RESUMO

PURPOSE: To explore the value of tissue quantitative diffusion analysis of ultrasound elastography in the diagnosis of early-stage chronic kidney disease (CKD). METHODS: The observation group comprised 54 patients with early-stage CKD treated at Fuzhou No 7 Hospital, and the control group consisted of 40 healthy individuals who underwent physical examinations at the same hospital. The renal parenchyma of the participants were examined using ultrasonography, color Doppler ultrasonography, and tissue quantitative diffusion analysis of ultrasound elastography. Renal dimensions (diameter, thickness, and renal parenchyma thickness), interlobar artery blood flow parameters, and 11 elastic characteristic values were analyzed and compared between the two groups. The area under the receiver-operating characteristic (ROC) curve, cut-off values, sensitivity, and specificity were calculated using the ROC curve analysis. RESULTS: There were no significant differences in the blood flow parameters of the interlobar artery and the dimensions of renal meridians between the two groups. In the observation group, the mean (MEAN) decreased, while the blue area ratio and skewness, increased, compared to the control group (p < 0.05). In addition, the ROC curve revealed that the blue area ratio, MEAN, and skewness had significant diagnostic value (the area under the curve > 0.7). Notably, the best cut-off value of the MEAN was found to be 106, indicating that a MEAN value less than 106 represented early-stage CKD. Also, this cutoff value had a sensitivity of 80% and a specificity of 81%. CONCLUSION: Tissue quantitative diffusion analysis of ultrasound elastography can quantitatively evaluate renal parenchymal damage in early-stage CKD using quantitative diffusion parameters, with the MEAN parameter, having a cutoff of 106, being particularly effective. This parameter and cutoff value offer a valuable tool for the early detection and diagnosis of CKD, potentially improving patient outcomes through earlier intervention. CLINICAL TRIAL NUMBER: Not applicable.

Assuntos

Técnicas de Imagem por Elasticidade , Insuficiência Renal Crônica , Humanos , Técnicas de Imagem por Elasticidade/métodos , Masculino , Feminino , Insuficiência Renal Crônica/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto , Idoso , Diagnóstico Precoce , Rim/diagnóstico por imagem , Rim/irrigação sanguínea , Curva ROC , Sensibilidade e Especificidade

RESUMO

BACKGROUND: Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. OBJECTIVE: To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. METHODS: The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. RESULTS: The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P < 0.0001). As compared with placebo, dexmedetomidine treatment led to more subjects achieving Ramsay scale ≥ 3 or UMSS ≥ 2, and shorter time to reach desired parental separation, Ramsay scale ≥ 3 and UMSS ≥ 2 (all P < 0.0001). Adverse events were reported in 90.7% and 84.0% of subjects in the dexmedetomidine and placebo groups, respectively, and all the events were mild or moderate in severity. CONCLUSIONS: This novel dexmedetomidine nasal spray presented effective pre-anesthetic sedation in children with a tolerable safety profile.

Assuntos

Dexmedetomidina , Hipnóticos e Sedativos , Sprays Nasais , Humanos , Dexmedetomidina/administração & dosagem , Masculino , Feminino , Método Duplo-Cego , Pré-Escolar , Hipnóticos e Sedativos/administração & dosagem , Criança , Administração Intranasal , China , Medicação Pré-Anestésica/métodos

