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1.
Sci Rep ; 14(1): 11026, 2024 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744903

RESUMEN

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02-1.09), vascular dementia (HR, 1.08; 95% CI 1.01-1.15), and non-Alzheimer's disease non-vascular dementia (HR, 1.09; 95% CI 1.03-1.14). No significant association was observed for Alzheimer's disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.


Asunto(s)
Bancos de Muestras Biológicas , Demencia , Composición Familiar , Humanos , Femenino , Masculino , Reino Unido/epidemiología , Demencia/epidemiología , Demencia/etiología , Persona de Mediana Edad , Anciano , Factores de Riesgo , Estudios Prospectivos , Incidencia , Modelos de Riesgos Proporcionales , Encéfalo/patología , Biobanco del Reino Unido
2.
Heliyon ; 10(8): e28916, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38655362

RESUMEN

Context: Shenyu Ningshen (SYNS) tablet is the first pure Chinese medicinal small compound preparation approved for clinical trials for the treatment of depression in China. Clinical experiments confirmed that the formulation had a significant Improvement effect against depression due to the deficiency of both qi and yin. It has been shown to exhibit noticeable anti-inflammatory effect in an animal model of depression. Our previous study showed that SYNS could effectively inhibit the inflammatory response in a depression model. Aim of the study: The purpose of this study was to investigate the protective effects of SYNS on neurons and explore whether the underlying mechanism was associated with A1s. Materials and methods: The depression model of solitary raising-chronic restraint stress (CRS) rats was established; body weight examination, sugar water preference test, open field test, and histological analysis were performed to preliminarily verify the efficacy of the formulation. Subsequently, neuronal nucleus (NeuN) and synaptic-associated proteins (MAP2 and PSD95) were labeled, and the protective effect of SYNS on hippocampal neurons was observed based on the fluorescence intensity of the above indicators. Western blotting, histological examination, and immunofluorescence were used to evaluate the inhibitory effects of SYNS on neuroinflammation and activation of A1s in CRS depression model. Results: SYNS improved behavioral indicators such as weight loss, pleasure loss, and reduced exercise volume in CRS rat model. SYNS restored the CRS-induced histopathological changes in the hippocampus. SYNS showed a certain degree of protective effect on synapses. Further, SYNS inhibited the activation of A1s by inhibiting neuroinflammatory factors in the hippocampus. Conclusion: Our results showed that SYNS had a certain degree of neuroprotective effect, which might be related to its inhibition of the inflammatory response and A1s.

3.
J Ethnopharmacol ; 328: 118056, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38490287

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Urinary tract infections (UTIs) are globally prevalent infectious diseases, predominantly caused by uropathogenic Escherichia coli (UPEC). The misuse of antibiotics has led to the emergence of several drug-resistant strains. Traditional Chinese Medicine (TCM) has its own advantages in the treatment of UTIs. HJ granules is a herbal formula used for the treatment of UTIs. However, its mechanism of action is not clear. AIM OF THE STUDY: The aim of this study was to investigate the therapeutic efficacy and mechanism of action of HJ granules in a rat model of UTI caused by Escherichia coli (E coli) CFT073. MATERIALS AND METHODS: SD rats were selected to establish a rat UTI model by injecting UPEC strain CFT073 into the bladder using the transurethral placement method. HJ granules were administered to rats after modelling and the efficacy of HJ granule was investigated by measuring urinary decanalogue, inflammatory factors in bladder tissue and pathological changes in the bladder after 3d of administration. Expression of sonic hedgehog (SHH), NOD-like receptor thermoprotein domain 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and activation of cysteinyl aspartate specific proteinase-1 (caspase-1) were detected by western blotting and immunofluorescence staining in rat bladder tissue. NLRP3, ASC and caspase-1, a cysteine-containing aspartic protein, were expressed and activated. RESULTS: The results showed that infection of rats with UPEC resulted in increased pH and erythrocytes in bladder irrigation fluid; increased expression of IL-1ß, IL-6 and SHH and decreased expression of IL-10 in bladder tissue; and significant upregulation of the expression of both SHH and NLRP3 inflammasom and significant activation of NLRP3 inflammasom. HJ granules significantly increased the concentration of IL-10 in the bladder, inhibited the expression of SHH and NLRP3 inflammasom in bladder tissue, and suppressed the activation of NLRP3 inflammasom, thereby reducing inflammatory lesions in bladder tissue. CONCLUSION: HJ granules may improve bladder injury and treat UTIs by inhibiting the expression and activation of NLRP3 inflammasom.


