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1.
Adv Healthc Mater ; : e2401619, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011810

RESUMO

Increased inflammatory responses and oxidative stress at the wound site following skin trauma impair healing. Furthermore, skin scarring places fibroblasts under severe mechanical stress and aggravates pathological fibrosis. A novel liposomal composite hydrogel is engineered for wound microenvironment remodeling, incorporating dual-loaded liposomes into gelatin methacrylate to create a nanocomposite hydrogel. Notably, tetrahydrocurcumin (THC) and hepatocyte growth factor (HGF) are encapsulated in the hydrophobic and hydrophilic layers of liposomes, respectively. The composite hydrogel maintains porous nanoarchitecture, demonstrating sustainable THC and HGF release and enhanced mechanical properties and biocompatibility. This system effectively promotes cell proliferation and angiogenesis and attenuates apoptosis. It decreases the expression of the inflammatory factors by inhibiting the high-mobility group box /receptor for advanced glycation end product/NF-κB (HMGB1/RAGE/NF-κB)pathway and increases macrophage polarization from M1 to M2 in vitro, effectively controlling inflammatory responses. It exhibits remarkable antioxidant properties by scavenging excess reactive oxygen species and free radicals. Most importantly, it effectively prevents scar formation by restraining the transforming growth factor beta (TGF-ß)/Smads pathway that downregulates associated fibrotic factors. It demonstrates strong therapeutic effects against inflammation and fibrosis in a rat skin wound model with biosafety, advancing the development of innovative hydrogel-based therapeutic delivery strategies for clinical scarless wound therapy.

2.
J Nanobiotechnology ; 22(1): 387, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951841

RESUMO

Metal-organic frameworks (MOFs) are metal-organic skeleton compounds composed of self-assembled metal ions or clusters and organic ligands. MOF materials often have porous structures, high specific surface areas, uniform and adjustable pores, high surface activity and easy modification and have a wide range of prospects for application. MOFs have been widely used. In recent years, with the continuous expansion of MOF materials, they have also achieved remarkable results in the field of antimicrobial agents. In this review, the structural composition and synthetic modification of MOF materials are introduced in detail, and the antimicrobial mechanisms and applications of these materials in the healing of infected wounds are described. Moreover, the opportunities and challenges encountered in the development of MOF materials are presented, and we expect that additional MOF materials with high biosafety and efficient antimicrobial capacity will be developed in the future.


Assuntos
Estruturas Metalorgânicas , Cicatrização , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Cicatrização/efeitos dos fármacos , Humanos , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Porosidade , Infecção dos Ferimentos/tratamento farmacológico
3.
Front Pharmacol ; 15: 1394730, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974036

RESUMO

Background: There have been numerous studies on NMDA receptors as therapeutic targets for depression. However, so far, there has been no comprehensive scientometric analysis of this field. Thus, we conducted a scientometric analysis with the aim of better elucidating the research hotspots and future trends in this field. Methods: Publications on NMDAR in Depression between 2004 and 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Then, VOSviewer, CiteSpace, Scimago Graphica, and R-bibliometrix-were used for the scientometric analysis and visualization. Results: 5,092 qualified documents were identified to scientometric analysis. In the past 20 years, there has been an upward trend in the number of annual publications. The United States led the world in terms of international collaborations, publications, and citations. 15 main clusters were identified from the co-cited references analysis with notable modularity (Q-value = 0.7628) and silhouette scores (S-value = 0.9171). According to the keyword and co-cited references analysis, treatment-resistant depression ketamine (an NMDAR antagonist), oxidative stress, synaptic plasticity, neuroplasticity related downstream factors like brain-derived neurotrophic factor were the research hotspots in recent years. Conclusion: As the first scientometric analysis of NMDAR in Depression, this study shed light on the development, trends, and hotspots of research about NMDAR in Depression worldwide. The application and potential mechanisms of ketamine in the treatment of major depressive disorder (MDD) are still a hot research topic at present. However, the side effects of NMDAR antagonist like ketamine have prompted research on new rapid acting antidepressants.

