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1.
Immunol Cell Biol ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714318

RESUMO

The development of in vitro models is essential for a comprehensive understanding and investigation of pulmonary fibrosis (PF) at both cellular and molecular levels. This study presents a literature review and an analysis of various cellular models used in scientific studies, specifically focusing on their applications in elucidating the pathogenesis of PF. Our study highlights the importance of taking a comprehensive approach to studing PF, emphasizing the necessity of considering multiple cell types and organs and integrating diverse analytical perspectives. Notably, primary cells demonstrate remarkable cell growth characteristics and gene expression profiles; however, their limited availability, maintenance challenges, inability for continuous propagation and susceptibility to phenotypic changes over time significantly limit their utility in scientific investigation. By contrast, immortalized cell lines are easily accessible, cultured and continuously propagated, although they may have some phenotypic differences from primary cells. Furthermore, in vitro coculture models offer a more practical and precise method to explore complex interactions among cells, tissues and organs. Consequently, when developing models of PF, researchers should thoroughly assess the advantages, limitations and relevant mechanisms of different cell models to ensure their selection is consistent with the research objectives.

2.
J Nanobiotechnology ; 22(1): 227, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711078

RESUMO

BACKGROUND: Elevated interstitial fluid pressure within tumors, resulting from impaired lymphatic drainage, constitutes a critical barrier to effective drug penetration and therapeutic outcomes. RESULTS: In this study, based on the photosynthetic characteristics of algae, an active drug carrier (CP@ICG) derived from Chlorella pyrenoidosa (CP) was designed and constructed. Leveraging the hypoxia tropism and phototropism exhibited by CP, we achieved targeted transport of the carrier to tumor sites. Additionally, dual near-infrared (NIR) irradiation at the tumor site facilitated photosynthesis in CP, enabling the breakdown of excessive intratumoral interstitial fluid by generating oxygen from water decomposition. This process effectively reduced the interstitial pressure, thereby promoting enhanced perfusion of blood into the tumor, significantly improving deep-seated penetration of chemotherapeutic agents, and alleviating tumor hypoxia. CONCLUSIONS: CP@ICG demonstrated a combined effect of photothermal/photodynamic/starvation therapy, exhibiting excellent in vitro/in vivo anti-tumor efficacy and favorable biocompatibility. This work provides a scientific foundation for the application of microbial-enhanced intratumoral drug delivery and tumor therapy.


Assuntos
Chlorella , Portadores de Fármacos , Fotossíntese , Animais , Camundongos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Humanos , Terapia Combinada , Fotoquimioterapia/métodos , Neoplasias/terapia , Antineoplásicos/farmacologia , Camundongos Endogâmicos BALB C , Sistemas de Liberação de Medicamentos/métodos , Verde de Indocianina/farmacocinética , Verde de Indocianina/química , Feminino
3.
Front Immunol ; 15: 1389173, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745666

RESUMO

Tumor immunotherapy is a promising approach for addressing the limitations of conventional tumor treatments, such as chemotherapy and radiotherapy, which often have side effects and fail to prevent recurrence and metastasis. However, the effectiveness and sustainability of immune activation in tumor immunotherapy remain challenging. Tumor immunogenic cell death, characterized by the release of immunogenic substances, damage associated molecular patterns (DAMPs), and tumor associated antigens, from dying tumor cells (DTCs), offers a potential solution. By enhancing the immunogenicity of DTCs through the inclusion of more immunogenic antigens and stimulating factors, immunogenic cell death (ICD) based cancer vaccines can be developed as a powerful tool for immunotherapy. Integrating ICD nanoinducers into conventional treatments like chemotherapy, photodynamic therapy, photothermal therapy, sonodynamic therapy, and radiotherapy presents a novel strategy to enhance treatment efficacy and potentially improve patient outcomes. Preclinical research has identified numerous potential ICD inducers. However, effectively translating these findings into clinically relevant applications remains a critical challenge. This review aims to contribute to this endeavor by providing valuable insights into the in vitro preparation of ICD-based cancer vaccines. We explored established tools for ICD induction, followed by an exploration of personalized ICD induction strategies and vaccine designs. By sharing this knowledge, we hope to stimulate further development and advancement in the field of ICD-based cancer vaccines.


