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Diabetic kidney disease （DKD） is a common microvascular complication of diabetics mellitus （DM） and the leading cause of end-stage renal disease （ESRD）. Renal interstitial fibrosis （RIF） is the primary pathological basis for DKD progression to ESRD， which significantly increases the mortality rate of DKD patients and burdens patients and society， and it is thus a clinical problem that needs to be solved urgently. The pathogenesis of RIF is complex and mainly associated with excessive deposition of extracellular matrix （ECM）， epithelial-mesenchymal transition （EMT）， oxidative stress， inflammation， and autophagy. Multiple signaling pathways such as transforming growth factor-β1/Smad （TGF-β1/Smad）， nuclear transcription factor-κB （NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， secretory glycoprotein/β-catenin （Wnt/β-catenin）， mammalian target of rapamycin （mTOR）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， neurogenic site-gap homologous protein （Notch）， and nuclear factor E2-associated factor 2 （Nrf2） mediate the development of RIF， which are currently novel targets for DKD therapy. Due to the complexity of its pathogenesis， the current Western medical treatment mainly focuses on essential treatment to improve metabolism， which has poor efficacy and is difficult to prevent the progression of DKD， so it is significant to find new treatment methods clinically. In recent years， many studies have proved that traditional Chinese medicine can alleviate oxidative stress， inhibit inflammatory response， and regulate cellular autophagy by modulating relevant signaling pathways， so as to treat RIF in DKD， which has the advantages of multi-pathway， multi-targeting， multi-linking， and significant therapeutic efficacy. However， there is still a lack of relevant summary. By reviewing the latest research reports in China and abroad， this article examines the roles of the signaling pathways mentioned above in the occurrence and development of RIF in DKD and the recent research progress in the intervention of RIF in DKD by traditional Chinese medicine via these pathways， aiming to provide new ideas and references for further scientific research and clinical practice.
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Neuroinflammation is a common pathological feature of neurodegenerative diseases （NDs）. Microglia （MG）， a resident macrophage in the brain with a unique developmental origin， is the core driver of neuroinflammation. It can participate in the occurrence and development of NDs through different polarization states and play a key role in regulating neurogenesis and synapse shaping and maintaining homeostasis. MG can be divided into M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype according to its function. The inflammatory mediators released by the M1 phenotype can lead to nerve degeneration and myelin sheath damage， while the activation of the M2 phenotype is required to inhibit the inflammatory response and promote tissue repair. With the advantages of multi-pathway， multi-target， and bidirectional regulation， traditional Chinese medicine can regulate the polarization balance of MG and has dual effects on NDs such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis. The active components of traditional Chinese medicine and its compound can inhibit the activation of MG by regulating phosphatidylinositol-3-kinases/protein kinase B（PI3K/Akt）， NOD-like receptor thermal protein domain associated protein 3（NLRP3）， signal transducer and activator of transcription factor1（STAT1）， nuclear transcription factor kappa B（NF-κB）， and other pathways， promote the polarization of M1 phenotype to M2 phenotype， reduce the expression of interleukin（IL）-6， tumor necrosis factor-α（TNF-α）， and other pro-inflammatory factors， and increase the secretion of IL-10， arginase-1（Arg-1）， and other anti-inflammatory factors. It can also reduce β-amyloid deposition and tau protein expression in Alzheimer's disease， alleviate dopaminergic neuronal damage in Parkinson's disease， and relieve demyelination， inflammatory cell infiltration， and related clinical symptoms of multiple sclerosis. The bidirectional regulation of the M1/M2 polarization balance of MG by traditional Chinese medicine is a potential strategy for the treatment of NDs. This paper focused on the targets of the regulation of MG polarization balance by traditional Chinese medicine monomer and its compound in the treatment of NDs， so as to further study and summarize the existing research results and provide ideas and basis for the future treatment of NDs.