4.
J Nanobiotechnology ; 22(1): 342, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890721

RESUMO

Acute lung injury (ALI) is a common complication in patients with severe burns and has a complex pathogenesis and high morbidity and mortality rates. A variety of drugs have been identified in the clinic for the treatment of ALI, but they have toxic side effects caused by easy degradation in the body and distribution throughout the body. In recent years, as the understanding of the mechanism underlying ALI has improved, scholars have developed a variety of new nanomaterials that can be safely and effectively targeted for the treatment of ALI. Most of these methods involve nanomaterials such as lipids, organic polymers, peptides, extracellular vesicles or cell membranes, inorganic nanoparticles and other nanomaterials, which are targeted to reach lung tissues to perform their functions through active targeting or passive targeting, a process that involves a variety of cells or organelles. In this review, first, the mechanisms and pathophysiological features of ALI occurrence after burn injury are reviewed, potential therapeutic targets for ALI are summarized, existing nanomaterials for the targeted treatment of ALI are classified, and possible problems and challenges of nanomaterials in the targeted treatment of ALI are discussed to provide a reference for the development of nanomaterials for the targeted treatment of ALI.


Assuntos
Lesão Pulmonar Aguda , Queimaduras , Nanoestruturas , Lesão Pulmonar Aguda/tratamento farmacológico , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Queimaduras/tratamento farmacológico , Animais , Pulmão , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química
5.
J Int Med Res ; 52(6): 3000605241253759, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38853406

RESUMO

Treatment of lower limb ischemia in patients with diabetes is challenging because of the location of the ulcers and the complexity of their pathogenesis. Carbon dioxide fractional laser (CO2FL) therapy in conjunction with tibial periosteum distraction could become a substitute for conventional methods. We herein describe a patient diagnosed with ischemic diabetic foot with a complex ulcer in the upper third of the tibia. Laser irradiation (Deep FX mode with 30 mJ of energy and 10% density) was applied to the entire region of skin below the knee after surface anesthesia, and this treatment was performed twice a week until the ulcer healed. Computed tomography angiography showed successful establishment of a blood supply to the back of the right foot after treatment. Skin grafting was successfully performed, with only a few wounds remaining on the foot 8 months after treatment. The pain score was significantly decreased at the last follow-up. No complications occurred. This case report provides guidance for the performance of CO2FL, a fast, easy, accurate treatment in patients with diabetes. CO2FL can target lower limb arterial occlusive disease accompanied by refractory ulcers, addressing the underlying vascular occlusion and dysfunction as well as promoting microcirculation and wound healing.


Assuntos
Pé Diabético , Isquemia , Lasers de Gás , Extremidade Inferior , Humanos , Pé Diabético/terapia , Pé Diabético/cirurgia , Lasers de Gás/uso terapêutico , Isquemia/etiologia , Isquemia/terapia , Masculino , Extremidade Inferior/irrigação sanguínea , Idoso , Pessoa de Meia-Idade , Cicatrização , Resultado do Tratamento
6.
ACS Nano ; 18(24): 15845-15863, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38832685

RESUMO

Nanozyme-driven catalytic therapy provides a promising treatment strategy for bacterial biofilm-infected wounds. However, the single functionality and limited catalytic efficiency of nanozyme-based materials often restrict the effectiveness of wound infection treatment. In this study, CuCo2O4 nanoflowers with multiple enzymatic activities were prepared for antibacterial/antibiofilm treatment by cuproptosis-like death. CuCo2O4 exhibited peroxidase-like (POD-like) and oxidase-like (OXD-like) dual enzyme activities that generated large amounts of •OH and O2•-. Moreover, the glutathione peroxidase-like (GSH-Px-like) activity of CuCo2O4 was able to reduce the overexpression of GSH in the wound microenvironment, enhancing the therapeutic effects of reactive oxygen species (ROS). The morphology of CuCo2O4 was modified using a hydrothermal method with PEG4000 as the solvent, resulting in the exposure of more active center sites and a significant improvement in enzyme catalytic activity. The in vitro results demonstrated the pronounced disruption effect of CuCo2O4 on biofilms formed by bacteria. In vivo, CuCo2O4 significantly promoted angiogenesis, collagen deposition, and cell proliferation. Transcriptome sequencing revealed that elevated ROS levels in bacteria led to cell membrane damage and metabolic disruption. In addition, Cu2+ overload in bacteria induces lipid peroxidation accumulation and disrupts the respiratory chain and tricarboxylic acid (TCA) cycle, ultimately leading to bacterial cuproptosis-like death. This therapeutic strategy, which combines the synergistic effects of multiple enzyme-like activities with cuproptosis-like death, provides an approach for treating biofilm infections.


