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1.
J Control Release ; 370: 866-878, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38685386

RESUMO

Glioblastoma (GBM) as one of the most lethal brain tumours, remains poor therapeutic index due to its typical characters including heterogeneous, severe immune suppression as well as the existence of blood brain barrier (BBB). Immune sonodynamic (ISD) therapy combines noninvasive sonodynamic therapy with immunotherapy, which has great prospects for the combinational treatment of GBM. Herein, we develop macrophage cell membrane cloaked reactive oxygen species (ROS) responsive biomimetic nanoparticles, co-delivering of sonosensitizer Ce6 and JQ1 (a bromo-domain protein 4 (BRD4) inhibitor which can down-regulate PD-L1) and realizing potent GBM ISD therapy. The ApoE peptide decorated macrophage membrane coating endows these biomimetic nanoparticles with low immunogenicity, efficient BBB permeability, prolonged blood circulation half-live and good biocompatibility. The ROS responsive polymeric inner core could be readily degraded as triggered by excessive ROS under the ultrasound once they accumulated in tumour cells, fast release encapsulated drugs. The generation of ROS not only killed tumour cells via sonodynamic therapy, but also induced immunogenic cell death (ICD) and further activated the anti-tumour immune response. The released JQ1 inhibited tumour cell proliferation and augmented the immune activities by inhibiting the PD-L1 expression on the surface of tumour cells. The cascade sonodynamic and immune therapy resulted in significantly improved median survival time in both orthotopic GL261 and PTEN deficient immunosuppressive CT2A GBM mice models. Therefore, our developed biomimetic nanoparticle platform provides a promising combinational therapy strategy to treat immune suppressive GBM.

2.
BMJ Open ; 14(4): e079434, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569709

RESUMO

INTRODUCTION: Postoperative pain after thoracic surgery impairs patients' quality of life and increases the incidence of respiratory complications. Optimised analgesia strategies include minimally invasive incisions, regional analgesia and early chest tube removal. However, little is known about the optimal analgesic regimen for uniportal video-assisted thoracoscopic surgery (uVATS). METHODS AND ANALYSIS: We will conduct a single-centre, prospective, single-blind, randomised trial. The effects of postoperative analgesia will be tested using thoracic paravertebral block (PVB) in combination with patient-controlled intravenous analgesia (PVB+PCIA), erector spinae plane block (ESPB) in combination with patient-controlled intravenous analgesia (ESPB+PCIA) or PCIA alone; 102 patients undergoing uVATS will be enrolled in this study. Patients will be randomly assigned to the PVB group (30 mL of 0.33% ropivacaine with dexamethasone), ESPB group (40 mL of 0.25% ropivacaine with dexamethasone) or control groups. PCIA with sufentanil will be administered to all patients after surgery. The primary outcome will be total opioid consumption after surgery. Secondary outcomes include postoperative pain score; postoperative chronic pain at rest and during coughing; sensations of touch and pain in the chest wall, non-opioid analgesic consumption; length of stay; ambulation time, the total cost of hospitalisation and long-term postoperative analgesia. Adverse reactions to analgesics and adverse events related to the regional blocks will also be recorded. The statisticians will be blinded to the group allocation. Comparison of the continuous data among the three groups will be performed using a one-way analysis of variance to assess differences among the means. ETHICS AND DISSEMINATION: The results will be published in patient education courses, academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT06016777.


Assuntos
Qualidade de Vida , Cirurgia Torácica Vídeoassistida , Humanos , Ropivacaina , Cirurgia Torácica Vídeoassistida/métodos , Estudos Prospectivos , Método Simples-Cego , Analgésicos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Analgésicos Opioides/uso terapêutico , Analgesia Controlada pelo Paciente , Dexametasona , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Small Methods ; : e2400096, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461538

