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1.
Gene ; : 149056, 2024 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-39490646

RESUMO

Renal fibrosis is a crucial factor in the progression of chronic kidney diseases. Previous studies have suggested that apigenin (API) has potential in ameliorating renal fibrosis, but its therapeutic mechanism remains unclear. This study aims to elucidate the mechanisms by which API treats renal fibrosis using network pharmacology and experimental validation. Initially, we used the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and GeneCards database to identify molecular targets of API and associated genes. Next, we constructed a network of API-renal fibrosis targets, followed by protein-protein interaction (PPI) analysis. Subsequent analyses, such as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We also performed molecular docking studies to explore API's interactions with key proteins. To validate API's mechanism in treating renal fibrosis, we used a Human Kidney-2 (HK-2) cell model of epithelial-mesenchymal transition (EMT) induced by transforming growth factor-ß1 (TGF-ß1). We identified 77 API target genes, 8434 renal fibrosis target genes, and 64 intersection genes, which were primarily enriched in nuclear factor kappa-B (NF-κB) and Phosphatidylinositide 3-kinases/protein kinase B (PI3K-AKT) pathways. API significantly inhibited EMT in TGF-ß1-induced HK-2 cells by regulating the expression of α-Smooth muscle actin (α-SMA) and E-cadherin and suppressing the protein expression of p-PI3K, p-AKT, and p-P65, which are related to the PI3K-AKT and NF-κB pathways. However, co-administration of the PI3K agonist 740Y-P counteracted API's inhibitory effects on these protein expressions. In summary, these findings highlight API's therapeutic potential in treating renal fibrosis by modulating EMT in renal tubular epithelial cells via the PI3K-AKT and NF-κB pathways.

2.
Cytojournal ; 21: 31, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39411170

RESUMO

Objective: Metaplastic breast carcinoma (MBC) is a special type of morphologically heterogeneous and aggressively invasive breast cancer. MBC is characterized by the transformation of tumor epithelium into squamous epithelium and/or mesenchymal components, including differentiation into spindle cells, chondrocytes, and osteocytes. Due to its rarity and invasiveness, there is a paucity of research on MBC prognosis. Furthermore, there are currently no treatment guidelines for MBC. This study analyzed the clinicopathological characteristics, immunophenotype, and prognostic features of MBC. Our aim was to better characterize MBC, thereby identifying potential prognostic factors and new treatment methods. Moreover, we also describe an MBC case treated experimentally with anti-vascular targeted therapy. Material and Methods: We retrospectively analyzed clinical pathological data on 54 female patients with MBC from Shaanxi Provincial People's Hospital and the XiJing Hospital of Air Force Medical University. These cases were diagnosed with MBC between January 1st, 2013, and October 1st, 2018. All patients were from the northwest region of China. The gross morphological, histological, and immunohistochemical features of MBC were analyzed. Kaplan-Meier analysis was used to calculate the survival rate, and univariate analysis was performed to identify significant prognostic factors. In addition, the treatment of an MBC patient with anti-angiogenic therapy was described, and a relevant literature review was conducted. Results: MBC was diagnosed in 32 left breasts and 22 right breasts from 54 women aged 21-76 years (median age of 57 years). The maximum tumor diameter ranged from 0.6 to 14 cm (average of 4.1 cm). Of the 54 patients, 47 underwent surgical treatment, with lymph node metastasis found in 17.0% (8/47). According to the World Health Organization classification criteria for breast tumors, the study cohort consisted of 15 cases of squamous cell carcinoma, ten cases of spindle cell carcinoma, nine cases of carcinoma with associated stromal differentiation, 18 cases of mixed carcinoma, and two cases of adenocarcinoma with squamous differentiation. Based on the American Joint Committee on Cancer clinical staging criteria, the patients were classified as Stage I (10 cases, 18.5%), Stage II (26 cases, 48.1%), Stage III (11 cases, 20.4%), and Stage IV (7 cases, 13.0%). Immunohistochemical analysis revealed that 94.4% of patients had triple-negative breast cancer (TNBC), 47 cases showed mutant tumor protein 53 (TP53) expression, 29 cases showed positive epidermal growth factor receptor (EGFR) expression, 43 cases showed positive E-cadherin expression, and 37 cases showed positive Cluster of Differentiation 24 expression. The Ki-67 index ranged from 20% to 90%. Univariate analysis showed that the Ki-67 index was not significantly associated with either progression-free survival (PFS) or overall survival (OS) in MBC patients. Patients with negative axillary lymph nodes had significantly better PFS and OS than those with positive nodes (P < 0.05), and patients with clinical stage I-II disease had better PFS and OS than those with stage III-IV disease (P < 0.05). Patients treated with anthracycline-containing chemotherapy had significantly better PFS than those who did not receive chemotherapy. Univariate analysis revealed that the high expression of EGFR correlated with worse PFS (P < 0.05). The type of surgical approach employed did not affect the prognosis of MBC patients. Following the application of anti-angiogenic therapy, a rapid partial response was observed in an MBC patient with carcinoma and associated stromal differentiation. This patient subsequently underwent surgery and radiation therapy and has now achieved over 6 years of PFS. Conclusion: MBC is a heterogeneous group of tumors with high malignancy and poor prognosis. The large majority is TNBC and exhibits unique immune phenotypes. The poor PFS of MBC patients may be related to EGFR expression, which could become a potential therapeutic target in these patients. Surgery remains the primary treatment method for MBC. The present study found that sentinel lymph node biopsy was feasible in appropriate patients, and that chemotherapy regimens incorporating anthracycline-class drugs did not appear to improve OS. Anti-angiogenic therapy holds promise as a potentially effective treatment approach for MBC, and the optimization of systemic treatment strategies should be a priority in the management of these patients.

