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BACKGROUND: Diabetic kidney disease (DKD) is a major complication of diabetes mellitus. Renal tubular epithelial cell (TEC) damage, which is strongly associated with the inflammatory response and mesenchymal trans-differentiation, plays a significant role in DKD; However, the precise molecular mechanism is unknown. The recently identified microRNA-630 (miR-630) has been hypothesized to be closely associated with cell migration, apoptosis, and autophagy. However, the association between miR-630 and DKD and the underlying mechanism remain unknown. AIM: To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats. METHODS: Streptozotocin was administered to six-week-old male rats to create a hyperglycemic diabetic model. In the second week of modeling, the rats were divided into control, DKD, negative control of lentivirus, and miR-630 overexpression groups. After 8 wk, urine and blood samples were collected for the kidney injury assays, and renal tissues were removed for further molecular assays. The target gene for miR-630 was predicted using bioinformatics, and the association between miR-630 and toll-like receptor 4 (TLR4) was confirmed using in vitro investigations and double luciferase reporter gene assays. Overexpression of miR-630 in DKD rats led to changes in body weight, renal weight index, basic blood parameters and histopathological changes. RESULTS: The expression level of miR-630 was reduced in the kidney tissue of rats with DKD (P < 0.05). The miR-630 and TLR4 expressions in rat renal TECs (NRK-52E) were measured using quantitative reverse transcription polymerase chain reaction. The mRNA expression level of miR-630 was significantly lower in the high-glucose (HG) and HG + mimic negative control (NC) groups than in the normal glucose (NG) group (P < 0.05). In contrast, the mRNA expression level of TLR4 was significantly higher in these groups (P < 0.05). However, miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Furthermore, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were significantly higher in the HG and HG + mimic NC groups than in NG group (P < 0.05). However, the levels of these cytokines were significantly lower in the HG + miR-630 mimic group than in the HG + mimic NC group (P < 0.05). Notably, changes in protein expression were observed. The HG and HG + mimic NC groups showed a significant decrease in E-cadherin protein expression, whereas TLR4, α-smooth muscle actin (SMA), and collagen IV protein expression increased (P < 0.05). Conversely, the HG + miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4, α-SMA, and collagen IV protein expression than in the HG + mimic NC group (P < 0.05). The miR-630 targets TLR4 gene expression. In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC. Additionally, rats treated with miR-630 agomir showed significant reductions in urinary albumin, blood glucose, TLR4, and proinflammatory markers (TNF-α, IL-1ß, and IL-6) expression levels (P < 0.05). Moreover, these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells. CONCLUSION: MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4, and has a protective effect on DKD.
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High suicide risk represents a serious problem in patients with major depressive disorder (MDD), yet treatment options that could safely and rapidly ameliorate suicidal ideation remain elusive. Here, we tested the feasibility and preliminary efficacy of the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) in reducing suicidal ideation in patients with MDD. Thirty-two MDD patients with moderate to severe suicidal ideation participated in the current study. Suicidal ideation and depression symptoms were assessed before and after 5 days of open-label SAINT. The neural pathways supporting rapid-acting antidepressant and suicide prevention effects were identified with dynamic causal modelling based on resting-state functional magnetic resonance imaging. We found that 5 days of SAINT effectively alleviated suicidal ideation in patients with MDD with a high response rate of 65.63%. Moreover, the response rates achieved 78.13% and 90.63% with 2 weeks and 4 weeks after SAINT, respectively. In addition, we found that the suicide prevention effects of SAINT were associated with the effective connectivity involving the insula and hippocampus, while the antidepressant effects were related to connections of the subgenual anterior cingulate cortex (sgACC). These results show that SAINT is a rapid-acting and effective way to reduce suicidal ideation. Our findings further suggest that distinct neural mechanisms may contribute to the rapid-acting effects on the relief of suicidal ideation and depression, respectively.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/terapia , Ideación Suicida , Hipocampo , Imagen por Resonancia Magnética , Antidepresivos/uso terapéuticoRESUMEN
Intestinal organoid transplantation is a promising therapy for the treatment of mucosal injury. However, how the transplanted organoids regulate the immune microenvironment of recipient mice and their role in treating intestinal ischemia-reperfusion (I/R) injury remains unclear. Here, we establish a method for transplanting intestinal organoids into intestinal I/R mice. We find that transplantation improve mouse survival, promote self-renewal of intestinal stem cells and regulate the immune microenvironment after intestinal I/R, depending on the enhanced ability of macrophages polarized to an anti-inflammatory M2 phenotype. Specifically, we report that L-Malic acid (MA) is highly expressed and enriched in the organoids-derived conditioned medium and cecal contents of transplanted mice, demonstrating that organoids secrete MA during engraftment. Both in vivo and in vitro experiments demonstrate that MA induces M2 macrophage polarization and restores interleukin-10 levels in a SOCS2-dependent manner. This study provides a therapeutic strategy for intestinal I/R injury.
