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1.
Medicine (Baltimore) ; 103(23): e38534, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847734

RESUMO

RATIONALE: Crouzon syndrome is an extremely rare craniofacial dysplasia, which is mainly caused by the early ossification and closure of the coronal suture of the skull. Craniofacial deformities can cause stenosis of the nasal cavity and posterior nasal meatus, resulting in sleep apnea. PATIENT CONCERNS: A 9-year-old boy with sleep snoring for 6 years, progressive aggravation in the past 1 month and accompanied by apnea during sleep. DIAGNOSES: This case was diagnosed with Crouzon syndrome complicated with severe obstructive sleep apnea and severe hypoxemia. INTERVENTIONS: After adenoidectomy, he was admitted to the pediatric intensive care unit with ventilator-assisted respiration. During this period, the blood oxygen saturation fluctuated greatly. After trying to extubate, the blood oxygen was difficult to maintain and had to be intubated again. After active treatment, extubation was successful. OUTCOMES: The wound of nasopharynx recovered well and the sleep state was significantly improved 3 months postoperation. LESSONS: It is suggested that the time of ventilator-assisted breathing should be prolonged and the perioperative airway management should be strengthened in order to reduce the risk of postoperative complications.


Assuntos
Adenoidectomia , Disostose Craniofacial , Apneia Obstrutiva do Sono , Criança , Humanos , Masculino , Adenoidectomia/métodos , Disostose Craniofacial/complicações , Disostose Craniofacial/cirurgia , Respiração Artificial/métodos , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/cirurgia
2.
Materials (Basel) ; 17(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38793489

RESUMO

The effects of adding nickel on the phase transition temperature, microstructure, and mechanical properties of medium-carbon spring steel have been investigated. The results show that adding nickel reduces the martensite start (Ms) temperature, improves hardenability, and refines the sub-microstructure of the martensite, thereby improving yield stress. The yield strength of martensitic steel increases by approximately 100 MPa due to a synergistic combination of grain refinement strengthening and dislocation strengthening, with an increase in the nickel content from 0 wt.% to 1 wt.%. The cryogenic impact toughness of martensitic steel also improved with a higher nickel content due to packet and block refinement and an increase in the proportion of high-angle grain boundaries (HAGBs).

3.
Adv Mater ; 36(23): e2311291, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38408154

RESUMO

Radiotherapy, a widely used therapeutic strategy for esophageal squamous cell carcinoma (ESCC), is always limited by radioresistance of tumor tissues and side-effects on normal tissues. Herein, a signature based on four core genes of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is developed to predict prognosis and assess immune cell infiltration, indicating that the cGAS-STING pathway and radiotherapy efficacy are closely intertwined in ESCC. A novel lipid-modified manganese diselenide nanoparticle (MnSe2-lipid) with extraordinarily uniform sphere morphology and tumor microenvironment (TME) responsiveness is developed to simultaneously overcome radioresistance and reduce side-effects of radiation. The uniform MnSe2 encapsulated lipid effectively achieves tumor accumulation. Octadecyl gallate on surface of MnSe2 forming pH-responsive metal-phenolic covalent realizes rapid degradation in TME. The released Mn2+ promotes radiosensitivity by generating reactive oxygen species induced by Fenton-like reaction and activating cGAS-STING pathway. Spontaneously, selenium strengthens immune response by promoting secretion of cytokines and increasing white blood cells, and performs antioxidant activity to reduce side-effects of radiotherapy. Overall, this multifunctional remedy which is responsive to TME is capable of providing radiosensitivity by cGAS-STING pathway-mediated immunostimulation and chemodynamic therapy, and radioprotection of normal tissues, is highlighted here to optimize ESCC treatment.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Nanopartículas , Tolerância a Radiação , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Animais , Nanopartículas/química , Linhagem Celular Tumoral , Camundongos , Ácido Gálico/química , Ácido Gálico/farmacologia , Ácido Gálico/análogos & derivados , Lipídeos/química , Selênio/química , Selênio/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Protetores contra Radiação/farmacologia , Protetores contra Radiação/química , Manganês/química , Radiossensibilizantes/química , Radiossensibilizantes/farmacologia
4.
Nat Rev Cancer ; 24(1): 72-87, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38040850

