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1.
J Ethnopharmacol ; 336: 118736, 2025 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-39186991

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Zhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription "Er-Xian Decoction" documented in the esteemed "Clinical Manual of Chinese Medical Prescription". While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined. AIM OF THE STUDY: This study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation. MATERIALS AND METHODS: Utilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16 S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods. RESULTS: ZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1ß and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. With a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16 S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus, Prevotella_9, unclassified_Bacilli, and unclassified_rumen_bacterium_JW32. Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species. CONCLUSION: ZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Metabolómica , Farmacología en Red , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Masculino , Ratas , Antirreumáticos/farmacología , Antirreumáticos/uso terapéutico , Citocinas/sangre , Citocinas/metabolismo , Transducción de Señal/efectos de los fármacos
2.
Cell Mol Life Sci ; 81(1): 408, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287634

RESUMEN

Diabetic kidney disease (DKD) is the predominant type of end-stage renal disease. Increasing evidence suggests thatglomerular mesangial cell (MC) inflammation is pivotal for cell proliferation and DKD progression. However, the exactmechanism of MC inflammation remains largely unknown. This study aims to elucidate the role of inflammatoryfactor high-mobility group box 1 (Hmgb1) in DKD. Inflammatory factors related to DKD progression are screened viaRNA sequencing (RNA-seq). In vivo and in vitro experiments, including db/db diabetic mice model, CCK-8 assay, EdUassay, flow cytometric analysis, Co-IP, FISH, qRT-PCR, western blot, single cell nuclear RNA sequencing (snRNA-seq),are performed to investigate the effects of Hmgb1 on the inflammatory behavior of MCs in DKD. Here, wedemonstrate that Hmgb1 is significantly upregulated in renal tissues of DKD mice and mesangial cells cultured withhigh glucose, and Hmgb1 cytopasmic accumulation promotes MC inflammation and proliferation. Mechanistically,Hmgb1 cytopasmic accumulation is two-way regulated by MC-specific cyto-lncRNA E130307A14Rik interaction andlactate-mediated acetylated and lactylated Hmgb1 nucleocytoplasmic translocation, and accelerates NFκB signalingpathway activation via directly binding to IκBα. Together, this work reveals the promoting role of Hmgb1 on MCinflammation and proliferation in DKD and helps expound the regulation of Hmgb1 cytopasmic accumulation in twoways. In particular, Hmgb1 may be a promising therapeutic target for DKD.


Asunto(s)
Nefropatías Diabéticas , Proteína HMGB1 , Células Mesangiales , FN-kappa B , Transducción de Señal , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Animales , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Células Mesangiales/metabolismo , Células Mesangiales/patología , Ratones , FN-kappa B/metabolismo , Masculino , Proliferación Celular , Progresión de la Enfermedad , Ratones Endogámicos C57BL , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Citosol/metabolismo , Humanos , Inflamación/patología , Inflamación/metabolismo
3.
Transl Cancer Res ; 13(8): 4257-4277, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39262476

