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1.
J Nanobiotechnology ; 22(1): 609, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39380011

RESUMO

The photothermal conversion properties of tellurium (Te) nanoparticles have been extensively investigated, rendering them a promising candidate for tumor photothermal therapy. However, there is still room for improvement in the development of efficient Te-based drug delivery systems. Here, Te nanoparticles are mineralized with bioactive molecules within attenuated Salmonella (S-Te), which are subsequently taken up by macrophages (RAW264.7) to construct a double-camouflaged delivery platform (RS-Te). Remarkably, RS-Te retains superior photothermal properties under near-infrared irradiation. The mineralization process eliminates bacterial proliferation potential, thereby mitigating the risk of excessive bacterial growth in vivo. Furthermore, the uptake of bacteria by macrophages not only polarizes them into M1 macrophages to induce an anti-tumor immune response but also circumvents any adverse effects caused by complex antigens on the bacterial surface. The results show that RS-Te can effectively accumulate and retain in tumors. RS-Te-mediated photothermal immunotherapy largely promotes the maturation of dendritic cells and priming of cytotoxic T cells induced by near-infrared laser irradiation. Moreover, RS-Te can switch the activation of macrophages from an immunosuppressive M2 phenotype to a more inflammatory M1 state. The double-camouflaged delivery system may offer highly efficient and safe cancer treatment.


Assuntos
Imunoterapia , Macrófagos , Terapia Fototérmica , Telúrio , Telúrio/química , Animais , Camundongos , Células RAW 264.7 , Imunoterapia/métodos , Terapia Fototérmica/métodos , Nanopartículas/química , Neoplasias/terapia , Salmonella , Linhagem Celular Tumoral , Feminino , Camundongos Endogâmicos BALB C , Sistemas de Liberação de Medicamentos/métodos , Linfócitos T Citotóxicos/imunologia , Células Dendríticas/imunologia
2.
J Photochem Photobiol B ; 260: 113024, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39276447

RESUMO

Ovarian aging is a serious clinical concern. Few safe and effective methods are currently available to improve ovarian functions. Photobiomodulation (PBM) is a safe and noninvasive physical therapy that can modulate a series of biological processes. Recently, several studies have noted its potential to improve the function of ovary and reproductive cells. However, the effects of PBM treatment on natural ovarian aging remain unclear. In this study, we used a naturally reproductive aging mouse model to observe the effect of PBM on ovarian function. Young and aged female ICR mice were treated with or without PBM for 2 months. PBM was performed using a semiconductor InGaAlP laser emitting at 650 nm (80 mW, 6.7 mW/cm2 for 5 or 10 min, resulting in a dose of 2 or 4 J/cm2, respectively). After treatment, the effects of PBM and its role in oxidative stress, inflammation, and mitochondrial function were investigated. We found that PBM (4 J/cm2) effectively recovered the levels of sex hormones, increased the number of primordial and growing follicles, improved angiogenesis, and decreased cell apoptosis in naturally aged mice. Moreover, PBM reduced oxidative stress, inhibited chronic ovarian inflammation, and improved mitochondrial function in aged ovaries. Similar protective effects of PBM were observed in a hydrogen peroxide-induced oxidative stress model of human granulosa cell line (KGN) in vitro. Increased cell viability, cell proliferation, hormone secretion, mitochondrial membrane potential, and adenosine triphosphate levels and decreased apoptosis and oxidative stress were detected in KGN cells after PBM treatment. Collectively, this study suggest that PBM treatment is beneficial for restoring ovarian function in naturally reproductive aging mice and has a significant protective effect against oxidative stress damage in KGN cells. The mechanisms underlying the benefits of PBM in ovarian aging include antioxidant stress, reduction of inflammation, and preservation of mitochondrial function. Therefore, this study emphasizes the potential of PBM as a therapeutic intervention to ameliorate ovarian aging.

