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1.
Neurosurg Rev ; 47(1): 141, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578556

RESUMO

BACKGROUND AND PURPOSE: The classic Shamblin system fails to provide valuable guidance in many Shamblin's III carotid body tumors (III-CBTs) due to the variable forms of carotid arteries and the complex anatomic relationships in parapharyngeal space. We proposed a modified classification to separately divide III-CBTs into different subgroups on the basis of arterial relevant features and anatomical relevant features. MATERIALS AND METHODS: From 2020 to 2023, a total of 129 III-CBTs at a single institution were retrospectively analyzed. All cases were independently classified as arterial-relevant and anatomical-relevant subgroups. The pre-, peri- and postoperative data were summarized and compared accordingly. RESULTS: Among the 129 cases, 69 cases were identified as "Classical type", 23 cases as "Medial type", 27 cases as "Lateral type" and 10 cases as "Enveloped type" according to arterial morphologies. Besides, 76 cases were identified as "Common type", 15 cases as "Pharynx- invasion type", 18 cases as "Skull base-invasion type" and 20 cases as "Mixed type" according to anatomical relationships. "Enveloped type" of tumors in arterial-relevant classification and "Mixed type" of tumors in anatomical-relevant classification are the most challenging cases for surgeons with the lowest resection rate, highest incidence of carotid arteries injury and postoperative stroke. CONCLUSION: The modified classifications provide comprehensive understanding of different III-CBTs which are applicable for individualized treatment in clinical practice.


Assuntos
Tumor do Corpo Carotídeo , Humanos , Tumor do Corpo Carotídeo/cirurgia , Tumor do Corpo Carotídeo/patologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Vasculares , Artérias Carótidas/patologia , Incidência , Resultado do Tratamento
2.
Fitoterapia ; 175: 105944, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38580033

RESUMO

Chelidonium majus L. contained alkaloids as its main component, exhibiting various biological activities, particularly antibacterial activity. This study aimed to extract alkaloids from C. majus L. (total alkaloids) and evaluate their antibacterial activity both in vitro and in vivo. Reflux extraction was carried out on C. majus L., and the extract was purified with HPD-600 macroporous resin and 732 cation exchange resin columns. Infection modeling of Caenorhabditis elegans (C. elegans) was established to investigate the impact of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) on the motility, longevity, and reactive oxygen species (ROS) levels of wild-type worms (N2 strain). The effects of total alkaloids on longevity and ROS were further evaluated in infected N2 worms. Additionally, the effect of total alkaloids on the stress resistance of C. elegans and the mechanism of action were investigated. By utilizing CB1370, DR26 and CF1038 transgenic strains of C. elegans to identify whether the antibacterial activity of total alkaloids was dependent on DAF-2/DAF-16 pathway. The results showed that total alkaloids exhibited a significant antibacterial activity against both MRSA and MSSA (MIC 31.25 µg/mL). Compared with MSSA, the MRSA exhibited a stronger inhibitory effect on the movement behavior and development of worms, along with faster pathogenicity and unique virulence factors. Total alkaloids also displayed the ability to extend the lifespan of C. elegans under oxidative stress and heat stress, and reduce the expression of ROS. The antibacterial activity of total alkaloids was primarily dependent on the DAF-2/DAF-16 pathway, and the presence of functional DAF-2 was deemed essential in total alkaloids mediated immune response against MRSA. Moreover, the antibacterial and anti-infection effects of total alkaloids were found to be associated with the daf-16 gene fragment.


Assuntos
Alcaloides , Antibacterianos , Caenorhabditis elegans , Chelidonium , Staphylococcus aureus Resistente à Meticilina , Caenorhabditis elegans/efeitos dos fármacos , Animais , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/isolamento & purificação , Chelidonium/química , Espécies Reativas de Oxigênio/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Longevidade/efeitos dos fármacos , Proteínas de Caenorhabditis elegans , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Chelidonium majus
3.
Int J Nanomedicine ; 19: 2625-2638, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505169