RESUMEN

Background: Hepatocellular carcinoma (HCC) remains one of the most lethal cancers globally. Patients with advanced HCC tend to have poor prognoses and shortened survival. Recently, data from bulk RNA sequencing have been employed to discover prognostic markers for various cancers. However, they fall short in precisely identifying core molecular and cellular activities within tumor cells. In our present study, we combined bulk-RNA sequencing (bulk RNA-seq) data with single-cell RNA sequencing (scRNA-seq) to develop a prognostic model for HCC. The goal of our research is to uncover new biomarkers and enhance the accuracy of HCC prognosis prediction. Methods: Integrating single-cell sequencing data with transcriptomics were used to identify epithelial-mesenchymal transition (EMT)-related genes (ERGs) implicated in HCC progression and their clinical significance was elucidated. Utilizing marker genes derived from core cells and ERGs, we constructed a prognostic model using univariate Cox analysis, exploring a multitude of algorithmic combinations, and further refining it through multivariate Cox analysis. Additionally, we conducted an in-depth investigation into the disparities in clinicopathological features, immune microenvironment composition, immune checkpoint expression, and chemotherapeutic drug sensitivity profiles between high- and low-risk patient cohorts. Results: We developed a prognostic model predicated on the expression profiles of eight signature genes, namely HSP90AA1, CIRBP, CCR7, S100A9, ADAM17, ENG, PGF, and INPP4B, aiming at predicting overall survival (OS) outcomes. Notably, patients classified with high-risk scores exhibited a propensity towards diminished OS rates, heightened frequencies of stage III-IV disease, increased tumor mutational burden (TMB), augmented immune cell infiltration, and diminished responsiveness to immunotherapeutic interventions. Conclusions: This study presented a novel prognostic model for predicting the survival of HCC patients by integrating scRNA-seq and bulk RNA-seq data. The risk score emerges as a promising independent prognostic factor, showing a correlation with the immune microenvironment and clinicopathological features. It provided new clinical tools for predicting prognosis and aided future research into the pathogenesis of HCC.

4.
Am J Case Rep ; 25: e943908, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39223781

RESUMEN

BACKGROUND Cardiac calcified amorphous tumor (CCAT), a peculiar and uncommon non-neoplastic cardiac lesion, was initially characterized by Reynolds and colleagues in the medical literature in 1997. This distinctive entity is hallmarked by its unique feature of pedunculated and diffused calcifications, primarily infiltrating the cardiac structures, with a predilection for the mitral valve annulus initially, followed in sequence by the right atrium, right ventricle, left atrium, left ventricle, and tricuspid valve annulus. The nature of CCATs, despite being benign, poses diagnostic dilemmas, as they frequently masquerade as malignant tumors due to their clinical presentations, which resemble those caused by potential complications such as obstructive masses and thromboembolic events. CASE REPORT A 50-year-old man presented to our hospital with shortness of breath. He had been short of breath for more than 5 years after repeated activities. Transthoracic echocardiography showed a mobile high echogenic mass from the middle of the right ventricular wall and pericardial effusion and right heart insufficiency. The electrocardiogram (ECG) results demonstrated a sinus rhythm, complete right bundle branch block, and T-wave alterations. Additionally, the chest computed tomography (CT) scan revealed a slightly enlarged heart with a lack of density and calcification in the right ventricle. He had an uneventful postoperative recovery after the resection of the cardiac tumor. The mass had not continued to grow when we compared it with preoperative cardiac color doppler echocardiography, after 3 months follow-up. CONCLUSIONS CCAT is a rare non-neoplastic cardiac entity. Diagnosis of CCAT poses a challenge due to the absence of distinct clinical features and its frequent misidentification as a malignant tumor mimic. Surgical resection serves as the sole treatment for symptom relief.


Asunto(s)
Calcinosis , Neoplasias Cardíacas , Ventrículos Cardíacos , Humanos , Masculino , Persona de Mediana Edad , Calcinosis/diagnóstico , Calcinosis/cirugía , Diagnóstico Diferencial , Ecocardiografía , Neoplasias Cardíacas/diagnóstico , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/cirugía , Tomografía Computarizada por Rayos X
5.
Nat Commun ; 15(1): 7704, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231978

RESUMEN

Emergent superconductivity at the LaAlO3/KTaO3 interfaces exhibits a mysterious dependence on the KTaO3 crystallographic orientations. Here by soft X-ray angle-resolved photoemission spectroscopy, we directly resolve the electronic structure of the LaAlO3/KTaO3 interfacial superconductors and the non-superconducting counterpart. We find that the mobile electrons that contribute to the interfacial superconductivity show strong k⊥ dispersion. Comparing the superconducting and non-superconducting interfaces, the quasi-three-dimensional electron gas with over 5.5 nm spatial distribution ubiquitously exists and shows similar orbital occupations. The signature of electron-phonon coupling is observed and intriguingly dependent on the interfacial orientations. Remarkably, the stronger electron-phonon coupling signature correlates with the higher superconducting transition temperature. Our observations help scrutinize the theories on the orientation-dependent superconductivity and offer a plausible and straightforward explanation. The interfacial orientation effect that can modify the electron-phonon coupling strength over several nanometers sheds light on the applications of oxide interfaces in general.

