RESUMO
An ideal tumor treatment strategy involves therapeutic approaches that can enhance the immunogenicity of the tumor microenvironment while simultaneously eliminating the primary tumor. A cholic acid-modified iridium(III) (Ir3) photosensitizer, targeted to the endoplasmic reticulum (ER), has been reported to exhibit potent type I and type II photodynamic therapeutic effects against triple-negative breast cancer (MDA-MB-231). This photosensitizer induces pyroptotic cell death mediated by gasdermin E (GSDME) through photodynamic means and enhances tumor immunotherapy. Mechanistic studies have revealed that complex Ir3 induces characteristics of damage-related molecular patterns (DAMPs) in MDA-MB-231 breast cancer cells under light conditions. These include cell-surface calreticulin (CRT) eversion, extracellular high mobility group box 1 (HMGB1) and ATP release, accompanied by ER stress and increased reactive oxygen species (ROS). Consequently, complex Ir3 promotes dendritic cell maturation and antigen presentation under light conditions, fully activates T cell-dependent immune response in vivo, and ultimately eliminates distant tumors while destroying primary tumors. In conclusion, immune regulation and targeted intervention mediated by metal complexes represent a new and promising approach to tumor therapy. This provides an effective strategy for the development of combined targeted therapy and immunotherapy.
RESUMO
Copper-cobalt bimetallic nitrogen-doped carbon-based nanoenzymatic materials (CuCo@NC) were synthesized using a one-step pyrolysis process. A three-channel colorimetric sensor array was constructed for the detection of seven antioxidants, including cysteine (Cys), uric acid (UA), tea polyphenols (TP), lysine (Lys), ascorbic acid (AA), glutathione (GSH), and dopamine (DA). CuCo@NC with peroxidase activity was used to catalyze the oxidation of TMB by H2O2 at three different ratios of metal sites. The ability of various antioxidants to reduce the oxidation products of TMB (ox TMB) varied, leading to distinct absorbance changes. Linear discriminant analysis (LDA) results showed that the sensor array was capable of detecting seven antioxidants in buffer and serum samples. It could successfully discriminate antioxidants with a minimum concentration of 10 nM. Thus, multifunctional sensor arrays based on CuCo@NC bimetallic nanoenzymes not only offer a promising strategy for identifying various antioxidants but also expand their applications in medical diagnostics and environmental analysis of food.
Assuntos
Antioxidantes , Carbono , Colorimetria , Cobre , Nitrogênio , Nitrogênio/química , Colorimetria/métodos , Carbono/química , Antioxidantes/química , Antioxidantes/análise , Cobre/química , Cobalto/química , Peróxido de Hidrogênio/química , Humanos , Catálise , Limite de Detecção , Glutationa/química , Glutationa/sangue , Dopamina/sangue , Dopamina/análise , Dopamina/química , Benzidinas/química , Polifenóis/química , Polifenóis/análise , Ácido Ascórbico/química , Ácido Ascórbico/sangue , Ácido Ascórbico/análise , Oxirredução , Ácido Úrico/sangue , Ácido Úrico/química , Ácido Úrico/análise , Cisteína/química , Cisteína/sangueRESUMO
Sarcoidosis is a systemic granulomatous disease characterized by non-caseating epithelioid cell granulomas. One of its immunological hallmarks is the differentiation of CD4 + naïve T cells into Th1/Th17 cells, accompanied by the release of numerous pro-inflammatory cytokines. The TL1A/DR3 signaling pathway plays a crucial role in activating effector lymphocytes, thereby triggering pro-inflammatory responses. The primary aim of this investigation was to scrutinize the impact of anti-TL1A monoclonal antibody on the dysregulation of Th1/Th17 cells and granuloma formation in sarcoidosis. Initially, the abnormal activation of the TL1A/DR3 signaling pathway in pulmonary tissues of sarcoidosis patients was confirmed using qPCR and immunohistochemistry techniques. Subsequently, employing a murine model of sarcoidosis, the inhibitory effects of anti-TL1A monoclonal antibody on the TL1A/DR3 signaling pathway in sarcoidosis were investigated through qPCR, immunohistochemistry, and Western blot experiments. The influence of anti-TL1A monoclonal antibody on granulomas was assessed through HE staining, while their effects on sarcoidosis Th1/Th17 cells and associated cytokine mRNA levels were evaluated using flow cytometry and qPCR, respectively. Immunofluorescence and Western blot experiments corroborated the inhibitory effects of anti-TL1A monoclonal antibody on the aberrant activation of the PI3K/AKT signaling pathway in sarcoidosis. The findings of this study indicate that the TL1A/DR3 signaling pathway is excessively activated in sarcoidosis. Anti-TL1A monoclonal antibody effectively inhibit this abnormal activation in sarcoidosis, thereby alleviating the dysregulation of Th1/Th17 cells and reducing the formation of pulmonary granulomas. This effect may be associated with the inhibition of the downstream PI3K/AKT signaling pathway. Anti-TL1A monoclonal antibody hold promise as a potential novel therapeutic intervention for sarcoidosis.
