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1.
J Magn Reson Imaging ; 59(5): 1769-1776, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37501392

RESUMO

BACKGROUND: The status of the hypothalamic-pituitary-gonadal (HPG) axis is important for assessing the onset of physiological or pathological puberty. The reference standard gonadotropin-releasing hormone (GnRH) stimulation test requires hospital admission and repeated blood samples. A simple noninvasive method would be beneficial. OBJECTIVES: To explore a noninvasive method for evaluating HPG axis activation in children using an MRI radiomics model. STUDY TYPE: Retrospective. POPULATION: Two hundred thirty-nine children (83 male; 3.6-14.6 years) with hypophysial MRI and GnRH stimulation tests, randomly divided a training set (168 children) and a test set (71 children). FIELD STRENGTH/SEQUENCE: 3.0 T, 3D isotropic fast spin echo (CUBE) T1-weighted imaging (T1WI) sequences. ASSESSMENT: Radiomics features were extracted from sagittal 3D CUBE T1WI, and imaging signatures were generated using the least absolute shrinkage and selection operator (LASSO) with 10-fold cross-validation. Diagnostic performance for differential diagnosis of HPG status was compared between a radiomics model and MRI features (adenohypophyseal height [aPH] and volume [aPV]). STATISTICAL TESTS: Receiver operating characteristic (ROC) and decision curve analysis (DCA). A P value <0.05 was considered statistically significant. RESULTS: Eight hundred fifty-one radiomics features were extracted and reduced to 10 by the LASSO method in the training cohort. The radiomics model based on CUBE T1WI showed good performance in assessment of HPG axis activation with an area under the ROC curve (AUC) of 0.81 (95% CI: 0.71, 0.91) in the test set. The AUC of the radiomics model was significantly higher than that of aPH (0.81 vs. 0.65) but there was no significant difference compared to aPV (0.81 vs. 0.78, P = 0.58). In DCA analysis, the radiomics signature showed higher net benefit over the aPV and aPH models. DATA CONCLUSIONS: The MRI radiomics model has potential to assess HPG axis activation status noninvasively, potentially providing valuable information in the diagnosis of patients with pathological puberty onset. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.


Assuntos
Eixo Hipotalâmico-Hipofisário-Gonadal , Adeno-Hipófise , Criança , Humanos , Masculino , Estudos Retrospectivos , Radiômica , Imageamento por Ressonância Magnética/métodos , Adeno-Hipófise/diagnóstico por imagem , Hormônio Liberador de Gonadotropina
2.
Chem Biol Interact ; 382: 110640, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37473909

RESUMO

Diabetic kidney disease (DKD) is an essential cause of end-stage renal disease. The ongoing inflammatory response in the proximal tubule promotes the progression of DKD. Timely and effective blockade of the inflammatory process to protect the kidney during DKD progression is a proven strategy. The purpose of this study was to investigate the protective effect of loganin on diabetic nephropathy in vivo and in vitro and whether this effect was related to the inhibition of pyroptosis. The results indicated that loganin reduced fasting blood glucose, blood urea nitrogen and serum creatinine concentrations, and alleviated renal pathological changes in DKD mice. In parallel, loganin downregulated the expression of pyroptosis related proteins in the renal tubules of DKD mice and decreased serum levels of interleukin-1beta (IL-1ß) and interleukin-18 (IL-18). Furthermore, in vitro experiments showed that loganin attenuated high glucose-induced HK-2 cell injury by reducing the expression of pyroptosis-related proteins, and cytokine levels were also decreased. These fundings were also confirmed in the polyphyllin VI (PPVI) -induced HK-2 cell pyroptosis model. Loganin reduces high glucose induced HK-2 cells pyroptosis by inhibiting reactive oxygen species (ROS) production and NOD-like receptor protein 3 (NLRP3) inflammasome activation. In conclusion, the inhibition of pyroptosis via inhibition of the NLRP3/Caspase-1/Gasdermin D (GSDMD) pathway might be an essential mechanism for loganin treatment of DKD.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Proteínas NLR , Nefropatias Diabéticas/tratamento farmacológico , Rim/metabolismo , Glucose/farmacologia
3.
Phytother Res ; 37(7): 2965-2978, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36879546