6.
Biomaterials ; 314: 122829, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39276410

RESUMEN

Developing drug delivery systems capable of achieving deep tumor penetration is a challenging task, yet there is a significant demand for such systems in cancer treatment. Hitchhiking on tumor-derived extracellular vesicles (EVs) represents a promising strategy for enhancing drug penetration into tumors. However, the limited drug assembly on EVs restricts its further application. Here, we present a novel approach to efficiently attach antitumor drugs to EVs using an engineered cell membrane-based vector. This vector includes the AS1411 aptamer for tumor-specific targeting, the vesicular stomatitis virus glycoprotein (VSV-G) for tumor cell membrane fusion, and a photosensitizer as the therapeutic agent while ensuring optimal drug encapsulation and stability. Upon injection, photosensitizers are firstly transferred to the tumor cell membrane and subsequently piggybacked onto EVs with the inherent secretion process. By hitchhiking with EVs, photosensitizers can be transferred layer by layer deep into the solid tumors. The results suggest that this EVs-hitchhiking strategy enables photosensitizers to penetrate deeply into tumor tissue, thereby enhancing the efficacy of phototherapy. This study offers broad application prospects for delivering drugs deeply into tumor tissues.

7.
Poult Sci ; 103(10): 104090, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39096826

RESUMEN

The size of the initial primordial follicle pool in the ovary depends on primordial follicle formation, which determines the female reproductive lifespan. However, the molecular regulation of primordial follicle formation in chickens remains unclear. In this study, the left ovaries of chickens were collected at 2 d posthatch (dph), 5.5 dph, and 10.5 dph to examine the formation of primordial follicles. Single-cell mRNA sequencing (scRNA-seq) and spatial transcriptomic analysis were performed to explore the ovarian microenvironment and identify regulatory pathways involved in the formation of primordial follicles in chickens. Histomorphological analysis of chicken ovary tissues revealed the presence of germ cell cysts at 1 dph, which began to disintegrate at 2 dph. Primordial follicles appeared at 5.5 dph and continued to develop into larger-diameter follicles. scRNA-seq and spatial transcriptomic analysis revealed 24 cellular clusters involved in chicken primordial follicle formation. The metabolic pathway of steroid hormone synthesis was found in pregranulosa and pretheca cells. Histological analysis showed that chicken ovaries did not form primordial follicles after the inhibition of the steroid hormone synthesis pathway by simvastatin or tamoxifen. In addition, mRNA transcriptomic and bioinformatics analyses revealed that GREB1 was a downstream gene of the steroid hormone synthesis pathway during the formation of chicken primordial follicles. This study provides a valuable foundation for investigating primordial follicle formation in avian species and optimizing their reproductive performance.


Asunto(s)
Pollos , Folículo Ovárico , Análisis de la Célula Individual , Animales , Pollos/genética , Pollos/crecimiento & desarrollo , Pollos/fisiología , Folículo Ovárico/fisiología , Femenino , Análisis de Secuencia de ARN/veterinaria , Transcriptoma , Hormonas Esteroides Gonadales/metabolismo
8.
Int Immunopharmacol ; 140: 112834, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39116495

