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1.
Microorganisms ; 12(5)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38792773

RESUMO

Plant growth-promoting rhizobacterial strain FP607T was isolated from the rhizosphere of beets in Wuhan, China. Strain FP607T exhibited significant antagonism toward several phytopathogenic bacteria, indicating that FP607T may produce antimicrobial metabolites and has a stronger biocontrol efficacy against plant pathogens. Growth-promoting tests showed that FP607T produced indole-3-acetic acid (IAA), NH3, and ferritin. The genome sequence of strain FP607T was 6,590,972 bp long with 59.0% G + C content. The optimum temperature range was 25-30 °C, and the optimum pH was 7. The cells of strain FP607T were Gram-negative, short, and rod-shaped, with polar flagella. The colonies on the King's B (KB) agar plates were light yellow, smooth, and circular, with regular edges. A phylogenetic analysis of the 16S rRNA sequence and a multilocus sequence analysis (MLSA) showed that strain FP607T was most closely related to the type of strain Pseudomonas farris SWRI79T. Based on a polyphasic taxonomic approach, strain FP607T was identified as a novel species within the genus Pseudomonas, for which the name Pseudomonas wuhanensis sp. nov. was proposed. The type of strain used was FP607T (JCM 35688, CGMCC 27743, and ACCC 62446).

2.
Nano Lett ; 24(15): 4691-4701, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38588212

RESUMO

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Imunoterapia , Radioimunoterapia , Glucose , Glucose Oxidase , Imunossupressores , Ácido Láctico , Neoplasias/terapia , Linhagem Celular Tumoral
3.
Free Radic Biol Med ; 218: 26-40, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38570172

RESUMO

Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in ferroptosis by regulating the cellular antioxidant response and maintaining redox balance. However, compounds that induce ferroptosis through dual antioxidant pathways based on Nrf2 have not been fully explored. In our study, we investigated the impact of Gambogic acid (GA) on MCF-7 cells and HepG2 cells in vitro. The cytotoxicity, colony formation assay and cell cycle assay demonstrated potent tumor-killing ability of GA, while its effect was rescued by ferroptosis inhibitors. Furthermore, RNA sequencing revealed the enrichment of ferroptosis pathway mediated by GA. In terms of ferroptosis indicators detection, evidences for GA were provided including reactive oxygen species (ROS) accumulation, alteration in mitochondrial membrane potential (MMP), disappearance of mitochondrial cristae, lipid peroxidation induction, malondialdehyde (MDA) accumulation promotion, iron ion accumulation as well as glutathione (GSH)/thioredoxin (Trx) depletion. Notably, Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) successfully rescued GA-induced MDA accumulation. In terms of mechanism, Nrf2 was found to play a pivotal role in GA-induced ferroptosis by inducing protein alterations through the iron metabolism pathway and GSH/Trx dual antioxidant pathway. Furthermore, GA exerted good antitumor activity in vivo through GSH/Trx dual antioxidant pathway, and Fer-1 significantly attenuated its efficacy. In conclusion, our findings first provided new evidence for GA as an inducer of ferroptosis, and Nrf2-mediated GSH/Trx dual antioxidant system played an important role in GA-induced ferroptosis.


Assuntos
Antioxidantes , Ferroptose , Glutationa , Fator 2 Relacionado a NF-E2 , Quinoxalinas , Espécies Reativas de Oxigênio , Compostos de Espiro , Xantonas , Ferroptose/efeitos dos fármacos , Xantonas/farmacologia , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Glutationa/metabolismo , Animais , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Células MCF-7 , Células Hep G2 , Ensaios Antitumorais Modelo de Xenoenxerto , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Antineoplásicos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Cicloexilaminas/farmacologia , Fenilenodiaminas/farmacologia , Proliferação de Células/efeitos dos fármacos
4.
Clin Interv Aging ; 19: 613-626, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646591