3.
Psychol Res Behav Manag ; 17: 3443-3453, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39385810

RESUMO

Objective: COVID-19-related lockdown can lead to mental health problem, which displays heterogeneous between individuals. The aim of this study was to explore the association between mental health, social support and psychological capital state of professional staff with different personalities during the COVID-19 pandemic in China. Methods: A cross-section study was conducted via online survey using the questionnaires of General Health Questionnaire (GHQ-12), Multidimensional Scale of Perceived Social Support (MSPSS), Psychological Capital Questionnaire (PCQ), Eysenck Personality Questionnaire-Revision Short Scale of China (EPQ-RSC). A total of 626 employees were included. Multiple regression analysis was performed to investigate the association of psychological capital, perceived social support, EPQ-N and EPQ-E and their interactions in general mental health. Results: About 2.7% of professionals had mental health. The married had a higher mental health score than the single (P<0.05). The regular exercising workers had the lowest mental health score (P<0.05), and higher psychological capital and social support scores than the non-exercising ones (P<0.01). Multivariate analysis showed that the interaction between social support, psychological capital and neuroticism was statistically significant (ß=-0.161, P<0.001) in general mental health with neuroticism ranking the top (ß=0.352, P<0.001). Mediation analysis showed that social support modified the effect of psychological capital on mental health, accounting for 25.5% of the total effect, and that both social support and psychological capital mediated the effect of neuroticism or extroversion differentially on mental health. Conclusion: Neuroticism is an influencing factor on mental health of professional staff. Social support and psychological capital played a partial mediating role in the effect of neuroticism or extroversion differentially on mental health in China. The findings suggest that during the COVID-19 pandemic, more social support and psychological capital are needed for the professional individuals with neuroticism to alleviate their stress and improve mental health.

