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1.
Opt Lett ; 49(13): 3697-3700, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950245

RESUMEN

In this paper, the Fourier spectrum of an image in microsphere-assisted microscopy (MAM) and the wavenumber decomposition of the Poynting vector of the dipole model are compared for the first time to study the super-resolution performance within several wavelengths in MAM. Firstly, an experiment using microsphere-assisted microscopy is performed, and the fast Fourier transformation (FFT) spectra of the images along the distance are studied. Then the Poynting vector in the point dipole field is theoretically investigated based on the spectral decomposition of dyadic Green's function. Our study finds that the result of decomposition of the Poynting vector corresponds with the propagation results of components with different transverse wavenumbers kρ in an experiment. Even when kρ reaches 1.7k0, the waves can still arrive outside one wavelength. Our work is the first effort (to our knowledge) to associate the Fourier spectrum and the decomposition of the Poynting vector together, and it may contribute to the quantitative exploration of super-resolution performance in MAM in the future.

2.
Br J Cancer ; 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951697

RESUMEN

BACKGROUND: DNMT3A is a crucial epigenetic regulation enzyme. However, due to its heterogeneous nature and frequent mutation in various cancers, the role of DNMT3A remains controversial. Here, we determine the role of DNMT3A in non-small cell lung cancer (NSCLC) to identify potential treatment strategies. METHODS: To investigate the role of loss-of-function mutations of DNMT3A in NSCLC, CRISPR/Cas9 was used to induce DNMT3A-inactivating mutations. Epigenetic inhibitor library was screened to find the synthetic lethal partner of DNMT3A. Both pharmacological inhibitors and gene manipulation were used to evaluate the synthetic lethal efficacy of DNMT3A/KDM1A in vitro and in vivo. Lastly, MS-PCR, ChIP-qPCR, dual luciferase reporter gene assay and clinical sample analysis were applied to elucidate the regulation mechanism of synthetic lethal interaction. RESULTS: We identified DNMT3A is a tumour suppressor gene in NSCLC and KDM1A as a synthetic lethal partner of DNMT3A deletion. Both chemical KDM1A inhibitors and gene manipulation can selectively reduce the viability of DNMT3A-KO cells through inducing cell apoptosis in vitro and in vivo. We clarified that the synthetic lethality is not only limited to the death mode, but also involved into tumour metastasis. Mechanistically, DNMT3A deficiency induces KDM1A upregulation through reducing the methylation status of the KDM1A promoter and analysis of clinical samples indicated that DNMT3A expression was negatively correlated with KDM1A level. CONCLUSION: Our results provide new insight into the role of DNMT3A in NSCLC and elucidate the mechanism of synthetic lethal interaction between KDM1A and DNMT3A, which might represent a promising approach for treating patients with DNMT3A-deficient tumours.

3.
Nano Lett ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38949785

RESUMEN

The ion permeability and selectivity of membranes are crucial in nanofluidic behavior, impacting industries ranging from traditional to advanced manufacturing. Herein, we demonstrate the engineering of ion-conductive membranes featuring angstrom-scale ion-transport channels by introducing ionic polyamidoamine (PAMAM) dendrimers for ion separation. The exterior quaternary ammonium-rich structure contributes to significant electrostatic charge exclusion due to enhanced local charge density; the interior protoplasmic channels of PAMAM dendrimer are assembled to provide additional degrees of free volume. This facilitates the monovalent ion transfer while maintaining continuity and efficient ion screening. The dendrimer-assembled hybrid membrane achieves high monovalent ion permeance of 2.81 mol m-2 h-1 (K+), reaching excellent mono/multivalent selectivity up to 20.1 (K+/Mg2+) and surpassing the permselectivities of state-of-the-art membranes. Both experimental results and simulating calculations suggest that the impressive ion selectivity arises from the significant disparity in transport energy barrier between mono/multivalent ions, induced by the "exterior-interior" synergistic effects of bifunctional membrane channels.