RESUMEN

BACKGROUND: Atherosclerotic (AS) plaques require a dense necrotic core and a robust fibrous cap to maintain stability. While previous studies have indicated that the traditional Chinese medicine Huang Lian Jie Du Decoction (HLJDD) possesses the capability to stabilize AS plaques, the underlying mechanisms remain obscure. This study aims to delve deeper into the potential mechanisms by which HLJDD improves AS through an integrated research strategy. METHODS: Leveraging an AS model in ApoE-/- mice exposed to a high-fat diet (HFD), we scrutinized the therapeutic effects of HLJDD using microscopic observations, oil red O staining, HE staining and Masson staining. Employing comprehensive techniques of network pharmacology, bioinformatics, and molecular docking, we elucidated the mechanism by which HLJDD stabilizes AS plaques. In vitro experiments, utilizing ox-LDL-induced macrophages and apoptotic vascular smooth muscle cells (VSMCs), assessed the impact of HLJDD on efferocytosis and the role of SLC2A1. RESULTS: In vivo experiments showcased the efficacy of HLJDD in reducing the quantity of aortic plaques, diminishing lipid deposition, and enhancing plaque stability in AS mice. Employing network pharmacology and machine learning, we pinpointed SLC2A1 as a crucial regulatory target. Molecular docking further validated the binding of HLJDD components with SLC2A1. The experiments demonstrated a dose-dependent upregulation in SLC2A1 expression by HLJDD, amplifying efferocytosis. Importantly, this effect was reversed by the SLC2A1 inhibitor STF-31, highlighting the pivotal role of SLC2A1 as a target. CONCLUSION: The HLJDD can modulate macrophage efferocytosis by enhancing the expression levels of SLC2A1, thereby improving the stability of atherosclerotic plaques.


Asunto(s)
Medicamentos Herbarios Chinos , Transportador de Glucosa de Tipo 1 , Macrófagos , Placa Aterosclerótica , Animales , Placa Aterosclerótica/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Ratones , Masculino , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Transportador de Glucosa de Tipo 1/genética , Dieta Alta en Grasa , Ratones Endogámicos C57BL , Fagocitosis/efectos de los fármacos , Humanos , Simulación del Acoplamiento Molecular , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Modelos Animales de Enfermedad , Apoptosis/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Lipoproteínas LDL/metabolismo , Células RAW 264.7 , Ratones Noqueados para ApoE , Eferocitosis
9.
Int J Biol Macromol ; 277(Pt 4): 134459, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39111471

RESUMEN

Water stress, a significant abiotic stressor, significantly hampers crop growth and yield, posing threat to food security. Despite the promising potential of nanoparticles (NPs) in enhancing plant stress tolerance, the precise mechanisms underlying the alleviation of water stress using O-Carboxymethyl chitosan nanoparticles (O-CMC-NPs) in maize remain elusive. In this study, we synthesized O-CMC-NPs and delved into their capacity to mitigate water stress (waterlogging and drought) in maize seedlings. Structural characterization revealed spherical O-CMC-NPs with a size of approximately 200 nm. These NPs accumulated near the seed embryo and root tip, resulting in a substantial increase in fresh and dry weights. The application of O-CMC-NPs to water-stressed maize seedlings remarkedly elevated the chlorophyll content and activity of various antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and polyphenol oxidase (PPO). The malondialdehyde (MDA) content was significantly reduced compared to the untreated control. Additionally, the expression of stress-responsive genes, such as ZmSOD, ZmCAT, ZmPOD, ZmTIFY, ZmACO, ZmPYL2, ZmNF-YC12, and ZmEREB180, were significantly upregulated in the O-CMC-NPs treated seedlings. These findings unveil the novel role of O-CMC-NPs in enhancing plant stress tolerance, suggesting their potential application in safeguarding maize seedlings under water stress conditions and facilitating the recovery from oxidative damage.