RESUMO

Purpose: This study aims to investigate how the type of anesthesia used during major orthopedic surgery may impact adverse short-term postoperative outcomes depending on frailty. Methods: To conduct this investigation, we recruited individuals aged 65 years and older who underwent major orthopedic surgery between March 2022 and April 2023 at a single institution. We utilized the FRAIL scale to evaluate frailty. The primary focus was on occurrences of death or the inability to walk 60 days after the surgery. Secondary measures included death within 60 days; inability to walk without human assistance at 60 days; death or the inability to walk without human assistance at 30 days after surgery, the first time out of bed after surgery, postoperative blood transfusion, length of hospital stay, hospital costs, and the occurrence of surgical complications such as dislocation, periprosthetic fracture, infection, reoperation, wound complications/hematoma. Results: In a study of 387 old adult patients who had undergone major orthopedic surgery, 41.3% were found to be in a frail state. Among these patients, 262 had general anesthesia and 125 had neuraxial anesthesia. Multifactorial logistic regression analyses showed that anesthesia type was not linked to complications. Instead, frailty (OR 4.04, 95% CI 1.04 to 8.57, P< 0.001), age (OR 1.05, 95% CI 1.00-1.10, P= 0.017), and aCCI scores, age-adjusted Charlson Comorbidity Index, (OR 1.36, 95% CI 1.12 to 1.66, P= 0.002) were identified as independent risk factors for death or new walking disorders in these patients 60 days after surgery. After adjusting for frailty, anesthesia methods was not associated with the development of death or new walking disorders in these patients (P > 0.05). Conclusion: In different frail populations, neuraxial anesthesia is likely to be comparable to general anesthesia in terms of the incidence of short-term postoperative adverse outcomes.


Assuntos
Fragilidade , Tempo de Internação , Procedimentos Ortopédicos , Complicações Pós-Operatórias , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Anestesia Geral/efeitos adversos , Idoso Fragilizado , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Procedimentos Ortopédicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Fatores de Risco
6.
JACS Au ; 4(2): 441-453, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38425924

RESUMO

A small chemical modification of the nucleobase structure can significantly enhance the photoactivity of DNA, which may incur DNA damage, thus holding promising applications in photochemotherapy treatment of cancers or pathogens. However, single substitution confers only limited phototoxicity to DNA. Herein, we combine femtosecond and nanosecond time-resolved spectroscopy with high-level ab initio calculations to disentangle the excited-state dynamics of 6-methylthioguanine (me6-TG) under variable wavelength UVA excitation (310-330 nm). We find that double substitution of nucleobases (thionation and methylation) boosts the photoactivity by introducing more reactive channels. Intriguingly, 1nNπ*, rather than 1nSπ*, acts as the doorway state engendering the formation of the long-lived reactive triplet state in me6-TG. The 1nNπ* induces a low spin-orbit coupling of 8.3 cm-1, which increases the intersystem crossing (ISC) time (2.91 ± 0.14 ns). Despite the slowed ISC, the triplet quantum yield (ΦT) still accounts for a large fraction (0.6 ± 0.1), consistent with the potential energy surface that favors excited-state bifurcation to 1nNπ*min (3.36 ± 0.15 ps) rather than 1ππ*min (5.05 ± 0.26 ps), such that the subsequent ISC to triplet via 1nNπ*min constitutes the main relaxation pathway in me6-TG. Although this ΦT is inferior to its single-substituted predecessor 6-thioguanine (6-TG, 0.8 ± 0.2), the effect of thionation in synergy with methylation opens a unique C-S bond cleavage pathway through crossing to a repulsive 1πσ* state, generating thiyl radicals as highly reactive intermediates that may invoke biological damage. This photodissociation channel is extremely difficult for conventional nucleobases. These findings demonstrate the synergistic effects of double functionality substitution in modulating excited-state dynamics and enhancing the photolabile character of DNA nucleobases, providing inspirations for the rational design of advanced photodynamic and photochemotherapy approaches.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38536209

RESUMO

Three bacterial strains, FP250T, FP821, and FP53, were isolated from the rhizosphere soil of oilseed rape, licorice, and habanero pepper in Anhui Province, Xinjiang Uygur Autonomous Region, and Jiangsu Province, PR China, respectively. All strains were shown to grow at 4-37 °C and pH 6.0-9.0, and in the presence of 0-4.0 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences or housekeeping genes (16S rRNA, gyrB, rpoB, and rpoD) and phylogenomic analysis showed that strains FP250T, FP821, and FP53 belong to the genus Pseudomonas, and are closely related to Pseudomonas kilonensis DSM 13647T, Pseudomonas brassicacearum JCM 11938T, Pseudomonas viciae 11K1T, and Pseudomonas thivervalensis DSM 13194T. The DNA G+C content of strain FP205T was 59.8 mol%. The average nucleotide identity and digital DNA-DNA hybridization values of strain FP205T with the most closely related strain were 93.2 % and 51.4 %, respectively, which is well below the threshold for species differentiation. Strain FP205T contained summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c), summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) as major fatty acids, and diphosphatidylglycerol along with phosphatidylethanolamine and aminophospholipid as major polar lipids. The predominant isoprenoid quinone was ubiquinone-9. Based on these phenotypic, phylogenetic, and chemotaxonomic results, strain FP205T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas hefeiensis sp. nov. is proposed. The type strain is FP205T (=ACCC 62447T=JCM 35687T).


