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1.
Front Vet Sci ; 11: 1424711, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983771

RESUMO

The aim of this study was to investigate the effect of hesperidin on the liver and kidney dysfunctions induced by nickel. The mice were divided into six groups: nickel treatment with 80 mg/kg, 160 mg/kg, 320 mg/kg hesperidin groups, 0.5% CMC-Na group, nickel group, and blank control group. Histopathological techniques, biochemistry, immunohistochemistry, and the TUNEL method were used to study the changes in structure, functions, oxidative injuries, and apoptosis of the liver and kidney. The results showed that hesperidin could alleviate the weight loss and histological injuries of the liver and kidney induced by nickel, and increase the levels of lactate dehydrogenase (LDH), alanine aminotransferase (GPT), glutamic oxaloacetic transaminase (GOT) in liver and blood urea nitrogen (BUN), creatinine (Cr) and N-acetylglucosidase (NAG) in kidney. In addition, hesperidin could increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) in the liver and kidney, decrease the content of malondialdehyde (MDA) and inhibit cell apoptosis. It is suggested that hesperidin could help inhibit the toxic effect of nickel on the liver and kidney.

2.
Immun Inflamm Dis ; 12(7): e1338, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38990142

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) infection is an important risk factor for Coronavirus Disease 2019 (COVID-19), but data on the prevalence of COVID-19 among people living with HIV (PLWH) is limited in low-income countries. Our aim was to assess the seroprevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies and associated factors among PLWH in Sierra Leone. METHODS: We conducted a cross-sectional survey of PLWH aged 18 years or older in Sierra Leone between August 2022 and January 2023. Participants were tested for SARS-CoV-2 antibodies using a rapid SARS-CoV-2 antibody (immunoglobulin M/immunoglobulin G [IgG]) kits. Stepwise logistic regression was used to explore factors associated with SARS-CoV-2 antibody seroprevalence with a significance level of p < .05. RESULTS: In our study, 33.4% (1031/3085) participants had received a COVID-19 vaccine, and 75.7% were SARS-CoV-2 IgG positive. Higher IgG seroprevalence was observed in females (77.2% vs. 71.4%, p = .001), adults over 60 years (88.2%), those with suppressed HIV RNA (80.7% vs. 51.7%, p < .001), antiretroviral therapy (ART)-experienced individuals (77.9% vs. 44.6%, p < .001), and vaccinated participants (80.7% vs. 73.2%, p < .001). Patients 60 years or older had the highest odds of IgG seroprevalence (adjusted odds ratio [aOR] = 2.73, 95% CI = 1.68-4.65). Female sex (aOR = 1.28, 95%CI = 1.05-1.56), COVID-19 vaccination (aOR = 1.54, 95% CI = 1.27-1.86), and ART (aOR = 2.20, 95% CI = 1.56-3.11) increased the odds, whereas HIV RNA ≥ 1000 copies/mL (aOR = 0.32, 95% CI = 0.26-0.40) reduced the odds of IgG seroprevalence. CONCLUSIONS: We observed a high seroprevalence of SARS-CoV-2 antibody among PLWH in Sierra Leone. We recommend the introduction of targeted vaccination for PLWH with a high risk of severe COVID-19, especially those with an unsuppressed HIV viral load.


Assuntos
Anticorpos Antivirais , COVID-19 , Infecções por HIV , Imunoglobulina G , SARS-CoV-2 , Humanos , Masculino , Feminino , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/sangue , Serra Leoa/epidemiologia , Estudos Soroepidemiológicos , Adulto , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Estudos Transversais , Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Adulto Jovem , Fatores de Risco , Adolescente , Idoso , Vacinas contra COVID-19/imunologia
3.
Angew Chem Int Ed Engl ; : e202407929, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837292

RESUMO

Mechanically interlocked molecules (MIMs) are promising platform for developing functionalized artificial molecular machines. The construction of chiral MIMs with appealing circularly polarized luminescence (CPL) properties has boosted their potential application in biomedicine and optical industry. However, there is currently little knowledge about the CPL emission mechanism as well as the emission dynamics of these related MIMs. Herein, we demonstrate that time-resolved circularly polarized luminescence (TRCPL) spectroscopy combined with transient absorption (TA) spectroscopy offers a feasible approach to elucidate the origins of CPL emission in pyrene-functionalized topologically chiral [2]catenane as well as in a series of pyrene-functionalized chiral molecules. For the first time, direct evidence differentiating the chiroptical signals originating from either topological (local state emission) or Euclidean chirality (excimer state emission) in these pyrene-functionalized chiral molecules has been discovered. Our work not only establishes a novel and ideal methodology to study CPL mechanism, but also provides a theoretical foundation for the rational design of novel chiral materials in the future.