Asunto(s)
Infecciones por Escherichia coli , Infecciones Urinarias , Escherichia coli Uropatógena , Ratas , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Escherichia coli , Interleucina-10 , Proteínas Hedgehog , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/patología , Ratas Sprague-Dawley , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/patología , Caspasa 1/metabolismo
4.
Environ Sci Pollut Res Int ; 31(14): 20772-20791, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38393568

RESUMEN

Light is a basic requirement to drive carbon metabolism in plants and supports life on earth. Spectral quality greatly affects plant morphology, physiology, and metabolism of various biochemical pathways. Among visible light spectrum, red, blue, and green light wavelengths affect several mechanisms to contribute in plant growth and productivity. In addition, supplementation of red, blue, or green light with other wavelengths showed vivid effects on the plant biology. However, response of plants differs in different species and growing conditions. This review article provides a detailed view and interpretation of existing knowledge and clarifies underlying mechanisms that how red, blue, and green light spectra affect plant morpho-physiological, biochemical, and molecular parameters to make a significant contribution towards improved crop production, fruit quality, disease control, phytoremediation potential, and resource use efficiency.


Asunto(s)
Luz Verde , Plantas , Fenómenos Fisiológicos de las Plantas , Desarrollo de la Planta , Luz
6.
BMC Cardiovasc Disord ; 24(1): 63, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38254017

RESUMEN

BACKGROUND: To evaluate the changes of right ventricular (RV) myocardial perfusion and function in patients with hypertrophic cardiomyopathy (HCM) by myocardial contrast echocardiography (MCE) and speckle tracking (2D-STE), and to explore the relationship between RV myocardial perfusion and strain. METHODS: Conventional ultrasound, MCE and 2D-STE were performed on 29 HCM patients and 21 healthy subjects to analyze RV myocardial perfusion, RV global strain, RV free wall strain, and strain of each segment. The correlation between RV myocardial perfusion and strain was further analyzed in HCM patients. RESULTS: MCE results showed that the regional myocardial perfusion of the RV in HCM patients was decreased. Compared with the normal control group, the mean slope (ß) in the middle and apical segments of the RV free wall, and the peak intensity (A), ß, myocardial blood flow (MBF) of the ventricular septum decreased in HCM patients (P < 0.05). RV function was impaired in HCM patients. The RV global strain (RV GLS), and the strain of RV free wall and each segment were lower than those in the normal control group (P < 0.05). Correlation analysis showed that there was a certain correlation between RV myocardial perfusion and strain, such as the ß of the whole RV in HCM group had a positive correlation with the strain of the middle segment of the interventricular septum (r = 0.550, P = 0.002). CONCLUSIONS: The regional myocardial perfusion and strain of the RV in HCM patients are reduced, and there is a positive correlation between them, suggesting that the reduction of myocardial strain may be related to the impairment of myocardial microcirculation.


Asunto(s)
Cardiomiopatía Hipertrófica , Humanos , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Miocardio , Perfusión , Ultrasonografía , Ventrículos Cardíacos/diagnóstico por imagen
7.
J Ethnopharmacol ; 324: 117741, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38224794