Assuntos
Ácidos Graxos , Rizosfera , Composição de Bases , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , China
8.
Phlebology ; 39(2): 108-113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37936273

RESUMO

INTRODUCTION: The objective of this study is to evaluate and compare the effectiveness of endovenous microwave ablation (EMA) and high ligation and strippingn (HLS) of the great saphenous vein (GSV) in the treatment of varicose veins. METHODS: We included 182 patients in each EMA and HLS groups. Follow-up outcomes included AVVQ, VCSS, chronic venous insufficiency questionnaire-14 (CIVIQ14) score, clinical recurrence rate of varicose vein treatment, and patient satisfaction during the 1-year follow-up period. RESULTS: At the 1-year follow-up, no significant difference was found in the clinical recurrence rate of varicose veins between the EMA and HLS groups (p = .75). The duration of the operation and the length of hospital stay for patients in the EMA group was shorter than that for the HLS group (p < .01). The Aberdeen Varicose Vein Questionnaire (AVVQ), Venous Clinical Severity Score (VCSS) score, and ecchymosis were lower for patients who underwent EMA surgery (p < .01). CONCLUSION: Our research results confirm that EMA improves patients' quality of life with lower limb varicose veins, with EMA showing higher patient satisfaction.


Assuntos
Terapia a Laser , Varizes , Insuficiência Venosa , Humanos , Veia Safena/cirurgia , Qualidade de Vida , Micro-Ondas/uso terapêutico , Resultado do Tratamento , Varizes/cirurgia , Ligadura , Insuficiência Venosa/cirurgia , Terapia a Laser/métodos
9.
Naunyn Schmiedebergs Arch Pharmacol ; 397(3): 1749-1762, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37728623

RESUMO

In this study, we aimed to explore the effects of curcumin on the progression of colorectal cancer and its underlying mechanisms involved. Cell proliferation, apoptosis and invasion were determined through CCK-8 assay, colony formation assay, EdU assay, flow cytometry, and transwell invasion assay, respectively. The protein expression of Bax, MMP2, USP4 and LAMP3 was measured using western blot. Pearson correlation coefficient was used to evaluate the relationship between USP4 and LAMP3. Co-IP was also conducted to determine the interaction between USP4 and LAMP3. Xenograft tumor model was established to explore the role of curcumin in colorectal cancer in vivo. IHC was utilized to measure the expression of Bax, MMP2, USP4 and LAMP3 in tumor tissues from mice. Curcumin significantly accelerated cell apoptosis, and inhibited cell proliferation and invasion in LoVo and HCT-116 cells. LAMP3 was augmented in colorectal cancer tissues and cells, and curcumin could reduce the expression of LAMP3. Curcumin decreased LAMP3 expression to exhibit the inhibition role in the progression of colorectal cancer. USP4 interacted with LAMP3, and positively regulated LAMP3 expression in colorectal cancer cells. LAMP3 overexpression could reverse the suppressive effects of USP4 knockdown on the development of colorectal cancer. Curcumin downregulated USP4 to impeded the progression of colorectal cancer via repressing LAMP3 expression. In addition, curcumin obviously restrained tumor growth in mice through downregulating USP4 and LAMP3 expression. These data indicated that curcumin exert the anti-tumor effects on the development of colorectal cancer through modulating the USP4/LAMP3 pathway.


