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1.
Nano Lett ; 24(15): 4354-4361, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38563599

RESUMO

The recent focus of cancer therapeutics research revolves around modulating the immunosuppressive tumor microenvironment (TME) to enhance efficacy. The tumor stroma, primarily composed of cancer-associated fibroblasts (CAFs), poses significant obstacles to therapeutic penetration, influencing resistance and tumor progression. Reprogramming CAFs into an inactivated state has emerged as a promising strategy, necessitating innovative approaches. This study pioneers the design of a nanoformulation using pioglitazone, a Food and Drug Administration-approved anti-diabetic drug, to reprogram CAFs in the breast cancer TME. Glutathione (GSH)-responsive dendritic mesoporous organosilica nanoparticles loaded with pioglitazone (DMON-P) are designed for the delivery of cargo to the GSH-rich cytosol of CAFs. DMON-P facilitates pioglitazone-mediated CAF reprogramming, enhancing the penetration of doxorubicin (Dox), a therapeutic drug. Treatment with DMON-P results in the downregulation of CAF biomarkers and inhibits tumor growth through the effective delivery of Dox. This innovative approach holds promise as an alternative strategy for enhancing therapeutic outcomes in CAF-abundant tumors, particularly in breast cancer.


Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Nanopartículas , Humanos , Feminino , Pioglitazona/farmacologia , Pioglitazona/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Microambiente Tumoral
2.
Ann Med Surg (Lond) ; 86(4): 2357-2360, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576994

RESUMO

Introduction and importance: Intraspinal tuberculoma is rare and challenging situation, which results in serious neurological dysfunctions. Case presentation: This case report shows an intraspinal tuberculoma with osseous involvement in a 31-year-old male patient with subacute progressing neurologic deficit. His medical history included tuberculosis of pulmonary and intestinal 8 years previously, at which time he had been treated with intestinal obstruction operation and antituberculosis treatment. A quadruple antituberculosis treatment was carried out after admission; however, his neurological condition was steadily worsening. He underwent debulking of mass for decompression and pathological analysis revealed intraspinal tuberculoma. The patient was prescribed a 12-month course of antituberculosis therapy, and a good clinical outcome was obtained subsequently. Clinical discussion: This case was treated by microsurgical resection and antituberculosis therapy, and the outcome was favourable. Conclusion: Intraspinal tuberculoma should be considered when an intraspinal mass is found with a history of tuberculosis, it can be effectively diagnosed by MRI and treated by the combination of medical and surgical treatments.

3.
Ann Med Surg (Lond) ; 86(3): 1794-1797, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38463120

RESUMO

Introduction and importance: Contralateral subdural effusion (CSDE) is a rare complication secondary to decompressive craniectomy (DC), which can lead to encephalocele and neurologic deterioration. The authors report a case that confirm the existence of unidirectional membrane valve, and cranioplasty is an effective treatment for CSDE. Case presentation: The authors reported a case of 43-year-old female was diagnosed with ruptured intracranial aneurysm and treated with interventional embolization. She underwent DC because of postoperative cerebral infarction subsequently. Her conscious state deteriorated accompanied by encephalocele in postoperative 2 week. A craniocerebral computed tomography (CT) confirmed the diagnosis of CSDE with cerebral hernia. A compression bandaging of the skull defect was applicated, whereas, her conscious state progressive deteriorated. She was transferred to the author's hospital where she underwent burr-hole drainage and clinical symptom has been improved. However, a relapse of CSDE was observed after the removal of drainage tube. Continuous lumbar drainage was employed, and which was ineffective for CSDE in this case. Finally, she underwent cranioplasty, with the help of drainage of subdural effusion, CSDE was completely resolved. Clinical discussion: CSDE is occasionally observed in patients after DC. Intracranial pressure (ICP) gradient and unidirectional membrane valve are the possible mechanisms of CSDE. At present, there is no optimal therapy for CSDE. For symptomatic CSDE patients, one or more treatment measures should be applicated. Conclusion: Cranioplasty is one of the curative and optimal method to treat symptomatic CSDE patients, early cranioplasty combined with burr-hole drainage should be performed for conservative treatment failed and intractable cases.