RESUMO

Although there are various advancements in biomedical in the past few decades, there are still challenges in the treatment of brain diseases. The main difficulties are the inability to deliver a therapeutic dose of the drug to the brain through the blood-brain barrier (BBB) and the serious side effects of the drug. Thus, it is essential to select biocompatible drug carriers and novel therapeutic tools to better enhance the effect of brain disease treatment. In recent years, biomimetic nanoparticles (BNPs) based on natural cell membranes, which have excellent biocompatibility and low immunogenicity, are widely used in the treatment of brain diseases to enable the drug to successfully cross the BBB and target brain lesions. BNPs can prolong the circulation time in vivo, are more conducive to drug aggregation in brain lesions. Cell membranes (CMs) from cancer cells (CCs), red blood cells (RBCs), white blood cells (WBCs), and so on are used as biomimetic coatings for nanoparticles (NPs) to achieve the ability to target, evade clearance, or stimulate the immune system. This review summarizes the application of different cell sources as BNPs coatings in the treatment of brain diseases and discusses the possibilities and challenges of clinical translation.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38326979

RESUMO

BACKGROUND AND AIM: The study aims to evaluate the feasibility of body mass index (BMI)-based individualized small bowel preparation for computed tomography enterography (CTE). METHODS: In this prospective randomized controlled study, patients undergoing CTE were randomly assigned to the individualized group or standardized group. Those in individualized group were given different volumes of mannitol solution based on BMI (1000 mL for patients with BMI < 18.5 kg/m2 , 1500 mL for patients with 18.5 kg/m2  ≤ BMI < 25 kg/m2 and 2000 mL for patients with BMI ≥ 25 kg/m2 ) while patients in the standardized group were all asked to consume 1500-mL mannitol solution. CTE images were reviewed by two experienced radiologists blindly. Each segment of the small bowel was assessed for small bowel image quality and disease detection rates. Patients were invited to record a diary regarding adverse events and acceptance. RESULTS: A total of 203 patients were enrolled and randomly divided into two groups. For patients with BMI < 18.5 kg/m2 , 1000-mL mannitol solution permitted a significantly lower rate of flatulence (P = 0.045) and defecating frequency (P = 0.011) as well as higher acceptance score (P = 0.015), but did not affect bowel image quality and diseases detection compared with conventional dosage. For patients with BMI ≥ 25 kg/m2 , 2000-mL mannitol solution provided better overall image quality (P = 0.033) but comparable rates of adverse events and patients' acceptance compared with conventional dosage. CONCLUSIONS: Individualized bowel preparation could achieve both satisfactory image quality and patients' acceptance thus might be an acceptable alternative in CTE.

5.
Cell Death Dis ; 15(2): 111, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316760

RESUMO

Osteoclasts consume an amount of adenosine triphosphate (ATP) to perform their bone resorption function in the development of osteoporosis. However, the mechanism underlying osteoclast energy metabolism has not been fully elucidated. In addition to glucose, glutamine (Glu) is another major energy carrier to produce ATP. However, the role of Glu metabolism in osteoclasts and the related molecular mechanisms has been poorly elucidated. Here we show that Glu is required for osteoclast differentiation and function, and that Glu deprivation or pharmacological inhibition of Glu transporter ASCT2 by V9302 suppresses osteoclast differentiation and their bone resorptive function. In vivo treatment with V9302 improved OVX-induced bone loss. Mechanistically, RNA-seq combined with in vitro and in vivo experiments suggested that Glu mediates the role of IL-17 in promoting osteoclast differentiation and in regulating energy metabolism. In vivo IL-17 treatment exacerbated OVX-induced bone loss, and this effect requires the participation of Glu or its downstream metabolite α-KG. Taken together, this study revealed a previously unappreciated regulation of IL-17 on energy metabolism, and this regulation is Glu-dependent. Targeting the IL-17-Glu-energy metabolism axis may be a potential therapeutic strategy for the treatment of osteoporosis and other IL-17 related diseases.