Assuntos
Neoplasias Colorretais , Curcumina , Humanos , Animais , Camundongos , Curcumina/farmacologia , Curcumina/uso terapêutico , Linhagem Celular Tumoral , Metaloproteinase 2 da Matriz , Proteína X Associada a bcl-2 , Proliferação de Células , Apoptose , Neoplasias Colorretais/metabolismo , Movimento Celular , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/farmacologia , Proteína 3 de Membrana Associada ao Lisossomo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/farmacologia
10.
Cytokine ; 173: 156423, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37979212

RESUMO

Isthmin is a polypeptide secreted by adipocytes that was first detected in Xenopus gastrula embryos. Recent studies have focused on the biological functions of isthmin in growth and development, angiogenesis, and metabolism. Distinct spatiotemporal expression of isthmin-1 (ISM-1) was observed during growth and development. ISM-1 plays an important role in the occurrence and development of cancer by regulating cell proliferation, migration, angiogenesis, and immune microenvironments. Moreover, ISM-1, as a newly identified insulin-like adipokine, increases adipocyte glucose uptake and inhibits hepatic lipid synthesis. However, the biological function of ISM-1 remains largely unknown. In this review, we highlight the structure and physiological functions of isthmin and explore its application potential, contributing to a better understanding of its function and providing prevention and treatment strategies for various diseases.


Assuntos
Trombospondinas , Proliferação de Células , Glucose , Insulina , Fígado/metabolismo , Humanos , Animais , Trombospondinas/fisiologia
11.
Int J Syst Evol Microbiol ; 73(12)2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38117210

RESUMO

Two bacterial strains, FP1935T and FP1962, were isolated from the rhizosphere soil of cucumber and Chieh-qua plants, respectively, in Jilin Province, PR China. These strains were Gram-stain-negative, aerobic, rod-shaped and motile with one or two polar flagella. Analysis of the 16S rRNA gene sequences revealed that they represented members of the genus Pseudomonas, with the highest similarity to Pseudomonas silesiensis A3T (99.45 %), Pseudomonas frederiksbergensis JAJ28T (99.45 %), Pseudomonas mandelii NBRC 103147T (99.38 %), Pseudomonas piscium P50T (99.27 %) and Pseudomonas meliae CFBP 3225T (99.18 %). The DNA G+C contents of FP1935T and FP1962 were 58.99 mol% and 58.98 mol%, respectively. The results of in silico genome-based analyses indicated that these strains were distinct from other species in the genus Pseudomonas, as the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values were below the recommended thresholds of 95 % (ANI) and 70 % (dDDH) for prokaryotic species delineation, with no values exceeding 94.1 and 55.8 %, respectively, compared with any other related species. The results of phenotypic and chemotaxonomic tests confirmed their differentiation from their closest relatives. The fatty acid profiles of both strains mainly consisted of summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C12 : 0 and C16 : 0. The predominant respiratory quinone was Q-9. Polar lipids include phosphatidylethanolamine, unidentified aminophospholipids, unidentified lipids and an unidentified phospholipid. On the basis of these phenotypic and genotypic results, we propose the name Pseudomonas cucumis sp. nov. for these novel strains. The type strain is FP1935T (=ACCC 62445T=JCM 35690T).


Assuntos
Cucumis , RNA Ribossômico 16S/genética , Rizosfera , Composição de Bases , Ácidos Graxos/química , Filogenia , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana
12.
J Cancer Res Clin Oncol ; 149(20): 17837-17848, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37943356

RESUMO

PURPOSE: To compare the long-term clinical and oncologic outcomes of laparoscopic partial nephrectomy (LPN) and laparoscopic radical nephrectomy (LRN) in patients with renal cell carcinoma (RCC) > 4 cm. METHODS: We retrospectively reviewed the records of all patients who underwent LPN or LRN in our department from January 2012 to December 2017. Of the 151 patients who met the study selection criteria, 54 received LPN, and 97 received LRN. After propensity-score matching, 51 matched pairs were further analyzed. Data on patients' surgical data, complications, histologic data, renal function, and survival outcomes were collected and analyzed. RESULTS: Compared with the LRN group, the LPN group had a longer operative time (135 min vs. 102.5 min, p = 0.001), larger intraoperative bleeding (150 ml vs. 50 ml, p < 0.001), and required longer stays in hospital (8 days vs. 6 days, p < 0.001); however, the level of ECT-GFR was superior at 3, 6, and 12 months (all p < 0.001). Similarly, a greater number of LRN patients developed CKD compared with LPN until postoperative 12 months (58.8% vs. 19.6%, p < 0.001). In patients with preoperative CKD, LPN may delay the progression of the CKD stage and even improve it when compared to LRN treatment. There were no significant differences between the two groups for OS, CSS, MFS, and PFS (p = 0.06, p = 0.30, p = 0.90, p = 0.31, respectively). The surgical method may not be a risk factor for long-term survival prognosis. CONCLUSION: LPN preserves renal function better than LRN and has the potential value of significantly reducing the risk of postoperative CKD, but the long-term survival prognosis of patients is comparable.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Insuficiência Renal Crônica , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Estudos Retrospectivos , Resultado do Tratamento , Laparoscopia/métodos , Nefrectomia/métodos , Insuficiência Renal Crônica/cirurgia
13.
BMC Gastroenterol ; 23(1): 354, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828423