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Zhisou Powder (ZSP), a traditional Chinese medicine (TCM) prescription, has been widely used in the clinic for the treatment of post-infectious cough (PIC). However, the exact mechanism is not clear. AIM OF THE STUDY: The aim of this study was to investigate the ameliorative effect of ZSP on PIC in mice. The possible mechanisms of action were screened based on network pharmacology, and the potential mechanisms were explored through molecular docking and in vivo experimental validation. MATERIALS AND METHODS: Lipopolysaccharide (LPS) (80µg/50 µL) was used to induce PIC in mice, followed by daily exposure to cigarette smoke (CS) for 30 min for 30 d to establish PIC model. The effects of ZSP on PIC mice were observed by detecting the number of coughs and cough latency, peripheral blood and bronchoalveolar lavage fluid (BALF) inflammatory cell counts, enzyme-linked immunosorbent assay (ELISA), and histological analysis. The core targets and key pathways of ZSP on PIC were analyzed using network pharmacology, and TRPA1 and TRPV1 were validated using RT-qPCR and western blotting assays. RESULTS: ZSP effectively reduced the number of coughs and prolonged the cough latency in PIC mice. Airway inflammation was alleviated by reducing the expression levels of the inflammatory mediators TNF-α and IL-1ß. ZSP modulated the expression of Substance P, Calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) in BALF. Based on the results of network pharmacology, the mechanism of action of ZSP may exert anti-neurogenic airway-derived inflammation by regulating the expression of TRPA1 and TRPV1 through the natural active ingredients α-spinastero, shionone and didehydrotuberostemonine. CONCLUSION: ZSP exerts anti-airway inflammatory effects through inhibition of TRPA1/TRPV1 channels regulating neuropeptides to alleviate cough hypersensitivity and has a favorable therapeutic effect on PIC model mice. It provides theoretical evidence for the clinical application of ZSP.


Asunto(s)
Lipopolisacáridos , Canales Catiónicos TRPV , Ratones , Animales , Canal Catiónico TRPA1/metabolismo , Lipopolisacáridos/toxicidad , Polvos/uso terapéutico , Simulación del Acoplamiento Molecular , Canales Catiónicos TRPV/metabolismo , Tos/inducido químicamente , Tos/tratamiento farmacológico , Tos/metabolismo , Inflamación/patología , Antiinflamatorios/efectos adversos
8.
Nat Prod Res ; 38(6): 933-940, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37144394

RESUMEN

Previous studies on Ranunculus sceleratus L. have shown the existence of coumarins and their anti-inflammatory effect. Phytochemical work was conducted to investigate the bioactive compounds, leading to the isolation of two undescribed benzopyran derivatives, namely ranunsceleroside A (1) and B (3), together with two known coumarins (2, 4) from the whole plant of R. sceleratus L. All compounds were structurally identified by extensive spectroscopic analysis and then investigated for their inhibitory effect on nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) production induced by lipopolysaccharide (LPS) in RAW 264.7 murine macrophages, repectively. As a result, compound 1-4 presented inhibitory effects on the production of NO, TNF-α, IL-1ß, and IL-6 in a concentration-dependent manner, which provides a potential chemical basis for the traditional use of R. sceleratus L. as an anti-inflammatory plant.


Asunto(s)
Benzopiranos , Ranunculus , Animales , Ratones , Benzopiranos/farmacología , Células RAW 264.7 , Lipopolisacáridos/farmacología , Interleucina-6 , Factor de Necrosis Tumoral alfa , Cumarinas/farmacología , Antiinflamatorios/farmacología , Interleucina-1beta , Óxido Nítrico
9.
Ann Rheum Dis ; 83(1): 72-87, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-37775153

RESUMEN

OBJECTIVES: To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss. METHODS: L-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by µCT and histomorphometry. In vitro, effects of L-arginine on osteoclast differentiation were analysed by RNA-seq and mass spectrometry (MS). Seahorse, Single Cell ENergetIc metabolism by profilIng Translation inHibition and transmission electron microscopy were used for detecting metabolic changes in osteoclasts. Moreover, arginine-associated metabolites were measured in the serum of rheumatoid arthritis (RA) and pre-RA patients. RESULTS: L-arginine inhibited arthritis and bone loss in all three models and directly blocked TNFα-induced murine and human osteoclastogenesis. RNA-seq and MS analyses indicated that L-arginine switched glycolysis to oxidative phosphorylation in inflammatory osteoclasts leading to increased ATP production, purine metabolism and elevated inosine and hypoxanthine levels. Adenosine deaminase inhibitors blocking inosine and hypoxanthine production abolished the inhibition of L-arginine on osteoclastogenesis in vitro and in vivo. Altered arginine levels were also found in RA and pre-RA patients. CONCLUSION: Our study demonstrated that L-arginine ameliorates arthritis and bone erosion through metabolic reprogramming and perturbation of purine metabolism in osteoclasts.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Resorción Ósea , Humanos , Ratones , Animales , Osteoclastos , Artritis Reumatoide/patología , Artritis Experimental/patología , Inflamación/metabolismo , Ratones Transgénicos , Arginina/farmacología , Inosina/metabolismo , Inosina/farmacología , Hipoxantinas/metabolismo , Hipoxantinas/farmacología , Purinas/farmacología
11.
Heliyon ; 9(11): e21829, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38045126

