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Remote patient-monitoring systems are helpful since they can provide timely and effective healthcare facilities. Such online telemedicine is usually achieved with the help of sophisticated and advanced wearable sensor technologies. The modern type of wearable connected devices enable the monitoring of vital sign parameters such as: heart rate variability (HRV) also known as electrocardiogram (ECG), blood pressure (BLP), Respiratory rate and body temperature, blood pressure (BLP), respiratory rate, and body temperature. The ubiquitous problem of wearable devices is their power demand for signal transmission; such devices require frequent battery charging, which causes serious limitations to the continuous monitoring of vital data. To overcome this, the current study provides a primary report on collecting kinetic energy from daily human activities for monitoring vital human signs. The harvested energy is used to sustain the battery autonomy of wearable devices, which allows for a longer monitoring time of vital data. This study proposes a novel type of stress- or exercise-monitoring ECG device based on a microcontroller (PIC18F4550) and a Wi-Fi device (ESP8266), which is cost-effective and enables real-time monitoring of heart rate in the cloud during normal daily activities. In order to achieve both portability and maximum power, the harvester has a small structure and low friction. Neodymium magnets were chosen for their high magnetic strength, versatility, and compact size. Due to the non-linear magnetic force interaction of the magnets, the non-linear part of the dynamic equation has an inverse quadratic form. Electromechanical damping is considered in this study, and the quadratic non-linearity is approximated using MacLaurin expansion, which enables us to find the law of motion for general case studies using classical methods for dynamic equations and the suitable parameters for the harvester. The oscillations are enabled by applying an initial force, and there is a loss of energy due to the electromechanical damping. A typical numerical application is computed with Matlab 2015 software, and an ODE45 solver is used to verify the accuracy of the method.
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Eletrocardiografia , Frequência Cardíaca , Dispositivos Eletrônicos Vestíveis , Frequência Cardíaca/fisiologia , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Eletrocardiografia/métodos , Eletrocardiografia/instrumentação , Fontes de Energia Elétrica , Internet das Coisas , Cinética , Telemedicina/instrumentaçãoRESUMO
Self-powered biomedical devices, which are the new vision of Internet Of Things (IOT) healthcare, are facing many technical and application challenges. Many research works have reported biomedical devices and self-powered applications for healthcare, along with various strategies to improve the monitoring time of self-powered devices or to eliminate the dependence on electrochemical batteries. However, none of these works have especially assessed the development and application of healthcare devices in an African context. This article provides a comprehensive review of self-powered devices in the biomedical research field, introduces their applications for healthcare, evaluates their status in Africa by providing a thorough review of existing biomedical device initiatives and available financial and scientific cooperation institutions in Africa for the biomedical research field, and highlights general challenges for implementing self-powered biomedical devices and particular challenges related to developing countries. The future perspectives of the aforementioned research field are provided, as well as an architecture for improving this research field in developing countries.
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Pesquisa Biomédica , Fenômenos Físicos , África , Fontes de Energia Elétrica , CabeçaRESUMO
Heart aging is characterized by structural and diastolic dysfunction of the heart. However, there is still no effective drug to prevent and treat the abnormal changes in cardiac function caused by aging. Here, we present the preventive effects of emodin and its derivative Kanglexin (KLX) against heart aging. We found that the diastolic dysfunction and cardiac remodeling in mice with D-galactose (D-gal)-induced aging were markedly mitigated by KLX and emodin. In addition, the senescence of neonatal mouse cardiomyocytes induced by D-gal was also reversed by KLX and emodin treatment. However, KLX exhibited better anti-heart aging effects than emodin at the same dose. Dysregulated mitophagy was observed in aging hearts and in senescent neonatal mouse cardiomyocytes, and KLX produced a greater increase in mitophagy than emodin. The mitophagy-promoting effects of KLX and emodin were ascribed to their abilities to enhance the protein stability of Parkin, a key modulator in mitophagy, with different potencies. Molecular docking and SPR analysis demonstrated that KLX has a higher affinity for the ubiquitin-like (UBL) domain of Parkin than emodin. The UBL domain might contribute to the stabilizing effects of KLX on Parkin. In conclusion, this study identifies KLX and emodin as effective anti-heart aging drugs that activate Parkin-mediated mitophagy and outlines their putative therapeutic importance.