RESUMO

Assessing the bioaccessibility and bioavailability of cadmium (Cd) is crucial for effective evaluation of the exposure risk associated with intake of Cd-contaminated rice. However, limited studies have investigated the influence of gut microbiota on these two significant factors. In this study, we utilized in vitro gastrointestinal simulators, specifically the RIVM-M (with human gut microbial communities) and the RIVM model (without gut microbial communities), to determine the bioaccessibility of Cd in rice. Additionally, we employed the Caco-2 cell model to assess bioavailability. Our findings provide compelling evidence that gut microbiota significantly reduces Cd bioaccessibility and bioavailability (p<0.05). Notably, strong in vivo-in vitro correlations (IVIVC) were observed between the in vitro bioaccessibilities and bioavailabilities, as compared to the results obtained from an in vivo mouse bioassay (R2 = 0.63-0.65 and 0.45-0.70, respectively). Minerals such as copper (Cu) and iron (Fe) in the food matrix were found to be negatively correlated with Cd bioaccessibility in rice. Furthermore, the results obtained from the toxicokinetic (TK) model revealed that the predicted urinary Cd levels in the Chinese population, based on dietary Cd intake adjusted by in vitro bioaccessibility from the RIVM-M model, were consistent with the actual measured levels (p > 0.05). These results indicated that the RIVM-M model represents a potent approach for measuring Cd bioaccessibility and underscore the crucial role of gut microbiota in the digestion and absorption process of Cd. The implementation of these in vitro methods holds promise for reducing uncertainties in dietary exposure assessment.

Assuntos

Disponibilidade Biológica , Cádmio , Microbioma Gastrointestinal , Oryza , Oryza/metabolismo , Cádmio/metabolismo , Humanos , Animais , Camundongos , Células CACO-2 , Contaminação de Alimentos/análise , Poluentes do Solo/metabolismo , Poluentes do Solo/análise

RESUMO

Enhanced mortality, relapse rates, and increased prevalence of Clostridioides difficile infection (CDI) emphasize the need for better therapies and management approaches. Modulating host immune response to ameliorate CDI-associated immunopathology may provide new advantages to currently inadequate antibiotic therapies. Here, we identified progranulin (PGRN) as an important immune target upregulated in response to CDI. PGRN-deficient mice displayed dramatically higher mortality and aggravated epithelial barrier disruption compared with wild type (WT) mice after CDI despite equivalent levels of bacterial burden or toxin in the large intestine. Mechanistically, PGRN protection was mediated by IL-22 production from CD4+ T helper cells, as demonstrated by a decrease in colonic IL-22-producing CD4+ T helper cells in the intestine of PGRN-deficient mice upon CDI and a boost of IL-22-producing CD4+ T helper cells activated by PGRN ex vivo. Clinical evidence suggests that CDI patients had significantly higher serum levels of PGRN compared with healthy controls, which was significantly and positively correlated with IL-22. Our findings thus indicate a critical role for PGRN-promoted CD4+ T cell IL-22 production in shaping gut immunity and reestablishing the intestinal barrier during CDI. As an alternative to pathogen-targeted therapy, this study may provide a new host-directed therapeutic strategy to attenuate severe, refractory CDI.

Assuntos

Clostridioides difficile , Infecções por Clostridium , Interleucina 22 , Interleucinas , Camundongos Endogâmicos C57BL , Progranulinas , Animais , Interleucinas/metabolismo , Progranulinas/metabolismo , Progranulinas/genética , Infecções por Clostridium/imunologia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/prevenção & controle , Camundongos , Humanos , Camundongos Knockout , Feminino , Masculino , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo

RESUMO

Diseases transmitted by arthropod-borne viruses such as West Nile virus (WNV) and chikungunya virus (CHIKV) pose threat to global public health. Unfortunately, to date, there is no available approved drug for severe symptoms caused by both viruses. It has been reported that reverse transcriptase inhibitors can effectively inhibit RNA polymerase activity of RNA viruses. We screened the anti-WNV activity of the FDA-approved reverse transcriptase inhibitor library and found that 4 out of 27 compounds showed significant antiviral activity. Among the candidates, etravirine markedly inhibited WNV infection in both Huh 7 and SH-SY5Y cells. Further assays revealed that etravirine inhibited the infection of multiple arboviruses, including yellow fever virus (YFV), tick-borne encephalitis virus (TBEV), and CHIKV. A deeper study at the phase of action showed that the drug works primarily during the viral replication process. This was supported by the strong interaction potential between etravirine and the RNA-dependent RNA polymerase (RdRp) of WNV and alphaviruses, as evaluated using molecular docking. In vivo, etravirine significantly rescued mice from WNV infection-induced weight loss, severe neurological symptoms, and death, as well as reduced the viral load and inflammatory cytokines in target tissues. Etravirine showed antiviral effects in both arthrophlogosis and lethal mouse models of CHIKV infection. This study revealed that etravirine is an effective anti-WNV and CHIKV arbovirus agent both in vitro and in vivo due to the inhibition of viral replication, providing promising candidates for clinical application.