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Macrófagos , Daño por Reperfusión , Ratones , Animales , Organoides/trasplante , Isquemia/terapiaRESUMEN
OBJECTIVE: This study aimed to analyze the role of mitochondrial Omi/HtrA2 signaling pathway in neuronal apoptosis in patients with cerebral hemorrhage (CH). METHODS: In this retrospective analysis, the clinical data of 60 patients with CH who received craniotomy or minimally invasive intracranial hematoma (MIIH) were included in the case group, which was sub-divided into a craniotomy group (n=22) and a minimally invasive group (n=38) depending on the type of surgery. The brain tissue specimens of the above patients were retained in the surgical specimen repository of Yuhuan Second People's Hospital. Another 15 normal brain tissue samples retained in the surgical specimen repository were included in the normal group. The expression levels of Omi/HtrA2, X-linked inhibitor of apoptosis protein (XIAP), poly-adenosine diphosphate-ribose polymerase (PARP), pro-caspase 3, and pro-caspase 9 were determined using Western blotting. RESULTS: The case group exhibited a higher proportion of neuronal apoptosis, higher expression levels of Omi/HtrA2, PARP, and pro-caspase 3 and 9, higher activities of caspase 3 and caspase 9 (P < 0.05), and lower XIAP expression (P < 0.05) in brain tissue than the normal group. The proportion of neuronal cell apoptosis in brain tissues was positively correlated with the expression of Omi/HtrA2, PARP, and pro-caspase 3 and pro-caspase 9 (r > 0, P < 0.05), and the activity of caspase 3 and caspase 9 was negatively correlated with XIAP expression (r < 0, P < 0.05). Compared with the craniotomy group, the minimally invasive group demonstrated higher efficacy and hematoma removal rate, shorter hematoma removal time, hematoma drainage time, operation time, and hospital stay, less intraoperative bleeding, and lower postoperative complication rates (P < 0.05). The minimally invasive group showed higher expression level of serum XIAP and lower levels of serum caspase 3 and caspase 9 than the craniotomy group (P < 0.05). CONCLUSIONS: Mitochondrial Omi/HtrA2 signaling pathway may be involved in neuronal apoptosis. MIIH has the advantages of high efficacy, high hematoma clearance rate, and few complications for the treatment of CH.
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OBJECTIVE: Reduced left ventricular ejection fraction (LVEF) is common in hemodialysis (HD) patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is considered an important determinant of cardiovascular events. The aim of the study was to evaluate the relationship between Lp-PLA2 and LVEF in HD patients. METHODS: Fifty-seven HD patients with coronary heart disease were enrolled. Predialysis and postdialysis venous whole blood samples were collected. The patients were divided into preserved and reduced LVEF groups. The relationship between Lp-PLA2 and LVEF was assessed. RESULTS: A significant difference in C-reactive protein (CRP) and Lp-PLA2 was observed, with higher levels noted in patients with reduced LVEF (P ≤ .001). Both Lp-PLA2 and CRP were negatively correlated with LVEF in the HD patients. Only Lp-PLA2 remained associated with LVEF in multiple regression analysis. CONCLUSION: Lipoprotein-associated phospholipase A2 levels are associated with LVEF and could potentially be used to evaluate chronic heart failure with reduced LVEF in HD patients for risk stratification management.
