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1.
Medicine (Baltimore) ; 103(19): e37999, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38728502

RESUMO

Glioma is a typical malignant tumor of the nervous system. It is of great significance to identify new biomarkers for accurate diagnosis of glioma. In this context, THOC6 has been studied as a highly diagnostic prognostic biomarker, which contributes to improve the dilemma in diagnosing gliomas. We used online databases and a variety of statistical methods, such as Wilcoxon rank sum test, Dunn test and t test. We analyzed the mutation, location and expression profile of THOC6, revealing the network of THOC6 interaction with disease. Wilcoxon rank sum test showed that THOC6 is highly expressed in gliomas (P < 0.001). Dunn test, Wilcoxon rank sum test and t test showed that THOC6 expression was correlated with multiple clinical features. Logistic regression analysis further confirmed that THOC6 gene expression was a categorical dependent variable related to clinical features of poor prognosis. Kaplan-Meier survival analysis showed that the overall survival (OS) of glioma patients with high expression of THOC6 was poor (P < 0.001). Both univariate (P < 0.001) and multivariate (P = 0.04) Cox analysis confirmed that THOC6 gene expression was an independent risk factor for OS in patients with glioma. ROC curve analysis showed that THOC6 had a high diagnostic value in glioma (AUC = 0.915). Based on this, we constructed a nomogram to predict patient survival. Enrichment analysis showed that THOC6 expression was associated with multiple signal pathways. Immuno-infiltration analysis showed that the expression of THOC6 in glioma was closely related to the infiltration level of multiple immune cells. Molecular docking results showed that THOC6 might be the target of anti-glioma drugs. THOC6 is a novel diagnostic factor and prognostic biomarker of glioma.


Assuntos
Biomarcadores Tumorais , Neoplasias Encefálicas , Biologia Computacional , Glioma , Simulação de Acoplamento Molecular , Humanos , Glioma/genética , Glioma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Biologia Computacional/métodos , Prognóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Feminino , Masculino , Estimativa de Kaplan-Meier
2.
PLoS One ; 19(5): e0301358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38771804

RESUMO

Drug-resistant bacteria arising from antibiotic abuse infections have always been a serious threat to human health. Killing bacteria with toxic reactive oxygen species (ROS) is an ideal antibacterial method for treating drug-resistant bacterial infections. Here, we prepared Pt-Ru bimetallic nanoclusters (Pt-Ru NCs) with higher peroxidase (POD)-like activity than Pt monometallic nanoclusters. Pt-Ru can easily catalyze the decomposition of H2O2 to produce ·OH, thereby catalyzing the transformation of 3,3',5,5'-tetramethylbiphenylamine (TMB) to blue oxidized TMB (oxTMB). We utilized the POD-like activity of the Pt-Ru NCs for antibacterial therapy. The results showed that at doses of 40 µg/mL and 16 µg/mL, the Pt-Ru NCs exhibited extraordinary antibacterial activity against E. coli and S. aureus, demonstrating the enormous potential of Pt-Ru NCs as antibacterial agents.


Assuntos
Antibacterianos , Escherichia coli , Nanopartículas Metálicas , Platina , Rutênio , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Platina/química , Platina/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Rutênio/química , Rutênio/farmacologia , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Peroxidase/metabolismo , Peróxido de Hidrogênio/química , Catálise , Humanos
3.
J Surg Case Rep ; 2024(4): rjae195, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572291

RESUMO

Actinomycosis remains a rare and often underdiagnosed cause of appendicitis with only 10% of cases diagnosed prior to surgery. It is an important cause to consider particularly in the setting of an indolent infection with nonspecific symptoms. We present a 22 years old male who presented with 3 weeks history of lower abdominal pain who underwent laboratory investigations and imaging studies suggestive of acute appendicitis. He underwent an emergency laparoscopic caecectomy with histopathology of the specimen suggestive of actinomycosis. He recovered well postoperatively and was discharged home with a prolonged course of oral penicillins. Preoperative diagnosis of actinomycosis is uncommon and accounts for ~10% of cases. Definitive diagnosis is usually through histopathology or tissue/fluid culture. Treatment usually involves a combination of surgical resection and antibiotic therapy with a success rate of >90%.