Assuntos
Reabsorção Óssea , Glutamina , Interleucina-17 , Osteoclastos , Osteoporose , Humanos , Trifosfato de Adenosina/metabolismo , Reabsorção Óssea/metabolismo , Diferenciação Celular , Metabolismo Energético , Glutamina/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Osteoclastos/metabolismo , Osteogênese , Osteoporose/metabolismo , Ligante RANK/metabolismo
6.
BMJ Open ; 14(1): e079841, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167285

RESUMO

INTRODUCTION: Postoperative laryngopharyngeal discomfort after extubation can lead to severe throat pain, dysphagia, or postoperative tongue oedema. Possible mechanisms include increased oral pressure, obstruction of venous and lymphatic return in the neck, and increased capillary hydrostatic pressure, which leads to oedema of the tongue and upper airway. However, real-time monitoring indicators of anaesthesia are lacking. Therefore, we designed this study to accurately measure the contact force of the tracheal tube on the tongue in different surgical positions during general anaesthesia. METHODS AND ANALYSIS: This prospective single-centre observational study will enrol 54 patients undergoing elective surgery under general anaesthesia for>2 hours with endotracheal tube application from 1 July 2023 to 30 June 2024. Patients will be divided into the supine (Supine group) and high-risk (Flexion group) groups. Dynamic changes in the contact force between the tracheal tube and tongue will be measured using T-Scan technology. All patients will be followed up for 7 days postoperatively. The primary endpoint is postoperative laryngopharyngeal discomfort. Secondary outcomes include the time to the first successful recovery of oral intake of fluids and solid food, and airway-related events. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Ethics Committee of Clinical Research of China-Japan Friendship Hospital (2023-KY-219, approved on 14 September 2023). Informed consent will be obtained during anaesthesia evaluation. This study aims to explore the characteristics of the contact force on the tongue caused by endotracheal intubation in different surgical positions and to provide a better understanding of the risk factors and prevention of postoperative laryngopharyngeal discomfort. The findings of this study will be presented at our hospital, reported on ClinicalTrials.gov, and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05987293.


Assuntos
Anestesia Geral , Intubação Intratraqueal , Humanos , Estudos de Coortes , Estudos Prospectivos , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Anestesia Geral/métodos , Edema , Estudos Observacionais como Assunto
7.
Int J Biol Sci ; 19(13): 4278-4290, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37705739

RESUMO

Radionuclide drug conjugates (RDCs) with antibodies serve as a novel approach for the treatment of malignant tumors including glioblastoma. However, RDCs require optimal antibodies to work efficiently. Hu4G4, a novel B7-H3-targeting humanized monoclonal IgG1 antibody, is highly specific for the human B7-H3 protein (a marker of tumor cells, including glioblastoma cells). Herein, we established 131I-labeled hu4G4 (131I-hu4G4) and showed that it specifically bound to B7-H3 with high affinity (Kd = 0.99 ± 0.07 nM) and inhibited the growth of U87 cells in vitro. 131I-hu4G4 displayed potent in situ antitumor activity in a mouse model of glioma based on GL261 Red-Fluc-B7-H3 cells. More importantly, 131I-hu4G4 remodeled the tumor microenvironment and promoted the transformation of glioma from "cold" to "hot" tumors by promoting CD4+ and CD8+ T cell infiltration and the polarization of M2 to M1. Therefore, the antitumor activity observed with 131I-hu4G4, together with its ability to enhance antitumor immune responses, makes it a novel candidate for radioimmunotherapy of glioblastoma.


Assuntos
Glioblastoma , Glioma , Humanos , Animais , Camundongos , Glioblastoma/radioterapia , Microambiente Tumoral , Radioimunoterapia , Glioma/radioterapia , Anticorpos Monoclonais Humanizados
8.
Chemosphere ; 341: 140118, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37690552