RESUMEN

This literature review will summarize the liability issues, risks, and ultrasound recommendations for diagnosing obstetrics diseases. One liability issue is related to misdiagnosis or failure to detect abnormalities during an ultrasound examination. Ultrasound images can be subjective interpretations, and errors may occur due to factors such as operator skill, equipment limitations, or fetal positioning. Another liability concern is related to the potential adverse effects of ultrasound exposure on both the mother and fetus. While extensive research has shown that diagnostic ultrasound is generally safe when used appropriately, there are still uncertainties regarding long-term effects. Some studies suggest a possible association between prolonged or excessive exposure to ultrasound waves and adverse outcomes such as low birth weight, developmental delays, or hearing impairment. Additionally, obtaining informed consent from patients is crucial in mitigating liability risks. Patients should be informed about the purpose of the ultrasound examination, its benefits, limitations, potential risks (even if minimal), and any alternative diagnostic options available. This ensures that patients know the procedure and can make informed decisions about their healthcare. Proper documentation helps establish a clear record of the care provided and can serve as evidence in any legal disputes.

13.
Front Immunol ; 14: 1249878, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37781385

RESUMEN

Background: Disseminated tuberculosis is an uncommon but devastating form of tuberculosis, possibly developing with the immune response of patients. COVID-19 infection may produce an immunosuppressive effect with possible implications for tuberculosis dissemination. Case presentation: A 17-year-old female patient with a history of tuberculous pleurisy presented to the hospital with a high fever and life-threatening dyspnea after contracting a COVID-19 infection. Her condition deteriorated rapidly with grand mal epilepsy and acute gastrointestinal bleeding with a grossly depressed CD4 T-cell count, which was indicative of her profoundly immunosuppressed state. After identifying Mycobacterium tuberculosis in her cerebrospinal fluid and a subcutaneous abscess in her left lower back, she was diagnosed with disseminated tuberculosis involving both lungs, the central nervous system, the terminal ileum, the liver, bilateral adnexal tissue, and subcutaneous soft tissue in accordance with the chest and abdominal CT. Empirical treatment was initiated with dexamethasone (5 mg/day) and an anti-tuberculosis regimen of isoniazid, rifampicin, pyrazinamide, amikacin, and meropenem, which was replaced with faropenem after she left the hospital. The therapeutic effect was considered satisfied in the second month of follow-up. Conclusion: To the best of our knowledge, we report the first case report of disseminated tuberculosis after COVID-19 infection. Tuberculosis may disseminate and progress during the COVID-19 pandemic, requiring more significant studies to provide better diagnosis and treatment options for the co-infection.


Asunto(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis Pleural , Humanos , Niño , Femenino , Adolescente , Pandemias , Isoniazida/uso terapéutico
14.
Medicine (Baltimore) ; 102(42): e35129, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37861561