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AIM:To identify transcriptional differences between the ocular surface ectoderm(OSE)and surface ectoderm(SE)using RNA-seq, and elucidate the OSE transcriptome landscape and the regulatory networks involved in its development.METHODS:OSE and SE cells were differentiated from human embryonic stem(hES)cells. Differentially expressed genes(DEGs)between OSE and SE were analyzed using RNA-seq. Based on the DEGs, we performed gene ontology(GO)analysis, Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis, and protein-protein interaction(PPI)network analysis. Transcription factors(TFs)and hub genes were screened. Subsequently, TF-gene and TF-miRNA regulatory networks were constructed using the NetworkAnalyst platform.RESULTS:A total of 4 182 DEGs were detected between OSE and SE cells, with 2 771 up-regulated and 1 411 down-regulated genes in OSE cells. GO-BP analysis revealed that up-regulated genes in OSE were enriched in the regulation of ion transmembrane transport, axon development, and modulation of chemical synaptic transmission. Down-regulated genes were primarily involved in nuclear division, chromosome segregation, and regulation of cell cycle phase transition. KEGG analysis indicated that up-regulated genes in OSE cells were enriched in signaling pathways such as cocaine addiction, axon guidance, and amphetamine addiction, while down-regulated genes were enriched in proteoglycans in cancer, ECM-receptor interaction, protein digestion and absorption, and cytokine-cytokine receptor interaction. Additionally, compared with SE, 204 TFs(including FOS, EGR1, POU5F1, SOX2, and PAX6)were up-regulated, and 80 TFs(including HAND2, HOXB6, HOXB5, HOXA5, and HOXB8)were down-regulated in OSE cells. Furthermore, we identified 6 up-regulated and 9 down-regulated hub genes in OSE cells, and constructed TF-gene and TF-miRNA regulatory networks based on these hub genes.CONCLUSIONS:The transcriptome characteristics of OSE and SE cells were elucidated through RNA-seq analysis. These findings may provide a novel insight for studies on the development and in vitro directed induction of OSE and corneal epithelial cells.
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The NLRP3 inflammasome is a cellular multimeric protein complex that plays a crucial role in inflammation and immune responses. It consists of three main components: Nod-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing(ASC)and cysteine protease 1(caspase-1). Uveitis is a broad term encompassing a range of inflammatory diseases that primarily affect the iris, ciliary body, vitreous, retina and choroid. It is considered a major cause of blindness globally. Numerous studies have demonstrated the involvement of NLRP3 inflammasome in the onset and progression of uveitis, indicating its potential as a significant therapeutic target for uveitis in the future. This article provides an overview of the structure, biological functions and activation pathways of the NLRP3 inflammasome, as well as the current research progress on its association with different types of uveitis. Additionally, it discusses the application potential of the NLRP3 inflammasome in the treatment of uveitis.
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ABSTRACT Purpose: to report scientific evidence on the impact of aphasia on central auditory processing and map the contribution of auditory training to aphasic individuals. Methods: a scoping review approaching national and international databases (SciELO, LILACS, PubMed, Scopus, and Cochrane Library) and the gray literature (Google Scholar and Open Grey). The inclusion criteria covered articles that addressed the interface between central auditory processing and aphasia, excluding duplicates, literature reviews, and scientific abstracts. Literature Review: the review comprised 13 articles that met the eligibility criteria for this study. Seven of the selected articles assessed central auditory processing, four used electrophysiological examinations (such as auditory brainstem response and long-latency auditory evoked potentials) to assess the auditory pathway, and only one analyzed the intervention in aphasic individuals with auditory training. Conclusion: scientific evidence points to an important change in aphasic people's central auditory processing, with impaired figure-ground, auditory closure, temporal resolution and ordering, and binaural integration. Moreover, it is relevant to assess auditory processing, given the contribution of auditory training in speech-language-hearing therapy for a better prognosis in the rehabilitation of aphasia.
RESUMO Objetivo: reportar as evidências científicas do impacto da afasia no Processamento Auditivo Central e mapear a contribuição do Treinamento Auditivo para a população afásica. Métodos: trata-se de uma revisão de escopo realizada nas bases de dados nacionais e internacionais: Scielo, Lilacs, Pubmed, Scopus, Cochrane Library e com uma busca adicional à literatura cinzenta no Google Scholar e Open Grey. Os critérios de inclusão abrangeram artigos que abordassem a interface do processamento auditivo central e afasia, excluindo-se as duplicações, artigos de revisão da literatura e resumos científicos. Revisão de Literatura: selecionaram-se 13 artigos que cumpriram os critérios de elegibilidade deste estudo. Dos artigos selecionados, sete apresentaram a avaliação do Processamento Auditivo Central, quatro apresentaram os exames eletrofisiológicos - como os exames de Potencial Evocado Auditivo de Tronco Encefálico (PEATE) e Potencial Evocado Auditivo de Longa Latência (PEALL) - para avaliação da via auditiva e apenas um estudo analisou a intervenção dos indivíduos afásicos por meio do treinamento auditivo. Conclusão: as evidências científicas apontam importante alteração no Processamento Auditivo Central dos afásicos, apresentando prejuízos nas habilidades auditivas de figura-fundo, fechamento auditivo, resolução e ordenação temporal e integração binaural. Ainda, demonstra-se como relevante a avaliação do processamento, devido à contribuição do Treinamento Auditivo nas terapias fonoaudiológicas para um melhor prognóstico na reabilitação das afasias.