4.
Int J Biol Macromol ; 266(Pt 1): 131221, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554926

RESUMO

Oral ulceration is the most common oral mucosal disease. Oral mucosal ulcers are extremely painful, may interfere with eating and speaking, and potentially complicate systemic symptoms in severe cases. The humid and highly dynamic environment of the oral cavity makes local drug administration for treating oral mucosal ulcers challenging. To overcome these challenges, we designed and prepared a novel dissolving microneedle (MN) patch containing multiple drugs in a core-shell to promote oral ulcer healing. The MNs contained a methacrylate gelatin shell layer of basic fibroblast growth factor (bFGF), a hyaluronic acid (HA) core loaded with dexamethasone (DXMS), and zeolite imidazoline framework-8 (ZIF-8) encapsulated in the HA-based backplane. Progressive degradation of gelatin methacryloyl (GelMA) from the tip of the MN patch in the oral mucosa resulted in sustained bFGF release at the lesion site, significantly promoting cell migration, proliferation, and angiogenesis. Moreover, the rapid release of HA and, subsequently, DXMS inhibited inflammation, and the remaining MN backing after the tip dissolved behaved as a dressing, releasing ZIF-8 for its antimicrobial effects. This novel, multifunctional, transmucosal core-shell MN patch exhibited excellent anti-inflammatory, antimicrobial, and pro-healing effects in vivo and in vitro, suggesting that it can promote oral ulcer healing.


Assuntos
Gelatina , Ácido Hialurônico , Metacrilatos , Mucosa Bucal , Agulhas , Úlceras Orais , Cicatrização , Ácido Hialurônico/química , Gelatina/química , Animais , Úlceras Orais/tratamento farmacológico , Úlceras Orais/patologia , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Metacrilatos/química , Cicatrização/efeitos dos fármacos , Ratos , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Masculino , Camundongos , Humanos
5.
Heliyon ; 10(6): e27451, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38496844

RESUMO

The role of traditional Chinese medicine (TCM) in treating diseases is receiving increasing attention. Chinese herbal medicine is an important part of TCM with various applications and the active ingredients extracted from Chinese herbal medicines have physiological and pathological effects. Tissue engineering combines cell biology and materials science to construct tissues or organs in vitro or in vivo. TCM has been proposed by the World Health Organization as an effective treatment modality. In recent years, the potential use of TCM in tissue engineering has been demonstrated. In this review, the classification and efficacy of TCM active ingredients and delivery systems are discussed based on the TCM theory. We also summarized the current application status and broad prospects of Chinese herbal active ingredients in different specialized biomaterials in the field of tissue engineering. This review provides novel insights into the integration of TCM and modern Western medicine through the application of Chinese medicine in tissue engineering and regenerative medicine.

6.
Water Res ; 254: 121404, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38442608

RESUMO

Acidic pit lakes (APLs) emerge as reservoirs of acid mine drainage in flooded open-pit mines, representing extreme ecosystems and environmental challenges worldwide. The bioremediation of these oligotrophic waters necessitates the addition of organic matter, but the biogeochemical response of APLs to exogenous organic matter remains inadequately comprehended. This study delves into the biogeochemical impacts and remediation effects of digestate-derived organic matter within an APL, employing a multi-omics approach encompassing geochemical analyses, amplicon and metagenome sequencing, and ultra-high resolution mass spectrometry. The results indicated that digestate addition first stimulated fungal proliferation, particularly Ascomycetes and Basidiomycetes, which generated organic acids through lignocellulosic hydrolysis and fermentation. These simple compounds further supported heterotrophic growth, including Acidiphilium, Acidithrix, and Clostridium, thereby facilitating nitrate, iron, and sulfate reduction linked with acidity consumption. Nutrients derived from digestate also promoted the macroscopic development of acidophilic algae. Notably, the increased sulfate reduction-related genes primarily originated from assimilatory metabolism, thus connecting sulfate decrease to organosulfur increase. Assimilatory and dissimilatory sulfate reduction collectively contributed to sulfate removal and metal fixation. These findings yield multi-omics insights into APL biogeochemical responses to organic matter addition, enhancing the understanding of carbon-centered biogeochemical cycling in extreme ecosystems and guiding organic amendment-based bioremediation in oligotrophic polluted environments.


