Asp (RGD) nanoprobe is prepared for magnetic resonance imaging (MRI) of the collaterals. Rat models are constructed by occluding the middle cerebral artery for imaging studies of cerebral ischemia and ischemia-reperfusion on 7.0 Tesla MRI using susceptibility-weighted imaging sequence. To show the binding specificity to the collaterals, the imaging results acquired with the Fe3 O4 -RGD nanoprobe and the Fe3 O4 mother nanoparticles, respectively, are carefully compared. In addition, an RGD blocking experiment is also carried out to support the excellent binding specificity of the Fe3 O4 -RGD nanoprobe. Following the above experiments, cerebral ischemia-reperfusion studies show the collateral dynamics upon reperfusion, which is very important for the prognosis of various revascularization therapies in the clinic. The current study has, for the first time, enabled the direct observation of collaterals in a quasi-real time fashion and further disclosed that the antegrade flow upon reperfusion dominates the blood supply of primary ischemic tissue during the early stage of infarction, which is significantly meaningful for clinical treatment of stroke.


Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Compuestos Férricos/química , Imagen por Resonancia Magnética , Sondas Moleculares/química , Nanopartículas/química , Accidente Cerebrovascular/diagnóstico por imagen , Células 3T3 , Animales , Isquemia Encefálica/complicaciones , Isquemia Encefálica/patología , Circulación Colateral , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Hidrodinámica , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/patología , Masculino , Ratones , Nanopartículas/ultraestructura , Tamaño de la Partícula , Polietilenglicoles/química , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/complicaciones , Daño por Reperfusión/patología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/patología
10.
Small ; 12(5): 556-76, 2016 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-26680328

RESUMEN

Many challenges for advanced sensitive and noninvasive clinical diagnostic imaging remain unmatched. In particular, the great potential of magnetic nano-probes is intensively discussed to further improve the performance of magnetic resonance imaging (MRI), especially for cancer diagnosis. Based on recent achievements, here the concepts of magnetic nanoparticle-based MRI contrast agents and tumor-specific imaging probes are critically summarized. Advances in their synthesis, biocompatible chemical and biofunctional surface modifications, and current strategies for further developing them into multimodality imaging probes are discussed. In addition, how engineered versus unintended surface coatings such as protein coronas affect the biocompatibility and performance of MRI nano-probes is also considered. To stimulate progress in the field, future strategies and relevant challenges that still need to be resolved in the field conclude this review.


Asunto(s)
Medios de Contraste/química , Imagen por Resonancia Magnética/métodos , Nanopartículas/química , Animales , Humanos , Fenómenos Magnéticos , Nanopartículas/ultraestructura , Nanotecnología , Propiedades de Superficie
11.
Orthop Traumatol Surg Res ; 110(4): 103853, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38428485

RESUMEN

OBJECTIVES: Whether the application of MBP plus cannulated screws works for old femoral neck fractures (OFNF) is unknown. The purpose of this study is to present a case series of OFNF in young adults using calcar buttress plate and three cannulated screws with autologous iliac bone grafts. METHODS: We conducted a retrospective study of eleven young patients (6 males and 5 females) with femoral neck fractures who were treated with open reduction and internal fixation at a single center between 2013 and 2021. The subjects had trauma-to-surgery intervals longer than 3weeks and all were fixed with a calcar buttress plate combined with three cannulated screws, which were supplemented by autologous iliac bone grafts. RESULTS: All eleven cases achieved radiological union under the surgery technique, which occurred on average at 4.46±1.29months after surgery. Complications included femoral neck shortening in all cases, heterotopic ossification in three cases, and osteonecrosis of the femoral head in two cases. One patient with osteonecrosis of the femoral head received total hip arthroplasty. In follow-ups of 24-52months, the median Harris hip score was 81.64±15.39. CONCLUSIONS: The medial buttress plate in combination with three cannulated screws and iliac autograft may be a good choice for treating old femoral neck fractures in young adults. LEVEL OF EVIDENCE: IV, case series.


