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Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressant medications and remain the cornerstone of systemic lupus erythematosus (SLE) therapy. However, ongoing exposure to GCs has the potential to elicit multiple adverse effects. Considering the irreplaceability of GCs in SLE therapy, it is important to explore the optimal regimen of GCs. Here, we compared the long-term efficacy and safety of pulsed and oral GC therapy in a lupus-prone mouse model. Mice were grouped using a randomized block design. We monitored survival rates, proteinuria, serum autoantibodies, and complement 3 (C3) levels up to 28 weeks of age, and assessed renal damage, bone quality, lipid deposition in the liver and marrow, glucose metabolic parameters, and levels of hormones of the hypothalamic-pituitary-adrenal (HPA) axis. Finally, we explored the mechanisms underlying the superior efficacy of the pulse regimen over oral prednisone regimen. We found that both GC regimens alleviated the poor survival rate, proteinuria, and glomerulonephritis, while also reducing serum autoantibodies and increasing the level of C3. The pulsed GC regimen showed less resistance to insulin, less suppression of the HPA axis, less bone loss, and less bone marrow fat deposition than the oral GC regimen. Additionally, GC-induced leucine zipper (GILZ) was significantly overexpressed in the GC pulse group. These results suggest that the GC pulse regimen ameliorated symptoms in lupus-prone mice, with fewer side effects, which may be related to GILZ overexpression. Our findings offer a potentially promising GC treatment option for SLE.
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Glucocorticoides , Lupus Eritematoso Sistémico , Metilprednisolona , Ratones Endogámicos MRL lpr , Prednisona , Animales , Lupus Eritematoso Sistémico/tratamiento farmacológico , Metilprednisolona/farmacología , Metilprednisolona/administración & dosificación , Glucocorticoides/farmacología , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Prednisona/farmacología , Prednisona/efectos adversos , Prednisona/administración & dosificación , Ratones , Femenino , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Autoanticuerpos/sangre , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Complemento C3/metabolismo , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Proteinuria/tratamiento farmacológicoRESUMEN
Toll-like receptors (TLRs) represent a prominent category of pattern recognition receptors that have been extensively investigated for their pivotal role in combating pathogen incursions. Despite this, there has been a notable absence of comprehensive identification and exploration of the immune response associated with the TLR family genes in C. altivelis. This study successfully identified and named fourteen genes as Catlr1-1, Catlr1-2, Catlr2-1, Catlr2-2, Catlr3, Catlr5, Catlr7, Catlr8, Catlr9, Catlr13-1, Catlr13-2, Catlr18, Catlr21, and Catlr22. A series of bioinformatic analysis were performed, encompassing analysis of protein properties, examination of gene structures, evolutionary assessments, and prediction of protein tertiary structures. The expression patterns of Catlr genes were analyzed in five immune tissues: liver, spleen, kidney, gill, and intestine, in both healthy and bacterial stimulated-fish. The results showed that different tissue and different genes showed differed expression patterns after V. harveyi infection, indicating the involvement of all Catlr members in mounting immune responses following infection in various tissues. Additionally, histological evaluations of immune tissues unveiled varying levels of damage. In conclusion, this investigation into the TLR gene family offers novel information that contribute to a more profound comprehension of the immune response mechanisms in C. altivelis.