4.
Cell Death Dis ; 15(7): 500, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39003253

RESUMEN

In recent years, immunotherapy, particularly PD-1 antibodies, have significantly enhanced the outcome of gastric cancer patients. Despite these advances, some patients do not respond well to treatment, highlighting the need to understand resistance mechanisms and develop predictive markers of treatment effectiveness. This study retrospectively analyzed data from 106 patients with stage IV gastric cancer who were treated with first-line immunotherapy in combination with chemotherapy. By comparing plasma cytokine levels between patients resistant and sensitive to PD-1 antibody therapy, the researchers identified elevated IL-4 expression in the resistant patients. Mechanical investigations revealed that IL-4 induces metabolic changes in macrophages that activate the PI3K/AKT/mTOR pathway. This alteration promotes ATP production, enhances glycolysis, increases lactic acid production, and upregulates FcγRIIB expression in macrophages. Ultimately, these changes lead to CD8+ T cell dysfunction and resistance to PD-1 antibody therapy in gastric cancer. These findings highlight the role of IL-4-induced macrophage polarization and metabolic reprogramming in immune resistance and verify IL-4 as potential targets for improving treatment outcomes in gastric cancer patients.


Asunto(s)
Inmunoterapia , Interleucina-4 , Macrófagos , Receptores de IgG , Transducción de Señal , Neoplasias Gástricas , Regulación hacia Arriba , Humanos , Interleucina-4/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Receptores de IgG/metabolismo , Inmunoterapia/métodos , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/terapia , Masculino , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Receptores de Interleucina-4/metabolismo , Persona de Mediana Edad , Animales , Anciano
5.
Imeta ; 3(3): e188, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38898980

RESUMEN

Wastewater biotreatment systems harbor a rich diversity of microorganisms, and the effectiveness of biotreatment systems largely depends on the activity of these microorganisms. Specifically, viruses play a crucial role in altering microbial behavior and metabolic processes throughout their infection phases, an aspect that has recently attracted considerable interest. Two metagenomic approaches, viral-like particle-concentrated (VPC, representing free viral-like particles) and non-concentrated (NC, representing the cellular fraction), were employed to assess their efficacy in revealing virome characteristics, including taxonomy, diversity, host interactions, lifestyle, dynamics, and functional genes across processing units of three wastewater treatment plants (WWTPs). Our findings indicate that each approach offers unique insights into the viral community and functional composition. Their combined use proved effective in elucidating WWTP viromes. We identified nearly 50,000 viral contigs, with Cressdnaviricota and Uroviricota being the predominant phyla in the VPC and NC fractions, respectively. Notably, two pathogenic viral families, Asfarviridae and Adenoviridae, were commonly found in these WWTPs. We also observed significant differences in the viromes of WWTPs processing different types of wastewater. Additionally, various phage-derived auxiliary metabolic genes (AMGs) were active at the RNA level, contributing to the metabolism of the microbial community, particularly in carbon, sulfur, and phosphorus cycling. Moreover, we identified 29 virus-carried antibiotic resistance genes (ARGs) with potential for host transfer, highlighting the role of viruses in spreading ARGs in the environment. Overall, this study provides a detailed and integrated view of the virosphere in three WWTPs through the application of VPC and NC metagenomic approaches. Our findings enhance the understanding of viral communities, offering valuable insights for optimizing the operation and regulation of wastewater treatment systems.

6.
Front Pharmacol ; 15: 1396354, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38873428

RESUMEN

Natural polyphenols may have a role in counteracting oxidative stress, which is associated with aging and several bone-related diseases. Chlorogenic acid (CGA) is a naturally occurring polyphenolic compound formed by the esterification of caffeic and quininic acids with osteogenic, antioxidant, and anti-inflammatory properties. This review discusses the potential of CGA to enhance osteogenesis by increasing the osteogenic capacity of mesenchymal stem cells (MSCs), osteoblast survival, proliferation, differentiation, and mineralization, as well as its ability to attenuate osteoclastogenesis by enhancing osteoclast apoptosis and impeding osteoclast regeneration. CGA can be involved in bone remodeling by acting directly on pro-osteoclasts/osteoblasts or indirectly on osteoclasts by activating the nuclear factor kB (RANK)/RANK ligand (RANKL)/acting osteoprotegerin (OPG) system. Finally, we provide perspectives for using CGA to treat bone diseases.

