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Sepsis is a life-threatening condition caused by an excessive inflammatory response to an infection. However, the precise regulatory mechanism of sepsis remains unclear. Using a strand-specific RNA-sequencing, we identified 115 hub differentially expressed long noncoding RNAs (lncRNAs) and 443 mRNAs in septic patients, primarily participated in crucial pathways including neutrophil extracellular trap (NET) formation and toll-like receptor signaling. Notably, NETs related gene aquaporin-9 (AQP9) and its associated lncRNAs exhibited significant upregulation in septic neutrophils. Functional experiments revealed AQP9 interacts with its lncRNAs to augment the formation of neutrophil NETs. In murine sepsis models, AQP9 inhibition with phloretin reduced proinflammatory cytokine production and lung damage. These findings provide crucial insights into the regulatory role of AQP9 in sepsis, unraveling its interaction with associated lncRNAs in transmitting downstream signals, holding promise in informing the development of novel therapeutic strategies aimed at ameliorating the debilitating effects of sepsis.
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Aquaporinas , Armadilhas Extracelulares , Neutrófilos , RNA Longo não Codificante , RNA Mensageiro , Sepse , Sepse/imunologia , Sepse/genética , Sepse/metabolismo , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/imunologia , Humanos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Neutrófilos/imunologia , Camundongos , Masculino , Aquaporinas/genética , Aquaporinas/metabolismo , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Transdução de SinaisRESUMO
Prostate cancer is one of the most common cancers and leading cause of death due to cancer across the globe. This persuaded researchers to devise innovative treatment modalities that may prove effective, safe, and demonstrate better outcomes in terms of patient morbidity and survival. The advancement in theranostics such as lutetium-177 (177Lu)-PSMA-617 radioligand therapies can target prostate cancer cells causing negligible or no damage to most of the normal tissues in patients. It has been proven to effectively improve the quality of life and progression-free survival. In this study, stage IV metastatic castration-resistant prostate cancer patients were treated with 177Lu-PSMA-617, and the therapeutic response and safety of 177Lu-PSMA-617 radioligand therapy were evaluated six months after the treatment. Additionally, molecular docking studies were also conducted to find the possible mechanism at the molecular level that causes the effectiveness of 177Lu-PSMA-617 in prostate cancer.
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Dipeptídeos , Compostos Heterocíclicos com 1 Anel , Lutécio , Neoplasias de Próstata Resistentes à Castração , Radioisótopos , Compostos Radiofarmacêuticos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias de Próstata Resistentes à Castração/patologia , Lutécio/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Dipeptídeos/uso terapêutico , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Idoso , Simulação de Acoplamento Molecular , Antígeno Prostático Específico , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Brassica campestris (syn. Brassica rapa) is often known as mustard and is grown worldwide owing to its health-promoting characteristics associated with the presence of nutrients and phytochemicals. Along with the nutritional components, B. campestris also contains anti-nutrients (phytates, oxalates, tannins, alkaloids, saponins) that can cause adverse severe health effects to consumers, including rashes, nausea, headaches, bloating and nutritional deficiencies. In the present study, heating (blanching) and fermentation (Lactiplantibacillus plantarum) treatments were applied to reduce the load of the anti-nutrients of B. campestris leaves harvested at three different growth stages: the first stage (fourth week), the second stage (sixth week) and the third stage (eighth week). Results revealed that fermentation treatment using Lp. plantarum increases the ash (5.4 to 6%), protein (9 to 10.4%) and fiber (9.6 to 10.7%) contents, whereas moisture (0.91 to 0.82%), fat (9.9 to 9.1%) and carbohydrate (64.5 to 64.2%) contents decreased among B. campestris samples, and the trend was similar for all three stages. Blanching and fermentation lead to the reduction in phytates (46, 42%), saponins (34, 49%), tannins (1, 10%), oxalates (15, 7%) and alkaloids (10, 6%), separately as compared to raw samples of B. campestris leaves. In contrast, fermentation had no considerable effect on phytochemical contents (total phenolic and total flavonoids) and antioxidant potential (DPPH and FRAP). The action of blanching followed by fermentation caused more decline in the aforementioned toxicants load as compared to blanching or fermentation alone. Structural modifications in blanching and the biochemical conversions in fermentation lead to enhanced stability of nutrients and antioxidant potential. Taken together, these findings suggest blanching followed by fermentation treatments as a reliable, cost-effective and safer approach to curtail the anti-nutrient load without affecting the proximate composition, phytochemical attributes and antioxidant activity.