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1-Alquil-2-acetilglicerofosfocolina Esterasa , Ventrículos Cardíacos , Humanos , Biomarcadores , Proteína C-Reactiva , Ventrículos Cardíacos/química , Diálisis Renal , Factores de Riesgo , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
There are significant differences in the susceptibility of populations to intestinal ischemia/reperfusion (I/R), but the underlying mechanisms remain elusive. Here, we show that mice exhibit significant differences in susceptibility to I/R-induced enterogenic sepsis. Notably, the milnacipran (MC) content in the enterogenic-sepsis-tolerant mice is significantly higher. We also reveal that the pre-operative fecal MC content in cardiopulmonary bypass patients, including those with intestinal I/R injury, is associated with susceptibility to post-operative gastrointestinal injury. We reveal that MC attenuates mouse I/R injury in wild-type mice but not in intestinal epithelial aryl hydrocarbon receptor (AHR) gene conditional knockout mice (AHRflox/flox) or IL-22 gene deletion mice (IL-22-/-). Collectively, our results suggest that gut microbiota affects susceptibility to I/R-induced enterogenic sepsis and that gut microbiota-derived MC plays a pivotal role in tolerance to intestinal I/R in an AHR/ILC3/IL-22 signaling-dependent manner, revealing the pathological mechanism, potential prevention and treatment drugs, and treatment strategies for intestinal I/R.
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Microbioma Gastrointestinal , Daño por Reperfusión , Ratones , Animales , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Transducción de Señal , Ratones Noqueados , IsquemiaRESUMEN
Stroke is the leading cause of disability globally in need of novel and effective methods of rehabilitation. Intermittent theta burst stimulation (iTBS) has been adopted as a Level B recommendation for lower limb spasticity in guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Nonetheless, the methodological differences and deficits of existing work bring about heterogenous results and therefore limit the universal clinical use of rTMS in lower extremity (LE) rehabilitation. The variation of stimulated targets across motor cortex contributes mainly to these heterogeneities. This narrative review includes studies of rTMS on LE motor function rehabilitation in patients after stroke until now. Some analyses of brain imaging and electromagnetic simulation and quantification through computational modeling were also performed. rTMS appears capable of fostering LE motor rehabilitation after stroke, but the actually stimulated targets are considerably bias making it difficult to confirm effectiveness. The main reason for this phenomenon is probably inaccurate targeting of motor cortical leg representation. An underlying updated method is proposed as Individual-Target TMS (IT-TMS) combined with brain imaging. rTMS is a promising validated method for LE function regaining. Future studies should systematically compare the effects of IT-TMS with traditional rTMS using large samples in random clinical trials. This article is categorized under: Neuroscience > Clinical Neuroscience.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Rehabilitación de Accidente Cerebrovascular/métodos , Estimulación Magnética Transcraneal/métodos , Resultado del Tratamiento , Accidente Cerebrovascular/terapia , Extremidad InferiorRESUMEN
BACKGROUND: Myocardial injury is a major complication of sepsis and a key factor affecting prognosis. Therefore, early and accurate diagnosis and timely management of sepsis-induced cardiomyopathy (SICM) are of great significance for the prevention and treatment of sepsis. The gut microbiota has been shown to be closely associated with sepsis or myocardial injury, but the association between the gut microbiota and SICM is not fully understood. This study aimed to explore the link between gut microbiota composition and SICM. METHODS: A case-control and single-center study of clinical features and gut microbiota profiles by Metagenome and Virome was conducted in SICM patients (n = 15) and sepsis-uninduced cardiomyopathy patients (SNICM, n = 16). RESULTS: Compared with SNICM patients, SICM patients showed significant myocardial injury and higher 28-day mortality, SOFA scores, lactate levels, and infection levels on admission. Meanwhile, differences in the composition of gut bacteria, archaea, fungi, and viruses were analyzed between the two groups. Differential gut bacteria or viruses were found to have a good predictive effect on SICM. Furthermore, gut bacteria and viruses that differed between the two groups were strongly related. The abundance of Cronobacter and Cronobacter phage was higher in the SICM group than in the SNICM group, and the receiver operating characteristic curve showed that Cronobacter and Cronobacter phage both had a good predictive effect on SICM. CONCLUSIONS: SICM patients may have specific gut microbiota signatures, and Cronobacter and Cronobacter phages have a good ability to identify and diagnose SICM.