7.
Materials (Basel) ; 17(11)2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38893849

RESUMEN

Two-dimensional (2D) violet phosphorus (VP) plays a significant role in the applications of photonic and optoelectronic devices due to its unique optical and electrical properties. The ultrafast carrier dynamics and nonlinear optical absorption properties were systematically investigated here. The intra- and inter-band ultrafast relaxation times of 2D VP nanosheets were measured to be ~6.83 ps and ~62.91 ps using the pump-probe method with a probe laser operating at 1.03 µm. The nonlinear absorption coefficient ßeff, the saturation intensity Is, the modulation depth ΔR, and the nonsaturable loss were determined to be -2.18 × 104 cm/MW, 329 kW/cm2, 6.3%, and 9.8%, respectively, by using the Z-scan and I-scan methods, indicating the tremendous saturable absorption property of 2D VP nanosheets. Furthermore, the passively Q-switched Nd:YVO4 laser was realized with the 2D VP nanosheet-based SA, in which the average output power of 700 mW and the pulse duration of 478 ns were obtained. These results effectively reveal the nonlinear optical absorption characteristics of VP nanosheets, demonstrating their outstanding light-manipulating capabilities and providing a basis for the applications of ultrafast optical devices. Our results verify the excellent saturable absorption properties of 2D VP, paving the way for its applications in pulsed laser generation.

8.
Foods ; 13(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38928742

RESUMEN

The low rehydration properties of commercial soy protein powder (SPI), a major plant-based food ingredient, have limited the development of plant-based foods. The present study proposes a treatment of soy lecithin modification combined with Alcalase hydrolysis to improve the rehydration of soy protein powder, as well as other processing properties (emulsification, viscosity). The results show that the soy protein-soy lecithin complex powder, which is hydrolyzed for 30 min (SPH-SL-30), has the smallest particle size, the smallest zeta potential, the highest surface hydrophobicity, and a uniform microstructure. In addition, the value of the ratio of the α-helical structure/ß-folded structure was the smallest in the SPH-SL-30. After measuring the rehydration properties, emulsification properties, and viscosity, it was found that the SPH-SL-30 has the shortest wetting time of 3.04 min, the shortest dispersion time of 12.29 s, the highest solubility of 93.17%, the highest emulsifying activity of 32.42 m2/g, the highest emulsifying stability of 98.33 min, and the lowest viscosity of 0.98 pa.s. This indicates that the treatment of soy lecithin modification combined with Alcalase hydrolysis destroys the structure of soy protein, changes its physicochemical properties, and improves its functional properties. In this study, soy protein was modified by the treatment of soy lecithin modification combined with Alcalase hydrolysis to improve the processing characteristics of soy protein powders and to provide a theoretical basis for its high-value utilization in the plant-based food field.

9.
Am J Cancer Res ; 14(5): 2507-2522, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38859852

RESUMEN

Colorectal cancer (CRC) is among the most prevalent malignant tumors, known for its high heterogeneity. Although many treatments and medications are available, the long-term survival rate of CRC patients is far from satisfactory. Pyroptosis is closely related to tumor progression. This study aimed to identify pyroptosis-related genes (PRGs) and candidate biomarkers to predict the prognosis of CRC patients. Used bioinformatics, we identified PRGs and subsequently screened 288 co-expression genes between pyroptosis-related modules and differentially expressed genes in CRC. Among these hub genes, we selected the top 24 for further analysis and found that Radical S-Adenosyl Methionine Domain Containing 2 (RSAD2) was a novel biomarker associated with the progression of CRC. We developed a risk model for RSAD2, which proved to be an independent prognostic indicator. The receiver operator characteristic analysis showed that the model had an acceptable prognostic value for patients with CRC. In addition, RSAD2 also affects the tumor immune microenvironment and prognosis of CRC. We further validated RSAD2 expression in CRC patients using RT-qPCR and the role of RSAD2 in pyroptosis. Taken together, this study comprehensively assessed the expression and prognostic value of RSAD2 in patients with CRC. These findings may offer a new direction for early CRC screening and development of future immunotherapy strategies.