4.
Sci Total Environ ; 945: 174019, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38885713

RESUMO

Emerging evidence suggests that plants experiencing abiotic stress actively seek help from soil microbes. However, the empirical evidence supporting this strategy is limited, especially in response to heavy metal stress. We used integrated microbial community profiling and culture-based methods to investigate the interaction between mercury (Hg) stress, the entophytic root microbiome, and maize seedlings. The results of the pot experiment showed that soil Hg (20 mg/kg) strongly inhibited maize growth, indicating its strong phytotoxicity. Furthermore, Hg stress significantly altered the structure of the bacterial and fungal communities and enriched the potentially pathogenic Fusarium sp., suggesting that soil Hg stress may enhance the bio-stress induced by Fusarium species in maize. Additionally, soil Hg also led to the enrichment of beneficial bacterial members of Streptomyces, Lysobacter, and Sphingomonas (defined as differential species), which were also identified as keystone species in the Hg treatment by the analysis of co-occurrence networks. Therefore, it can be postulated that the members of Streptomyces, Lysobacter, and Sphingomonas function as stress-alleviating microbes. We successfully isolated the representatives of these stress-alleviating microbes. As expected, these strains mitigated the detrimental effects of Hg stess for the maize seedlings, suggesting that plants recruit the stress-alleviated microbiota to combat Hg stress. This study provides insights into the potential of manipulating the root microbiome to enhance plant growth in polluted environments.


Assuntos
Mercúrio , Microbiota , Raízes de Plantas , Microbiologia do Solo , Poluentes do Solo , Zea mays , Mercúrio/toxicidade , Zea mays/microbiologia , Zea mays/efeitos dos fármacos , Poluentes do Solo/toxicidade , Raízes de Plantas/microbiologia , Microbiota/efeitos dos fármacos , Endófitos/fisiologia , Estresse Fisiológico
5.
Sci Total Environ ; 946: 174057, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914340

RESUMO

Root-associated microbiota provide great fitness to hosts under environmental stress. However, the underlying microecological mechanisms controlling the interaction between heavy metal-stressed plants and the microbiota are poorly understood. In this study, we screened and isolated representative amplicon sequence variants (strain M4) from rhizosphere soil samples of Trifolium repens L. growing in areas with high concentrations of heavy metals. To investigate the microecological mechanisms by which T. repens adapts to heavy metal stress in abandoned mining areas, we conducted potting experiments, bacterial growth promotion experiments, biofilm formation experiments, and chemotaxis experiments. The results showed that high concentrations of heavy metals significantly altered the rhizosphere bacterial community structure of T. repens and significantly enriched Microbacterium sp. Strain M4 was demonstrated to significantly increased the biomass and root length of T. repens under heavy metal stress. Additionally, L-proline and stigmasterol could promote bacterial growth and biofilm formation and induce chemotaxis for strain M4, suggesting that they are key rhizosphere secretions of T. repens for Microbacterium sp. recruitment. Our results suggested that T. repens adapted the heavy metal stress by reshaping rhizosphere secretions to modify the rhizosphere microbiota.

6.
Chem Sci ; 15(19): 7178-7186, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38756822

RESUMO

In order to investigate the effect of macrocyclization and catenation on the regulation of vibration-induced emission (VIE), the typical VIE luminogen 9,14-diphenyl-9,14-dihydrodibenzo[a, c]phenazine (DPAC) was introduced into the skeleton of a macrocycle and corresponding [2]catenane to evaluate their dynamic relaxation processes. As investigated in detail by femtosecond transient absorption (TA) spectra, the resultant VIE systems revealed precisely tunable emissions upon changing the solvent viscosity, highlighting the key effect of the formation of [2]catenane. Notably, the introduction of an additional pillar[5]arene macrocycle featuring unique planar chirality endows the resultant chiral VIE-active [2]catenane with attractive circularly polarized luminescence in different states. This work not only develops a new strategy for the design of new luminescent systems with tunable vibration induced emission, but also provides a promising platform for the construction of smart chiral luminescent materials for practical applications.