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Abstract Background: In 1996 Iturralde et al. published an algorithm based on the QRS polarity to determine the location of the accessory pathways (AP), this algorithm was developed before the massive practice of invasive electrophysiology. Purpose: To validate the QRS-Polarity algorithm in a modern cohort of subjects submitted to radiofrequency catheter ablation (RFCA). Our objective was to determinate its global accuracy and its accuracy for parahisian AP. Methods: We conducted a retrospective analysis of patients with Wolff-Parkinson-White (WPW) syndrome who underwent an electrophysiological study (EPS) and RFCA. We employed the QRS-Polarity algorithm to predict the AP anatomical location and we compared this result with the real anatomic location determined in the EPS. To determine accuracy, the Cohen's kappa coefficient (k) and the Pearson correlation coefficient were used. Results: A total of 364 patients were included (mean age 30 years, 57% male). The global k score was 0.78 and the Pearson's coefficient was 0.90. The accuracy for each zone was also evaluated, the best correlation was for the left lateral AP (k of 0.97). There were 26 patients with a parahisian AP, who showed a great variability in the ECG features. Employing the QRS-Polarity algorithm, 34.6% patients had a correct anatomical location, 42.3% had an adjacent location and only 23% an incorrect location. Conclusion: The QRS-Polarity algorithm has a good global accuracy; its precision is high, especially for left lateral AP. This algorithm is also useful for the parahisian AP.
Resumen Antecedentes: En 1996 Iturralde y colaboradores publicaron un algoritmo basado en la polaridad del QRS para determinar la ubicación de las vías accesorias (VA), este algoritmo fue desarrollado antes de la práctica masiva de la electrofisiología invasiva. Objetivo: Validar el algoritmo de la polaridad del QRS en una cohorte moderna de sujetos sometidos a ablación con catéter por radiofrecuencia (ACRF). Nuestro objetivo fue determinar su precisión global y su precisión para las VA parahisianas. Métodos: Realizamos un análisis retrospectivo de pacientes con síndrome de Wolff-Parkinson-White (WPW) a los que se les realizó estudio electrofisiológico (EEF) y ACRF. Empleamos el algoritmo de la polaridad del QRS para predecir la ubicación anatómica de la VA y comparamos este resultado con la ubicación anatómica real determinada en el EEF. Para determinar la precisión se utilizaron el coeficiente kappa de Cohen (k) y el coeficiente de correlación de Pearson. Resultados: Se incluyeron un total de 364 pacientes (edad media 30 años, 57 % varones). La puntuación k global fue de 0,78 y el coeficiente de Pearson de 0,90. También se evaluó la precisión para cada zona, la mejor correlación fue para las VA laterales izquierdas (k de 0.97). Hubo 26 pacientes con VA parahisianas, que mostraron una gran variabilidad en las características del ECG. Empleando el algoritmo de la polaridad del QRS, el 34,6 % de los pacientes tenía una ubicación anatómica correcta, el 42,3 % tenía una ubicación adyacente y solo el 23 % una ubicación incorrecta. Conclusión: El algoritmo de la polaridad del QRS tiene una buena precisión global; su precisión es alta, especialmente para VA lateral izquierdo. Este algoritmo también es útil para la VA parahisiana.