4.
Materials (Basel) ; 17(5)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38473660

RESUMO

In this study, the effects of Z-0°, Z-67°, Z-90°, I-67°, and S-67° scanning strategies on the surface morphology, microstructure, and corrosion resistance of the specimens in SLM316L were systematically studied. The results show that the partition scanning path can effectively improve the manufacturing quality of the specimen, reduce the cumulative roughness layer by layer, and increase the density of the specimen. The scan path of the island partition of the fine partition is better than that of the strip partition; moreover, the 67° rotation between each layer reduces the accumulation of the height difference of the melt pool, fills the scanning gap of the previous layer, and improves the molding quality of the sample. Electrochemical tests were performed in an aqueous solution of NaCl (3.5 wt%), including open-circuit potential (OCP), dynamic potential polarization, and electrochemical impedance spectroscopy (EIS). The results show that the specimen with a 67° rotation between each layer achieves stability of the surface potential in a short time, and the I-67° specimen exhibits good corrosion performance, while the Z-0° specimen has the worst corrosion resistance.

5.
J Agric Food Chem ; 72(10): 5416-5427, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477043

RESUMO

Schizophyllum commune, a fleshy fungus, is an important medicinal and food-homologous mushroom in China. In this work, eight undescribed sesquiterpenes schizomycins A-H (1-8) and one new meroterpenoid schizomycin I (9) together with three known analogues (10-12) were isolated from fruiting bodies of S. commune. Their planar structures were established by extensive spectroscopic and mass spectrometric data. The absolute configurations of compounds 1, 2, and 4 were determined by single crystal X-ray diffraction, and compounds 3 and 5-9 were confirmed by electronic circular dichroism calculations. Anti-inflammatory activities of all isolated compounds were evaluated for their inhibitory effects on IL-6 and IL-1ß production in RAW 264.7 cells. Among them, compound 7 exhibited significant IL-6 inhibitory activity with an IC50 value of 3.6 µM. The results of molecular docking showed that compound 7 interacts with amino acid residues (Gly117, Lys118, Asp120, Thr166, and Try168) of the IL-6 receptor protein through hydrogen bonding.


Assuntos
Ascomicetos , Schizophyllum , Sesquiterpenos , Schizophyllum/química , Schizophyllum/metabolismo , Interleucina-6/metabolismo , Simulação de Acoplamento Molecular , Dicroísmo Circular , Carpóforos , Sesquiterpenos/metabolismo , Estrutura Molecular
6.
Eur J Med Chem ; 269: 116314, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38527379

RESUMO

OSMAC strategy is a useful tool for discovering series of metabolites from microorganism. Five new sambutoxin derivatives (1-2, 4, 8-9), together with seven known compounds (3, 5-7, 10-12), were isolated from Talaromyces sp. CY-3 under OSMAC strategy and guidance of molecular networking. Their planar structures and absolute configurations were determined by NMR, HRESIMS, ECD spectra and common biosynthetic pathway. In bioassay, compounds 1-12 showed cytotoxicity to tumor cell lines with IC50 values in the range of 1.76-49.13 µM. The antitumor molecular mechanism of 10 was also explored. In vitro compound 10 significantly inhibited the growth and proliferation of two lung cancer cell lines (A549 and H1703). Furthermore, colony formation, EdU analysis, flow cytometry and Western blot analysis showed that 10 could induce cell cycle arrest in G0/G1 phase by promoting the expression of p53 and p21. The molecular mechanism of its antitumor effects in vitro is that 10 arrests the cell cycle by activating the p21/CyclinD1/Rb signaling pathway and the p53 pathway. Our results identified a lead small molecule compound with efficient antitumor growth and proliferation activity.


Assuntos
Antineoplásicos , Piridinas , Talaromyces , Talaromyces/química , Antineoplásicos/química , Proteína Supressora de Tumor p53 , Linhagem Celular Tumoral , Estrutura Molecular
7.
Meat Sci ; 211: 109440, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38324956

RESUMO

This study aimed to investigate the effects of exercise on muscle fiber conversion, muscle development and meat quality in the biceps femoris (BF) muscle of Sunit sheep. Twelve Sunit sheep with similar body weight were divided into two groups: control group (C group) and exercise group (E group), E group lambs underwent 6 km of exercise training per day for 90 d. The findings revealed that compared with the C group, exercise training enhanced the expression of MyHC IIa mRNA, decreased the number ratio of type IIB muscle fibers and the expression of MyHC IIb mRNA (P < 0.05). Furthermore, the E group lamb displayed higher creatine kinase (CK) activity, and lactic acid levels (P < 0.05), while glycogen content and lactic dehydrogenase (LDH) activity showed opposite trends (P < 0.05). Exercise significantly up-regulated the mRNA expression of AMP-activated protein kinase α1 (AMPKα1), sirtuin1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), cytochrome c oxidase IV (COX IV), protein kinase B (Akt), mammalian target of rapamycin (mTOR) and p70 Ribosomal S6 Kinase 1 (p70s6k1) (P < 0.05), suggesting exercise promoted muscle fiber conversion by mediating AMPK/PGC-1α pathway, and improved skeletal muscle development via Akt/mTOR pathway. Besides, backfat thickness and pH45min value in the E group decreased significantly, while the pH24, a*, and shear force value increased significantly (P < 0.05). To conclude, this study suggested that exercise training can be used to alter muscle fiber characteristics and muscle development in lamb production.