Assuntos
Antibacterianos , Biofilmes , Cobre , Espécies Reativas de Oxigênio , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Espécies Reativas de Oxigênio/metabolismo , Cobre/química , Cobre/farmacologia , Animais , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Catálise , Camundongos
7.
Lancet Digit Health ; 6(7): e458-e469, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38849291

RESUMO

BACKGROUND: Accurately distinguishing between malignant and benign thyroid nodules through fine-needle aspiration cytopathology is crucial for appropriate therapeutic intervention. However, cytopathologic diagnosis is time consuming and hindered by the shortage of experienced cytopathologists. Reliable assistive tools could improve cytopathologic diagnosis efficiency and accuracy. We aimed to develop and test an artificial intelligence (AI)-assistive system for thyroid cytopathologic diagnosis according to the Thyroid Bethesda Reporting System. METHODS: 11 254 whole-slide images (WSIs) from 4037 patients were used to train deep learning models. Among the selected WSIs, cell level was manually annotated by cytopathologists according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) guidelines of the second edition (2017 version). A retrospective dataset of 5638 WSIs of 2914 patients from four medical centres was used for validation. 469 patients were recruited for the prospective study of the performance of AI models and their 537 thyroid nodule samples were used. Cohorts for training and validation were enrolled between Jan 1, 2016, and Aug 1, 2022, and the prospective dataset was recruited between Aug 1, 2022, and Jan 1, 2023. The performance of our AI models was estimated as the area under the receiver operating characteristic (AUROC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. The primary outcomes were the prediction sensitivity and specificity of the model to assist cyto-diagnosis of thyroid nodules. FINDINGS: The AUROC of TBSRTC III+ (which distinguishes benign from TBSRTC classes III, IV, V, and VI) was 0·930 (95% CI 0·921-0·939) for Sun Yat-sen Memorial Hospital of Sun Yat-sen University (SYSMH) internal validation and 0·944 (0·929 - 0·959), 0·939 (0·924-0·955), 0·971 (0·938-1·000) for The First People's Hospital of Foshan (FPHF), Sichuan Cancer Hospital & Institute (SCHI), and The Third Affiliated Hospital of Guangzhou Medical University (TAHGMU) medical centres, respectively. The AUROC of TBSRTC V+ (which distinguishes benign from TBSRTC classes V and VI) was 0·990 (95% CI 0·986-0·995) for SYSMH internal validation and 0·988 (0·980-0·995), 0·965 (0·953-0·977), and 0·991 (0·972-1·000) for FPHF, SCHI, and TAHGMU medical centres, respectively. For the prospective study at SYSMH, the AUROC of TBSRTC III+ and TBSRTC V+ was 0·977 and 0·981, respectively. With the assistance of AI, the specificity of junior cytopathologists was boosted from 0·887 (95% CI 0·8440-0·922) to 0·993 (0·974-0·999) and the accuracy was improved from 0·877 (0·846-0·904) to 0·948 (0·926-0·965). 186 atypia of undetermined significance samples from 186 patients with BRAF mutation information were collected; 43 of them harbour the BRAFV600E mutation. 91% (39/43) of BRAFV600E-positive atypia of undetermined significance samples were identified as malignant by the AI models. INTERPRETATION: In this study, we developed an AI-assisted model named the Thyroid Patch-Oriented WSI Ensemble Recognition (ThyroPower) system, which facilitates rapid and robust cyto-diagnosis of thyroid nodules, potentially enhancing the diagnostic capabilities of cytopathologists. Moreover, it serves as a potential solution to mitigate the scarcity of cytopathologists. FUNDING: Guangdong Science and Technology Department. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Aprendizado Profundo , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/patologia , China , Estudos Retrospectivos , Biópsia por Agulha Fina , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Sensibilidade e Especificidade , Glândula Tireoide/patologia , Idoso , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia
8.
Adv Healthc Mater ; : e2400101, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38794907

RESUMO

Acute wounds are converted to chronic wounds due to advanced age and diabetic complications. Nanozymes catalyze ROS production to kill bacteria without causing drug resistance, while microneedles (MNs) can break through the skin barrier to deliver drugs effectively. Nanozymes can be intergrateded into MNs delivery systems to improve painless drug delivery. It can also reduce the effective dose of drug sterilization while increasing delivery efficiency and effectively killing wounded bacteria while preventing drug resistance. This paper describes various types of metal nanozymes from previous studies and compares their mutual enhancement with nanozymes. The pooled results show that the MNs, through material innovation, are able to both penetrate the scab and deliver nanozymes and exert additional anti-inflammatory and bactericidal effects. The catalytic effect of some of the nanozymes can also accelerate the lysis of the MNs or create a cascade reaction against inflammation and infection. However, the issue of increased toxicity associated with skin penetration and clinical translation remains a challenge. This study reviews the latest published results and corresponding challenges associated with the use of MNs combined with nanozymes for the treatment of wounds, providing further information for future research.