Asunto(s)
Placas Óseas , Tornillos Óseos , Trasplante Óseo , Fracturas del Cuello Femoral , Fijación Interna de Fracturas , Ilion , Humanos , Masculino , Fracturas del Cuello Femoral/cirugía , Femenino , Estudios Retrospectivos , Fijación Interna de Fracturas/métodos , Adulto , Ilion/trasplante , Adulto Joven , Trasplante Óseo/métodos , Resultado del Tratamiento , Autoinjertos
12.
Front Bioeng Biotechnol ; 12: 1331218, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38576449

RESUMEN

Osteoarthritis (OA) is the most common degenerative disease of the joint with irreversible cartilage damage as the main pathological feature. With the development of regenerative medicine, mesenchymal stem cells (MSCs) have been found to have strong therapeutic potential. However, intraarticular MSCs injection therapy is limited by economic costs and ethics. Exosomes derived from MSC (MSC-Exos), as the important intercellular communication mode of MSCs, contain nucleic acid, proteins, lipids, microRNAs, and other biologically active substances. With excellent editability and specificity, MSC-Exos function as a targeted delivery system for OA treatment, modulating immunity, inhibiting apoptosis, and promoting regeneration. This article reviews the mechanism of action of MSC-Exos in the treatment of osteoarthritis, the current research status of the preparation of MSC-Exos and its application of drug delivery in OA therapy.

13.
ACS Appl Mater Interfaces ; 16(17): 21383-21399, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38626424

RESUMEN

Osteoarthritis (OA) progression is highly associated with chondrocyte mitochondrial dysfunction and disorders of catabolism and anabolism of the extracellular matrix (ECM) in the articular cartilage. The mitochondrial unfolded protein response (UPRmt), which is an integral component of the mitochondrial quality control (MQC) system, is essential for maintaining chondrocyte homeostasis. We successfully validated the pivotal role of activating transcription factor 5 (ATF5) in upregulating the UPRmt, mitigating IL-1ß-induced inflammation and mitochondrial dysfunction, and promoting balanced metabolism in articular cartilage ECM, proving its potential as a promising therapeutic target for OA. Modified mRNAs (modRNAs) have emerged as novel and efficient gene delivery vectors for nucleic acid therapeutic approaches. In this study, we combined Atf5-modRNA (modAtf5) with engineered exosomes derived from bone mesenchymal stem cells (ExmodAtf5) to exert cytoprotective effects on chondrocytes in articular cartilage via Atf5. However, the rapid localized metabolization of ExmodAtf5 limits its application. PLGA-PEG-PLGA (Gel), an injectable thermosensitive hydrogel, was used as a carrier of ExmodAtf5 (Gel@ExmodAtf5) to achieve a sustained release of ExmodAtf5. In vitro and in vivo, the use of Gel@ExmodAtf5 was shown to be a highly effective strategy for OA treatment. The in vivo therapeutic effect of Gel@ExmodAtf5 was evidenced by the preservation of the intact cartilage surface, low OARSI scores, fewer osteophytes, and mild subchondral bone sclerosis and cystic degeneration. Consequently, the combination of ExmodAtf5 and PLGA-PEG-PLGA could significantly enhance the therapeutic efficacy and prolong the exosome release. In addition, the mitochondrial protease ClpP enhanced chondrocyte autophagy by modulating the mTOR/Ulk1 pathway. As a result of our research, Gel@ExmodAtf5 can be considered to be effective at alleviating the progression of OA.


Asunto(s)
Factores de Transcripción Activadores , Condrocitos , Exosomas , Mitocondrias , Osteoartritis , ARN Mensajero , Respuesta de Proteína Desplegada , Osteoartritis/patología , Osteoartritis/metabolismo , Osteoartritis/terapia , Exosomas/metabolismo , Exosomas/química , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Respuesta de Proteína Desplegada/efectos de los fármacos , Factores de Transcripción Activadores/metabolismo , Factores de Transcripción Activadores/química , Factores de Transcripción Activadores/genética , ARN Mensajero/metabolismo , ARN Mensajero/genética , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Humanos , Células Madre Mesenquimatosas/metabolismo , Hidrogeles/química , Masculino , Cartílago Articular/metabolismo , Cartílago Articular/patología , Cartílago Articular/efectos de los fármacos
14.
Adv Healthc Mater ; : e2401103, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691848