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) stands as a significant global health challenge, distinguished by its aggressive progression from the esophageal epithelium. Central to this malignancy is sphingolipid metabolism, a critical pathway that governs key cellular processes, including apoptosis and immune regulation, thereby influencing tumor behavior. The advent of single-cell and transcriptome sequencing technologies has catalyzed significant advancements in oncology research, offering unprecedented insights into the molecular underpinnings of cancer. METHODS: We explored sphingolipid metabolism-related genes in ESCC using scRNA-seq data from GEO and transcriptome data from TCGA. We assessed 97 genes in epithelial cells with AUCell, UCell, and singscore algorithms, followed by bulk RNA-seq and differential analysis to identify prognosis-related genes. Immune infiltration and potential immunotherapeutic strategies were also investigated, and tumor gene mutations and drug treatment strategies were analyzed. RESULT: Our study identified distinct gene expression patterns, highlighting ARSD, CTSA, DEGS1, and PPTQ's roles in later cellular stages. We identified seven independent prognostic genes and created a precise nomogram for prognosis. CONCLUSION: This study integrates single-cell and transcriptomic data to provide a reliable prognostic model associated with sphingolipid metabolism and to inform immunotherapy and pharmacotherapy for ESCC at the genetic level. The findings have significant implications for precision therapy in esophageal cancer.

RESUMO

Plasmodium vivax malaria remains a global health challenge, with approximately 6.9 million estimated cases in 2022. The parasite has a dormant liver stage, the hypnozoite, which reactivates to cause repeated relapses over weeks, months, or years. These relapses erode patient health, contribute to the burden of malaria, and promote transmission. Radical cure to prevent relapses requires administration of an 8-aminoquinoline, either primaquine or tafenoquine. However, malaria treatment guidelines updated by the World Health Organization (WHO) in October 2023 restrict primaquine use for women breastfeeding children < 6 months of age, or women breastfeeding older children if their child is G6PD deficient or if the child's G6PD status is unknown. Primaquine restrictions assume that 8-aminoquinoline exposures in breast milk would be sufficient to cause haemolysis in the nursing infant should they be G6PD deficient. WHO recommendations for tafenoquine are awaited. Notably, the WHO recommends that infants are breastfed for the first 2 years of life, and exclusively until 6 months old. Repeated pregnancies, followed by extended breastfeeding leaves women in P. vivax endemic regions potentially vulnerable to relapses for many years. This puts women's health at risk, increases the malaria burden, and perpetuates transmission, hindering malaria control and elimination. The benefits of lifting restrictions on primaquine administration to breastfeeding women are significant, avoiding the adverse consequences of repeated episodes of acute malaria, such as severe anaemia. Recent data challenge the restriction of primaquine in breastfeeding women. Clinical pharmacokinetic data in breastfeeding infants ≥ 28 days old show that the exposure to primaquine is very low and less than 1% of the maternal exposure, indicating negligible risk to infants, irrespective of their G6PD status. Physiologically-based pharmacokinetic modelling complements the clinical data, predicting minimal primaquine exposure to infants and neonates via breast milk from early post-partum. This article summarizes the clinical and modelling evidence for a favourable benefit:risk evaluation of P. vivax radical cure with primaquine for breastfeeding women without the need for infant G6PD testing, supporting a change in policy. This adjustment to current treatment guidelines would support health equity in regard to effective interventions to protect women and their children, enhance malaria control strategies, and advance P. vivax elimination.