4.
Environ Microbiome ; 19(1): 74, 2024 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-39397007

RESUMO

Environmental gradients can influence morpho-physiological and life-history differences in natural populations. It is unclear, however, to what extent such gradients can also modulate phenotypic differences in other organismal characteristics such as the structure and function of host-associated microbial communities. In this work, we addressed this question by assessing intra-specific variation in the diversity, structure and function of environmental-associated (sediment and water) and animal-associated (skin and gut) microbiota along an environmental gradient of pollution in one of the most urbanized coastal areas in the world. Using the tropical sea cucumber Holothuria leucospilota, we tested the interplay between deterministic (e.g., environmental/host filtering) and stochastic (e.g., random microbial dispersal) processes underpinning host-microbiome interactions and microbial assemblages. Overall, our results indicate that microbial communities are complex and vary in structure and function between the environment and the animal hosts. However, these differences are modulated by the level of pollution across the gradient with marked clines in alpha and beta diversity. Yet, such clines and overall differences showed opposite directions when comparing environmental- and animal-associated microbial communities. In the sea cucumbers, intrinsic characteristics (e.g., body compartments, biochemistry composition, immune systems), may underpin the observed intra-individual differences in the associated microbiomes, and their divergence from the environmental source. Such regulation favours specific microbial functional pathways that may play an important role in the survival and physiology of the animal host, particularly in high polluted areas. These findings suggest that the interplay between both, environmental and host filtering underpins microbial community assembly in H. leucospilota along the pollution gradient in Hong Kong.

5.
Biosensors (Basel) ; 14(10)2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39451718

RESUMO

Triton X-100 (TX-100) is a commonly used surfactant in the manufacture of biosensors. The factors limiting the use of TX-100 in biosensors are environmental concerns. In this study, the binary system of sodium dodecyl benzene sulfonate (SDBS) and fatty alcohol-polyoxyethlene ether (AEO) was investigated from the physicochemical principle of surfactant interaction and its application in biosensors. The results demonstrated that a mixture of SDBS and AEO at an appropriate molar ratio had a comparable activity to TX-100 in terms of surface activity, micelle formation, dynamic adsorption, foaming, emulsifying, and cell permeability. Theory and experimentation support the idea that SDBS-AEO might take the place of TX-100 in the manufacturing of biosensors. This study contributes to the development of alternatives to TX-100 and provides a new perspective for an in-depth study of the interaction mechanism of additives in biosensor design.


Assuntos
Técnicas Biossensoriais , Octoxinol , Tensoativos , Tensoativos/química , Benzenossulfonatos/química , Adsorção , Micelas , Propriedades de Superfície , Polietilenoglicóis/química , Álcoois Graxos
6.
Molecules ; 29(20)2024 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-39459211

RESUMO

A balanced inflammatory response is crucial for the organism to defend against external infections, however, an exaggerated response may lead to detrimental effects, including tissue damage and even the onset of disease. Therefore, anti-inflammatory drugs are essential for the rational control of inflammation. In this study, we found that a previously screened peptide TaY (KEKKEVVEYGPSSYGYG) was able to inhibit the LPS-induced RAW264.7 inflammatory response by decreasing a series of proinflammatory cytokines, such as TNF-α, IL-6, and nitric oxide (NO). To elucidate the underlying mechanism, we conducted further investigations. Western blot analysis showed that TaY reduced the phosphorylation of key proteins (IKK-α/ß, IκB-α,NF-κB (P65)) in the TLR4-NF-κB signaling pathway and inhibited the inflammatory response. Furthermore, molecular docking and molecular dynamic simulations suggested that TaY binds to the hydrophobic pocket of MD2 through hydrogen bonding and hydrophobic interactions, potentially competing with LPS for MD2 binding. Collectively, TaY is a promising candidate for the development of novel therapeutic strategies against inflammatory disorders.


Assuntos
Inflamação , Lipopolissacarídeos , Antígeno 96 de Linfócito , Simulação de Acoplamento Molecular , NF-kappa B , Transdução de Sinais , Camundongos , Animais , Transdução de Sinais/efeitos dos fármacos , NF-kappa B/metabolismo , Células RAW 264.7 , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Antígeno 96 de Linfócito/metabolismo , Antígeno 96 de Linfócito/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Peptídeos/química , Peptídeos/farmacologia , Simulação de Dinâmica Molecular , Citocinas/metabolismo , Receptor 4 Toll-Like/metabolismo , Ligação Proteica , Óxido Nítrico/metabolismo
7.
Molecules ; 29(20)2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39459344

RESUMO

Perovskite solar cells (PSCs) are gaining prominence in the photovoltaic industry due to their exceptional photoelectric performance and low manufacturing costs, achieving a significant power conversion efficiency of 26.4%, which closely rivals that of silicon solar cells. Despite substantial advancements, the effective area of high-efficiency PSCs is typically limited to about 0.1 cm2 in laboratory settings, with efficiency decreasing as the area increases. The limitation poses a major obstacle to commercialization, as large-area, high-quality perovskite films are crucial for commercial applications. This paper reviews current techniques for producing large-area perovskites, focusing on slot-die coating, a method that has attracted attention for its revolutionary potential in PSC manufacturing. Slot-die coating allows for precise control over film thickness and is compatible with roll-to-roll systems, making it suitable for large-scale applications. The paper systematically outlines the characteristics of slot-die coating, along with its advantages and disadvantages in commercial applications, suggests corresponding optimization strategies, and discusses future development directions to enhance the scalability and efficiency of PSCs, paving the way for broader commercial deployment.