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Bacteriófagos , Cardiomiopatías , Microbioma Gastrointestinal , Sepsis , Humanos , Estudios de Casos y Controles , Disbiosis/complicaciones , Cardiomiopatías/etiología , Bacterias/genética , Sepsis/complicacionesRESUMEN
In tumor research, the occurrence and origin of tumors are the fundamental problems. In the 1970s, the basic discussion of the developmental biology problem of tumors was proposed, and it was believed that tumorigenesis is closely related to developmental biology. Tumors are abnormal biological structures in organisms, and their biological behavior is very similar to that of the early embryo. Many tumor-related genes also serve regulatory roles in the normal development and differentiation of embryos. However, it remains unclear whether gene expression in early embryos has any similarities with tumor cells. In this study, to compare the similarities and differences in gene expression between early embryos and tumor cells, reverse transcription-quantitative PCR was conducted to determine and compare the relative expression levels of nine tumor-related genes in the brain glioma cell line, T98G, and in the early embryo of Spodoptera litura, which is fast-growing, low-cost, easily accessible and easy to observe. The expression of tumor-related genes in early embryos and the similarity of regulatory mechanisms between early embryonic development and tumor growth were explored. In conclusion, tumor growth may be regarded as an abnormal embryogenic activation that happens in the organs of adult individuals.
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The rapid development of economy and society leads to the rapid expansion of cities, resulting in the atrophy of urban ecological space and the decline of ecological function, as well as a serious threat to urban ecological security. It is of great significance for the sustainable development of a city to systematically analyze the structure of urban ecological space and put forward targeted protection and optimization measures. Taking Changzhou City as the research area and considering the natural ecological function and social service function of urban ecological space, we constructed two ecological networks, the "source-corridor" ecological network based on natural ecology and the "supply-demand" ecological network based on human ecology. For the "source-corridor" ecological network, quantitative analysis was mainly carried out from the importance of nodes, network connectivity and stability. For the "supply-demand" ecological network, quantitative analysis was mainly carried out from the importance of nodes, supply-demand equilibrium and stability. The results showed that the levels of connectivity and stability of the "source-corridor" ecological network in the main urban area of Changzhou were not high, the stability level of the "supply-demand" ecological network was general, and there was spatial mismatch between service supply and demands. From the perspective of connectivity and stability improvement, an optimization scheme of "source-corridor" ecological network with 12 additional source nodes and 57 corridors was proposed. From the perspective of supply-demand balance and stability improvement, an optimization scheme of "supply-demand" ecological network with 22 new supply nodes was proposed. Compared with the original "source-corridor" ecological network, the connectivity level of the optimized network was improved by 10%, and the network stability was improved by 0.05. Compared with the initial "supply-demand" ecological network, the service level of the optimized network was improved by 4%, and the network stability was improved by 0.10. Finally, we integrated the two ecological networks, and formulated the implementation plan of protection and management for both the current protected patches and the new ecological nodes.
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Conservación de los Recursos Naturales , Ecosistema , China , Ciudades , Ecología , HumanosRESUMEN
BACKGROUND: The effects of omega-3 fatty acid on cardiovascular health obtained inconsistent results. A systematic review and meta-analysis were therefore conducted to assess the effects of omega-3 fatty acid supplementation for primary and secondary prevention strategies of major cardiovascular outcomes. METHODS: The databases of PubMed, Embase, and the Cochrane library were systematically searched from their inception until September 2020. Relative risks (RRs) with 95% confidence intervals were used to assess effect estimates by using the random-effects model. RESULTS: Twenty-eight randomized controlled trials involving 136,965 individuals were selected for the final meta-analysis. Omega-3 fatty acid was noted to be associated with a lower risk of major cardiovascular events (RR, 0.94; 95% CI, 0.89-1.00; P = .049) and cardiac death (RR, 0.92; 95% CI, 0.85-0.99; P = .022). However, no significant differences was noted between omega-3 fatty acid and the control for the risks of all-cause mortality (RR, 0.97; 95% CI, 0.92-1.03; P = .301), myocardial infarction (RR, 0.90; 95% CI, 0.80-1.01; P = .077), and stroke (RR, 1.02; 95% CI, 0.94-1.11; P = .694). CONCLUSIONS: Major cardiovascular events and cardiac death risks could be avoided with the use of omega-3 fatty acid. However, it has no significant effects on the risk of all-cause mortality, myocardial infarction, and stroke.
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Enfermedades Cardiovasculares , Ácidos Grasos Omega-3 , Infarto del Miocardio , Accidente Cerebrovascular , Enfermedades Cardiovasculares/prevención & control , Causas de Muerte , Muerte , Ácidos Grasos Omega-3/uso terapéutico , HumanosRESUMEN
Intestinal ischemia/reperfusion (I/R) is a common pathophysiological process in clinical severe patients, and the effect of intestinal I/R injury on the patient's systemic pathophysiological state is far greater than that of primary intestinal injury. In recent years, more and more evidence has shown that intestinal microbiota and its metabolites play an important role in the occurrence, development, diagnosis and treatment of intestinal I/R injury. Intestinal microbiota is regulated by host genes, immune response, diet, drugs and other factors. The metabolism and immune potential of intestinal microbiota determine its important significance in host health and diseases. Therefore, targeting the intestinal microbiota and its metabolites may be an effective therapy for the treatment of intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury. This review focuses on the role of intestinal microbiota and its metabolites in intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury, and summarizes the latest progress in regulating intestinal microbiota to treat intestinal I/R injury and intestinal I/R-induced extraintestinal organ injury.