10.
ACS Omega ; 9(22): 23266-23282, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38854573

RESUMEN

The sandstones interbedded with shales in the lacustrine black shale have great potential to become important targets for oil and gas exploration, but there has been a lack of systematic research regarding their types and genesis. This study focused on the investigation of the Triassic Chang 73 member deep lacustrine sandstone. Eleven lithofacies are identified and classified into three different types of deposits: ash fall and intra- and extra-basinal turbidite deposits. Vitric tuff, pumice-bearing shale, and ash are the main ash fall lithofacies. The presence of reverse grading and a significant concentration of plant fragments/micas suggest extra-basinal turbidite deposits. However, the collapse of deltaic intrabasinal sediments has been well sorted and does not contain plant debris and low-density materials. These three different types of sediments combined with a humid climate are the main causes for the deposition of a large number of sandstone layers in the deep lacustrine environment. Furthermore, the abundant volcanic eruptions are associated with increased organic matter accumulation and promoted the bloom of algae. In addition, the generated oil in the black shales would then migrate and accumulate in the interbedded sandstones. This research provides geological evidence for the prospective prediction of lacustrine shale oil accumulations.

11.
J Adv Res ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38825314

RESUMEN

BACKGROUND: Tumor metastasis represents a stepwise progression and stands as a principal determinant of unfavorable prognoses among cancer patients. Consequently, an in-depth exploration of its mechanisms holds paramount clinical significance. Cancer-associated fibroblasts (CAFs), constituting the most abundant stromal cell population within the tumor microenvironment (TME), have garnered robust evidence support for their pivotal regulatory roles in tumor metastasis. AIM OF REVIEW: This review systematically explores the roles of CAFs at eight critical stages of tumorigenic dissemination: 1) extracellular matrix (ECM) remodeling, 2) epithelial-mesenchymal transition (EMT), 3) angiogenesis, 4) tumor metabolism, 5) perivascular migration, 6) immune escape, 7) dormancy, and 8) premetastatic niche (PMN) formation. Additionally, we provide a compendium of extant strategies aimed at targeting CAFs in cancer therapy. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review delineates a structured framework for the interplay between CAFs and tumor metastasis while furnishing insights for the potential therapeutic developments. It contributes to a deeper understanding of cancer metastasis within the TME, facilitating the utilization of CAF-targeting therapies in anti-metastatic approaches.

12.
BMC Endocr Disord ; 24(1): 77, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38831300

RESUMEN

OBJECTIVE: This study aimed to analyze the factors influencing glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: Baseline data, encompassing basic information, lifestyle habits, and treatment of 305 T2DM patients from March 2021 to January 2023, were collected and analyzed using SPSS 26.0 software. RESULTS: Univariate and multivariate logistic regression analyses identified insulin therapy (OR = 2.233; 95%Cl = 1.013-4.520; P = 0.026) and regular clinic visits (OR = 0.567; 95%Cl = 0.330-0.973; P = 0.040) as independent factors influencing glycemic control. No observed interactions between the two variables were noted. CONCLUSION: History of insulin therapy and regular clinic visits were significantly and independently associated with glycated hemoglobin control in T2DM patients. Tailored interventions based on individual circumstances are recommended to optimize glycemic control.


Asunto(s)
Glucemia , Diabetes Mellitus Tipo 2 , Hemoglobina Glucada , Control Glucémico , Hipoglucemiantes , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Estudios Transversales , Femenino , Masculino , China/epidemiología , Persona de Mediana Edad , Glucemia/análisis , Glucemia/metabolismo , Hemoglobina Glucada/análisis , Hipoglucemiantes/uso terapéutico , Anciano , Insulina/uso terapéutico , Insulina/administración & dosificación , Adulto , Pronóstico
13.
Acta Pharm Sin B ; 14(6): 2554-2566, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38828147

RESUMEN

Oncolytic viruses (OVs), a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact, are emerging as promising living anticancer agents. Unlike traditional drugs composed of non-replicating compounds or biomolecules, the replicative nature of viruses confer unique pharmacokinetic properties that require further studies. Despite some pharmacokinetics studies of OVs, mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague. Here, we characterized the pharmacokinetic profile of oncolytic virus M1 (OVM) in immunocompetent mouse tumor models and identified the JAK‒STAT pathway as a key modulator of OVM pharmacokinetics. By suppressing the JAK‒STAT pathway, early OVM pharmacokinetics are ameliorated, leading to enhanced tumor-specific viral accumulation, increased AUC and Cmax, and improved antitumor efficacy. Rather than compromising antitumor immunity after JAK‒STAT inhibition, the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment, providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade, such as anti-PD-L1. Taken together, this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