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Heavy metals, generally characterized by high densities and atomic weights, are ubiquitous in the environment and are a public health concern due to the several health issues they pose to humans. Of all heavy metals, lead and cadmium among others are known to be capable of inducing multiple health effects even at a low rate of exposure. Hypertension (HYP), a major cause of death and a risk factor for other cardiovascular diseases, is known to be caused by both lead and cadmium. While the mechanism underlying the development of HYP induced by independent exposure to lead and cadmium has been well studied, the mechanism underlying the induction and progression of HYP upon lead and cadmium co-exposure remains mildly explored. Hence, this study aimed to elucidate the mechanism using a toxicogenomic approach. The set of genes affected by both heavy metals was identified using the comparative toxicogenomics database (CTD) while HYP targets were retrieved from the Gene Cards database. The shared genes between the heavy metals and the disease were identified and subjected to further analysis. The results of our analysis revealed the signaling pathways that are dysregulated by lead and cadmium co-exposure while oxidative stress, inflammation, and endothelial dysfunction were revealed as processes pertinent to the induction and progression of HYP by lead and cadmium co-exposure. Biomarkers that could be used for prognosis evaluation were also identified. Ultimately, this study supports and advances the growing body of finding on the roles played by lead and cadmium co-exposure in inducing HYP.
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Introduction: Face transplantation has gained recognition, changing the clinicalsurgical scenario for restoring complex facial defects, as it attributes functional and aesthetic recovery to patients who have suffered serious accidents. At the time of writing this article, in official publications, 43 patients had already undergone facial transplantation worldwide. Face transplantation has numerous pieces of evidence that can irrefutably provide improvements to the patient. For this, preoperative care for the patient must be carefully established so that there is good surgical performance. Case Report: Male patient, 46 years old, reports that, at the age of 6, he had burns due to exposure to gasoline, with 72% of his body surface burned, showing sequelae of burns and surgical reconstructions on the face, with redundant and ptotic skin flap on the left cheek, absence of upper and lower lip and exposure of lower teeth. Conclusion: It is important to publicize this innovative procedure in different medical specialties and preoperative care through a thorough investigation, which attributes better surgical effectiveness, allowing the rescue of their facial identity, once stigmatized.
Introdução: O transplante de face adquiriu reconhecimento, alterando o panorama clínico-cirúrgico para a restauração de defeitos faciais complexos, visto que atribui recuperação funcional e estética a pacientes que sofreram acidentes graves. Até o momento da redação deste artigo, em publicações oficiais, 43 pacientes já haviam realizado o transplante facial em todo mundo. O transplante de face possui inúmeras evidências que podem fornecer melhorias ao paciente de forma irrefutável. Para isso, cuidados pré-operatórios ao paciente devem ser cuidadosamente estabelecidos para que haja um bom desempenho cirúrgico. Relato de Caso: Paciente sexo masculino, 46 anos, relata que, aos 6 anos de idade, teve queimadura por exposição à gasolina, com 72% de superfície corporal queimada, apresentando sequelas de queimaduras e reconstruções cirúrgicas na face, com retalho cutâneo redundante e ptótico em bochecha esquerda, ausência de lábio superior e inferior e exposição dos dentes inferiores. Conclusão: Ressalta-se a importância da divulgação desse procedimento inovador em diferentes especialidades médicas e dos cuidados pré-operatórios através de uma investigação minuciosa, que atribuem uma melhor eficácia cirúrgica, possibilitando o resgate de sua identidade facial, uma vez estigmatizada.
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Diabetic retinopathy （DR） is one of the most common chronic microvascular complications of diabetes mellitus. It has a high rate of blindness， and the age of onset is gradually getting younger， which seriously affects the physical and mental health and quality of life of patients. The disease is retinal damage induced by diabetes mellitus， which is a kind of fundus disease with the main manifestations of fundus hemorrhage， hard exudation， microhemangioma， cotton-wool spots， neovascularization， etc. In traditional Chinese medicine （TCM）， it is classified into the category of "diabetic cataracts" and other diseases. At present， there is no effective method to prevent the progress of the disease in modern medicine， so it is particularly important to choose a reasonable and effective intervention to prevent and treat DR. Studies have confirmed that TCM has unique advantages in the treatment of DR. It can use its advantages of multiple bioactive components， multiple targets， and multiple pathways to intervene in the development process of DR from various aspects. By searching for the relevant literature on the progress of the intervention of DR with TCM monomers and compounds， this paper mainly reviews the relevant research results of the treatment of DR with multiple signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa-B（NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， nuclear factor erythroid 2-related factor （Nrf2）/hemeoxygenase-1 （HO-1）， Hippo， advanced glycation end products （AGEs）/receptor for advanced glycation end products （RAGE）， and Akt/glycogen synthase kinase-3β （GSK-3β）， so as to provide more ideas and directions for the clinical prevention and treatment of DR.