RESUMO

Acute lung injury (ALI) caused by acute bacterial infection remains a common life-threatening lung disease. An increased inflammatory response is the basis for the occurrence and development of ALI. Most antibiotics can only reduce the bacterial load but do not protect from lung damage because of an excessive immune response. Chrysophanol (chrysophanic acid, Chr), as a natural anthraquinone extracted from Rheum palmatum L., has various biological functions, including anti-inflammatory, anti-cancer activities, and ameliorative effects on cardiovascular diseases. Considering these properties, we investigated the effect of Chr in Klebsiella pneumoniae (KP)-induced ALI mice and its potential mechanism. Our results showed that Chr had protective effects against KP-infected mice, including increased survival rate, decreased bacterial burden, reduced recruitment of immune cells, and reduced reactive oxygen species level of lung macrophages. Chr reduced the expression of inflammatory cytokines by inhibiting the toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signaling pathway and inflammasome activation and strengthening autophagy. Overactivation of the TLR4/NF-κB signaling pathway by the activator Neoseptin 3 led to Chr losing control of inflammatory cytokines in cells, resulting in increased cell death. Similarly, overactivation of the c-Jun N-terminal kinase signaling pathway using the activator anisomycin resulted in Chr losing its inhibitory effect on NOD-like receptor thermal protein domain associated protein 3 (NFRP3) inflammasome activation, and cell viability was reduced. In addition, autophagy was blocked by siBeclin1, so Chr could not reduce inflammatory factors, and cell viability was markedly inhibited. Collectively, this work unravels the molecular mechanism underpinning Chr-alleviated ALI via inhibiting pro-inflammatory cytokines. Thus, Chr is a potential therapeutic agent for KP-induced ALI.


Assuntos
Lesão Pulmonar Aguda , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Klebsiella pneumoniae/metabolismo , Inflamassomos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Antraquinonas/farmacologia , Antraquinonas/uso terapêutico , Pulmão , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia
4.
Biomed Pharmacother ; 160: 114340, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36738503

RESUMO

Renal fibrosis, an important pathological change in the development of diabetic kidney disease (DKD), urgently needs new treatment methods clinically. The Jiedu Tongluo Baoshen (JTBF) formula was created based on the theory of toxic damage to the kidney collaterals, and a variety of active ingredients in JTBF have inhibitory effects on epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM). In this study, the Ultra Performance Liquid Chromatography (UPLC) was employed to analyze the effective ingredients in the JTBF formula. After screening in the PubChem database, we identified 94 active compounds of JTBF and predicted the SIRT1 pathway as potential targets through network pharmacology. In addition, in the high fat diet (HFD)+Streptozocin (STZ)-induced DKD rat model and high glucose (HG)-induced NRK-52E cell model, JTBF treatment activates the phosphorylation of LKB1 and AMPK and enhances the autophagy activity of NRK-52E cells, thereby reducing the accumulation of EMT and ECM. These results have been confirmed in vivo and in vitro experiments. JTBF enhances the autophagy activity of renal tubular epithelial cells and inhibits the progression of DKD renal fibrosis by activating the SIRT1/LKB1/AMPK signal pathway. This study provides new insights into the molecular mechanism of JTBF to prevent and treat DKD renal fibrosis.


Assuntos
Proteínas Quinases Ativadas por AMP , Nefropatias Diabéticas , Ratos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Sirtuína 1/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/metabolismo , Fibrose , Células Epiteliais , Autofagia , Transição Epitelial-Mesenquimal
5.
Phytomedicine ; 108: 154531, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36375237

RESUMO

BACKGROUND: Ophiocordyceps sinensis (OS), a medicinal fungus, has been made into OS preparations, which are frequently used as adjunctive therapy for patients with Diabetic Kidney Disease (DKD) in China. It is necessary to assess the efficacy and safety of OS preparations in the adjunctive treatment of DKD by conducting a systematic review and meta-analysis. OBJECTIVE: Ophiocordyceps sinensis preparations were evaluated for their efficacy and safety as adjunctive therapy to conventional drugs (angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)) for DKD. METHODS: We searched seven electronic literature databases for randomized controlled trials (RCTs) comparing ACEI/ARB and OS combined with ACEI/ARB from inception up to March 2022. Two reviewers extracted data and assessed the risk of bias independently. Evidence certainty was rated using the GRADE system. Standardized mean difference (SMD) or mean difference (MD) was pooled with random effects models and was reported with corresponding 95% confidence intervals (CIs). Meta-analysis, sensitivity analysis and Egger's test were performed using R software (version 14.2) (PROSPERO registration no. CRD42021248634). RESULTS: Thirty eight RCTs involving 3167 patients met the inclusion criteria. No trials were reported with outcomes about kidney disease progression and cardiovascular events. In meta-analysis, compared with the control group of ACEI/ARB alone, OS combined with ACEI/ARB can achieve better effects in the treatment of DKD on reducing serum creatinine (Scr) [MDScr =-11.48 95% CI [-15.78, -7.18], p < 0.01], blood urea nitrogen (BUN) [MDBUN= -1.00, 95% CI [-1.44, -0.55], p < 0.01], ß2-microglobulin (ß2-MG) [SMDß2-MG= -1.32, 95% CI [-2.27, -0.37], p < 0.01], cystatin C (CysC) [MDCysC=-0.64, 95% CI [-0.83, -0.45], p < 0.01], 24-h urine proteinuria (24hUP) [SMD24hUP= -1.99, 95% CI [-2.68; -1.31], p < 0.01], urine microalbumin (UALB) [MDUALB= -37.41, 95% CI [-44.76, -30.06], p < 0.01] and decreasing urinary albumin excretion rate (UAER) [MDUAER= -24.11, 95% CI [-30.54, -17.68], p < 0.01] and albumin creatinine ratio (ACR) [SMDACR = 1.01, 95% CI [-1.73, -0.29], p < 0.01]. The OS adjuvant treatment also improved outcomes of blood pressure, blood glucose, blood lipid, inflammation and oxidative stress. No significant change in fasting blood glucose (FPG), glycated hemoglobin (HbA1c), malondialdehyde (MDA), and transforming growth factor beta 1 (TGF-ß1) was detected. Yet, no significant difference was found about the adverse events between the two groups. CONCLUSIONS: Ophiocordyceps sinensis preparation combined with ACEI/ARB has beneficial influence on renal function, decrease proteinuria, dyslipidemia, and even oxidative stress and inflammation in DKD patients. However, there is no trial that evaluated outcomes of kidney disease progression and cardiovascular events. Future study should move beyond surrogate endpoints to actual cardiovascular or renal outcome benefits with an aim to explore effects of OS preparation in the long-term.


