Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 403
Filtrar
1.
J Int Med Res ; 52(4): 3000605241239856, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38656269

RESUMO

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn's disease and thyroid diseases. Graves' disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.


Assuntos
Anticorpos Monoclonais Humanizados , Doença de Graves , Psoríase , Humanos , Psoríase/tratamento farmacológico , Psoríase/complicações , Psoríase/patologia , Feminino , Adulto , Doença de Graves/tratamento farmacológico , Doença de Graves/complicações , Anticorpos Monoclonais Humanizados/uso terapêutico , Resultado do Tratamento
2.
J Int Med Res ; 52(4): 3000605241238141, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38565321

RESUMO

In recent years, radiomics has emerged as a novel research methodology that plays a crucial role in the diagnosis and treatment of ischemic stroke. By integrating multimodal medical imaging techniques such as computed tomography and magnetic resonance imaging, radiomics offers in-depth insights into aspects such as the extent of brain tissue damage and hemodynamics. These data help physicians to accurately assess patient condition, select optimal treatment strategies, and predict recovery trajectories and long-term prognoses, thereby enhancing treatment efficacy and reducing the risk of complications. With the anticipated further advancements in radiomic technology, this methodology has great potential for expanded applications in the early detection, treatment, and prognosis of ischemic stroke. The present narrative review explores the burgeoning field of radiomics and its transformative impact on ischemic stroke.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/diagnóstico por imagem , 60570 , Prognóstico , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Acidente Vascular Cerebral/diagnóstico por imagem
3.
Elife ; 132024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573307

RESUMO

The perinuclear theca (PT) is a dense cytoplasmic web encapsulating the sperm nucleus. The physiological roles of PT in sperm biology and the clinical relevance of variants of PT proteins to male infertility are still largely unknown. We reveal that cylicin-1, a major constituent of the PT, is vital for male fertility in both mice and humans. Loss of cylicin-1 in mice leads to a high incidence of malformed sperm heads with acrosome detachment from the nucleus. Cylicin-1 interacts with itself, several other PT proteins, the inner acrosomal membrane (IAM) protein SPACA1, and the nuclear envelope (NE) protein FAM209 to form an 'IAM-cylicins-NE' sandwich structure, anchoring the acrosome to the nucleus. WES (whole exome sequencing) of more than 500 Chinese infertile men with sperm head deformities was performed and a CYLC1 variant was identified in 19 patients. Cylc1-mutant mice carrying this variant also exhibited sperm acrosome/head deformities and reduced fertility, indicating that this CYLC1 variant most likely affects human male reproduction. Furthermore, the outcomes of assisted reproduction were reported for patients harbouring the CYLC1 variant. Our findings demonstrate a critical role of cylicin-1 in the sperm acrosome-nucleus connection and suggest CYLC1 variants as potential risk factors for human male fertility.


Assuntos
Acrossomo , Infertilidade Masculina , Animais , Humanos , Masculino , Camundongos , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Infertilidade Masculina/genética , Proteínas de Membrana/genética , Sêmen , Cabeça do Espermatozoide , Espermatozoides
4.
J Matern Fetal Neonatal Med ; 37(1): 2338440, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38604949