Assuntos
Anticorpos Monoclonais , Granuloma , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Sarcoidose , Transdução de Sinais , Células Th1 , Células Th17 , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Animais , Células Th1/imunologia , Células Th17/imunologia , Transdução de Sinais/efeitos dos fármacos , Humanos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/imunologia , Granuloma/imunologia , Granuloma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/imunologia , Feminino , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/imunologia , Masculino , Sarcoidose/imunologia , Sarcoidose/tratamento farmacológico , Camundongos , Adulto , Pessoa de Meia-Idade , Membro 25 de Receptores de Fatores de Necrose Tumoral/metabolismo , Membro 25 de Receptores de Fatores de Necrose Tumoral/imunologia , Pulmão/imunologia , Pulmão/patologia , Citocinas/metabolismo , Citocinas/imunologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB CRESUMO
Time series data complexity presents new challenges in clustering analysis across fields such as electricity, energy, industry, and finance. Despite advances in representation learning and clustering with Variational Autoencoders (VAE) based deep learning techniques, issues like the absence of discriminative power in feature representation, the disconnect between instance reconstruction and clustering objectives, and scalability challenges with large datasets persist. This paper introduces a novel deep time series clustering approach integrating VAE with metric learning. It leverages a VAE based on Gated Recurrent Units for temporal feature extraction, incorporates metric learning for joint optimization of latent space representation, and employs the sum of log likelihoods as the clustering merging criterion, markedly improving clustering accuracy and interpretability. Experimental findings demonstrate a 27.16% improvement in average clustering accuracy and a 47.15% increase in speed on industrial load data. This study offers novel insights and tools for the thorough analysis and application of time series data, with further exploration of VAE's potential in time series clustering anticipated in future research.
Assuntos
Algoritmos , Análise por Conglomerados , Aprendizado Profundo , HumanosRESUMO
Liver fibrosis is a coordinated response to tissue injury that is mediated by immune cell interactions. A mitochondria-regulated information-processing (MIP) nanosystem that promotes immune cell communication and interactions to inhibit liver fibrosis is designed. The MIP nanosystem mimics the alkaline amino acid domain of mitochondrial precursor proteins, providing precise targeting of the mitochondria. The MIP nanosystem is driven by light to modulate the mitochondria of hepatic stellate cells, resulting in the release of mitochondrial DNA into the fibrotic microenvironment, as detected by macrophages. By activating the STING signaling pathway, the developed nanosystem-induced macrophage phenotype switches to a reparative subtype (Ly6Clow) and downstream immunostimulatory transcriptional activity, fully restoring the fibrotic liver to its normal tissue state. The MIP nanosystem serves as an advanced information transfer system, allowing precise regulation of trained immunity, and offers a promising approach for effective liver fibrosis immunotherapy with the potential for clinical translation.