RESUMO

To maintain a comfortable and healthy indoor environment without large amounts of energy consumption is of great importance. The progress of multifunctional indoor coatings with formaldehyde photodegradation and humidity buffering capability is necessary. From the viewpoints of circular economy, the preparation of effective photocatalysts (denoted as sFCC/GCN-x and ESF/GCN-y) via the decoration of recycling industrial wastes (i.e., spent fluid catalytic cracking catalysts (sFCC) and enhancement silica fume (ESF)) onto graphitic carbon nitride (GCN) by using a simple route is reported. The obtained results show that the prepared sFCC/GCN-0.15 and ESF/GCN-0.15 photocatalysts have the rate constants of formaldehyde degradation of 0.0075 and 0.0082 min-1, respectively, which are superior to that of pristine GCN (0.0044 min-1) under visible-light irradiation. The enhanced transfer kinetics of photogenerated electrons and declined recombination of electron-hole pairs may account for the surpassing photocatalytic performance. Results obtained from electron paramagnetic resonance spectra and Mott-Schottky plots indicate that the formation of ï½¥O2- via the reaction of O2 with electrons generated on the conduction band is the major reaction pathway to photodegrade formaldehyde under visible light. To further assess the real applications of prepared photocatalysts, the sFCC/GCN-0.15 and ESF/GCN-0.15 are used to fabricate the multifunctional coatings (denoted as s- and E-coatings) with sFCC and ESF as the main compositions. Experimentally, the E-coatings could reach the formaldehyde degradation efficiency of ca. 84.5% after 3 h of visible light irradiation and excellent humidity buffering ability (293.8 g m-2) which is at least 10-folds higher than commercial coatings (28.9 g m-2). This notable progress of humidity buffering capacity on E-coatings can be attributed to their surface textural properties. Most importantly, this study exemplifies the valorization of inorganic silica wastes to produce sustainable and multifunctional coatings which may offer the practical and cost-effective applications in the indoor living space.


Assuntos
Formaldeído , Catálise , Gases , Umidade , Fotólise
9.
Heliyon ; 9(8): e18892, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37593640

RESUMO

An effective disaster prevention map ensures public safety and efficient evacuation during emergencies. Emergency evacuation information design in Taiwan is in its nascent stages. This study focuses on individuals' understanding, behavior, and decision-making during disaster prevention to devise suitable disaster prevention map norms. We examined the Emergency Planning Zone's existing disaster prevention methods and surveyed the community to understand their disaster prevention concepts and needs. We conducted two experiments: the first tested the comprehension of existing disaster prevention maps and identified their issues, while the second evaluated a redesigned map based on Experiment 1's findings. We discovered that all age groups agree on needing accurate, fast information and diverse evacuation route options. Experiment 1 revealed disproportionate assembly point icons on the existing map, leading to navigation difficulties. The map also failed to mark landmarks, road names, and blocked intersections accurately. The redesigned map in Experiment 2 addressed these issues, showing that improving map information design aids recognition and memory, and bridges wayfinding behavior gaps in people with different spatial abilities. We suggest marking evacuation routes on maps, placing corresponding signs on-site, and locating assembly points near landmarks for easier navigation.

10.
Chem Sci ; 14(31): 8401-8407, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37564418

RESUMO

Herein, a triphenylamine derivative (TP-3PY) possessing 4-(4-bromophenyl)pyridine (PY) as an electron-accepting group and tris[p-(4-pyridylvinyl)phenyl]amine (TPA) with large two-photon absorption cross-sections as an electron-donating group was obtained, and showed intense absorption in the visible light region (λmax = 509 nm) and weak near-infrared (NIR) fluorescence emission at 750 nm. After complexation with cucurbit[8]uril (CB[8]), TP-3PY showed bright NIR fluorescence emission at 727 nm and phosphorescence emission at 800 nm. When the supramolecular assembly (TP-3PY⊂CB[8]) further interacted with dodecyl-modified sulfonatocalix[4]arene (SC4AD), the fluorescence and phosphorescence emissions were further enhanced at 710 and 734 nm, respectively. However, only the fluorescence emission of TP-3PY was enhanced in the presence of cucurbit[7]uril (CB[7]) and SC4AD. More interestingly, the photoluminescence of TP-3PY⊂CB[8]@SC4AD and TP-3PY⊂CB[7]@SC4AD assemblies could be excited by both visible (510 nm) and NIR light (930 nm). Finally, these ternary supramolecular assemblies with bright NIR light emission were applied to lysosome imaging of tumor cells and real-time biological imaging of mice.

