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ETHNOPHARMACOLOGICAL RELEVANCE: Treatment options for hepatic fibrosis, a prevalent liver condition closely linked to cirrhosis, are currently limited. While Guizhi Fuling Wan (GFW), a pill derived from traditional Chinese herbs, has been reported to possess hepatoprotective properties, its therapeutic effect and mechanism in hepatic fibrosis remain elusive. AIM OF THE STUDY: This study aimed to evaluate the anti-fibrotic impact of GFW and its underlying mechanisms in both in vivo and in vitro settings. MATERIALS AND METHODS: Tetrachloromethane (CCl4) was used to induce hepatic fibrosis in male rats. In vitro, activation of hepatic stellate cells (HSCs) was triggered by platelet-derived growth factor-BB (PDGF-BB). In vivo, liver function, pathological alterations, and HSC activation were evaluated. Additionally, the impact of GFW on the activated phenotypes of Lieming Xu-2 (LX-2) cells was examined in vitro. Network pharmacology was employed to identify the potential targets of GFW in hepatic fibrosis. Lastly, the impact of GFW on the PTEN/AKT/mTOR pathway and PTEN ubiquitination in HSCs was investigated. RESULTS: GFW alleviated CCl4-induced liver damage and scarring in rats in a dose-dependent manner and suppressed HSC activation in vivo. Moreover, GFW inhibited the proliferation, migration, differentiation, and extracellular matrix (ECM) production of activated HSCs in vitro. GFW also promoted autophagy and apoptosis of HSCs. Meanwhile, network pharmacology and in vitro studies suggested that GFW inhibits the AKT/mTOR pathway by preventing PTEN degradation by suppressing ubiquitination. CONCLUSION: GFW attenuates Ccl4-induced hepatic fibrosis in male rats by regulating the PTEN/AKT/mTOR signaling pathway, positioning it as a potential candidate for the treatment of hepatic fibrosis.
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Medicamentos Herbarios Chinos , Células Estrelladas Hepáticas , Cirrosis Hepática , Fosfohidrolasa PTEN , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Humanos , Masculino , Ratas , Tetracloruro de Carbono , Línea Celular , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Cirrosis Hepática/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfohidrolasa PTEN/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Background: The hemoglobin to red cell distribution width ratio (HRR) has been experimentally associated with the prognosis of acute ischemic stroke (AIS). However, its relationship with mechanical thrombectomy (MT) for AIS remains unclear. Therefore, this study aimed to investigate the relationship between HRR at admission, follow-up HRR, and clinical outcomes in patients undergoing MT. Methods: Acute ischemic stroke patients undergoing MT were consecutively enrolled from January 2017 to December 2022. Demographic, clinical, and laboratory information were collected. HRR was measured by dividing hemoglobin (Hb) by red cell distribution width (RDW) at admission and after 24 h of MT. Clinical outcomes after 3 months were evaluated using the modified Rankin Scale (mRS). The primary outcome was poor prognosis (mRS > 2) at 3 months, while the secondary outcome was death within 3 months. Results: A total of 310 patients were analyzed, of whom 216 patients (69.7%) had poor prognosis, and 92 patients (29.6%) died. Patients with a poor prognosis and death had significantly lower HRR levels at admission and after 24 h. HRR at admission was not associated with clinical outcomes according to multivariable logistic regression analysis. However, HRR after 24 h was significantly associated with poor prognosis (adjusted odds ratio [OR]: 0.646, 95% confidence interval [CI]: 0.520-0.803, p < 0.001) and death (adjusted OR: 0.615, 95% CI: 0.508-0.744, p < 0.001). Receiver-operating characteristic curve analysis demonstrated the predictive ability of HRR after 24 h, with areas under the curves of 0.790 for poor prognosis and 0.771 for death. Conclusion: Rapidly measurable HRR levels are an independent marker of outcome after MT in AIS patients. This may provide a reliable auxiliary outcome measure for clinical routine and interventional therapy.