Assuntos
Ecossistema , Lagos , Lagos/química , Biodegradação Ambiental , Multiômica , Ácidos , Sulfatos/metabolismo
7.
J Cancer ; 15(5): 1182-1190, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38356714

RESUMO

Background: Oral Submucosal Fibrosis (OSF) and Oral Leukoplakia (OLK) are well-known oral potentially malignant disorders, and cases of Oral Submucosal Fibrosis concomitant Oral Leukoplakia (OSF+OLK) are now being reported clinically. DNA image cytometry is an objective and non-invasive method for monitoring the risk of precancerous lesions in the oral cavity. Methods: A total of 111 patients with clinically characterized oral mucosal lesions underwent simultaneous and independent histopathological and DNA imaging cytometry assessments. Clinical data were also collected for each patient. Results: The frequency of DNA content abnormality was higher in the tongue than in other oral sites (P = 0.003) for OLK. The frequency of DNA content abnormality was higher in the tongue than in other oral sites (P = 0.035) for OSF+OLK. The differences of DNA content abnormality in age, sex, dietary habit, smoking, and alcohol intake were not observed in OLK and OSF+OLK. The study indicates an association between DNA content abnormality and pathological examination in OSF+OLK ( χ2 test, P = 0.007). OLK showed higher sensitivity and specificity than OSF, while the sensitivity and specificity of OSF+OLK are higher than OLK only and OSF only. Conclusion: DNA image cytometry can be utilized as an adjunctive device for the initial detection of oral potentially malignant disorders that require further clinical management.

8.
Cancer Cell ; 42(3): 413-428.e7, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38402609

RESUMO

KRASG12C inhibitors (adagrasib and sotorasib) have shown clinical promise in targeting KRASG12C-mutated lung cancers; however, most patients eventually develop resistance. In lung patients with adenocarcinoma with KRASG12C and STK11/LKB1 co-mutations, we find an enrichment of the squamous cell carcinoma gene signature in pre-treatment biopsies correlates with a poor response to adagrasib. Studies of Lkb1-deficient KRASG12C and KrasG12D lung cancer mouse models and organoids treated with KRAS inhibitors reveal tumors invoke a lineage plasticity program, adeno-to-squamous transition (AST), that enables resistance to KRAS inhibition. Transcriptomic and epigenomic analyses reveal ΔNp63 drives AST and modulates response to KRAS inhibition. We identify an intermediate high-plastic cell state marked by expression of an AST plasticity signature and Krt6a. Notably, expression of the AST plasticity signature and KRT6A at baseline correlates with poor adagrasib responses. These data indicate the role of AST in KRAS inhibitor resistance and provide predictive biomarkers for KRAS-targeted therapies in lung cancer.


Assuntos
Acetonitrilas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Piperazinas , Pirimidinas , Animais , Camundongos , Humanos , Proteínas Proto-Oncogênicas p21(ras) , Genes ras , Mutação
9.
J Exp Med ; 221(3)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38284990

RESUMO

Human lung adenosquamous cell carcinoma (LUAS), containing both adenomatous and squamous pathologies, exhibits strong cancer plasticity. We find that ALK rearrangement is detectable in 5.1-7.5% of human LUAS, and transgenic expression of EML4-ALK drives lung adenocarcinoma (LUAD) formation initially and squamous transition at late stage. We identify club cells as the main cell-of-origin for squamous transition. Through recapitulating lineage transition in organoid system, we identify JAK-STAT signaling, activated by EML4-ALK phase separation, significantly promotes squamous transition. Integrative study with scRNA-seq and immunostaining identify a plastic cell subpopulation in ALK-rearranged human LUAD showing squamous biomarker expression. Moreover, those relapsed ALK-rearranged LUAD show notable upregulation of squamous biomarkers. Consistently, mouse squamous tumors or LUAD with squamous signature display certain resistance to ALK inhibitor, which can be overcome by combined JAK1/2 inhibitor treatment. This study uncovers strong plasticity of ALK-rearranged tumors in orchestrating phenotypic transition and drug resistance and proposes a potentially effective therapeutic strategy.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Neoplasias Pulmonares/genética , Pulmão , Receptores Proteína Tirosina Quinases , Proteínas de Fusão Oncogênica/genética
10.
Int J Surg Case Rep ; 115: 109291, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38280343