RESUMEN

Intervertebral disc degeneration (IVDD) is the primary cause of low back pain, with oxidative stress being a recognized factor that causes its development. Presently, low back pain imposes a significant global economic burden. However, the effectiveness of treatments for IVDD remains extremely limited. Therefore, this study aims to explore innovative and effective IVDD treatments by focusing on oxidative stress as a starting point. In this study, an injectable reactive oxygen species-responsive hydrogel (PVA-tsPBA@SLC7A11 modRNA) is developed, designed to achieve rapid loading and selective release of chemically synthesized modified mRNA (modRNA). SLC7A11 modRNA is specifically used to upregulate the expression of the ferroptosis marker SLC7A11. The local injection of PVA-tsPBA@SLC7A11 modRNA into the degenerated intervertebral disc (IVD) results in the cleavage of PVA-tsPBA, leading to the release of enclosed SLC7A11 modRNA. The extent of SLC7A11 modRNA release is directly proportional to the severity of IVDD, ultimately ameliorating IVDD by inhibiting ferroptosis in nucleus pulposus cells (NPCs). This study proposes an innovative system of PVA-tsPBA hydrogel-encapsulated modRNA, representing a potential novel treatment strategy for patients with early-stage IVDD.

15.
Viruses ; 15(1)2023 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-36680218

RESUMEN

Oncolytic herpes simplex virus (oHSV) is a type of virus that selectively targets and kills cancer cells, leaving normal cells unharmed. Accurate viral titer is of great importance for the production and application of oHSV products. Droplet digital PCR (ddPCR) is known for having good reproducibility, not requiring a standard curve, not being affected by inhibitors, and being precise even in the detection of low copies. In the present study, we developed a droplet digital PCR assay for the quantification of HSV-1 and applied it in the oHSV production. The established ddPCR showed good specificity, linearity, a low limit of quantification, great reproducibility, and accuracy. The quantification result was well-associated with that of plaque assay and CCID50. Amplification of the purified virus without DNA extraction by ddPCR presented similar results to that from the extracted DNA, confirming the good resistance against PCR inhibitors. With the ddPCR, viral titer could be monitored in real time during the production of oHSV; the optimal harvest time was determined for the best virus yield in each batch. The ddPCR can be used as a useful tool for the quantification of oHSV and greatly facilitate the manufacturing process of oHSV products.


Asunto(s)
Herpesvirus Humano 1 , Viroterapia Oncolítica , Herpesvirus Humano 1/genética , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa
16.
Sci Rep ; 13(1): 5101, 2023 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-36991007

RESUMEN

Progressive massive pulmonary fibrosis among coal miners has unexpectedly increased. It would likely due to the greater generation of smaller rock and coal particles produced by powerful equipment used in modern mines. There is limited understanding of the relationship between micro- or nanoparticles with pulmonary toxicity. This study aims to determine whether the size and chemical characteristics of typical coal-mining dust contribute to cellular toxicity. Size range, surface features, morphology, and elemental composition of coal and rock dust from modern mines were characterized. Human macrophages and bronchial tracheal epithelial cells were exposed to mining dust of three sub- micrometer and micrometer size ranges at varying concentrations, then assessed for cell viability and inflammatory cytokine expression. Coal had smaller hydrodynamic size (180-3000 nm) compared to rock (495-2160 nm) in their separated size fractions, more hydrophobicity, less surface charge, and consisted of more known toxic trace elements (Si, Pt, Fe, Al, Co). Larger particle size had a negative association with in-vitro toxicity in macrophages (p < 0.05). Fine particle fraction, approximately 200 nm for coal and 500 nm for rock particles, explicitly induced stronger inflammatory reactions than their coarser counterparts. Future work will study additional toxicity endpoints to further elucidate the molecular mechanism causing pulmonary toxicity and determine a dose-response curve.


Asunto(s)
Minas de Carbón , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Tamaño de la Partícula , Polvo/análisis , Pulmón/química , Carbón Mineral/análisis
17.
Environ Health (Wash) ; 1(5): 315-323, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-38028320

RESUMEN

Electronic cigarettes (e-cigs) have become increasingly popular, especially among youth, raising concerns about their potential health risks. JUUL and Tank devices are two common types of e-cigs that deliver aerosols with varying nicotine levels and flavors. However, the differences in the aerosols generated from different devices and their corresponding cytotoxicity and pulmonary injury effects remain poorly understood. This study addresses these knowledge gaps by characterizing the aerosols of JUUL and Tank e-cig devices and testing their toxic effects on THP-1 and BEAS-2B human cell lines as well as the C57BL/6J mouse model. In our study, the lower-voltage device, the 3.7 V JUUL generates 2.72 mg/puff aerosols by using e-liquid containing 3% nicotine salt (i.e., nicotine benzoate), which is less than the 11.06 mg/puff aerosols generated by the 7.5 V Tank using e-liquid containing 2.4% freebase nicotine. Yet, the cytotoxicity results reveal that JUUL aerosols induced higher toxicity and increased production of pro-inflammation cytokines compared to Tank aerosols per puff. Additionally, we observed that JUUL induced more severe pulmonary inflammation and DNA damage compared to Tank after normalizing for cotinine, a nicotine metabolite, in vivo. Our findings suggest that the device design plays a more important role in e-cig aerosol-induced toxicity than the composition of the e-liquid or voltage. These results provide valuable insights into the health risks associated with various electronic-cig devices and offer an approach for evaluating them.