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Maternal immune activation (MIA) resulting from viral infections during pregnancy is linked to increased rates of neurodevelopmental disorders in offspring. However, the mechanisms underlying MIA-induced neurobehavioral abnormalities remain unclear. Here, we used a poly (I:C)-induced MIA mouse model to demonstrate the presence of multiple behavioral deficits in male offspring. Through RNA sequencing (RNA-seq), we identified significant upregulation of genes involved in axonogenesis, synaptogenesis, and glutamatergic synaptic neurotransmission in the mPFC of MIA mice. Electrophysiological analyses further revealed an excitatory-inhibitory (E/I) synaptic imbalance in mPFC pyramidal neurons, leading to hyperactivity in this brain region. Cannabidiol (CBD) effectively alleviated the behavioral abnormalities observed in MIA offspring by reducing glutamatergic transmission and enhancing GABAergic neurotransmission of mPFC pyramidal neurons. Activation of GPR55 by lipid lysophosphatidylinositol (LPI), an endogenous GPR55 agonist, specifically in the mPFC of healthy animals led to MIA-associated behavioral phenotypes, which CBD could effectively reverse. Moreover, we found that a GPR55 antagonist can mimic CBD's beneficial effects, indicating that CBD's therapeutic effects are mediated via the LPI-GPR55 signaling pathway. Therefore, we identified mPFC as a primary node of a neural network that mediates MIA-induced behavioral abnormalities in offspring. Our work provides insights into the mechanisms underlying the developmental consequences of MIA and identifies CBD as a promising therapeutic approach to alleviate these effects.
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Obesity imposes a global health threat and calls for safe and effective therapeutic options. Here, we found that protein-rich diet significantly reduced body fat storage in fruit flies, which was largely attributed to dietary cysteine intake. Mechanistically, dietary cysteine increased the production of a neuropeptide FMRFamide (FMRFa). Enhanced FMRFa activity simultaneously promoted energy expenditure and suppressed food intake through its cognate receptor (FMRFaR), both contributing to the fat loss effect. In the fat body, FMRFa signaling promoted lipolysis by increasing PKA and lipase activity. In sweet-sensing gustatory neurons, FMRFa signaling suppressed appetitive perception and hence food intake. We also demonstrated that dietary cysteine worked in a similar way in mice via neuropeptide FF (NPFF) signaling, a mammalian RFamide peptide. In addition, dietary cysteine or FMRFa/NPFF administration provided protective effect against metabolic stress in flies and mice without behavioral abnormalities. Therefore, our study reveals a novel target for the development of safe and effective therapies against obesity and related metabolic diseases.
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Cisteína , Drosophila , Animales , Ratones , Tejido Adiposo/metabolismo , Cisteína/metabolismo , Dieta , Drosophila/metabolismo , Drosophila melanogaster , FMRFamida/metabolismo , ObesidadRESUMEN
Lack of maternal care and attention during infancy and childhood increases the likelihood of developing a range of neuropsychiatric disorders, such as social deficits, working memory impairment, and anxiety-like behaviors, in adulthood. However, the neuroregulatory signaling through which early-life stress causes behavioral and cognitive abnormalities in the offspring is largely unexplored. Here, we show that in mice, unpredictable maternal separation (MS) during the early postnatal period impairs neuronal development in the medial prefrontal cortex (mPFC) and results in long-lasting behavioral changes. Additionally, MS disrupts excitatory neurotransmission and inhibits the neuronal activity of pyramidal neurons in the mPFC. Differentially expressed gene (DEG) analysis of RNA sequencing (RNA-seq) data of mPFC showed that dopamine D1 receptor (D1R) was significantly downregulated in MS animals. Finally, we show that pharmacological activation of D1R signaling specifically in the mPFC improves neuronal excitability and rescues behavioral and cognitive dysfunction of MS mice, whereas pharmacologically inhibiting of D1R in the mPFC mimics MS-induced behavioral abnormalities in control mice. Together, our results identify D1R signaling in the mPFC, at least in part, as a potential therapeutic target for the behavioral and cognitive abnormalities caused by deprivation of maternal care in early life.
