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1.
Front Immunol ; 15: 1360955, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633259

RESUMO

With a shortage of organs for transplant, the use of marginal donors can be an effective measure to meet the shortfall. Myelodysplastic syndromes (MDS) are considered an absolute contraindication for organ donation because of the high invasive potential. Currently, organ transplantation from donors with a past history of MDS has not been reported. In this paper, we report the successful clinical experience of one liver transplantation and two kidney transplantations, with organs donated by a 39-year-old patient diagnosed with a past history of MDS following intracranial hemorrhage. Four and a half years after transplantation, the three recipients are all doing well. However, it is still not clear to what extent organs donated by patients with a past history of MDS can be safely transplanted. This report provides support for the careful use of marginal donors. With effective treatment and full peer assessment, livers and kidneys from donors with a past history of MDS may be safely transplanted.


Assuntos
Transplante de Fígado , Síndromes Mielodisplásicas , Humanos , Adulto , Doadores de Tecidos , Rim , Fígado
2.
Medicine (Baltimore) ; 103(13): e37347, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552080

RESUMO

BACKGROUND: Diabetic macular edema (DME) is the main cause of irreversible vision loss in patients with diabetes mellitus (DM), resulting in a certain burden to patients and society. With the increasing incidence of DME, more and more researchers are focusing on it. METHODS: The papers related to DME between 2012 and 2022 from the Web of Science core Collection were searched in this study. Based on CiteSpace and VOS viewer, these publications were analyzed in terms of spatiotemporal distribution, author distribution, subject classification, topic distribution, and citations. RESULTS: A total of 5165 publications on DME were included. The results showed that the research on DME is on a steady growth trend. The country with the highest number of published documents was the US. Wong Tien Yin from Tsinghua University was the author with the most published articles. The journal of Retina, the Journal of Retinal and Vitreous Diseases had a large number of publications. The article "Mechanisms of macular edema: Beyond the surface" was the highly cited literature and "Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema" had the highest co-citation frequency. The treatment, diagnosis, pathogenesis, as well as etiology and epidemiological investigation of DME, have been the current research direction. Deep learning has been widely used in the medical field for its strong feature representation ability. CONCLUSIONS: The study revealed the important authoritative literature, journals, institutions, scholars, countries, research hotspots, and development trends in in the field of DME. This indicates that communication and cooperation between disciplines, universities, and countries are crucial. It can advance research in DME and even ophthalmology.


Assuntos
Retinopatia Diabética , Edema Macular , Humanos , Retinopatia Diabética/complicações , Edema Macular/epidemiologia , Edema Macular/etiologia , Ranibizumab , Bevacizumab , Bibliometria
3.
Virol Sin ; 39(2): 301-308, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452856

RESUMO

Hand, foot, and mouth disease (HFMD) is a common pediatric illness mainly caused by enteroviruses, which are important human pathogens. Currently, there are no available antiviral agents for the therapy of enterovirus infection. In this study, an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed. Using this screening system, we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors. Fangchinoline (FAN), a bis-benzylisoquinoline alkaloid, exhibits potential inhibitory effects against various enteroviruses that cause HFMD, such as EV-A71, CV-A10, CV-B3 and CV-A16. Further investigations revealed that FAN targets the early stage of the enterovirus life cycle. Through the selection of FAN-resistant EV-A71 viruses, we demonstrated that the VP1 protein could be a potential target of FAN, as two mutations in VP1 (E145G and V258I) resulted in viral resistance to FAN. Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.


Assuntos
Antivirais , Benzilisoquinolinas , Farmacorresistência Viral , Antivirais/farmacologia , Humanos , Benzilisoquinolinas/farmacologia , Farmacorresistência Viral/genética , Replicação Viral/efeitos dos fármacos , Enterovirus Humano A/efeitos dos fármacos , Enterovirus Humano A/genética , Avaliação Pré-Clínica de Medicamentos , Genes Reporter , Ensaios de Triagem em Larga Escala , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/antagonistas & inibidores , Enterovirus/efeitos dos fármacos , Enterovirus/genética , Linhagem Celular , Proteínas de Fluorescência Verde/genética
4.
Brain Res ; 1824: 148676, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37956747