8.
Sci Rep ; 14(1): 25106, 2024 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-39443623

RESUMO

This study aims to observe the clinical efficacy and safety of rigid gas permeable corneal contact lenses (RGP-CLs) wearing after femtosecond laser-assisted minimally invasive lamellar keratoplasty (FL-MILK) in progressive and advanced keratoconus eyes. Twenty-five patients (27 eyes) fitted with RGP-CLs after FL-MILK were enrolled, and 22 grading-matched keratoconus patients (23 eyes) as a control group. Corneal morphological data, diopter, best corrected vision, corneal endothelium, non-invasive tear film rupture time (NIBUT), corneal perception and comfort questionnaire were analysed before and after wearing RGP-CLs. In the FL-MILK group, the flat K, steep K and Kmax of the corneal anterior surface were decreased by 3.05D, 3.48D and 7.17D respectively after surgery (P = 0.011, 0.004 and 0.007). The central corneal thickness increased by 175.29 µm (P < 0.001). The basic curve of RGP-CLs after surgery was about 0.23 mm flatter than that before surgery (P = 0.013). There was no statistical difference in the best corrected vision and the comfort of wearing RGP-CLs before and after FL-MILK (P = 0.923, 0.391). Compared with the control group, there was no significant difference in vision improvement by RGP-CLs (P = 0.669). During the follow-up, the comfort of wearing RGP-CLs in the two groups was good, and no obvious adverse events were observed. This study showed MILK significantly increases corneal thickness and flattens corneal curvature, achieving good RGP-CLs corrected vision.


Assuntos
Lentes de Contato , Transplante de Córnea , Ceratocone , Humanos , Ceratocone/cirurgia , Ceratocone/reabilitação , Feminino , Masculino , Adulto , Transplante de Córnea/métodos , Transplante de Córnea/efeitos adversos , Adulto Jovem , Acuidade Visual , Córnea/cirurgia , Córnea/fisiopatologia , Córnea/patologia , Resultado do Tratamento , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
9.
Medicine (Baltimore) ; 103(42): e40073, 2024 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-39432628

RESUMO

Myocardial infarction (MI) is one of the leading causes of death worldwide because of its high morbidity and mortality. Traditional Chinese Medicine compounds play a crucial role in preventing cardiovascular diseases. Danggui Sini Decoction (DSD) is widely used clinically for cardiovascular diseases. However, the mechanism, main components, and main targets of DSD in treating MI are still unclear. In this study, we utilized network pharmacology and molecular docking for exploration. MI-related genes were examined using the Genecards database, and the active ingredients of DSD were screened based on System Pharmacology Database and Analysis Platform of Traditional Chinese Medicine by oral bioavailability ≥ 30% and drug-likeness ≥ 0.18. The protein-protein interaction network diagram was generated using the STRING database. The DAVID web platform was used to carry out gene ontology and Kyoto encyclopedia of gene and genome signaling pathway analysis. DSD's screening study revealed 120 primary active ingredients and 561 putative active target genes. The main therapeutic targets were TP53, EGFR, AKT1, IL6, TNF, STAT3, IL1B, CTNNB1, SRC, MYC, JUN, and INS. Gene ontology and Kyoto encyclopedia of gene and genome analyses revealed that DSD treatment of MI mainly involves the positive regulation of the ERK1 and ERK2 cascades, positive regulation of cell proliferation, inflammatory responses, aging, and the MAPK cascade, along with other biological processes. The molecular docking results indicate that DSD drugs may interact with AKT1, EGFR, TP53, and TNF through formononetin, isorhamnetin, ß-Sitosterol, and kaempferol, potentially contributing to the treatment of MI. By utilizing a multi-component, multi-pathway, and multi-target mode of action, DSD may have the potential to prevent MI.