Assuntos
Vacinas Anticâncer , Morte Celular Imunogênica , Neoplasias , Humanos , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Morte Celular Imunogênica/efeitos dos fármacos , Neoplasias/imunologia , Neoplasias/terapia , Animais , Imunoterapia/métodos , Antígenos de Neoplasias/imunologia
5.
Front Nutr ; 11: 1342113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721026

RESUMO

Background: Sarcopenia, a condition characterized by diminished skeletal muscle mass, strength, and function, accompanied by inflammation and oxidative stress, remains an area of limited exploration concerning its correlation with the Oxidative Balance Score (OBS). Methods: Leveraging data from the 2011-2018 National Health and Nutrition Examination Survey (NHANES), we meticulously examined 16 dietary and four lifestyle factors to derive the OBS. Adjusting appendicular skeletal muscle mass (ASM) by body mass index (BMI) served as the designated marker for sarcopenia. To scrutinize the association between OBS and sarcopenia, we conducted weighted logistic regression and engaged in sensitivity analysis. Furthermore, we implemented subgroup analysis and interaction tests to gain comprehensive insights into the relationship across diverse populations. Results: In a sample comprising 6,677 individuals aged 20-59, logistic regression illuminated a negative association between OBS and sarcopenia [OR = 0.942 (0.920, 0.964), p < 0.001]. Robust associations were also discerned between diseases and both dietary and lifestyle OBS. Subgroup analysis unveiled a more pronounced negative association in older, married/living with partner or more educated individuals. Moreover, this association persisted in populations grappling with comorbidities such as hypertension, diabetes, cancer, and arthritis. Conclusion: Our study posits a perceptible link between OBS and the prevalence of sarcopenia among American adults.

6.
Heliyon ; 10(9): e29883, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38699036

RESUMO

Background: Labor epidural analgesia (LEA) may influence gut microbiota. We explored the association between LEA and gut microbiota for both mothers and their newborns. Methods: In this prospective cohort study, parturients aged 25-35 years with a gestational age of 37-42 weeks and planned vaginal delivery were recruited. Twenty-one parturients received LEA (the LEA group), and 24 did not (the control group). Maternal and neonatal fecal samples were collected, and the gut microbiota profiles were analyzed using the 16S rRNA gene sequencing. The impact of LEA on gut microbiota was assessed using the general liner models. Results: We showcased the gut microbiota profile from the phyla to species levels based on data on 45 mother-newborn dyads. The results of α- and ß-diversity suggested significant changes in gut microbiota between the LEA and control groups. After adjusting for baseline confounders, the administration of LEA had positive correlations with R. ilealis (ß = 91.87, adjusted P = 0.007) in mothers; LEA also had negative correlations with A. pittii (ß = -449.36, adjusted P = 0.015), P. aeruginosa (ß = -192.55, adjusted P = 0.008), or S. maltophilia (ß = -142.62, adjusted P = 0.001) in mothers, and with Muribaculaceae (ß = -2702.77, adjusted P = 0.003) in neonates. Conclusion: LEA was associated with changes in maternal and neonatal gut microbiota, and future studies are still required to assess their impact on clinical outcomes and explore the mechanisms.