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To reduce the amount of energy consumed in integrated circuits, high efficiency with the lowest energy is always expected. Self-drive device is one of the options in the pursuit of low power nanodevices. It is a typical strategy to form an internal electric field by constructing a heterojunction in self-drive semiconductor system. Here, a two-step method is proposed to prepare high quality centimeter-sized 2D tellurium (Te) thin film with hall mobility as high as 37.3â cm2â V-1 s-1, and the 2D Te film is further assembled with silicon to form a heterojunction for self-drive photodetector, which can realize effective detection from visible to near infrared bands. The photodetectivity of the heterojunctions can reach 1.58×1011 Jones under the illumination of 400â nm@ 1.615â mW/cm2 and 2.08×108 Jones under the illumination of 1550â nm@ 1.511â mW/cm2 without bias. Our experiments demonstrate the potential of 2D tellurium thin films for wide band and near infrared integrated device applications.
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Tetrazoles and their derivatives are essential for compound synthesis due to their versatility, effectiveness, stability in air, and cost-efficiency. This has stimulated interest in developing techniques for their production. In this work, four compounds, tetrazolo[1,5-c]pyrimidin-5-amine (1), N-(4-azidopyrimidin-2-yl)nitramide (2), tetrazolo[1,5-c]pyrimidin-5(6H)-one (3), and tetrazolo[1,5-a]pyrimidin-5-amine (4), were obtained from commercially available reagents and straightforward synthetic methodologies. These new compounds were characterized by infrared (IR), 13C, and 1H NMR spectroscopy, differential scanning calorimetry (DSC), and single-crystal X-ray diffraction. The solvent, temperature, and electron-donating group (EDG) factors that were responsible for the steering of azido-tetrazole equilibrium in all compounds were also studied. In addition, the detonation performance of the target compounds was calculated by using heats of formation (HOFs) and crystal densities. Hirshfeld surface analysis was used to examine the intermolecular interactions of the four synthesized compounds. The results show that the excellent properties of 1-4 are triggered by ionic bonds, hydrogen bonds, and π-π stacking interactions, indicating that these compounds have the potential to be used in the development of high-performance energetic materials. Additionally, DFT analysis is in support of experimental results, which proved the effect of different factors that can influence the azido-tetrazole equilibrium in the synthesized pyrimidine derivatives in the solution.
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OBJECTIVE: To ascertain the utility of maximum standardised uptake value (SUVmax) in 18F-FDG PET-CT in predicting metastatic disease burden in hepatocellular carcinoma (HCC) patients. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Nuclear Medicine and PET-CT Imaging, Institute of Nuclear Medicine and Oncology (INMOL), Lahore, Pakistan, from April to October 2022. METHODOLOGY: 18F-FDG PET-CT data of 87 patients were analysed prospectively. Patients were considered regardless of resection status. The SUVmax measurements were performed, and their association with metastases was determined. Molecular docking studies were conducted to determine a mechanism behind the higher SUVmax at the metastatic sites. RESULTS: A higher number of patients (49) was found to have metastasis (1 to 5 in numbers) and demonstrated higher SUVmax, especially in cases of pre-surgery and post-transplant state. A positive correlation existed between SUVmax of pre-surgery (r = 0.419, p = 0.001) and post-transplant patients (r = 0.779, p = 0.001). Molecular docking studies revealed a strong binding affinity (-5.18± 0.25 kcal/mol) between the hexokinase (HK-II) and 18F-FDG. CONCLUSION: SUVmax positively correlated with metastatic tumour burden. The strong binding affinity between the HK-II and 18F-FDG may be the reason. 18F-FDG PET-CT appeared beneficial in providing prognostic information for HCC in a selected group. KEY WORDS: Hepatocellular carcinoma, 18F-FDG, Positron emission tomography, Maximum standardised uptake value, SUVmax, HK-II binding, PET-CT, Metastases.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Simulação de Acoplamento Molecular , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Tomografia por Emissão de PósitronsRESUMO
The development of low-cost earth-abundant electrocatalysts to produce ammonia (NH3) with high efficiency for the nitrogen (N2) reduction reaction (NRR) remains challenging. Herein, we propose the development of highly efficient ultrathin nitrogen-vacancy-rich molybdenum nitride nanosheets (MoN-NV) for NRR using basic electrolytes under ambient conditions. In 0.1 M KOH, this catalyst attained a high faradaic efficiency (FE) of â¼14% with an NH3 yield of 22.5 µg h-1 mg-1cat at -0.3 V vs. a reversible hydrogen electrode under ambient conditions. The characterization results and electrochemical studies disclosed that nitrogen vacancies in the MoN-NV nanosheets played a critical role in the enhanced electrocatalytic activity for NRR. Furthermore, the recycling tests confirmed the stability of the catalyst during NRR electrolysis.