Assuntos
Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Infarto do Miocárdio , Farmacologia em Rede , Mapas de Interação de Proteínas , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Infarto do Miocárdio/tratamento farmacológico , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Transdução de Sinais/efeitos dos fármacos , Sitosteroides/farmacologia , Sitosteroides/uso terapêutico
10.
Adv Sci (Weinh) ; : e2404342, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39340833

RESUMO

Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic potentiation via presynaptic mechanism. In corroboration with this, nociceptor-specific ablation of TRPC3/6 produces comparable pain relief. Mechanistic analysis reveals that upon peripheral inflammation, TRPC3/6 in primary sensory neurons get recruited via released bradykinin acting on B1/B2 receptors, facilitating BDNF secretion from spinal nociceptor terminals, which in turn potentiates synaptic transmission through TRPC3/6 and eventually results in mechanical pain hypersensitivity. Antagonizing TRPC3/6 in DRG relieves mechanical pain hypersensitivity in mice and nociceptor hyperexcitability in human. Thus, TRPC3/6 in nociceptors is crucially involved in pain plasticity and constitutes a promising therapeutic target against mechanical pain hypersensitivity with minor side effects.

11.
Biomark Med ; 18(17-18): 759-770, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39269771

RESUMO

Aim: To investigate the systemic immune-inflammation index and prognostic immune nutritional index in the prognostic evaluation of oral squamous cell carcinoma.Materials & methods: We analyzed retrospectively the relationship between systemic immune-inflammation index, prognostic immune nutritional index and clinicopathological variables and the overall survival of 262 patients who underwent radical surgery.Results: Multivariate analysis showed high systemic immune-inflammation index (Hazard ratio = 3.062, 95% CI: 1.021-8.251), low prognostic immune nutritional index (Hazard ratio = 0.297, 95% CI: 0.139-0.636), tumor node metastasis classification 3-4 (Hazard ratio = 9.862, 95% CI: 4.658-20.880) patients have worse overall survival.Conclusion: Preoperative systemic immune-inflammation index and prognostic immune nutritional index are independent risk factors for prognostic survival status in oral squamous cell carcinoma.


[Box: see text].


Assuntos
Carcinoma de Células Escamosas , Inflamação , Neoplasias Bucais , Humanos , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , Neoplasias Bucais/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico , Inflamação/imunologia , Idoso , Estudos Retrospectivos , Avaliação Nutricional , Adulto , Estado Nutricional , Idoso de 80 Anos ou mais , Modelos de Riscos Proporcionais , Fatores de Risco
12.
Bioorg Chem ; 153: 107801, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39244973

RESUMO

Resistance to proteasome inhibitors like Bortezomib is a major challenge in the treatment of multiple myeloma (MM). Proteolysis targeting chimeras (PROTACs), an emerging therapeutic approach that induces selective degradation of target proteins, offer a promising solution to overcome drug resistance. In this study, we designed and synthesized novel small-molecule PROTACs that induce 20S proteasome subunit ß5 degradation as a strategy to overcome Bortezomib resistance. These 20S proteasome subunit ß5 PROTACs demonstrated considerable binding affinity to 20S proteasome subunit ß5 and cereblon (CRBN), effectively induced 20S proteasome subunit ß5 degradation, and exhibited potent antiproliferative activity against a panel of cancer cell lines. Notably, PROTACs 12f and 14 displayed robust antitumor effects against both the pharyngeal carcinoma cell line FaDu and the Bortezomib-resistant MM cell line KM3/BTZ in vitro and in vivo with excellent safety profiles. Taken together, our findings highlight the potential of PROTACs 12f and 14 as novel 20S proteasome subunit ß5-degrading agents for the treatment of pharyngeal carcinoma and overcoming Bortezomib resistance in MM.