RESUMO
Dysregulated skin microbiota and compromised immune responses are the major etiological factors for non-healing diabetic wounds. Current antibacterial strategies fail to orchestrate immune responses and indiscriminately eradicate bacteria at the wound site, exacerbating the imbalance of microbiota. Drawing inspiration from the beneficial impacts that probiotics possess on microbiota, a living microecological hydrogel containing Lactobacillus plantarum and fructooligosaccharide (LP/FOS@Gel) is formulated to remodel dysregulated skin microbiota and reinstate compromised immune responses, cultivating a conducive environment for optimal wound healing. LP/FOS@Gel acts as an "evocator," skillfully integrating the skin microecology, promoting the proliferation of Lactobacillus, Ralstonia, Muribaculum, Bacillus, and Allobaculum, while eradicating colonized pathogenic bacteria. Concurrently, LP/FOS@Gel continuously generates lactic acid to elicit a reparative macrophage response and impede the activation of the nuclear factor kappa-B pathway, effectively alleviating inflammation. As an intelligent microecological system, LP/FOS@Gel reinstates the skin's sovereignty during the healing process and effectively orchestrates the harmonious dialogue between the host immune system and microorganisms, thereby fostering the healing of diabetic infectious wounds. These remarkable attributes render LP/FOS@Gel highly advantageous for pragmatic clinical applications.
RESUMO
Anatomizing mixed-phases, referring to analyzing the mixing profiles and quantifying the phases' proportions in a material, which is of great significance in the genuine applications. Here, by using second-harmonic generation (SHG) polarimetry and piezoresponse force microscopy (PFM) techniques, this work elucidates the contributions and distributions of two different symmetric phases mixed in an archetype monoaxial molecular ferroelectric, diisopropylammonium chloride (DIPACl). The two competing phases are preferred in thermodynamics or kinetic process respectively, and this work evidences the switching behavior between the two competing phases facilitated by an external electrical field as opposed to a heating process. This research contributes novel insights into phase engineering in the field of molecular ferroelectrics and is poised to serve as a potent analytical tool for subsequent applications.
RESUMO
Endoplasmic reticulum stress (ERS) plays a crucial role in the pathogenesis of diabetic nephropathy (DN), and it is often accompanied by an increase in reactive oxygen species (ROS) production. However, the precise relationship between NFE2-related factor-2 (Nrf2), a key regulator of ROS balance, and ERS in DN remains elusive. This study aimed to investigate the impact of Nrf2 on ERS and its therapeutic potential in DN. Herein, ERS-related changes, including increased activating transcription factor-6 (ATF6), glucose-regulated protein 78 (GRP78), and transcription factor C/EBP homologous protein (CHOP) expression, were observed in the renal tissues of streptozotocin-induced DN mice and high glucose cultured human renal proximal tubular (HK-2) cells. Nrf2 knockdown increased the sensitivity of HK-2 cells to ERS under high glucose conditions, underscoring the regulatory role of Nrf2 in ERS modulation. Notably, upregulating Nrf2 in ezetimibe-treated diabetic mice restored ERS markers and ameliorated albuminuria, glomerular hypertrophy, mesangial expansion, and tubulointerstitial fibrosis. Furthermore, the inhibition of ERS in HK-2 cells by the ROS scavenger, N-acetylcysteine, highlights the interplay between ROS and ERS. This study, for the first time, elucidates that the upregulation of Nrf2 may alleviate the negative influence of ROS-mediated ERS, presenting a promising therapeutic avenue for delaying the progression of DN. These findings suggest a potential strategy for targeting Nrf2 and ERS in developing novel therapeutic interventions for DN.
Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2 , Espécies Reativas de Oxigênio , Regulação para Cima , Animais , Humanos , Masculino , Camundongos , Linhagem Celular , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/tratamento farmacológico , Chaperona BiP do Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
RATIONALE AND OBJECTIVES: Gliomas are aggressive brain tumors with a poor prognosis. Assessing treatment response is challenging because magnetic resonance imaging (MRI) may not distinguish true progression (TP) from pseudoprogression (PsP). This review aims to discuss imaging techniques and liquid biopsies used to distinguish TP from PsP. MATERIALS AND METHODS: This review synthesizes existing literature to examine advances in imaging techniques, such as magnetic resonance diffusion imaging (MRDI), perfusion-weighted imaging (PWI) MRI, and liquid biopsies, for identifying TP or PsP through tumor markers and tissue characteristics. RESULTS: Advanced imaging techniques, including MRDI and PWI MRI, have proven effective in delineating tumor tissue properties, offering valuable insights into glioma behavior. Similarly, liquid biopsy has emerged as a potent tool for identifying tumor-derived markers in biofluids, offering a non-invasive glimpse into tumor evolution. Despite their promise, these methodologies grapple with significant challenges. Their sensitivity remains inconsistent, complicating the accurate differentiation between TP and PSP. Furthermore, the absence of standardized protocols across platforms impedes the reliability of comparisons, while inherent biological variability adds complexity to data interpretation. CONCLUSION: Their potential applications have been highlighted, but gaps remain before routine clinical use. Further research is needed to develop and validate these promising methods for distinguishing TP from PsP in gliomas.
RESUMO
Personalized in situ tumor vaccination is a promising immunotherapeutic modality. Currently, seeking immunogenic cell death (ICD) to generate in situ tumor vaccines is still mired by insufficient immunogenicity and an entrenched immunosuppressive tumor microenvironment (TME). Herein, a series of tetrazine-functionalized ruthenium(II) sonosensitizers have been designed and screened for establishing a bioorthogonal-activated in situ tumor vaccine via oncolytic pyroptosis induction. Based on nanodelivery-augmented bioorthogonal metabolic glycoengineering, the original tumor is selectively remolded to introduce artificial target bicycle [6.1.0] nonyne (BCN) into cell membrane. Through specific bioorthogonal ligation with intratumoral BCN receptors, sonosensitizers can realize precise membrane-anchoring and synchronous click-activation in desired tumor sites. Upon ultrasound (US) irradiation, the activated sonosensitizers can intensively disrupt the cell membrane with dual type I/II reactive oxygen species (ROS) generation for a high-efficiency sonodynamic therapy (SDT). More importantly, the severe membrane damage can eminently evoke oncolytic pyroptosis to maximize tumor immunogenicity and reverse immunosuppressive TME, ultimately eliciting powerful and durable systemic antitumor immunity. The US-triggered pyroptosis is certified to effectively inhibit the growths of primary and distant tumors, and suppress tumor metastasis and recurrence in "cold" tumor models. This bioorthogonal-driven tumor-specific pyroptosis induction strategy has great potential for the development of robust in situ tumor vaccines.
Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Piroptose , Neoplasias/terapia , Vacinação , Ultrassonografia , Imunossupressores , Microambiente Tumoral , Linhagem Celular TumoralRESUMO
We present the preparation of CoCu bimetallic nanoclusters (Co@Cu-BNCs) by a hydrothermal and one-step pyrolysis method to build a colorimetric and electrochemical dual-mode sensing platform for uric acid (UA) detection. In the presence of H2O2, Co@Cu-BNCs with peroxidase-mimicking activity may convert colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue-colored oxidized TMB (oxTMB). However, due to the inhibitory effect of uric acid (UA) on the oxidation process of TMB, the characteristic absorption peak intensity of oxTMB decreased when UA was added into a mixed solution. In this approach, a colorimetric assay platform for the detection of UA was demonstrated, with a linear range of 0.1-195 µM and a low limit of detection of 0.06 µM (S/N ratio of 3). In addition, an even wider detection range is achieved in the electrochemical method, due to the pronounced electrocatalytic activity of Co@Cu-BNCs. The surface of the glassy carbon electrode was modified with Co@Cu-BNCs to build an electrochemical sensor for detecting UA. The sensor achieves a wider linear range from 2 to 1000 µM and a limit of detection of 0.61 µM (S/N ratio of 3). Moreover, the detection of UA in a human serum sample showed satisfactory results. The results proved that the colorimetric and electrochemical dual-mode detection platform was sensitive, convenient and accurate.