3.
Food Chem ; 463(Pt 2): 141126, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39276559

RESUMO

In apples, a bottleneck effect in calcium (Ca) transport within fruit stalk has been observed. To elucidate that how auxin affects Ca forms and distribution in the apple fruit stalk, we investigated the effects of different concentrations of auxin treatment (0, 10, 20, and 30 mg·L-1) on Ca content, forms, distribution, and fruit quality during later stages of fruit expansion. The results showed that auxin treatment led to a dramatic reduction in total Ca content in stalk, while an approximately 30 % increase in fruit. Furthermore, auxin treatment effectively enhanced the functionality of xylem vessels in vascular bundles of the stalk in bagged apples. Finally, TOPSIS method was used to assess fruit quality, with treatments ranked as follows: IAA20 > NAA20 > IAA30 > IAA10 > CK > NPA. The findings lay a foundation for further studies on the bottleneck in Ca transport within stalk, uneven distribution of Ca in fruit, and provide insights into Ca utilization efficiency in bagged apples.

4.
J Cosmet Dermatol ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327749

RESUMO

BACKGROUND: Radiofrequency (RF) has been widely used for rejuvenation treatments, but without knowledge of the effective temperature of the target tissues or guidance on treatment parameters, it often leads to adverse reactions and pain. The aim of this study was to demonstrate that thermal stimulation can produce facial rejuvenation effects and to determine the optimal bipolar RF treatment parameters for treating facial fine lines. METHODS: A bipolar RF device combined with CORE Technology was used in this study. Ex vivo studies were conducted on both miniature swine and human skin, utilizing thermographic thermometry and histological analysis. In vivo swine studies were conducted using histological analysis and electron microscopy. A clinical trial was conducted, and the results were evaluated using the Alexiades Comprehensive Grading Scale (ACGS) and Global Aesthetic Improvement Scale (GAIS) scales. RESULTS: The bipolar RF technology can produce a significant effect by thermally stimulating collagen within just 2 weeks without causing thermal damage. A clinical trial involving 46 patients showed a noticeable rejuvenating effect of the bipolar RF device, especially on fine wrinkles. CONCLUSION: This study confirmed that thermal stimulation, rather than thermal damage, is sufficient to achieve rejuvenation effects. The study also found a range of bipolar RF treatment parameters that are both safe and effective for facial fine lines.

5.
Front Bioeng Biotechnol ; 12: 1387474, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39193227

RESUMO

Background and Purpose: The risk of skin injuries in space is increasing with longer space missions and a growing astronaut population. This highlights the importance of understanding the adverse effects of weightlessness on wound healing. The objective of this research was to examine the therapeutic potential of Low-Level Light Therapy (LLLT) on skin healing processes under simulated microgravity (SMG) conditions and uncover the underlying molecular mechanisms, thus providing innovative solutions and a sound theoretical basis for space skin injuries. Methods: Hindlimb unloading (HU) mice models were used to simulate weightlessness conditions, with or without a complete management of LLLT for 14 days. A systematic testing consisting of HE, Masson and immunohistochemical staining was performed against the standardized mouse tissue specimens. In vitro assessment of cellular biological functions under SMG conditions was carried out in the rotation system of culture (RSOC) using HaCaT and NIH3T3 cell-lines. Results: Under SMG conditions, LLLT significantly reduced skin wound area in HU mice, especially on Days 10 (p < 0.001), accompanied by increased collagen deposition and elevated levels of Ki67 and CD31. Moreover, LLLT showed impressive anti-inflammatory effects represented by the reduced in pro-inflammatory markers including LY6G, F4/80 and CD86, as well as the decreased levels of IL-1ß, IL-6 and TNF-α. Conversely, an elevation in the anti-inflammatory marker CD206 was observed. By employing bioinformatics technology, we further found the PI3K/AKT signaling was prominent in the KEGG pathway analysis and CCR2 acted as a hub gene in the interaction network. Therefore, we demonstrated that LLLT could enhance the phosphorylation of PI3K/AKT and reduce CCR2 expression under SMG conditions, while CCR2 knockdown promoted the phosphorylation of PI3K/AKT, suggesting an important role of CCR2/PI3K/AKT signal axis in LLLT-accelerated wound healing under SMG conditions. Conclusion: LLLT induced activation of the PI3K/AKT signaling pathway through suppression of CCR2 expression, which significantly enhanced skin wound healing under SMG conditions.s.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39172178