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Envelhecimento/efeitos dos fármacos , Antraquinonas/farmacologia , Emodina/farmacologia , Cardiopatias/patologia , Mitofagia/efeitos dos fármacos , Animais , Benzofuranos , Modelos Animais de Doenças , Feminino , Galactose/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Miócitos Cardíacos/efeitos dos fármacos , Quinolinas , Distribuição Aleatória , Ubiquitina-Proteína Ligases/efeitos dos fármacosRESUMO
Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal and progressive fibro-proliferative lung disease, and fibroblast-to-myofibroblast differentiation is a crucial process in the development of IPF. Elongation factor-2 kinase (eEF2K) has been reported to play an important role in various disease types, but the role of eEF2K in IPF is unknown. In this study, we investigated the role of eEF2K in normal lung fibroblast (NHLF) proliferation, differentiation, apoptosis, and autophagy as well as the interaction between eEF2K and p38 MAPK signaling through in vitro experiments. We found that the inhibition of eEF2K markedly augmented cell proliferation and differentiation, suppressed apoptosis and autophagy, and reversed the anti-fibrotic effects of a p38 MAPK inhibitor. Together, our results indicate that eEF2K might inhibit TGF-ß1-induced NHLF proliferation and differentiation and activate NHLF cell apoptosis and autophagy through p38 MAPK signaling, which might ameliorate lung fibroblast-to-myofibroblast differentiation.
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Quinase do Fator 2 de Elongação/metabolismo , Fibroblastos/metabolismo , Miofibroblastos/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Autofagia/efeitos dos fármacos , Diferenciação Celular/fisiologia , Sobrevivência Celular , Células Cultivadas , Humanos , Pulmão/metabolismoRESUMO
It has recently been recognized that a subset of asthma patients suffer from glucocorticoid (GC) insensitivity, and glucocorticoid receptor-ß (GR-ß) is associated with corticosteroid resistance, but the underlying mechanisms remain unknown. Here we demonstrated that Interleukin-17A induced glucocorticoid sensitivity in human bronchial epithelial cells (16HBE) is enhanced, which is depend on E4 promoter-binding protein 4 (E4BP4) mediated GR-ß expression. Our data show that the expression of E4BP4 is significantly up-regulated in 16HBE cells, and the depletion of E4BP4 dramatically decreased glucocorticoid sensitivity in IL-17A induced 16HBE cells. Mechanistic studies revealed that E4BP4 plays a crucial role in Interleukin-17A induced glucocorticoid sensitivity in 16HBE cells via down-regulating GR-ß, which is probably mediated by PI3K/Akt activation. Collectively, we can draw the conclusion that E4BP4 contribute to enhance the GCs sensitivity, which may offer a new strategy for therapeutic intervention for GC-insensitive asthma.
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Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Brônquios/metabolismo , Regulação para Baixo/fisiologia , Glucocorticoides/metabolismo , Receptores de Glucocorticoides/metabolismo , Asma/metabolismo , Células Cultivadas , Células Epiteliais , Humanos , Interleucina-17/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Regulação para Cima/fisiologiaRESUMO
Nonsyndromic hearing loss has been shown to have high genetic heterogeneity. In this report, we aimed to disclose the genetic causes of the subjects from the ten Chinese deaf families who did not have pathogenic common genes/mutation. Next-generation sequencing (NGS) of 142 known deafness genes was performed in the probands of ten families followed by cosegregation analysis of all family members. We identified novel pathogenic variants in six families including p.D1806E/p.R1588W, p.R964W/p.R1588W, and p.G17C/p.G1449D in CDH23; p.T584M/p.D1939N in LOXHD1; p.P1225L in MYO7A; and p.K612X in EYA4. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family. In four families, no pathogenic variants were identified. Our study provided better understanding of the mutation spectrum of hearing loss in the Chinese population.