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Privación Materna , Corteza Prefrontal , Ratones , Animales , Corteza Prefrontal/metabolismo , Transmisión Sináptica , Neuronas/metabolismo , Receptores de Dopamina D1/metabolismoRESUMEN
Obesity, a growing health problem in the world, is related to a series of mental disorders, including anxiety and depression. XiaoYao San (XYS), a prescription of traditional Chinese medicine (TCM), has been widely used in the clinical treatment of anxiety and depression in China. However, the efficacy of XYS on obesity-related neuropsychiatric dysfunction and the underlying neural mechanisms remain unclear. Here, using a high-fat diet (HFD)-induced obese model, we found that XYS treatment significantly improves obesity-related anxiety- and depression-like behaviors and alters the gut microbiome, particularly by increasing the relative abundance of Faecalibaculum rodentium (F. rodentium), in mice. Interestingly, selective supplementation with F. rodentium or its metabolic products, short-chain fatty acids (SCFAs), is sufficient to rescue anxiety- and depression-like behaviors in HFD-fed mice. Next, we determined that the transcriptional level of dopamine D2 receptor (DRD2), which activation usually inhibits inflammation in the central nervous system (CNS), is significantly increased in the medial prefrontal cortex (mPFC) of XYS-treated mice when compared with that of vehicle-treated controls. Moreover, enriched pathways analysis with the differential expression genes (DEGs) showed that some of these DEGs are enriched in neuroinflammatory pathways. We further noticed that treatment with XYS contributes to controlling microglial activation and proinflammatory responses in the mPFC and hippocampus of HFD-fed mice. Overall, this study reveals that XYS rescues HFD-induced anxiety and depression via modulating gut microbiota-derived metabolites and that XYS is a potential therapeutic strategy for treating obesity-associated mental disorders.
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Dieta Alta en Grasa , Microbioma Gastrointestinal , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Microbioma Gastrointestinal/fisiología , Depresión/tratamiento farmacológico , Ratones Endogámicos C57BL , Ansiedad/tratamiento farmacológico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/inducido químicamenteRESUMEN
INTRODUCTION: Hiccup is a common disease that not only occurred on adults but also on infants, which can severely do harm to patients' physical and psychological health. Metoclopramide has been reported to have effects on intractable hiccup. However, there is a limited evidence that describes the efficacy and safety of metoclopramide in the treatment of intractable hiccup. The aim of this article is to obtain evidence on the effectiveness and safety of metoclopramide in treating patients with intractable hiccup. METHODS AND ANALYSIS: We will search the following databases, including PubMed, Cochrane Library, Embase, Web of Science, CBM, Wan-fang, VIP database, CNKI and MEDLINE from their inception to 11 November 2021. All the randomised controlled trials associated with metoclopramide in treating intractable hiccup will be included. Articles screened, selected and extracted will be performed by two researchers independently. The risk of bias will be assessed by using the Cochrane Collaboration. We will carry out the meta-analysis by using RevMan V.5.4 software. PROSPERO REGISTRATION NUMBER: CRD42021293000.
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Hipo , Adulto , Manejo de Datos , Hipo/tratamiento farmacológico , Humanos , Metaanálisis como Asunto , Metoclopramida/efectos adversos , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del TratamientoRESUMEN
Background: Indocyanine green angiography (ICGA) has been used to identify and preserve the parathyroid glands (PGs), and to evaluate PGs viability and function during thyroid surgery. However, evidence on the utilization of IGCA in thyroid cancer and robotic surgery is lacking. The efficacy of IGCA remains to be evaluated in PTC patients undergoing bilateral axillo-breast approach robotic thyroidectomy (BABA RT) and central neck dissection (CND). Methods: From March 2020 to August 2021, 81 papillary thyroid cancer (PTC) patients receiving total thyroidectomy and CND were enrolled in this retrospective analysis. An intravenous bolus of 7.5 mg ICG was administrated three times in the ICGA group (n=34). Medical records were reviewed and analyzed, including the baseline characteristics, surgical parameters, PGs-related parameters, and perioperative PTH and calcium levels. Results: The mean number of total identified PGs and preserved PGs were significantly more in the ICG group than in the control group (3.74 ± 0.45 vs. 3.15 ± 0.55, P<0.001; 3.12 ± 0.64 vs. 2.74 ± 0.57, P=0.007, respectively), as were PTH and calcium levels on POD 1 (23.16 ± 18.32 vs. 6.06 ± 7.74, P=0.039; 2.13 ± 0.11 vs. 2.08 ± 0.08, P=0.024, respectively). While there were no differences in PTH levels on POD 30. Additionally, patients with at least one well vascularized PG had higher ioPTH 3 and PTH on POD 1, which significantly suggested the absence of postoperative hypocalcemia. Although not statistically significant, ICGA seemed superior to relative ioPTH decline and ioPTH 3 in predicting postoperative hypocalcemia. Conclusion: In PTC patients undergoing BABA RT and CND, ICGA is a simple, safe, effective, and cost-effective tool in better identification and preservation of PGs as well as evaluation of PGs viability and function, with the potential to preserve more PGs, guide more appropriate autotransplantation, and accurately predict postoperative hypocalcemia.