Assuntos

Antimaláricos , Aleitamento Materno , Malária Vivax , Primaquina , Humanos , Malária Vivax/tratamento farmacológico , Malária Vivax/prevenção & controle , Antimaláricos/uso terapêutico , Primaquina/uso terapêutico , Feminino , Equidade em Saúde , Lactente , Plasmodium vivax/efeitos dos fármacos

RESUMO

Hydrazine (N2H4) has been extensively utilized as a highly reactive chemical reagent. However, it is also seriously harmful to human beings and ecosystem. Thus, the development of an efficient detecting method for hydrazine is desirable. Here, caffeic acid was chose as starting material to synthesize a new ratiometric fluorescent probe HPA for detecting hydrazine. This probe possessed the specific recognition ability for hydrazine over other analytes with low detection limit (0.106 µM) and extremely short time (60 s). The sensing mechanism of probe HPA for hydrazine was proved by 1H NMR titration and theoretical calculations. In addition, the probe HPA was loaded on paper strip for rapid quantitative detection of hydrazine with the aid of a software (Image J). The effective detecting performances of probe HPA for hydrazine were verified in environmental water samples as well as in living cells. Thus, HPA has great potential for detection and analysis of hydrazine in health supervision and environmental protection.

RESUMO

Based on the joint analysis of multi-omic data and the biological experiments, we demonstrate that FOXF1 inhibits invasion and metastasis of lung adenocarcinoma cells and enhances anti-tumor immunity via regulating MFAP4/FAK signal axis in this study. The levels of FOXF1 and MFAP4 are significantly down-regulated in LUAD, and the increased levels of two genes can improve the clinical prognosis of LUAD patients. Fluorescein reporter gene determination, chromatin immunoprecipitation and gene co-expression analysis indicate that MFAP4 level is positively regulated by transcription factor FOXF1. The function enrichment analysis shows that the levels of FOXF1 and MFAP4 are closely associated with an enrichment of tumor metastasis signatures. FOXF1 can inhibit the migration and invasion of LAUD cells by transcriptionally activating MFAP4 expression. And the overexpression of FOXF1/MFAP4 can reduce focal adhesion kinase (FAK) phosphorylation, while their knockdown result in the opposite effects. The increased levels of FOXF1/MFAP4 enhance the antitumor immunity by increasing the infiltration of dendritic cells and CD4+ T cells, and the interactions between LUAD cells and immune cells, and activating multiple anti-tumor immunity-related pathways. In conclusion, our study reveals the potential function of FOXF1/MFAP4/FAK signal axis in inhibiting metastasis of LUAD cells and modulating anti-tumor immunity of LUAD patients.

Assuntos

Adenocarcinoma de Pulmão , Fatores de Transcrição Forkhead , Neoplasias Pulmonares , Invasividade Neoplásica , Transdução de Sinais , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , Quinase 1 de Adesão Focal/metabolismo , Quinase 1 de Adesão Focal/genética , Movimento Celular , Camundongos , Animais , Proteína-Tirosina Quinases de Adesão Focal/metabolismo

RESUMO

Ginseng, from the roots of Panax ginseng C. A. Meyer, is a widely used herbal medicine in Asian countries, known for its excellent therapeutic properties. The growth of P. ginseng is depend on specific and strict environments, with a preference for wetness but intolerance for flooding. Under excessive soil moisture, some irregular rust-like substances are deposited on the root epidermis, causing ginseng rusty symptoms (GRS). This condition leads to a significant reduce in yield and quality, resulting in substantial economic loses. However, there is less knowledge on the cause of GRS and there are no effective treatments available for its treatment once it occurs. Unsuitable environments lead to the generation of large amounts of reactive oxygen species (ROS). We investigated the key indicators associated with the stress response during different physiological stages of GRS development. We observed a significant change in ROS level, MDA contents, antioxidant enzymes activities, and non-enzymatic antioxidants contents prior to the GRS. Through the analysis of soil features with an abundance of moisture, we further determined the source of ROS. The levels of nitrate reductase (NR) and nitric oxide synthase (NOS) activities in the inter-root soil of ginseng with GRS were significantly elevated compared to those of healthy ginseng. These enzymes boost nitric oxide (NO) levels, which in turn showed a favorable correlation with the GRS. The activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase first rose and then decreased as GRS developed. Excess soil moisture causes a decrease in oxygen levels. This activated NR and NOS in the soil, resulting in a production of excess NO. The NO then diffused into the ginseng root and triggered a burst of ROS through NADPH located on the cell membrane. Additionally, Fe2+ in soil was oxidized to red Fe3+, and finally led to GRS. This conclusion was also verified by the Sodium Nitroprusside (SNP), a precursor compound producing NO. The presence of NO from NR and NOS in water-saturated soil is responsible for the generation of ROS. Among these, NO is the main component that contribute to the occurrence of GRS.