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Surdez/genética , Mutação , Povo Asiático/genética , China , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , LinhagemRESUMO
BACKGROUND/AIMS: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, and it is usually characterized by chronic inflammation, oxidative stress, and altered microRNA expression. The aim of this study is to investigate how the effects of iridoids with genipin stem nucleus inhibit PCOS complications. The interactions between iridoids were investigated, as well. METHODS: The chronic inflammation cell model was induced using lipopolysaccharide (LPS) in the RAW 264.7 and KGN cell lines. Levels of mRNA and protein expression were quantified using real time-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The target of the iridoids was identified using the drug affinity responsive target stability (DARTS) method. The ability to scavenge free radicals was evaluated using the DPPH radical scavenging method and the ultra oxygen anion (O2-) radical scavenging method. RESULTS: The cells recovered from the inflammatory conditions and showed significantly decreased levels of interleukins after treatment with iridoids. The iridoids were demonstrated to target NF-κB, inhibit the phosphorylation and degradation of IκB, inhibit the nuclear entry of NF-κB, and inhibit the expression of inflammatory factors. Though only genipin showed an efficient ability to scavenge O2-, the iridoids, IκB inhibitor (BAY 11-7085), and NF-κB inhibitor (PDTC) could inhibit LPS-induced oxidative stress on the cells, indicating that the iridoids exert their anti-oxidant effects via the NF-κB pathway. The expression levels of microRNAs (miRNAs) were also altered by LPS, but the iridoids could scarcely rescue the abnormal condition. CONCLUSION: Chronic inflammation may be an important incentive for oxidative stress and abnormal microRNA expression in PCOS, and iridoids can protect patients from inflammatory damage by regulating the NF-κB pathway.
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Inflamação/metabolismo , NF-kappa B/metabolismo , Síndrome do Ovário Policístico/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Feminino , Imunofluorescência , Humanos , Inflamação/induzido quimicamente , Iridoides , Lipopolissacarídeos , Camundongos , NF-kappa B/antagonistas & inibidores , Nitrilas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Células RAW 264.7 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Sulfonas/farmacologiaRESUMO
The investigation of agents for the treatment of osteoporosis has been a long-standing effort. The Wnt pathway plays an important role in bone formation and regeneration, and expression of Wnt pathway inhibitors, Dickkopf-1 (DKK1), appears to be associated with changes in bone mass. Inactivation of DKK1 leads to substantially increased bone mass in genetically manipulated animals. DKK1-derived peptides (DDPs) were added to BMP2-stimulated MC3T3-E1 preosteoblastic cells in vitro to evaluate inhibitory activity of DDPs in MC3T3-E1 cell differentiation. Study was extended in vivo on old female mice to show whether or not inhibition of endogenous DKK1 biological activity using DDPs vaccination approach leads to increase of bone formation, bone density, and improvement of bone microstructure. We reported that synthetic DDPs were able to reduce alkaline phosphatase activity, prevent mineralization and inhibit the differentiation of MC3T3-E1 cells in vitro. Furthermore, vaccination with these DDPs in aged female mice 4 times for a total period of 22 weeks promoted bone mass and bone microstructure. 3D microCT and histomorphometric analysis showed that there were significant increase in bone mineral densities, improvement of bone microstructure and promotion of bone formation in the vaccinated mice, especially in the mice vaccinated with DDP-A and DDP-C. Histological and scanning electron microscopy image analysis also indicated that vaccination increased trabecular bone mass and significantly decreased fragmentation of bone fibers. Taken together, these preclinical results suggest that vaccination with DDPs represents a promising new therapeutic approach for the treatment of bone-related disorders, such as osteoporosis.
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Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Osteogênese/fisiologia , Osteoporose/prevenção & controle , Vacinas/farmacologia , Absorciometria de Fóton , Envelhecimento , Animais , Western Blotting , Modelos Animais de Doenças , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Varredura , Osteoporose/metabolismo , Peptídeos/imunologia , Vacinação , Microtomografia por Raio-XRESUMO
OBJECTIVES: Acute kidney injury (AKI) caused by cisplatin (CDDP) is a complex, critical illness with no effective or specific treatment. The purpose of the study was to assess the protective effect of protopanaxadiol (PPD) on the kidneys in CDDP-induced AKI models and its possible mechanisms. METHODS: In vitro, the protection of PPD was assessed in HK-2. KM mice were injected with CDDP to induce AKI models in vivo. The determination of blood urea nitrogen and serum creatinine (SCr) was performed, and pathological changes were examined by histopathological examination. Immunostaining and western blot analyses were used to analyze the expression levels of proteins. RESULTS: PPD can increase the viability of HK-2 cells damaged by CDDP, improve cell morphology, and alleviate the symptoms of AKI in mice. In addition, PPD can down-regulate the protein expression of TRF and up-regulate the protein expression of Ferritin heavy chain, Glutathione peroxidase 4, and ferroptosis suppressor protein 1 reduce the iron content in cells and kidney tissues, and restore the antioxidant defense system. CONCLUSION: PPD has an inhibitory effect on cisplatin-induced nephrotoxicity, which may be related to the inhibition of ferroptosis by regulating iron metabolism and lipid peroxidation.