RESUMO

BACKGROUND: Noninvasive prenatal testing (NIPT) is the most common method for prenatal aneuploidy screening. Low fetal fraction (LFF) is the primary reason for NIPT failure. Consequently, factors associated with LFF should be elucidated for optimal clinical implementation of NIPT. METHODS: In this study, NIPT data from January 2019 to December 2022 from the laboratory records and obstetrical and neonatal data from the electronic medical records were collected and analyzed. Subjects with FF >3.50% were assigned to the control group, subjects with FF <3.50% once were assigned to the LFF group, and subjects with FF <3.50% twice were assigned to the repetitive low fetal fraction (RLFF) group. Factors, including body mass index (BMI), gestational age, maternal age, twin pregnancy, and in vitro fertilization (IVF) known to be associated with LFF were assessed by Kruskal-Wallis H test and logistic regression. Clinical data on first trimester pregnancy-associated plasma protein-A (PAPP-A), beta-human chorionic gonadotropin (ß-hCG), gestational age at delivery, birth weight at delivery, and maternal diseases were obtained from the hospital's prenatal and neonatal screening systems (twin pregnancy was not included in the data on gestational age at delivery and the control group did not include data on maternal diseases.), and were analyzed using Kruskal-Wallis H test and Chi-square test. RESULTS: Among the total of 63,883 subjects, 63,605 subjects were assigned to the control group, 197 subjects were assigned to the LFF group, and 81 subjects were assigned to the RLFF group. The median of BMI in the three groups was 22.43 kg/m2 (control), 25.71 kg/m2 (LFF), and 24.54 kg/m2 (RLFF). The median gestational age in the three groups was 130 days (control), 126 days (LFF), and 122/133 days (RLFF). The median maternal age in the three groups was 29 (control), 29 (LFF), and 33-years-old (RLFF). The proportion of twin pregnancies in the three groups was 3.3% (control), 10.7% (LFF), and 11.7% (RLFF). The proportion of IVF in the three groups was 4.7% (control), 11.7% (LFF), and 21.3% (RLFF). The factors significantly associated with LFF included BMI [2.18, (1.94, 2.45), p < 0.0001], gestational age [0.76, (0.67, 0.87), p < 0.0001], twin pregnancy [1.62, (1.02, 2.52), p = 0.0353], and IVF [2.68, (1.82, 3.86), p < 0.0001]. The factors associated with RLFF included maternal age [1.54, (1.17, 2.05), p = 0.0023] and IVF [2.55, (1.19, 5.54), p = 0.016]. Multiples of the median (MOM) value of ß-hCG and pregnant persons' gestational age at delivery were significantly decreased in the LFF and RLFF groups compared to the control group. CONCLUSION: According to our findings based on the OR value, factors associated strongly with LFF include a high BMI and the use of IVF. Factors associated less strongly with LFF include early gestational age and twin pregnancy, while advanced maternal age and IVF were independent risk factors for a second LFF result.


Body mass index, gestational age, maternal age, twin pregnancy, and in vitro fertilization are associated with fetal fraction. We added the repetitive low fetal fraction population and used a large normal population as a control to identify the main factors associated with low fetal fraction.


Assuntos
Ácidos Nucleicos Livres , Teste Pré-Natal não Invasivo , Gravidez , Recém-Nascido , Feminino , Humanos , Gonadotropina Coriônica Humana Subunidade beta , Diagnóstico Pré-Natal/métodos , Primeiro Trimestre da Gravidez , DNA , Proteína Plasmática A Associada à Gravidez
5.
Int J Biol Sci ; 20(6): 2202-2218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617530

RESUMO

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The poor prognosis of this malignancy is attributed mainly to the persistent activation of cancer signaling for metastasis. Here, we showed that protein tyrosine phosphatase-like A domain containing 1 (PTPLAD1) is down-regulated in highly metastatic CRC cells and negatively associated with poor survival of CRC patients. Systematic analysis reveals that epithelial-to-mesenchymal transition (EMT) and mitochondrial fusion-to-fission (MFT) transition are two critical features for CRC patients with low expression of PTPLAD1. PTPLAD1 overexpression suppresses the metastasis of CRC in vivo and in vitro by inhibiting the Raf/ERK signaling-mediated EMT and mitofission. Mechanically, PTPLAD1 binds with PHB via its middle fragment (141-178 amino acids) and induces dephosphorylation of PHB-Y259 to disrupt the interaction of PHB-Raf, resulting in the inactivation of Raf/ERK signaling. Our results unveil a novel mechanism in which Raf/ERK signaling activated in metastatic CRC induces EMT and mitochondrial fission simultaneously, which can be suppressed by PTPLAD1. This finding may provide a new paradigm for developing more effective treatment strategies for CRC.


Assuntos
Aminoácidos , Neoplasias do Colo , Humanos , Transição Epitelial-Mesenquimal/genética , Dinâmica Mitocondrial , Proibitinas , Transdução de Sinais , Quinases raf
6.
PeerJ ; 12: e16887, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38436019