Assuntos

Óxido Nítrico , Panax , Raízes de Plantas , Espécies Reativas de Oxigênio , Solo , Panax/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Óxido Nítrico/metabolismo , Solo/química , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico , Antioxidantes/metabolismo , Óxido Nítrico Sintase/metabolismo , Nitrato Redutase/metabolismo , Doenças das Plantas

RESUMO

A new species, Dindymusalbonotum Zhao & Cao, sp. nov., and two newly recorded species, Euscopusrobustus Stehlík, 2005 and Brancucciana (Rubriascopus) orientalis Stehlík & Jindra, 2008, belonging to the family Pyrrhocoridae Amyot & Serville, 1843 (Hemiptera, Heteroptera, Pyrrhocoroidea) from China are described and illustrated.

RESUMO

Ciliary neurotrophic factor (CNTF) acts as a potent neuroprotective agent in neuronal survival and regeneration, and can also induce the differentiation of several stem cells into neurons, which highlights the broad application of CNTF in biomedicine. However, large-scale production of bioactive recombinant human CNTF protein remains to be explored. Herein, this study aims to express a bioactive human CNTF protein on a large scale by genetically engineering a silk gland bioreactor of silkworm. Our results showed that CNTF protein was successfully expressed in the middle silk gland (MSG) of silkworm, which can be secreted into the silks with the amount of 3.2 mg/g cocoons. The fabrication of human CNTF-functionalized silk material was able to promote proliferation and migration of neural cells when compared to the natural silk protein. Importantly, this functional silk material could also facilitate neurite outgrowth of mouse retinal ganglion cell (RGC-5) cells. All these data demonstrated a high bioactivity of the recombinant human CNTF protein expressed in the MSG of silkworm. The further fabrication of different silk materials with CNTF bioactivity will give biomedical applications in tissue engineering and neuroregeneration.

RESUMO

Silk-producing animals use spigots to generate natural silk fibers for various purposes. These natural looms must be able to withstand prolonged silk extrusion. To gain insight into the functional basis of spigots, we report on the structural design of the spigot of the silkworm Bombyx mori. The B. mori spigot exhibits a unique triple-ridged strip surface structure, consisting of cuticle proteins, resilin, chitin, and metal ions (such as K and Ca). This multi-microstructure endows the spigot with superior hierarchical mechanical properties, enabling it to function as a spinning tool for silk formation, thereby influencing the structure and performance of the silk. These findings demonstrate new pathways for achieving specialized functions in confined spaces, providing theoretical support for understanding the natural spinning mechanism and inspiring new directions for developing innovative biomimetic materials.