9.
Microorganisms ; 12(5)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38792846

RESUMO

Both pandemic and seasonal influenza are major health concerns, causing significant mortality and morbidity. Current influenza drugs primarily target viral neuraminidase and RNA polymerase, which are prone to drug resistance. Polyoxometalates (POMs) are metal cation clusters bridged by oxide anions. They have exhibited potent anti-tumor, antiviral, and antibacterial effects. They have remarkable activity against various DNA and RNA viruses, including human immunodeficiency virus, herpes simplex virus, hepatitis B and C viruses, dengue virus, and influenza virus. In this study, we have identified sodium polyoxotungstate (POM-1) from an ion channel inhibitor library. In vitro, POM-1 has been demonstrated to have potent antiviral activity against H1N1, H3N2, and oseltamivir-resistant H1N1 strains. POM-1 can cause virion aggregation during adsorption, as well as endocytosis. However, the aggregation is reversible; it does not interfere with virus adsorption and endocytosis. Our results suggest that POM-1 exerts its antiviral activity by inhibiting the nuclear import of viral ribonucleoprotein (vRNP). This distinct mechanism of action, combined with its wide range of efficacy, positions POM-1 as a promising therapeutic candidate for influenza treatment and warrants further investigation.

10.
Adv Mater ; 36(26): e2401724, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38575151

RESUMO

Simultaneously achieving a high photoluminescence quantum yield (PLQY), ultrashort exciton lifetime, and suppressed concentration quenching in thermally activated delayed fluorescence (TADF) materials is desirable yet challenging. Here, a novel acceptor-donor-acceptor type TADF emitter, namely, 2BO-sQA, wherein two oxygen-bridged triarylboron (BO) acceptors are arranged with cofacial alignment and positioned nearly orthogonal to the rigid dispirofluorene-quinolinoacridine (sQA) donor is reported. This molecular design enables the compound to achieve highly efficient (PLQYs up to 99%) and short-lived (nanosecond-scale) blue TADF with effectively suppressed concentration quenching in films. Consequently, the doped organic light-emitting diodes (OLEDs) base on 2BO-sQA achieve exceptional electroluminescence performance across a broad range of doping concentrations, maintaining maximum external quantum efficiencies (EQEs) at over 30% for doping concentrations ranging from 10 to 70 wt%. Remarkably, the nondoped blue OLED achieves a record-high maximum EQE of 26.6% with a small efficiency roll-off of 14.0% at 1000 candelas per square meter. By using 2BO-sQA as the sensitizer for the multiresonance TADF emitter ν-DABNA, TADF-sensitized fluorescence OLEDs achieve high-efficiency deep-blue emission. These results demonstrate the feasibility of this molecular design in developing TADF emitters with high efficiency, ultrashort exciton lifetime, and minimal concentration quenching.

11.
Health Sci Rep ; 7(4): e1988, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572119

RESUMO

Background and Aims: To assess patient comfort, wound healing, and scarring at the 6-month follow-up of split-skin graft donor sites treated with Ba-Hao burn ointment (BHBO) gauze, a compound preparation of traditional Chinese medicine since 1970s, compared with petrolatum gauze. Methods: Thirty patients admitted to the Department of Burns of the First Affiliated Hospital of Anhui Medical University between September 2021 and September 2022 participated in this randomized, prospective, self-control clinical study. After harvesting the split skin, donor sites were divided into two parts along the midline. BHBO gauze was applied to half of the donor wounds, and petrolatum gauze was applied to the other half. The wound healing time, pain scores on the postoperative Days 3, 6, and 9, and Vancouver Scar Scale (VSS) score at the 6-month follow-up were assessed. Results: The wound healing time was significantly shorter in the BHBO group than in the control group (10.07 ± 1.48 days vs. 11.50 ± 1.74 days, p < 0.001). On postoperative Days 3 and 6, the pain scores quantified by visual analog scores were significantly lower in the BHBO group than in the control group (5.33 ± 1.54 and 4.17 ± 1.51, respectively vs. 7.57 ± 1.41 and 5.20 ± 1.47, respectively). The difference in the visual analog scale score on postoperative Day 9 between the groups was not significant (p > 0.05). Microbiological assessment revealed the absence of bacterial contamination in both groups. At the 6-month follow up, the VSS score was significantly lower in the BHBO group (6.67 ± 1.92) than in the control group (9.57 ± 1.55). Conclusion: BHBO resulted in faster donor-site healing, reduced postoperative pain, and improved scar quality at the 6-month follow-up than petrolatum gauze alone.