RESUMO

INTRODUCTION AND IMPORTANCE: We present the case of a 17 years old girl with per rectal haemorrhage secondary to pelvic arteriovenous malformations (AVM) and potentially haemorrhoids. Pelvic AVMs are rare and extremely variable in their clinical presentation, size and location and pose a therapeutic challenge. Focus has turned towards interventional radiological procedures with angioembolisation as the main treatment form for pelvic AVMs. CASE PRESENTATION: A 17 years old girl presented to a rural hospital with significant per rectal bleeding requiring transfer to a tertiary centre with interventional radiology capabilities. Diagnostic imaging determined the presence of a pelvic AVM as well as haemorrhoid. She had no prior history of haemorrhoids, per rectal bleeding or per vaginal bleeding. Further diagnostic imaging including a digital subtraction angiography and MRI pelvis was performed and her case was discussed at a multidisciplinary meeting where the decision was made for angioembolisation of a large right rectal AVM as well as precautionary banding of haemorrhoids that had developed secondary to outflow obstruction. A repeat CT mesenteric angiogram a month later demonstrated diminished appearances of the rectal AVM. CLINICAL DISCUSSION: Pelvic AVMs are a rare entity and are not a common cause for per rectal bleeding. There is currently no direct consensus on the optimum management of complex pelvic AVMs particularly those that present with a second pathology such as haemorrhoids. Surgical management often results in recurrence or rapid progression of the AVM lesion and recruitment of new blood supply further complicates the problem. Selective embolisation allows for control of haemorrhage and utilises chemical agents as well as detachable coils and balloons. However, postoperative pain and swelling can still be expected and multiple transcatheter embolisations may be required. CONCLUSION: The treatment of symptomatic pelvic AVMs is complex and requires a multidisciplinary approach with careful radiological planning prior to embolisation. Angioembolisation is becoming increasingly prevalent and multiple embolisation procedures may be required to reach the desired therapeutic effect.

12.
Mater Today Bio ; 22: 100782, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37706204

RESUMO

Oral ulcers have periodicity and recurrence, and the etiology and causative mechanisms remain unclear; therefore, it is difficult to treat oral ulcers effectively. Current clinical treatment methods mainly include pain relief and administration of anti-inflammatories to prevent secondary infections and a prolonged recurrence cycle. However, these traditional treatment methods are administered independently and are susceptible to muscle movements and constant salivary secretion in the mouth, resulting in ineffective drug functioning. Therefore, development of a novel treatment to reduce wound infection and accelerate wound healing for oral ulcers is required for effective treatment. Herein, we report a multifunctional polysaccharide composite microneedle patch based on hyaluronic acid (HA) and hydroxypropyl trimethyl ammonium chloride chitosan (HACC) loaded with dexamethasone (DXMS) and basic fibroblast growth factor (bFGF) for oral ulcer healing. DXMS and bFGF encapsulated the HA tip portion of the microneedle patch, endowing the microneedle patches with anti-inflammatory and angiogenic properties. HACC was applied to the back of the microneedle patch, adding antibacterial properties. The experimental results indicated that the prepared dressings exhibited good antibacterial activity and effectively promoted cell migration growth and angiogenesis. More importantly, animal experiments have shown that multifunctional microneedle patches can effectively promote oral ulcer healing. Thus, these novel multifunctional polysaccharide composite microneedle patches have great potential for oral ulcers treatment.