RESUMO

Previous studies have demonstrated that the combination of photodynamic therapy, photothermal therapy and chemotherapy is highly effective in treating hepatocellular carcinoma (HCC). However, the clinical application of this approach has been hindered by the lack of efficient and low-toxicity drug delivery platforms. To address this issue, we developed a novel biomimetic nanocarrier platform named ZID@RM, which utilizes ZIF8 functional nanoparticles encapsulated with macrophage membrane and loaded with indocyanine green and doxorubicin. The bionic nanocarrier platform has good biocompatibility, reducing the risk of rapid clearance by macrophages and improving the targeting ability for HCC cells. Under the dual regulation of acidity and infrared light, ZID@RM stimulated the generation of abundant reactive oxygen species within HCC cells, induced tumor cell pyroptosis and promoted the release of damage-associated molecular patterns to induce immune responses. In the future, this technology platform has the potential to provide personalized and improved healthcare by using patients' own macrophage membranes to create an efficient drug delivery system for tumor therapy.Graphical abstract Scheme 1 Schematic representation of the synthesis of a biomimetic nanomedicine delivery platform (ZID@RM) and its application in tumor imaging-guided combination therapy.

7.
World Neurosurg ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39094940

RESUMO

BACKGROUND: Currently, there is no established criterion for determining when interventional treatment is necessary or which strategy is appropriate for basilar artery (BA) aneurysms. Through this study, we aimed to propose an algorithm that can effectively determine the optimal endovascular treatment (EVT) option for BA aneurysms. METHODS: We enrolled patients with BA aneurysms from June 2016 to December 2022 and performed procedures based on the algorithm. The analysis included demographic, clinical, and aneurysmal characteristics, procedural details, complications, angiographic outcomes, and clinical outcomes. RESULTS: This study included 124 patients (mean age 55.0 years) with a BA aneurysm who underwent EVT. Of these, 21 aneurysms were treated in the setting of subarachnoid hemorrhage. The majority of the aneurysms were located at the basilar apex (74), followed by the basilar trunk (30) and vertebrobasilar junction (20). Coiling was used in 18.5% of the cases, while stent-assisted coiling embolization was chosen for 58.9%. Overlapping stents were used in 12.9%, flow diverter implantation in 3.2%, Y/T stent techniques in 4.8%, and stent adjunctive coiling with unilateral vertebral artery occlusion in only 1.6%. Procedure-related complications occurred in 15 patients (12.1%). The patients had a modified Rankin Scale score of 0.74 ± 1.62; 98 (86.7%) had a good prognosis with modified Rankin Scale scores ranging from 0 to 2 at the last follow-up. Digital subtraction angiography was performed on 105 (84.7%) patients, revealing that 101 (81.5%) achieved complete or near-complete occlusion. CONCLUSIONS: The criteria for EVT of BA aneurysms based on multi-characteristics were safe and effective. However, further evidence from large cohort studies is needed.