14.
Talanta ; 277: 126341, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38823329

RESUMEN

A highly sensitive ultra-small ratiometric fluorescence nanosphere probe was successfully manufactured to detect Sunset Yellow (SY). The probe, CMCS@N, S-CDs/Rh6G, was formed through the encapsulation of N, S-CDs and Rh6G within carboxymethyl chitosan (CMCS) through in situ cross-linking. Remarkably, our nanosphere probe had an average grain diameter of 6.80 nm and exhibited excellent dispersibility without the need for additional solvents. The probe exhibited a strong linear relationship with SY concentration in the range of 0.26-100 µM, with a low detection limit of 0.078 µM. Furthermore, SY demonstrated strong fluorescence quenching capability on our nanosphere probe, with the fluorescence quenching mechanism involving a combined effects of inner filter effect (IFE) and static quenching. Notably, our nanosphere probe retained the bacteriostatic properties of CMCS, with a substantial bacteriostasis rate of 77.58 %, introducing novel potential applications.

15.
Comput Biol Med ; 177: 108631, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38824787

RESUMEN

The incident light reflected from the cornea is rich in information about the human surroundings, and these reflected rays are imaged by the camera, which can be used for research on human consciousness and gaze analysis, and produce certain help in the fields of psychology, human computer interaction and disease diagnosis. However, limited by the low corneal reflection ability, when a high-definition camera captures corneal reflecting rays, a large amount of color and texture interference from the iris can seriously contaminate the corneal reflection images, resulting in low usability and ubiquity of corneal reflection images. In this paper, we propose a corneal reflection image extraction method with multiple eye images as input. We align the iris regions of multiple eye images with the help of iris localization method, and by comparing multiple iris regions, we obtain the complementary iris regions, so that the iris interference in the corneal reflection region can be stripped completely. A large number of experiments have demonstrated that our work can effectively mitigate iris interference and effectively improve the quality of corneal reflection images.


Asunto(s)
Córnea , Procesamiento de Imagen Asistido por Computador , Humanos , Córnea/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Iris/diagnóstico por imagen , Algoritmos
16.
Int J Biol Macromol ; 274(Pt 1): 133315, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38914390

RESUMEN

In this study, changes in the structural and functional properties of soybean protein isolate (SPI)-naringenin (NG) complexes under different amounts of naringenin treatments were explored, elucidating the effect of the complexes as fat replacers at the 15 % substitution level on the properties of low-fat cream. Finally, the correlation between the structure and function of the complex and the properties of low-fat cream was further analyzed. The addition of NG promotes the increase of SPI aggregation and particle size, and reduces the interfacial tension of the complex. Meanwhile, at the mass ratio of 48:3, NG and SPI formed a dendritic network structure suitable for stabilizing cream. The fat properties of cream indicate that low-fat creams stabilized by appropriate proportions of SPI-NG complexes displayed small and dense fat crystal network structures. In addition, low-fat cream stabilized by the SPI-NG complexes have improved whipping time, overrun, firmness, storage stability and rheological properties compared to natural SPI. It is worth noting that the overall quality of the cream stabilized by the SPI-NG complex with a mass ratio of 48:3 was almost close to that of full-fat cream. Therefore, this study promotes the potential applications of protein-polyphenol complexes as fat replacers in the food industry.

17.
Front Microbiol ; 15: 1362880, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38699476

RESUMEN

Cyanobacteria, which have a photoautotrophic lifestyle, are threatened by ultraviolet solar rays and the reactive oxygen species generated during photosynthesis. They can adapt to environmental conditions primarily because of their DNA damage response and repair mechanisms, notably an efficient homologous recombination repair system. However, research on double-strand break (DSB) repair pathways, including the Holliday junction (HJ) resolution process, in Synechocystis sp. PCC6803 is limited. Here, we report that SynRuvC from cyanobacteria Synechocystis sp. PCC6803 has classical HJ resolution activity. We investigated the structural specificity, sequence preference, and biochemical properties of SynRuvC. SynRuvC strongly preferred Mn2+ as a cofactor, and its cleavage site predominantly resides within the 5'-TG↓(G/A)-3' sequence. Interestingly, novel flap endonuclease and replication fork intermediate cleavage activities of SynRuvC were also determined, which distinguish it from other reported RuvCs. To explore the effect of SynRuvC on cell viability, we constructed a knockdown mutant and an overexpression strain of Synechocystis sp. PCC6803 (synruvCKD and synruvCOE) and assessed their survival under a variety of conditions. Knockdown of synruvC increased the sensitivity of cells to MMS, HU, and H2O2. The findings suggest that a novel RuvC family HJ resolvase SynRuvC is important in a variety of DNA repair processes and stress resistance in Synechocystis sp. PCC6803.