RESUMO

Purpose: Psoriasis is a chronic and recurrent inflammatory dermatitis characterized by T cell imbalance and abnormal keratinocyte proliferation. MicroRNAs (miRNAs) hold promise as therapeutic agents for this disease; however, their clinical application is hindered by poor stability and limited skin penetration. This study demonstrates the utilization of Framework Nucleic Acid (FNA) for the topical delivery of miRNAs in psoriasis treatment. Methods: By utilizing miRNA-125b as the model drug, FNA-miR-125b was synthesized via self-assembly. The successful synthesis and stability of FNA-miR-125b in bovine fetal serum (FBS) were verified through gel electrophoresis. Subsequently, flow cytometry was employed to investigate the cell internalization on HaCaT cells, while qPCR determined the effects of FNA-miR-125b on cellular functions. Additionally, the skin penetration ability of FNA-miR-125b was assessed. Finally, a topical administration study involving FNA-miR-125b cream on imiquimod (IMQ)-induced psoriasis mice was conducted to evaluate its therapeutic efficacy. Results: The FNA-miR-125b exhibited excellent stability, efficient cellular internalization, and potent inhibition of keratinocyte proliferation. In the psoriasis mouse model, FNA-miR-125b effectively penetrated the skin tissue, resulting in reduced epidermal thickness and PASI score, as well as decreased levels of inflammatory cytokines.


Assuntos
MicroRNAs , Psoríase , Animais , Bovinos , Camundongos , MicroRNAs/genética , Queratinócitos , Pele , Psoríase/tratamento farmacológico , Psoríase/induzido quimicamente , Imiquimode/uso terapêutico , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
4.
Pediatr Nephrol ; 39(5): 1447-1457, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38041747

RESUMO

BACKGROUND: Split kidney function (SKF) is critical for treatment decision in pediatric patients with hydronephrosis and is commonly measured using renal scintigraphy (RS). Non-contrast-enhanced magnetic resonance urography (NCE-MRU) is increasingly used in clinical practice. This study aimed to investigate the feasibility of using NCE-MRU as an alternative to estimate SKF in pediatric patients with hydronephrosis, compared to RS. METHODS: Seventy-five pediatric patients with hydronephrosis were included in this retrospective study. All patients underwent NCE-MRU and RS within 2 weeks. Kidney parenchyma volume (KPV) and texture analysis parameters were obtained from T2-weighted (T2WI) in NCE-MRU. The calculated split KPV (SKPV) percent and texture analysis parameters percent of left kidney were compared with the RS-determined SKF. RESULTS: SKPV showed a significant positive correlation with SKF (r = 0.88, p < 0.001), while inhomogeneity was negatively correlated with SKF (r = - 0.68, p < 0.001). The uncorrected and corrected prediction models of SKF were established using simple and multiple linear regression. Bland-Altman plots demonstrated good agreement of both predictive models. The residual sum of squares of the corrected prediction model was lower than that of the uncorrected model (0.283 vs. 0.314) but not statistically significant (p = 0.662). Subgroup analysis based on different MR machines showed correlation coefficients of 0.85, 0.95, and 0.94 between SKF and SKPV for three different scanners, respectively (p < 0.05 for all). CONCLUSIONS: NCE-MRU can be used as an alternative method for estimating SKF in pediatric patients with hydronephrosis when comparing with RS. Specifically, SKPV proves to be a simple and universally applicable indicator for predicting SKF.


Assuntos
Hidronefrose , Urografia , Criança , Humanos , Estudos Retrospectivos , Urografia/métodos , Hidronefrose/diagnóstico por imagem , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cintilografia , Espectroscopia de Ressonância Magnética
5.
Disaster Med Public Health Prep ; 17: e555, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38053415

RESUMO

OBJECTIVE: This study assesses the difference in professional attitudes among medical students, both before and after coronavirus disease 2019 (COVID-19), and identifies the determinants closely associated with it, while providing precise and scientific evidence for implementing precision education on such professional attitudes. METHODS: A pre-post-like study was conducted among medical students in 31 provinces in mainland China, from March 23, to April 19, 2021. RESULTS: The proportion of medical students whose professional attitudes were disturbed after the COVID-19 pandemic, was significantly lower than before the COVID-19 pandemic (χ2 = 15.6216; P < 0.0001). Compared with the "undisturbed -undisturbed" group, the "undisturbed-disturbed" group showed that there was a 1.664-fold risk of professional attitudes disturbed as grade increased, 3.269-fold risk when others suggested they choose a medical career rather than their own desire, and 7.557-fold risk for students with COVID-19 in their family, relatives, or friends; while the "disturbed-undisturbed" group showed that students with internship experience for professional attitudes strengthened was 2.933-fold than those without internship experience. CONCLUSIONS: The professional attitudes of medical students have been strengthened during the COVID-19 pandemic. The results provide evidence of the importance of education on professional attitudes among medical students during public health emergencies.