7.
iScience ; 27(5): 109766, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38711448

RESUMO

Swift and accurate diagnosis for earlier-stage monkeypox (mpox) patients is crucial to avoiding its spread. However, the similarities between common skin disorders and mpox and the need for professional diagnosis unavoidably impaired the diagnosis of earlier-stage mpox patients and contributed to mpox outbreak. To address the challenge, we proposed "Super Monitoring", a real-time visualization technique employing artificial intelligence (AI) and Internet technology to diagnose earlier-stage mpox cheaply, conveniently, and quickly. Concretely, AI-mediated "Super Monitoring" (mpox-AISM) integrates deep learning models, data augmentation, self-supervised learning, and cloud services. According to publicly accessible datasets, mpox-AISM's Precision, Recall, Specificity, and F1-score in diagnosing mpox reach 99.3%, 94.1%, 99.9%, and 96.6%, respectively, and it achieves 94.51% accuracy in diagnosing mpox, six like-mpox skin disorders, and normal skin. With the Internet and communication terminal, mpox-AISM has the potential to perform real-time and accurate diagnosis for earlier-stage mpox in real-world scenarios, thereby preventing mpox outbreak.

8.
Health Commun ; : 1-10, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693691

RESUMO

Pornography is spreading more and more widely due to websites, applications, and social media. It has attracted the attention of a large number of researchers who are sometimes divided on the impact of pornography. However, the relationship between pornography and sexual violence myths has received little scholarly attention in China. Based on the 3AM model and previous research, the study examined hostile sexism (HS) as a mediator and perceived realism as a moderator in the links between pornography use frequency and sexual violence myths in a sample of Chinese men (N = 376). The results showed that although pornography use and sexual violence myths did not directly correlate with one another, there was an indirect correlation through HS. Further, perceived realism moderated the relationship between pornography use frequency and HS. When participants' perceived realism was high (i.e. +1 SD), the indirect effect of HS was strong; when participants' perceived realism was low (i.e. -1 SD), the indirect effect of HS was not significant. Taken together, the findings reveal the cross-cultural consistency of the 3AM theory in China, and the findings provide new insight into the potential impact of pornography on sexism. At the same time, the results suggest an increase in appropriate education and interventions to reduce the incidence of sexual violence.

9.
Langmuir ; 40(18): 9669-9675, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38648519

RESUMO

With the fast development of the smart lifestyle in recent years, simple and flexible body condition monitoring has become more and more important. However, currently, commercially available motion-sensing devices always lack flexibility or at a high cost. This article has fully explored the merits of a commercial and easily available material of carbon fiber powder (CFP) and prepared CFP-based screen printing inks. This conductive ink can be directly and quickly printed onto a variety of different flexible common substrates, such as paper, cotton fabrics, etc., to prepare flexible sensors. At the same time, as a result of the good photothermal performance and conductivity of CFP, the printed flexible sensors have fast and stable performance on thermal and human motion detection. The use of CFP as the smart element to construct a wearable device will offer a choice for the intelligent industry.

10.
Medicine (Baltimore) ; 103(16): e37895, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640287

RESUMO

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma, also known as extranodal marginal zone lymphoma, is more commonly detected in the stomach and rarely in the breast. Our study presented a clinical and pathological examination of a patient diagnosed with breast MALT lymphoma, supplemented with pertinent research, to offer guidance for the diagnosis and treatment of this condition. PEOPLE CONCERNS: The occurrence of breast MALT lymphoma has risen in the past decade, but its etiology, progression and treatment response are less well-studied. DIAGNOSIS: Breast MALT lymphoma was diagnosed by excisional biopsy and histopathology. INTERVENTIONS: Following breast MALT lymphoma diagnosis, the patient was transferred to the hematology department for further treatment, and she made the decision to continue observing. OUTCOMES: After 3 months of observation, the patient remained asymptomatic. CONCLUSION: Breast MALT lymphoma is an indolent disease with an asymptomatic presentation, There are no standardized treatment guidelines for breast MALT lymphoma, treatment must be tailored to the patient willingness to treat and the severity of the disease. Hence, in order to give patients a better chance of cure, more research is needed to explore its pathogenesis and more clinical trials are needed investigate the treatment of this disease.