RESUMEN

BACKGROUND: Acute ischemic stroke (AIS) is characterized by high morbidity, disability, mortality, recurrence, and economic burden. Clinical trials have demonstrated that the clinical efficacy of combining oral Chinese patent medicines (CPMs) with chemical drugs (CDs) is better than that of CDs alone. In this study, we performed a network meta-analysis (NMA) of RCTs to assess the efficacy of different CPMs in combination with CDs in the treatment of AIS. METHODS: Search 6 databases from the beginning to January 10, 2023. The Cochrane Risk of Bias tool assessed the methodological quality of the included studies. The NMA was then performed using the STATA 13.0 program. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the studied treatments, and cluster analysis was used to compare the effects of CPMs between 2 different outcomes. RESULTS: A total of 94 eligible RCTs, involving 9581 participants, were included in this analysis. Nine CPMs, including Nao-mai-li granule (NML), Nao-mai-tai granule (NMT), Qi-long granule (QL), Long-sheng-zhi capsule (LSZ), Nao-xin-tong capsule (NXT), Nao-xue-shu oral liquid (NXS), Tong-xin-luo capsule (TXL), Xiao-shuan-chang-rong capsule (XSCR), and Xue-shuan-xin-mai-ning capsule (XSXMN) were included. Regarding the clinical effective rate, all types of CPMs + CDs treatments were significantly better than CDs treatments alone, with significant differences among the 9 selected CPMs. Compared with CDs, results showed that NXS + CDs performed best in improving clinical effective rate [OR = 4.73; 95% CI: 1.26-17.78; (SUCRA: 76.1%)]. TXL + CDs showed the most effective effect in alleviating National Institutes of Health Stroke Scale (NIHSS) [MD = -3.84; 95% CI: -5.23, -2.45; (SUCRA: 81.6%)]; NXT + CDs were most effective in improving Barthel index [MD = 13.05; 95% CI: 3.98-22.12; (SUCRA: 63.5%)]. Combined with other outcome indicators and the results of cluster analysis, NXS + CDs may assist in the potential optimal treatment regimen for AIS. CONCLUSION: In conclusion, CPMs were found to be beneficial as adjuvant therapy in patients with AIS. Taking into account the clinical effective rate and other outcomes, NXS + CDs may be the most effective option to improve the condition of AIS patients.


Asunto(s)
Accidente Cerebrovascular Isquémico , Humanos , Metaanálisis en Red , Medicamentos sin Prescripción , Resultado del Tratamiento
15.
Environ Sci Pollut Res Int ; 30(55): 117892-117908, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37874516

RESUMEN

Modified nanoscale zero-valent iron (NZVI) exhibited great potential for the remediation of heavy metal contaminated river sediments, but its mechanisms and environmental risks are still unclear. This study systematically discussed the performance and the mechanisms of modified NZVI materials, i.e., sodium alginate-coated NZVI (SNZVI), rhamnolipid-coated NZVI (RNZVI), and graphene oxide-loaded NZVI (GNZVI), for the stabilization of Cd in sediment, with the exploration of their stability to Cd at various pH values and Fe dissolution rate. Compared with the control, the toxicity characteristic leaching procedure (TCLP) leachable Cd decreased by 52.66-96.28%, and the physiologically based extraction test (PBET) extractable Cd decreased by 44.68-70.21% after 56 days of incubation with the immobilization efficiency varying according to GNZVI > RNZVI > SNZVI > NZVI. Besides, the adsorption behavior of Cd on materials was fitted with the Freundlich model and classified as an endothermic, spontaneous, and chemical adsorption process. SEM-EDX, XRD, and FTIR results verified that the stabilization mechanisms of Cd were principally based on the adsorption, complexation of Cd2+ with secondary Fe minerals (including Fe2O3, γ-Fe2O3, and γ-FeOOH) and precipitation (Cd(OH)2). From the risk assessment results, it was observed that the materials were favorable for Cd stabilization at a pH range from 7 to 11, meanwhile, the leaching concentration of Fe in the overlying water was detected below the limit value. These findings pave the way to developing an effective strategy to remediate Cd contaminated river sediments.


Asunto(s)
Restauración y Remediación Ambiental , Metales Pesados , Contaminantes Químicos del Agua , Hierro , Cadmio , Ríos , Adsorción
16.
Open Med (Wars) ; 18(1): 20230797, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37771422