11.
Sci Total Environ ; 902: 166056, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37558073

RESUMO

Duckweed is a cadmium (Cd) hyperaccumulator. However, its enrichment characteristics and physiological responses to Cd have not been systematically studied. The physiological responses, enrichment characteristics, diversity of endophytic bacterial communities, and isolation of Cd-resistant endophytes in duckweed (Lemna minor 0014) were studied for different durations and Cd concentrations. The results indicated that peroxidase (POD) and catalase (CAT) activities decreased while superoxide dismutase activity first increased and then decreased with increasing Cd stress duration. POD activities, CAT activities, and O2- increased as Cd concentrations increased. Malondialdehyde content and Cd accumulation in duckweed increased with increasing concentrations and time. This endophytic diversity study identified 488 operational taxonomic units, with the dominant groups being Proteobacteria, Firmicutes, and Actinobacteria. Paenibacillus sp. Y11, a strain tolerant to high concentrations of Cd and capable of significantly promoting duckweed growth, was isolated from the plant. Our study revealed the effects of heavy metals on aquatic plants, providing a theoretical basis for the application of duckweed in water pollution.


Assuntos
Araceae , Metais Pesados , Paenibacillus , Poluentes do Solo , Cádmio/toxicidade , Poluentes do Solo/toxicidade , Antioxidantes/farmacologia
12.
Nat Commun ; 14(1): 4557, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37507371

RESUMO

Glioblastoma (GBM) remains the most lethal malignant tumours. Gboxin, an oxidative phosphorylation inhibitor, specifically restrains GBM growth by inhibiting the activity of F0F1 ATPase complex V. However, its anti-GBM effect is seriously limited by poor blood circulation, the blood brain barrier (BBB) and non-specific GBM tissue/cell uptake, leading to insufficient Gboxin accumulation at GBM sites, which limits its further clinical application. Here we present a biomimetic nanomedicine (HM-NPs@G) by coating cancer cell-mitochondria hybrid membrane (HM) on the surface of Gboxin-loaded nanoparticles. An additional design element uses a reactive oxygen species responsive polymer to facilitate at-site Gboxin release. The HM camouflaging endows HM-NPs@G with unique features including good biocompatibility, improved pharmacokinetic profile, efficient BBB permeability and homotypic dual tumour cell and mitochondria targeting. The results suggest that HM-NPs@G achieve improved blood circulation (4.90 h versus 0.47 h of free Gboxin) and tumour accumulation (7.73% ID/g versus 1.06% ID/g shown by free Gboxin). Effective tumour inhibition in orthotopic U87MG GBM and patient derived X01 GBM stem cell xenografts in female mice with extended survival time and negligible side effects are also noted. We believe that the biomimetic Gboxin nanomedicine represents a promising treatment for brain tumours with clinical potential.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Humanos , Feminino , Animais , Camundongos , Glioblastoma/patologia , Nanomedicina , Linhagem Celular Tumoral , Membranas Mitocondriais/patologia , Barreira Hematoencefálica/metabolismo , Mitocôndrias , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo
13.
J Orthop Surg Res ; 18(1): 464, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37370161