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Injúria Renal Aguda , Cisplatino , Ferroptose , Sapogeninas , Cisplatino/toxicidade , Animais , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/metabolismo , Ferroptose/efeitos dos fármacos , Camundongos , Sapogeninas/farmacologia , Humanos , Masculino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Modelos Animais de Doenças , Linhagem Celular , Peroxidação de Lipídeos/efeitos dos fármacos , Ferro/metabolismo , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacosRESUMO
There are limited published studies on patient activation among patients with systemic lupus erythematosus (SLE) in China. Disease activity can significantly influence a patient's perception of their condition, subsequently impacting patient activation. However, the mechanisms through which disease activity influences patient activation remain poorly understood. This study aimed to investigate patient activation among patients with SLE in China and explore the influencing factors. We conducted a cross-sectional study from June to December 2021 at a rheumatology and immunology department of a tertiary hospital in Chengdu, China. Data were collected by questionnaire, including general information, disease activity, quality of chronic illness care, health literacy, self-efficacy, motivation, social support, and patient activation. A patient activation model was constructed based on the conceptual framework derived from the individual and family self-management theory. To evaluate the moderating effect of disease activity on patient activation model, participants were divided into two subgroups (low disease activity group and high disease activity group). 426 SLE patients were included. The mean score of patient activation among SLE patients was 63.28 ± 11.82, indicating that most SLE patients lacked skills and confidence to stick with health-promoting behaviors. Health literacy, social support, and self-efficacy had the greatest effect on patient activation. In the multi-group analysis, social support and health literacy contributed more to patient activation in SLE patients with high and low disease activity, respectively. Patient activation among SLE patients in China was at the third level. Healthcare professionals should help them adhere to health-promoting behaviors. Health literacy, social support, and self-efficacy are vital factors for patient activation. These factors should be prioritized based on disease activity when developing individually tailored interventions for patient activation.
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Letramento em Saúde , Lúpus Eritematoso Sistêmico , Humanos , Participação do Paciente , Estudos Transversais , Inquéritos e QuestionáriosRESUMO
BACKGROUND: This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model. METHODS: CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter. RESULTS: Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth. CONCLUSION: GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.
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Cabelo , Fator de Crescimento Insulin-Like I , Células-Tronco Mesenquimais , Cordão Umbilical , Animais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Humanos , Meios de Cultivo Condicionados/farmacologia , Camundongos , Cordão Umbilical/citologia , Cabelo/crescimento & desenvolvimento , Cabelo/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Gelatina/química , Alicerces Teciduais/química , Camundongos Endogâmicos C57BL , Células Cultivadas , Fator 7 de Crescimento de Fibroblastos/metabolismoRESUMO
Here, amphiphile GCH based on glutamide-cyanostilbene is designed and synthesized, it is found that it can assembly in acetonitrile, and shows circular dichroism signals. After Z-E isomerizaition by UV irradiation, the CD signal of the assembly can be inverted. Unexpectedly, after another heating and cooling process, the circular dichroism signals can be totally inverted even though the E-isomers are in minority. Finally, the molecular dynamics (MD) simulations deeply elucidate the supramolecuar chirality inversion mechanism. This work brings some new insights into the control of chirality inversion, which may provide a perspective for the smart chiroptical materials construction.
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The development of drought has spatial and temporal synchronization. Previous studies usually explore the spatial and temporal evolution of drought separately. Moreover, existing approaches are based on a fixed overlapping area and do not consider the variable drought cluster area during development. This study proposes an improved and simple approach to derive dynamic overlapping area threshold for 3-dimensional droughts extraction. Based on the one monthly Nonparametric Standardized Precipitation Index (NSPI), this improved approach was applied for investigating the migration characteristics of meteorological drought events in the Loess Plateau of China. Then, Random Forest and Extreme Gradient Boosting model with Shapley additive explanation values were used to quantify the importance of driving factors on the dynamics of drought characteristics. The results showed that: (1) the improved approach has a better performance on identifying prolonged droughts than the method using a fixed overlap area threshold; (2) spatially, meteorological drought events with high severity (DS), long duration (DD), large effected area (DA) and fast migration velocity (DV) mainly occur in the central region; (3) temporally, droughts are expected to aggravate with significantly increased DS and DA which are mainly caused by increased temperature and vegetation; and (4) meteorological droughts have a preferred westward migration direction and three dominant migration paths, which are crucial for local drought prevention and control. The findings of this study provide new perspectives on drought migration characteristics, which are important for the exploration of drought-driven mechanisms, risk assessment and future prediction.