Assuntos
Doenças Cardiovasculares , Cordyceps , Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Proteinúria/tratamento farmacológico , Progressão da Doença , Inflamação , Albuminas
6.
Artigo em Inglês | MEDLINE | ID: mdl-36497725

RESUMO

The objectives of this study were to evaluate the cadmium adsorption capacity of iron-organic associations (Fe-OM) formed by laccase-mediated modification and assess the effect of Fe-OM on the immobilization of cadmium in paddy soil. Leaf organic matter (OM) was extracted from Changshan grapefruit leaves, and then dissolved organic matter (Lac-OM) and precipitated organic matter (Lac-P) were obtained by laccase catalytic modification. Different Fe-OM associations were obtained by co-precipitation of Fe with OM, Lac-OM, and Lac-P, respectively, and the adsorption kinetics, adsorption edge, and isothermal adsorption experiments of Cd on Fe-OM were carried out. Based on the in situ generation of Fe-OM, passivation experiments on Cd-contaminated soils with a high geological background were carried out. All types of Fe-OM have a better Cd adsorption capacity than ferrihydrite (FH). The theoretical maximum adsorption capacity of the OM-FH, Lac-OM-FH, and Lac-P-FH were 2.2, 2.53, and 2.98 times higher than that of FH, respectively. The adsorption of Cd on Fe-OM is mainly chemisorption, and the -OH moieties on the Fe-OM surface form an inner-sphere complex with the Cd ions. Lac-OM-FH showed a higher Cd adsorption capacity than OM-FH, which is related to the formation of more oxygen-containing groups in the organic matter modified by laccase. The immobilization effect of Lac-OM-FH on active Cd in soil was also higher than that of OM-FH. The Lac-OM-FH formed by laccase-mediated modification has better Cd adsorption performance, which can effectively inactivate the activity of Cd in paddy soil.


Assuntos
Cádmio , Poluentes do Solo , Cádmio/análise , Solo , Ferro , Poluentes do Solo/análise , Lacase , Adsorção
7.
Front Mol Biosci ; 9: 1051866, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406272

RESUMO

Ferroptosis is characterized by the accumulation of iron and lipid peroxidation products, which regulates physiological and pathological processes in numerous organs and tissues. A growing body of research suggests that ferroptosis is a key causative factor in a variety of skeletal muscle diseases, including sarcopenia, rhabdomyolysis, rhabdomyosarcoma, and exhaustive exercise-induced fatigue. However, the relationship between ferroptosis and various skeletal muscle diseases has not been investigated systematically. This review's objective is to provide a comprehensive summary of the mechanisms and signaling factors that regulate ferroptosis, including lipid peroxidation, iron/heme, amino acid metabolism, and autophagy. In addition, we tease out the role of ferroptosis in the progression of different skeletal muscle diseases and ferroptosis as a potential target for the treatment of multiple skeletal muscle diseases. This review can provide valuable reference for the research on the pathogenesis of skeletal muscle diseases, as well as for clinical prevention and treatment.