Assuntos
Músculo Esquelético , Proteínas Proto-Oncogênicas c-akt , Animais , Ovinos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Serina-Treonina Quinases TOR/metabolismo , RNA Mensageiro/metabolismo , Carne , Desenvolvimento Muscular , Mamíferos/genética , Mamíferos/metabolismo
8.
Heliyon ; 10(4): e26185, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38404864

RESUMO

Background: We aimed to establish and validate a prognostic nomogram model for improving the prediction of 30-day mortality of gastrointestinal bleeding (GIB) in critically ill patients with severe sepsis. Methods: In this retrospective study, the current retrospective cohort study extracted data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, then partitioned the cohort randomly into training and validation subsets. The cohort was partitioned into training and validation subsets randomly. Our primary endpoint was 30-day all-cause mortality. To reduce data dimensionality and identify predictive variables, the least absolute shrinkage and selection operator (LASSO) regression was employed. A prediction model was constructed by multivariate logistic regression. Model performance was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results: The analysis included 1435 total patients, comprising 1005 in the training cohort and 430 in the validation cohort. We found that age, smoking status, glucose, (BUN), lactate, Sequential Organ Failure Assessment (SOFA) score, mechanical ventilation≥48h (MV), parenteral nutrition (PN), and chronic obstructive pulmonary disease (COPD) independently influenced mortality in sepsis patients with concomitant GIB. The C-indices were 0.746 (0.700-0.792) and 0.716 (0.663-0.769) in the training and validation sets, respectively. Based on the area under the curve (AUC) and DCA, the nomogram exhibited good discrimination for 30-day all-cause mortality in sepsis with GIB. Conclusions: For sepsis patients complicated with GIB, we created a unique nomogram model to predict the 30-day all-cause mortality. This model could be a significant therapeutic tool for clinicians in terms of personalized treatment and prognosis prediction.

9.
Int J Cardiol Heart Vasc ; 50: 101341, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38313452

RESUMO

Background: Early identification of patients at high risk of operative mortality is important for acute type A aortic dissection (TAAD). We aimed to investigate whether patients with distinct risk stratifications respond differently to anti-inflammatory pharmacotherapy. Methods: From 13 cardiovascular hospitals, 3110 surgically repaired TAAD patients were randomly divided into a training set (70%) and a test set (30%) to develop and validate a risk model to predict operative mortality using extreme gradient boosting. Performance was measured by the area under the receiver operating characteristic curve (AUC). Subgroup analyses were performed by risk stratifications (low versus middle-high risk) and anti-inflammatory pharmacotherapy (absence versus presence of ulinastatin use). Results: A simplified risk model was developed for predicting operative mortality, consisting of the top ten features of importance: platelet-leukocyte ratio, D-dimer, activated partial thromboplastin time, urea nitrogen, glucose, lactate, base excess, hemoglobin, albumin, and creatine kinase-MB, which displayed a superior discrimination ability (AUC: 0.943, 95 % CI 0.928-0.958 and 0.884, 95 % CI 0.836-0.932) in the derivation and validation cohorts, respectively. Ulinastatin use was not associated with decreased risk of operative mortality among each risk stratification, however, ulinastatin use was associated with a shorter mechanical ventilation duration among patients with middle-high risk (defined as risk probability >5.0 %) (ß -1.6 h, 95 % CI [-3.1, -0.1] hours; P = 0.048). Conclusion: This risk model reflecting inflammatory, coagulation, and metabolic pathways achieved acceptable predictive performances of operative mortality following TAAD surgery, which will contribute to individualized anti-inflammatory pharmacotherapy.