Assuntos
COVID-19 , Estudantes de Medicina , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Escolaridade
6.
Front Immunol ; 14: 1289477, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38146373

RESUMO

Parasitoid wasps control pests via a precise attack leading to the death of the pest. However, parasitoid larvae exhibit self-protection strategies against bracovirus-induced reactive oxygen species impairment. This has a detrimental effect on pest control. Here, we report a strategy for simulating Microplitis bicoloratus bracovirus using Mix-T dsRNA targeting 14 genes associated with transcription, translation, cell-cell communication, and humoral signaling pathways in the host, and from wasp extracellular superoxide dismutases. We implemented either one-time feeding to the younger instar larvae or spraying once on the corn leaves, to effectively control the invading pest Spodoptera frugiperda. This highlights the conserved principle of "biological pest control," as elucidated by the triple interaction of parasitoid-bracovirus-host in a cooperation strategy of bracovirus against its pest host.


Assuntos
Polydnaviridae , Vespas , Animais , Spodoptera , Polydnaviridae/genética , Interações Hospedeiro-Parasita , Larva
7.
Front Immunol ; 14: 1280007, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143760

RESUMO

Background: Anaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK+ ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment. Case presentation: The adolescent patient received autologous T cells containing sequences encoding VH domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023. Conclusion: Taken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK+ ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment. Trial registration number: NCT04767308.


Assuntos
Linfoma Anaplásico de Células Grandes , Receptores de Antígenos Quiméricos , Adolescente , Humanos , Diagnóstico Diferencial , Linfoma Anaplásico de Células Grandes/terapia , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores Proteína Tirosina Quinases/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/uso terapêutico , Linfócitos T/patologia
8.
Ann Hematol ; 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37749317

RESUMO

Post-transplant lymphoproliferative disorder (PTLD) is a common secondary malignancy after transplantation, which has been recognized as a life-threatening complication. Hodgkin lymphoma (HL)-type PTLD is the rarest of four subtypes of PTLD, which has no treatment guideline due to its rarity. HL-type PTLD includes classical HL-type PTLD (cHL-PTLD) and HL-like PTLD. In our study, we reported the case of successful treatment using brentuximab vedotin (BV) plus sirolimus for a patient with classical HL-type PTLD in detail. Lymph node biopsy showed a picture of classical HL with mixed cellularity subtype, and immunophenotyping suggested CD30 strong positivity. Due to his impaired physical condition, we decided against intensive chemotherapy and started BV treatment with immunosuppressive agents switched to sirolimus. The 66-year-old patient with cHL-PTLD had achieved a durable complete remission for over a 1-year follow-up period. Additionally, we analyzed the clinical profile and outcomes in PTLD patients who used BV monotherapy or combined therapy by literature review. In summary, this case-based review might provide clues that treatment of cHL-PTLD with new modalities such as BV monotherapy or combination therapy, together with improvements in the immunosuppressive regimens like sirolimus, might be a feasible and chemotherapy-free approach, but warrants further evaluation in a larger patient cohort.

9.
Nucl Med Commun ; 44(2): 142-149, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36630218

RESUMO

AIM: The urokinase plasminogen activator receptor (uPAR) is a promising biomarker for cancer diagnosis and therapy. We herein fabricated a new type of uPAR-targeted imaging probe Al18F-NOTA-VC and preliminarily evaluated its potential application in PET imaging of the glioma model in vivo. METHODS: Peptide VC was synthesized and identified by MALDI-TOF-MS. The IC50 between VC/precursor NOTA-VC and uPAR was then determined before the synthesis and purification of Al18F-NOTA-VC, followed by further studies of in-vitro properties of Al18F-NOTA-VC. Meanwhile, the AE105-based probe followed a similar procedure in-vitro test. Finally, the PET imaging properties, including uPAR-targeting ability and the metabolism of Al18F-NOTA-VC, were investigated. RESULTS: The VC and NOTA-VC were obtained successfully and demonstrated a good affinity with uPAR. Followed by Al18F labeling successfully, excellent properties, including the serum stability, water solubility, and specificity of Al18F-NOTA-VC, were obtained in-vitro test compared with AE105 based probe. An excellent tumor uptake and renal excretion data of Al18F-NOTA-VC were acquired from in-vivo U87MG tumor model PET imaging, consistent with the subsequent biodistribution study. CONCLUSION: In addition to the excellent specificity and high tumor/normal tissue contrast for uPAR-targeted PET imaging of U87MG tumor, Al18F-NOTA-VC possessed promising clearance ability by renal system route. These excellent properties facilitated Al18F-NOTA-VC to be a promising imaging agent for uPAR high-expressing tumors and, thus, provided a paradigm for developing peptide-based probes for uPAR-associated disease diagnosis.