18.
Am J Transl Res ; 16(4): 1383-1392, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715838

RESUMEN

OBJECTIVE: This study aimed to establish an early warning model for stroke recurrence in acute ischemic stroke patients based on Traditional Chinese Medicine (TCM) syndrome theory. METHODS: This retrospective study collected the data of 1741 patients with ischemic stroke from 7 clinical centers between July 2016 and November 2019. Distance correlation coefficient, mutual information entropy, and statistical correlation test were used for univariate analysis. Cox proportional hazards regression model was applied to construct and validate the stroke recurrence warning model at different time. The area under the ROC curve (AUC) was used to evaluate the early warning ability of the model. RESULTS: We successfully constructed the early warning model. The median follow-up time was 1.42 years (95% CI [1.37, 1.47]). Recurrence events occurred in 175 patients, with a cumulative recurrence rate of 10.05% (95% CI [8.64, 11.47]). The AUC of the model was 0.64±0.02 in the training set and 0.70±0.03 in the validation set. CONCLUSION: The TCM syndrome model can give an early warning for the recurrence of stroke and provide reference for the secondary prevention of ischemic stroke.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38733463

RESUMEN

Neuroinflammation is considered an important factor that leads to cognitive impairment. Microglia play a crucial role in neuroinflammation, which leads to cognitive impairment. This study aimed at determining whether temporin-GHaR peptide (GHaR) could improve cognitive function and at uncovering the underlying mechanisms. We found that GHaR treatment alleviated LPS-induced cognitive impairment and inhibited activation of microglia in LPS-induced mice. Furthermore, GHaR inhibited activation of endoplasmic reticulum stress (ERS) and the NF-κB signaling pathway in LPS-induced mice. In vitro, GHaR inhibited M1 polarization of BV2 cells and suppressed TNF-α and IL-6 secretion. Additionally, GHaR neuronal cell viability and apoptosis were induced by LPS-activated microglia-conditioned medium. Moreover, in LPS-induced BV2 cells, GHaR inhibited activation of ERS and the NF-κB signaling pathway. In summary, GHaR improved LPS-induced cognitive and attenuated inflammatory responses via microglial activation reversal. In conclusion, the neuroprotective effects of GHaR were mediated via the ERS signaling pathway.

20.
Transl Oncol ; 46: 101994, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38776708

RESUMEN

Cervical cancer ranks fourth in women in terms of incidence and mortality. The RNA-binding protein YTH N6-methyladenosine RNA-binding protein F2 (YTHDF2) contributes to cancer progression by incompletely understood mechanisms. We show how YTHDF2 controls the fate of cervical cancer cells and whether YTHDF2 could be a valid target for the therapy of cervical cancer. Sphere formation and alkaline phosphatase staining assays were performed to evaluate tumor stemness of cervical cancer cells following YTHDF2 knockdown. Apoptosis was detected by flow cytometry and TUNEL assay. The compounds 4PBA and SP600125 were used to investigate the correlation between JNK, endoplasmic reticulum stress, tumor stemness, and apoptosis. Data from The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) revealed that GLI family zinc finger 2 (GLI2) might be the target of YTHDF2. The transcription inhibitor actinomycin D and dual-luciferase reporter gene assays were employed to investigate the association between the GLI2 mRNA and YTHDF2. Nude mouse xenografts were generated to assess the effects of YTHDF2 knockdown on cervical cancer growth in vivo. Knockdown of YTHDF2 up-regulated the expression of GLI2, leading to JNK phosphorylation and endoplasmic reticulum stress. These processes inhibited the proliferation of cervical cancer cells and their tumor cell stemness and promotion of apoptosis. In conclusion, the knockdown of YTHDF2 significantly affects the progression of cervical cancer cells, making it a potential target for treating cervical cancer.

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