12.
Burns ; 50(5): 1223-1231, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38490834

RESUMO

INTRODUCTION: One of the most common traumatic injuries, burn injuries lead to at least 180,000 deaths each year worldwide. Massive burns result in severe tissue loss and increase the rate of infection. Eschar excision with skin grafting is the gold standard of treatments for massive burns. Retaining dermis tissue is the key to ensuring the survival of skin grafts and rapidly closing exposed tissues. Traditional eschar excision with Humby or Weck knife controls the depth of excision until the dermis, but ensuring the accuracy of excision is challenging. Hydrosurgery minimizes damage to uninjured tissues during the removal of necrotic tissues. A foot pedal is used to adjust debridement depth for precise debridement. To figure out the clinical advantages and risks of using hydrosurgery in treating massive burns, this study has been conducted. METHOD: Forty-two patients with massive burns and total body surface area (TBSA) of > 30% were treated at the First Affiliated Hospital of Anhui Medical University from May 2020 to January 2023. They underwent hydrosurgical eschar excision with MEEK microskin graft (n = 23) or tangential excision with MEEK microskin graft (n = 19). RESULT: No statistically significant differences (p > 0.05) in the following demographics were found between the two groups: age, weight, TBSA, deep-partial-thickness burn, gender, inhalation injury, shock, excision area, and MEEK ratio. By contrast, statistically significant differences in per unit area of operation time, per unit area of operation spending, hospitalization cost, hospitalization duration, wound-healing time, skin graft survival, and scar quality were found between hydrosurgical excision group with MEEK microskin graft and conventional excision group with MEEK microskin graft. CONCLUSION: The hydrosurgical excision system showed better clinical effects for patients with massive burns.


Assuntos
Superfície Corporal , Queimaduras , Desbridamento , Transplante de Pele , Humanos , Queimaduras/cirurgia , Masculino , Feminino , Transplante de Pele/métodos , Adulto , Estudos Retrospectivos , Desbridamento/métodos , Pessoa de Meia-Idade , Adulto Jovem , Tempo de Internação/estatística & dados numéricos , Adolescente , Resultado do Tratamento
13.
Burns ; 50(5): 1247-1258, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38503573

RESUMO

OBJECTIVE: Research indicates that long noncoding RNAs (lncRNAs) contribute significantly to fibrotic diseases. Although lncRNAs may play a role in hypertrophic scars after burns, its mechanisms remain poorly understood. METHODS: Using chip technology, we compared the lncRNA expression profiles of burn patients and healthy controls (HCs). Microarray results were examined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) to verify their reliability. The biological functions of differentially expressed mRNAs and the relationships between genes and signaling pathways were investigated by Gene Ontology (GO) and pathway analyses, respectively. RESULTS: In contrast with HCs, it was found that 2738 lncRNAs (1628 upregulated) and 2166 mRNAs (1395 upregulated) were differentially expressed in hypertrophic scars after burn. Results from RT-PCR were consistent with those from microarray. GO and pathway analyses revealed that the differentially expressed mRNAs are mainly associated with processes related to cytokine secretion in the immune system, notch signaling, and MAPK signaling. CONCLUSION: The lncRNA expression profiles of hypertrophic scars after burn changed significantly compared with HCs. It was believed that the transcripts could be used as potential targets for inhibiting abnormal scar formation in burn patients.