RESUMO

Systemic antiplatelet treatment represents a promising option to improve the therapeutic outcomes and therapeutic efficacy of chemotherapy and immunotherapy due to the critical contribution of platelets to tumour progression. However, until recently, targeting platelets as a cancer therapeutic has been hampered by the elevated risk of haemorrhagic and thrombocytopenic (low platelet count) complications owing to the lack of specificity for tumour-associated platelets. Recent work has advanced our understanding of the molecular mechanisms responsible for the contribution of platelets to tumour progression and metastasis. This has led to the identification of the biological changes in platelets in the presence of tumours, the complex interactions between platelets and tumour cells during tumour progression, and the effects of platelets on antitumour therapeutic response. In this Review, we present a detailed picture of the dynamic roles of platelets in tumour development and progression as well as their use in diagnosis, prognosis and monitoring response to therapy. We also provide our view on how to overcome challenges faced by the development of precise antiplatelet strategies for safe and efficient clinical cancer therapy.


Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Plaquetas/patologia , Plaquetas/fisiologia , Imunoterapia
5.
Cureus ; 15(10): e47825, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38022201

RESUMO

Neurofibromatosis type 1 (NF1) is a genetic disorder involving multiple organs. Vascular involvement is a rare complication among NF1 patients. We report a case of a 59-year-old female NF1 patient who presented with a massive hematoma over the scapular area after undergoing acupuncture treatment. Contrast-enhanced CT and MRI demonstrated a slightly hyperdense mass measuring 24.2 × 10.3 cm in size, and multiple enlarged and tortuous malformed vessels were seen arising from the left subclavian artery. Arterial embolization and subsequent surgical mass resection were successfully performed. This case indicates that minor injuries such as acupuncture-related ones could cause severe hemorrhage in patients with vascular malformation related to NF1. Endovascular angiography and embolization proved to be effective in localizing the culprit vessel and stopping active bleeding in our patient.

6.
Int J Mol Sci ; 24(19)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37834462

RESUMO

Autophagy is an evolutionarily conserved mechanism for degrading and recycling various cellular components, functioning in both normal development and stress conditions. This process is tightly regulated by a set of autophagy-related (ATG) proteins, including ATG2 in the ATG9 cycling system and ATG5 in the ATG12 conjugation system. Our recent research demonstrated that autophagy-mediated compartmental cytoplasmic deletion is essential for pollen germination. However, the precise mechanisms through which autophagy regulates pollen germination, ensuring its fertility, remain largely unknown. Here, we applied multi-omics analyses, including transcriptomic and metabolomic approaches, to investigate the downstream pathways of autophagy in the process of pollen germination. Although ATG2 and ATG5 play similar roles in regulating pollen germination, high-throughput transcriptomic analysis reveals that silencing ATG5 has a greater impact on the transcriptome than silencing ATG2. Cross-comparisons of transcriptome and proteome analysis reveal that gene expression at the mRNA level and protein level is differentially affected by autophagy. Furthermore, high-throughput metabolomics analysis demonstrates that pathways related to amino acid metabolism and aminoacyl-tRNA biosynthesis were affected by both ATG2 and ATG5 silencing. Collectively, our multi-omics analyses reveal the central role of autophagy in cellular metabolism, which is critical for initiating pollen germination and ensuring pollen fertility.


Assuntos
Autofagia , Multiômica , Proteínas Relacionadas à Autofagia/genética , Autofagia/genética , Proteína 12 Relacionada à Autofagia/genética , Pólen/genética , Pólen/metabolismo , Germinação/genética
7.
J Orthop Surg Res ; 18(1): 563, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37537684

RESUMO

Spinal metastasis is a common secondary malignant tumor of the bone, often resulting in spinal cord and nerve root compression, leading to obvious pain and related compression symptoms. This condition has a high incidence and mortality rate. The treatment approach for most patients with spinal metastasis is primarily palliative. Consultation with a multidisciplinary team is widely accepted as a comprehensive treatment approach for patients with spinal metastases. With advancements in research and technology, the evaluation and treatment of spinal metastatic cancer are continuously evolving. This study provides an overview of surgical treatment, minimally invasive treatment, and radiotherapy for spinal metastatic cancer and also analyzes the clinical effects, advantages, and current limitations associated with various treatment approaches.