RESUMO

BACKGROUND: This study will focus on exploring the clinical characteristics of rectal cancer (RC) patients with Second Primary Malignancies (SPMs) and constructing a prognostic nomogram to provide clinical treatment decisions. METHODS: We determined the association between risk factors and overall survival (OS) while establishing a nomogram to forecast the further OS status of these patients via Cox regression analysis. Finally, we evaluated the performance of the prognostic nomogram to predict further OS status. RESULTS: Nine parameters were identified to establish the prognostic nomogram in this study, and, the C-index of the training set and validation set was 0.691 (95%CI, 0.662-0.720) and 0.731 (95%CI, 0.676-0.786), respectively. The calibration curve showed a high agreement between the predicted and actual results, and the receiver operating characteristic (ROC) curves verified the superiority of our model for clinical usefulness. In addition, the nomogram classification could more precisely differentiate risk subgroups and improved the discrimination of SPMs' prognosis. CONCLUSIONS: We systematically explored the clinical characteristics of SPMs after RC and constructed a satisfactory nomogram.


Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Programa de SEER , Nomogramas , Curva ROC , Prognóstico
14.
Drugs Aging ; 40(11): 991-1007, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37863867

RESUMO

Age-related macular degeneration (AMD) is one of the main causes of visual impairment and severe visual loss, and can progress to two advanced forms-neovascularization and atrophic. The field of anti-AMD drugs has undergone huge developments in recent years, from single-target intravitreal administration to current clinical studies with multi-target and non-invasive agents, offering interesting new pharmacological opportunities for the treatment of this disease. Hence, we summarize some of the approved anti-vascular endothelial growth factor (VEGF) drugs for neovascular AMD, especially their structural characteristics, clinical manifestations, dosing regimens, and safety issues of the anti-VEGF drugs highlighted. In addition, advances in atrophic AMD drug research are also briefly described.


Assuntos
Neovascularização de Coroide , Degeneração Macular Exsudativa , Humanos , Inibidores da Angiogênese/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Preparações Farmacêuticas , Neovascularização de Coroide/tratamento farmacológico , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Injeções Intravítreas , Ranibizumab/uso terapêutico
15.
ACS Nano ; 17(17): 17217-17232, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37584451

RESUMO

Macrophage-mediated cellular phagocytosis (MMCP) plays a critical role in conducting antitumor immunotherapy but is usually impaired by the intrinsic phagocytosis evading ability of tumor cells and the immunosuppressive tumor microenvironment (TME). Herein, a MMCP-boosting hydrogel (TCCaGM) was elaborately engineered by encapsulating granulocyte-macrophage colony-stimulating factor (GM-CSF) and a therapeutic nanoplatform (TCCaN) that preloaded with the tunicamycin (Tuni) and catalase (CAT) with the assistance of CaCO3 nanoparticles (NPs). Strikingly, the hypoxic/acidic TME was efficiently alleviated by the engineered hydrogel, "eat me" signal calreticulin (CRT) was upregulated, while the "don't eat me" signal CD47 was downregulated on tumor cells, and the infiltrated DCs were recruited and activated, all of which contributed to boosting the macrophage-mediated phagocytosis and initiating tumor-specific CD8+ T cells responses. Meanwhile, the remodeled TME was beneficial to accelerate the polarization of tumor-associated macrophages (TAMs) to the antitumoral M1-like phenotype, further heightening tumoricidal immunity. With the combination of PD-1 antibody (αPD-1), the designed hydrogel significantly heightened systemic antitumor immune responses and long-term immunological effects to control the development of primary and distant tumors as well as suppress tumor metastasis and recurrence, which established an optimal strategy for high-performance antitumor immunotherapy.