Assuntos
Queimaduras , Cicatriz Hipertrófica , RNA Longo não Codificante , RNA Mensageiro , Humanos , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/etiologia , Queimaduras/metabolismo , Queimaduras/complicações , Queimaduras/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Masculino , Feminino , Adulto , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Estudos de Casos e Controles , Pessoa de Meia-Idade , Adulto Jovem , Regulação para Cima , Perfilação da Expressão Gênica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Adolescente , Análise de Sequência com Séries de Oligonucleotídeos , Ontologia Genética
14.
Antimicrob Agents Chemother ; 68(4): e0135023, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38470034

RESUMO

Influenza remains a significant threat to public health. In severe cases, excessive inflammation can lead to severe pneumonia or acute respiratory distress syndrome, contributing to patient morbidity and mortality. While antivirals can be effective if administered early, current anti-inflammatory drugs have limited success in treating severe cases. Therefore, discovering new anti-inflammatory agents to inhibit influenza-related inflammatory diseases is crucial. Herein, we screened a drug library with known targets using a human monocyte U937 infected with the influenza virus to identify novel anti-inflammatory agents. We also evaluated the anti-inflammatory effects of the hit compounds in an influenza mouse model. Our research revealed that JAK inhibitors exhibited a higher hit rate and more potent inhibition effect than inhibitors targeting other drug targets in vitro. Of the 22 JAK inhibitors tested, 15 exhibited robust anti-inflammatory activity against influenza virus infection in vitro. Subsequently, we evaluated the efficacy of 10 JAK inhibitors using an influenza mouse model and observed that seven provided protection ranging from 40% to 70% against lethal influenza virus infection. We selected oclacitinib as a representative compound for an extensive study to further investigate the in vivo therapeutic potential of JAK inhibitors for severe influenza-associated inflammation. Our results revealed that oclacitinib effectively suppressed neutrophil and macrophage infiltration, reduced pro-inflammatory cytokine production, and ultimately mitigated lung injury in mice infected with lethal influenza virus without impacting viral titer. These findings suggest that JAK inhibitors can modulate immune responses to influenza virus infection and may serve as potential treatments for influenza.IMPORTANCEAntivirals exhibit limited efficacy in treating severe influenza when not administered promptly during the infection. Current steroidal and nonsteroidal anti-inflammatory drugs demonstrate restricted effectiveness against severe influenza or are associated with significant side effects. Therefore, there is an urgent need for novel anti-inflammatory agents that possess high potency and minimal adverse reactions. In this study, 15 JAK inhibitors were identified through a screening process based on their anti-inflammatory activity against influenza virus infection in vitro. Remarkably, 7 of the 10 selected inhibitors exhibited protective effects against lethal influenza virus infection in mice, thereby highlighting the potential therapeutic value of JAK inhibitors for treating influenza.


Assuntos
Doenças Transmissíveis , Influenza Humana , Inibidores de Janus Quinases , Infecções por Orthomyxoviridae , Orthomyxoviridae , Pirimidinas , Sulfonamidas , Humanos , Animais , Camundongos , Influenza Humana/tratamento farmacológico , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Citocinas , Infecções por Orthomyxoviridae/tratamento farmacológico , Inflamação/tratamento farmacológico , Doenças Transmissíveis/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Antivirais/uso terapêutico , Antivirais/farmacologia , Pulmão
15.
Adv Healthc Mater ; 13(16): e2303599, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38331398

RESUMO

Free radicals are secreted following skin damage and cause oxidative stress and inflammatory reactions that increase the difficulty of wound healing. In this study, copper-based nanozyme Cu2Se nanosheets (NSs) are synthesized by an anion-exchange strategy and apply to wounds with F127 hydrogels to investigate the healing effect of this nanozyme composite hydrogels on wounds. Cu2Se NSs have a large number of catalytically active centers, are simple to synthesize, require few reaction conditions and have a short synthesis cycle. In vitro experiments have shown that Cu2Se NSs possess superoxide dismutase (SOD)-like activity and nitrogen radical scavenging activity and promote angiogenesis and fibroblast migration. The doping of Cu2Se NSs into the F127 hydrogel does not have a significantly affect on the properties of the hydrogel. This hybridized hydrogel not only adapts to the irregular and complex morphology of acute wounds but also prolongs the duration of nanozyme action on the wound, thus promoting wound healing. Transcriptomic analysis further reveals the potential therapeutic mechanism of the Cu2Se/F127 hydrogel in promoting acute wound healing. Animal experiments have shown that the Cu2Se/F127 hydrogel has good biosafety. The Cu2Se/F127 hydrogel provides an innovative idea for the development of hydrogel dressings for the treatment of acute wounds.