10.
Sci Rep ; 14(1): 3177, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326344

RESUMO

At present, clinical outcomes of pancreatic cancer patients are still poor. New therapeutic targets for pancreatic cancer are urgently needed. Previous studies have indicated that Microtubule Associated Monooxygenase, Calponin and LIM Domain Containing 2 (MICAL2) is highly expressed in many tumors and promotes tumor progression. However, the role played by MICAL2 in pancreatic cancer remains unclear. Based on gene expression and clinical information from multiple datasets, we used comprehensive bioinformatics analysis in combination with tissue microarray to explore the function and clinical value of MICAL2. The results showed that MICAL2 was highly expressed in pancreatic cancer tissue and exhibited potential diagnostic capability. High expression of MICAL2 was also associated with poor prognosis and acted as an independent prognostic factor. MICAL2, mainly expressed in fibroblasts of pancreatic cancer, was closely related to metastasis and immune-related features, such as epithelial-mesenchymal transformation, extracellular cell matrix degradation, and inflammatory response. Furthermore, higher MICAL2 expression in pancreatic cancer was also associated with an increase in cancer-associated fibroblasts as well as M2 macrophage infiltration, and a reduction in CD8 + T cell infiltration, thereby facilitating the formation of an immunosuppressive microenvironment. Our results helped elucidate the clinical value and function in metastasis and immunity of MICAL2 in pancreatic cancer. These findings provided potential clinical strategies for diagnosis, targeted therapy combination immunotherapy, and prognosis in patients with pancreatic cancer.


Assuntos
Oxigenases de Função Mista , Neoplasias Pancreáticas , Humanos , Biomarcadores , Calponinas , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Prognóstico , Microambiente Tumoral/genética
11.
Food Res Int ; 176: 113837, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38163689

RESUMO

Under natural physiological conditions, anthocyanins can keep bright and stable color for a long time due to the relatively stable acid-base environment of plant vacuoles and the copigmentation from various copigment substances, such as polyphenols, nucleotides, metallic ions and other substances. Therefore, the copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale yellow organic molecules (copigments). These interactions are usually manifested in both hyperchromic effect and bathochromic shifts. In addition to making anthocyanins more stable, the copigmentation also could make an important contribution to the diversification of their tone. Based on the molecular structure of anthocyanins, this review focuses on the interaction mode of auxochrome groups or copigments with anthocyanins and their effects on the chemical and color stability of anthocyanins.


Assuntos
Antocianinas , Polifenóis , Antocianinas/química , Estrutura Molecular , Íons
12.
Int J Mol Med ; 53(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38214365

RESUMO

Following the publication of this article, a concerned reader drew to the Editor's attention that, in Fig. 9C on p. 2478 showing the results of Transwell invasion assay experiments, unexpected areas of similarity were identified in terms of the cellular patterns revealed both within the data panels for the six different experiments portrayed in this figure, and comparing among them. After having conducted an internal investigation, the Editor of International Journal of Molecular Medicine has reached the conclusion that the overlapping sections of data shown in this figure were unlikely to have arisen by coincidence. Therefore, on the grounds of a lack of confidence in the integrity of these data, the Editor has decided that the article should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused, and thanks the interested reader for drawing this matter to our attention. [International Journal of Molecular Medicine 42: 2469­2480, 2018; DOI: 10.3892/ijmm.2018.3853].

13.
Chem Commun (Camb) ; 60(11): 1404-1407, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38174640

RESUMO

A high temperature phenyl-mediated addition-cyclization-dehydrogenation mechanism to form peri-fused polycyclic aromatic hydrocarbon (PAH) derivatives-illustrated through the formation of dibenzo[e,l]pyrene (C24H14)-is explored through a gas-phase reaction of the phenyl radical (C6H5˙) with triphenylene (C18H12) utilizing photoelectron photoion coincidence spectroscopy (PEPICO) combined with electronic structure calculations. Low-lying vibrational modes of dibenzo[e,l]pyrene exhibit out-of-plane bending and are easily populated in high temperature environments such as combustion flames and circumstellar envelopes of carbon stars, thus stressing dibenzo[e,l]pyrene as a strong target for far-IR astronomical surveys.