Assuntos
Compressão da Medula Espinal , Neoplasias da Coluna Vertebral , Humanos , Neoplasias da Coluna Vertebral/secundário , Qualidade de Vida , Dor/etiologia , Cuidados Paliativos , Medula Espinal , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia
8.
Nat Commun ; 14(1): 4898, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37580346

RESUMO

Conformational cooperativity is a universal molecular effect mechanism and plays a critical role in signaling pathways. However, it remains a challenge to develop artificial molecular networks regulated by conformational cooperativity, due to the difficulties in programming and controlling multiple structural interactions. Herein, we develop a cooperative strategy by programming multiple conformational signals, rather than chemical signals, to regulate protein-oligonucleotide signal transduction, taking advantage of the programmability of allosteric DNA constructs. We generate a cooperative regulation mechanism, by which increasing the loop lengths at two different structural modules induced the opposite effects manifesting as down- and up-regulation. We implement allosteric logic operations by using two different proteins. Further, in cell culture we demonstrate the feasibility of this strategy to cooperatively regulate gene expression of PLK1 to inhibit tumor cell proliferation, responding to orthogonal protein-signal stimulation. This programmable conformational cooperativity paradigm has potential applications in the related fields.


Assuntos
Oligonucleotídeos , Transdução de Sinais , Regulação Alostérica , Conformação Molecular
9.
Nano Lett ; 23(16): 7743-7749, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37406355

RESUMO

Photodynamic molecular beacons (PMBs) are highly appealing for activatable photodynamic therapy (PDT), but their applications are hindered by limited therapeutic efficacy. Here, by molecular engineering of enzyme-responsive units in the loop region of DNA-based PMBs, we present for the first time the modular design of an enzyme/microRNA dual-regulated PMB (D-PMB) to achieve cancer-cell-selective amplification of PDT efficacy. In the design, the "inert" photosensitizers in D-PMB could be repeatedly activated in the presence of both tumor-specific enzyme and miRNA, leading to amplified generation of cytotoxic singlet oxygen species and therefore enhanced PDT efficacy in vitro and in vivo. By contrast, low photodynamic activity could be observed in healthy cells, as D-PMB activation has been largely avoided by the dual-regulatable design. This work presents a cooperatively activated PDT strategy, which enables enhanced therapeutic efficacy with improved tumor-specificity and thus conceptualizes an approach to expand the repertoire of designing smart tumor treatment modality.


Assuntos
MicroRNAs , Neoplasias , Fotoquimioterapia , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Oxigênio Singlete , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Linhagem Celular Tumoral
10.
Front Immunol ; 14: 1173952, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37313406