13.
Adv Sci (Weinh) ; 10(29): e2302918, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37698552

RESUMO

Atherosclerosis, the leading cause of death worldwide, is responsible for ≈17.6 million deaths globally each year. Most therapeutic drugs for atherosclerosis have low delivery efficiencies and significant side effects, and this has hampered the development of effective treatment strategies. Diversified nanomaterials can improve drug properties and are considered to be key for the development of improved treatment strategies for atherosclerosis. The pathological mechanisms underlying atherosclerosis is summarized, rationally designed nanoparticle-mediated therapeutic strategies, and potential future therapeutic targets for nanodelivery. The content of this study reveals the potential and challenges of nanoparticle use for the treatment of atherosclerosis and highlights new effective design ideas.


Assuntos
Aterosclerose , Nanopartículas , Nanoestruturas , Humanos , Sistemas de Liberação de Medicamentos , Composição de Medicamentos , Nanopartículas/uso terapêutico , Aterosclerose/tratamento farmacológico
14.
ANZ J Surg ; 93(11): 2675-2679, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37530228

RESUMO

BACKGROUND: Accurate staging of colon cancer is imperative in directing treatment and prognostication. Existing literature on pre-operative accuracy of FDG-PET/CT in detecting lymph node disease often combines colon and rectal cancer, examines rectal cancers alone, and rarely assesses colon cancer in isolation. Our aim was to assess pre-operative utility of FDG-PET/CT in detecting lymph node disease in colon cancer. METHODS: A retrospective cohort analysis was performed at a single Australian institution between 2017 and 2022 to identify treatment naive primary colonic tumours. Primary outcome was sensitivity and specificity using formal surgical histopathology as gold standard. Secondary outcomes were patient and tumour factors predictive of FDG-PET/CT positive disease including pre-operative CEA, mismatch repair status, duration to surgery, and tumour T-stage. RESULTS: Three hundred and thirty-nine patients were identified. Thirty-four had pre-operative FDG-PET/CT without neoadjuvant therapy. The mean surgical lymph node harvest was 18 nodes. Twenty-five patients had moderately differentiated tumours. The median duration between FDG-PET/CT and operation was 17 days. Pre-operative FDG-PET/CT suggested positive lymph node involvement in 12 patients. Compared to final lymph node histopathology, FDG-PET/CT had a sensitivity of 53%, specificity of 82%, positive predictive value of 75%, negative predictive value of 64% and accuracy of 68%. There was no significant difference between groups for secondary outcomes. CONCLUSION: FDG-PET/CT has moderate specificity but poor sensitivity in the detection of lymph node involvement in colon cancer. Its utility should likely remain isolated to investigating equivocal lesions or follow up of known PET avid disease.


Assuntos
Neoplasias do Colo , Linfadenopatia , Humanos , Fluordesoxiglucose F18/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluoretos , Tomografia Computadorizada por Raios X , Estudos Retrospectivos , Estadiamento de Neoplasias , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Austrália , Tomografia por Emissão de Pósitrons , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Sensibilidade e Especificidade , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Compostos Radiofarmacêuticos
15.
Int J Biol Macromol ; 251: 126333, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37586633

RESUMO

Oral ulcers are common in the oral mucosa. Frequent occurrences of oral ulcers commonly afflict patients, seriously impacting their daily life. Treatments with good anti-inflammatory and antibacterial properties are important for promoting the healing of oral ulcers. In this study, a multifunctional, soluble hyaluronic acid (HA) microneedle (MN) patch was prepared to promote oral ulcer healing. The tip layer of the MN patch was loaded with triamcinolone acetonide (TA) and epidermal growth factor (EGF) to inhibit inflammation and promote angiogenesis. Zeolitic imidazolate framework-8 (ZIF-8) was loaded onto the base layer of the MN patch, which effectively released Zn2+ to mediate antibacterial effects. In addition, HA exerts a protective effect on the mucous membrane. Owing to these properties, the multifunctional MN patches were found to have good anti-inflammatory, antibacterial, and tissue-healing abilities, indicating that the multifunctional MN patch design successfully promoted the healing of oral ulcers.