8.
Biomed Res Int ; 2022: 4469766, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046447

RESUMO

Background: Diabetic osteoporosis (DOP) is a progressive osteoblast dysfunction induced by high glucose, which has negative impacts on bone homeostasis. Qizhi Kebitong formula (QKF) is a traditional Chinese medicine (TCM) formula for treating DOP. However, its role in the protection of DOP has not been clarified yet. Here, we aimed to explore the potential mechanisms of QKF on DOP development via in vivo experiment. Methods: Network pharmacology was used to detect the key targets and signaling pathways of QKF on DOP. The effects of QKF on DOP were examined by the phenotypic characteristics, micro-CT, and hematoxylin-eosin (H&E) staining. The predicted targets and pathways were validated by a streptozocin- (STZ-) induced mouse model. Subsequently, the levels of the selected genes and proteins were analyzed using qRT-PCR and Western blot. Finally, AutoDock and PyMOL were used for molecular docking. Results: In this study, 90 active compounds and 2970 related disease targets have been found through network pharmacology. And QKF could improve the microstructures of femur bone mass, reduce inflammatory cell infiltration, and downregulate the levels of TNF-α, IKBKB, IL-6, and IL-1ß. Moreover, the underlying effect of PI3K/Akt/NF-κB pathways was also recommended in the treatment. Conclusion: Altogether, our findings suggested that QKF could markedly alleviate osteoblast dysfunction by modulating the key targets and PI3K/Akt/NF-κB signaling pathway.


Assuntos
Diabetes Mellitus , Medicamentos de Ervas Chinesas , Osteoporose , Animais , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Osteoporose/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estreptozocina
9.
Mol Ther Oncolytics ; 26: 314-329, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36090477

RESUMO

Glioma is the most common primary malignant intracranial tumor. Owing to highly aggressive invasiveness and metastatic properties, the prognosis of this disease remains poor even with surgery, radiotherapy, and chemotherapy. Rutin is a glycoside natural flavonoid that modulates microglia inflammatory profile and improves anti-glioma activity. Here, a glycoside flavonoid was extracted and named purple sweet potato delphinidin-3-rutin (PSPD3R). In an experiment using the subcutaneous xenograft model of human glioblastoma (GBM) and alamar blue assay, we found that PSPD3R suppressed the glioma proliferation both in vitro and in vivo. Flow cytometry assay and transmission electron microscopy observation revealed that PSPD3R stimulated glioma cell autophagy and apoptosis. High-throughput microRNA (miRNA) sequencing showed that PSPD3R substantially affected the miRNA expression of U251 cells. Acridine orange staining and immunoblotting indicated that PSPD3R regulated autophagy via Akt/Creb/miR-20b-5p in glioma cells. Luciferase reporter assays showed that autophagy-related gene 7 (Atg7) mRNA was the target gene of miR-20b-5p. The downregulation of miR-20b-5p inhibited glioma proliferation in vivo. In summary, PSPD3R regulated autophagy in glioma via the Akt/Creb/miR-20b-5p/Atg7 axis. This work unraveled the molecular mechanism of PSPD3R-induced autophagy in glioma and revealed its potential as a therapeutic agent for glioma treatment.

10.
J Ethnopharmacol ; 293: 115246, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35398500

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been applied to diabetic kidney disease (DKD). A large number of animal trials each year focus on TCM for DKD, but the evidence for these preclinical studies is not clear. AIM OF THE STUDY: The aim of this study was to study the therapeutic effect of Jiedu Tongluo Baoshen formula (JTBF) on DKD proteinuria and renal protection. At the same time, it is verified that JTBF can reduce podocyte injury by enhancing autophagy function, and then achieve the effect of proteinuria. MATERIALS AND METHODS: We use high performance liquid chromatography to detect and analyze the fingerprint of JTBF to find the chemical composition. Subsequently, we constructed a DKD rat model induced by high-fat diet and streptozocin (HFD + STZ). Urine and blood biochemical automatic analyzer were used to detect 24-h urine protein quantification (24 h-UP) and renal function. The renal pathological changes were observed by H&E and transmission electron microscopy (TEM), and the levels of autophagy-related proteins and mRNA in podocytes were detected by immunohistochemistry, RT-qPCR and Western Blot. The chemical composition of JTBF was screened from traditional Chinese medicine systems pharmacol (TCMSP) and PubChem databases, and the potential targets and associated pathways of JTBF were predicted using kyoto encyclopedia of genes and genomes (KEGG) and protein-protein interaction (PPI) network analysis in network pharmacology, and confirmed in animal experiments and histopathological methods. RESULTS: We discovered 77 active ingredients of JTBF. Through animal experiments, it was found that JTBF reduced 24 h-UP and promoted the expression of podocin, nephrin, and WT-1 in podocytes, thereby reducing podocyte damage. At the same time, JTBF activates the expression of podocyte autophagy-related proteins (beclin-1, LC3 and P62). Subsequently, through network pharmacology predictions, 208 compounds were obtained from JTBF, and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) was a potential signal pathway. JTBF was obtained in DKD rat kidney tissue to inhibit the expression of PI3K, Akt and mTOR related proteins. CONCLUSIONS: JTBF enhance podocyte autophagy to reduce podocyte damage, thereby effectively treating DKD proteinuria and protecting kidney function.