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Lupus nephritis (LN) is a kidney disease that occurs after systemic lupus erythematosus (SLE) affects the kidneys. Pentraxin 3 (PTX3) is highly expressed in the serum of patients with LN. Renal PTX3 deposition is directly related to clinical symptoms such as proteinuria and inflammation. The excessive proliferation of mesangial cells (MCs) is one of the representative pathological changes in the progression of LN, which is closely related to its pathogenesis. Protopanaxadiol (PPD) is the main component of ginsenoside metabolism and has not been reported in LN. The aim of this study was to investigate the relationship between PTX3 and mesangial cell proliferation and to evaluate the potential role and mechanism of PPD in improving LN. PTX3 is highly expressed in the kidneys of LN patients and LN mice and is positively correlated with renal pathological indicators, including proteinuria and PCNA. The excessive expression of PTX3 facilitated the proliferation of MCs, facilitated the activation of the MAPK/ERK1/2 signaling pathway, and increased the expression of HIF-1α. Further studies showed that PPD can effectively inhibit the abnormal proliferation of MCs with high expression of PTX3 and significantly improve LN symptoms such as proteinuria in MRL/lpr mice. The mechanism may be related to the inhibition of the PTX3/MAPK/ERK1/2 pathway. In this study, both in vitro, in vivo, and clinical sample results show that PTX3 is involved in the regulation of MCs proliferation and the early occurrence of LN. Natural active compound PPD can improve LN by regulating the PTX3/MAPK/ERK1/2 pathway.
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Proteína C-Reativa , Nefrite Lúpica , Sistema de Sinalização das MAP Quinases , Sapogeninas , Componente Amiloide P Sérico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/metabolismo , Animais , Sapogeninas/farmacologia , Proteína C-Reativa/metabolismo , Camundongos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Feminino , Componente Amiloide P Sérico/metabolismo , Proliferação de Células/efeitos dos fármacos , Adulto , Masculino , Camundongos Endogâmicos MRL lpr , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologiaRESUMO
Constant efforts have been made to move towards maintaining the positive anti-inflammatory functions of glucocorticoids (GCs) while minimizing side effects. The anti-inflammatory effect of GCs is mainly attributed to the inhibition of major inflammatory pathways such as NF-κB through GR transrepression, while its side effects are mainly mediated by transactivation. Here, we investigated the selective glucocorticoid receptor modulator (SGRM)-like properties of a plant-derived compound. In this study, glucocorticoid receptor (GR)-mediated alleviation of inflammation by SP-8 was investigated by a combination of in vitro, in silico, and in vivo approaches. Molecular docking and cellular thermal shift assay suggested that SP-8 bound stably to the active site of GR via hydrogen bonding and hydrophobic interactions. SP-8 activated GR, induced GR nuclear translocation, and inhibited NF-κB pathway activation. Furthermore, SP-8 did not up-regulate the gene and protein expression of PEPCK and TAT in HepG2 cells, and it did not induce fat deposition like GC and has little effect on bone metabolism. Interestingly, SP-8 upregulated GR protein expression and did not cause GR phosphorylation at Ser211 in RAW264.7 cells. This work proved that SP-8 dissociated characteristics of transrepression and transactivation can be separated. In addition, the in vitro and in vivo anti-inflammatory effects of SP-8 were confirmed in LPS-induced RAW 264.7 cells and in a mouse model of DSS-induced ulcerative colitis, respectively. In conclusion, SP-8 might serve as a potential SGRM and might hold great potential for therapeutic use in inflammatory diseases.