7.
Angew Chem Int Ed Engl ; 63(26): e202402949, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644342

RESUMO

Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e- oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post-generation radical reinforcement. Namely, non-oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo-triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO2 -), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO2 - is released along with a bright rhodamine dye (RD565), whose fluorescence is a reliable and convenient build-in reporter for the localization, kinetics, and dose of ONOOCO2 - generation. Upon photolysis of NPCD565 in 4T1 cells, damage-associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor-bearing mouse model showcased the potent tumor-killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO2 -, and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer.


Assuntos
Carbono , Imunoterapia , Rodaminas , Animais , Camundongos , Rodaminas/química , Carbono/química , Fototerapia , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Corantes Fluorescentes/química
8.
PLoS One ; 19(4): e0293421, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38656963

RESUMO

The spray system mechanism during a gas explosion in an underground square pipeline is complex. In this paper, the underground square of Fuxin City is selected as the research object. FLACS numerical simulation software is used to analyze the spatial and temporal distribution characteristics of a gas explosion in an underground square pipeline with an unopened spray system using combustion and combustion rate models. Different spray pressures were compared and analyzed to determine the optimal spray control pressure, and the spray system mechanism was clarified. The results revealed that the gas explosion overpressure is divided into the overpressure gentle, overpressure rising, and overpressure decay stages, corresponding to a trend of rapid growth and slow decline. The influence of spray pressure on the gas explosion exhibits a promotion-inhibition-promotion trend, corresponding to 0-0.2 MPa, 0.2-0.6 MPa, and 0.6-1.6 Mpa, respectively. The peak overpressure and overpressure propagation rates are the lowest at 0.6 MPa, and the explosion suppression effect is the most pronounced. The spray system mechanism varies with the explosion overpressure stages. Generally, the time to peak value, that is, the peak time, the overall duration of the explosion, and the duration of the explosion stage decrease, whereas the peak explosion overpressure decreases.


Assuntos
Explosões , Gases , Pressão , Explosões/prevenção & controle , Modelos Teóricos , Simulação por Computador
9.
J Phys Chem Lett ; 15(10): 2765-2771, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482678

RESUMO

Gilvocarcin V (GV) is a natural antibiotic exhibiting excellent antitumor activities and remarkably low toxicity in near-ultraviolet or visible light-dependent treatment. Notwithstanding, the [2 + 2] cycloaddition reaction between GV and thymine has been proven to be the key for its function in photodynamic therapy, and crucial mechanistic details about such a reaction are poorly understood. In this study, the electronic relaxation pathways and photoaddition reaction are characterized by femto- to nanosecond time-resolved spectroscopy combined with quantum chemical calculation. Our results reveal that ultrafast intersystem crossing (<3 ps) leads to the population of a local triplet excited state in DNA-intercalated GV. Such a state can further induce the formation of a biradical state, which is identified as the important reactive precursor for photoaddition between GV and thymine. The overall photoaddition quantum efficiency is determined to be 11.57 ± 1.0%. These results are essential to the elucidation of the DNA photoaddition mechanism of C-aryl glycoside-based artificial photocytotoxic agents and could help further development of those medicines.


Assuntos
Cumarínicos , Glicosídeos , Timina , Timina/química , DNA/química , Antibacterianos
10.
J Chem Phys ; 160(12)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38526107

RESUMO

Proflavine (PF), an acridine DNA intercalating agent, has been widespread applied as an anti-microbial and topical antiseptic agent due to its ability to suppress DNA replication. On the other hand, various studies show that PF intercalation to DNA can increase photogenotoxicity and has potential chances to induce carcinomas of skin appendages. However, the effects of PF intercalation on the photophysical and photochemical properties of DNA have not been sufficiently explored. In this study, the excited state dynamics of the PF intercalated d(GC)9 • d(GC)9 and d(AT)9 • d(AT)9 DNA duplex are investigated in an aqueous buffer solution. Under 267 nm excitation, we observed ultrafast charge transfer (CT) between PF and d(GC)9 • d(GC)9 duplex, generating a CT state with an order of magnitude longer lifetime compared to that of the intrinsic excited state reported for the d(GC)9 • d(GC)9 duplex. In contrast, no excited state interaction was detected between PF and d(AT)9 • d(AT)9. Nevertheless, a localized triplet state with a lifetime over 5 µs was identified in the PF-d(AT)9 • d(AT)9 duplex.