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Hipocalcemia , Procedimientos Quirúrgicos Robotizados , Neoplasias de la Tiroides , Angiografía , Calcio , Humanos , Hipocalcemia/cirugía , Verde de Indocianina , Estudios Retrospectivos , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , TiroidectomíaRESUMEN
In this paper, carbon-coated Zn doped CdS core-shell photocatalyst (Zn-CdS@C) was fabricated via one-pot solvothermal method. The obtained Zn-CdS@C architectures displayed enhanced performance in photocatalytic antibiotic removal process. The Zn doped sites and carbon shell could all contribute to the prolonged lifetime of charge carriers and furthermore, result in the improved photoactivity. Moreover, the carbon shell could effectively improve the corrosion resistance of sulfide photocatalyst. We hope this study could provide novel insights into the fabrication of highly-efficient carbon-coated core-shell nanostructure toward wastewater treatment.
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Carbono , Sulfuros , Antibacterianos , Catálisis , Sulfuros/química , ZincRESUMEN
Hepatic pathological angiogenesis (HPA) is the key event of hepatic fibrosis (HF). Xueshisanjia powder (XSSJS), a Chinese herbal compound, is beneficial for alleviating pathological angiogenesis of hepatic tissue. The present study attempts to reveal the effect and mechanism of XSSJS via regulating miR-29b-3p/VEGFA axis against pathological angiogenesis in HF. In in vitro model, human embryonic kidney 293T cells were transfected with miR-29b-3p mimics, whereby the expression of miR-29b-3p was tested by real-time quantitative polymerase chain reaction (RT-qPCR), ensued by Luciferase assay determining the relationship between miR-29b-3p and vascular endothelial cell growth factor A (VEGFA). In addition, miR-29b-3p mimic transfected into the activated hepatic stellate cell T6 (HSC-T6). The Cell-Counting-Kit 8 (CCK8) and 5-Bromodeoxyuridine (BrdU) staining were first utilized to detect the antiproliferative efficiency of XSSJS following the XSSJS compound serum intervention, and then used to observe the expression of transforming growth factor-ß (TGF-ß), VEGFA, platelet-derived growth factor (PDGF) via RT-PCR, Western blot (WB), and Immunofluorescence (IF) methods. During the in vivo model, XSSJS with boil-free granules were fed to Wistar rats with liver fibrosis caused by intraperitoneal injection of pig serum followed by the transfection of miR-29b-3p adeno-associated virus (AAV). Hematoxylin-Eosin (HE) staining was used for histopathology assessment. The expression of miR-29b-3p, VEGFA, PDGF, TGF-ß have been investigated in liver tissue using RT-PCR, WB, IF. The results verified that XSSJS could up-regulate miR-29b-3p and suppress the expression of VEGFA, PDGA, and TGF-ß. In mechanism, miR-29b-3p primarily targeted the 3'UTR of VEGFA. In conclusion, XSSJS could modulate miR-29b-3p/VEGFA axis to inhibit the pathological angiogenesis of HF.
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MicroARNs , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Proliferación Celular/genética , Cirrosis Hepática/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Neovascularización Patológica/metabolismo , Factor de Crecimiento Derivado de Plaquetas , Ratas , Ratas Wistar , Porcinos , Factor de Crecimiento Transformador beta/genéticaRESUMEN
Neuropsychiatric dysfunction and reactive microglia are hallmarks of high-fat diet (HFD)-induced obesity, yet whether these reactive microglia contribute to HFD-induced obesity-related behavioral abnormalities and the underlying mechanisms remain unclear. Here, we show that HFD feeding causes social deficits and anxiety-like behaviors with impaired neuronal activity and alters the gut microbiota, particularly by depleting Lactobacillus reuteri (L. reuteri), in mice. The profiles of microbiome and metabolome in HFD-fed mice predict that specific microbial taxa and their metabolites regulate HFD-induced obesity-related behavioral abnormalities. Oral treatment with the L. reuteri reduces microglial activation and increases dendritic spine density, thus ameliorates social deficits and anxiety in HFD-fed mice. HFD-fed mice that are administered L. reuteri are also found to accumulate butyrate in their gut, sera and brain. Moreover, supplementation of butyrate improves behavioral abnormalities and modulates microglial homeostasis in HFD-fed mice. In addition, selectively removal of microglia through a pharmacologic approach can rescue dendritic spine loss and increase neuronal activity that profoundly alleviates social deficits and anxiety arising from HFD-induced obesity. Overall, this study reveals an unexpected pivotal role of gut commensal-derived butyrate in HFD-induced social deficits and anxiety-like behaviors through regulation of microglial homeostasis and identifies a potential probiotic treatment for HFD-induced obesity-related behavioral abnormalities.