Assuntos
Autofagia , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Podócitos , Proteinúria , Animais , Proteínas Relacionadas à Autofagia/metabolismo , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Podócitos/efeitos dos fármacos , Proteinúria/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
11.
Clin Rheumatol ; 41(5): 1499-1509, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35088208

RESUMO

OBJECTIVE: To analyze 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) image features in different types of systemic vasculitis and explore its classification and diagnostic significance for systemic vasculitis. METHODS: Clinical and 18F-FDG PET/CT imaging data of 71 consecutive patients (34 males, 37 females, mean age 53.4 ± 20.5 years) who were examined at Peking University People's Hospital and diagnosed with active systemic vasculitis were analyzed retrospectively, and 18F-FDG PET/CT imaging features of different types of systemic vasculitis were analyzed in patients with positive 18F-FDG PET/CT findings. RESULTS: The proportions of large-, medium-, small-, and variable-vessel vasculitis were 36.6%, 15.5%, 29.6%, and 18.3%, respectively, and 93.0% of patients had positive findings on PET/CT, of which 63.6% had vascular involvement and 53.0% had extravascular involvement. Different types of vasculitis had different lesion sites, distribution patterns, and morphological changes. Large-vessel vasculitis mainly affected the aorta and its branches to the head and neck. Takayasu arteritis showed segmental involvement of the vascular and morphological changes of the vessel wall. Giant cell arteritis manifested as diffuse vascular involvement, which usually involved the temporal artery and the abdominal aorta and its branches. Medium-vessel vasculitis polyarteritis nodosa manifested as diffuse vascular involvement of both lower extremities. Small-vessel vasculitis anti-neutrophil cytoplasmic antibody-associated vasculitis manifested as granulomatous inflammation of extravascular regions. Variable-vessel vasculitis Behcet's disease involved both blood vessels and extravascular regions. CONCLUSION: Different types of systemic vasculitis show characteristic manifestations in 18F-FDG PET/CT images, which may be useful for the diagnosis and classification of systemic vasculitis. KEY POINTS: • Determining an early diagnosis of systemic vasculitis may be challenging. • Different types of systemic vasculitis show characteristic manifestations in 18F-FDG PET/CT images. • 18F-FDG PET/CT may be useful for the diagnosis and classification of systemic vasculitis.


Assuntos
Arterite de Células Gigantes , Vasculite Sistêmica , Adulto , Idoso , Feminino , Fluordesoxiglucose F18 , Arterite de Células Gigantes/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Vasculite Sistêmica/diagnóstico por imagem
12.
Int J Mol Sci ; 22(21)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34768852

RESUMO

Given the rise of morbidity and mortality caused by Klebsiella pneumoniae (KP), the increasing number of strains resistant to antibiotics, and the emergence of hypervirulent Klebsiella pneumonia, treatment of KP infection becomes difficult; thus, novel drugs are necessary for treatment. Anthocyanins, or natural flavonoids, have an extensive effect against bacterial infection. However, few studies on anti-KP are identified. Here, we evaluated the therapeutic effect of purple sweet potato anthocyanins (PSPAs) on KP, containing 98.7% delphinidin 3-sambubioside. Results showed that KP-infected mice after PSPAs treatment manifested decreased mortality, weakened lung injury, dampened inflammatory responses, and reduced bacterial systemic dissemination in vivo. In Vitro, PSPAs significantly suppressed pyroptosis and restricted NLRP3 inflammasome activation in alveolar macrophages infected with KP. As for the mechanism, PSPAs promote mitophagy by recruiting Parkin to the mitochondria. PSPAs-conferred mitophagy increased mitochondrial membrane potential and decreased mitochondrial reactive oxygen species and mitochondrial DNA, resulting in impaired NLRP3 inflammasome activation. In addition, the promotion of mitophagy by PSPAs required the Nrf2 signaling pathway. Collectively, these findings suggest that PSPAs are a potential option for the treatment of KP infection.


Assuntos
Antocianinas/farmacologia , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Animais , Antocianinas/análise , Antocianinas/química , Linhagem Celular , DNA Mitocondrial/genética , Modelos Animais de Doenças , Feminino , Inflamação/tratamento farmacológico , Ipomoea batatas/química , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/patogenicidade , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/prevenção & controle , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/microbiologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo
13.
Phytomedicine ; 93: 153742, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34624808