14.
Open Heart ; 10(2)2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38070883

RESUMO

OBJECTIVE: Cabrol shunt has been introduced for surgical repair of type A aortic dissection (TAAD) without robust evidence supporting its routine preventive use. METHODS: Adult patients with TAAD from China 5A study were included if surgically repaired between 2016 and 2022. Primary outcome was operative mortality according to Society of Thoracic Surgeons criterion. Overall, we compared clinical outcomes in patients with and without Cabrol shunt, and subgroup analysis were further examined between Cabrol shunt and outcome among patients with or without root replacement. RESULTS: 3283 patients were finally identified for analysis, with median age of 51 (IQR 41-59) years, 2389 men, and 2201 treated with Cabrol shunt technique. Cabrol shunt-treated patients were more severely ill before surgery than those without Cabrol shunt. Overall, the rate of operative mortality was 6.6% (146/2201 in Cabrol shunt group and 71/1082 in non-Cabrol shunt group), with no association between Cabrol shunt and operative mortality (OR 1.012 (95% CI 0.754 to 1.357); p=0.938). Stratified by root replacement, Cabrol shunt was associated with similar risk of operative mortality either in patients without root replacement (OR 1.054 (0.747 to 1.487); p=0.764) or in patients with root replacement (OR 1.194 (0.563 to 2.536); p=0.644) (P interaction=0.765). Results were similar in multiple sensitivity analysis. CONCLUSION: Cabrol shunt was not associated with either a greatly lowered or an increased risk of operative mortality, regardless of aortic root replacement. Our study did not support the use of Cabrol shunt as a routine preventive strategy in the treatment of TAAD. TRIAL REGISTRATION NUMBER: NCT04398992.


Assuntos
Dissecção Aórtica , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aorta/cirurgia , China
15.
Int J Mol Sci ; 24(22)2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-38003285

RESUMO

Four new sorbicillinoids, named trichodermolide E (1), trichosorbicillin J (2), bisorbicillinolide B (3), and demethylsorbiquinol (5), together with eight known compounds (4, 6-12), were isolated from the cultures of the mangrove-derived fungus Trichoderma reesei BGRg-3. The structures of the new compounds were determined by analyzing their detailed spectroscopic data, while the absolute configurations were further determined through electronic circular dichroism calculations. Snatzke's method was additionally used to determine the absolute configurations of the diol moiety in 1. In a bioassay, compounds 7 and 10 performed greater inhibitory activities on interleukin-6 and interleukin-1ß than the positive control (dexamethasone) at the concentration of 25 µM. Meanwhile, compounds 5 and 6 showed potent effects with stronger inhibition than dexamethasone on IL-1ß at the same concentration.


Assuntos
Hypocreales , Trichoderma , Interleucina-6 , Interleucina-1beta , Trichoderma/química , Dicroísmo Circular , Dexametasona , Estrutura Molecular
16.
J Am Chem Soc ; 145(44): 23910-23917, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37883710

RESUMO

The merger of electrochemistry and transition metal catalysis has emerged as a powerful tool to join two electrophiles in an enantioselective manner. However, the development of enantioselective electroreductive cross-couplings of olefins remains a challenge. Inspired by the advantages of the synergistic use of electrochemistry with nickel catalysis, we present here a Ni-catalyzed enantioselective electroreductive cross-coupling of acrylates with aryl halides and alkyl bromides, which affords chiral α-aryl carbonyls in good to excellent enantioselectivity. Additionally, this catalytic reaction can be applied to (hetero)aryl chlorides, which is difficult to achieve by other methods. The combination of cyclic voltammetry analysis with electrode potential studies suggests that the NiI species activates aryl halides by oxidative addition and alkyl bromides by single-electron transfer.

17.
Cell Commun Signal ; 21(1): 308, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904190

RESUMO

BACKGROUND: Integrins are closely related to mechanical conduction and play a crucial role in the osteogenesis of human mesenchymal stem cells. Here we wondered whether tensile stress could influence cell differentiation through integrin αVß3. METHODS: We inhibited the function of integrin αVß3 of human mesenchymal stem cells by treating with c(RGDyk). Using cytochalasin D and verteporfin to inhibit polymerization of microfilament and function of nuclear Yes-associated protein (YAP), respectively. For each application, mesenchymal stem cells were loaded by cyclic tensile stress of 10% at 0.5 Hz for 2 h daily. Mesenchymal stem cells were harvested on day 7 post-treatment. Western blotting and quantitative RT-PCR were used to detect the expression of alkaline phosphatase (ALP), RUNX2, ß-actin, integrin αVß3, talin-1, vinculin, FAK, and nuclear YAP. Immunofluorescence staining detected vinculin, actin filaments, and YAP nuclear localization. RESULTS: Cyclic tensile stress could increase the expression of ALP and RUNX2. Inhibition of integrin αVß3 activation led to rearrangement of actin filaments and downregulated the expression of ALP, RUNX2 and promoted YAP nuclear localization. When microfilament polymerization was inhibited, ALP, RUNX2, and nuclear YAP nuclear localization decreased. Inhibition of YAP nuclear localization could reduce the expression of ALP and RUNX2. CONCLUSIONS: Cyclic tensile stress promotes early osteogenesis of human mesenchymal stem cells via the integrin αVß3-actin filaments axis. YAP nuclear localization participates in this process of human mesenchymal stem cells. Video Abstract.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Humanos , Citoesqueleto de Actina/metabolismo , Diferenciação Celular , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Integrina alfaVbeta3/metabolismo , Células-Tronco Mesenquimais/metabolismo , Vinculina/metabolismo
18.
Vaccines (Basel) ; 11(9)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37766104