Assuntos
Benzidinas , Colorimetria , Ácido Úrico , Humanos , Colorimetria/métodos , Peróxido de Hidrogênio , Oxirredução , PeroxidasesRESUMO
Sodium layered-oxides (NaxTMO2) sustain severe interfacial stability issues when subjected to battery applications. Particularly at high potential, the oxidation limits including transition metal dissolution and solid electrolyte interphase reformation are intertwined upon the cathode, resulting in poor cycle ability. Herein, by rearranging the complex and structure of the Helmholtz absorption plane adjacent to NaxTMO2 cathodes, the mechanism of constructing stable cathode/electrolyte interphase (CEI) to push up oxidation limits is clarified. The strong absorbent fluorinated anions replace the solvents into the inner Helmholtz plane, thereby reorganizing the Helmholtz absorption structure and spontaneously inducing anion-dominated interphase to envelop more active sites for layered oxides. More importantly, such multi-component CEI proves effective for the long-term durability of a series of manganese-based oxide cathodes, which achieves a 1500-cycles lifetime against high oxidation voltage limit beyond 4.3 V. This work unravels the key role of breaking high-oxidation limits in attaining higher energy density of layered-oxide systems.
RESUMO
Aureobasidium pullulans produced poly-L-malic acid (PMA) as the main metabolite in fermentation but with relatively low productivity and yield limiting its industrial application. In this study, A. pullulans ZX-10 was engineered to overexpress cytosolic malate dehydrogenase (MDH) and pyruvate carboxylase (PYC) and PMA synthetase (PMS) using a high-copy yeast episomal plasmid with the gpdA promoter from Aspergillus nidulans. Overexpressing endogenous PMS and heterologous MDH and PYC from Aspergillus oryzae respectively increased PMA production by 19 % - 37 % (0.64 - 0.74 g/g vs. 0.54 g/g for wild type) in shake-flask fermentations, demonstrating the importance of the reductive tricarboxylic acid (rTCA) pathway in PMA biosynthesis. A. pullulans co-expressing MDH and PYC produced 96.7 g/L PMA at 0.90 g/Lâh and 0.68 g/g glucose in fed-batch fermentation, which were among the highest yield and productivity reported. The engineered A. pullulans with enhanced rTCA pathway is advantageous and promising for PMA production.
Assuntos
Aureobasidium , Ácidos Tricarboxílicos , Aureobasidium/metabolismo , Fermentação , Malatos/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMO
This study aims to investigate the potential role of lactose on cereulide biosynthesis by emetic Bacillus cereus in dairy matrices. The cereulide yields in whole milk and lactose-free milk were investigated using the emetic reference strain F4810/72. To eliminate the influence of complex food substrates, the LB medium model was further used to characterize the effect of lactose on cereulide produced by F4810/72 and five other emetic B. cereus strains. Results showed that the lactose-free milk displayed a 13-fold higher amount of cereulide than whole milk, but the cereulide level could be reduced by 91 % when the lactose content was restored. The significant inhibition of lactose on cereulide yields of all tested B. cereus strains was observed in LB medium, showing a dose-dependent manner with inhibition rates ranging of 89-98 %. The growth curves and lactose utilization patterns of all strains demonstrated that B. cereus cannot utilize lactose as a carbon source and lactose might act as a signal molecule to regulate cereulide production. Moreover, lactose strongly repressed the expression of cereulide synthetase genes (ces), possibly by inhibiting the key regulator Spo0A at the transcriptional level. Our findings highlight the potential of lactose as an effective strategy to control cereulide production in food.
Assuntos
Bacillus cereus , Depsipeptídeos , Animais , Bacillus cereus/genética , Eméticos/metabolismo , Lactose/metabolismo , Leite/metabolismo , Depsipeptídeos/farmacologiaRESUMO
Describing the dynamic behavior of water confined in clay minerals is a fascinating challenge and crucial in many research areas, ranging from materials science and geotechnical engineering to environmental sustainability. Water is the most abundant resource on Earth, and the high reactivity of naturally occurring hydrous clay minerals used since prehistoric times for a variety of applications means that water-clay interaction is a ubiquitous phenomenon in nature. We have attempted to experimentally distinguish the rotational dynamics and translational diffusion of two distinct populations of interlayer water, confined and ultraconfined, in the sodium (Na) forms of two smectite clay minerals, montmorillonite (Mt) and hectorite (Ht). Samples hydrated at a pseudo one-layer hydration (1LH) state under ambient conditions were studied with quasi-elastic neutron scattering (QENS) between 150 and 300 K. Using a simplified revised jump-diffusion and rotation-diffusion model (srJRM), we observed that while interlayer water near the ditrigonal cavity in Ht forms strong H-bonds to both adjacent surface O and structural OH, H-bonding of other more prevalent interlayer water with the surface O is weaker compared to Mt, inducing a higher temperature for dynamical changes of confined water. Given the lower layer charge and faster dynamics observed for Ht compared to Mt, we consider this strong evidence confirming the influence of the interlayer cation and surfaces on confined water dynamics.