Assuntos
Glioblastoma , Humanos , Glioblastoma/diagnóstico por imagem , Glioblastoma/metabolismo , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Distribuição Tecidual , Linhagem Celular Tumoral , Peptídeos/química , Tomografia por Emissão de Pósitrons/métodos , Imagem Molecular
10.
Ecology ; 104(4): e3981, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36695044

RESUMO

Tree roots not only acquire readily-usable soil nutrients but also affect microbial decomposition and manipulate nutrient availability in their surrounding soils, that is, rhizosphere effects (REs). Thus, REs challenge the basic understanding of how plants adapt to the environment and co-exist with other species. Yet, how REs vary among species in response to species-specific bulk soil nutrient cycling is not well-known. Here, we studied how plant-controlled microbial decomposition activities in rhizosphere soils respond to those in their corresponding bulk soils and whether these relations depend on species-specific nutrient cycling in the bulk soils. We targeted 55 woody species of different clades and mycorrhizal types in three contrasting biomes, namely a temperate forest, a subtropical forest, and a tropical forest. We found that microbial decomposition activities in rhizosphere soils responded linearly to those in their corresponding bulk soils at the species level. Thereafter, we found that REs (parameters in rhizosphere soils minus those in corresponding bulk soils) of microbial decomposition activities had negative linear correlations with microbial decomposition activities in corresponding bulk soils. A multiple factor analysis revealed that soil organic carbon, total nitrogen, and soil water content favored bulk soil decomposition activities in all three biomes, showing that the magnitude of REs varied along a fast-slow nutrient cycling spectrum in bulk soils. The species of fast nutrient cycling in their bulk soils tended to have smaller or even negative REs. Therefore, woody plants commonly utilize both positive and negative REs as a nutrient-acquisition strategy. Based on the trade-offs between REs and other nutrient-acquisition strategies, we proposed a push and pull conceptual model which can bring plant nutrient-acquisition cost and plant carbon economics spectrum together in the future. This model will facilitate not only the carbon and nutrient cycling but also the mechanisms of species co-existence in forest ecosystems.


Assuntos
Ecossistema , Rizosfera , Solo , Carbono/análise , Plantas , Nutrientes/análise , Microbiologia do Solo , Raízes de Plantas
11.
Anal Chim Acta ; 1237: 340617, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36442943

RESUMO

Neutrophil elastase (NE) is an important regulator of immune response and is widely regarded as a biomarker for inflammatory diseases. To date, all the NE probe is designed by linking pentafluoropropionyl and amino-containing fluorophores through amide bond. This method is limited by the fluorophores, which must contain amino functional groups. To overcome this problem, we use the self-immolative group to convert hydroxyl groups to fluorophores HFC (4-trifluoromethyl-7-hydroxyl coumarin) into amino groups, and to connect recognition groups (pentafluoropropionyl) to construct a novel NE fluorescent probe HFC-NE. Predictably, HFC-NE can detect NE activity selectively and sensitively with many advantages, such as good water solubility and biocompatibility, high fluorescence enhancement and high affinity. Besides, HFC-NE is successfully applied to real-time and specific detection of NE activity in living cells and zebrafish models. These excellent outcomes confirmed that this strategy based on self-immolative group is a useful method to design more NE fluorescent probes.


Assuntos
Corantes Fluorescentes , Elastase de Leucócito , Animais , Peixe-Zebra , Fluorescência , Ionóforos
12.
Front Neurol ; 13: 971673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090860