Assuntos
Neoplasias da Mama , Linfoma de Zona Marginal Tipo Células B , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/terapia , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Biópsia
11.
Transl Cancer Res ; 13(3): 1290-1313, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38617504

RESUMO

Background: Chromatin regulators (CRs) are implicated in the development of cancer, but a comprehensive investigation of their role in colon adenocarcinoma (COAD) is inadequate. The purpose of this study is to find CRs that can provide recommendations for clinical diagnosis and treatment, and to explore the reasons why they serve as critical CRs. Methods: We obtained data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Weighted Gene Co-Expression Network Analysis (WGCNA) screened tumor-associated CRs. LASSO-Cox regression was used to construct the model and to screen key CRs together with support vector machine (SVM), the univariate Cox regression. We used single-cell data to explore the expression of CRs in cells and their communication. Immune infiltration, immune checkpoints, mutation, methylation, and drug sensitivity analyses were performed. Gene expression was verified by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Pan-cancer analysis was used to explore the importance of hub CRs. Results: We finally obtained 32 tumor-associated CRs. The prognostic model was constructed based on RCOR2, PPARGC1A, PKM, RAC3, PHF19, MYBBP1A, ORC1, and EYA2 by the LASSO-Cox regression. Single-cell data revealed that the model was immune-related. Combined with immune infiltration analysis, immune checkpoint analysis, and tumor immune dysfunction and exclusion (TIDE) analysis, the low-score risk group had more immune cell infiltration and better immune response. Mutation and methylation analysis showed that multiple CRs may be mutated and methylated in colon cancer. Drug sensitivity analysis revealed that the low-risk group may be more sensitive to several drugs and PKM was associated with multiple drugs. Combined with machine learning, PKM is perhaps the most critical gene in CRs. Pan-cancer analysis showed that PKM plays a role in the prognosis of cancers. Conclusions: We developed a prognostic model for COAD based on CRs. Increased expression of the core gene PKM is linked with a poor prognosis in several malignancies.

12.
Front Psychol ; 15: 1340456, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646122

RESUMO

Background: In Chinese medicine, the mental focus and emotional stability of acupuncturists are key to optimal clinical outcomes. Many renowned acupuncturists utilize Traditional Chinese Qigong practices to enhance their concentration and emotional regulation abilities. Nevertheless, the existing literature lacks comprehensive evidence addressing this matter. Methods: This study will enroll 99 acupuncturists and randomly allocate them to one of three groups: Baduanjin, aerobic exercise, or a waiting-list control. The Baduanjin group will undertake 24 weeks of training, with three one-hour sessions weekly. The aerobic group will engage in brisk walking for the same duration and frequency. The control group will not receive any specific training. Assessments of emotion regulation, attention, cognitive functions, finger sensation, and athletic ability will be conducted at baseline (-1 week), mid-intervention (12 weeks), and post-intervention (24 weeks). Additionally, 20 participants from each group will undergo fMRI scans before and after the intervention to explore brain functional and structural changes relating to emotion, attention, cognition, motor skills, and sensory perception. Discussion: This study aims to contribute valuable insights into the effectiveness of Qigong practice, specifically Baduanjin, in enhancing emotional regulation, attention, and cognitive functions in acupuncturists and to investigate the neuroimaging mechanisms behind these effects. Ethics and dissemination: Approved by the Sichuan Regional Ethics Review Committee on Traditional Chinese Medicine (No. 2023KL - 118) and adhering to the Declaration of Helsinki. Results will be shared through policy briefs, workshops, peer-reviewed journals, and conferences.Clinical trial registrationwww.chictr.org.cn, ChiCTR2300076447.

13.
Small ; : e2401651, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38660702

RESUMO

A pH and redox dual responsive amphiphilic viologen is synthesized, which can be reversibly transformed among the zwitterionic (SVa), monovalent anionic (SV+), and divalent anionic (SVH2+) forms upon pH variation, exhibiting pH-controllable redox responsive properties. Switchable Pickering emulsions with different droplet size and viscosity are prepared by the mixture of hydrophilic silica nanoparticles and the viologens (SV+ or SVH2+) at acidic conditions, while such combination yielded an oil-in-dispersion emulsion at neutral pH value. Not only can rapid reversible demulsification/stabilization of the Pickering emulsions be achieved by redox reactions, but the rate of redox-demulsification can also be controlled by pH trigger. The dual-responsive amphiphilic viologens have potential applications in developing intelligent colloid materials and molecular logic systems.