Assuntos
Adjuvantes Imunológicos , Neoplasias , Humanos , Adjuvantes Imunológicos/farmacologia , Microambiente Tumoral , Linfócitos T CD8-Positivos , Hidrogéis/farmacologia , Macrófagos , Neoplasias/terapia , Neoplasias/patologia , Fagocitose , Antígeno CD47 , Imunoterapia
16.
Cell Signal ; 110: 110830, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37516395

RESUMO

Cellular signalling cues lead to the initiation of apoptotic pathways and often result in the activation of caspases which in turn cause the generation of proteolytically generated protein fragments with new or altered functions. Mounting number of studies reveal that the activity of these proteolytically activated protein fragments can be counteracted via their selective degradation by the N-degron degradation pathways. Here, we investigate the proteolytically generated fragment of the PKC theta kinase, where we demonstrate the first report on the stability of this pro-apoptotic protein fragment. We have determined that the pro-apoptotic cleaved fragment of PKC-theta is unstable in cells because its N-terminal lysine targets it for proteasomal degradation via the N-degron degradation pathway and this degradation is inhibited by mutating the destabilizing N-termini, knockdown of the UBR1 and UBR2 E3 ligases. Tellingly, we demonstrate that the metabolic stabilization of the cleaved fragment of PKC-theta or inhibition of the N-degron degradation augments the apoptosis-inducing effect of staurosporine in Jurkat cells. Notably, we have unveiled that the cleaved fragment of PKC theta, per se, can induce apoptotic cell death in Jurkat T-cell leukemia. Our results expand the functional scope of mammalian N-degron degradation pathways, and support the notion that targeting N-degron degradation machinery may have promising therapeutic implications in cancer cells.


Assuntos
Caspases , Ubiquitina-Proteína Ligases , Animais , Humanos , Proteína Quinase C-theta/metabolismo , Caspases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Apoptose , Células Jurkat , Proteólise , Mamíferos/metabolismo
17.
Huan Jing Ke Xue ; 44(6): 3270-3277, 2023 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-37309945

RESUMO

The adsorption performances of ammonia nitrogen (NH+4-N) in water by unmodified biochar are ineffective. In this study, nano zero-valent iron-modified biochar (nZVI@BC) was prepared to remove NH+4-N from water. The NH+4-N adsorption characteristics of nZVI@BC were investigated through adsorption batch experiments. The composition and structure characteristics of nZVI@BC were analyzed using scanning electron microscopy, energy spectrum analysis, BET-N2 surface area (SSA), X-ray diffraction, and FTIR spectra to explore the main adsorption mechanism of NH+4-N by nZVI@BC. The results showed that the composite synthesized at the iron to biochar mass ratio of 1:30 (nZVI@BC1/30) performed well in NH+4-N adsorption at 298 K. The maximum adsorption amount of nZVI@BC1/30 at 298 K was remarkably increased by 45.96% and reached 16.60 mg·g-1. The pseudo-second-order model and Langmuir model fitted well with the adsorption process of NH+4-N by nZVI@BC1/30. There was competitive adsorption between coexisting cations and NH+4-N, and the sequence of coexisting cations to the adsorption of NH+4-N by nZVI@BC1/30 was Ca2+> Mg2+> K+> Na+. The adsorption mechanism of NH+4-N by nZVI@BC1/30 could be mainly attributed to ion exchange and hydrogen bonding. In conclusion, nano zero-valent iron-modified biochar can improve the adsorption performance of NH+4-N and enhance the application potential of biochar in the field of nitrogen removal from water.