16.
Water Res ; 243: 120415, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37517152

RESUMO

Acidic pit lakes represent hydrological features resulting from the accumulation of acid mine drainage in mining operations. Long-term monitoring is essential for these extreme and contaminated environments, yet tracking investigations integrating microbial geochemical dynamics in acidic pit lakes have been lacking thus far. This study integrated historical data with field sampling to track decadal biogeochemical changes in an acidic pit lake. With limited artificial disturbance, significant and sustained biogeochemical changes were observed over the past decade. Surface water pH slowly increased from 2.8 to a maximum of 3.6, with a corresponding increase in bottom water pH to around 3.9, despite the accumulation of externally imported sulfate and metals. Elevated nutrient levels stimulated the macroscopic growth of Chlorophyta, resulting in a shift from reddish-brown to green water with floating algal bodies. Furthermore, microalgae-fixed organic carbon promoted the transition from the initial chemolithotrophy-based population dominated by Acidiphilium and Ferrovum to a heterotrophic community. The increase in heterotrophic iron- and sulfate-reducers may cause an elevation in ferrous levels and a decline in copper concentrations. However, most metals were not removed from the water column, potentially due to insufficient biosulfidogenesis or sulfide reoxidation. These findings offer novel insights into microbial succession in extreme ecosystem evolution and contribute to the management and remediation of acidic pit lakes.


Assuntos
Lagos , Microbiota , Metais , Sulfatos , Água
17.
J Colloid Interface Sci ; 650(Pt B): 1125-1137, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37473473

RESUMO

Nanozyme-based synergistic catalytic therapies for tumors have attracted extensive research attention. However, the unsatisfactory efficiency and negative impact of the tumor microenvironment (TME) hinder its clinical applications. In this study, we provide an easy method to prepare transition metals loaded onto pyrrolic nitrogen-rich g-C3N4 (PN-g-C3N4) for forming metal-N4 sites. This N-rich material effectively transfers electrons from g-C3N4 to metal-N4 sites, promotes the oxidation-reduction reaction of metals with different valence states, and improves material reusability. Under TME conditions, copper ions loaded onto PN-g-C3N4 (Cu-PN-g-C3N4, CPC) can produce ·OH through a Fenton-like reaction for tumor inhibition. This Fenton-like reaction and tumor cell inhibition can be improved further by a photodynamic effect caused by light irradiation. We introduced upconversion nanoparticles (UCNPs) into CPC to obtain nano-enzymes (UCNPs@Cu-PN-g-C3N4, UCPC) for effectively penetrating the tissue, which emits light corresponding to the UV absorption region of CPC when excited with 980 nm near-infrared (NIR) light. The nanoplatform can reduce H2O2 concentration upon exposure to NIR light; this induces an increase in dissolved oxygen content and produces a higher supply of reactive oxygen species (ROS) for destroying tumor cells. Owing to the narrow bandgap (1.92 eV) of UCPC under 980 light irradiation, even under the condition of hypoxia, the excited electrons in the conduction band can reduce insoluble O2 through a single electron transfer process, thus effectively generating O2•-. Nanoenzyme materials with catalase properties produce three types of ROS (·OH, O2•- and 1O2) when realizing chemodynamic and photodynamic therapies. An excellent therapeutic effect was established by killing cells in vitro and the tumor-inhibiting effect in vivo, proving that the prepared nanoenzymes have an effective therapeutic effect and that the endogenous synergistic treatment of multiple treatment technologies can be realized.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Pirróis/farmacologia , Cobre/farmacologia , Microambiente Tumoral , Peróxido de Hidrogênio/farmacologia , Fotoquimioterapia/métodos , Oxigênio , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
18.
MedComm (2020) ; 4(3): e259, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37284583

RESUMO

Gene therapy, a medical approach that involves the correction or replacement of defective and abnormal genes, plays an essential role in the treatment of complex and refractory diseases, such as hereditary diseases, cancer, and rheumatic immune diseases. Nucleic acids alone do not easily enter the target cells due to their easy degradation in vivo and the structure of the target cell membranes. The introduction of genes into biological cells is often dependent on gene delivery vectors, such as adenoviral vectors, which are commonly used in gene therapy. However, traditional viral vectors have strong immunogenicity while also presenting a potential infection risk. Recently, biomaterials have attracted attention for use as efficient gene delivery vehicles, because they can avoid the drawbacks associated with viral vectors. Biomaterials can improve the biological stability of nucleic acids and the efficiency of intracellular gene delivery. This review is focused on biomaterial-based delivery systems in gene therapy and disease treatment. Herein, we review the recent developments and modalities of gene therapy. Additionally, we discuss nucleic acid delivery strategies, with a focus on biomaterial-based gene delivery systems. Furthermore, the current applications of biomaterial-based gene therapy are summarized.