RESUMO

Background: The incidence and risk factors of acute kidney injury (AKI) in patients with malignancies receiving immune checkpoint inhibitors (ICIs) are being extensively reported with their widespread application. Objective: This study aimed to quantify the incidence and identify risk factors of AKI in cancer patients treated with ICIs. Methods: We searched the electronic databases of PubMed/Medline, Web of Science, Cochrane and Embase before 1 February 2023 on the incidence and risk factors of AKI in patients receiving ICIs and registered the protocol in PROSPERO (CRD42023391939). A random-effect meta-analysis was performed to quantify the pooled incidence estimate of AKI, identify risk factors with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) and investigate the median latency period of ICI-AKI in patients treated with ICIs. Assessment of study quality, meta-regression, and sensitivity and publication bias analyses were conducted. Results: In total, 27 studies consisting of 24048 participants were included in this systematic review and meta-analysis. The overall pooled incidence of AKI secondary to ICIs was 5.7% (95% CI: 3.7%-8.2%). Significant risk factors were older age (OR: 1.01, 95% CI: 1.00-1.03), preexisting chronic kidney disease (CKD) (OR: 2.90, 95% CI: 1.65-5.11), ipilimumab (OR: 2.66, 95% CI: 1.42-4.98), combination of ICIs (OR: 2.45, 95% CI: 1.40-4.31), extrarenal immune-related adverse events (irAEs) (OR: 2.34, 95% CI: 1.53-3.59), and proton pump inhibitor (PPI) (OR: 2.23, 95% CI: 1.88-2.64), nonsteroidal anti-inflammatory drug (NSAID) (OR: 2.61, 95% CI: 1.90-3.57), fluindione (OR: 6.48, 95% CI: 2.72-15.46), diuretic (OR: 1.78, 95% CI: 1.32-2.40) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) (pooled OR: 1.76, 95% CI: 1.15-2.68) use. Median time from ICIs initiation to AKI was 108.07 days. Sensitivity and publication bias analyses indicated robust results for this study. Conclusion: The occurrence of AKI following ICIs was not uncommon, with an incidence of 5.7% and a median time interval of 108.07 days after ICIs initiation. Older age, preexisting chronic kidney disease (CKD), ipilimumab, combined use of ICIs, extrarenal irAEs, and PPI, NSAID, fluindione, diuretics and ACEI/ARB use are risk factors for AKI in patients receiving ICIs. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023391939.


Assuntos
Injúria Renal Aguda , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Ipilimumab , Antagonistas de Receptores de Angiotensina , Incidência , Inibidores da Enzima Conversora de Angiotensina , Neoplasias/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Anti-Inflamatórios não Esteroides
11.
Adv Healthc Mater ; 12(24): e2300673, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37139567

RESUMO

The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.


Assuntos
COVID-19 , Nanofibras , Humanos , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/química , Ligação Proteica , Peptídeos
12.
ACS Appl Mater Interfaces ; 15(16): 19833-19846, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37052616

RESUMO

Radiation gastroenteritis represents one of the most prevalent and hazardous complications of abdominopelvic radiotherapy, which not only severely reduces patients' life quality but also restricts radiotherapy efficacy. However, there is currently no clinically available oral radioprotector for this threatening disease due to its complex pathogenesis and the harsh gastrointestinal environment. To this end, this study developed a facile but effective oral radioprotector, ergothioneine hyaluronate (EGT@HA) gel, protecting against radiation gastroenteritis by synergistically regulating oxidative stress, inflammation, and gut microbiota. In vitro and cellular experiments verified the chemical stability and free radical scavenging ability of EGT and its favorable cellular radioprotective efficacy by inhibiting intracellular reactive oxidative species (ROS) generation, DNA damage, mitochondrial damage, and apoptosis. At the in vivo level, EGT@HA with prolonged gastrointestinal residence mitigated radiation-induced gastrointestinal tissue injury, apoptosis, neutrophil infiltration, and gut flora dysbiosis. For the first time, this work investigated the protective effects of EGT@HA gel on radiation gastroenteritis, which not only hastens the advancement of the novel gastrointestinal radioprotector but also provides a valuable gastrointestinal radioprotection paradigm by synergistically modulating oxidative stress, inflammation, and gut microbiota disturbance.


Assuntos
Ergotioneína , Gastroenterite , Microbioma Gastrointestinal , Lesões por Radiação , Humanos , Ergotioneína/genética , Ergotioneína/farmacologia , Antioxidantes/farmacologia , Disbiose/tratamento farmacológico , Disbiose/prevenção & controle , Apoptose , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle
13.
Sci Adv ; 9(9): eabq8225, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36857458