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Butiratos , Microglía , Animales , Dieta Alta en Grasa , Microbioma Gastrointestinal , Ratones , ObesidadRESUMEN
Ample evidence indicates that maternal immune activation (MIA) during gestation is linked to an increased risk for neurodevelopmental and psychiatric disorders, such as autism spectrum disorder (ASD), anxiety and depression, in offspring. However, the underlying mechanism for such a link remains largely elusive. Here, we performed RNA sequencing (RNA-seq) to examine the transcriptional profiles changes in mice in response to MIA and identified that the expression of Scn1a gene, encoding the pore-forming α-subunit of the brain voltage-gated sodium channel type-1 (NaV1.1) primarily in fast-spiking inhibitory interneurons, was significantly decreased in the medial prefrontal cortex (mPFC) of juvenile offspring after MIA. Moreover, diminished excitatory drive onto interneurons causes reduction of spontaneous gamma-aminobutyric acid (GABA)ergic neurotransmission in the mPFC of MIA offspring, leading to hyperactivity in this brain region. Remarkably, treatment with low-dose benzodiazepines clonazepam, an agonist of GABAA receptors, completely prevented the behavioral abnormalities, including stereotypies, social deficits, anxiety- and depression-like behavior, via increasing inhibitory neurotransmission as well as decreasing neural activity in the mPFC of MIA offspring. Our results demonstrate that decreased expression of NaV1.1 in the mPFC leads to abnormalities in maternal inflammation-related behaviors and provides a potential therapeutic strategy for the abnormal behavioral phenotypes observed in the offspring exposed to MIA.
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Clonazepam/uso terapéutico , Moduladores del GABA/uso terapéutico , Neuronas GABAérgicas/inmunología , Trastornos Mentales/inmunología , Efectos Tardíos de la Exposición Prenatal/inmunología , Transmisión Sináptica/inmunología , Animales , Clonazepam/farmacología , Femenino , Moduladores del GABA/farmacología , Agonistas de Receptores de GABA-A/farmacología , Agonistas de Receptores de GABA-A/uso terapéutico , Neuronas GABAérgicas/química , Neuronas GABAérgicas/efectos de los fármacos , Masculino , Trastornos Mentales/inducido químicamente , Trastornos Mentales/prevención & control , Ratones , Ratones Endogámicos C57BL , Canal de Sodio Activado por Voltaje NAV1.1/biosíntesis , Canal de Sodio Activado por Voltaje NAV1.1/inmunología , Poli I-C/toxicidad , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/inmunología , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/prevención & control , Receptores de GABA-A/inmunología , Transmisión Sináptica/efectos de los fármacosRESUMEN
Social experiences during early life are thought to be critical for proper social and emotional development. Conversely, social insults during development causes long-lasting behavioral abnormalities later in life. However, how juvenile social deprivation influences social and emotional behaviors remains poorly understood. Here, we show that juvenile social isolation induces a shift in microbial ecology that negatively impacts social and emotional behaviors in adulthood. These behavioral changes, which occur during this critical period are transferable to antibiotic pre-treated mice by fecal microbiota transplant. In addition, juvenile social isolation decreases the expression of oxytocin receptor (OXTR) in the medial prefrontal cortex (mPFC), and increases the amounts of fecal propionic acid (PA), a short-chain fatty acid derived from gut micobiota. Accordingly, infusion with an OXTR antagonist (OXTR-A, l-368,899) specifically in the mPFC or supplementation of PA both can cause social deficits and anxiety-like behaviors in group housed mice. Collectively, our findings reveal that juvenile social experience regulates prefrontal cortical OXTR expression through gut microbiota-produced PA and that is essential for normal social and emotional behaviors, thus providing a cellular and molecular context to understand the consequences of juvenile social deprivation.