RESUMO

Groupitizing is a well-established strategy in numerosity perception that enhances speed and sensory precision. Building on the ATOM theory, Anobile proposed the sensorimotor numerosity system, which posits a strong link between number and action. Previous studies using motor adaptation technology have shown that high-frequency motor adaptation leads to underestimation of numerosity perception, while low-frequency adaptation leads to overestimation. However, the impact of motor adaptation on groupitizing, and whether visual motion adaptation produces similar effects, remain unclear. In this study, we investigate the persistence of the advantage of groupitizing after motor adaptation and explore the effects of visual motion adaptation. Surprisingly, our findings reveal that proprioceptive motor adaptation weakens the advantage of groupitizing, indicating a robust effect of motor adaptation even when groupitizing is employed. Moreover, we observe a bidirectional relationship, as groupitizing also weakens the adaptation effect. These results highlight the complex interplay between motor adaptation and groupitizing in numerosity perception. Furthermore, our study provides evidence that visual motion adaptation also has an adaptation effect, but does not fully replicate the effects of proprioceptive motor adaptation on groupitizing. In conclusion, our research underscores the importance of groupitizing as a valuable strategy in numerosity perception, and sheds light on the influence of motion adaptation on this strategy.


Assuntos
Propriocepção , Tecnologia , Movimento (Física) , Percepção
7.
Angew Chem Int Ed Engl ; 63(18): e202402369, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38446496

RESUMO

Solar-energy-driven photoreduction of CO2 is promising in alleviating environment burden, but suffers from low efficiency and over-reliance on sacrificial agents. Herein, rhenium (Re) is atomically dispersed in In2O3 to fabricate a 2Re-In2O3 photocatalyst. In sacrificial-agent-free photoreduction of CO2 with H2O, 2Re-In2O3 shows a long-term stable efficiency which is enhanced by 3.5 times than that of pure In2O3 and is also higher than those on Au-In2O3, Ag-In2O3, Cu-In2O3, Ir-In2O3, Ru-In2O3, Rh-In2O3 and Pt-In2O3 photocatalysts. Moreover, carbon-based product of the photoreduction overturns from CO on pure In2O3 to CH3OH on 2Re-In2O3. Re promotes charge separation, H2O dissociation and CO2 activation, thus enhancing photoreduction efficiency of CO2 on 2Re-In2O3. During the photoreduction, CO is a key intermediate. CO prefers to desorption rather than hydrogenation on pure In2O3, as CO binds to pure In2O3 very weakly. Re strengthens the interaction of CO with 2Re-In2O3 by 5.0 times, thus limiting CO desorption but enhancing CO hydrogenation to CH3OH. This could be the origin for photoreduction product overturn from CO on pure In2O3 to CH3OH on 2Re-In2O3. The present work opens a new way to boost sacrificial-agent-free photoreduction of CO2.

8.
Cytopathology ; 35(3): 398-403, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38441189

RESUMO

The cytomorphology of MPNST in effusion specimens is rarely described. In this paper, the detailed cytopathological and immunohistochemical characteristics of metastatic MPNST has been described in pleural effusion. Patients' medical history and the judicious utilization of ancillary studies contribute to ensure precise cytological diagnoses. The cytomorphology of malignant peripheral nerve sheath tumour (MPNST) in effusion specimens can be diagnostically challenging. The author presents detailed cytopathological and immunohistochemical characteristics of a case of metastatic MPNST in pleural effusion.


Assuntos
Segunda Neoplasia Primária , Neurofibrossarcoma , Derrame Pleural Maligno , Derrame Pleural , Humanos , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/patologia
9.
Ecotoxicol Environ Saf ; 275: 116230, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38552389

RESUMO

Epidemiological evidence on the health effects of pesticide exposure among greenhouse workers is limited, and the mechanisms are lacking. Building upon our team's previous population study, we selected two pesticides, CPF and EB, with high detection rates, based on the theoretical foundation that the liver serves as a detoxifying organ, we constructed a toxicity model using HepG2 cells to investigate the impact of individual or combined pesticide exposure on the hepatic metabolism profile, attempting to identify targeted biomarkers. Our results showed that CPF and EB could significantly affect the survival rate of HepG2 cells and disrupt their metabolic profile. There were 117 metabolites interfered by CPF exposure, which mainly affected ABC transporter, biosynthesis of amino acids, center carbon metabolism in cancer, fatty acid biosynthesis and other pathways, 95 metabolites interfered by EB exposure, which mainly affected center carbon metabolism in cancer, HIF-1 signaling pathway, valine, leucine and isoleucine biosynthesis, fatty acid biosynthesis and other pathways. The cross analysis and further biological experiments confirmed that CPF and EB pesticide exposure may affect the HIF-1 signaling pathway and valine, leucine and isoleucine biosynthesis in HepG2 cells, providing reliable experimental evidence for the prevention and treatment of liver damage in greenhouse workers.