14.
Mar Environ Res ; 202: 106733, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39255628

RESUMO

Variation in nitrogen (N) availability significantly influences population dynamics and the productivity of marine phytoplankton. As N availability in the ocean is conditioned by the N source, it is important to understand the capacity of phytoplankton organisms to adjust their physiology and dynamics under different N conditions. We investigated the growth dynamics of Thalassiosira weissflogii, a coastal diatom, in response to different N sources (Nitrate, NO3-; Ammonium, NH4+; urea, CH4N2O) and availabilities (45 and 5 µM). Our findings demonstrate that T. weissflogii can display plastic adjustments in population dynamics to different N sources. These responses evidenced a greater preference for NH4+ and urea than NO3-, particularly under high N availability. The relative growth rate (µ) is higher (1.18 ± 0.01) under NH4+-high treatment compared to NO3--high (1.01 ± 0.01). The carrying capacity (K) varied only among concentrations, indicating equal N utilization efficiency for biomass production. No effects of N source were detected under the low concentration, suggesting that the preference for NH4⁺ and urea was diminished by limited nitrogen supply due to potential interactions. These results provide valuable insights into the physiological flexibility of T. weissflogii to varying N conditions, shedding light on the ecological success and resilience of this species in highly variable coastal environments.

15.
Phytomedicine ; 134: 155957, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39181101

RESUMO

BACKGROUND: Type 2 diabetes (T2DM) is one of the major metabolic diseases and poses a serious challenge to human life and global economic development. Jinqi Jiangtang Tablets (JQJT) is effective in ameliorating the effects of T2DM, but the mechanism of JQJT is unclear. PURPOSE: This study integrated metabolomics and transcriptomics to reveal the mechanism by which JQJT improves T2DM. METHODS: The T2DM mouse model was established, and the effects of JQJT on improving T2DM were evaluated by determining the levels of blood lipids, fasting blood glucose (FBG), insulin metabolism and hepatic lipid accumulation in mice after JQJT administration for 8 weeks. Serum metabolites were detected using ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry (UPLC-Q-TOF-MS) technology, and mouse liver differential genes were detected using transcriptomic technology. Correlation analysis was used to extract metabolites and RNA with correlations, and potential pathways were enriched and constructed using the common pathway analysis function of MetaboAnalyst 5.0. Finally, the expression of key target proteins and genes was verified by Western blot (WB) and Polymerase Chain Reaction (PCR) to further elucidate the mechanism by which JQJT improves T2DM. RESULTS: JQJT reduced FBG and lipid levels, improved insulin resistance (IR) and hepatic lipoatrophy in mice. A total of 35 differentially abundant metabolites were identified by metabolomics, and 328 differential genes were detected by transcriptomics. The integrated metabolomics and transcriptomics results suggested that JQJT may ameliorate T2DM mainly by regulating glucose and lipid metabolic pathways. WB and PCR results showed that JQJT regulates the insulin signaling pathway, involved in fatty acid metabolism, glycogen synthesis and catabolism. CONCLUSIONS: JQJT improved IR in T2DM mice by regulating the insulin signaling pathway, improving glycogen synthesis and glycolysis, and increasing hepatic triglyceride and fatty acid metabolism.


Assuntos
Glicemia , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Fígado , Metabolômica , Animais , Medicamentos de Ervas Chinesas/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Camundongos , Glicemia/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Insulina/sangue , Insulina/metabolismo , Comprimidos , Transcriptoma/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Perfilação da Expressão Gênica , Lipídeos/sangue
16.
Nat Commun ; 15(1): 6628, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103372

RESUMO

We have determined the crystal structure of a pseudoknot (PK)-containing hammerhead ribozyme that closely resembles the pistol ribozyme, with essentially identical secondary structure and connectivity. The activity is more sensitive to deletion of the G8 2'OH than to the absence of magnesium ions, indicating that the catalytic mechanism is the same as the extended hammerhead, and distinct from the pistol ribozyme. Here we show that nucleophilic attack is almost perfectly in-line, and the G8 2'OH is well positioned to act as general acid, being directed towards the O5' leaving group, and 2.9 Å away from it. Despite the similarity in overall structure to the pistol ribozyme, the local structure close to the cleavage site differs, and the PK hammerhead retains its unique mechanistic identity and demonstrates enhanced activity over other hammerhead ribozymes under standard conditions.