RESUMO

The olfactory bulbectomy (OBX) animal model of depression reproduces the behavioral and neurochemical changes observed in depressed patients. We assessed the therapeutic effects of the Jieyu Chufan (JYCF) capsule on OBX rats. JYCF ameliorated the hedonic and anxiety-like behavior of OBX rats and attenuated the cortical and hippocampal damage. JYCF enhanced the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), fibroblast growth factor 2 (FGF2), and adiponectin (ADPN) in the cortex and hippocampus of OBX rats. JYCF also reduced cortisol levels and restored the levels of excitatory neurotransmitters, such as 5-hydroxytryptamine (5-HT), acetylcholine (ACH), and glutamic acid (Glu), in the brain tissue of OBX rats. Our results suggest that JYCF preserves the synaptic structure by increasing the levels of synaptophysin (SYN) and postsynaptic density protein 95 (PSD95) and alleviates the histological alterations of brain tissue by activating AKT/PKA-CREB-BDNF pathways, and by upregulating ADPN and FGF2 expression in OBX rats. JYCF exerts multiple therapeutic effects on depression, including modulating neurotransmitters, repairing neuronal damage, and maintaining synaptic integrity. These findings support the potential of JYCF as a novel antidepressant agent with therapeutic effects on depression and related neurological disorders.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Depressão , Humanos , Ratos , Animais , Depressão/tratamento farmacológico , Depressão/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Neurotransmissores/metabolismo , Bulbo Olfatório/metabolismo , Modelos Animais de Doenças
5.
Eye Contact Lens ; 50(2): 102-105, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37988104

RESUMO

OBJECTIVE: To determine whether fibroblast growth factor receptor (FGFR)-targeting drug could impact human meibomian gland. METHODS: We followed up with three patients who were using pemigatinib for 4 to 10 weeks. The patients were evaluated for their ocular surface disease index, best-corrected visual acuity, Schirmer test, cornea staining, meibum expressibility score, tear meniscus height, noninvasive tear film breakup time, and meibomian gland area. The distribution of the FGFR family, FGF7, and FGF10 were evaluated by immunofluorescence staining and Western blot in fresh tarsal tissues from deidentified patients who underwent lid plastic surgeries. RESULTS: All patients developed apparent meibomian gland atrophy, shortening and narrowing of ducts, and significantly increased meibum expressibility and decreased noninvasive tear film breakup time within 5 to 8 weeks. Laboratory evaluations confirmed that human meibomian gland expresses abundant fibroblast growth factor receptors. CONCLUSIONS: These findings indicate that meibomian gland is a target tissue of FGFR inhibitors, and patients who use these drugs may develop meibomian gland dysfunction.


Assuntos
Síndromes do Olho Seco , Doenças Palpebrais , Disfunção da Glândula Tarsal , Humanos , Glândulas Tarsais/metabolismo , Disfunção da Glândula Tarsal/metabolismo , Lágrimas/metabolismo , Síndromes do Olho Seco/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 48(20): 5623-5631, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38114155

RESUMO

This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.


Assuntos
Doença das Coronárias , Função Ventricular Esquerda , Ratos , Animais , Volume Sistólico , Ratos Sprague-Dawley , Doença das Coronárias/tratamento farmacológico , Metabolômica
7.
J Cancer ; 14(18): 3496-3507, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38021164

RESUMO

Background: Neuroblastoma (NB) is a cancer that arises from neural-crest-derived sympathoadrenal lineage. Less is known about the pathogenesis and molecular characteristics of MYCN non-amplified (MYCN-NA) NB. Methods: We constructed a signature model targeting mucin family according to RNA sequencing data from GSE49710 dataset, and validated the prognostic performance. We also analyzed the gene expression matrix using DESeq2 R packages to screen the most differential mucin in high-risk NB samples. We further assessed its prognostic value, particularly in MYCN-NA NB samples. Moreover, we performed functional experiments to evaluate the impact of MUC15 overexpression on the migration of MYCN-NA NB cell lines. Results: The 8-mucin signature model showed good prognostic performance in the GSE49710 dataset. Among the mucin genes, MUC15 was significantly upregulated in the high-risk NB cohort and was associated with poor prognosis, especially in MYCN-NA NB samples. Furthermore, MUC15 overexpression and exogenous MUC15 protein enhanced the migration of MYCN-NA NB cell lines. Mechanistically, MUC15 promoted the phosphorylation of focal adhesion kinase (FAK) by inhibiting the expression of MYCT1, a target of c-Myc. Conclusions: Our findings suggested a potential network in controlling NB cell metastasis. Targeting MUC15 in MYCN-NA NB patients could be a promising therapeutic strategy.