Assuntos
Substâncias Intercalantes , Proflavina , Proflavina/química , Análise Espectral , Substâncias Intercalantes/química , DNA/química
12.
Mol Biol Rep ; 51(1): 339, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393419

RESUMO

BACKGROUND: Age-related macular degeneration (AMD) is a prevalent source of visual impairment among the elderly population, and its incidence has risen in tandem with the increasing longevity of humans. Despite the progress made with anti-VEGF therapy, clinical outcomes have proven to be unsatisfactory. METHOD: We obtained differentially expressed genes (DEGs) of AMD patients and healthy controls from the GEO database. GO and KEGG analyses were used to enrich the DEGs. Weighted gene coexpression network analysis (WGCNA) was used to identify modules related to AMD. SVM, random forest, and least absolute shrinkage and selection operator (LASSO) were employed to screen hub genes. Gene set enrichment analysis (GSEA) was used to explore the pathways in which these hub genes were enriched. CIBERSORT was utilized to analyze the relationship between the hub genes and immune cell infiltration. Finally, Western blotting and RT‒PCR were used to explore the expression of hub genes in AMD mice. RESULTS: We screened 1084 DEGs in GSE29801, of which 496 genes were upregulated. These 1084 DEGs were introduced into the WGCNA, and 94 genes related to AMD were obtained. Seventy-nine overlapping genes were obtained by the Venn plot. These 79 genes were introduced into three machine-learning methods to screen the hub genes, and the genes identified by the three methods were TNC, FAP, SREBF1, and TGF-ß2. We verified their diagnostic function in the GSE29801 and GSE103060 datasets. Then, the hub gene co-enrichment pathways were obtained by GO and KEGG analyses. CIBERSORT analysis showed that these hub genes were associated with immune cell infiltration. Finally, we found increased expression of TNC, FAP, SREBF1, and TGF-ß2 mRNA and protein in the retinas of AMD mice. CONCLUSION: We found that four hub genes, namely, FAP, TGF-ß2, SREBF1, and TNC, have diagnostic significance in patients with AMD and are related to immune cell infiltration. Finally, we determined that the mRNA and protein expression of these hub genes was upregulated in the retinas of AMD mice.


Assuntos
Degeneração Macular , Fator de Crescimento Transformador beta2 , Humanos , Idoso , Animais , Camundongos , Fator de Crescimento Transformador beta2/genética , Degeneração Macular/genética , Retina , Western Blotting , RNA Mensageiro
13.
J Am Chem Soc ; 146(3): 1839-1848, 2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38194423

RESUMO

Epigenetic modifications impart important functionality to nucleic acids during gene expression but may increase the risk of photoinduced gene mutations. Thus, it is crucial to understand how these modifications affect the photostability of duplex DNA. In this work, the ultrafast formation (<20 ps) of a delocalized triplet charge transfer (CT) state spreading over two stacked neighboring nucleobases after direct UV excitation is demonstrated in a DNA duplex, d(G5fC)9•d(G5fC)9, made of alternating guanine (G) and 5-formylcytosine (5fC) nucleobases. The triplet yield is estimated to be 8 ± 3%, and the lifetime of the triplet CT state is 256 ± 22 ns, indicating that epigenetic modifications dramatically alter the excited state dynamics of duplex DNA and may enhance triplet state-induced photochemistry.


Assuntos
DNA , Epigênese Genética , DNA/química , DNA/efeitos da radiação , Raios Ultravioleta
14.
Angew Chem Int Ed Engl ; 63(12): e202319502, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38279667

RESUMO

Aiming at the construction of novel stimuli-responsive fluorescent system with precisely tunable emissions, the typical 9,14-diphenyl-9,14-dihydrodibenzo[a, c]phenazine (DPAC) luminogen with attractive vibration-induced emission (VIE) behavior has been introduced into [2]rotaxane as a stopper. Taking advantage of their unique dual stimuli-responsiveness towards solvent and anion, the resultant [2]rotaxanes reveal both tunable VIE and switchable circularly polarized luminescence (CPL). Attributed to the formation of mechanical bonds, DPAC-functionalized [2]rotaxanes display interesting VIE behaviors including white-light emission upon the addition of viscous solvent, as evaluated in detail by femtosecond transient absorption (TA) spectra. In addition, ascribed to the regulation of chirality information transmission through anion-induced motions of chiral wheel, the resolved chiral [2]rotaxanes reveal unique switchable CPL upon the addition of anion, leading to significant increase in the dissymmetry factors (glum ) values with excellent reversibility. Interestingly, upon doping the chiral [2]rotaxanes in stretchable polymer, the blend films reveal remarkable emission change from white light to light blue with significant 6.5-fold increase in glum values up to -0.035 under external tensile stresses. This work provides not only a new design strategy for developing molecular systems with fluorescent tunability but also a novel platform for the construction of smart chiral luminescent materials for practical use.