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Enfermedades de los Peces , Proteínas de Peces , Perfilación de la Expresión Génica , Filogenia , Receptores Toll-Like , Vibrio , Animales , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Proteínas de Peces/química , Perfilación de la Expresión Génica/veterinaria , Receptores Toll-Like/genética , Receptores Toll-Like/inmunología , Receptores Toll-Like/química , Enfermedades de los Peces/inmunología , Vibrio/fisiología , Vibriosis/inmunología , Vibriosis/veterinaria , Inmunidad Innata/genética , Regulación de la Expresión Génica/inmunología , Familia de Multigenes , Alineación de Secuencia/veterinaria , Secuencia de AminoácidosRESUMEN
The gut microbiota has become an essential component of the host organism and plays a crucial role in the host immune system, metabolism, and physiology. Nevertheless, our comprehension of how the fish gut microbiota contributes to enhancing nutrient utilization in the diet and improving host growth performance remains unclear. In this study, we employed a comprehensive analysis of the microbiome, metabolome, and transcriptome to analyze intestines of the normal control group and the antibiotic-treated model group of T. ovatus to investigate how the gut microbiota enhances fish growth performance and uncover the underlying mechanisms. First, we found that the growth performance of the control group was significantly higher than that of the antibiotic-treated model under the same feeding conditions. Subsequent multiomics analyses showed that the gut microbiota can improve its own composition by mediating the colonization of some probiotics represented by Lactobacillus in the intestine, improving host metabolic efficiency with proteins and lipids, and also influencing the expression of genes in signaling pathways related to cell proliferation, which together contribute to the improved growth performance of T. ovatus. Our results demonstrated the important contribution of gut microbiota and its underlying molecular mechanisms on the growth performance of T. ovatus.
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Microbioma Gastrointestinal , Nutrientes , Animales , Nutrientes/metabolismo , Transcriptoma , Metaboloma , Probióticos , Peces/microbiología , Peces/metabolismo , Peces/crecimiento & desarrollo , Intestinos/microbiologíaRESUMEN
Introduction: Asian citrus psyllid (ACP, Diaphorina citri) is an important transmission vector of "Candidatus Liberibacter asiaticus" (CLas), the causal agent of Huanglongbing (HLB), the most destructive citrus disease in the world. As there are currently no HLB-resistant rootstocks or varieties, the control of ACP is an important way to prevent HLB. Some viruses of insect vectors can be used as genetically engineered materials to control insect vectors. Methods: To gain knowledge on viruses in ACP in China, the prevalence of five RNA and DNA viruses was successfully determined by optimizing reverse transcription polymerase chain reaction (RT-PCR) in individual adult ACPs. The five ACP-associated viruses were identified as follows: diaphorina citri bunyavirus 2, which was newly identified by high-throughput sequencing in our lab, diaphorina citri reovirus (DcRV), diaphorina citri picorna-like virus (DcPLV), diaphorina citri bunyavirus (DcBV), and diaphorina citri densovirus-like virus (DcDV). Results: DcPLV was the most prevalent and widespread ACP-associated virus, followed by DcBV, and it was detected in more than 50% of all samples tested. DcPLV was also demonstrated to propagate vertically and found more in salivary glands among different tissues. Approximately 60% of all adult insect samples were co-infected with more than one insect pathogen, including the five ACP-associated viruses and CLas. Discussion: This is the first time these viruses, including the newly identified ACP-associated virus, have been detected in individual adult ACPs from natural populations in China's five major citrus-producing provinces. These results provide valuable information about the prevalence of ACP-associated viruses in China, some of which have the potential to be used as biocontrol agents. In addition, analysis of the change in prevalence of pathogens in a single insect vector is the basis for understanding the interactions between CLas, ACP, and insect viruses.
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The reduction of soluble U(VI) to insoluble and less toxic U(IV) by photocatalysis is an effective method to control uranium contamination. The graphitic carbon nitride nanosheet (CNN)/UiO-66 composites (CNNU) were prepared by thermal polymerization and solvothermal methods for the removal of U(VI). The morphology, crystal structure and optical properties of composites were analyzed by SEM, XRD, BET, UV-DRS, PL and EIS. The results showed the introduction of UiO-66 increased the specific surface of CNN from 9.07 m2/g to 46.24 m2/g, and effectively suppressed the recombination of photogenerated electrons and holes and improved the photocatalytic activity. The U(VI) removal capacity by adsorption and photocatalysis of CNNU was reached 779.47 mg/g, which significantly higher than that of adsorption (478.38 mg/g). The adsorption process was found to conform to the pseudo-second-order kinetic model and the Langmuir isothermal model. Meanwhile, U(VI) adsorbed on the CNNU was reduced to U(IV) via e- and ·O2- generated in the photocatalytic process. Therefore, this outstanding performance of CNNU in U(VI) removal is attributed to the synergistic effect of adsorption and photocatalytic reduction.