8.
Antiviral Res ; 220: 105757, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37984567

RESUMO

Despite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Currently, the development of affordable vaccine against Omicron variant of concern (VOC) is necessary. Here, we assessed the safety and immunogenicity of a SARS-CoV-2 vaccine consisting of a live Newcastle disease virus vector expressing the spike (S) protein of Omicron BA.1 administrated intranasally (IN) or intramuscularly (IM) in Golden Syrian hamster model. Immunogenicity studies showed that the prime-boost regimen elicited high antibody titers and the modified S antigen (Sm-F) could induce robust antibody response in low dosage immunization through IN route. Sera of the immunized hamsters provided effective cross-neutralizing activity against different Omicron variants, the prototype and delta strains of SARS-CoV-2. Moreover, the vaccine could provide complete immunoprotection in hamsters against the Omicron BA.1 challenge by either intranasal or intramuscular immunization. Overall, our study provides an alternative nasal vaccine against the SARS-CoV-2 Omicron variants.


Assuntos
Antígenos de Grupos Sanguíneos , COVID-19 , Vacinas , Animais , Cricetinae , Humanos , Vírus da Doença de Newcastle/genética , SARS-CoV-2 , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Vacinação , Imunização , Mesocricetus , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Neutralizantes , Anticorpos Antivirais
9.
Artigo em Inglês | MEDLINE | ID: mdl-37883775

RESUMO

Objective: To observe the therapeutic effect of pulsatile intravenous insulin therapy (PIVIT) combined with critical value early warning nursing on diabetic ketoacidosis (DKA). Methods: Ninety-six DKA patients treated in our hospital between May 2021 and February 2023 were selected as the research subjects, of which 53 cases received PIVIT (research group) and the other 43 cases received insulin intravenous infusion therapy (control group). The blood glucose (BG), condition, pH control time and the incidence of adverse reactions were analyzed in the two groups. Changes in pre- and post-treatment BG, cardiac function, ß-Hydroxybutyric acid (ß-HBA), lactate (Lac), and blood ketone body (BKB) were determined before and after treatment. In addition, patients' psychological status was assessed using the Self-rating Depression/Anxiety Scale (SDS/SAS) and their satisfaction with the nursing services was investigated. Results: The research group took less time to control BG, condition, and pH value than control group, with lower BG, ß-HBA, Lac, and BKB levels and better cardiac function after treatment (P < .05). No notable differences were identified between groups in terms of adverse reactions, SAS and SDS scores, and nursing satisfaction (P > .05). Conclusions: PIVIT combined with critical value early warning nursing can alleviate the acidosis of DKA patients more quickly and effectively.

10.
RSC Adv ; 13(42): 29152-29162, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37800130

RESUMO

Topical administration of curcumin (CUR), a natural polyphenol with potent anti-inflammation and analgesic activities, provides a potential approach for local skin diseases. However, the drug delivery efficiency is highly limited by skin barriers and poor bioavailability of CUR. Herein, we propose hydrogel containing CUR-encapsulated dipeptide-1-modified nanostructured lipid carriers (CUR-DP-NLCs gel) to enhance topical drug delivery, and improve the topical therapeutic effect. The prepared CUR-DP-NLCs were characterized and were suitably dispersed into the Pluronic F127 hydrogel for topical application. The optimized CUR-DP-NLCs had a particle size of 152.6 ± 3.47 nm, a zeta potential of -33.1 ± 1.46 mV, an entrapment efficiency of 99.83 ± 0.14%, and a spherical morphology. X-ray diffraction (XRD) studies confirmed that CUR was successfully entrapped by the NLCs in an amorphous form. CUR-DP-NLCs gel exhibited sustained release over 48 h and significantly increased the skin retention of CUR. In vitro skin retention of CUR with CUR-DP-NLCs gel was 2.14 and 2.85 times higher than that of unmodified NLCs gel and free CUR, respectively. Fluorescence microscopy imaging revealed the formed nanoparticles accumulated in the hair follicles with prolonged retention time to form a drug reservoir. The hematoxylin-eosin staining showed that CUR-DP-NLCs gel could change the microstructure of skin layers and disturb the skin barriers. After topical administration to mice, CUR-DP-NLCs gel showed better analgesic and anti-inflammatory activities with no potentially hazardous skin irritation. These results concluded that CUR-DP-NLCs gel is a promising strategy to increase topical drug delivery of CUR in the treatment of local skin diseases.