15.
Nat Commun ; 15(1): 405, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195782

RESUMO

Nanoscale optoelectrodes hold the potential to stimulate optically individual neurons and intracellular organelles, a challenge that demands both a high-density of photoelectron storage and significant charge injection. Here, we report that zinc porphyrin, commonly used in dye-sensitized solar cells, can be self-assembled into nanorods and then coated by TiO2. The J-aggregated zinc porphyrin array enables long-range exciton diffusion and allows for fast electron transfer into TiO2. The formation of TiO2(e-) attracts positive charges around the neuron membrane, contributing to the induction of action potentials. Far-field cranial irradiation of the motor cortex using a 670 nm laser or an 850 nm femtosecond laser can modulate local neuronal firing and trigger motor responses in the hind limb of mice. The pulsed photoelectrical stimulation of neurons in the subthalamic nucleus alleviates parkinsonian symptoms in mice, improving abnormal stepping and enhancing the activity of dopaminergic neurons. Our results suggest injectable nanoscopic optoelectrodes for optical neuromodulation with high efficiency and negligible side effects.


Assuntos
Irradiação Craniana , Neurônios Dopaminérgicos , Animais , Camundongos , Potenciais de Ação , Difusão
16.
Environ Sci Pollut Res Int ; 31(2): 1941-1953, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38044401

RESUMO

The combination of biochar and bacteria is a promising strategy for the remediation of Cd-polluted soils. However, the synergistic mechanisms of biochar and bacteria for Cd immobilization remain unclear. In this study, the experiments were conducted to evaluate the effects of the combination of biochar and Pseudomonas sp. AN-B15, on Cd immobilization, soil enzyme activity, and soil microbiome. The results showed that biochar could directly reduce the motility of Cd through adsorption and formation of CdCO3 precipitates, thereby protecting bacteria from Cd toxicity in the solution. In addition, bacterial growth further induces the formation of CdCO3 and CdS and enhances Cd adsorption by bacterial cells, resulting in a higher Cd removal rate. Thus, bacterial inoculation significantly enhances Cd removal in the presence of biochar in the solution. Moreover, soil incubation experiments showed that bacteria-loaded biochar significantly reduced soil exchangeable Cd in comparison with other treatments by impacting soil microbiome. In particular, bacteria-loaded biochar increased the relative abundance of Bacillus, Lysobacter, and Pontibacter, causing an increase in pH, urease, and arylsulfatase, thereby passivating soil exchangeable Cd and improving soil environmental quality in the natural alkaline Cd-contaminated soil. Overall, this study provides a systematic understanding of the synergistic mechanisms of biochar and bacteria for Cd immobilization in soil and new insights into the selection of functional strain for the efficient remediation of the contaminated environments by bacterial biochar composite.


Assuntos
Cádmio , Poluentes do Solo , Cádmio/análise , Poluentes do Solo/análise , Carvão Vegetal , Solo , Bactérias
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013092

RESUMO

@#Magnetic fields are safe and used in noninvasive physical therapies. Numerous studies have confirmed that magnetic fields have good osteogenic effects and certain value for clinical application in accelerating orthodontic tooth movement, promoting bone-implant integration, promoting fracture healing and improving the effects of distraction osteogenesis. Magnetic fields are expected to become applied as effective auxiliary methods for treating oral diseases. To support the clinical application of magnetic fields, this article reviews the applications of magnetic fields in the oral cavity, the biological effects on bone cells and the molecular mechanisms through which magnetic fields regulate bone metabolism. The biological effects of magnetic fields on bone cells include promoting osteogenesis by osteoblasts and mesenchymal stem cells and inhibiting bone resorption by osteoclasts. At the molecular level, bone cells sense and respond to magnetic stimulation, and through various mechanisms, such as displacement currents, Lorentz forces, and free radical pair effects, stimuli are transformed into biologically recognizable electrical signals that activate complex downstream signaling pathways, such as the P2 purinergic receptor signaling pathway, adenosine receptor signaling pathway, transforming growth factor-β receptor signaling pathway, mammalian target of rapamycin (mTOR) pathway, and Notch pathway. In addition, magnetic parameters, which are the factors affecting the osteogenic effects of magnetic fields, are discussed. However, the mechanisms of the osteogenic effects of magnetic fields are unclear, and further studies of these mechanisms could provide effective strategies for bone regeneration and periodontal tissue regeneration. In addition, considering the target of magnetic field therapies, combination with other drugs could lead to new strategies for the treatment of oral diseases.