18.
Adv Biol (Weinh) ; 5(1): e2000193, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33724732

RESUMEN

Molecular imaging can provide functional and molecular information at the cellular or subcellular level in vivo in a noninvasive manner. Activatable nanoprobes that can react to the surrounding physiological environment or biomarkers are appealing agents to improve the efficacy, specificity, and sensitivity of molecular imaging. The physiological parameters, including redox status, pH, presence of enzymes, and hypoxia, can be designed as the stimuli of the activatable probes. However, the success rate of imaging nanoprobes for clinical translation is low. Herein, the recent advances in nanoparticle-based activatable imaging probes are critically reviewed. In addition, the challenges for clinical translation of these nanoprobes are also discussed in this review.


Asunto(s)
Colorantes Fluorescentes , Nanopartículas , Imagen Molecular , Oxidación-Reducción
19.
Int J Biol Macromol ; 193(Pt B): 1986-1995, 2021 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-34767881

RESUMEN

Hydrophobic cellulose laurate (CL) with high degree of substitution has been successfully synthesized. The mechanical property, water-resistance, antimicrobial activity, barrier properties and food decontamination of cellulose-laurate-curcumin films (CL-Cux, x = 0.1, 0.5, and 1) were investigated. The results showed that the mechanical properties of CL-Cux hardly change after soaking in water for 24 h, probably due to the strong hydrophobicity of cellulose laurate. CL-Cu1 represented a good photoinduced antibacterial effect against S. aureus. After irradiation of white light at 60 mW·cm-2 for 20 min, the inhibition efficiency reached to 95 ± 2.02%, probably owing to the generated active 1O2. In comparison with CL-Cu1 stored in natural light, the bacteriostatic effect of CL-Cu1 in dark storage was better, and the inhibition rate of CL-Cu1 remained 80 ± 1.22 at 60th day. The stabler excited state of curcumin in hydrophobic cellulose laurate was probably assigned to inhibition of tautomerism or conformational transition, which was beneficial to the generation of singlet oxygen. CL-Cu1 can significantly inhibit the growth of TVBN and TVC values of chilled meat upon white light irradiation, indicating the potential application of cellulose-laurate-curcumin films in food decontamination.


Asunto(s)
Antibacterianos/farmacología , Celulosa/farmacología , Curcumina/farmacología , Conservación de Alimentos/métodos , Lauratos/farmacología , Carne/microbiología , Embalaje de Alimentos/métodos , Interacciones Hidrofóbicas e Hidrofílicas , Staphylococcus aureus/efectos de los fármacos
20.
Carbohydr Polym ; 272: 118476, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34420735

RESUMEN

The methods to obtain cellulose-chitosan composite films exhibiting excellent water-resisting and antibacterial abilities have been widely explored. Cellulose-chitosan-citric films (C-Chx-F) were successfully obtained by a facile coating of chitosan-citric complex on the surface of cellulose. The occurrence of nonenzymatic browning at 80 °C improved the thermal stability, water-resistance, mechanical property and oxygen-barrier ability of C-Chx-F membranes. C-Ch3-F hydrogel showed excellent breaking stress of 6.03 ± 0.25 MPa, and elastic module of 27.09 ± 1.21 MPa, probably assigned to nonenzymatic browning. Under different test temperatures, the nonenzymatic browning and the content of chitosan-citric complex will significantly improve the oxygen barrier property of membranes (P < 0.05), and C-Ch3-F membrane represented the value of oxygen permeation below the detection level. Excellent antibacterial capability of C-Chx-F hydrogels demonstrated that polycationic chitosan-citric complex immobilized in films still retained excellent antibacterial ability. The excellent decontamination in meat preservation endowed C-Chx-F films with potential application in food packaging.


Asunto(s)
Quitosano , Embalaje de Alimentos , Antibacterianos , Celulosa , Staphylococcus aureus
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