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Estructuras Metalorgánicas , Ácidos Ftálicos , Uranio , Adsorción , Uranio/química , Luz SolarRESUMEN
Salinity, being an indispensable abiotic factor crucial for the survival of marine organisms, has demonstrated diverse alterations globally in response to the current trend of global warming. In this study, the effect of chronic low salinity stress on teleosts' sex differentiation was investigated using Cynoglossus semilaevis, an economically important fish with both genetic and environmental sex determination system. The cultivation experiment was conducted employing artificially simulated seawater of 20 ppt and ambient sea water of 30 ppt to rear juveniles C. semilaevis. Throughout the experiment, the growth performance was assessed and the histology of gonadal development was examined, a significantly lower masculinization rate was observed in LS group. To gain further insights, transcriptome analysis was conducted using raw reads obtained from 53 libraries derived from gonads of 55 days post fertilization (dpf) and 100 dpf juveniles in both LS and CT groups. GO/KEGG enrichment were further proceeded, Terms and pathways involved in reproduction ability, germ cell proliferation, immune function, steroid metabolism etc., were illuminated and a possible crosstalk between HPI and HPG axis was proposed. WGCNA was conducted and two hub genes, hspb8-like and Histone H2A.V were exhibited to be of great significance in the changes of masculinization rate. Our findings provided solid reference for sex differentiation study of GSD + ESD species in a constantly changing ocean environment, as well as practice guiding significance for the environmental management for the culture of C. semilaevis.
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Peces Planos , Lenguado , Animales , Peces Planos/metabolismo , Perfilación de la Expresión Génica , GónadasRESUMEN
The humpback grouper (Cromileptes altivelis), a medium-sized coral reef teleost, is a naturally rare species distributed in the tropical waters of the Indian and Pacific Oceans. It has high market value, but artificial reproduction and breeding remain limited and need to be improved. Here, we assembled the genome with 1.08 Gb, with a contig N50 of 43.78 Mb. A total of 96.59% of the assembly anchored to 24 pseudochromosomes using Hi-C technology. It contained 24,442 protein-coding sequences, of which 99.3% were functionally annotated. The completeness of the assembly was estimated to be 97.3% using BUSCO. The phylogenomic analysis suggested that humpback grouper should be classified into the genus Epinephelus rather than Cromileptes. The comparative genomic analysis revealed that the gene families related to circadian entrainment were significantly expanded. The high-quality reference genome provides useful genomic tools for exploiting the genomic resource of humpback grouper and supports the functional genomic study of this species in the future.
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Lubina , Genoma , Animales , Cromosomas , Sistemas de Lectura AbiertaRESUMEN
BACKGROUND: This study aimed to observe changes of rats' brain infarction and blood vessels during neonatal hypoxic ischemic encephalopathy (NHIE) modeling by Transcranial Doppler Ultrasonography (TCD) so as to assess the feasibility of TCD in evaluating NHIE modeling. METHODS: Postnatal 7-days (d)-old Sprague Dawley (SD) rats were divided into the Sham group, hypoxic-ischemic (HI) group, and hypoxia (H) group. Rats in the HI group and H group were subjected to hypoxia-1 hour (h), 1.5 h and 2.5 h, respectively. Evaluation on brain lesion was made based on Zea-Longa scores, hematoxylin-eosin (HE) staining and Nissl staining. The brain infarction and blood vessels of rats were monitored and analyzed under TCD. Correlation analysis was applied to reveal the connection between hypoxic duration and infarct size detected by TCD or Nissl staining. RESULTS: In H and HI modeling, longer duration of hypoxia was associated with higher Zea-Longa scores and more severe nerve damage. On the 1 d after modeling, necrosis was found in SD rats' brain indicated by HE and Nissl staining, which was aggravated as hypoxic duration prolonged. Alteration of brain structures and blood vessels of SD rats was displayed in Sham, HI and H rats under TCD. TCD images for coronal section revealed that brain infarct was detected at the cortex and there was marked cerebrovascular back-flow of HI rats regardless of hypoxic duration. On the 7 d after modeling, similar infarct was detected under TCD at the cortex of HI rats in hypoxia-1 h, 1.5 h and 2.5 h groups, whereas the morphological changes were deteriorated with longer hypoxic time. Correlation analysis revealed positive correlation of hypoxic duration with infarct size detected by histological detection and TCD. CONCLUSIONS: TCD dynamically monitored cerebral infarction after NHIE modeling, which will be potentially served as a useful auxiliary method for future animal experimental modeling evaluation in the case of less animal sacrifice.