18.
Sci Rep ; 13(1): 22804, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38129557

RESUMO

The goal of this study was to develop a ferroptosis-based molecular signature that can predict recurrence-free survival (RFS) in patients with prostate cancer (PCa). In this study, we obtained ferroptosis-related genes (FRGs) in FerrDb database and clinical transcriptome data in TCGA database and GEO database. Consensus cluster analysis was used to identify three molecular markers of ferroptosis in PCa with differential expression of 40 FRGs, including PD-L1 expression levels. We conducted a new ferroptosis-related signature for PCa RFS using four FRGs identified through univariate and multivariate Cox regression analyses. The signature was validated in the training, testing, and validation cohorts, and it demonstrated remarkable results in the area under the time-dependent receiver operating characteristic (ROC) curve of 0.757, 0.715, and 0.732, respectively. Additionally, we observed that younger patients, those with stage T III and stage T IV, stage N0, cluster 1, and cluster 2 PCa were more accurately predicted by the signature as independent predictors of RFS. DU-145 and RWPE-1 cells were successfully analyzed by qRT-PCR and Western blot for ASNS, GPT2, RRM2, and NFE2L2. In summary, we developed a novel ferroptosis-based signature for RFS in PC, utilizing four FRGs identified through univariate and multivariate Cox regression analyses. This signature was rigorously validated across training, testing, and validation cohorts, demonstrating exceptional performance as evidenced by its ROC curves. Notably, our findings indicate that this signature is particularly effective as an independent predictor of RFS in younger patients or those with stage T III and T IV, stage N0, and in clusters 1 and 2. Finally, we confirmed the expression of these four FRGs in DU-145 and RWPE-1 cell lines.


Assuntos
Ferroptose , Neoplasias da Próstata , Masculino , Humanos , Ferroptose/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Biomarcadores , Western Blotting , Linhagem Celular
19.
Chem Sci ; 14(42): 11689-11698, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37920344

RESUMO

The biological function of radicals is a broad continuum from signaling to killing. Yet, biomedical exploitation of radicals is largely restricted to the theme of healing-by-killing. To explore their potential in healing-by-signaling, robust radical generation methods are warranted. Acyl radicals are endogenous, exhibit facile chemistry and elicit matrix-dependent biological outcomes. Their implications in health and disease remain untapped, primarily due to the lack of a robust generation method with spatiotemporal specificity. Fusing the Norrish chemistry into the xanthene scaffold, we developed a novel general and modular molecular design strategy for photo-triggered generation of acyl radicals, i.e., acyl-caged rhodamine (ACR). A notable feature of ACR is the simultaneous release of a fluorescent probe for cell redox homeostasis allowing real-time monitoring of the biological outcome of acyl radicals. With a donor of the endogenous acetyl radical (ACR575a), we showcased its capability in precise and continuous modulation of the cell redox homeostasis from signaling to stress, and induction of a local oxidative burst to promote differentiation of neural stem cells (NSCs). Upon intracerebral-injection of ACR575a and subsequent fiber-optical activation, early AD mice exhibited enhanced differentiation of NSCs toward neurons, reduced formation of Aß plaques, and significantly improved cognitive abilities, including learning and memory.

20.
Phys Chem Chem Phys ; 25(43): 29698-29708, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37882726

RESUMO

Two triplet excitons are generated through an ultrafast photophysical process, namely singlet fission (SF), providing a solution for efficient solar energy usage. In this work, we provide an effective guideline for designing SF materials by adjusting the planarity in cyclopentadithiophene (CPDT) derivatives. A practical strategy is proposed for tuning the quinoidal-biradical resonance structures by varying the electron push-pull groups of CPDTs for SF. The localized, delocalized, and intermediate charge-transfer excited configurations are predicted in the singlet excited state via computational simulations, which is further confirmed by ultrafast spectroscopy. Deduced from the potential energy surfaces in the low-lying excited states and transient absorption, the delocalized excited state is formed in 2.1 ps via postulated intramolecular SF in a polar solvent, followed by the ultrafast formation of the free triplet state with a lifetime of 6.8 ps. In comparison with different cross-conjugated chromophores, it is found that the increase in the charge separation could enhance the triplet-pair generation for iSF. We expect that by introducing symmetry-breaking modifications in the electronic configurations and adjusting the separation between the push-pull groups of CPDTs, it should be possible to prolong the duration of the free triplet state by preventing recombination within the triplet-pair excited configuration.

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