8.
Curr Microbiol ; 81(10): 324, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180522

RESUMO

It turns out that the more than trillion microorganisms living in the host's digestive tract are crucial for maintaining nutrient intake, environmental suitability, and physiological mechanism. Xinjiang fine-wool sheep is an exclusive breed for wool in China, which has excellent stress tolerance. In this study, we collected feces and blood samples of 20 Xinjiang fine-wool sheep under the same genetic characteristics, the Fine-Wool Sheep (FWS) group and the Control Fine-Wool Sheep (CFWS) group were set up according to the differs in phenotypic characteristics of their wool. By 16S rRNA amplicon sequence, ITS1 region amplicons and Targeted Metabolomics, we analyzed the microbial community structure of fecal microorganisms and Short Chain Fatty Acids (SCFAs) in serum of the Xinjiang fine-wool sheep. Fecal microbial sequencing showed that the bacterial composition and structure were similar between the two groups, whereas there were significant differences in the composition and structure of the fungal community. It was also found that the abundant of Neocallimastigomycota in the intestinal fungal community of FWS was higher. In addition, the results of the serum SCFAs content analysis showed that butyric acid was significantly differences than those two groups. Correlation analysis between SCFAs and bacteria found that butyric acid metabolism had positively correlated (P < 0.05) with Ruminococcus and UCG-005. Overall, our data provide more supplement about the gut microbes community composition and structure of the Xinjiang fine-wool sheep. These results might be useful for improving gut health of sheep and taking nutritional control measure to improve production traits of animals in future.


Assuntos
Bactérias , Ácidos Graxos Voláteis , Fezes , Microbioma Gastrointestinal , Sequenciamento de Nucleotídeos em Larga Escala , RNA Ribossômico 16S , Animais , Ovinos/microbiologia , Fezes/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/isolamento & purificação , China , RNA Ribossômico 16S/genética , Ácidos Graxos Voláteis/metabolismo , Fungos/genética , Fungos/classificação , Fungos/metabolismo , Lã/microbiologia , Filogenia
9.
Gene ; 927: 148758, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38977109

RESUMO

The gut microbiota is a treasure trove of carbohydrate-active enzymes (CAZymes). To explore novel and efficient CAZymes, we analyzed the 4,142 metagenome-assembled genomes (MAGs) of the horse gut microbiota and found the MAG117.bin13 genome (Bacteroides fragilis) contains the highest number of polysaccharide utilisation loci sites (PULs), indicating its high capability for carbohydrate degradation. Bioinformatics analysis indicate that the PULs region of the MAG117.bin13 genome encodes many hypothetical proteins, which are important sources for exploring novel CAZymes. Interestingly, we discovered a hypothetical protein (595 amino acids). This protein exhibits potential CAZymes activity and has a lower similarity to CAZymes, we named it BfLac2275. We purified the protein using prokaryotic expression technology and studied its enzymatic function. The hydrolysis experiment of the polysaccharide substrate showed that the BfLac2275 protein has the ability to degrade α-lactose (156.94 U/mg), maltose (92.59 U/mg), raffinose (86.81 U/mg), and hyaluronic acid (5.71 U/mg). The enzyme activity is optimal at pH 5.0 and 30 ℃, indicating that the hypothetical protein BfLac2275 is a novel and multifunctional CAZymes in the glycoside hydrolases (GHs). These properties indicate that BfLac2275 has broad application prospects in many fields such as plant polysaccharide decomposition, food industry, animal feed additives and enzyme preparations. This study not only serves as a reference for exploring novel CAZymes encoded by gut microbiota but also provides an example for further studying the functional annotation of hypothetical genes in metagenomic assembly genomes.


Assuntos
Microbioma Gastrointestinal , Glicosídeo Hidrolases , Metagenoma , Animais , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/metabolismo , Glicosídeo Hidrolases/química , Microbioma Gastrointestinal/genética , Cavalos , Genoma Bacteriano , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Especificidade por Substrato , Filogenia
10.
Int Immunopharmacol ; 139: 112745, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39059099