14.
Angew Chem Int Ed Engl ; : e202405444, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637320

RESUMO

Unlocking the full potential of mRNA immunotherapy necessitates targeted delivery to specific cell subsets in the spleen. Four-component lipid nanoparticles (LNPs) utilized in numerous clinical trials are primarily limited in hepatocyte and muscular targeting, highlighting the imperative demand for targeted and simplified non-liver mRNA delivery systems. Herein, we report the rational design of one-component ionizable cationic lipids to selectively deliver mRNA to the spleen and T cells with high efficacy. Unlike the tertiary amine-based ionizable lipids involved in LNPs, the proposed cationic lipids rich in secondary amines can efficiently deliver mRNA both in vitro and in vivo as the standalone carriers. Furthermore, these vectors facilitate efficacious mRNA delivery to the T cell subsets following intravenous administration, demonstrating substantial potential for advancing immunotherapy applications. This straightforward strategy extends the utility of lipid family for extrahepatic mRNA delivery, offering new insights into vector development beyond LNPs to further the field of precise mRNA therapy.

15.
Food Chem ; 450: 139287, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38640541

RESUMO

The effects of ultrasonic pretreatment on the drying characteristics and microstructure of strawberry slices were investigated. The rehydration characteristics of freeze-dried products, which were pre-frozen at -20 °C and - 80 °C were explored, with a focus on water mobility and distribution. The ultrasonic pretreatment significantly increased the water mobility of the strawberry slices, resulting in a reduction in their water content. However, the application of ultrasound significantly decreased the rehydration speed, indicating a lower moisture absorption capacity in the pretreated sample. The micrographs revealed that the structure of the tissue was more uniform after ultrasonic treatment, and water loss was accelerated. In addition, the contact angle measurements showed that the samples were more hydrophobic after ultrasonic treatment, and the eutectic temperature and fold point of the samples increased. Therefore, this study found that ultrasonic-assisted freeze vacuum drying technology effectively reduces hygroscopicity, improves product storage, and represents a potential method for dried production.

16.
Artigo em Inglês | MEDLINE | ID: mdl-38625732

RESUMO

A novel Gram-stain-negative and facultatively anaerobic bacterium, designated A6E488T, was isolated from intertidal sediment collected from Xiaoshi Island, Weihai, PR China (122° 1' E 37° 31' N). Cells of strain A6E488T were rod-shaped with widths of 0.3-0.4 µm and lengths of 1.1-1.8 µm. The optimal growth conditions were determined to be in 1 % (w/v) NaCl, at 37 °C, and at pH 7.0. The predominant fatty acids (≥10 %) were C19 : 0 cyclo ω8c (59.7 %) and summed feature 8 (13.8 %, C18 : 1 ω7c and/or C18 : 1 ω6c). The sole isoprenoid quinone was Q-10. Oxidase activity was negative but catalase activity was positive. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid, one unidentified glycolipid, and one unidentified lipid. Based on phylogenetic analysis of 16S rRNA gene sequences, strain A6E488T showed the highest sequence similarity to Microbaculum marinum MCCC 1K03192T (97.6 %). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain A6E488T and M. marinum MCCC 1K03192T did not exceed 78 and 22 %, respectively. These values are below the recommended thresholds of 95 % (ANI) and 70 % (dDDH) for prokaryotic species delineation. On the basis of gene annotation, it was observed that strain A6E488T possesses the capability for thiosulphate oxidation, suggesting that this strain might be important in the sulphur cycle. Based on the results of phenotypic, genotypic, and chemical characterization, strain A6E488T is considered to represent a novel species of the genus Microbaculum, for which the name Microbaculum marinisediminis sp. nov. is proposed. The type strain is A6E488T (=KCTC 92197T=MCCC 1H00516T).