11.
J Environ Sci (China) ; 134: 96-107, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37673537

RESUMO

Amorphous manganese oxides (MnOx) were synthesized by facile hydrothermal reactions between potassium permanganate and manganese acetate. Synthesis parameters, including hydrothermal time and temperature and molar ratio of precursors, significantly affected the ozone removal performance and structure property of MnOx. Amorphous MnOx-1.5, which was prepared at the Mn2+/Mn7+ molar ratio of 1.5 under hydrothermal conditions of 120°C and 2 hr, showed the highest ozone removal rate of 93% after 480 min at the room temperature, RH (relative humidity) = 80% and WHSV (weight hourly space velocity) = 600 L/(g·hr). The morphology, composition and structure of catalysts were investigated with X-ray diffractometer (XRD), Raman spectra, N2 physisorption, field emission scanning electron microscope (FESEM), X-ray photoelectron spectroscopy (XPS), H2 temperature-programmed reduction (H2-TPR), O2 temperature-programmed desorption (O2-TPD) and in situ diffuse reflectance infrared Fourier transform spectroscopy (in situ DRIFTS). It was confirmed that high catalytic activity of amorphous MnOx for ozone removal was mainly ascribed to its abundant oxygen vacancies, high oxygen mobility and large specific surface area.


Assuntos
Ozônio , Manganês , Oxigênio , Óxidos
12.
Front Neurorobot ; 17: 1234129, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37622128

RESUMO

Introduction: Metric learning, as a fundamental research direction in the field of computer vision, has played a crucial role in image matching. Traditional metric learning methods aim at constructing two-branch siamese neural networks to address the challenge of image matching, but they often overlook to cross-source and cross-view scenarios. Methods: In this article, a multi-branch metric learning model is proposed to address these limitations. The main contributions of this work are as follows: Firstly, we design a multi-branch siamese network model that enhances measurement reliability through information compensation among data points. Secondly, we construct a non-local information perception and fusion model, which accurately distinguishes positive and negative samples by fusing information at different scales. Thirdly, we enhance the model by integrating semantic information and establish an information consistency mapping between multiple branches, thereby improving the robustness in cross-source and cross-view scenarios. Results: Experimental tests which demonstrate the effectiveness of the proposed method are carried out under various conditions, including homologous, heterogeneous, multi-view, and crossview scenarios. Compared to the state-of-the-art comparison algorithms, our proposed algorithm achieves an improvement of ~1, 2, 1, and 1% in terms of similarity measurement Recall@10, respectively, under these four conditions. Discussion: In addition, our work provides an idea for improving the crossscene application ability of UAV positioning and navigation algorithm.

13.
Psychol Res Behav Manag ; 16: 2635-2645, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465044

RESUMO

Background: Recently, the importance of individual differences has been recognized in the literature of general life satisfaction and domain-specific satisfaction, however, empirical research exploring the relationship between individual differences in self-regulatory focus and financial satisfaction remains relatively sparse, and less is known about the underlying processes that may mediate this relationship. The current study addressed these gaps by investigating whether and how self-regulatory focus (promotion vs prevention) as a motivational trait is related to college students' financial satisfaction. A model was tested in which this association was sequentially mediated by the effects of construal level and opportunity cost consideration. Methods: A total of 552 college students (38.6% male; ages 19-25) completed a packet of questionnaires that measured trait regulatory focus, construal level, opportunity cost consideration, and financial satisfaction. Results: The mediation model was tested via multiple regression analyses and bootstrapping procedure. The results supported a sequential mediation model, suggesting that predominantly promotion-focused regulation is associated with information construal at a more abstract level, increasing the consideration of opportunity costs, and subsequently enhancing financial satisfaction. Discussion: These findings can broaden our understanding of how trait regulatory focus potentially influences financial satisfaction, offering new directions towards improving college students' financial satisfaction.