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Ansiedad/metabolismo , Microbioma Gastrointestinal/fisiología , Corteza Prefrontal/metabolismo , Propionatos/metabolismo , Receptores de Oxitocina/metabolismo , Aislamiento Social , Animales , Conducta Animal , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: XQLF (Xiaoqinglong formula) is the most commonly used prescription of traditional Chinese medicine in the treatment of asthma. XQLF combined with western medicine has been used to treat bronchial asthma in more and more cases, and good results have been achieved. Therefore, this meta-analysis aimed to evaluate the adjuvant treatment of traditional Chinese medicine classic herbal formula XQLF with bronchial asthma in acute attack. METHODS: The following electronic databases were systematically searched from inception to April 2019: PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), WanFang, VIP Database for Chinese Technical Periodicals, and China Biology Medicine (CBM). Two reviewers searched these databases and independently evaluated all the eligible articles for inclusion. Stata 14.0 was used for data synthesis and analysis. RESULTS: A total of 33 RCTs (randomized controlled trials) including 2176 patients were enrolled. All of the patients in these studies were in the acute attack stage of asthma. We conducted subgroup analysis according to the duration of treatment, which was 14 days, 10 days, and 7 days, respectively. The overall results show that adjuvant treatment with XQLF significantly improve CER (clinical efficacy rate) (RR = 1.17; 95% CI, 1.14 to 1.21; P < 0.0001) and promote pulmonary function including FEV1 (WMD = 0.35; 95% CI, 0.27 to 0.43; P < 0.0001), PEF (SMD = 1.02; 95% CI, 0.49 to 1.55; P < 0.0001), and FVC (WMD = 0.51; 95% CI, 0.35 to 0.66; P < 0.0001). The adjuvant treatment of XQLF can also reduce serum IgE concentration (SMD = -1.39; 95% CI, 1.92 to -0.85; P < 0.0001) and serum EOS concentration at 14 days (WMD = -39.85; 95% CI, -56.20 to -23.49; P < 0.0001). CONCLUSION: This study finally showed that XQLF has the auxiliary effect of improving the efficiency, promoting the lung function, and reducing the serum IgE in the treatment of acute attack asthma. This trial is registered with CRD42019133549.
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Myopathy is a muscle disease in which muscle fibers do not function properly, and eventually cause severe diseases, such as muscular dystrophy. The properly regeneration of skeletal muscle plays a pivotal role to maintain the muscle function after muscle injury. The aim of this study is to determine whether andrographolide plays an effect role on regulating skeletal muscle regeneration. Mouse satellite cells, C2C12 cells and Cardiotoxin (CTX) intramuscular injection induced acute skeletal muscle injury model were used to evaluate whether andrographolide is essential for skeletal muscle regeneration. The underling mechanism detected using immunohistochemistry stain, western blot, real time PCR. Andrographolide promotes mouse skeletal muscle regeneration. In cardiotoxin induced skeletal muscle injury model, andrographolide treatment enhanced myotube generation and promoted myotube fusion. Andrographolide treatment dramatically increased expression of myotube differentiation related genes, including Desmin, MyoD, MyoG, Myomaker, Tnni2, Dmd, Myoz1 and Myoz3. For the mechanism studies, we observed that andrographolide treatment significantly promoted histone modification, such as H3K4Me2, H3K4Me3 and H3K36Me2, both in vivo and in vitro. Treatment with DZNep, a Lysine methyltransferase EZH2 inhibitor, significantly attenuated andrographolide-induced expression of Myf5, Myomaker, Skeletal muscle α-actin, MyoD and MyoG. Taken together, our data in this study demonstrate andrographolide epigenetically drives differentiation and fusion of myotube, eventually promotes skeletal muscle regeneration. This should be a therapeutic treatment for skeletal muscle regeneration after muscle damage.
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Diterpenos/farmacología , Epigénesis Genética/efectos de los fármacos , Desarrollo de Músculos/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Regeneración/fisiología , Animales , Antiinflamatorios/farmacología , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Células Cultivadas , Epigénesis Genética/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Desarrollo de Músculos/fisiología , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/fisiología , Músculo Esquelético/citología , Músculo Esquelético/fisiología , Mioblastos/efectos de los fármacos , Mioblastos/fisiología , Regeneración/efectos de los fármacosRESUMEN
The aim of this study is to investigate the therapeutic role of Tanshinone II A, a key integrant from salvia miltiorrhiza, against pathological vascular remodeling. Completed ligation of mouse left common carotid arteries animal model and rat smooth muscle cells used to investigate the role of Tanshinone II A in regulating pathological vascular remodeling through hematoxylin and eosin staining, immunohistochemistry staining, immunofluorescence staining, adenovirus infection, real time PCR and western blotting. Our data demonstrated that Tanshinone II A treatment suppresses vascular injury-induced neointima formation. In vitro studies on rat smooth muscle cell indicated that Tanshinone II A treatment attenuates PDGF-BB induced cell growth, and promotes smooth muscle cell differentiated marker genes expression that induced by rapamycin treatment. Tanshinone II A treatment significant inhibits rat smooth muscle cell proliferation and migration. Tanshinone II A promotes KLF4 expression during smooth muscle phenotypic switching. Overexpression of KLF4 exacerbates Tanshinone II A mediated smooth muscle cell growth inhibition. Tanshinone II A plays a pivotal role in regulating pathological vascular remodeling through KLF4 mediated smooth muscle cell phenotypic switching. This study demonstrated that Tanshinone II A is a potential therapeutic agent for vascular diseases.