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The tiered medical treatment system stands as a cornerstone in the deepening reforms of China′s medical and health sectors, playing a crucial role in building a healthy China. Exploring the harmonious coexistence mechanism of multiple entities on the supply and demand sides of the tiered diagnosis and treatment system, and promoting the formation of a scientific and reasonable tiered diagnosis and treatment order, has become an urgent public proposition that needs to be answered and has significant social impact. Addressing the challenges in China′s tiered medical treatment system, particularly its need for a more systematic, comprehensive, and collaborative approach, this study is informed by a thorough literature review. Based on the harmonious management and symbiosis theories, the authors proposed a theoretical concept and future research path for the formation of a harmonious symbiotic mechanism in the tiered diagnosis and treatment system, in order to pave the way for exploring the harmonious symbiotic mechanism in the tiered diagnosis and treatment system.
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Objective:To investigate the metabolic profile of fatty acids in elderly frail patients, and its value as a biomarker of frailty.Methods:Forty-nine older adults were recruited, of whom 19 were non-frail while 15 were in the pre-frail or frail phase.Targeted metabolomics was used to detect the serum levels of fatty acids, concerning 38 short-, medium-and long-chain fatty acids.Results:Metabolomics indicated elevated levels of 9 long-chain fatty acids in the serum of the elderly frail patients, with a 1.056-fold increase in the risk of fatigue for every 1 unit increase in the level of HOMO-γ-linolenic acid( OR=2.056, P=0.016). No metabolic differences were found between the pre-frail and non-frail groups.Three and seven long-chain fatty acids were negatively correlated with the grip strength and gait speed, respectively.The γ-linolenic acid was positively correlated with body mass index(BMI), percent body fat, visceral fat area and other indicators reflecting adipose tissue.However, no correlation was found between skeletal muscle, laboratory indicators or fatty acids.Five metabolic pathways were correlated with frailty, namely fatty acid biosynthesis, fatty acid metabolism, fatty acid elongation in mitochondria, linoleic acid metabolism and α-linolenic acid metabolism. Conclusions:Nine unsaturated fatty acids, including HOMO-γ-linolenic acid and γ-linolenic acid, may be potential biomarkers of frailty in the elderly.However, the value of fatty acid metabolomics for identifying pre-frail elderly people needs to be further investigated.
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Myopia has become a global public health concern with its increasing prevalence.It is the interaction result of genetic and environmental factors.Exploration of the changes of metabolites in myopia is helpful to know new clues about its pathogenic mechanism.Metabolomics focuses on the integral analysis of all small molecular metabolites (relative molecular mass <1 000) which form a biological system and it is used as an effective tool to discover potential biomarkers.Metabolomic analysis of the myopic population could discover the metabolic changes related to myopia and screen the markers with potential biological significance, which can be used in the early diagnosis and treatment of myopia.It has been found that metabolites related to oxidative stress and inflammation play an important role in the development of myopia.Abnormal energy metabolism and amino acid metabolism are associated with myopic fundus changes.In addition, classical myopia-associated metabolites such as retinoic acid, dopamine and vitamin D, other metabolites such as melatonin, cyclic adenosine monophosphate and 5-hydroxy indole acetic acid, as well as multiple metabolic pathways such as fatty acid metabolism and mitochondrial metabolism are all closely related to myopia.This article systematically reviewed metabolomics researches on myopia, providing clues for better prevention and control of myopia in the future.
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Chinese materia medica can inhibit the proliferation, invasion, migration and expression of drug-resistant proteins of lung cancer stem cells (LCSCs), and induce apoptosis and delay self-renewal, as well as exert anti-tumor effects by interfering with their ecological niche, immune microenvironment and aerobic glycolysis, etc. The biomarkers involved mainly include CD133, CD44, ALDH and ABCG2, while the related signaling pathways are Wnt/β-catenin, Hedgehog, and Notch. The research on the intervention of LCSCs by Traditional Chinese Medicine (TCM) is generally few, mostly concentrated in basic research, and the selected experimental indicators have a high repetition rate, involving fewer cell types and signaling pathways; there is a relative lack of clinical trials, which lack an organic connection with basic experiments. In the future, the quality of research is expected to be improved, and in-depth study of TCM with anti-lung cancer stem cell effect should be carried out, with the purpose to promote the precise treatment of lung cancer.