Assuntos
Clorpirifos , Inseticidas , Ivermectina/análogos & derivados , Praguicidas , Humanos , Clorpirifos/toxicidade , Clorpirifos/metabolismo , Praguicidas/toxicidade , Células Hep G2 , Leucina , Isoleucina , Carbono , Valina , Ácidos Graxos , Inseticidas/toxicidade , Inseticidas/metabolismo
11.
Sci Rep ; 14(1): 6331, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491005

RESUMO

In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine's effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.


Assuntos
COVID-19 , Psoríase , Humanos , COVID-19/epidemiologia , Estudos Transversais , Prevalência , SARS-CoV-2 , Vacinas contra COVID-19 , China/epidemiologia , Progressão da Doença , Psoríase/complicações , Psoríase/epidemiologia
13.
Front Pharmacol ; 15: 1348410, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379904

RESUMO

The global prevalence of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) is rapidly increasing, revealing a strong association between these two diseases. Currently, there are no curative medication available for the comorbidity of T2DM and AD. Ceramides are structural components of cell membrane lipids and act as signal molecules regulating cell homeostasis. Their synthesis and degradation play crucial roles in maintaining metabolic balance in vivo, serving as important mediators in the development of neurodegenerative and metabolic disorders. Abnormal ceramide metabolism disrupts intracellular signaling, induces oxidative stress, activates inflammatory factors, and impacts glucose and lipid homeostasis in metabolism-related tissues like the liver, skeletal muscle, and adipose tissue, driving the occurrence and progression of T2DM. The connection between changes in ceramide levels in the brain, amyloid ß accumulation, and tau hyper-phosphorylation is evident. Additionally, ceramide regulates cell survival and apoptosis through related signaling pathways, actively participating in the occurrence and progression of AD. Regulatory enzymes, their metabolites, and signaling pathways impact core pathological molecular mechanisms shared by T2DM and AD, such as insulin resistance and inflammatory response. Consequently, regulating ceramide metabolism may become a potential therapeutic target and intervention for the comorbidity of T2DM and AD. The paper comprehensively summarizes and discusses the role of ceramide and its metabolites in the pathogenesis of T2DM and AD, as well as the latest progress in the treatment of T2DM with AD.

14.
Kaohsiung J Med Sci ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385859

RESUMO

Diabetic foot ulcer (DFU) is a serious complication of diabetic patients which negatively affects their foot health. This study aimed to estimate the role and mechanism of the miR-200 family in DNA damage of diabetic wound healing. Human foreskin fibroblasts (HFF-1 cells) were stimulated with high glucose (HG). Db/db mice were utilized to conduct the DFU in vivo model. Cell viability was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assays. Superoxide dismutase activity was determined using detection kits. Reactive oxygen species determination was conducted via dichlorodihydrofluorescein-diacetate assays. Enzyme-linked immunosorbent assay was used to evaluate 8-oxo-7,8-dihydro-2'deoxyguanosine levels. Genes and protein expression were analyzed by quantitative real-time polymerase chain reaction, western blotting, or immunohistochemical analyses. Luciferase reporter gene and RNA immunoprecipitation assays determined the interaction with miR-200a/b/c-3p and GLI family zinc finger protein 2 (GLI2) or ataxia telangiectasia mutated (ATM) kinase. HG repressed cell proliferation and DNA damage repair, promoted miR-200a/b/c-3p expression, and suppressed ATM and GLI2. MiR-200a/b/c-3p inhibition ameliorated HG-induced cell proliferation and DNA damage repair repression. MiR-200a/b/c-3p targeted ATM. Then, the silenced ATM reversed the miR-200a/b/c-3p inhibition-mediated alleviative effects under HG. Next, GLI2 overexpression alleviated the HG-induced cell proliferation and DNA damage repair inhibition via miR-200a/b/c-3p. MiR-200a/b/c-3p inhibition significantly promoted DNA damage repair and wound healing in DFU mice. GLI2 promoted cell proliferation and DNA damage repair by regulating the miR-200/ATM axis to enhance diabetic wound healing in DFU.