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide, yet no effective medication for this disease is available. Cochlioquinone B derivative (CoB1), purified from Salvia miltiorrhiza endophytic Bipolaris sorokiniana, affects the defense against pulmonary pathogens by regulating inflammatory responses. However, the effect of CoB1 on lung cancer and the underlying molecular mechanisms remain unknown. In the present study, we investigate the protective effects of CoB1 on lung cancer and explore its underlying mechanism. METHOD: We examined the inhibitory effect of CoB1 on lung cancer cells (A549 cells) by MTT and colony formation assay. The effect of CoB1 on cytostatic autophagy in lung cancer cells was verified by Western blot, transmission electron microscopy, and confocal microscopy. The differentially expressed miRNAs were identified using quantitative RT-PCR. Luciferase assay and Northern blot were performed to verify the correlation between miRNA-125b and Foxp3. Protein expression in autophagy-related pathways was detected by Western blot. Xenograft tumor models were constructed to explore the inhibitory effect of CoB1 and the role of miRNA-125b as a suppressor in lung cancer in vivo. RESULT: CoB1 inhibited lung cancer cell proliferation by inducing cytostatic autophagy both in vitro and in vivo. CoB1-induced autophagy was related to blocking of the PI3K/Akt1/mTOR signaling pathway. In addition, CoB1 induced miR-125b expression via activating the TAK1/MKK4/JNK/Smad axis, thereby reducing Foxp3 expression and further inducing autophagy. CONCLUSION: This study is the first to report the specific inhibitory function of CoB1 purified from Salvia miltiorrhiza endophytic Bipolaris sorokiniana in lung cancer, which may be due to the induction of autophagy. This study provides evidence and novel insights into the anticancer efficacy of CoB1.


Assuntos
Citostáticos , Neoplasias Pulmonares , MicroRNAs , Autofagia , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Transcrição Forkhead , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
14.
Front Pharmacol ; 12: 632378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33767629

RESUMO

Phosphatidylinositol 3 kinase (PI3K) is a key molecule in the initiation of signal transduction pathways after the binding of extracellular signals to cell surface receptors. An intracellular kinase, PI3K activates multiple intracellular signaling pathways that affect cell growth, proliferation, migration, secretion, differentiation, transcription and translation. Dysregulation of PI3K activity, and as aberrant PI3K signaling, lead to a broad range of human diseases, such as cancer, immune disorders, diabetes, and cardiovascular diseases. A growing number of studies have shown that PI3K and its signaling pathways play key roles in the pathophysiological process of atherosclerosis. Furthermore, drugs targeting PI3K and its related signaling pathways are promising treatments for atherosclerosis. Therefore, we have reviewed how PI3K, an important regulatory factor, mediates the development of atherosclerosis and how targeting PI3K can be used to prevent and treat atherosclerosis.

15.
Chemosphere ; 269: 128693, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33121804

RESUMO

A plant bionic in situ soil remediation system was designed to rehabilitate acidic cadmium (Cd)-contaminated soil in a high geological background area, Kaihua County of Zhejiang Province in China. In this system, citric acid, an environmental-friendly organic compound, was adopted to activate soil Cd. The soil solution was driven into the plant bionic root using a solar powered simulated transpiration system. Activated Cd in the soil solution was adsorbed by the modified polyurethane foam (DTC-LPEI-PUF) in the bionic root. Under the acidic conditions caused by citric acid (pH = 4.5), DTC-LPEI-PUF could effectively adsorb Cd, and the adsorption rate reached equilibrium after 5 h. Theoretical calculations suggested that the absorption behavior followed pseudo -second order kinetics, and the saturated adsorption capacity of Cd by DTC-LPEI-PUF was 89.05 mg/g, obeying Langmuir isothermal adsorption models. In addition, the main ions in soil, such as calcium (Ca) and magnesium (Mg), had little effect on the adsorption by DTC-LPEI-PUF. However, iron ions (Fe3+) significantly influenced the adsorption of Cd by DTC-LPEI-PUF. After 28 d of an in situ remediation, the total contents of Cd in contaminated soil declined from 3.63 mg/kg to 2.69 mg/kg, i.e., 26% of the total Cd was removed. In addition, after remediation, the removal of available Cd reached 47%. Our results demonstrate that the proposed plant bionic in situ remediation system has a promising prospect for application to rehabilitate Cd-contaminated soil in a high geological background area, although the technology needs further improvement.


Assuntos
Recuperação e Remediação Ambiental , Poluentes do Solo , Biônica , Cádmio/análise , China , Solo , Poluentes do Solo/análise
16.
Theranostics ; 9(16): 4730-4739, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367253