Assuntos
Cobre , Hidrogéis , Superóxido Dismutase , Cicatrização , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Superóxido Dismutase/metabolismo , Superóxido Dismutase/química , Cobre/química , Cobre/farmacologia , Camundongos , Humanos , Masculino , Selênio/química , Selênio/farmacologia
16.
J Nanobiotechnology ; 22(1): 9, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38169389

RESUMO

Glomerulonephritis (GN) is the most common cause of end-stage renal failure worldwide; in most cases, it cannot be cured and can only delay the progression of the disease. At present, the main treatment methods include symptomatic therapy, immunosuppressive therapy, and renal replacement therapy. However, effective treatment of GN is hindered by issues such as steroid resistance, serious side effects, low bioavailability, and lack of precise targeting. With the widespread application of nanoparticles in medical treatment, novel methods have emerged for the treatment of kidney diseases. Targeted transportation of drugs, nucleic acids, and other substances to kidney tissues and even kidney cells through nanodrug delivery systems can reduce the systemic effects and adverse reactions of drugs and improve treatment effectiveness. The high specificity of nanoparticles enables them to bind to ion channels and block or enhance channel gating, thus improving inflammation. This review briefly introduces the characteristics of GN, describes the treatment status of GN, systematically summarizes the research achievements of nanoparticles in the treatment of primary GN, diabetic nephropathy and lupus nephritis, analyzes recent therapeutic developments, and outlines promising research directions, such as gas signaling molecule nanodrug delivery systems and ultrasmall nanoparticles. The current application of nanoparticles in GN is summarized to provide a reference for better treatment of GN in the future.


Assuntos
Nefropatias Diabéticas , Glomerulonefrite , Nefrite Lúpica , Humanos , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/metabolismo , Rim/metabolismo , Nanotecnologia
17.
J Nanobiotechnology ; 22(1): 17, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172992

RESUMO

There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials.


Assuntos
Produtos Biológicos , Doenças Inflamatórias Intestinais , Nanopartículas , Humanos , Espécies Reativas de Oxigênio/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Espécies Reativas de Nitrogênio/metabolismo
18.
Int Wound J ; 21(1): e14341, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37548136

RESUMO

To evaluate the efficacy of one-step acellular dermis combined with autologous split thickness skin grafting in the treatment of burn or trauma wounds by a multicenter controlled study. In patients with extensive burns, it is even difficult to repair the wounds due to the shortage of autologous skin. The traditional skin grafting method has the disadvantages of large damage to the donor site, insufficient skin source and unsatisfactory appearance, wear resistance and elasticity of the wound tissue after skin grafting. One-step acellular dermis combined with autologous ultra-thin split thickness skin graft can achieve better healing effect in the treatment of burn and trauma wounds. A total of 1208 patients who underwent single-layer skin grafting and one-step composite skin grafting in the First Affiliated Hospital of Wannan Medical College, Wuhan Third People's Hospital and Lu 'an People's Hospital from 2019 to 2022 were retrospectively analysed. The total hospitalization cost, total operation cost, hospitalization days after surgery, wound healing rate after 1 week of skin grafting and scar follow-up at 6 months after discharge were compared and studied. The total cost of hospitalization and operation in the composite skin grafting group was significantly higher than those in the single-layer autologous skin grafting group. The wound healing rate after 1 week of skin grafting and the VSS score of scar in the follow-up of 6 months after discharge were better than those in the single-layer skin grafting group. One-step acellular dermis combined with autologous ultra-thin split thickness skin graft has high wound healing rate, less scar, smooth appearance and good elasticity in repairing burn and trauma wounds, which can provide an ideal repair method for wounds.


Assuntos
Derme Acelular , Queimaduras , Humanos , Cicatriz/cirurgia , Estudos Retrospectivos , Transplante de Pele/métodos , Queimaduras/cirurgia , Transplante Autólogo
19.
Adv Healthc Mater ; 13(8): e2302566, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37931140