Asunto(s)
Quitosano , Nanopartículas , Plantones , Zea mays , Zea mays/efectos de los fármacos , Zea mays/metabolismo , Quitosano/análogos & derivados , Quitosano/química , Quitosano/farmacología , Nanopartículas/química , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Plantones/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Agua/química , Antioxidantes/metabolismo , Estrés Fisiológico/efectos de los fármacos , Deshidratación , Proteínas de Plantas/metabolismo , Clorofila/metabolismo , Malondialdehído/metabolismo
13.
Adv Healthc Mater ; : e2401675, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177146

RESUMEN

Aluminum adjuvants remain the most commonly used vaccine adjuvants. Being rather effective in triggering humoral immunity, however, aluminum adjuvants usually show limited abilities in activating cellular immunities. Herein, by adding manganese ions during the preparation of aluminum adjuvant, a manganese-modified aluminum (Mn-Al) adjuvant is obtained, which can effectively stimulate both humoral and cellular immune responses. Such Mn-Al adjuvant can enhance antigen adsorption and promote antigen internalization by dendritic cells (DCs). Subsequently, the released Mn2+ can activate the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway to further promote DC activation. When combines with the model antigen ovalbumin (OVA), the Mn-Al-adjuvantes vaccine can induce high levels of antigen-specific antibody titers and high proportions of antigen-specific cytotoxic T cells in vivo. Moreover, the Mn-Al-adjuvanted vaccine elicited stronger antigen-specific humoral and cellular immune responses than high-dose of the aluminum-based adjuvant. Additionally, immunization of mice with OVA in the presence of the Mn-Al adjuvant significantly inhibited the growth of B16-OVA tumors. Furthermore, when formulated with human papillomavirus antigens, Mn-Al-adjuvanted vaccines show better in vivo vaccination performance than aluminum-adjuvanted vaccines. Therefore, the manganese-modified aluminum adjuvant may thus become a new vaccine adjuvant with the potential to replace conventional aluminum adjuvants.

14.
Int Immunopharmacol ; 141: 112890, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39137627

RESUMEN

BACKGROUND: Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. QingRe HuoXue Formula (QRHXF), a common prescription of traditional Chinese medicine, has a definite effect on the clinical treatment of AS, but its mechanism remains to be further explored. PURPOSE: The current study aimed to demonstrate the effectiveness of the QRHXF in the treatment of AS and further reveal its potential pharmacological mechanisms. METHODS: Explore the potential mechanisms of QRHXF in treating AS through network pharmacology, machine learning, transcriptome analysis, and molecular docking, then validate them through animal experiments and PCR experiments. RESULTS: The results indicate that through network pharmacology and machine learning methods, 10 genes including COL1A1 and CCR7 have been identified as potential candidate genes for QRHXF treatment of atherosclerosis. Molecular docking indicates that the key active compounds of QRHXF have good binding affinity with the predicted genes. Two key genes, COL1A1 and CCR7, were identified through transcriptome sequencing analysis of the aortic tissue of APOE-/- mice in the AS model. Finally, the animal and PCR experiment found that QRHXF can effectively reduce the formation of aortic plaques in APOE-/- mice of the AS model, lower blood lipid levels in mice, and upregulate the mRNA expression level of COL1A1, promoting the formation of fibrosis within plaques. CONCLUSIONS: We revealed the inflammatory and immune pathways underlying QRHXF treatment for AS, and verified through transcriptome sequencing and experiments that QRHXF can promote the expression of COL1A1, thereby increasing the stability of AS plaques.


Asunto(s)
Aterosclerosis , Cadena alfa 1 del Colágeno Tipo I , Biología Computacional , Medicamentos Herbarios Chinos , Aprendizaje Automático , Simulación del Acoplamiento Molecular , Animales , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/genética , Biología Computacional/métodos , Ratones , Humanos , Masculino , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Placa Aterosclerótica/tratamiento farmacológico
15.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(8): 673-680, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39215665