RESUMO

18F-FDG PET / CT is used clinically for the detection of extramedullary lesions in patients with relapsed acute leukemia (AL). However, the visual analysis of 18F-FDG diffuse bone marrow uptake in detecting bone marrow involvement (BMI) in routine clinical practice is still challenging. This study aims to improve the diagnostic performance of 18F-FDG PET/CT in detecting BMI for patients with suspected relapsed AL. Methods: Forty-one patients (35 in training group and 6 in independent validation group) with suspected relapsed AL were retrospectively included in this study. All patients underwent both bone marrow biopsy (BMB) and 18F-FDG PET/CT within one week. The BMB results were used as the gold standard or real "truth" for BMI. The bone marrow 18F-FDG uptake was visually diagnosed as positive and negative by three nuclear medicine physicians. The skeletal volumes of interest were manually drawn on PET/CT images. A total of 781 PET and 1045 CT radiomic features were automatically extracted to provide a more comprehensive understanding of the embedded pattern. To select the most important and predictive features, an unsupervised consensus clustering method was first performed to analyze the feature correlations and then used to guide a random forest supervised machine learning model for feature importance analysis. Cross-validation and independent validation were conducted to justify the performance of our model. Results: The training group involved 16 BMB positive and 19 BMB negative patients. Based on the visual analysis of 18F-FDG PET, 3 patients had focal uptake, 8 patients had normal uptake, and 24 patients had diffuse uptake. The sensitivity, specificity, and accuracy of visual analysis for BMI diagnosis were 62.5%, 73.7%, and 68.6%, respectively. With the cross-validation on the training group, the machine learning model correctly predicted 31 patients in BMI. The sensitivity, specificity, and accuracy of the machine learning model in BMI detection were 87.5%, 89.5%, and 88.6%, respectively, significantly higher than the ones in visual analysis (P < 0.05). The evaluation on the independent validation group showed that the machine learning model could achieve 83.3% accuracy. Conclusions:18F-FDG PET/CT radiomic analysis with machine learning model provided a quantitative, objective and efficient mechanism for identifying BMI in the patients with suspected relapsed AL. It is suggested in particular for the diagnosis of BMI in the patients with 18F-FDG diffuse uptake patterns.


Assuntos
Medula Óssea/diagnóstico por imagem , Leucemia/diagnóstico por imagem , Doença Aguda , Adolescente , Adulto , Idoso , Medula Óssea/patologia , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Leucemia/patologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/administração & dosagem , Recidiva , Estudos Retrospectivos , Adulto Jovem
17.
Sci Total Environ ; 671: 149-156, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-30928744

RESUMO

Disgusting fishy odor problems have become a major concern in drinking water quality, and are commonly related to algal proliferation in source water. Unlike the typical musty/earthy odorants 2-methylisoborneol (MIB) and geosmin, identification of the corresponding fishy odorants is still a big challenge. In this study, two species of fishy-odor-producing algae, Ochromonas sp. and Cryptomonas ovate, were cultured to explore the odor production characteristics and typical odorants. When algae were ruptured in the stationary and decline phases, fishy odor intensities of 4 to 8 characterized by FPA were produced. However, some frequently reported aldehydes that could cause fishy odor, including n-hexanal, 2-octenal, heptanal, 2,4-heptanal and 2,4-decadienal, were not detected in either of the cultured algae. The possible fishy odor-causing compounds were further identified by combining gas chromatography-olfactometry (GC-O/MS) and comprehensive two-dimensional gas chromatography (GC × GC-TOFMS) using retention indices (RIs). From GC-O/MS analysis, twelve and six olfactometry peaks with various odor characteristics were identified in Ochromonas sp. and Cryptomonas ovate, respectively, of which three and two olfactometry peaks showed fishy odor characteristics. 2-Nonenal, 2,4-octadienal, fluorene and 2-tetradecanone were identified as fishy odorants in Ochromonas sp., and 1-octen-3-ol, 6-methyl-5-hepten-2-one, 1-octen-3-one, 2-nonenal and 2,4-octadienal were identified in Cryptomonas ovate. Other identified compounds, including butyl butanoate (fragrant odor), ionone (fragrant odor), bis (2-chloroisopropyl) ether (chemical odor) etc., did not show fishy features. Therefore, the fishy odor might be a synthetic and comprehensive odor, which resulted from the combination of different odorants and their synergistic effects. The results of this study will be helpful for understanding fishy odor problems, which will provide support for fishy odor management and control in the drinking water industry.


Assuntos
Criptófitas/química , Ochromonas/química , Odorantes/análise , Cromatografia Gasosa , Monitoramento Ambiental , Olfatometria
18.
Ann Nucl Med ; 28(4): 349-55, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24519437

RESUMO

OBJECTIVE: The study aimed to investigate the incidence of bone uptake of tracer on Tc-99m MIBI imaging and explore its influencing factors and significance for diagnosis of metabolic bone disease (MBD) in patients with hyperparathyroidism (HPT). METHODS: Seventy-nine consecutive patients with histopathologically confirmed HPT (63 primary and 16 secondary) who had preoperative Tc-99m MIBI imaging were retrospectively evaluated. Serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) were measured for all patients, and serum alkaline phosphatase (ALP) was measured for 62 patients. Of the 79 patients, 50 underwent bone mineral density (BMD) examination and 30 underwent bone scintigraphy. The incidence and characteristics of abnormal bone uptake of MIBI were recorded. Mann-Whitney test was performed to determine if serum iPTH, Ca, P, ALP, and BMD were different between the patients with and without MIBI bone uptake. Logistic regression analysis was used to analyze the factors that influence the bone uptake of MIBI. The concordance rate between Tc-99m MIBI imaging and bone scintigraphy in delineating MBD was calculated. RESULTS: Tc-99m MIBI imaging disclosed the abnormal bone uptake of tracer in 22 (27.8 %) patients. Of them, 19 showed diffusely increased activity in skeleton, 2 showed focal uptake in brown tumors, and one showed both above patterns. Patients with bone uptake MIBI had higher level of serum iPTH (Z = -4.34, P < 0.001) and ALP (Z = -3.50, P < 0.001) than those without bone uptake. Logistic regression analysis also showed that bone uptake of MIBI was correlated with serum iPTH (OR = 4.42, P < 0.001) and ALP (OR = 3.21, P = 0.002). Among the 30 patients that underwent bone scintigraphy, 76.7 % patients showed signs of MBD, and the concordance rate between Tc-99m MIBI imaging and bone scintigraphy was 60 % for detecting MBD. CONCLUSIONS: Bone uptake of MIBI in patients with HPT is commonly related to a high level of iPTH and ALP; it probably reflects an active stage of MBD, and it should be monitored during the conventional Tc-99m MIBI scintigraphy.