14.
Toxicol Appl Pharmacol ; 474: 116629, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37468076

RESUMO

Thiacloprid (THIA) is a kind of neonicotinoid, a widely used insecticide class. Animal studies of adult and prenatal exposure to THIA have revealed deleterious effects on mammalian sperm fertility and embryonic development. A recent cross-sectional study linked higher THIA concentrations to delayed genitalia development stages in adolescent boys, suggesting that pubertal exposure to THIA may adversely affect reproductive development in immature males. Hence, this study aimed to investigate the effects of daily oral administration of THIA during puberty on the reproductive system of developing male mice. Young male C57 BL/6 J mice aged 21 days were administrated with THIA at concentrations of 10 (THIA-10), 50 (THIA-50) and 100 mg/kg (THIA-100) for 4 weeks by oral gavage. It is found that exposure to 100 mg/kg THIA diminished sexual behavior in immature male mice, caused a decrease in the spermatogenic cell layers and irregular arrangement of the seminiferous epithelium, and down-regulated the mRNA levels of spermatogenesis-related genes Ddx4, Scp3, Atg5, Crem, and Ki67, leading to an increase of sperm abnormality rate. In addition, THIA exposure at 50 and 100 mg/kg reduced the serum levels of testosterone and FSH, and decreased the expression levels of Star and Cyp11a1 related to testosterone biosynthesis. THIA exposure at 10 mg/kg did not produce any of the above significant changes. In conclusion, the high dose of THIA exposure impaired reproductive function in immature mice. It seems that THIA has no detrimental effects on the reproductive system of mice at low dose of 10 mg/kg.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Testículo , Gravidez , Feminino , Camundongos , Masculino , Animais , Humanos , Sêmen , Espermatogênese , Testosterona , Neonicotinoides/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Mamíferos
15.
Front Microbiol ; 14: 1179824, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275133

RESUMO

Introduction: The type III effector RipAA of Ralstonia solanacearum GMI1000 plays a critical role in the incompatible interaction on Nicotiana benthamiana. Methods: The RipAA was transiently expressed in N. benthamiana by Agrobacterium-mediated transformation. Chemical staining with trypan blue and DAB were conducted to examine the cell death and the accumulation of hydrogen peroxide (H2O2), respectively. The expression of the marker genes for salicylic acid (SA) and jasmonic acid (JA) signaling was evaluated by quantitative reverse transcription PCR (qRT-PCR). The proteins interacted with RipAA was identified from N. benthamiana by yeast two-hybrid and pull-down assays. A TRV-mediated gene silencing was used to assess the role of host gene in response to RipAA expression and R. solanacearum infection. Results and discussion: RipAA induced the accumulation of hydrogen peroxide (H2O2) and genome DNA degradation in N. benthamiana, which were accompanied by a hypersensitive reaction. Simultaneously, the marker genes for salicylic acid (SA) signaling were induced and those for jasmonic acid (JA) signaling were reduced. N. benthamiana chloroplastic AtpB, the ATPase ß subunit, was identified as an interactor with RipAA. The silencing of atpB in N. benthamiana resulted in the inability of RipAA to induce a hypersensitive response, a compatible interaction with GMI1000, and an enhanced sensitivity to bacterial wilt. Our data support the concept that RipAA determines host-range specificity by targeting the host chloroplastic AtpB.

16.
Virol Sin ; 38(3): 470-479, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37127212

RESUMO

COVID-19 has become a global public health crisis since its outbreak in China in December 2019. Currently there are few clinically effective drugs to combat SARS-CoV-2 infection. The main protein (Mpro), papain-like protease (PLpro) and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 are involved in the viral replication, and might be prospective targets for anti-coronavirus drug development. Here, we investigated the antiviral activity of oridonin, a natural small-molecule compound, against SARS-CoV-2 infection in vitro. The time-of-addition analysis showed that oridonin efficiently inhibited SARS-CoV-2 infection by interfering with the genome replication at the post-entry stage. Mechanistically, the inhibition of viral replication by oridonin depends on the oxidation activity of α, ß-unsaturated carbonyl. Further experiments showed that oridonin not only effectively inhibited SARS-CoV-2 Mpro activity, but also had some inhibitory effects on PLpro-mediated deubiquitinating and viral polymerase-catalyzed RNA elongation activities at high concentrations. In particular, oridonin could inhibit the bat SARS-like CoV and the newly emerged SARS-CoV-2 omicron variants (BA.1 and BA.2), which highlights its potential as a pan-coronavirus antiviral agent. Overall, our data provide strong evidence that oridonin is an efficient antiviral agent against SARS-CoV-2 infection.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Peptídeo Hidrolases/farmacologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Inibidores de Proteases/farmacologia
17.
18.
J Environ Sci (China) ; 131: 151-161, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37225376

RESUMO

Manganese-based catalysts were widely developed for catalytic removal of ozone, and the low stability and water inactivation are major challenges. To improve removal performance of ozone, three methods were applied to modify amorphous manganese oxides, including acidification, calcination and Ce modification. The physiochemical properties of prepared samples were characterized, and the catalytic activity for ozone removal was evaluated. All modification methods can promote the removal of ozone by amorphous manganese oxides, and Ce modification showed the most significant enhancement. It was confirmed that the introduction of Ce markedly changed the amount and property of oxygen vacancies in amorphous manganese oxides. Superior catalytic activity of Ce-MnOx can be ascribed to its more content and enhanced formation ability of oxygen vacancies, larger specific surface area and higher oxygen mobility. Furthermore, the durability tests under high relative humidity (80%) determined that Ce-MnOx showed excellent stability and water resistance. These demonstrate the promising potential of amorphously Ce-modified manganese oxides for catalytic removal of ozone.