RESUMEN

Objective To investigate the effects and underlying mechanisms of tetratricopeptide repeat domain 36 (TTC36) on injury of HK2 renal tubular epithelial cell. Methods HK2 stable cell lines expressing either TTC36 and an empty vector control-CMV-Flag were generated with lentivirus . The mRNA expression level of tumor necrosis factor α (TNF-α), inducible nitric oxide synthase(iNOS), interleukin 6(IL-6), C-C motif chemokine ligand 2(CCL2), IL-1ß, inhibitor of nuclear factor κB α(IκBα) and nuclear factor κB p65(NF-κB p65) were analyzed by real time quantitative PCR (qRT-PCR). Flow cytometry was used to quantify cell apoptosis. Cell proliferation was evaluated by using cell counting kit-8(CCK-8) assay. The protein expression levels of iNOS, TNF-α, caspase-3, cleaved-caspase-3(c-caspase-3), Bcl2 associated X protein(BAX), proliferating cell nuclear antigen (PCNA), zonula occludens 1(ZO-1), IκBα, NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were determined by Western blot analysis. IκBα protein expression level was further analyzed by Western blot after being treated with cycloheximide (CHX) and MG132. Results Compared with the control group, the expression of inflammatory molecules were reduced after the overexpression of TTC36 in HK2 cells. TTC36 inhibited the apoptosis of HK2 cells, and the expression of apoptosis-related proteins c-caspase-3 and BAX were significantly decreased in the TTC36 overexpression group. Upregulation of TTC36 promoted cell proliferation and strengthened the expressions of PCNA and ZO-1. Meanwhile, the expression of IκBα was significantly increased, while that of NF-κB p65 and p-NF-κB p65 was markedly downregulated. Furthermore, TTC36 overexpression substantially prolonged the half-life of IκBα in HK2 cells after being treated with CHX. MG132 could restore the changes of IκBα caused by overexpression of TTC36. Conclusion Overexpression of TTC36 inhibits the inflammatory response of HK2 cells, reduces cell apoptosis, promotes proliferation, and strengthens tight junctions. The mechanism may be to inhibit the activation of NF-κB signaling pathway by enhancing the expression of IκBα, thereby reducing the cell damage caused by inflammatory response.


Asunto(s)
Apoptosis , Proliferación Celular , Inhibidor NF-kappaB alfa , FN-kappa B , Transducción de Señal , Humanos , Transducción de Señal/efectos de los fármacos , Inhibidor NF-kappaB alfa/metabolismo , Inhibidor NF-kappaB alfa/genética , FN-kappa B/metabolismo , FN-kappa B/genética , Apoptosis/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Inflamación/genética , Inflamación/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Transcripción ReIA/metabolismo , Factor de Transcripción ReIA/genética , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Túbulos Renales/metabolismo , Túbulos Renales/citología
17.
Sci China Life Sci ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39190128

RESUMEN

Understanding the maintenance and shift in reproductive strategies is a fundamental question in evolutionary research. Although many efforts have been made to compare different reproductive strategies, the association between reproductive strategies and lineage divergence is largely unknown. To explore the impact of different reproductive strategies on lineage divergence, we investigated the evolution of clonality in Saxifraga sect. Irregulares+Heterisia. By integrating several lines of evidence, we found that the loss of clonality in Irregulares+Heterisia was associated with a progressive increase in diversification rate and intraspecific morphological diversity but with a reduction in species distribution range. Our findings provide insights into the ecological and evolutionary effects of different reproductive strategies, suggesting the necessity of integrating clonality into ecological and evolutional research.