RESUMO

Up to 75% of bladder cancer patients suffer from recurrence due to postoperative tumor implantation. However, clinically used Bacillus Calmette-Guerin (BCG) treatment failed to inhibit the recurrence. Here, we report a bispecific glycopeptide (bsGP) that simultaneously targets CD206 on tumor-associated macrophages (TAMs) and CXCR4 on tumor cells. bsGP repolarizes protumoral M2-like TAMs to antitumor M1-like that mediated cytotoxicity and T cell recruitment. Meanwhile, bsGP is cleaved by the MMP-2 enzyme to form nanostructure for the long-term inhibition of CXCR4 downstream signaling, resulting in reduced tumor metastasis and promoted T cell infiltration. In orthotopic bladder tumor models, bsGP reduced the postoperative recurrence rate to 22%. In parallel, the recurrence rates of 89 and 78% were treated by doxycycline and BCG used in clinic, respectively. Mechanistic studies reveal that bsGP reduces the matrix microenvironment barrier, increasing the spatially redirected CD8+ T cells to tumor cells. We envision that bis-targeting CD206 and CXCR4 may pave the way to inhibit tumor metastasis and recurrence.


Assuntos
Microambiente Tumoral , Neoplasias da Bexiga Urinária , Humanos , Vacina BCG , Linfócitos T CD8-Positivos , Recidiva Local de Neoplasia , Glicopeptídeos
14.
Artigo em Chinês | MEDLINE | ID: mdl-36987954

RESUMO

Objective:To explore the relationship between sleep status and the disease in children with recurrent vertigo(RVC) by analyzing the objective sleep condition of children with recurrent vertigo. Methods:According to the diagnostic criteria of RVC, 50 children with RVC and 20 normal controls without RVC were selected. According to the vertigo questionnaire score, the RVC group was divided into mild, moderate and severe groups according to severity. Continuous polysomnography(PSG) was performed for all participants, and SPSS 25.0 statistical software was used to analyze the monitoring results. Results:①There were significant differences in sleep time of each period, total sleep time and sleep efficiency between RVC group and control group(P<0.05), but there was no significant difference in sleep latency(P>0.05). The specific manifestations were that the proportion of sleep time in N1 and N2 phases increased, the proportion of sleep time in N3 and REM phases decreased, the total sleep time and sleep efficiency decreased in RVC group. ②The abnormal rate of sleep apnea hypopnea index, that is, the proportion of AHI≥5 times/h and the abnormal rate of lowest blood oxygen saturation in RVC group were higher than those in normal control group. There was significant difference between the two groups(P<0.05). ③There were significant differences in the proportion of AHI≥5 times/h and lowest SpO2 among mild group, moderate group and severe group(P<0.05). ④There was no significant correlation between the degree of vertigo and the abnormal rate of AHI in children with RVC, but there was a negative correlation between the degree of vertigo and the abnormal rate of lowest SpO2 in children with RVC. Conclusion:Children with RVC are often accompanied by sleep disorders, clinicians should pay attention to both the symptoms of vertigo and sleep condition in children. Polysomnography is non-invasive and operable, providing a new idea to the auxiliary examination of RVC in children. It is of certain clinical significance for the comprehensive treatment of children with RVC to actively improve vertigo symptoms and pay attention to improving sleep quality.


Assuntos
Apneia Obstrutiva do Sono , Humanos , Criança , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Sono , Tontura , Vertigem/diagnóstico
15.
Adv Mater ; 35(24): e2211332, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36971342

RESUMO

The tumor-associated macrophages (TAMs) in intratumoral hypoxic regions are key drivers of immune escape. Reprogramming the hypoxic TAMs to antitumor phenotype holds great therapeutic benefits but remains challenging for current drugs. Here, an in situ activated nanoglycocluster is reported to realize effective tumor penetration and potent repolarization of hypoxic TAMs. Triggered by the hypoxia-upregulated matrix metalloproteinase-2 (MMP-2), the nanoglycocluster is self-assembled from the administered mannose-containing precursor glycopeptides and presents densely-arrayed mannoses to multivalently engage with mannose receptors on M2-like TAMs for efficient phenotype switch. By virtue of the high diffusivity of precursor glycopeptides due to their low molecular mass and weak affinity with TAMs in perivascular regions, the nanoglycoclusters are capable of substantially accumulating in hypoxic areas to strongly interact with local TAMs. This enables the efficient repolarization of overall TAMs with a higher rate than the small-molecule drug R848 and CD40 antibody, and beneficial therapeutic effects in mouse tumor models especially when combining with PD-1 antibody. This on-demand activated immunoagent is endowed with tumor-penetrating properties and inspires the design of diverse intelligent nanomedicines for hypoxia-related cancer immunotherapy.