Assuntos
Manganês , Ozônio , Oxigênio , Óxidos , Água
19.
RSC Adv ; 13(16): 10840-10846, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37033427

RESUMO

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide as well as a significant cause of mortality. The conventional treatment could cause serious side effects and induce drug resistance, recurrence and metastasis of cancers. Hence, specific targeting of cancer cells without affecting the normal tissues is currently an urgent necessity in cancer therapy. The emerging of peptide-drug conjugates (PDC) is regarded as a promising approach to address malignant tumors. LWJ-M30, a conjugate of DM1 and B6 peptide, targeted transferrin receptors (TfRs) on the surface of the CRC cells, showing a powerful anti-cancer effect. LWJ-M30 significantly inhibited the HCT116 cells proliferation and migration in vitro. LWJ-M30 also dramatically decreased the level of polymeric tubulin, while the disruption of microtubules caused the cell cycle to be arrested in the G2/M phase. LWJ-M30 induced the HCT116 cells apoptosis both in vivo and in vitro. The results in vivo demonstrated that LWJ-M30 could inhibit the HCT116 growth without affecting the mouse body weight. Taking these results together, our data indicated that LWJ-M30 could improve the therapeutic effects of DM1 while reducing the systemic toxicity in normal tissues.

20.
Artigo em Inglês | MEDLINE | ID: mdl-37060624

RESUMO

Coronary heart disease (CHD) has become the leading cause of mortality, morbidity, and disability worldwide. Though the therapeutic effect of Xuefu Zhuyu Decoction (XFZY) on CHD has been demonstrated in China, the active ingredients and molecular mechanisms of XFZY have not been elucidated. The purpose of the current study is to explore the molecular mechanisms of XFZY in the treatment of CHD via network pharmacology, metabolomics, and experimental validation. First, we established a CHD rat model by permanently ligating the left anterior descending coronary artery (LAD), and evaluated the therapeutic effect of XFZY by hemorheology and histopathology. Second, network pharmacology was employed to screen the active ingredients and potential targets of XFZY for the treatment of CHD. Metabolomic was applied to identify the molecules present in the serum after XFZY treatment. Third, the results of network pharmacology and metabolomics were further analyzed by Cytoscape to elucidate the core ingredients and pathways. Finally, the obtained key pathways were verified by transmission electron microscopy and immunofluorescence assay. The results showed that XFZY was effective in the treatment of CHD in the rat model, and the highest dose exerted the best effect. Network pharmacology analysis revealed 215 active ingredients and 129 key targets associated with XFZY treatment of CHD. These targets were enriched in pathways of cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, proteoglycans in cancer, chemical carcinogenesis - receptor activation, HIF-1 signaling, et al. Serum metabolomic identified 1081 metabolites involved in the therapeutic effect of XFZY on CHD. These metabolites were enriched in taurine and hypotaurine metabolism, histidine metabolism, retrograde endocannabinoid signaling pathways, et al. Cytoscape analysis combining the data from serum metabolomic and network pharmacology revealed that energy metabolism as the core pathway for XFZY treatment of CHD. Electron microscope observation identified changes in the level of autophagy in the mitochondrial structure of cardiomyocytes. Immunofluorescence assay showed that the expression levels of autophagy-related proteins LC3-B and P62/SQSTM1 were consistent with the levels of autophagy observed in mitochondria. In conclusion, our findings suggest that the possible mechanisms of XFZY in the treatment of CHD are reducing the level of autophagy, improving energy metabolism, and maintaining mitochondrial homeostasis in cardiomyocytes. Our study also shows that the combined strategies of network pharmacology, metabolomics, and experimental validation may provide a powerful approach for TCM pharmacology study.


Assuntos
Aterosclerose , Doença das Coronárias , Medicamentos de Ervas Chinesas , Ratos , Animais , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Metabolômica , Aterosclerose/tratamento farmacológico
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