18.
Cancer Med ; 12(13): 14731-14741, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37199378

RESUMO

PURPOSE: Meeting intervention requirements is crucial in behavioral trials. We examined patterns and predictors of physical activity (PA) adherence and contamination in a 1-year individualized randomized controlled PA behavioral intervention in childhood cancer survivors (CCS). METHODS: CCS aged ≥16 at enrolment, <16 at diagnosis, and ≥5 years in remission were identified from the Swiss Childhood Cancer Registry. We asked participants randomized to the intervention group to perform an additional ≥2.5 h of intense PA/week and controls to continue as usual. Adherence to the intervention was assessed by online diary (adherent if ≥2/3 of individual PA goal reached) and contamination for the control group by pre- and post-questionnaire including PA levels (contaminated if >60 min increase/week in PA). Predictors of adherence/contamination including quality of life (36-Item Short Form Survey) were assessed by questionnaire. We used logistic (control group) and mixed logistic regression models (exercise group) to estimate predictors of study adherence and contamination. RESULTS: One hundred and forty-four survivors (30.4 ± 8.7 years old, 43% females) were included. Adherence was 48% (35/73) in the intervention group, while 17% (12/71) of controls contaminated group allocation. Predictors for PA adherence were female sex (OR 2.35, p = 0.03), higher physical (OR 1.34, p = 0.01) and mental quality of life (OR 1.37, p = 0.001), and week into the intervention (OR 0.98, p < 0.001). Clear differences in PA behavior of adherent and non-adherent participants were seen from week four. No significant predictors for contamination were found for controls. CONCLUSION: Adherence to PA behavior interventions remain challenging in both groups. Further long-term trials should consider intense motivational support within the first month, more detailed data collection for the control group, adjustments to power calculations and other study designs to minimize non-adherence and contamination.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Feminino , Criança , Adulto Jovem , Adulto , Masculino , Qualidade de Vida , Neoplasias/terapia , Exercício Físico , Inquéritos e Questionários
19.
Adv Healthc Mater ; 12(23): e2300323, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37212324

RESUMO

Tumor immunotherapy is commonly hindered by inefficient delivery and presentation of tumor antigens as well as immunosuppressive tumor microenvironment. To overcome these barriers, a tumor-specific nanovaccine capable of delivering tumor antigens and adjuvants to antigen-presenting cells and modulating the immune microenvironment to elicit strong antitumor immunity is reported. This nanovaccine, named FCM@4RM, is designed by coating the nanocore (FCM) with a bioreconstituted cytomembrane (4RM). The 4RM, which is derived from fused cells of tumorous 4T1 cells and RAW264.7 macrophages, enables effective antigen presentation and stimulation of effector T cells. FCM is self-assembled from Fe(II), unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG), and metformin (MET). CpG, as the stimulator of toll-like receptor 9, induces the production of pro-inflammatory cytokine and the maturation of cytotoxic T lymphocytes (CTLs), thereby enhancing antitumor immunity. Meanwhile, MET functions as the programmed cell death ligand 1 inhibitor and can restore the immune responses of T cells against tumor cells. Therefore, FCM@4RM exhibits high targeting capabilities toward homologous tumors that develop from 4T1 cells. This work offers a paradigm for developing a nanovaccine that systematically regulates multiple immune-related processes to achieve optimal antitumor immunotherapy.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Humanos , Neoplasias/terapia , Linfócitos T Citotóxicos , Imunoterapia , Antígenos de Neoplasias , Microambiente Tumoral
20.
Huan Jing Ke Xue ; 44(4): 2215-2222, 2023 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-37040970

RESUMO

With the rapid development of urbanization in China, the number of gas stations in cities is increasing. The composition of oil products in gas stations is complex and diverse, and a series of pollutants will be generated in the process of oil diffusion. Polycyclic aromatic hydrocarbons (PAHs) produced by gas stations can pollute the nearby soil and affect human health. In this study, soil samples (0-20 cm) near 117 gas stations in Beijing were collected, and the contents of seven PAHs were analyzed. Based on the BP neural network model, the contents of PAHs in soil of Beijing gas stations in 2025 and 2030 were predicted. The results showed that the total concentrations of the seven PAHs were 0.01-3.53 mg·kg-1. The concentrations of PAHs were lower than the soil environmental quality risk control standard for soil contamination of development land (Trial) GB 36600-2018. At the same time, the toxic equivalent concentrations (TEQ) of the above seven PAHs were lower than the standard value (1 mg·kg-1) of the World Health Organization (WHO), which they indicate a lower risk to human health. The prediction results showed that the rapid development of urbanization had a positive correlation with the increase in soil PAHs content. By 2030, the content of PAHs in Beijing gas station soil will continue to grow. The predicted concentrations of PAHs in the soil of Beijing gas stations in 2025 and 2030 were 0.085-4.077 mg·kg-1and 0.132-4.412 mg·kg-1, respectively. The contents of seven PAHs were lower than the soil pollution risk screening value of GB 36600-2018; however, the concentration of PAHs increased over time.The contents of PAHs in Chaoyang, Fengtai, and Haidian were relatively higher, which requires further attention.

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