15.
Reprod Sci ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267808

RESUMO

The effective combination of semen cryopreservation and artificial insemination has a positive effect on the conservation of germplasm resources, production and breeding, etc. However, during the process of semen cryopreservation, the sperm cells are very susceptible to different degrees of physical, chemical, and oxidative stress damage. Oxidative damage is the most important factor that reduces semen quality, which is affected by factors such as dilution equilibrium, change of osmotic pressure, cold shock, and enzyme action during the freezing-thawing process, which results in the aggregation of a large amount of reactive oxygen species (ROS) in sperm cells and affects the quality of semen after thawing. Therefore, the method of adding antioxidants to semen cryoprotective diluent is usually used to improve the effect of semen cryopreservation. The aim of this experiment was to investigate the effects of adding five antioxidants (GLP, Mito Q, NAC, SLS, and SDS) to semen cryoprotection diluent on the cryopreservation effect of semen from Saanen dairy goats. The optimal preservation concentrations were screened by detecting sperm viability, plasma membrane integrity, antioxidant capacity, and acrosomal enzyme activities after thawing, and the experimental results were as follows: the optimal concentrations of GLP, Mito Q, NAC, SLS, and SDS added to semen cryopreservation diluent at different concentrations were 0.8 mg/mL, 150 nmol/L, 0.6 mg/mL, 0.15 mg/ mL, 0.6 mg/mL, and 0.15 mg/mL. The optimal concentrations of the five antioxidants were added to the diluent and analyzed after 1 week of cryopreservation, and it was found that sperm viability, plasma membrane integrity, and mitochondrial activity were significantly enhanced after thawing compared with the control group (P < 0.05), and their antioxidant capacity was significantly enhanced (P < 0.05). Therefore, the addition of the above five antioxidants to goat sperm cryodilution solution had a better enhancement of sperm cryopreservation. This study provides a useful reference for exploring the improvement of goat semen cryoprotection effect.

16.
IEEE Trans Biomed Eng ; PP2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38231823

RESUMO

OBJECTIVE: Common pain assessment approaches such as self-evaluation and observation scales are inappropriate for children as they require patients to have reasonable communication ability. Subjective, inconsistent, and discontinuous pain assessment in children may reduce therapeutic effectiveness and thus affect their later life. METHODS: To address the need for suitable assessment measures, this paper proposes a spatiotemporal deep learning framework for scalp electroencephalogram (EEG)-based automated pain assessment in children. The dataset comprises scalp EEG data recorded from 33 pediatric patients with an arterial puncture as a pain stimulus. Two electrode reduction plans in line with clinical findings are proposed. Combining three-dimensional hand-crafted features and preprocessed raw signals, the proposed transformer-based pain assessment network (STPA-Net) integrates both spatial and temporal information. RESULTS: STPA-Net achieves superior performance with a subject-independent accuracy of 87.83% for pain recognition, and outperforms other state-of-the-art approaches. The effectiveness of electrode combinations is explored to analyze pain-related cortical activities and correspondingly reduce cost. The two proposed electrode reduction plans both demonstrate competitive pain assessment performance qualitatively and quantitatively. CONCLUSION AND SIGNIFICANCE: This study is the first to develop a scalp EEG-based automated pain assessment for children adopting a method that is objective, standardized, and consistent. The findings provide a potential reference for future clinical research.

18.
Allergy Asthma Immunol Res ; 16(1): 91-108, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38262393

RESUMO

PURPOSE: Airway remodeling is a critical feature of asthma. Secreted protein acidic and rich in cysteine (SPARC), which plays a cardinal role in regulating cell-matrix interactions, has been implicated in various fibrotic diseases. However, the effect of SPARC in asthma remains unknown. METHODS: We studied the expression of SPARC in human bronchial epithelial cells and serum of asthmatics as well as in the lung tissues of chronic asthma mice. The role of SPARC was examined by using a Lentivirus-mediated SPARC knockdown method in the ovalbumin (OVA)-induced asthma mice. The biological processes regulated by SPARC were identified using RNA sequencing. The function of SPARC in the remodeling process induced by transforming growth factor ß1 (TGFß1) was conducted by using SPARC small interfering RNA (siRNA) or recombinant human SPARC protein in 16HBE cells. RESULTS: We observed that SPARC was up-regulated in human bronchial epithelia of asthmatics and the asthmatic mice. The levels of serum SPARC in asthmatics were also elevated and negatively correlated with the forced expiratory volume in one second (FEV1) to forced vital capacity ratio (FVC) (r = -0.485, P < 0.01) and FEV1 (%predicted) (r = -0.425, P = 0.001). In the chronic asthmatic mice, Lentivirus-mediated SPARC knockdown significantly decreased airway remodeling and airway hyper-responsiveness. According to gene set enrichment analysis, negatively enriched pathways found in the OVA + short hairpin-SPARC group included ECM organization and collagen formation. In the lung function studies, knockdown of SPARC by siRNA reduced the expression of remodeling-associated biomarkers, cell migration, and contraction by blocking the TGFß1/Smad2 pathway. Addition of human recombinant SPARC protein promoted the TGFß1-induced remodeling process, cell migration, and contraction in 16HBE cells via the TGFß1/Smad2 pathway. CONCLUSIONS: Our studies provided evidence for the involvement of SPARC in the airway remodeling of asthma via the TGFß1/Smad2 pathway.