Assuntos
Neoplasias , Macrófagos Associados a Tumor , Animais , Camundongos , Metaloproteinase 2 da Matriz , Macrófagos , Imunoterapia , Neoplasias/terapia , Neoplasias/patologia , Hipóxia , Glicopeptídeos/farmacologia , Microambiente Tumoral
16.
J Am Chem Soc ; 2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36744911

RESUMO

How to optimize the enzyme-like catalytic activity of nanozymes to improve their applicability has become a great challenge. Herein, we present an l-cysteine (l-Cys) coordination-driven self-assembly strategy to activate polyvinylpyrrolidone (PVP)-modified Cu single-atom nanozymes MoOx-Cu-Cys (denoted as MCCP SAzymes) aiming at catalytic tumor-specific therapy. The Cu single atom content of MCCP can be rationally modulated to 10.10 wt %, which activates the catalase (CAT)-like activity of MoOx nanoparticles to catalyze the decomposition of H2O2 in acidic microenvironments to increase O2 production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO2 nanozymes and exhibits 14.3-fold higher affinity than natural catalase, as demonstrated by steady-state kinetics. We verify that the well-defined l-Cys-Cu···O active sites optimize CAT-like activity to match the active sites of natural catalase through an l-Cys bridge-accelerated electron transfer from Cys-Cu to MoOx disclosed by density functional theory calculations. Simultaneously, the high loading Cu single atoms in MCCP also enable generation of •OH via a Fenton-like reaction. Moreover, under X-ray irradiation, MCCP converts O2 to 1O2 for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.

17.
J Cell Physiol ; 238(4): 727-741, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36815285

RESUMO

Acute kidney injury (AKI) is characterized by a rapid reduction in kidney function caused by various etiologies. Tubular epithelial cell dysregulation plays a pivotal role in the pathogenesis of AKI. Tight junction (TJ) is the major molecular structure that connects adjacent epithelial cells and is critical in maintaining barrier function and determining the permeability of epithelia. TJ proteins are dysregulated in various types of AKI, and some reno-protective drugs can reverse TJ changes caused by insult. An in-depth understanding of TJ regulation and its causality with AKI will provide more insight to the disease pathogenesis and will shed light on the potential role of TJs to serve as novel therapeutic targets in AKI.


Assuntos
Injúria Renal Aguda , Junções Íntimas , Humanos , Junções Íntimas/metabolismo , Epitélio/metabolismo , Células Epiteliais/metabolismo , Proteínas de Junções Íntimas/metabolismo , Injúria Renal Aguda/patologia
18.
Regen Biomater ; 10: rbad004, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817975

RESUMO

Ferroptosis, a completely new form of regulated cell death, is mainly caused by an imbalance between oxidative damage and reductive protection and has shown great anti-cancer potential. However, existing small-molecule ferroptosis inducers have various limitations, such as poor water solubility, drug resistance and low targeting ability, hindering their clinical applications. Nanotechnology provides new opportunities for ferroptosis-driven tumor therapy. Especially, stimuli-responsive nanomaterials stand out among others and have been widely researched because of their unique spatiotemporal control advantages. Therefore, it's necessary to summarize the application of those stimuli-responsive nanomaterials in ferroptosis. Here, we describe the physiological feature of ferroptosis and illustrate the current challenges to induce ferroptosis for cancer therapy. Then, nanomaterials that induce ferroptosis are classified and elaborated according to the external and internal stimuli. Finally, the future perspectives in the field are proposed. We hope this review facilitates paving the way for the design of intelligent nano-ferroptosis inducers.