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Hipoxia-Isquemia Encefálica , Ratas , Animales , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Hipoxia-Isquemia Encefálica/patología , Ratas Sprague-Dawley , Animales Recién Nacidos , Ultrasonografía Doppler Transcraneal , Encéfalo/patología , Isquemia/patología , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/patología , Infarto Encefálico/patologíaRESUMEN
As a member of the forkhead box L gene family, foxl2 plays a significant role in gonadal development and the regulation of reproduction. During the evolution of deuterostome, whole genome duplication (WGD)-enriched lineage diversifications and regulation mechanisms occurs. However, only limited research exists on foxl2 duplication in teleost or other vertebrate species. In this study, two foxl2 paralogs, foxl2 and foxl2l, were identified in the transcriptome of spotted knifejaw (Oplegnathus punctatus), which had varying expressions in the gonads. The foxl2 was expressed higher in the ovary, while foxl2l was expressed higher in the testis. Phylogenetic reconstruction, synteny analysis, and the molecular evolution test confirmed that foxl2 and foxl2l likely originated from the first two WGD. The expression patterns test using qRT-PCR and ISH as well as motif scan analysis revealed evidence of potentially functional divergence between the foxl2 and foxl2l paralogs in spotted knifejaw. Our results indicate that foxl2 and foxl2l may originate from the first two WGD, be active in transcription, and have undergone functional divergence. These results shed new light on the evolutionary trajectories of foxl2 and foxl2l and highlights the need for further detailed functional analysis of these two duplicated paralogs.
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Peces , Vertebrados , Animales , Masculino , Femenino , Filogenia , Peces/genética , Vertebrados/genética , Genoma/genética , Transcriptoma/genéticaRESUMEN
BACKGROUND: Septic shock is the development of sepsis to refractory circulatory collapse and metabolic derangements, characterized by persistent hypotension and increased lactate levels. Anisodamine hydrobromide (Ani HBr) is a Chinese medicine used to improve blood flow in circulatory disorders. The purpose of this study was to determine the therapeutic efficacy of Ani HBr in the treatment of patients with septic shock. METHODS: This was a prospective, multicenter, randomized controlled trial focusing on patients with septic shock in 16 hospitals in China. Patients were randomly assigned in a 1:1 ratio to either the treatment group or the control group. The primary endpoint was 28-day mortality. The secondary outcomes included 7-day mortality, hospital mortality, hospital length of stay, vasopressor-free days within 7 days, etc. These indicators were measured and collected at 0, 6h, 24h, 48h, 72h and 7d after the diagnosis. RESULTS: Between September 2017 and March 2021, 404 subjects were enrolled. 203 subjects received Ani HBr and 201 subjects were assigned to the control group. The treated group showed lower 28-day mortality than the control group. Stratified analysis further showed significant differences in 28-day mortality between the two groups for patients with a high level of illness severity. We also observed significant differences in 7-day mortality, hospital mortality and some other clinical indicators between the two groups. CONCLUSION: Ani HBr might be an important adjuvant to conventional treatment to reduce 28-day mortality in patients with septic shock. A large-scale prospective randomized multicenter trial is warranted to confirm our results.