RESUMO

Acute kidney injury (AKI) manifests as a clinical syndrome characterised by the rapid accumulation of metabolic wastes, such as blood creatinine and urea nitrogen, leading to a sudden decline in renal function. Currently, there is a lack of specific therapeutic drugs for AKI. Previously, we identified gastrin-releasing peptide receptor (GRPR) as a pathogenic factor in AKI. In this study, we investigated the therapeutic potential of a novel Chinese medicine monomer, aurantiamide (AA), which exhibits structural similarities to our previously reported GRPR antagonist, RH-1402. We compared the therapeutic efficacy of AA with RH-1402 both in vitro and in vivo using various AKI models. Our results demonstrated that, in vitro, AA attenuated injury, necroptosis, and inflammatory responses in human renal tubular epithelial cells subjected to repeated hypoxia/reoxygenation and lipopolysaccharide stimulation. In vivo, AA ameliorated renal tubular injury and inflammation in mouse models of ischemia/reperfusion and cecum ligation puncture-induced AKI, surpassing the efficacy of RH-1402. Furthermore, molecular docking and cellular thermal shift assay confirmed GRPR as a direct target of AA, which was further validated in primary cells. Notably, in GRPR-silenced HK-2 cells and GRPR systemic knockout mice, AA failed to mitigate renal inflammation and injury, underscoring the importance of GRPR in AA's mechanism of action. In conclusion, our study has demonstrated that AA serve as a novel antagonist of GRPR and a promising clinical candidate for AKI treatment.


Assuntos
Injúria Renal Aguda , Camundongos Endogâmicos C57BL , Camundongos Knockout , Necroptose , Receptores da Bombesina , Animais , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Humanos , Necroptose/efeitos dos fármacos , Camundongos , Masculino , Linhagem Celular , Receptores da Bombesina/metabolismo , Receptores da Bombesina/antagonistas & inibidores , Inflamação/tratamento farmacológico , Modelos Animais de Doenças , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
11.
J Med Chem ; 67(16): 13829-13851, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39082833

RESUMO

Endometrial cancer (EC) is the most common cancer of the female reproductive tract, and there is an urgent need to develop new candidate drugs with good efficacy and safety to improve the survival rate and life quality of EC patients. Herein, a series of new azaphenothiazine derivatives were designed and synthesized and their anti-EC activities were evaluated. Among them, compound 33 showed excellent antiproliferative activities against both progesterone-sensitive ISK cells and progesterone-resistant KLE cells. Moreover, 33 could significantly inhibit colony formation and migration of EC cells and induce cell apoptosis. Remarkably, 33 significantly suppressed KLE xenograft tumor growth without influencing body weights or key organs. In addition, 33 exhibited good pharmacokinetic properties and low extrapyramidal side effects. Mechanism research indicated that 33 reduced Ca2+ levels in mitochondria by targeting GRP75 and disrupting its interaction with IP3R. Overall, 33 showed promising potential as an anti-EC candidate agent.


Assuntos
Antineoplásicos , Cálcio , Proliferação de Células , Neoplasias do Endométrio , Receptores de Inositol 1,4,5-Trifosfato , Mitocôndrias , Fenotiazinas , Humanos , Feminino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Animais , Fenotiazinas/farmacologia , Fenotiazinas/síntese química , Fenotiazinas/química , Fenotiazinas/uso terapêutico , Cálcio/metabolismo , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/metabolismo , Proliferação de Células/efeitos dos fármacos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Linhagem Celular Tumoral , Homeostase/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos Nus , Proteínas de Choque Térmico HSP70/metabolismo , Descoberta de Drogas , Relação Estrutura-Atividade , Camundongos Endogâmicos BALB C , Proteínas de Membrana
12.
Biomed Pharmacother ; 177: 117087, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38964178