RESUMO

Uneven lithium deposition poses a primary challenge for lithium-ion batteries, as it often triggers the growth of lithium dendrites, thereby significantly compromising battery performance and potentially giving rise to safety concerns. Therefore, the high level of safety must be guaranteed to achieve the large-scale application of battery energy storage systems. Here, we present a novel separator design achieved by incorporating a two-dimensional A-type molecular sieve coating onto the polypropylene separator surface, which functions as an effective lithium ion redistribution layer. The results demonstrated that even after undergoing 1000 cycles, the cell equipped with a two-dimensional A-type molecular sieve-Polypropylene (2D-A-PP) separator still maintains an impressive capacity retention rate of 70 %. In contrast, cells equipped with Polypropylene (PP) separators exhibit capacity retention rates below 50 % after only 500 cycles. Additionally, the incorporation of a two-dimensional molecular sieve enhances the mechanical properties of the PP separator, thereby bolstering battery safety. This study proposes a novel concept for the design of lithium-ion battery separator materials, offering a fresh perspective on the development of separators with exceptional thermal stability, enhanced porosity, superior electrolyte affinity, and effective inhibition of lithium dendrite formation.

RESUMO

Atrazine is a widely used herbicide in agricultural production. Previous studies have shown that atrazine affects hormone secretion and oocyte maturation in female reproduction. However, the specific mechanism by which atrazine affects ovarian function remains unclear. In this study, using a mouse gastric lavage model, we report that four weeks of atrazine exposure affects body growth, interferes with the estrous cycle, and increases the number of atretic follicles in mice. The expression levels of follicle development related factors StAR, BMP15, and AMH decreased. Metabolomic analysis revealed that atrazine activates an inflammatory response in ovarian tissue. Further studies confirmed that the expression levels of TNF-α, IL-6, and NF-κB increased in the ovaries of mice exposed to atrazine. Additionally, α-smooth muscle actin (α-SMA) accumulated in ovarian tissue, and transforming growth factor-ß (TGF-ß) signaling was activated, indicating the occurrence of tissue fibrosis. Moreover, mice exposed to atrazine produced fewer oocytes and exhibited reduced embryonic development. Furthermore, mice exposed to atrazine exhibited altered gut microbiota abundance and a disrupted colon barrier. Collectively, these findings suggest that atrazine exposure induces ovarian inflammation and fibrosis, disrupts ovarian homeostasis, and impairs follicle maturation, ultimately reducing oocyte quality.

Assuntos

Atrazina , Fibrose , Herbicidas , Inflamação , Ovário , Animais , Atrazina/toxicidade , Feminino , Camundongos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Herbicidas/toxicidade , Inflamação/induzido quimicamente

RESUMO

BACKGROUND: Repeated exposure to sevoflurane during early developmental stages is a risk factor for social behavioural disorders, but the underlying neuropathological mechanisms remain unclear. As the hippocampal cornu ammonis area 2 subregion (CA2) is a critical centre for social cognitive functions, we hypothesised that sevoflurane exposure can lead to social behavioural disorders by disrupting neuronal activity in the CA2. METHODS: Neonatal mice were anaesthetised with sevoflurane 3 vol% for 2 h on postnatal day (PND) 6, 8, and 10. Bulk RNA sequencing of CA2 tissue was conducted on PND 12. Social cognitive function was assessed by behavioural experiments, and in vivo CA2 neuronal activity was recorded by multi-channel electrodes on PND 60-65. RESULTS: Repeated postnatal exposure to sevoflurane impaired social novelty recognition in adulthood. It also caused a decrease in the synchronisation of neuronal spiking, gamma oscillation power, and spike phase-locking between GABAergic spiking and gamma oscillations in the CA2 during social interaction. After sevoflurane exposure, we observed a reduction in the density and dendritic complexity of CA2 GABAergic neurones, and decreased expression of transcription factors critical for GABAergic neuronal development after. CONCLUSIONS: Repeated postnatal exposure to sevoflurane disturbed the development of CA2 GABAergic neurones through downregulation of essential transcription factors. This resulted in impaired electrophysiological function in adult GABAergic neurones, leading to social recognition deficits. These findings reveal a potential electrophysiological mechanism underlying the long-term social recognition deficits induced by sevoflurane and highlight the crucial role of CA2 GABAergic neurones in social interactions.