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BACKGROUND: Sepsis is a life-threatening condition caused by an excessive inflammatory response to an infection, associated with high mortality. However, the regulatory mechanism of sepsis remains unclear. RESULTS: In this study, bioinformatics analysis revealed the novel key biomarkers associated with sepsis and potential regulators. Three public datasets (GSE28750, GSE57065 and GSE95233) were employed to recognize the differentially expressed genes (DEGs). Taking the intersection of DEGs from these three datasets, GO and KEGG pathway enrichment analysis revealed 537 shared DEGs and their biological functions and pathways. These genes were mainly enriched in T cell activation, differentiation, lymphocyte differentiation, mononuclear cell differentiation, and regulation of T cell activation based on GO analysis. Further, pathway enrichment analysis revealed that these DEGs were significantly enriched in Th1, Th2 and Th17 cell differentiation. Additionally, five hub immune-related genes (CD3E, HLA-DRA, IL2RB, ITK and LAT) were identified from the protein-protein interaction network, and sepsis patients with higher expression of hub genes had a better prognosis. Besides, 14 drugs targeting these five hub related genes were revealed on the basis of the DrugBank database, which proved advantageous for treating immune-related diseases. CONCLUSIONS: These results strengthen the new understanding of sepsis development and provide a fresh perspective into discriminating the candidate biomarkers for predicting sepsis as well as identifying new drugs for treating sepsis.
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Perfilação da Expressão Gênica , Sepse , Humanos , Perfilação da Expressão Gênica/métodos , Biomarcadores , Mapas de Interação de Proteínas/genética , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/genética , Biologia Computacional/métodos , Redes Reguladoras de GenesRESUMO
Glioblastoma (GBM) remains a challenging malignancy due to its aggressive nature and the lack of efficacious therapeutic interventions. Nanotechnology-based approaches exhibit promise in GBM treatment; however, the successful translation of these strategies from preclinical models to clinical settings is hindered by inefficient nanoparticle clearance from vital organs. Addressing this concern, we investigated the therapeutic potential of amrubicin (AMR) encapsulated within poly (lactic-co-glycolic acid) nanoparticles (AMR-PLGA-NPs) in combating temozolomide (TMZ) resistant GBM. The study demonstrated that AMR-PLGA-NPs exerted a pronounced inhibitory effect on the cellular viability and migratory capacity of TMZ-resistant GBM cells. Furthermore, these nanoparticles exhibited considerable efficacy in downregulating the PI3K/AKT signaling pathway, thereby inducing apoptosis specifically in TMZ-resistant glioma cells and glioma stem-like cells through the activation of PTEN. Notably,in vivoexperimentation revealed the ability of AMR-PLGA-NPs to traverse biological barriers within murine models. Collectively, these findings underscore the potential therapeutic utility of AMR-PLGA-NPs as a versatile nanoplatform for addressing the formidable challenges posed by GBM, particularly in mitigating drug resistance mechanisms. The study substantiates the stability and safety profile of AMR-PLGA-NPs, positioning them as a promising avenue for combating drug resistance in GBM therapeutics.