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ObjectiveUltra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UHPLC-Q-Orbitrap HRMS） was used to identify the metabolites of limonin in rats， and to explore the gender differences in the distribution of prototype components and metabolites in rats after single dose intragastric administration of limonin， as well as to speculate the metabolic pathways. MethodThe separation was performed on a Thermo Scientific Accucore™ C18 column（3 mm×100 mm， 2.6 μm） with 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） as mobile phase in a gradient elution mode（0-1 min， 5%B； 1-6 min， 5%-20%B； 6-18 min， 20%-50%B； 18-23 min， 50%-80%B； 23-25 min， 80%-95%B； 25-30 min， 95%B） at a flow rate of 0.3 mL·min-1 and a column temperature of 30 ℃. MS data of biological samples were collected under the positive ion mode of electrospray ionization（ESI） and in the scanning range of m/z 100-1 500. Plasma， tissues（heart， liver， spleen， lung， kidney， stomach and small intestine）， urine and fecal samples were collected and prepared after intragastric administration， and the prototype component and metabolites of limonin were identified. ResultThe prototype component of limonin were detected in the feces， stomach， small intestine of female and male rats， and in the heart， liver， spleen， lung and kidney tissues of female rats. A total of 23 metabolites related to limonin were detected in rats， of which 2， 1， 5， 4， 23 metabolites were detected in liver， stomach， small intestine， urine and feces， respectively， and the main metabolic pathways were hydrolysis， reduction， hydroxylation and methylation， etc. The distribution of some metabolites differed between male and female rats. ConclusionThe prototype component of limonin are mainly distributed in the stomach and small intestine in rats， and the distribution of prototype component and some metabolites are different by gender. Limonin is mainly excreted through feces with phase Ⅰ metabolites as the main ones. The results of this study can provide a reference for further elucidation of the effect of gender differences on the metabolism of limonin in vivo and its mechanism of action.
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Microgravity is a typical feature of the space. A large number of space flights and foundation simulation experiments have shown that cells show typical biological characteristics of aging, such as reduced cell proliferation and cell cycle arrest under microgravity or simulated microgravity. However, the molecular mechanism by which microgravity or simulated microgravity affects cellular senescence is not well understood. Understanding the mechanism controlling cellular senescence induced by microgravity environment is helpful for exploring anti-aging strategies and targeted interventions in space. In recent years, domestic and foreign scholars have carried out a number of researches and explorations on the effect of microgravity and simulated microgravity on cellular senescence as well as the related mechanisms. In this review, the latest research progress of this filed was summarized.
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OBJECTIVE@#To investigate the effect of emodin on high glucose (HG)-induced podocyte apoptosis and whether the potential anti-apoptotic mechanism of emodin is related to induction of adenosine-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)-mediated autophagy in podocytes (MPC5 cells) in vitro.@*METHODS@#MPC5 cells were treated with different concentrations of HG (2.5, 5, 10, 20, 40, 80 and 160 mmol/L), emodin (2, 4, 8 µ mol/L), or HG (40 mmol/L) and emodin (4 µ mol/L) with or without rapamycin (Rap, 100 nmol/L) and compound C (10 µ mol/L). The viability and apoptosis of MPC5 cells were detected using cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy marker light chain 3 (LC3) I/II, and AMPK/mTOR signaling pathway-related proteins were determined by Western blot. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy.@*RESULTS@#HG at 20, 40, 80 and 160 mmol/L dose-dependently induced cell apoptosis in MPC5 cells, whereas emodin (4 µ mol/L) significantly ameliorated HG-induced cell apoptosis and caspase-3 cleavage (P<0.01). Emodin (4 µ mol/L) significantly increased LC3-II protein expression levels and induced RFP-LC3-containing punctate structures in MPC5 cells (P<0.01). Furthermore, the protective effects of emodin were mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 µ mol/L) reversed emodin-induced autophagy activation.@*CONCLUSION@#Emodin ameliorated HG-induced apoptosis of MPC5 cells in vitro that involved induction of autophagy through the AMPK/mTOR signaling pathway, which might provide a potential therapeutic option for diabetic nephropathy.