Assuntos

Anestésicos Inalatórios , Animais Recém-Nascidos , Neurônios GABAérgicos , Hipocampo , Sevoflurano , Animais , Sevoflurano/farmacologia , Camundongos , Anestésicos Inalatórios/toxicidade , Anestésicos Inalatórios/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Comportamento Social , Reconhecimento Psicológico/efeitos dos fármacos , Feminino

RESUMO

Four isocoumarin derivatives (1-4) and five phenols (5-9) were obtained from the endophytic fungus Pezicula neosporulosa VDB39, which was isolated from the branches of Vaccinium dunalianum Wight (Ericaceae). Compound 1 is a new derivative of isocoumarin. The structures were elucidated by spectroscopic methods. Single X-ray crystallography confirmed the absolute configuration of compound 1. Additionally, the antiphytopathogenic fungi activity of isocoumarin derivatives (1-4) was evaluated.

RESUMO

Chikungunya virus (CHIKV) is a reemerging arbovirus causing disease on a global scale, and the potential for its epidemics remains high. CHIKV has caused millions of cases and heavy economic burdens around the world, while there are no available approved antiviral therapies to date. In this study, nifuroxazide, an FDA-approved antibiotic for acute diarrhea or colitis, was found to significantly inhibit a variety of arboviruses, although its antiviral activity varied among different target cell types. Nifuroxazide exhibited relatively high inhibitory efficiency in yellow fever virus (YFV) infection of the hepatoma cell line Huh7, tick-borne encephalitis virus (TBEV) and west nile virus (WNV) infection of the vascular endothelial cell line HUVEC, and CHIKV infection of both Huh7 cells and HUVECs, while it barely affected the viral invasion of neurons. Further systematic studies on the action stage of nifuroxazide showed that nifuroxazide mainly inhibited in the viral replication stage. In vivo, nifuroxazide significantly reduced the viral load in muscles and protected mice from CHIKV-induced footpad swelling, an inflammation injury within the arthrosis of infected mice. These results suggest that nifuroxazide has a potential clinical application as an antiviral drug, such as in the treatment of CHIKV infection.

Assuntos

Antivirais , Febre de Chikungunya , Vírus Chikungunya , Hidroxibenzoatos , Nitrofuranos , Replicação Viral , Animais , Camundongos , Humanos , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/fisiologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Replicação Viral/efeitos dos fármacos , Nitrofuranos/farmacologia , Nitrofuranos/uso terapêutico , Febre de Chikungunya/tratamento farmacológico , Febre de Chikungunya/virologia , Hidroxibenzoatos/farmacologia , Hidroxibenzoatos/uso terapêutico , Linhagem Celular , Carga Viral/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana

RESUMO

To optimize the ultrasonic-assisted biphasic aqueous extraction conditions for polyphenolic compounds from Vaccinium dunalianum Wight leaves and investigate their antioxidant and tyrosinase inhibition activities, single-factor experiments were conducted to investigate the effects of ethanol volume fraction (%), ammonium sulfate mass fraction (%), solid-liquid ratio (g/mL), ultrasonic temperature (°C), and ultrasonic time (min) on polyphenolic content during extraction. Based on these experiments, three key factors influencing extraction were selected for response surface methodology (RSM) optimization. The results indicated that under conditions of 26 % ethanol, 20 % ammonium sulfate, a solid-liquid ratio of 1 : 30, and extraction for 35 minutes at 50 °C, the polyphenol content reached 61.62 mg/g. The relative contents of 6'-O-caffeoylarbutin, ß-arbutin, and chlorogenic acid were 34.45 %, 4.56 %, and 31.06 %, respectively. The DPPH⋅ and ABTS+⋅ scavenging rates were above 95 % and 96 %, respectively, and the ferric reducing ability exhibited a significant dose-effect relationship. The inhibition rates of monophenolase and diphenolase activities of tyrosinase were 43.84 % and 35.73 %, respectively. The optimized process for ultrasonic-assisted biphasic aqueous extraction of polyphenols from Vaccinium dunalianum Wight leaves demonstrated significant antioxidant and tyrosinase inhibition activities.