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Microbioma Gastrointestinal , Daño por Reperfusión , Humanos , Intestinos , Daño por Reperfusión/metabolismoRESUMEN
Schizophrenia patients with auditory verbal hallucinations (AVHs) are diseased groups of serious psychosis with still unknown etiology. The aim of this research was to identify the neurophysiological correlates of auditory verbal hallucinations. Revealing the neural correlates of auditory hallucination is not merely of great clinical significance, but it is also quite essential to study the pathophysiological correlates of schizophrenia. In this study, 25 Schizophrenia patients with AVHs (AVHs group, 23.2 ± 5.35 years), 52 Schizophrenia patients without AVHs (non-AVHs group, 25.79 ± 5.63 years) and 28 healthy subjects (NC group, 26.14 ± 5.45 years) were enrolled. Dynamic functional connectivity was studied with a sliding-window method and functional connectivity states were then obtained with the k-means clustering algorithm in the three groups. We found that schizophrenia patients with AVHs were characterized by significant decreased static functional connectivity and enhanced variability of dynamic functional connectivity (non-parametric permutation test, Bonferroni correction, p < 0.05). In addition, the AVHs group also demonstrated increased number of brain states, suggesting brain dynamics enhanced in these patients compared with the non-AVHs group. Our findings suggested that there were abnormalities in the connection of brain language regions in auditory verbal hallucinations. It appears that the interruption of connectivity from the language region might be critical to the pathological basis of AVHs.
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Primary insomnia (PI) is among the most prevalent sleep-related disorders and has a far-reaching impact on daytime functioning. Repetitive transcranial magnetic stimulation (rTMS) has drawn attention because of its effectiveness and safety. The purpose of the current study was to detect changes in the topological organization of whole-brain functional networks and to determine their associations with the clinical treatment effects of rTMS. Resting-state functional magnetic resonance imaging (rsfMRI) data from 32 patients with PI were collected and compared with findings from 32 age- and gender-matched healthy controls (HCs). The patients were treated with Stanford accelerated intelligent neuromodulation therapy, which is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation protocol. Graph theoretical analysis was used to construct functional connectivity matrices and to extract the attribute features of small-world networks in insomnia. Scores on the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the associations between these clinical characteristics and functional metrics, were the primary outcomes. At baseline, the patients with PI showed inefficient small-world property and aberrant functional segregation and functional integration compared with the HCs. These properties showed renormalization after individualized rTMS treatment. Furthermore, low functional connectivity between the right insula and left medial frontal gyrus correlated with improvement in ISI scores. We highlight functional network dysfunctions in PI patients and provide evidence into the pathophysiological mechanisms involved and the possible mode of action of rTMS.
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Postpartum depression (PPD) is a depressive condition that is associated with a high risk of stressful life events, poor marital relationships, and even suicide. Neuroimaging techniques have enriched our understanding of cerebral mechanisms underlying PPD; namely, abnormalities in the amygdala-insula-frontal circuit might contribute to the pathogenesis of PPD. Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation repetitive transcranial magnetic stimulation (rTMS) protocol. It has been shown to be effective, safe, tolerable, and rapid acting for treating treatment-resistant depression, and may be a valuable tool in the treatment of PPD. The purpose of the current study was to detect inter-hemispheric connectivity changes and their relationship with the clinical treatment effects of rTMS. Resting-state fMRI data from 32 patients with PPD treated with SAINT were collected and compared with findings from 32 age matched healthy controls. Voxel-mirrored homotopic connectivity (VMHC) was used to analyze the patterns of interhemispheric intrinsic functional connectivity in patients with PPD. Scores on the 17-item Hamilton Depression Rating Scale, Edinburgh Postnatal Depression Scale (EPDS) scores, and the relationships between these clinical characteristics and VMHC were the primary outcomes. Patients with PPD at baseline showed reduced VMHC in the amygdala, insula, and medial frontal gyrus compared with the HCs. These properties showed a renormalization after individualized rTMS treatment. Furthermore, increased connectivity between the left and right insula after SAINT was significantly correlated with the improvement of EPDS scores. Our results reveal the disruptions in the intrinsic functional architecture of interhemispheric communication in patients with PPD, and provide evidence for the pathophysiological mechanisms and the effects of rTMS.