Assuntos
Conformação de Ácido Nucleico , RNA Catalítico , RNA Catalítico/química , RNA Catalítico/metabolismo , RNA Catalítico/genética , Catálise , Cristalografia por Raios X , Modelos Moleculares , Magnésio/metabolismo , Magnésio/química
17.
Biochim Biophys Acta Rev Cancer ; 1879(5): 189172, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-39151808

RESUMO

Macrophage-mediated programmed cell removal (PrCR) is crucial for the identification and elimination of needless cells that maintain tissue homeostasis. The efficacy of PrCR depends on the balance between pro-phagocytic "eat me" signals and anti-phagocytic "don't eat me" signals. Recently, a growing number of studies have shown that tumourigenesis and progression are closely associated with PrCR. In the tumour microenvironment, PrCR activated by the "eat me" signal is counterbalanced by the "don't eat me" signal of CD47/SIRPα, resulting in tumour immune escape. Therefore, targeting exciting "eat me" signalling while simultaneously suppressing "don't eat me" signalling and eventually inducing macrophages to produce effective PrCR will be a very attractive antitumour strategy. Here, we comprehensively review the functions of PrCR-activating signal molecules (CRT, PS, Annexin1, SLAMF7) and PrCR-inhibiting signal molecules (CD47/SIRPα, MHC-I/LILRB1, CD24/Siglec-10, SLAMF3, SLAMF4, PD-1/PD-L1, CD31, GD2, VCAM1), the interactions between these molecules, and Warburg effect. In addition, we highlight the molecular regulatory mechanisms that affect immune system function by exciting or suppressing PrCR. Finally, we review the research advances in tumour therapy by activating PrCR and discuss the challenges and potential solutions to smooth the way for tumour treatment strategies that target PrCR.


Assuntos
Macrófagos , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Macrófagos/metabolismo , Macrófagos/imunologia , Animais , Transdução de Sinais , Antígeno CD47/metabolismo , Evasão Tumoral
18.
J Cosmet Dermatol ; 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39180331

RESUMO

BACKGROUND: The picosecond neodymium yttrium aluminum garnet laser (PNYL) has been successfully used in treating acquired bilateral nevus of Ota-like macules (ABNOM). The 730-nm picosecond titanium sapphire laser (PTSL) is an emerging tool for pigmentary disorders. However, no studies have compared two different wavelengths of picosecond laser for the treatment of ABNOM. AIMS: To compare the efficacy and safety of the 730-nm PTSL with the 1064-nm PNYL in the treatment of ABNOM. METHODS: Fifteen participants with ABNOM were randomized to undergo a single session of either the 730-nm PTSL on one side of the face and 1064-nm PNYL on the other side. Efficacy and safety assessments were performed by blinded visual evaluations at baseline, 12 weeks, and 24 weeks posttreatment. Participants' satisfaction and adverse effects were recorded. RESULTS: Compared to baseline, The 730-nm PTSL-treated side showed better improvement than that of the 1064-nm PNYL-treated side at 24 weeks posttreatment (1.67 ± 1.047 vs. 0.87 ± 0.640, p = 0.027). There were no significant differences in pain sensation and participants' satisfaction between the two laser treatments. CONCLUSIONS: The 730-nm PTSL is more effective than the 1064-nm PNYL in the treatment of ABNOM.

19.
Perfusion ; : 2676591241237133, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39175255

RESUMO

Background: Extracorporeal life support echniques as an Adjunct to Advanced Cardiac Life Support is usually suitable for complex heart surgery such as cardiopulmonary bypass (CPB). Cerebral perfusion is a clinically feasible neuroprotective strategy; however, the lack of a reliable small animal model.Methods: Based on the rat model of ECLS we evaluate the effects of ECLS-CP using HE staining, Nissl staining, TUNEL staining and ELISA.Result: We found that ECLS combined with the cerebral perfusion model did not cause brain injury and immune inflammation. There was no difference between the two by a left carotid artery or right carotid artery CP.Conclusion: These experimental results can provide the experimental basis for selecting blood vessels for ECLS patients and clinical CP to offers a trustworthy animal model for future exploration of applying brain perfusion strategies during ECLS-CP.

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