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Non-muscle invasive bladder cancer (NMIBC) refers to a subtype of bladder carcinoma where cancer is localized in the inner lining of bladder. NMIBC consider as one of most costly malignancy and requires significant surgical and therapeutic measure. However, recurrence and progression of tumor is common in treated patients. Here we presented an integrated OMICs approach for the identification and inhibition of NMIBC specific genes. We utilized a case study where three group of patients were compared: 1) Relapsed tumors 2) recurrent tumors and 3) tumor in progression. Common transcriptome signature between patients facing recurrence and progression allowed us to identify three NMIBC specific genes FLT-1, WHSC-1 and CD34. We further utilized novel approach of Co-expressed gene-set enrichment analysis (COGENA) on the differentially expressed genes of this case study. Three drugs (paroxetine, adiphenine and H-89) with role of receptors inhibition were identified and predicted as repurposed drugs for the inhibition NMIBC specific genes. We further tested this hypothesis by performing molecular docking and simulation analysis between cancer specific proteins and drugs. FLT-1 have shown significant stable interaction with both drugs paroxetine and adiphenine whereas WHSC-1 have shown compact interaction with adiphenine and H-89. In the light of these evidence, we suggest that adiphenine could be repositioned as alternate targeted medicine for the treatment of NMIBC. In the future, this study will help for strengthening the strategies development at the molecular level for the control of carcinomas at early as well as detection of active and binding site, receptor-ligand interaction and also make drug repurposing for the early treatment of the carcinomas.Communicated by Ramaswamy H. Sarma.
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BACKGROUD: Arsenic trioxide (ATO), the first-line drug in treating acute premyelogenous leukemia, has the profound side effect of inducing endothelial mesenchymal transition (EndMT) and causing cardiac fibrosis. Diosgenin (DIO), a pharmaceutical compound found in Paris polyphylla, exhibits promising potential in safeguarding cardiovascular health by mitigating EndMT. PURPOSE: This study aims to explore the role and mechanism of DIO in ATO-induced myocardial fibrosis to provide a novel therapeutic agent for ATO-induced cardiac fibrosis. METHODS: Wistar rats were given DIO by gavage and ATO by tail vein. Cardiac function and fibrosis were evaluated by echocardiography and Masson's trichrome staining in rats. Human aortic endothelial cells (HAECs) were utilized to analyze ATO-induced EndMT in vitro. The cytoskeleton of HAECs was visualized using F-actin staining to observe cell morphology, while Dil-Ac-LDL staining was employed to assess cell functionality. EndMT-related factors (CD31 and α-SMA), glucocorticoid receptor (GR) and interleukin-6 (IL-6) were detected by immunofluorescence and Western blot in vivo and in vitro. Furthermore, GR was knocked down by si-GR, and IL-6 was blocked by IL-6 neutralizing antibody to verify their role in the effect of DIO on ATO-induced EndMT in HAECs. RESULTS: DIO exhibited significant efficacy in ATO-induced damage to both cardiac diastolic and systolic function, along with mitigating cardiac fibrosis. Additionally, DIO alleviated the loss of cytoskeletal anisotropy and enhanced the uptake of Dil-Ac-LDL in HAECs. Furthermore, it reversed the ATO-induced downregulation of endothelial-specific markers CD31 and GR, while suppressing the upregulation of mesenchymal markers α-SMA and IL-6, both in vivo and in vitro. Notably, the protective effect of DIO was compromised upon knockdown of GR, which also led to a reversal of DIO-induced IL-6 downregulation. Furthermore, the neutralization of IL-6 with specific antibodies abolished the ATO-induced changes related to EndMT. CONCLUSION: In this study, we clarified the protective effect of DIO on ATO-induced myocardial fibrosis against EndMT via the GR/IL-6 axis for the first time and provided a potential therapeutic agent for preventing heart damage caused by ATO.
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Trióxido de Arsênio , Diosgenina , Células Endoteliais , Fibrose , Ratos Wistar , Animais , Fibrose/tratamento farmacológico , Humanos , Masculino , Diosgenina/farmacologia , Diosgenina/análogos & derivados , Células Endoteliais/efeitos dos fármacos , Ratos , Interleucina-6/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Actinas/metabolismo , Miocárdio/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Transição Endotélio-MesênquimaRESUMO
Analogues of pyrrolo-[1,2,5]benzothiadiazepine were prepared and evaluated against Schistosoma japonica. The biological data revealed that most benzothiazepine derivatives show anti-schistosomal activity to some extent, while α-chloronation of the title compound and another bioisosteric derivative pyrrolo-[1,2,5]benzodiazepine displayed the most distinct worm killing activity. This study proved that benzodiazepine may serve as a novel structural skeleton for the development of anti-schistosomal agents.