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Sepsis , Choque Séptico , Humanos , Choque Séptico/tratamiento farmacológico , Enfermedad Crítica , Estudios ProspectivosRESUMEN
Decubitus ulcers are a common spinal cord injury (SCI) complication that puts patients' lives in danger and has emerged as a more prevalent issue in modern clinical rehabilitation and care. Decubitus ulcers in humans can currently be treated in a number of different ways, but there are fewer studies on how to treat and care for decubitus ulcers in macaques. To treat a 20-year-old adult male macaque monkey with SCI and decubitus ulcers after a quarter transection of the thoracic spinal cord, a number of scientific care procedures and pharmaceutical treatments, such as dietary changes and topical or intravenous administration of medication, were carried out and continuously monitored in real-time. In comparison to the untreated group, we observed a significant improvement in decubitus wound healing in the macaques. In this article, we provide a good protocol for decubitus ulcer care after SCI and suggest that future experimental animal modeling needs to focus on issues such as care for postoperative complications.
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Spinal cord injury (SCI) animal models have been widely created and utilized for repair therapy research, but more suitable experimental animals and accurate modeling methodologies are required to achieve the desired results. In this experiment, we constructed an innovative dorsal 1/4 spinal cord transection macaque model that had fewer severe problems, facilitating postoperative care and recovery. In essence, given that monkeys and humans share similar genetics and physiology, the efficacy of this strategy in a nonhuman primate SCI model basically serves as a good basis for its prospective therapeutic use in human SCI.
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Increasing the carotenoid content of nectarine (Prunus persica var. nucipersica) is of great significance for improving its quality and economic value. A two years study was carried out on 'Shuguang' nectarine to evaluate the effect of calcium chloride (Cl-Ca) and L-aspartic acid nano calcium [Ca (L-asp) - NPs] (nano-Ca) on carotenoid accumulation. The results show that both Cl-Ca and nano-Ca could increase the carotenoid content of nectarine fruit flesh, but the effect of nano-Ca was more significant. Nano-Ca is more easily absorbed by nectarine leaves and fruits, which improves the calmodulin activity of leaves, peel and flesh, and up-regulates the expression of carotenoid synthesis-related genes PpPSY, PpPDS, PpZDS, PpLCY-B, PpCHY-B and PpZEP. Nano-Ca also significantly up-regulated the expression of sucrose synthesis related genes PpSUS1 and PpSUS3 in leaves and sucrose transport related genes PpSUT2 and PpSUT4 in stem phloem, promoting the transport of more photosynthetic products to fruits, providing raw materials for carotenoid synthesis, and increasing the content of total sugars and ascorbic acid (Vc). In addition, nano-Ca can also up-regulate the expression levels of PpMYB10.1 and PpUFGT and promote total anthocyanins accumulation in peel. The results of our study will be useful for clarifying how nano-fertilizer improve the fruit quality of nectarine.
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Antocianinas , Frutas , Frutas/metabolismo , Antocianinas/metabolismo , Calcio/metabolismo , Carotenoides/metabolismo , Cloruro de Calcio , Regulación de la Expresión Génica de las Plantas , Sacarosa/metabolismoRESUMEN
GATA3 belongs to the GATA family, and it could interact with the target gene promoter. It has been reported to play a central role in regulating lymphocyte differentiation. In this study, the GATA3 cDNA sequence was identified by a homologous clone and the RACE technology from Japanese flounder (Paralichthys olivaceus). The full-length of the GATA3 cDNA sequence was 2904 bp, including 1332 bp open reading frame (ORF), 265 bp 5 '-untranslated region (5' UTR), and 1308 bp 3 '-UTR, encoding 443 amino acids. GATA3 protein sequence was conserved in vertebrates and invertebrates, including two zinc finger domains. qRT-PCR showed that the expression of GATA3 was high in the gill, kidney, and spleen. Expression of GATA3 slowly increased at the earlier stages and culminated at the late gastrula and somatic stages. Immunohistochemistry (IHC) results showed that the GATA3 protein was expressed in lymphocyte cells, undifferentiated basal and pillar cells of the gills, as well as lymphocyte cells and melanin macrophages of the kidney. The expression of GATA3 was significantly regulated in tissues and different types of lymphocytes after stimulation with Edwardsiella tarda. Dual-luciferase reporter assay indicated that the GATA3 protein could directly interact with promoters of target genes involved in the immune response. These findings suggested that GATA3 plays a major role in regulating the immune response. This study provided a theoretical basis for the immune response mechanism of teleost and a useful reference for later research on fish immunology.