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Abietanos/farmacología , Diferenciación Celular/genética , Expresión Génica/efectos de los fármacos , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Músculo Liso Vascular/crecimiento & desarrollo , Remodelación Vascular/efectos de los fármacos , Abietanos/uso terapéutico , Animales , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Células Cultivadas , Factor 4 Similar a Kruppel , Ratones , Fenotipo , Fitoterapia , Ratas Sprague-Dawley , Salvia miltiorrhiza , Enfermedades Vasculares/tratamiento farmacológicoRESUMEN
The prefrontal cortex (PFC) plays an important role in regulating anxiety-like phenotypes and social behaviors, and impairments in this brain region has been linked to social deficits in mammals. Childhood obesity is associated with an increased risk of neuropsychiatric behavioral abnormalities, including attenuated social preference and increased anxiety-like behaviors in adulthood. However, little data are available on the impact of obesity during adolescence on PFC-dependent behaviors. Herein, we use the mice pups to illuminate whether and how high-fat diet (HFD) feeding in adolescence affects medial prefrontal cortex (mPFC)-dependent behaviors, and what the underlying cellular and molecular mechanism is. We found that juvenile HFD feeding results in the accumulation of senescent astrocytes and microglia in the mPFC of mice. Furthermore, we found a causal link between the accumulation of senescent glial cells and HFD-induced neuropsychiatric behavioral abnormalities. Pharmacological clearance of senescent glial cells in HFD-fed mice enhances neuronal activity and reserves synaptic excitatory/inhibitory balance, thus preserving normal behaviors. Collectively, these results show that senescent glial cells play a significant role in the initiation and progression of juvenile obesity-mediated neuropsychiatric behavioral abnormalities, and suggest that targeting senescent glial cells may provide a therapeutic avenue for the treatment of obesity-related neuropsychiatric disorders in children.
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Trastornos Mentales/fisiopatología , Neuroglía/fisiología , Corteza Prefrontal/fisiología , Factores de Edad , Envejecimiento/fisiología , Animales , Ansiedad/etiología , Astrocitos/fisiología , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Encéfalo/fisiología , Cognición/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/fisiología , Neuroglía/metabolismo , Neuronas/fisiología , Corteza Prefrontal/metabolismo , Conducta SocialRESUMEN
BACKGROUND: Chronic hepatitis B is often complicated with different degrees of hepatic fibrosis, which affects the quality of life. Nucleoside analogs are recommended by almost all guidelines in the world for the treatment of chronic hepatitis B. At present, there is no specific and effective chemical and biological agents for hepatic fibrosis. In China, Chinese compound prescription combined with nucleoside analogs have been used to treat hepatic fibrosis of chronic hepatitis B patients in more and more cases, and good results have been achieved. Several Chinese compound prescriptions that have been made into proprietary Chinese medicine for the convenience of use. This article aims to systematically evaluate the efficacy and safety of Chinese medicine compounds assisting nucleoside analogs in the treatment of hepatic fibrosis in chronic hepatitis B patients. METHOD: The following databases will be searched from their inception to September 2019: PubMed, EMBASE, EBSCOhost, The Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical literature Database (CBM), VIP Database, Wanfang Database. Languages are limited to Chinese and English. The study includes randomized controlled trials using Chinese compound prescription combined with entecavir and Chinese compound prescription combined with tenofovir disoproxil fumarate to treat hepatic fibrosis of chronic hepatitis B patients. The primary outcomes including effective rate and biochemical parameters (levels of hyaluronic acid, laminin, pre-type-III collagen and type IV collagen will be tested. Additional outcomes include liver function indexes (levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin) and levels of hepatitis B virus DNA. Stata14.0 software will be used for meta-analysis. RESULT: The efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs for hepatic fibrosis of chronic hepatitis B patients will be assessed from the effective rate, biochemical parameters, liver function indexes, and levels of hepatitis B virus DNA. CONCLUSION: The conclusion of this study will be used to evaluate the efficacy and safety of Chinese compound prescriptions assisting nucleoside analogs in the treatment of hepatic fibrosis of chronic hepatitis B patients, as well as the adjuvant effectiveness of Chinese compound prescriptions in combined therapy. PROSPERO REGISTRATION NUMBER: CRD42020156859.