Subject(s)
Emodin/pharmacology , AMP-Activated Protein Kinases/metabolism , Podocytes , Caspase 3/metabolism , TOR Serine-Threonine Kinases/metabolism , Signal Transduction , Apoptosis , Sirolimus/pharmacology , Glucose/metabolism , AutophagyABSTRACT
CD24 is a highly glycosylated protein that is linked to the plasma membrane via a glycosylphosphatidylinositol anchor. As a universally expressed protein on immune cells, CD24 is also overexpressed in nearly 70% of human cancers including hepatocellular carcinoma, lung cancer and bladder cancer et al. Studies revealed that CD24 is involved in regulating cell proliferation, migration and invasion in cancer cells by interacting with P-selectin, activating Wnt and MAPK signaling pathway or other signaling molecules. Therefore, CD24-targeted siRNA or antibody has a great potential to exert anti-tumor effects by blocking the interaction. There are currently several agents or regiments targeting CD24 for the treatment of patients with various kinds of cancers that are undergoing assessment in the preclinical study at present. Recent studies revealed that CD24 was able to interact with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which located on the surface of macrophages, to compose a novel immune checkpoint. The binding of CD24 to Siglec-10 elicits an inhibitory signaling cascade, limits macrophage phagocytosis, evades immune surveillance, and promotes tumor growth, which suggested that CD24 may be a potential target in anti-tumor immunotherapy. In this review, we introduced the structure and function of CD24 and its role in cancer progression and anti-tumor immunity. Moreover, the progression in developing novel anti-cancer drugs or treatment strategies with the target of CD24 was summarized, which aims to provide a new insight in CD24-targeting therapy.
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Platelet-aggregation receptor 1 (PEAR1) is a transmembrane receptor identified in 2005 and expressed mainly on platelets and endothelial cells. PEAR1 is a receptor protein that contacts platelets with each other and plays an important role in platelet activation and aggregation. Endothelial cells play an important role in maintaining vascular tone and vascular repair, and PEAR1 regulates the process of tumourigenesis and development by affecting their proliferation and associated neovascularisation. In recent years, PEAR1 has gradually been recognized as a potential target for antithrombotic drugs. This review focuses on elucidating the mechanisms of platelet endothelial aggregation receptor 1 and related signaling pathways in platelets and endothelial cells, and provides new ideas for the study of drug therapy for tumour-associated thrombosis.
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AIM: To study the mechanism of Ginseng Yixin granules (QSYXG) in treating ejection fraction preserved heart failure (HFpEF) based on network pharmacology. METHODS: Effective chemical composition information of QSYXG particles was collected through TCMSP database; DisGeNET, GeneCards, OMIM database for obtaining HFpEF related targets; Metascape GO and KEGG enrichment analysis of the intersection targets of HFpEF; STRING Construction and analysis of the database PPI network; Cytoscape3.7.2 Software construction network diagram; Docking of the major active components to the core target with the AutoDock Vina software molecules, the results were visualized and analyzed with pymol. RESULTS: A total of 66 components and corresponding targets were obtained, HFpEF corresponds to 1 931 targets, The intersection of 127 targets, the main active ingredients are quercetin, kaempferol, β-sitosterol, etc.; TNF, AKT1, IL-6, P53 and JUN as the core targets, Good docking of the key components with the core targets; Mainly involving the positive regulation of gene expression, signal transduction, negative regulation of apoptotic process, positive regulation of cell proliferation and senescence, hypoxia response, negative regulation of gene expression, inflammatory response and so on, PI3K-Akt, AGE-RAG, MAPK, TNF, IL-17, and HIF-1 are the main associated signaling pathways. CONCLUSION: QSYXG may treat HFpEF by activating targets of TNF, AKT1, IL-6, P53, JUN, and regulating apoptotic process, cell proliferation, hypoxia response, and inflammatory response.
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Energy imbalance is eonsidered an important driver of human diseases. As an important energy sensor, AMPK plays a central role in maintaining energy homeostasis, making it a key target for disease prévention and treatment. As a new type of cell death, ferroptosis is related to the pathophysiologieal process of many diseases, and AMPK-related signaling pathway is an important way to regulate iron death. Understanding which pathway AMPK induces or inhibits ferroptosis will provide new ideas for the treatment of diseases in the future and provide new targets for new drug research. In this paper, we review the related litera-tures and explore the signaling pathways of AMPK regulating ferroptosis, wïth a brief description of the application of AMPK-mediated ferroptosis related signaling pathways in diseases, hoping to provide reference for later research.