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Desenho de Fármacos , Pirróis/farmacologia , Schistosoma japonicum/efeitos dos fármacos , Tiazepinas/farmacologia , Animais , Estrutura Molecular , Pirróis/síntese química , Pirróis/química , Relação Estrutura-Atividade , Tiazepinas/síntese química , Tiazepinas/químicaRESUMO
OBJECTIVE: Thermal ablation, including microwave ablation (MWA) and radiofrequency ablation (RFA), has been recommended for the treatment of primary hyperparathyroidism (PHPT) and refractory secondary hyperparathyroidism (SHPT). This meta-analysis was conducted to evaluate the efficacy and safety of MWA and RFA in patients with PHPT and refractory SHPT. METHODS: Databases including PubMed, EMbase, the Cochrane Library, CNKI (China National Knowledge Infrastructure), and Wanfang were searched from inception to December 5, 2022. Eligible studies comparing MWA and RFA for PHPT and refractory SHPT were included. Data were analyzed using Review Manager software, version 5.3. RESULTS: Five studies were included in the meta-analysis. Two were retrospective cohort studies, and three were RCTs. Overall, 294 patients were included in the MWA group, and 194 patients were included in the RFA group. Compared with RFA for refractory SHPT, MWA had a shorter operation time for a single lesion (P < 0.01) and a higher complete ablation rate for a single lesion ≥ 15 mm (P < 0.01) but did not show a difference in the complete ablation rate for a single lesion < 15 mm (P > 0.05). There were no significant differences between MWA and RFA for refractory SHPT concerning parathyroid hormone (P > 0.05), calcium (P > 0.05), and phosphorus levels (P > 0.05) within 12 months after ablation, except that calcium (P < 0.01) and phosphorus levels (P = 0.02) in the RFA group were lower than those in the MWA group at one month after ablation. There was no significant difference between MWA and RFA concerning the cure rate of PHPT (P > 0.05). There were no significant differences between MWA and RFA for PHPT and refractory SHPT concerning the complications of hoarseness (P > 0.05) and hypocalcaemia (P > 0.05). CONCLUSION: MWA had a shorter operation time for single lesions and a higher complete ablation rate for large lesions in patients with refractory SHPT. However, there was no significant difference in efficacy and safety between MWA and RFA in cases of both PHPT and refractory SHPT. Both MWA and RFA are effective treatment methods for PHPT and refractory SHPT.
Assuntos
Técnicas de Ablação , Ablação por Cateter , Hiperparatireoidismo Secundário , Ablação por Radiofrequência , Humanos , Cálcio , Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/métodos , Estudos Retrospectivos , Micro-Ondas/uso terapêutico , Ablação por Radiofrequência/efeitos adversos , Ablação por Radiofrequência/métodos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Resultado do Tratamento , Fósforo , Ablação por Cateter/efeitos adversosRESUMO
Non-muscle invasive bladder cancer (NMIBC) is one of the most common type of bladder cancer. Here, we have utilized an integrated transcriptomic-computational approach to identify alternate treatments to the NMIBC. In this study, we have performed the comprehensive comparative analysis between three groups of 36 patients with non-relapsed (NR), recurrence and progressive symptoms. Differentially expressed genes involved in the pathways associated with the NMIBC were identified. In silico protein-protein interaction (PPI) network was performed to create the network of the hub genes associated with NMIBC. Further, we compared NR individuals with two cohorts of patients with recurrent and progressive symptoms that lead to the identification of three major biomarkers CD34, FLT1 and WHSC1 genes. Concurrently, PPI also suggests that they are significant hub genes responsible for disease recurrence and progression. Furthermore, targeted genes WHSC-1 and FLT-1 were subjected to virtual screening for identification phytochemical inhibitors. Docking and molecular dynamics simulations concluded that the phytochemicals anonymously named 'UNK' and '6-hydroxycyanidin' are suitable for the inhibition of the proteins causing the NMIBC. In the future, this study will help for strengthening the strategies development at the molecular level for the control of carcinomas at early as well as detection of active and binding site, receptor-ligand interaction and also make drug designing for the early treatment of the carcinomas.Communicated by Ramaswamy H. Sarma.