19.
Signal Transduct Target Ther ; 8(1): 212, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37221195

RESUMO

Small GTPases including Ras, Rho, Rab, Arf, and Ran are omnipresent molecular switches in regulating key cellular functions. Their dysregulation is a therapeutic target for tumors, neurodegeneration, cardiomyopathies, and infection. However, small GTPases have been historically recognized as "undruggable". Targeting KRAS, one of the most frequently mutated oncogenes, has only come into reality in the last decade due to the development of breakthrough strategies such as fragment-based screening, covalent ligands, macromolecule inhibitors, and PROTACs. Two KRASG12C covalent inhibitors have obtained accelerated approval for treating KRASG12C mutant lung cancer, and allele-specific hotspot mutations on G12D/S/R have been demonstrated as viable targets. New methods of targeting KRAS are quickly evolving, including transcription, immunogenic neoepitopes, and combinatory targeting with immunotherapy. Nevertheless, the vast majority of small GTPases and hotspot mutations remain elusive, and clinical resistance to G12C inhibitors poses new challenges. In this article, we summarize diversified biological functions, shared structural properties, and complex regulatory mechanisms of small GTPases and their relationships with human diseases. Furthermore, we review the status of drug discovery for targeting small GTPases and the most recent strategic progress focused on targeting KRAS. The discovery of new regulatory mechanisms and development of targeting approaches will together promote drug discovery for small GTPases.


Assuntos
Neoplasias Pulmonares , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Descoberta de Drogas , Imunoterapia
20.
Int J Biol Macromol ; 241: 124511, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37086773

RESUMO

Developing an eco-friendly, sustainable and antibacterial adsorbent is significant for actual water treatment. Herein, a bio-based antibacterial adsorbent based on titanium dioxide (TiO2) nanoparticles functionalized chitosan (CS) was prepared through an in-situ hydrolysis strategy using titanium oxysulfate as the source of TiO2. The as-obtained CS/TiO2 nanocomposite was characterized by a variety of analytical techniques. According to the Langmuir mode, the adsorption capacity of CS/TiO2 reached 23.64 mg P g-1, almost 8 times higher than that of CS. In addition, the normalized adsorption capacity (adsorption value per Ti) of CS/TiO2 was calculated to be 102.68 mg P g-1 Ti-1, much higher than pure TiO2 (60.11 mg P g-1 Ti-1). Moreover, CS/TiO2 exhibited a highly selective capacity for phosphate removal in the presence of competing anions, and showed high stability in a wide pH range of 3.0-8.0. When the phosphate concentration was 2.0 mg P L-1, the removal efficiency of phosphate reached 99.5 % and the residual concentration was only 10 µg P L-1, which meets the USEPA standards for eutrophication prevention and control. In addition, after treatment by CS/TiO2, the phosphate concentration of two sewage water samples decreased from 1.50 and 1.0 mg P L-1 to <0.10 mg P L-1, meeting the standard of level II water based on the Environmental Quality Standard of China (GB3838-2002). Ligand exchange and electrostatic interactions are mainly responsible for phosphate adsorption by CS/TiO2. Furthermore, the CS/TiO2 nanocomposites exhibited excellent antibacterial activity, which could avoid biofouling contamination caused by microorganisms. Benefiting from the above advantages, the as-designed CS/TiO2 nanocomposite has great potential as a bio-based antibacterial adsorbent for phosphate capture or removal from wastewater.


Assuntos
Quitosana , Nanocompostos , Nanopartículas , Poluentes Químicos da Água , Titânio/farmacologia , Titânio/química , Fosfatos/química , Quitosana/farmacologia , Quitosana/química , Adsorção , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas/química , Concentração de Íons de Hidrogênio , Nanocompostos/química
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