Assuntos
Ácidos Graxos , Sedimentos Geológicos , Composição de Bases , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Nucleotídeos
17.
Anal Chem ; 96(15): 5913-5921, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38563119

RESUMO

CRISPR/Cas technology has made great progress in the field of live-cell imaging beyond genome editing. However, effective and easy-to-use CRISPR systems for labeling multiple RNAs of interest are still needed. Here, we engineered a CRISPR/dCas12a system that enables the specific recognition of the target RNA under the guidance of a PAM-presenting oligonucleotide (PAMmer) to mimic the PAM recognition mechanism for DNA substrates. We demonstrated the feasibility and specificity of this system for specifically visualizing endogenous mRNA. By leveraging dCas12a-mediated precursor CRISPR RNA (pre-crRNA) processing and the orthogonality of dCas12a from different bacteria, we further demonstrated the proposed system as a simple and versatile molecular toolkit for multiplexed imaging of different types of RNA transcripts in live cells with high specificity. This programmable dCas12a system not only broadens the RNA imaging toolbox but also facilitates diverse applications for RNA manipulation.


Assuntos
Sistemas CRISPR-Cas , RNA , RNA/genética , Sistemas CRISPR-Cas/genética , RNA Guia de Sistemas CRISPR-Cas , Edição de Genes/métodos , Bactérias/genética , Precursores de RNA
18.
BMJ Open ; 14(4): e077623, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38569691

RESUMO

INTRODUCTION: Considering the increasing incidence of Alzheimer's disease (AD) and mild cognitive impairment (MCI) worldwide, there is an urgent need to identify efficacious, safe and convenient treatments. Numerous investigations have been conducted on the use of supplements in this domain, with oral supplementation emerging as a viable therapeutic approach for AD or MCI. Nevertheless, given the multitude of available supplements, it becomes imperative to identify the optimal treatment regimen. METHODS AND ANALYSIS: Eight academic databases and three clinical trial registries will be searched from their inception to 1 June 2023. To identify randomised controlled trials investigating the effects of supplements on patients with AD or MCI, two independent reviewers (X-YZ and Y-QL) will extract relevant information from eligible articles, while the risk of bias in the included studies will be assessed using the Rob 2.0 tool developed by the Cochrane Collaboration. The primary outcome of interest is the overall cognitive function. Pair-wise meta-analysis will be conducted using RevMan V.5.3, while network meta-analysis will be carried out using Stata 17.0 and ADDIS 1.16.8. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The GRADE system will be employed to assess the quality of evidence. This study is scheduled to commence on 1 June 2023 and conclude on 1 October 2023. ETHICS AND DISSEMINATION: Ethics approval is not required for systematic review and network meta-analysis. The results will be submitted to a peer-reviewed journal or at a conference. TRIAL REGISTRATION NUMBER: PROSPERO (CRD42023414700).


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/tratamento farmacológico , Metanálise em Rede , Revisões Sistemáticas como Assunto , Disfunção Cognitiva/terapia , Cognição , Suplementos Nutricionais , Metanálise como Assunto
19.
Antioxidants (Basel) ; 13(4)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38671848

RESUMO

Glutathione (GSH), a robust endogenous antioxidant, actively participates in the modulation of the redox status of cysteine residues in proteins. Previous studies have indicated that GSH can prevent ß-cell failure and prediabetes caused by chronic oscillating glucose (OsG) administration. However, the precise mechanism underlying the protective effect is not well understood. Our current research reveals that GSH is capable of reversing the reduction in Nrf2 levels, as well as downstream genes Grx1 and HO-1, in the islet ß-cells of rats induced by chronic OsG. In vitro experiments have further demonstrated that GSH can prevent ß-cell dedifferentiation, apoptosis, and impaired insulin secretion caused by OsG. Additionally, GSH facilitates the translocation of Nrf2 into the nucleus, resulting in an upregulation of Nrf2-targeted genes such as GCLC, Grx1, HO-1, and NQO1. Notably, when the Nrf2 inhibitor ML385 is employed, the effects of GSH on OsG-treated ß-cells are abrogated. Moreover, GSH enhances the S-glutathionylation of Keap1 at Cys273 and Cys288, but not Cys151, in OsG-treated ß-cells, leading to the dissociation of Nrf2 from Keap1 and facilitating Nrf2 nuclear translocation. In conclusion, the protective role of GSH against OsG-induced ß-cell failure can be partially attributed to its capacity to enhance Keap1 S-glutathionylation, thereby activating the Nrf2 signaling pathway. These findings provide novel insights into the prevention and treatment of ß-cell failure in the context of prediabetes/diabetes, highlighting the potential of GSH.