RESUMO

Objective: To analyze the risk factors associated with adverse events after carotid endarterectomy (CEA) in patients with unilateral severe carotid stenosis and contralateral occlusion. Methods: Patients were recruited for CEA between August 2014 and February 2020. CEA was performed under general anesthesia. The carotid clamp time (CCT; long CCT: >20 min) is defined as the period between clamp-on and clamp-off for the stenotic carotid artery. The perioperative factors and postoperative adverse events were recorded. All patients were followed up for 1 year after CEA. Results: Sixty subjects (65.8 ± 7.2 years; 54 males) were included. Patients with adverse events had significantly longer CCT than those without adverse events (60% vs. 40%, P = 0.013). Univariate logistic regression analysis showed that a history of diabetes was significantly associated with adverse events (OR, 0.190; 95% CI, 0.045-0.814; P = 0.025); long CCT was significantly associated with adverse events (OR, 8.500; 95% CI, 1.617-44.682; P = 0.011). After adjusting for confounding factors, including age, sex, BMI, diabetes, PSV, long CCT, non-use of shunt, and history of stroke or TIA, the associations between diabetes and adverse events (OR, 0.113; 95% CI, 0.013-0.959; P = 0.046) were statistically significant; the associations between long CCT and adverse events (OR, 1.301; 95% CI, 1.049-1.613; P = 0.017) were statistically significant. Conclusions: A longer carotid clamp time (>20 min) and a history of diabetes may increase the risk of adverse events in patients with unilateral severe carotid stenosis and contralateral occlusion after CEA. With good preoperative evaluation and intraoperative monitoring, the use of shunts may not be needed intraoperatively in patients with unilateral severe carotid stenosis and contralateral occlusion.

13.
J Control Release ; 350: 435-447, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36030991

RESUMO

The cross-talk between hyperproliferative keratinocytes and activated immune cells is responsible for the progression of psoriasis. The strategy to alleviate psoriasis through inhibiting the abnormal proliferation of keratinocytes remains challenging due to limited therapeutic effects and low skin penetration of drugs. Herein we designed an ultrasound-triggered phase-transition nanodroplet that could produce cavitation to enhance skin penetration and effectively generate reactive oxygen species (ROS) to induce keratinocyte apoptosis for psoriasis treatment. After ultrasound stimulation, the perfluoro-n-pentane (PFP) liquid core of the nanodroplets vaporized, and the Haematoporphyrin monomethyl ether (HMME) encapsulated in the nanodroplets generated plenty of intracellular ROS which caused the apoptosis of HaCat cells through inducing mitochondrial dysfunction. In addition, the blank nanodroplets successfully inhibited the secretion of IL-6 and TNF-α from macrophages and dendritic cells in vitro due to the anti-inflammatory effect of POPG. For the skin penetration test, the phase-transition nanodroplets could effectively accumulate in the epidermis of the skin and generate intracellular ROS. The in-vivo anti-psoriasis experiment demonstrated that the phase-transition nanodroplets relieved the symptoms of psoriasis lesion and inhibited epidermal hyperplasia through induction of cell apoptosis under ultrasound irritation. Meanwhile, the inflammatory cytokines in the skin lesion almost decreased to the normal baseline level after SDT. Collectively, this study demonstrated a new strategy to inhibit keratinocyte hyperproliferation for psoriasis management based on sonodynamic responded nanodroplets.


Assuntos
Psoríase , Fator de Necrose Tumoral alfa , Anti-Inflamatórios/uso terapêutico , Éteres/farmacologia , Éteres/uso terapêutico , Humanos , Hiperplasia/tratamento farmacológico , Hiperplasia/patologia , Interleucina-6 , Queratinócitos , Psoríase/tratamento farmacológico , Psoríase/patologia , Espécies Reativas de Oxigênio
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 281: 121563, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35810672

RESUMO

Neutrophil elastase (NE), a serine proteinase, is a significant biomarker which is closely related to the progress of diseases. However, only few probes have been reported for detection of NE activity and cell imaging. And these probes have exhibited small Stokes shift, which leads to high fluorescence interferences. Furthermore, only one probe among them is able to image NE in vivo successfully. To overcome the above problems, we designed a novel coumarin-based fluorescent probe HNCOU-NE with large Stokes shift to visualize NE activity in living cells and zebrafish. The new probe HNCOU-NE for NE contains fluorophore HNCOU as the reporter and pentafluoroethyl as the enzyme-active trigger moiety. As expected, HNCOU-NE displays perfect detecting performance for sensing of NE, including good water solubility, large Stokes shift, high affinity and wide linear response concentration. In addition, HNCOU-NE has been successfully utilized for NE real-time detection and imaging in different living cells, exhibiting low cytotoxicity and excellent biocompatibility. Most importantly, endogenous NE fluorescence imaging experiments reveals that HNCOU-NE can distinguish liver cancer cells (HepG2) and other cells (293T, HeLa and SKOV3), illustrating its specific ability to diagnose liver cancer cells. Besides, probe HNCOU-NE also has the ability to specifically detect endogenous NE activity in living zebrafish. All the results indicate that HNCOU-NE is a valuable probe for qualitative and quantitative sensing of NE activity in vitro and in vivo.