Assuntos
Doenças Ósseas Metabólicas/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Hiperparatireoidismo/complicações , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Adolescente , Adulto , Idoso , Fosfatase Alcalina/sangue , Análise Química do Sangue , Densidade Óssea , Doenças Ósseas Metabólicas/complicações , Cálcio/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton Único , Imagem Corporal Total , Adulto Jovem
19.
PLoS One ; 8(12): e81471, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24363811

RESUMO

MicroRNAs (miRNAs) play crucial roles in regulating the expression of various stress responses genes in plants. To investigate soybean (Glycine max) miRNAs involved in the response to cadmium (Cd), microarrays containing 953 unique miRNA probes were employed to identify differences in the expression patterns of the miRNAs between different genotypes, Huaxia3 (HX3, Cd-tolerant) and Zhonghuang24 (ZH24, Cd-sensitive). Twenty six Cd-responsive miRNAs were identified in total. Among them, nine were detected in both cultivars, while five were expressed only in HX3 and 12 were only in ZH24. The expression of 16 miRNAs was tested by qRT-PCR and most of the identified miRNAs were found to have similar expression patterns with microarray. Three hundred and seventy six target genes were identified for 204 miRNAs from a mixture degradome library, which was constructed from the root of HX3 and ZH24 with or without Cd treatment. Fifty five genes were identified to be cleaved by 14 Cd-responsive miRNAs. Gene ontology (GO) annotations showed that these target transcripts are implicated in a broad range of biological processes. In addition, the expression patterns of ten target genes were validated by qRT-PCR. The characterization of the miRNAs and the associated target genes in response to Cd exposure provides a framework for understanding the molecular mechanism of heavy metal tolerance in plants.


Assuntos
Cádmio/toxicidade , Tolerância a Medicamentos/genética , Regulação da Expressão Gênica de Plantas/genética , Glycine max/genética , MicroRNAs/genética , Estresse Fisiológico/genética , Sequência de Bases , Biologia Computacional , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Biblioteca Gênica , Ontologia Genética , Genótipo , Análise em Microsséries , Dados de Sequência Molecular , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Especificidade da Espécie
20.
Zhonghua Yi Xue Za Zhi ; 93(17): 1327-9, 2013 May 07.
Artigo em Chinês | MEDLINE | ID: mdl-24029483

RESUMO

OBJECTIVE: To explore the diagnostic rationales for pelvic retroperitoneal tumors and summarize their therapeutic regimens. METHODS: A total of 16 retroperitoneal tumor patients were recruited. And their general information, previous medical history, physical examinations, auxiliary tests, surgical findings and postoperative pathological results were analyzed. RESULTS: Two cases were diagnosed through preoperative magnetic resonance imaging (MRI) while others found intraoperatively. Complete tumor resection was performed in all except for one case. Postoperative pathological examinations revealed 10 benign cases. And there was one case of pelvic endometriosis (mild cytologic atypia). Five cases were malignant. The operation duration was 1.45-8.5 hours and peri-operative bleeding volume 50-5000 ml. Among them, 12 patients had heavy adhesion in pelvic cavity, 7 cases underwent operations collaboratively with related departments because of surgical difficulties and vascular injury and bladder rupture occurred in 1 case. During the follow-ups, one case was lost, two patients died from disease recurrence and another one had a postoperative relapse at Month 4. The other 12 cases recovered well and had no recurrence. CONCLUSION: Surgery remains a key for retroperitoneal tumors. With a low diagnostic rate, they are often found surprisingly intraoperatively. Because of surgical difficulties and frequent complications, multi-departmental collaboration is necessary. Preoperative correct diagnosis and adequate preoperative preparation are essential. And MRI is an effective auxiliary examination.


Assuntos
Neoplasias Retroperitoneais/diagnóstico , Neoplasias Retroperitoneais/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade
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