Asunto(s)
Hepatitis B Crónica/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Nucleósidos/análogos & derivados , Antivirales/uso terapéutico , China/epidemiología , Virus ADN/efectos de los fármacos , Bases de Datos Factuales , Quimioterapia Combinada/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Guanina/análogos & derivados , Guanina/uso terapéutico , Hepatitis B Crónica/complicaciones , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/psicología , Pruebas de Función Hepática/métodos , Masculino , Nucleósidos/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Tenofovir/uso terapéutico , Metaanálisis como AsuntoRESUMEN
BACKGROUND: Chronic viral hepatitis b and its related complications have caused serious harm to human health and become a worldwide public health problem. Hepatitis b cirrhosis is one of the most common complications in Asia. Traditional Chinese medicine combined with antiviral therapy has become the first choice for clinical treatment of hepatitis b Cirrhosis. Biejia Pill is an effective prescription of traditional Chinese medicine in treating Compensatory period of cirrhosis, and there are more and more clinical reports about its validity in treating Compensatory period of cirrhosis. Therefore, we designed this study protocol to evaluate the adjuvant role of Biejia Pill in the treatment of Compensatory period of cirrhosis. METHOD: Electronic Databases, PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc, (CBM), will be systematically searched from inception to July 2019. Randomized controlled trials (RCTs) on Biejiajian Pill combined with Entecavir and Entecavir alone against Compensatory period of hepatitis b cirrhosis will be included; inclusion and exclusion criteria will be used to screen the trials. liver fibrosis biomarkers including ECM or its metabolites (serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), and type IV collagen (IV-C)) will be measured as primary outcomes. Liver function, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms will be measured as secondary outcomes. RevMan5 software will be used for literature quality evaluation and data synthesis and analysis. RESULT: To evaluate the efficacy and safety of Biejiajian Pill in combination therapy by observing the outcomes of serum liver fibrosis markers, adverse reactions and liver function. CONCLUSION: This study protocol will be used to evaluate the efficacy and safety of Biejia Pill in combination with entecavir in the treatment of Compensatory period of hepatitis b cirrhosis, as well as the adjuvant treatment of Biejia Pill in combination.PROSPERO registration number: CRD42019135402.
Asunto(s)
Antivirales/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Guanina/análogos & derivados , Hepatitis B/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Biomarcadores/sangre , Quimioterapia Combinada , Guanina/uso terapéutico , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/etiología , Cirrosis Hepática/virología , Revisiones Sistemáticas como AsuntoRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease with a poor prognosis characterized by transforming growth factor (TGF)-ß-induced proliferation, migration, and differentiation of fibroblasts, resulting in excessive extracellular matrix (ECM) deposition. Whether Kangfuxin oral liquid (KFXOL) has a protective function in pulmonary fibrosis is largely unknown. The goal of this study was to investigate the potential efficacy of KFXOL, as well as the underlying mechanism by which KFXOL regulates pulmonary fibrosis in vivo and in vitro. We found that KFXOL dramatically attenuated intratracheal bleomycin (BLM)-induced pulmonary fibrosis in terms of both severe alveolar architecture destruction and collagen deposition. KFXOL treatment significantly inhibited the proliferation, migration, and differentiation of pulmonary fibroblasts following activation using BLM/TGF-ß1 and normalized the expression of ECM deposition-related proteins, including matrix metalloproteinase (MMP)-1, MMP-9, and tissue inhibitor of metalloproteinases 1. These effects were mediated via the inhibition of TGF-ß1 and phosphorylated Smad2/3 activation in vivo. Taken together, our data suggest that KFXOL attenuates the development of pulmonary fibrosis via the TGF-ß1/Smad signaling pathway and thus has potential utility in the treatment of pulmonary fibrosis.