18.
Curr Med Imaging ; 20: e15734056307179, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39051582

RESUMEN

OBJECTIVE: The purpose of this study was to compare the image quality of different MRI sequences regarding the presentation of Dermatofibrosarcoma Protuberans (DFSP). MATERIALS AND METHODS: We retrospectively collected MRI images of 40 patients who had been pathologically diagnosed with DFSP, including 21 primary tumors and 19 recurrent tumors. The image quality of different MRI sequences was assessed subjectively by two radiologists, taking into account the display of the lesions, artifacts, and distortions, as well as the overall impact of the image quality. RESULTS: Among the 40 cases, 22 cases involved the trunk, 14 cases involved the shoulders and limbs, 2 cases involved the head and neck, 1 case involved the breast, and 1 case involved the groin. In terms of image quality, fat suppression T2-weighted images were superior to T1-weighted images and T2-weighted images (P<0.05). The difference between fat suppression T2-weighted images and contrast-enhanced images was not significant (P>0.05). As far as lesion contrast is concerned, diffusion-weighted images, fat suppression T2-weighted images, and contrast-enhanced images did not differ significantly (P>0.05). On the DWI images, there were severe magnetic artifacts and deformations. CONCLUSIONS: Fat suppression T2-weighted images and enhanced sequences produce the highest quality images, while diffusion-weighted images provide the best lesion contrast.


Asunto(s)
Dermatofibrosarcoma , Imagen por Resonancia Magnética , Neoplasias Cutáneas , Humanos , Dermatofibrosarcoma/diagnóstico por imagen , Femenino , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico por imagen , Anciano , Adolescente , Adulto Joven , Niño , Artefactos , Medios de Contraste
19.
Nano Lett ; 24(28): 8587-8594, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38967395

RESUMEN

Single-unit cell (1 UC) FeSe interfaced with TiOx or FeOx exhibits significantly enhanced superconductivity compared to that of bulk FeSe, with interfacial electron-phonon coupling (EPC) playing a crucial role. However, the reduced dimensionality in 1 UC FeSe, which may drive superconducting fluctuations, complicates our understanding of the enhancement mechanisms. We construct a new superconducting interface, 1 UC FeSe/SrVO3/SrTiO3. Here, the itinerant electrons of highly metallic SrVO3 films can screen all high-energy Fuchs-Kliewer phonons, including those of SrTiO3, making it the first FeSe/oxide system with screened interfacial EPC while maintaining the 1 UC FeSe thickness. Despite comparable doping levels, the heavily electron-doped 1 UC FeSe/SrVO3 exhibits a pairing temperature (Tg ∼ 48 K) lower than those of FeSe/SrTiO3 and FeSe/LaFeO3. Our findings disentangle the contributions of interfacial EPC from dimensionality in terms of enhancing Tg in FeSe/oxide interfaces, underscoring the critical importance of interfacial EPC. This FeSe/VOx interface also provides a platform for studying interfacial superconductivity.

20.
Exp Dermatol ; 33(8): e15121, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39081004

RESUMEN

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma characterized by the COL1A1-PDGFB fusion gene. This study utilized single-cell RNA sequencing to dissect the cellular and molecular landscape of primary DFSP. Distinct DFSP cell clusters, exhibiting fibroblast-like traits, revealed variations in pathways associated with proliferation, inflammation and metabolism. Differential gene expression analysis during the differentiation from tumour stem cells to DFSP cells unveiled SMOC2, DCN and TGFBR3 as potential regulators of tumour invasion and immune infiltration through VEGF/TGF-ß signalling modulation. Cellular communication analysis highlighted interactions within DFSP cell clusters and with endothelial cells, implicating molecules such as NAMPT, ANGPT2 and PTN in pathogenesis and treatment resistance. These findings offer insights into DFSP intratumour heterogeneity, elucidate molecular mechanisms underlying tumour behaviour, and suggest potential therapeutic targets.


Asunto(s)
Dermatofibrosarcoma , Análisis de la Célula Individual , Neoplasias Cutáneas , Dermatofibrosarcoma/genética , Dermatofibrosarcoma/patología , Dermatofibrosarcoma/metabolismo , Humanos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Análisis de Secuencia de ARN , Comunicación Celular/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Transducción de Señal , Diferenciación Celular , RNA-Seq , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteoglicanos , Receptores de Factores de Crecimiento Transformadores beta
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