RESUMEN

Recent studies revealed that endoplasmic reticulum (ER) stress played an emerging role of in valve calcification. Tanshinone IIA (TanIIA) has been a research hotspot in cardiovascular diseases. Previously we found that sodium TanIIA dampened the pathological phenotype transition of valvular interstitial cells (VICs) by affecting ER stress published in Chinese Journal. Here, we test the hypothesis that TanIIA attenuates the pro-osteogenic effects of oxidized low-density lipoprotein (oxLDL) in VICs by reducing induction of ER stress. Patients' aortic valve (AV) was collected, and porcine VICs were cultured for in vitro model. ER stress markers were tested in human leaflets by immunostaining. Immunoblotting were used to test the osteoblastic factors such as Runx2, osteocalcin, and ER stress markers GRP78, CHOP, XBP1, etc. Alkakine phosphate (ALP) activity assay were used to test the activity of ALP kinase. Pro-inflammatory gene expression was detected by polymerase chain reaction. As a result, ER stress markers were elevated in patients' calcified AVs. OxLDL induced osteogenesis and inflammation via promoting ER stress. TanIIA attenuated oxLDL induced ER stress. TanIIA also inhibited theosteoblastic factors and inflammatory cytokine expressions in VICs. In conclusion, our data provide evidence that TanIIA exerts anti-inflammation and anti-osteogenic effects in VICs by attenuating ER stress, and ER stress acts as an important regulator in oxLDL induced VICs' phenotype transition.

17.
Arthritis Res Ther ; 25(1): 151, 2023 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-37596660

RESUMEN

BACKGROUND: The early growth response 1 (EGR1) is a central transcription factor involved in systemic sclerosis (SSc) pathogenesis. Iguratimod is a synthesized anti-rheumatic disease-modifying drug, which shows drastic inhibition to EGR1 expression in B cells. This study is aiming to investigate the anti-fibrotic effect of iguratimod in SSc. METHODS: EGR1 was detected by immunofluorescence staining real-time PCR or western blot. Iguratimod was applied in EGR1 overexpressed or knockdown human dermal fibroblast, bleomycin pre-treated mice, tight skin 1 mice, and SSc skin xenografts. RNA sequencing was performed in cultured fibroblast and xenografts to identify the iguratimod regulated genes. RESULTS: EGR1 overexpressed predominantly in non-immune cells of SSc patients. Iguratimod reduced EGR1 expression in fibroblasts and neutralized changes of EGR1 response genes regulated by TGFß. The extracellular matrix (ECM) production and activation of fibroblasts were attenuated by iguratimod while EGR1 overexpression reversed this effect of iguratimod. Iguratimod ameliorated the skin fibrosis induced by bleomycin and hypodermal fibrosis in TSK-1 mice. Decreasing in the collagen content as well as the density of EGR1 or TGFß positive fibroblasts of skin xenografts from naïve SSc patients was observed after local treatment of iguratimod. CONCLUSION: Targeting EGR1 expression is a probable underlying mechanism for the anti-fibrotic effect of iguratimod.


Asunto(s)
Antirreumáticos , Proteína 1 de la Respuesta de Crecimiento Precoz , Esclerodermia Sistémica , Animales , Humanos , Ratones , Bleomicina/toxicidad , Cromonas , Fibrosis , Esclerodermia Sistémica/tratamiento farmacológico , Proteína 1 de la Respuesta de Crecimiento Precoz/efectos de los fármacos , Proteína 1 de la Respuesta de Crecimiento Precoz/genética
18.
Adv Mater ; 35(47): e2303165, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37493625

RESUMEN

The development of flexible lithium-ion batteries (LIBs) imposes demands on energy density and high mechanical durability simultaneously. Due to the limited deformability of electrodes, as well as the flat and smooth surface of the metal current collectors, stable/durable/reliable contact between electrode materials and the current collectors remains a challenge, in particular, for electrodes with high loading mass and heavily deformed batteries. Binders play an essential role in binding particles of electrode materials and adhering them to current collectors. Herein, inspired by spider silk, a binder for flexible LIBs is developed, which equips a cross-linked supramolecular poly(urethane-urea) to the polyacrylic acid. The binder imparts super high elastic restorability originating from the meticulously engineered hydrogen-bonding segments as well as extraordinary adhesion. The developed binder provides excellent flexibility and intact electrode morphologies without disintegration even when the electrode is largely deformed, enabling a stable cycling and voltage output even when the batteries are put under tough dynamic deformation tests. The flexible LIBs exhibit a high energy density of 420 Wh L-1 , which is remarkably higher than reported numbers. The unique binder design is greatly promising and offers a valuable material solution for LIBs with high-loading mass and flexible designs.