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Enfermedades de los Peces , Lenguado , Animales , ADN Complementario/genética , Secuencia de Aminoácidos , Inmunidad Innata/genética , Macrófagos/metabolismo , Proteínas de Peces/química , Edwardsiella tarda/fisiología , Filogenia , Regulación de la Expresión GénicaRESUMEN
Childhood-onset systemic lupus erythematosus (cSLE) is an autoimmune disease that results in significant damage and often needs more aggressive treatment. Compared to adult-onset SLE, cSLE has a stronger genetic background and more prevalent elevated type I Interferon expression. The management of cSLE is more challenging because the disease itself and treatment can affect physical, psychological and emotional growth and development. High dose oral glucocorticoid (GC) has become the rule for treating moderate to severe cSLE activity. However, GC-related side effects and potential toxicities are problems that cannot be ignored. Recent studies have suggested that GC pulse therapy can achieve disease remission rapidly and reduce GC-related side effects with a reduction in oral prednisone doses. This article reviews characteristics, including pathogenesis and manifestations of cSLE, and summarized the existing evidence on GC therapy, especially on GC pulse therapy in cSLE, followed by our proposal for GC therapy according to the clinical effects and pathogenesis.
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Enfermedades Autoinmunes , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Lupus Eritematoso Sistémico , Niño , Adulto , Humanos , Glucocorticoides/uso terapéutico , Prednisona , Lupus Eritematoso Sistémico/tratamiento farmacológicoRESUMEN
OBJECTIVE: The aim of this study is to identify whether low lupus disease activity status (LLDAS) and clinical remission (CR) of belimumab plus standard of care (SoC) therapy are achievable goals in childhood-onset SLE (cSLE). METHODS: This multicentre, one arm pre-post intervention study was conducted at 15 centers in China. The primary end point was to describe the proportion of patients who achieved LLDAS and CR after 3, 6, and 12 months after treatment with belimumab plus SoC therapy. A multiple regression model was used to impute missing data. A Poisson regression model was used to calculate the effect of belimumab treatment on the reduced risk of serious diseases and the incidence of new damage. RESULT: 193 (92.2% female) with active cSLE from 15 centers were included. At 3, 6 and 12 months, the proportion of LLDAS (CR) was 12.4% (1.0%), 25.6% (4.5%) and 70.3% (29.7%), respectively. The mean SELENA-SLEDAI score decreased from 11.0 at baseline to 3.7, 2.9 and 1.7 at 3, 6, and 12 months. At baseline, all patients received steroids at a mean (SD) prednisone equivalent dose of 31.0 (18.2) mg/day, which decreased to 19.4 (10.8) mg/day at month 3, 12.6 (7.2) mg/day at month 6 and 6.7 (5.3) mg/day at month 12. The symptoms and immunological indicators were also significantly improved. CONCLUSION: This is the first and largest sample size prospective clinical intervention study of cSLE patients treated with belimumab in China. LLDAS and CR were attainable treat-to-target of belimumab plus SoC therapy in cSLE.