19.
Eur Arch Otorhinolaryngol ; 280(5): 2435-2443, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36646937

RESUMO

OBJECTIVE: Bariatric surgery (BS) is considered one of the most effective treatments for obese individuals with Obstructive Sleep Apnea (OSA). However, otolaryngologists have raised concerns about the structural alterations caused by BS on the upper respiratory tract, especially, on the pharyngeal cavity. METHODS: In this study, we recruited 42 individuals who underwent BS at our hospital. They were divided into two groups based on apnea-hypopnea index (AHI): mild group (5 ≤ AHI < 15) and moderate-severe group (AHI ≥ 15). The participants were followed up for 12 months and several indicators, including body mass index (BMI), polysomnography (PSG), and acoustic pharyngometry (APh), were assessed repeatedly before surgery and at 3, 6, and 12 months (m) after surgery. RESULTS: Participants exhibited significant decreases in BMI (F = 128.1, P = 0.001) and total weight loss (F = 176.7, P < 0.001) after BS. The AHI value among obese patients with mild OSA decreased significantly within three months after surgery (0 day vs. 3 months, P < 0.01), and decreased significantly more than 12 months with moderate-to-severe patients (0 day vs. 3 months, 3 months vs. 6 months, 6 months vs. 12 months, P < 0.01). The therapeutic effect of OSA of the mild group was significantly better compared with that of the moderate-severe group at 6 months (mean rank = 28.13 vs. 14.21, P < 0.001) and 12 m (mean rank = 26.75 vs. 15.52, P = 0.001). The APh results revealed that the pharyngeal volume of the two groups increased significantly between 0 day and 6 months after surgery (P < 0.01). The oropharyngeal junction (OPJ) area and the glottal area were increased significantly between 0 day and 6 m after surgery (P < 0.01). CONCLUSION: BS can relieve apnea and OSA symptoms among obese patients with OSA, especially in the early postoperative period. Moreover, OSA severity was closely associated with OPJ and glottal areas, rather than pharyngeal cavity volume.


Assuntos
Cirurgia Bariátrica , Apneia Obstrutiva do Sono , Humanos , Obesidade/complicações , Obesidade/cirurgia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/diagnóstico , Cirurgia Bariátrica/efeitos adversos , Faringe/cirurgia , Período Pós-Operatório
20.
J Vasc Surg Venous Lymphat Disord ; 11(2): 318-325, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36179787

RESUMO

OBJECTIVE: Central venous occlusion (CVO) refractory to endovascular angioplasty is a critical challenge that threatens hemodialysis vascular access. In the present study, we evaluated the efficacy and safety of tunneled, cuffed central venous catheter (tCVC) placement via percutaneous superior vena cava (SVC) puncture in patients with refractory CVO. METHODS: Patients requiring maintenance hemodialysis with refractory CVO who had undergone percutaneous SVC puncture and tCVC insertion at a university-affiliated hospital from January 2016 to June 2020 were included. The patients were followed up until May 2021. The demographic information, complications, and catheter patency were analyzed. RESULTS: A total of 205 patients (105 women [51.2%]; mean age, 61 ± 15 years) were included. The SVC puncture and tCVC insertion were successfully performed in 194 patients, for a technical success rate of 94.6%. One patient had experienced a pleura injury and hemothorax and had required urgent thoracotomy. A total of 37 patients had presented with mild chest pain and were prescribed oral nonsteroidal anti-inflammatory drugs. During follow-up of the 194 patients with a successful procedure, catheter dysfunction due to thrombosis had occurred in 66 patients, catheter malposition had occurred in 5 patients, and catheter-related blood stream infection had developed in 6 patients. The 3-year primary patency rate was 64.2%, and the 3-year secondary patency rate was 76.3%. CONCLUSIONS: A tCVC placed through a percutaneous SVC puncture had a satisfactory technical success rate and long-term patency rate in patients requiring hemodialysis, providing an optional vascular access for those with exhausted central vein resources. SVC puncture also avoided the use of left-sided catheters and preserved central vein resources. Caution should be given to avoid potential complications such as pleura injury and hemothorax.


Assuntos
Cateteres Venosos Centrais , Veia Cava Superior , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Hemotórax , Diálise Renal , Punções
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