RESUMO

BACKGROUND: The Neurogenic Bladder Symptom Score-Short Form (NBSS-SF) evaluates the impact of disease-specific symptoms on the quality of life in individuals with neurogenic bladder (NB). There is no data on the validity and reliability of the NBSS-SF questionnaire in the Arabic language, so this study aimed to examine the psychometric characteristics of the Arabic NBSS-SF in patients with spinal cord injury (SCI). METHODS: International standards were followed when culturally adapting the questionnaire. The Arabic version was conducted in patients with neurogenic bladder caused by SCI twice within a 14 day period. Psychometric properties such as content validity, construct validity, internal consistency, and test-retest reliability were tested. Internal consistency and test-retest reliability was evaluated using Cronbach's alpha, and the Intraclass Correlation Coefficient (ICC), respectively. Construct validity was assessed by comparing the NBSS-SF with the Short Form (SF-12) and the Qualiveen questionnaire. RESULTS: One hundred and one patients with SCI participated in the study. The internal consistency for the overall NBSS-SF score (Cronbach's α of 0.82) and for each subdomain was variable (urinary incontinence 0.84; storage/voiding 0.72; consequences 0.57). ICC was 0.91 for the overall score and 0.94 for the urinary incontinence subdomain, 0.72 for storage/voiding, and 0.90 for consequences. The correlation analysis showed that the Arabic version of NBSS-SF has good construct validity. CONCLUSION: Our results showed that the Arabic version of NBSS-SF is a valid and reliable instrument for evaluating NB symptoms in the Arabic population suffering from SCI.


Assuntos
Traumatismos da Medula Espinal , Bexiga Urinaria Neurogênica , Incontinência Urinária , Humanos , Qualidade de Vida , Bexiga Urinaria Neurogênica/diagnóstico , Bexiga Urinaria Neurogênica/etiologia , Reprodutibilidade dos Testes , Idioma , Inquéritos e Questionários , Incontinência Urinária/complicações , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/epidemiologia , Psicometria
14.
Biosensors (Basel) ; 13(4)2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37185569

RESUMO

Highly bio-compatible organic semiconductors are widely used as biosensors, but their long-term stability can be compromised due to photo-degradation and structural instability. To address this issue, scientists have developed organic semiconductor nanoparticles (OSNs) by incorporating organic semiconductors into a stable framework or self-assembled structure. OSNs have shown excellent performance and can be used as high-resolution biosensors in modern medical and biological research. They have been used for a wide range of applications, such as detecting small biological molecules, nucleic acids, and enzyme levels, as well as vascular imaging, tumor localization, and more. In particular, OSNs can simulate fine particulate matters (PM2.5, indicating particulate matter with an aerodynamic diameter less than or equal to 2.5 µm) and can be used to study the biodistribution, clearance pathways, and health effects of such particles. However, there are still some problems that need to be solved, such as toxicity, metabolic mechanism, and fluorescence intensity. In this review, based on the structure and design strategies of OSNs, we introduce various types of OSNs-based biosensors with functional groups used as biosensors and discuss their applications in both in vitro and in vivo tracking. Finally, we also discuss the design strategies and potential future trends of OSNs-based biosensors. This review provides a theoretical scaffold for the design of high-performance OSNs-based biosensors and highlights important trends and future directions for their development and application.


Assuntos
Técnicas Biossensoriais , Nanopartículas , Pontos Quânticos , Distribuição Tecidual , Técnicas Biossensoriais/métodos , Semicondutores
17.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36982442

RESUMO

Osteoarthritis (OA), the most common chronic inflammatory joint disease, is characterized by progressive cartilage degeneration, subchondral bone sclerosis, synovitis, and osteophyte formation. Metformin, a hypoglycemic agent used in the treatment of type 2 diabetes, has been evidenced to have anti-inflammatory properties to treat OA. It hampers the M1 polarization of synovial sublining macrophages, which promotes synovitis and exacerbates OA, thus lessening cartilage loss. In this study, metformin prevented the pro-inflammatory cytokines secreted by M1 macrophages, suppressed the inflammatory response of chondrocytes cultured with conditional medium (CM) from M1 macrophages, and mitigated the migration of M1 macrophages induced by interleukin-1ß (IL-1ß)-treated chondrocytes in vitro. In the meantime, metformin reduced the invasion of M1 macrophages in synovial regions brought about by the destabilization of medial meniscus (DMM) surgery in mice, and alleviated cartilage degeneration. Mechanistically, metformin regulated PI3K/AKT and downstream pathways in M1 macrophages. Overall, we demonstrated the therapeutic potential of metformin targeting synovial M1 macrophages in OA.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Osteoartrite , Sinovite , Camundongos , Animais , Metformina/farmacologia , Metformina/uso terapêutico , Metformina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Macrófagos/metabolismo , Condrócitos/metabolismo , Sinovite/tratamento farmacológico , Sinovite/metabolismo
18.
Nat Commun ; 14(1): 1578, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949068

RESUMO

Diffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target.