Assuntos
Corantes Fluorescentes , Neoplasias Hepáticas , Animais , Cumarínicos , Células HeLa , Humanos , Elastase de Leucócito , Peixe-Zebra
15.
Front Immunol ; 13: 901593, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664011

RESUMO

A typical characteristics of polydnavirus (PDV) infection is a persistent immunosuppression, governed by the viral integration and expression of virulence genes. Recently, activation of caspase-3 by Microplitis bicoloratus bracovirus (MbBV) to cleave Innexins, gap junction proteins, has been highlighted, further promoting apoptotic cell disassembly and apoptotic body (AB) formation. However, whether ABs play a role in immune suppression remains to be determined. Herein, we show that ABs transmitted immunosuppressive signaling, causing recipient cells to undergo apoptosis and dismigration. Furthermore, the insertion of viral-host integrated motif sites damaged the host genome, stimulating eIF5A nucleocytoplasmic transport and activating the eIF5A-hypusination translation pathway. This pathway specifically translates apoptosis-related host proteins, such as P53, CypA, CypD, and CypJ, to drive cellular apoptosis owing to broken dsDNA. Furthermore, translated viral proteins, such Vank86, 92, and 101, known to complex with transcription factor Dip3, positively regulated DHYS and DOHH transcription maintaining the activation of the eIF5A-hypusination. Mechanistically, MbBV-mediated extracellular vesicles contained inserted viral fragments that re-integrated into recipients, potentially via the homologous recombinant repair system. Meanwhile, this stimulation regulated activated caspase-3 levels via PI3K/AKT 308 and 473 dephosphorylation to promote apoptosis of granulocyte-like recipients Sf9 cell; maintaining PI3K/AKT 473 phosphorylation and 308 dephosphorylation inhibited caspase-3 activation leading to dismigration of plasmatocyte-like recipient High Five cells. Together, our results suggest that integration-mediated eIF5A hypusination drives extracellular vesicles for continuous immunosuppression.


Assuntos
Vesículas Extracelulares , Polydnaviridae , Caspase 3 , Fosfatidilinositol 3-Quinases , Polydnaviridae/fisiologia , Proteínas Proto-Oncogênicas c-akt
16.
Artigo em Inglês | MEDLINE | ID: mdl-35657807

RESUMO

Redox regulation is an inherent feature of nature and plays a crucial role in the transport of ions/small molecules. However, whether redox status affects the biomolecule transport remains largely unknown. To explore the effects of redox status on biomolecule transport, herein, we constructed a glutathione/glutathione disulfide (GSH/GSSG)-driven and pillar[5]arene (P5)-modified artificial nanochannel for protein transport. The results indicate that hemoglobin (Hb) protein is selectively and effectively transported across the GSH-driven P5-modified nanochannel, which suggests that the redox status of the nanochannel could affect the process of protein transport. Therefore, this redox-driven nanochannel could provide a potential application for biomolecule detection and redox-controllable biomolecular drug release.

17.
Artigo em Inglês | MEDLINE | ID: mdl-35399638

RESUMO

Diabetes seriously endangers human health and causes a huge economic burden. With the improvement of people's living standard, the prevalence of diabetes is getting higher and higher, and age is becoming younger. It is an increasingly serious global problem. Therefore, it is imperative to find the drugs to treat diabetes. Ethnic medicine is an important part of the world's medicinal treasure house and has its own unique system. This study systematically combined the theoretical understanding of the prevention and treatment of diabetes of Tibetan, Mongolian, Miao, Dai, Uygur, and Yi people by searching the existing literature studies published until 2021, library collection resources (related ethnic monographs, medical books, standards of medicinal materials, etc.), CNKI, PubMed, and other databases and collected and sorted the relevant medicines. A total of 112 kinds of ethnic medicines for the prevention and treatment of diabetes have been discovered, including plant medicines (105 kinds), animal medicines (6 kinds), and fungal medicines (1 kind). The composition of family and genus, medicinal parts, and life forms of medicinal plants were analyzed, and the number of drugs used in the prevention and treatment of diabetes in each ethnic group was statistically analyzed. The results showed that Rosaceae was at the top of the list, and the drugs used in underground parts accounted for 33.90% of the total, and the medicinal plants were mainly herbaceous, and the Mongolians have the largest number of diabetes medicines. In addition, CNKI, PubMed, and other databases selected "medicinal materials name," "diabetes," and "hypoglycemia" as keywords, the top 30 medicinal materials reported in existing literature were listed, and their Chinese name, the Latin name of the original plant, family and genus, nationality used, medicinal parts, and active ingredients related to the prevention and treatment of diabetes were introduced in detail. Among the 30 medicines, Astragalus membranaceus, Pueraria lobata, and Coptis chinensis are the most commonly used. Through literature research, this study summarized the existing theories of ethnic medicine for the prevention and treatment of diabetes, collected and sorted out ethnic medicine, clarified the potential mechanism of ethnic medicine, and provided effective data compilation. Ethnic medicine has a long history of treating diabetes, and there are abundant medicinal materials, to provide a new idea and basis for treating diabetes.