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Antraciclinas , Neoplasias Encefálicas , Glioblastoma , Glioma , Animais , Camundongos , Antraciclinas/farmacologia , Apoptose , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Temozolomida/farmacologiaRESUMO
Nanozymes, emerging nanomaterials for wound healing, exhibit enzyme-like activity to modulate the levels of reactive oxygen species (ROS) at wound sites. Yet, the solo regulation of endogenous ROS by nanozymes often falls short, particularly in chronic refractory wounds with complex and variable pathological microenvironments. In this study, we report the development of a multifunctional wound dressing integrating a conventional alginate (Alg) hydrogel with a newly developed biodegradable copper hydrogen phosphate (CuP) nanozyme, which possesses good near-infrared (NIR) photothermal conversion capabilities, sustained Cu ion release ability, and pH-responsive peroxidase/catalase-mimetic catalytic activity. When examining acute infected wounds characterized by a low pH environment, the engineered Alg/CuP composite hydrogels demonstrated high bacterial eradication efficacy against both planktonic bacteria and biofilms, attributed to the combined action of catalytically generated hydroxyl radicals and the sustained release of Cu ions. In contrast, when applied to chronic diabetic wounds, which typically have a high pH environment, these composite hydrogels exhibit significant angiogenic performance. This is driven by the provision of catalytically generated dissolved oxygen and a beneficial supplement of Cu ions released from the degradable CuP nanozyme. Further, a mild thermal effect induced by NIR irradiation amplifies the catalytic activities and bioactivity of Cu ions, thereby enhancing the healing process of both infected and diabetic wounds. Our study validates that the synergistic integration of photothermal effects, catalytic activity, and released Cu ions can concurrently yield high antibacterial efficiency and tissue regenerative activity, rendering it highly promising for various clinical applications in wound healing.
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Cobre , Diabetes Mellitus , Espécies Reativas de Oxigênio , Bandagens , Alginatos , Antibacterianos/farmacologia , Hidrogéis/farmacologia , Íons , Concentração de Íons de HidrogênioRESUMO
Tc-99m labelled erythrocyte scan is a sensitive method for detection of gastrointestinal (GI) bleed and liver haemangioma but false positive results can occur, as in this case gallbladder is visualized which is not a common finding. Singlephoton emission computed tomography/computed tomography (SPECT-CT) is helpful to avoid such falsepositive results.
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Hemangioma , Neoplasias Hepáticas , Humanos , Vesícula Biliar/diagnóstico por imagem , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Hemangioma/complicações , Hemangioma/diagnóstico por imagem , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , CintilografiaRESUMO
Pyrimidine which is an important constituent of the genetic material of deoxyribonucleic acid, is identified with a large number of biological activities. Based on this, pyrimidine-derived Schiff bases (1-6) of hydroxy-1-naphthaldehyde were synthesized by using the condensation method. In addition, the molecular docking studies against topoisomerase II DNA gyrase, human hematopoietic cell kinase, urate oxidase from Aspergillus flavus, and cyclin-dependent kinase 8 to explore the antibacterial, antioxidant, antifungal, and anticancer properties respectively and binding affinities through bioinformatics approaches to determine the interaction among active molecules with the receptor. Hence, the computational docking analyses identified that all synthesized pyrimidine Schiff bases (1-6) are active and exhibited better binding affinities as compared to the standard drugs. Furthermore, all the prepared materials were characterized by using nuclear magnetic resonance, infrared, and elemental analysis. Additionally, the phase-transition and thermal decomposition temperatures were determined by differential scanning calorimetry and thermo-gravimetric analysis measurements. Moreover, the structures of pyrimidine-derived Schiff bases 1, 2, 3, 4, and 5 were also confirmed by the X-ray single-crystal diffraction technique. The pyrimidine-derived Schiff bases 5 possess significant antibacterial, antioxidant, antifungal, and anticancer agent properties which confirms its promising biological activities over standard drugs.
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Antifúngicos , Antioxidantes , Humanos , Antifúngicos/farmacologia , Simulação de Acoplamento Molecular , Bases de Schiff/farmacologia , Pirimidinas/farmacologia , Antibacterianos/farmacologiaRESUMO
Purpose: This research study was conducted to evaluate the impact of (68Ga)-tagged prostatic-specific membrane antigen (68Ga-PSMA) positron emission tomography and computed tomography (PET-CT), compare its role with conventional radiology in early staging of high-risk prostate cancer, and calculate the PSMA score evaluating its usefulness in 68Ga-PSMA PET-CT reporting in our patient population. Material and methods: 68Ga-PSMA PET-CT of 65 high-risk cases of prostate cancer was performed for staging purpo-ses. Any change in disease stage was noted after 68Ga-PSMA PET-CT findings and PSMA score leading to a change in the management plan. Results: Change in disease stage post-PSMA imaging was seen in 39% cases, high PSMA score (03) was noted in > 80% of upstaged cases, while low score (0) and (1) was seen in 65% and 35% down-staged individuals, respectively. Change in therapeutic decision-making was observed in 32% (21) of patients. Conclusions: 68Ga-PSMA PET-CT scans have a significant influence on the planned clinical management of high-risk prostate cancer patients; hence, they can be utilized as a replacement for radiological imaging tools, particularly in the detection of pelvic nodal and distant metastatic disease. PSMA score can be considered as an effective tool in standardized reporting of 68Ga-PSMA imaging.