Assuntos
Glioblastoma , Humanos , Células HEK293 , Ligantes , Glioblastoma/metabolismo , Transdução de Sinais , Animais , Camundongos , Invasividade Neoplásica , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Front Nutr ; 10: 1042522, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36845060

RESUMO

Background: There is only limited evidence for an association between calcium (Ca) and depression, and the relationship was inconsistent. Therefore, the aim of this study was to assess the relationship between dietary Ca and the risk of depressive symptoms in individuals over the age of 18 in the US. Methods: We extracted 14,971 participants from the US National Health and Nutrition Examination Survey (NHANES) 2007-2016 to probe their associations. Dietary Ca intake was measured through 24 h dietary recall method. Patients with the Patient Health Questionnaire-9 (PHQ-9) ≥ 10 scores were believed to have depressive symptoms. The association between dietary Ca and depressive symptoms was investigated using multivariate logistic regression, sensitivity analysis, and restricted cubic spline regression. Results: In this study, 7.6% (1,144/14,971) of them had depressive symptoms. After adjusting for sex, age, race, poverty to income ratio (PIR), marital status, education, body mass index (BMI), caffeine intake, carbohydrates intake, total energy intake, smoking status, alcohol consumption, physical activity, diabetes, hypertension, severe cardiovascular disease (CVD), cancer, serum vitamin D, serum Ca, and Ca supplement, the adjusted ORs value [95% confidence interval (CI)] of depression for the lowest category (Q1 ≤ 534 mg/day) vs. Q2-Q4 of Ca intake were 0.83 (0.69-0.99), 0.97 (0.65-0.95), and 0.80 (0.63-0.98) with the p for trend (p = 0.014). The relationship between dietary Ca intake and depressive symptoms was linear (non-linear p = 0.148). None of the interactions were significant except among races (p for interaction = 0.001). Conclusion: Association between dietary Ca and the prevalence of depressive symptoms in US adults. And Ca intake was negatively associated with the risk of depressive symptoms. As Ca intake increased, the prevalence of depressive symptoms decreased.

20.
Radiat Oncol ; 18(1): 14, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670447

RESUMO

OBJECTIVE: To systematically evaluate the guidelines for the diagnosis and treatment of radioactive enteritis, compare their differences and reasons and provide some reference for updating them. METHODS: This study used guidelines related to radiation enteritis by searching a database. Four independent reviewers used the AGREE II evaluation tool to evaluate the quality of the included guidelines, collate their main recommendations, and analyze the highest evidence supporting the main recommendations. RESULTS: Six diagnostic and therapeutic guidelines for radiation enteritis were included in this study, one of which, the American Society for Gastrointestinal Endoscopy guidelines, had an overall score of over 60%, which is worthy of clinical recommendation. In the diagnosis and treatment of radioactive rectal injury, the recommendations for hemorrhagic endoscopic treatment are mature and mainly include (I) argon plasma coagulation; (II) formalin treatment; (III) bipolar electrocoagulation; (IV) heater probe; (V) radiofrequency ablation; and (VI) cryoablation. CONCLUSION: The methodological quality of radioactive enteritis guidelines is unequal; even in the same guidelines, different domains have a large difference. For radioactive rectal damage diagnosis, a type of endoscopic treatment recommendation is more mature, but the overall diagnosis and treatment of radioactive enteritis still lacks high-quality research evidence.


Assuntos
Enterite , Lesões por Radiação , Doenças Retais , Humanos , Estados Unidos , Endoscopia , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Lesões por Radiação/terapia , Enterite/diagnóstico , Enterite/etiologia , Enterite/terapia
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