18.
AAPS PharmSciTech ; 23(3): 83, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35288813

RESUMO

Turmeric was the dried rhizome of Curcuma longa L., and its extract had important pharmacological effects such as anti-tumor, cholagogic, and antioxidant. However, curcuma extract had poor water solubility and low bioavailability, which had become the main limiting factor for its clinical application. The purpose of this study was to prepare PVP/VA-Poloxamer-188-curcuma extract solid dispersion (PAP-CSD) to improve the solubility and bioavailability of the curcuma extract. The intestinal absorption mechanism of solid dispersion of this extract was studied by one-way intestinal perfusion in rats. PAP-CSD,PVP/VA-curcuma extract solid dispersion (PA-CSD) and Poloxamer-188-curcuma extract solid dispersion (P-CSD) was able to improve the intestinal absorption of the curcuma extract (P < 0.05), and PAP-CSD (combined use of two carriers) was better than that of PA-CSD and P-CSD. CCK8 method was used to investigate the effects of the curcuma extract and PAP-CSD on the proliferation of hepatic stellate cells (HSC)-T6 cells. The inhibitory effect of PAP-CSD on the proliferation of HSC-T6 cells, related to the p38 MAPK pathway, was better than that of the curcuma extract.


Assuntos
Curcuma , Poloxâmero , Animais , Proliferação de Células , Perfusão , Extratos Vegetais/farmacologia , Ratos
20.
Hellenic J Cardiol ; 63: 32-39, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34147675

RESUMO

BACKGROUND: To investigate the effect of cholesterol accumulation in cells on the inflammatory process of acute myocardial infarction and cardiomyocytes and its mechanism. METHODS: Blood samples of 15 patients with myocardial infarction were clinically collected to detect enzyme levels of cholesterol and related myocardial parameters in the serum. Correlation analysis was carried out. At the cellular level, simulation of cholesterol entry and exit from cells was conducted by a liposome-loaded cholesterol model in this study, and BNP and inflammatory factors were detected with enzyme-linked immunosorbent assay. Moreover, to investigate the molecular mechanism of myocardial damage caused by cholesterol, Gramd1b and Prkaca of HL-1 were knocked down with small interference RNA technique. Then, inhibitor C3 was used to weaken RhoA activity to explore the level of cardiac muscle cell BNP in order to identify key protein target sites that may be involved in the process of cholesterol damage to cardiac muscle cells. RESULTS: Serum cholesterol concentration showed a significantly positive correlation with the levels of AST, CK, and LD in serum of patients with myocardial infarction. Cholesterol accumulation in cardiac muscle cells significantly increased the levels of BNP, inflammatory factors (IL-1ß, IL-6, TNF-α, and CCL-2) in cardiac muscle cells, which exacerbated cardiomyocyte damage. Conversely, cholesterol excretion caused significant downregulation of BNP and inflammatory factors. Moreover, after knocking down Gramd1b, the accumulation of cholesterol in myocardial cells decreased, the levels of BNP and inflammatory factors significantly reduced, and the degree of myocardial cell damage was weakened. Knockdown of Prkaca inhibited RhoA activity and reversed cholesterol-induced elevation of BNP and inflammatory factors. CONCLUSION: ASTER B-mediated intracellular accumulation of cholesterol in cardiac muscle cells may cause cardiomyocyte damage and inflammatory factor infiltration through PKA-Ca2+-RhoA pathways.


Assuntos
Infarto do Miocárdio , Miócitos Cardíacos , Colesterol , Humanos , Miocárdio
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