RESUMO

Thirteen previously undescribed lindenane sesquiterpenoid dimers (LSDs), named chlorahololides G-S (1-13), were isolated from the whole plants of Chloranthus holostegius var. shimianensis, along with ten known analogues (14-23). The structures and absolute configurations of compounds 1-13 were elucidated through comprehensive spectroscopic analysis, NMR and electronic circular dichroism (ECD) calculations, and X-ray single-crystal diffraction. Chlorahololide G (1) represents the first instance of LSDs formed via a C-15-C-9' carbon-carbon single bond, whose plausible biosynthetic pathway was also proposed. Chlorahololides I and J (3 and 4) were deduced to be rare 8,9-seco and 9-deoxy LSDs with C-11-C-7' carbon-carbon bond, respectively. The inhibitory activity against NLRP3 inflammasome activation was evaluated for all isolates, with six compounds (5, 7, 8, 17, 22, and 23) exhibiting significant effects, and IC50 values ranging from 2.99 to 8.73 µM. Additionally, a preliminary structure-activity relationship analysis regarding their inhibition of NLRP3 inflammasome activation was summarized. Compound 17 exhibited dose-dependent inhibition of nigericin-induced pyroptosis in J774A.1 cells. Molecular docking studies suggested a strong interaction between compound 17 and NLRP3.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sesquiterpenos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Inflamassomos/metabolismo , Inflamassomos/antagonistas & inibidores , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/química , Animais , Camundongos , Simulação de Acoplamento Molecular , Dimerização , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
13.
Cell Commun Signal ; 22(1): 357, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987851

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. METHODS: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155-/- mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. RESULTS: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated ß-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. CONCLUSIONS: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.


Assuntos
Senescência Celular , Células Epiteliais , Exossomos , Túbulos Renais , Macrófagos , MicroRNAs , Telômero , MicroRNAs/genética , MicroRNAs/metabolismo , Senescência Celular/genética , Exossomos/metabolismo , Exossomos/genética , Animais , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Macrófagos/metabolismo , Túbulos Renais/patologia , Túbulos Renais/metabolismo , Camundongos , Telômero/genética , Telômero/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Masculino , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologia , Fibrose/genética , Angiotensina II
14.
Talanta ; 278: 126496, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38996563

RESUMO

Dopamine is an important neurotransmitter in the body and closely related to many neurodegenerative diseases. Therefore, the detection of dopamine is of great significance for the diagnosis and treatment of diseases, screening of drugs and unraveling of relevant pathogenic mechanisms. However, the low concentration of dopamine in the body and the complexity of the matrix make the accurate detection of dopamine challenging. Herein, an electrochemical sensor is constructed based on ternary nanocomposites consisting of one-dimensional Pt nanowires, two-dimensional MXene nanosheets, and three-dimensional porous carbon. The Pt nanowires exhibit excellent catalytic activity due to the abundant grain boundaries and highly undercoordinated atoms; MXene nanosheets not only facilitate the growth of Pt nanowires, but also enhance the electrical conductivity and hydrophilicity; and the porous carbon helps induce significant adsorption of dopamine on the electrode surface. In electrochemical tests, the ternary nanocomposite-based sensor achieves an ultra-sensitive detection of dopamine (S/N = 3) with a low limit of detection (LOD) of 28 nM, satisfactory selectivity and excellent stability. Furthermore, the sensor can be used for the detection of dopamine in serum and in situ monitoring of dopamine release from PC12 cells. Such a highly sensitive nanocomposite sensor can be exploited for in situ monitoring of important neurotransmitters at the cellular level, which is of great significance for related drug screening and mechanistic studies.


Assuntos
Carbono , Dopamina , Técnicas Eletroquímicas , Nanocompostos , Nanofios , Platina , Dopamina/análise , Dopamina/sangue , Dopamina/química , Platina/química , Células PC12 , Nanofios/química , Nanocompostos/química , Animais , Carbono/química , Ratos , Porosidade , Técnicas Eletroquímicas/métodos , Neurônios/metabolismo , Limite de Detecção , Eletrodos
15.
Anal Chem ; 96(31): 12776-12783, 2024 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-39047235