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Objectives: This study aimed to analyze the general public's awareness of medicine information, safety, and adverse drug reactions in Quetta, Pakistan. Methods: A cross-sectional descriptive study was conducted using random sampling from April 2020 to April 2021 in Quetta. Samples were collected from respondents who met the inclusion criteria and had visited community pharmacies. The analysis was done using SPSS version 23. Bivariate and multivariate analyses were performed to assess factors associated with good knowledge. Results: Multivariate analysis revealed that purchase on prescription was a determining factor of knowledge regarding knowledge of pharmaceutical products and their provided information, medicines usage and safety, and Medication ADRs. Patients who bought medicines on prescriptions were more likely to have better knowledge. Patients having education were more likely to have better knowledge. Conclusion: Public awareness about medicine information, safety, and the information provided by manufacturers is crucial to ensuring that patients have access to accurate information about their medications and can make informed decisions about their health. Healthcare providers and regulatory bodies must work together to improve access to information and promote safe medication practices.
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Immune checkpoint blockade has emerged as a significant therapeutic development in immunotherapy during the past decade. However, only a small percentage of cancer patients respond to checkpoint blockade, suggesting that a fundamental knowledge of the underlying processes of immune checkpoint receptor signaling remains elusive and that novel therapeutic medications are needed. Here, the programmed cell death protein 1(PD-1) expressing nanovesicles were developed to enhance T cell activity. Iguratimod (IGU) and Rhodium (Rh) nanoparticles (NPs) were loaded in PD-1 nanovesicles (NVs) for synergistic therapeutic antitumor effects against lung cancer and metastasis. For the first time, this study revealed that IGU exhibits an antitumor effect by inhibiting the phosphorylation of mammalian target of rapamycin (mTOR) and Rh-NPs provided a photothermal effect by improving reactive oxygen species (ROS)-dependent apoptosis in lung cancer cells. IGU-Rh-PD-1 NVs also reduced the migration ability through the epithelial-mesenchymal transition (EMT) pathway. Furthermore, IGU-Rh-PD-1 NVs reached the targeted site and inhibited tumor growth in vivo. This strategy could boost T cell performance and simultaneously possess chemotherapeutic and photothermal therapy to serve as a new combination therapy for lung cancer and potentially other aggressive cancer.
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Neoplasias Pulmonares , Nanopartículas , Ródio , Humanos , Receptor de Morte Celular Programada 1 , Linhagem Celular TumoralRESUMO
Azobenzene-containing small molecules and polymers are functional photoswitchable molecules to form supramolecular nanomaterials for various applications. Recently, supramolecular nanomaterials have received enormous attention in material science because of their simple bottom-up synthesis approach, understandable mechanisms and structural features, and batch-to-batch reproducibility. Azobenzene is a light-responsive functional moiety in the molecular design of small molecules and polymers and is used to switch the photophysical properties of supramolecular nanomaterials. Herein, we review the latest literature on supramolecular nano- and micro-materials formed from azobenzene-containing small molecules and polymers through the combinatorial effect of weak molecular interactions. Different classes including complex coacervates, host-guest systems, co-assembled, and self-assembled supramolecular materials, where azobenzene is an essential moiety in small molecules, and photophysical properties are discussed. Afterward, azobenzene-containing polymers-based supramolecular photoresponsive materials formed through the host-guest approach, polymerization-induced self-assembly, and post-polymerization assembly techniques are highlighted. In addition to this, the applications of photoswitchable supramolecular materials in pH sensing, and CO2 capture are presented. In the end, the conclusion and future perspective of azobenzene-based supramolecular materials for molecular assembly design, and applications are given.