20.
J Ethnopharmacol ; : 118245, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38679399

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The process of atherosclerosis (AS) is complicated. Transcriptomics technology can assist in discovering the underlying mechanisms and exploring the key targets of Traditional Chinese Medicine (TCM) against atherosclerosis. AIM: This study aimed to investigate targets and signaling pathways significantly related to AS and the potential intervention targets of Xuefu Zhuyu decoction by transcriptomics. MATERIALS AND METHODS: AS models were established by subjecting ApoE-/- mice to an 8-week high-fat diet. Structural changes and plaque formation in the aortic root were observed using hematoxylin-eosin staining (HE staining), while Oil Red O staining was employed to visualize lipid deposition within the aortic root plaque. Movat staining and immunohistochemical staining were conducted to examine the components present in the aortic root plaque. Macrophage content within the plaques was observed through immunofluorescence. Additionally, mRNA sequencing was performed on aortic tissues to identify differentially expressed genes. Enrichment analysis was performed using GO and KEGG analysis. Visualization of the protein-protein interaction (PPI) network was achieved using Cytoscape 3.7.1 and STRING. Western blotting (WB) was employed to assess the protein expression of major differentially expressed genes in the aortic tissue. The drug freeze-dried powder of Xuefu Zhuyu decoction was prepared and the RAW264.7 cells were induced by lipopolysaccharide (LPS) to build an in vitro model. Real-time quantitative PCR was employed to measure the mRNA expression of major differential genes. RESULTS: After ApoE-/- mice were fed with an 8-week high-fat diet, observable changes included the thinning of the aortic root wall, the accumulation of foam cells within the plaque, and the formation of cholesterol crystals in the model group. Treatment with Xuefu Zhuyu (XFZY) decoction for 12 weeks significantly reduced the lipid deposition and the number of macrophages within the plaque (P < 0.05) and significantly increased the collagen content within the plaque (P < 0.01). Enrichment analysis revealed a high enrichment of the cytokine-cytokine receptor interaction pathway and chemokine signaling pathway. Noteworthy genes involved in this response included Ccl12, Ccl22, Cx3cr1, Ccr7, Ccr2, Tnfrsf25, and Gdf5. Xuefu Zhuyu decoction significantly downregulated the expression of CX3CL1 and CX3CR1 (P < 0.05) and upregulated the expression of GDF5 (P < 0.01). Compared with control group, the mRNA expressions of Ccl12, Ccl22, and Ccr2 were significantly upregulated in LPS-stimulated RAW264.7 cells (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction significantly downregulated the expression of Ccl12, Ccl22, Cx3cr1, Ccr7 and Ccr2 (P < 0.05 or P < 0.01). CONCLUSION: Xuefu Zhuyu decoction demonstrates effective regulation of plaque components, retarding plaque progression and preserving plaque stability by modulating lipid metabolism and inflammatory responses. Subsequent transcriptome analysis identified the cytokine-cytokine receptor interaction and chemokine signaling pathway as potential key pathways for the therapeutic effects of Xuefu Zhuyu decoction. This insight not only provides crucial avenues for further exploration into the mechanisms underlying Xuefu Zhuyu decoction but also offers valuable perspectives and hypotheses for enhancing disease prevention and treatment strategies.

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