19.
J Adv Res ; 2023 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-37499939

RESUMEN

INTRODUCTION: Vascular neointimal hyperplasia, a pathological process observed in cardiovascular diseases such as atherosclerosis and pulmonary hypertension, involves the abundant presence of vascular smooth muscle cells (VSMCs). The proliferation, migration, and autophagy of VSMCs are associated with the development of neointimal lesions. Circular RNAs (circRNAs) play critical roles in regulating VSMC proliferation and migration, thereby participating in neointimal hyperplasia. However, the regulatory roles of circRNAs in VSMC autophagy remain unclear. OBJECTIVES: We aimed to identify circRNAs that are involved in VSMC autophagy-mediated neointimal hyperplasia, as well as elucidate the underlying mechanisms. METHODS: Dual-luciferase reporter gene assay was performed to validate two competing endogenous RNA axes, hsa_circ_0001402/miR-183-5p/FKBP prolyl isomerase like (FKBPL) and hsa_circ_0001402/miR-183-5p/beclin 1 (BECN1). Cell proliferation and migration analyses were employed to investigate the effects of hsa_circ_0001402, miR-183-5p, or FKBPL on VSMC proliferation and migration. Cell autophagy analysis was conducted to reveal the role of hsa_circ_0001402 or miR-183-5p on VSMC autophagy. The role of hsa_circ_0001402 or miR-183-5p on neointimal hyperplasia was evaluated using a mouse model of common carotid artery ligation. RESULTS: Hsa_circ_0001402 acted as a sponge for miR-183-5p, leading to the suppression of miR-183-5p expression. Through direct interaction with the coding sequence (CDS) of FKBPL, miR-183-5p promoted VSMC proliferation and migration by decreasing FKBPL levels. Besides, miR-183-5p reduced BECN1 levels by targeting the 3'-untranslated region (UTR) of BECN1, thus inhibiting VSMC autophagy. By acting as a miR-183-5p sponge, overexpression of hsa_circ_0001402 increased FKBPL levels to inhibit VSMC proliferation and migration, while simultaneously elevating BECN1 levels to activate VSMC autophagy, thereby alleviating neointimal hyperplasia. CONCLUSION: Hsa_circ_0001402, acting as a miR-183-5p sponge, increases FKBPL levels to inhibit VSMC proliferation and migration, while enhancing BECN1 levels to activate VSMC autophagy, thus alleviating neointimal hyperplasia. The hsa_circ_0001402/miR-183-5p/FKBPL axis and hsa_circ_0001402/miR-183-5p/BECN1 axis may offer potential therapeutic targets for neointimal hyperplasia.

20.
Medicine (Baltimore) ; 102(27): e34162, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37417628

RESUMEN

PURPOSE: Clinical efficacy of Fuke Qianjin tablets combined with clomiphene citrate on infertility patients with polycystic ovary syndrome (PCOS) was expected to be retrospectively analyzed in this study. METHODS: In this paper, 100 infertility patients with PCOS were selected and divided into the observation and control groups based on different medications. Firstly, clinical data of both groups of patients were acquired. Then, the uterine receptivity and ovarian status, the levels of sex hormones, inflammation and oxidative stress, and the pregnancy outcomes between the 2 groups were compared and analyzed before and after treatment. RESULTS: After a variety of comparisons and analyses, Fuke Qianjin tablets combined with clomiphene citrate were confirmed to improve the uterine receptivity and ovarian status, levels of sex hormone, inflammation and oxidative stress, and pregnancy outcomes in infertility patients with PCOS. CONCLUSIONS: Overall, Fuke Qianjin tablets + clomiphene citrate treatment shows good clinical efficacy and is worth promotion in clinical practice.


Asunto(s)
Infertilidad Femenina , Síndrome del Ovario Poliquístico , Embarazo , Femenino , Humanos , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Estudios Retrospectivos , Inducción de la Ovulación , Clomifeno/uso terapéutico , Infertilidad Femenina/tratamiento farmacológico , Infertilidad Femenina/etiología , Inflamación/tratamiento farmacológico , Comprimidos , Fármacos para la Fertilidad Femenina/uso terapéutico
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