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Myocardial ischemia/reperfusion (I/R) injury is still a lack of effective therapeutic drugs, and its molecular mechanism is urgently needed. Studies have shown that the intestinal flora plays an important regulatory role in cardiovascular injury, but the specific mechanism has not been fully elucidated. In this study, we found that an increase in Ang II in plasma was accompanied by an increase in the levels of myocardial injury during myocardial reperfusion in patients with cardiopulmonary bypass. Furthermore, Ang II treatment enhanced mice myocardial I/R injury, which was reversed by caveolin-1 (CAV-1)-shRNA or strengthened by angiotensin-converting enzyme 2 (ACE2)-shRNA. The results showed that CAV-1 and ACE2 have protein interactions and inhibit each other's expression. In addition, propionate, a bacterial metabolite, inhibited the elevation of Ang II and myocardial injury, while GPR41-shRNA abolished the protective effects of propionate on myocardial I/R injury. Clinically, the propionate content in the patient's preoperative stool was related to Ang II levels and myocardial I/R injury levels during myocardial reperfusion. Taken together, propionate alleviates myocardial I/R injury aggravated by Ang II dependent on CAV-1/ACE2 axis through GPR41, which provides a new direction that diet to regulate the intestinal flora for treatment of myocardial I/R injury.
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Caveolina 1/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Miocardio/metabolismo , Propionatos/farmacología , Receptores Acoplados a Proteínas G/metabolismo , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/patología , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg-1·d-1. In order to search for SBT targets and related metabolites, the dysregulated genes and metabolites were detected by transcriptomics and metabolomics. Immune related indicators such as interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) were detected by ELISA. Treg cell disorders was analyzed by flow cytometry. Our results showed that SBT significantly alleviated the symptoms of OM rats and the inflammatory infiltration of ulcer tissues. After SBT administration, inflammatory related metabolic pathways including linoleic acid metabolism, valine, leucine and isoleucine biosynthesis were significantly altered. Furthermore, the production of proinflammatory factors like IL-17 and TNF-α, were also dramatically reduced after SBT administration. Besides, the infiltration degree of Treg cells in the spleen of OM modeling rats was significantly improved by SBT administration, thus maintaining the immune balance of the body. The current study demonstrates that SBT regulates inoleic acid metabolism, glycerophospholipid metabolism and amino acid metabolism, and inhibits IL-17/TNF signal transduction to restore Treg and Th17 cell homeostasis in OM rats, thereby alleviating chemotherapy-induced OM.
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Medicamentos Herbarios Chinos , Estomatitis , Animales , Metaboloma , Calidad de Vida , Ratas , Comprimidos , TranscriptomaRESUMEN
Suicidal ideation increases precipitously in patients with depression, contributing to the risk of suicidal attempts. Despite the recent advancement in transcranial magnetic stimulation, its effectiveness in depression disorder and its wide acceptance, the network mechanisms of the clinical response to suicidal ideation in major depressive disorder remain unclear. Independent component analysis for neuroimaging data allows the identification of functional network connectivity which may help to explore the neural basis of suicidal ideation in major depressive disorder. Resting-state functional magnetic resonance imaging data and clinical scales were collected from 30 participants (15 major depressive patients with suicidal ideation and 15 healthy subjects). Individual target-transcranial magnetic stimulation (IT-TMS) was then used to decrease the subgenual anterior cingulate cortex activity through the left dorsolateral prefrontal cortex. Thirty days post IT-TMS therapy, seven of 15 patients (46.67%) met suicidal remission criteria, and 12 patients (80.00%) met depression remission criteria. We found that IT-TMS could restore the abnormal functional network connectivity between default mode network and precuneus network, left executive control network and sensory-motor network. Furthermore, the changes in functional network connectivity between the default mode network and precuneus network were associated with suicidal ideation, and depressive symptoms were related to connectivity between left executive control network and sensory-motor network. These findings illustrate that IT-TMS is an effective protocol for the accurate restoration of impaired brain networks, which is consistent with clinical symptoms.