RESUMO

Current COVID-19 vaccines are effective countermeasures to control the SARS-CoV-2 virus pandemic by inducing systemic immune responses through intramuscular injection. However, respiratory mucosal immunization will be needed to elicit local sterilizing immunity to prevent virus replication in the nasopharynx, shedding, and transmission. In this study, we first compared the immunoprotective ability of a chimpanzee replication-deficient adenovirus-vectored COVID-19 vaccine expressing a stabilized pre-fusion spike glycoprotein from the ancestral SARS-CoV-2 strain Wuhan-Hu-1 (BV-AdCoV-1) administered through either aerosol inhalation, intranasal spray, or intramuscular injection in cynomolgus monkeys and rhesus macaques. Compared with intranasal administration, aerosol inhalation of BV-AdCoV-1 elicited stronger humoral and mucosal immunity that conferred excellent protection against SARS-CoV-2 infection in rhesus macaques. Importantly, aerosol inhalation induced immunity comparable to that obtained by intramuscular injection, although at a significantly lower dose. Furthermore, to address the problem of immune escape variants, we evaluated the merits of heterologous boosting with an adenovirus-based Omicron BA.1 vaccine (C68-COA04). Boosting rhesus macaques vaccinated with two doses of BV-AdCoV-1 with either the homologous or the heterologous C68-COA04 vector resulted in cross-neutralizing immunity against WT, Delta, and Omicron subvariants, including BA.4/5 stronger than that obtained by administering a bivalent BV-AdCoV-1/C68-COA04 vaccine. These results demonstrate that the administration of BV-AdCoV-1 or C68-COA04 via aerosol inhalation is a promising approach to prevent SARS-CoV-2 infection and transmission and curtail the pandemic spread.

19.
Nat Commun ; 14(1): 5601, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37699899

RESUMO

The immunomodulatory effects of ultraviolet B (UVB) radiation in human diseases have been described. Whether type 2 lung inflammation is directly affected by solar ultraviolet (UV) radiation is not fully understood. Here, we show a possible negative correlation between solar UVB radiation and asthmatic inflammation in humans and mice. UVB exposure to the eyes induces hypothalamus-pituitary activation and α-melanocyte-stimulating hormone (α-MSH) accumulation in the serum to suppress allergic airway inflammation by targeting group 2 innate lymphoid cells (ILC2) through the MC5R receptor in mice. The α-MSH/MC5R interaction limits ILC2 function through attenuation of JAK/STAT and NF-κB signaling. Consistently, we observe that the plasma α-MSH concentration is negatively correlated with the number and function of ILC2s in the peripheral blood mononuclear cells (PBMC) of patients with asthma. We provide insights into how solar UVB radiation-driven neuroendocrine α-MSH restricts ILC2-mediated lung inflammation and offer a possible strategy for controlling allergic diseases.


Assuntos
Asma , alfa-MSH , Humanos , Animais , Camundongos , Imunidade Inata , Leucócitos Mononucleares , Linfócitos , Inflamação , Pulmão
20.
Oncoimmunology ; 12(1): 2243112, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37577145

RESUMO

Group 2 innate lymphoid cells (ILC2s) are essential for orchestrating type 2 immune responses during allergic airway inflammation and infection. ILC2s have been reported to play a regulatory role in tumors; however, this conclusion is controversial. In this study, we showed that IL-33-activated ILC2s could boost CD8+ T-cell function through direct antigen cross-presentation. After activation by IL-33, ILC2s showed an enhanced potential to process antigens and prime CD8+ T cell activation. Activated ILC2s could phagocytose exogenous antigens in vivo and in vitro, promoting antigen-specific CD8+ T cell function to enhance antitumor immune responses. Administration of OVA-loaded ILC2s induces robust antitumor effects on the OVA-expressing tumor model. These findings suggested that the administration of tumor antigen-loaded ILC2s might serve as a potential strategy for cancer treatment.


Assuntos
Imunidade Inata , Linfócitos , Humanos , Interleucina-33 , Inflamação , Linfócitos T CD8-Positivos
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