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The earth's nitrogen cycle relies on the effective conversion of nitrogen (N2) to ammonia (NH3). As a result, the research and development of catalysts that are earth-abundant, inexpensive, and highly efficient but do not need precious metals is of the utmost significance. In this investigation, we present a controlled synthesis technique to the fabrication of an iron oxide (Fe2O3) nanosheet array by annealing at temperatures ranging from 350 to 550 °C. This array will be used for the electrochemical reduction of atmospheric N2 to NH3 in electrolytes. The Fe2O3 nanosheet array that was produced as a result displays outstanding electrochemical performance as well as remarkable stability. When compared to a hydrogen electrode working under normal temperature and pressure conditions, the Fe2O3 nanosheet array produces an impressive NH3 production rate of 18.04 g per hour per mg of catalytically active material in 0.1 M KOH electrolyte, exhibiting an enhanced Faradaic efficiency (FE) of 13.5% at -0.35 V. This is accomplished by exhibiting an enhanced Faradaic efficiency (FE) of 0.1 M KOH electrolyte. The results of experiments and electrochemical studies reveal that the existence of cation defects in the Fe2O3 nanosheets plays an essential part in the enhancement of the electrocatalytic activity that takes place during nitrogen reduction reactions (NRR). This study not only contributes to the expanding family of transition-metal-based catalysts with increased electrocatalytic activity for NRR, but it also represents a substantial breakthrough in the design of catalysts that are based on transition metals, so it's a win-win. In addition, the use of Fe2O3 nanosheets as electrocatalysts has a lot of potential in algal membrane bioreactors because it makes nitrogen fixation easier, it encourages algae growth, and it makes nitrogen cycling more resource-efficient.
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Amônia , Reatores Biológicos , Estudos Prospectivos , NitrogênioRESUMO
BACKGROUND: Bleomycin (BLM) is a chemotherapeutic agent with potent antitumor activity against the tumor. However, lung fibrosis is the main drawback that limits BLM use. Tumor targeted, safe, efficient and natural delivery of BLM is important to increase the effectiveness and reduce the toxic side effects. Although tumor derived Exosomes (Exo), provide a potential vehicle for in vivo drug delivery due to their cell tropism. This study primarily focuses on generating a natural delivery platform for Exo loaded with BLM and testing its therapeutic efficacy against cancer. METHODS: Exosomes were isolated from cancer cells and incubated with BLM. Exo were characterized by transmission electron microscopy, western blot analysis and nanoparticle tracking analysis. We performed in vitro and in vivo analyses to evaluate the effect of Exo-BLM. RESULTS: Exosomes loaded with BLM are highly cancer targeting and cause the cytotoxicity of tumor cells by ROS. The fluorescence images showed that Exo-BLM accumulated in cancer cells. The results revealed that Exo-BLM induces tumor cell apoptosis by the caspase pathway. In vivo, the treatment of Exo-BLM showed targeted ability and enhanced the antitumor activity. CONCLUSION: This study provides an avenue for specific BLM therapeutics with minimal side effects.
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Exossomos , Fibrose Pulmonar , Humanos , Bleomicina/farmacologia , Exossomos/metabolismo , Linhagem Celular Tumoral , Apoptose , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismoRESUMO
Nontraumatic surgical emergencies constitute a major bulk of general surgical practice. Most of the cases seen fall under routine, but now and then, a surgeon or emergency physician is faced with an unusual diagnosis or a rarer presentation of a usual diagnosis. Sharing among peers their experiences with these outliers of practice helps spread knowledge and increases the experience pool. We share our experience of a 66-year-old female who presented to our emergency with upper abdominal pain of one-day duration.
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The hostile oxidative wound microenvironment, defective angiogenesis, and uncontrolled release of therapeutic factors are major challenges in improving the diabetic wound healing. Herein, adipose-derived-stem-cell-derived exosomes (Exos) are first loaded into Ag@bovine serum albumin (BSA) nanoflowers (Exos-Ag@BSA NFs) to form a protective "pollen-flower" delivery structure, which are further encapsulated into the injectable collagen (Col) hydrogel (Exos-Ag@BSA NFs/Col) for concurrent remodeling of the oxidative wound microenvironment and precise release of Exos. The Exos-Ag@BSA NFs can selectively dissociate in an oxidative wound microenvironment, which triggers sustained release of Ag ions (Ag+ ) and cascades controllable release of "pollen-like" Exos at the target site, thus protecting Exos from oxidative denaturation. Such a wound-microenvironment-activated release property of Ag+ and Exos effectively eliminates bacteria and promotes the apoptosis of impaired oxidative cells, resulting in improved regenerative microenvironment. Additionally, Exos-Ag@BSA NFs/Col markedly accelerates wound healing and regeneration in vivo in a diabetic murine silicone-splinted excisional wound model by promoting blood perfusion, tissue granulation, collagen deposition, neovascularization, angiogenesis, and re-epithelization. It is anticipated that this work will inspire the development of more delicate and disease-specific therapeutic systems for clinical wound management.