RESUMO
Objective To observe the clinical efficacy of Modified Tongxie Yaofang(Important Formula for Relieving Diarrhea with Pain)in the treatment of patients with diarrhea-predominant irritable bowel syndrome(IBS-D)with liver-depression and spleen-deficiency syndrome.Methods Sixty patients with IBS-D of liver depression and spleen deficiency type were randomly divided into treatment group and control group,30 patients in each group.The patients in the treatment group were given modified Tongxie Yaofang,and the patients in the control group were given Pivacurium Bromide Tablets(Dicetel).Both groups were treated for a 4-week course of treatment.The changes of traditional Chinese medicine(TCM)syndrome scores,irritable bowel syndrome quality of life(IBS-QOL)scores,Hamilton Anxiety Scale(HAMA)scores of the two groups were observed before and after the treatment.Moreover,the efficacy for overall symptomatic improvement in the two groups was evaluated according to the grading of irritable bowel syndrome symptom severity score(IBS-SSS),and the efficacy for improving single symptom such as abdominal pain and diarrhea as well as the relapse after 4 weeks of drug cessation in the two groups were compared.Results(1)After 4 weeks of treatment,the total effective rate for overall symptomatic improvement in the treatment group was 83.33%(25/30),and that in the control group was 43.33%(13/30).The intergroup comparison(tested by chi-square test)showed that the efficacy for overall symptomatic improvement in the treatment group was significantly superior to that in the control group(P<0.01).(2)After 4 weeks of treatment,the total effective rate for improving single symptom of abdominal pain and diarrhea in the treatment group was 80.00%(24/30),90.00%(27/30),and that in the control group was 43.33%(13/30),46.67%(14/30),respectively.The intergroup comparison(tested by chi-square test)showed that the efficacy for improving single symptom of abdominal pain and diarrhea in the treatment group was significantly superior to that in the control group(P<0.01).(3)After 4 weeks of treatment,the TCM syndrome scores,IBS-QOL scores,and HAMA scores of patients in both groups were significantly decreased compared with those before treatment(P<0.05 or P<0.01),and the decrease in the treatment group was significantly superior to that in the control group(P<0.01).(4)After 4 weeks of drug withdrawal,the recurrence rate of the treatment group was 24.00%(6/25),which was significantly lower than that of the control group(61.54%,8/13),and the difference was statistically significant between the two groups(P<0.05).Conclusion Modified Tongxie Yaofang exerts certain effect in treating patients with IBS-D of liver depression and spleen deficiency type,and the decoction is effective on decreasing the scores of symptoms of abdominal pain and diarrhea as well as TCM syndrome scores,improving the quality of life of the patients,and alleviating the anxiety status of the patients.
RESUMO
Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the intestinal tract. There is currently no effective cure for IBD. The aim of this study was to evaluate the protective effect of low-intensity pulsed ultrasound (LIPUS) on lipopolysaccharide (LPS)-induced intestinal damage in a C57BL/6 mouse model. Colonic inflammation was induced by LPS injection (0.75 mg/kg, i.p.) for 7 days. A 1.0 MHz ultrasound transducer was used with a duty cycle of 5% and a repetition frequency of 1 Hz. LIPUS was applied to the abdominal region for 15 min/day from days 1 to 6 at both intensity of 0.5 W/cm2 or 1.0 W/cm2. Colonic samples were collected for macroscopic and westerm blotting analysis. First, the optimal dose of LPS for experiments was investigated. Our results demonstrated that LIPUS alleviates colonic damage by reducing colon shortening and increasing the levels of tight junction proteins such as Occludin and ZO-1. These findings show that abdominal LIPUS stimulation may be a novel therapeutic strategy for IBD through enhancement of tight junction protein levels and attenuation of colonic length.