RESUMO

Effectively controlling bacterial infection, reducing the inflammation and promoting vascular regeneration are all essential strategies for wound repair. Nanozyme technology has potential applications in the treatment of infections because its non-antibiotic dependent, topical and noninvasive nature. In wound management, copper-based nanozymes have emerged as viable alternatives to antibiotics. In this study, an ultrasmall cupric enzyme with high enzymatic activity is synthesized and added to a nontoxic, self-healing, injectable cationic guar gum (CG) hydrogel network. The nanozyme exhibits remarkable antioxidant properties under neutral conditions, effectively scavenging reactive nitrogen and oxygen species (RNOS). Under acidic conditions, Cu NDs have peroxide (POD) enzyme-like activity, which allows them to eliminate hydrogen peroxides and produce free radicals locally. Antibacterial experiments show that they can kill bacteria and remove biofilms. It reveals that low concentrations of Cu ND/CG decrease the expression of the inflammatory factors in cells and tissues, effectively controlling inflammatory responses. Cu ND/CG hydrogels also inhibit HIF-1α and promote VEGF expression in the wound with the ability to promote vascular regeneration. In vivo safety assessments reveal a favorable biosafety profile. Cu ND/CG hydrogels offer a promising solution for treating acute and infected wounds, highlighting the potential of innovative nanomaterials in wound healing.


Assuntos
Cobre , Infecção dos Ferimentos , Humanos , Oxigênio , Antibacterianos , Hidrogéis
20.
Burns ; 49(8): 1926-1934, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37827935

RESUMO

INTRODUCTION: Patients with extremely severe burns often require rapid wound closure with a tangential excision or escharectomy combined with a skin graft to reduce life-threatening complications such as infection. Traditional tangential excision surgery using the Watson or Humby knife does not allow accurate excision of necrotic tissue and often removes too much active tissue, which is detrimental to the rapid healing of the wound. Importantly, the Versajet hydrosurgical system, with its smaller handle, allows for more precise excision of necrotic burn tissue and preserves more active dermal tissue, positively affecting wound healing and scarring. This study compared the safety and efficacy of hydrosurgical combined with autologous skin grafting to conventional excision combined with autologous skin grafting in patients with extremely severe burn. METHODS: Information of sixty burn patients with total body surface area (TBSA) > 50 % treated at the first affiliated hospital of Anhui Medical University from January 2019 to August 2022 were analyzed. The patients were divided into a conventional debridement group (n = 37) and a hydrosurgical debridement group (n = 23) according to the approach used. The hydrosurgical debridement group and the conventional debridement group were compared from the difference between the duration of the first debridement surgery, wound healing time, the changes of red blood cells and hemoglobin concentration postoperative, total blood transfusion, hospitalization cost, skin grafting frequency, procalcitonin, wound bacterial culture, albumin and prealbumin. RESULTS: Information on age, gender, weight, inhalation injury, hypovolemic shock, preoperative procalcitonin, preoperative albumin, preoperative prealbumin, the operation frequency (n ≥ 3), preoperative trauma culture and postoperative trauma culture were compared between both groups (P > 0.05). Operative time and wound healing time were significantly shorter in patients with hydrosurgical debridement combined with autologous skin grafting than those in the control group (P < 0.05), while hospitalization costs were not significantly different between the two groups (P > 0.05). The changes of red blood cells and hemoglobin concentration during the postoperative period in the hydrosurgical debridement group were less significantly than those in the conventional debridement group (P < 0.05). The total amount of red blood cells transfused during hospitalization was significantly lower in the hydrosurgical debridement group than that in the conventional debridement group (P < 0.05), but the total amount of fresh frozen plasma transfused during hospitalization was not statistically significant between the two groups (P > 0.05). Albumin on the third day after surgery and prealbumin on the first, third and fifth day after surgery improved more significantly than those in the control group(P < 0.05), however, there were no significant differences between the two groups in albumin on the first and fifth postoperative days (P > 0.05). The PCT level in the conventional debridement group was significantly higher than that in the hydrosurgical debridement group on the first, third and fifth days after surgery(P < 0.05). CONCLUSION: The hydrosurgical debridement group presented with shorter operative time, less blood loss during surgery, faster postoperative nutritional recovery, less postoperative inflammatory response and faster wounds healing, and did not increase the hospitalization cost, postoperative bacterial culture of the wounds and the number of skin grafting surgeries. In patients with extremely severe burn, hydrosurgical debridement combined with autologous skin grafting group is safer and more effective than those in the conventional debridement combined with autologous skin grafting group.


Assuntos
Queimaduras , Pré-Albumina , Humanos , Desbridamento , Estudos Retrospectivos , Pró-Calcitonina , Queimaduras/cirurgia , Transplante de Pele , Albuminas , Hemoglobinas
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