RESUMO

The healthcare burden imposed by bacterial infections demands robust and accessible diagnostic methods that can be performed outside hospitals and centralized laboratories. Here, we report Pathogen Assay with Ratiometric Luminescence (PEARL), a sensitive and easy-to-operate platform for detecting pathogenic bacteria. The PEARL leveraged a color-changeable CRISPR-Cas12a sensor and recombinase polymerase amplification to elicit ratiometric bioluminescence responses to target inputs. This platform enabled robust and visualized identification of attomolar bacteria genome deoxyribonucleic acid according to the color changes of the reactions. In addition, the components of the color-changeable Cas12a sensor could be lyophilized for 3 month storage at ambient temperature and then be fully activated with the amplicons derived from crude bacterial lysates, reducing the requirements for cold-chain storage and tedious handling steps. We demonstrated that the PEARL assay is applicable for identifying the infections caused by Pseudomonas aeruginosa in different clinical specimens, including sputa, urines, and swabs derived from wounds. These results revealed the potential of PEARL to be used by untrained personnel, which will facilitate decentralized pathogen diagnosis in community- and resource-limited regions.


Assuntos
Sistemas CRISPR-Cas , Medições Luminescentes , Pseudomonas aeruginosa , Sistemas CRISPR-Cas/genética , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/genética , Humanos , Liofilização , Cor , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Técnicas Biossensoriais , Proteínas Associadas a CRISPR/metabolismo , Luminescência
16.
BMC Cancer ; 24(1): 762, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918690

RESUMO

BACKGROUND: Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. METHODS: We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram's predictive accuracy to rigorous independent validation. RESULTS: The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28-0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64-0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65-0.74). CONCLUSIONS: In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.


Assuntos
Quimiorradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Humanos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/patologia , Quimiorradioterapia/métodos , Prognóstico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , Adulto , Plaquetas/patologia , Idoso , Albumina Sérica/análise , Estadiamento de Neoplasias , Adulto Jovem , Modelos de Riscos Proporcionais , Contagem de Plaquetas , Biomarcadores Tumorais/sangue
17.
Nanomaterials (Basel) ; 14(12)2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38921866

RESUMO

Intensive increases in electrical energy storage are being driven by electric vehicles (EVs), smart grids, intermittent renewable energy, and decarbonization of the energy economy. Advanced lithium-sulfur batteries (LSBs) are among the most promising candidates, especially for EVs and grid-scale energy storage applications. In this topical review, the recent progress and perspectives of practical LSBs are reviewed and discussed; the challenges and solutions for these LSBs are analyzed and proposed for future practical and large-scale energy storage applications. Major challenges for the shuttle effect, reaction kinetics, and anodes are specifically addressed, and solutions are provided on the basis of recent progress in electrodes, electrolytes, binders, interlayers, conductivity, electrocatalysis, artificial SEI layers, etc. The characterization strategies (including in situ ones) and practical parameters (e.g., cost-effectiveness, battery management/modeling, environmental adaptability) are assessed for crucial automotive/stationary large-scale energy storage applications (i.e., EVs and grid energy storage). This topical review will give insights into the future development of promising Li-S batteries toward practical applications, including EVs and grid storage.

18.
Sensors (Basel) ; 24(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38894057

RESUMO

In this article, a novel cross-domain knowledge transfer method is implemented to optimize the tradeoff between energy consumption and information freshness for all pieces of equipment powered by heterogeneous energy sources within smart factory. Three distinct groups of use cases are considered, each utilizing a different energy source: grid power, green energy source, and mixed energy sources. Differing from mainstream algorithms that require consistency among groups, the proposed method enables knowledge transfer even across varying state and/or action spaces. With the advantage of multiple layers of knowledge extraction, a lightweight knowledge transfer is achieved without the need for neural networks. This facilitates broader applications in self-sustainable wireless networks. Simulation results reveal a notable improvement in the 'warm start' policy for each equipment, manifesting as a 51.32% increase in initial reward compared to a random policy approach.

19.
MedComm (2020) ; 5(6): e585, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38832213

RESUMO

How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno-occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity-based and pathological distortion-independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single-subject level. Thirty-three machine-learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC > 0.7). Notably, the FC feature-based model for long-term neurological outcomes performed very well (AUC > 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate "fingerprints" of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion.

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