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The advent of enzyme-facilitated cascade events in which endogenous substrates within the human body are used to generate reactive oxygen species (ROS) has spawned novel cancer treatment possibilities. In this study, a supramolecular cascade catalytic nanozyme system was successfully developed, exhibiting photothermal-enhanced multienzyme cascade catalytic and glutathione (GSH) depletion activities and ultimately triggering the apoptosis-ferroptosis synergistic tumor therapy. The nanozyme system was fabricated using ß-cyclodextrin-functionalized polydopamine (PDA) as the substrate, which was then entangled with polyoxometalate (POM) via electrostatic forces and assembled with adamantane-grafted hyaluronic acid and glucose oxidase (GOx) via host-guest supramolecular interaction for tumor targeting and GOx loading. The catalytic function of GOx facilitates the conversion of glucose to H2O2 and gluconic acid. In turn, this process affirms the propitious generation of hydroxyl radical (â¢OH) through the POM-mediated cascade catalysis. Additionally, the POM species actively deplete the intracellular GSH pool, initiating a cascade catalytic tumor therapy. In addition, the PDA-POM-mediated photothermal hyperthermia boosted the cascade catalytic effect and increased ROS production. This confers considerable promise for photothermal therapy (PTT)/nanocatalytic cancer therapy on supramolecular nanozyme systems. The in vitro and in vivo antitumor efficacy studies demonstrated that the supramolecular cascade catalytic nanozyme system was effective at reducing tumor development while maintaining an acceptable level of biocompatibility. Henceforth, this study is to widen the scope of cascade catalytic nanoenzyme production using supramolecular techniques, as well as endeavor to delineate a prospective pathway for the application of PTT-enhanced nanocatalytic tumor therapy.
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Peróxido de Hidrógeno , Neoplasias , Humanos , Estudios Prospectivos , Especies Reactivas de Oxígeno , Catálisis , Glucosa Oxidasa , Glutatión , Microambiente Tumoral , Línea Celular Tumoral , Neoplasias/tratamiento farmacológicoRESUMEN
Objective: This study aimed to investigate the feasibility of Transcranial Doppler Ultrasonography (TCD) in evaluating neonatal hypoxic-ischemic encephalopathy (NHIE) modeling through monitoring the alteration of cerebrovascular flow in neonatal hypoxic-ischemic (HI) rats. Methods: Postnatal 7-day-old Sprague Dawley (SD) rats were divided into the control group, HI group, and hypoxia (H) group. TCD was applied to assess the changes of cerebral blood vessels, cerebrovascular flow velocity, and heart rate (HR) in sagittal and coronal sections at 1, 2, 3, and 7 days after the operation. For accuracy, cerebral infarct of rats was examined by 2,3,5-Triphenyl tetrazolium chloride (TTC) staining and Nissl staining to simultaneously verify the establishment of NHIE modeling. Results: Coronal and sagittal TCD scans revealed obvious alteration of cerebrovascular flow in main cerebral vessels. Obvious cerebrovascular back-flow was observed in anterior cerebral artery (ACA), basilar artery (BA), middle cerebral artery (MCA) of HI rats, along with accelerated cerebrovascular flows in the left internal carotid artery (ICA-L) and BA, decreased flows in right internal carotid artery (ICA-R) relative to those in the H and control groups. The alterations of cerebral blood flows in neonatal HI rats indicated successful ligation of right common carotid artery. Besides, TTC staining further validated the cerebral infarct was indeed caused due to ligation-induced insufficient blood supply. Damage to nervous tissues was also revealed by Nissl staining. Conclusion: Cerebral blood flow assessment by TCD in neonatal HI rats contributed to cerebrovascular abnormalities observed in a real-time and non-invasive way. The present study elicits the potentials to utilize TCD as an effective means for monitoring the progression of injury as well as NHIE modeling. The abnormal appearance of cerebral blood flow is also beneficial to the early warning and effective detection in clinical practice.
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Nanomedicines can effectively penetrate tumor sites compared to traditionally used drugs. However, effective drugs that reach the interior of tumors remain limited. Based on studies of the complex tumor microenvironment, we summarized the barriers restricting tumor penetration of nanomedicines in this review. Penetration barriers are mainly caused by tumor blood vessels, stroma, and cell abnormalities. The repair of abnormal tumor blood vessels and tumor stroma and adjusting the physicochemical properties of nanoparticles are considered promising strategies to improve the tumor permeation of nanomedicines. The effects of nanoparticle properties, including size, shape, and surface charge, on tumor penetration were also reviewed. We expect to provide research ideas and a scientific basis for nanomedicines to increase intratumoral permeability and improve anti-tumor effects.