19.
J Ethnopharmacol ; 321: 117486, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38030027

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Taohe Chengqi Tang (JTCD) is a modified formulation of Traditional Chinese Medicine (TCM) known as Taohe Chengqi Decoction, which has been described in the ancient TCM literature "Treatise on Febrile Diseases". As a formula that can activate blood circulation and eliminate blood stasis and regulate Yin and Yang in traditional Chinese medicine applications, JTCD has been reported to be effective in the treatment of chronic liver disease and hepatic fibrosis (HF). AIM OF STUDY: The current study aimed to evaluate the effectiveness of JTCD in modulating hepatic macrophages by regulating the Notch signal pathway, and to further investigate the mechanisms underlying macrophage reprogramming that leads to HF. MATERIALS AND METHODS: Molecular assays were performed using in vitro cultures of human mononuclear THP-1 cells and human-derived hepatic stellate cells LX-2. CCl4-induced mice were utilized as an in vivo model to simulate HF. RESULTS: Our results demonstrated that JTCD exhibited dual effects by inhibiting hepatic stellate cell (HSCs) activation and modulating the polarisation of macrophages towards the M2 phenotype while decreasing the M1 phenotype. Network pharmacological analyses and molecular docking studies revealed that the Notch signal pathway was significantly enriched and played a crucial role in the therapeutic response of JTCD against HF. Moreover, through the establishment of a co-culture model, we validated that JTCD inhibited the Notch signal pathway in macrophages, leading to alterations in macrophage reprogramming, subsequent inhibition of HSC activation, and ultimately exerting anti-HF effects. CONCLUSION: In conclusion, our findings provide solid evidence for JTCD in treating HF, as it suppresses the Notch signal pathway in macrophages, regulates macrophage reprogramming, and inhibits HSC activation.


Assuntos
Cirrose Hepática , Transdução de Sinais , Camundongos , Humanos , Animais , Simulação de Acoplamento Molecular , Cirrose Hepática/metabolismo , Macrófagos , Técnicas de Cocultura , Células Estreladas do Fígado
20.
J Hazard Mater ; 465: 133088, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38016320

RESUMO

The substantial utilization of antibiotics causes their "pseudo-persistence" in offshore environments. Published studies on antibiotic surveillance in food webs have primarily emphasized on parent forms; however, the compositions and concentrations of conjugated antibiotics in aquatic organisms remain largely unexplored. This study systematically examined the distribution characteristics and trophodynamics of free antibiotics and their conjugated forms in an estuarine food web. Total antibiotic levels differed insignificantly between the surface and bottom waters. The total mean values of free antibiotics in crabs, fish, shrimps, sea cucumbers, and snails varied from 0.77 to 1.4 ng/g (wet weight). The numbers and values of antibiotics rose in these biological samples after enzymatic hydrolysis. Conjugated antibiotics accounted for 23.8-76.9% of the total antibiotics in the biological samples, revealing that conjugated forms play a non-negligible role in aquatic organisms. More number of antibiotics exhibited bioaccumulation capabilities after enzymatic hydrolysis. In the food web, the free forms of anhydroerythromycin and conjugated forms of trimethoprim and ciprofloxacin underwent trophic dilution, whereas the free forms of trimethoprim and conjugated forms of ofloxacin underwent trophic amplification. The present work provides new insights into the bioaccumulation and trophic transfer of free and conjugated antibiotics in food webs.


Assuntos
Cadeia Alimentar , Poluentes Químicos da Água , Animais , Antibacterianos/análise , Bioacumulação , Multimídia , Poluentes Químicos da Água/análise , Organismos Aquáticos , Peixes , Trimetoprima , Monitoramento Ambiental , China
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...