Assuntos
Doenças Inflamatórias Intestinais , Lipopolissacarídeos , Camundongos , Animais , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Colo , Inflamação/metabolismoRESUMO
Herein we report the colorimetry and an electrochemical for the determination of dopamine (DA) by using MnO2 nanoparticles and graphene nanosheets composite (MnO2@G) that display oxidase mimicking property. MnO2@G could directly oxidize colorless 3,3',5,5'-tetramethylbenzidine (TMB) into a blue product (oxTMB) without extra oxidants such as H2O2. Nevertheless, the presence of DA will inhibit the TMB oxidation due to the presence of the competitive reaction of MnO2@G and DA, giving a product color change from blue to colorless. A colorimetric assay for detect the concentration of DA was worked out according to this finding. Response is linear in the 0.1 to 15 µM DA concentration range, and the detection limit is 0.14 µM. Wider detection range is achieved in an electrochemical method which is due to the pronounced electrocatalytic activity of MnO2@G. The MnO2@G was modified on the surface of the glassy carbon electrode in order to fabricate one type electrochemical sensor. The sensor achieves a wide detection two linear ranges from 0.4 to 70 µM, with the detection limit of 1.16 µM. The detection of DA in real serum sample proved that the nanozyme based on MnO2@G could be developed into a colorimetry and electrochemical dual-readout sensing platform.
RESUMO
Persistent bacterial infections and excessive oxidative stress prevent the healing of diabetic ulcers, leading to an increased disability rate. Current treatments fail to kill bacteria while simultaneously relieving oxidative stress. Herein, a dynamic microenvironment-adaptable hydrogel (BP@CAu) with photothermal performance and reactive oxygen species scavenging is presented for diabetic ulcer healing. This hydrogel prepared using a dynamic borate-ester could respond to acidity in the infection microenvironment for a controllable drug release. An excellent photothermal conversion effect was integrated in the hydrogel, which exhibited strong antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. The hydrogel attenuated intracellular oxidative stress and inflammation and promoted cell migration. In a full-thickness skin defect model of diabetic rats, the BP@CAu hydrogel contributed to the fastest wound closure, with ideal reepithelialization, granulation tissue formation, and regeneration of blood vessels. Further mechanistic studies revealed that the hydrogel relieved oxidative stress and downregulated the expression of inflammatory cytokines, resulting in dramatic therapeutic effects on diabetic wounds. Therefore, this study provides a synergistic therapeutic strategy for efficient photothermal performance and reactive oxygen species scavenging in diabetic ulcers.
Assuntos
Diabetes Mellitus Experimental , Úlcera , Animais , Ratos , Espécies Reativas de Oxigênio , Hidrogéis/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Pele , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
At present, there is a lack of indicators, which can accurately predict the post-percutaneous coronary intervention (post-PCI) vessel-oriented composite endpoint (VOCE). Recent studies showed that the post-PCI quantitative flow ratio (QFR) can predict post-PCI VOCE. PubMed, Embase, and Cochrane were searched from inception to March 27, 2022, and the cohort studies about that the post-PCI QFR predicts post-PCI VOCE were screened. Meta-analysis was performed, including 6 studies involving 4518 target vessels. The results of the studies included in this meta-analysis all showed that low post-PCI QFR was an independent risk factor for post-PCI VOCE after adjusting for other factors, HR (95% CI) ranging from 2.718 (1.347-5.486) to 6.53 (2.70-15.8). Our meta-analysis showed that the risk of post-PCI VOCE was significantly higher in the lower post-PCI QFR group than in the higher post-PCI QFR group (HR: 4.14, 95% CI: 3.00-5.70, P < 0.001, I2 = 27.9%). Post-PCI QFR has a good predictive value for post-PCI VOCE. Trial Registration. This trial is registered with CRD42022322001.