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Astragaloside IV (AST) has been confirmed to have antiasthmatic effects. However, the underline mechanism is unclear. The study aimed to explore the treatment mechanism of AST based on autophagy of memory T cells. AST treatment significantly decreased the number of T effector cells in asthma mice blood and the nude mice that received AST-treated TCMs had relieved inflammation compared with the untreated group; meanwhile, we found that AST significantly decreased the autophagy level and inhibited OX40/OX40L signal pathway of lymphocytes. The results highlighted that AST regulated autophagy to inhibit differentiation of effector T-cell phenotype.
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Asma , Autofagia , Inflamación , Saponinas , Linfocitos T , Triterpenos , Animales , Saponinas/farmacología , Asma/tratamiento farmacológico , Triterpenos/farmacología , Triterpenos/química , Ratones , Autofagia/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Inflamación/tratamiento farmacológico , Ratones Desnudos , Estructura Molecular , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos BALB CRESUMEN
Cerebral ischemia/reperfusion (I/R) injury can result in different levels of cerebral impairment, and in severe cases, death. Curcumin, an essential bioactive component of turmeric, has a rich history as a traditional medicine for various ailments in numerous countries. Experimental and clinical research has established that curcumin offers a protective effect against cerebral I/R injury. Curcumin exerts its protective effects by acting on specific mechanisms such as antioxidant, anti-inflammatory, inhibition of ferroptosis and pyroptosis, protection of mitochondrial function and structure, reduction of excessive autophagy, and improvement of endoplasmic reticulum (ER) stress, which ultimately help to preserve the blood-brain barrier (BBB) and reducing apoptosis. There is currently a shortage of drugs undergoing clinical trials for the treatment of cerebral I/R injury, highlighting the pressing need for research and development of novel treatments to address this injury. The primary objective of this study is to establish a theoretical basis for future clinical applications of curcumin by delineating the mechanisms and protective effects of curcumin against cerebral I/R injury. Adapted with permission from [1].
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Isquemia Encefálica , Curcumina , Fármacos Neuroprotectores , Daño por Reperfusión , Humanos , Curcumina/farmacología , Curcumina/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Apoptosis , Daño por Reperfusión/prevención & control , Isquemia Encefálica/tratamiento farmacológicoRESUMEN
BACKGROUND: We have reported a positive correlation between S100 calcium-binding protein (S100) A8/S100A9 and sepsis-induced lung damage before. However, limited knowledge exists concerning the biological role of S100A8/A9 in pulmonary vascular endothelial barrier dysfunction, as well as the diagnostic value of S100A8/A9 in sepsis. METHODS: Sepsis was induced in C57BL/6J mice and S100A9-knockout (KO) mice through the cecal ligation and puncture (CLP). Pulmonary vascular leakage was determined by measuring extravasated Evans blue (EB). Reverse transcription polymerase chain reaction and the histological score were used to evaluate inflammation and lung injury, respectively. Recombinant S100A8/A9 (rhS100A8/A9) was used to identify the effects of S100A8/A9 on endothelial barrier dysfunction in human umbilical vein endothelial cells (HUVECs). Additionally, the diagnostic value of S100A8/A9 in sepsis was assessed using receiver operating characteristic. RESULTS: S100A8/A9 expression was up-regulated in the lungs of CLP-operated mice. S100A9 KO significantly reversed CLP-induced hypothermia and hypotension, resulting in an improved survival rate. S100A9 KO also decreased the inflammatory response, EB leakage, and histological scores in the lungs of CLP-operated mice. Occludin and VE-cadherin expressions were decreased in the lungs of CLP-operated mice; However, S100A9 KO attenuated this decrease. Moreover, CLP-induced signal transducer and activator of transcription 3 (STAT3) and p38/extracellular signal-regulated kinase (ERK) signalling activation and apoptosis were mitigated by S100A9 KO in lungs. In addition, rhS100A8/A9 administration significantly decreased occludin and VE-cadherin expressions, increased the phosphorylated (p)-ERK/ERK, p-p38/p38, and B-cell leukaemia/lymphoma 2 protein (Bcl-2)-associated X protein/Bcl-2 ratios in HUVECs. CONCLUSION: The present study demonstrated S100A8/A9 aggravated sepsis-induced pulmonary inflammation, vascular permeability, and lung injury. This was achieved, at least partially, by activating the P38/STAT3/ERK signalling pathways. Moreover, S100A8/A9 showed the potential as a biomarker for sepsis diagnosis.
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Lesión Pulmonar , Sepsis , Ratones , Animales , Humanos , Ocludina , Ratones Endogámicos C57BL , Calgranulina A/genética , Calgranulina A/metabolismo , Calgranulina B/genética , Pulmón/metabolismo , Ratones Noqueados , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismoRESUMEN
BACKGROUND: Hypertension is the most common cardiovascular disease, and its main harmful effect is chronic damage to target organs. In some patients with well-controlled blood pressure, target organ damage still occurs. GLP-1 agonists have significant cardiovascular benefits, but their antihypertensive effect is limited. The cardiovascular protective effect of GLP-1 is worth studying. METHODS: The ambulatory blood pressure of spontaneously hypertensive rats (SHRs) was detected by ambulatory blood pressure monitoring, and the characteristics of blood pressure and the effect of subcutaneous intervention with a GLP-1R agonist on blood pressure were observed. To explore the mechanism of the cardiovascular benefit of GLP-1R agonists in SHRs, we evaluated the effects of GLP-1R agonists on vasomotor function and calcium homeostasis in vascular smooth muscle cells (VSMCs) in vitro. RESULTS: Although the blood pressure of SHRs was significantly higher than that of WKY rats, the blood pressure variability of SHRs was also significantly higher than that of the control group. The GLP-1R agonist significantly reduced blood pressure variability in SHRs, but the antihypertensive effect was not obvious. GLP-1R agonists can significantly improve the cytoplasmic calcium overload of VSMCs in SHRs by upregulating the expression of NCX1, improving the systolic and diastolic functions of arterioles, and reducing blood pressure variability. CONCLUSIONS: Taken together, these results provide evidence that GLP-1R agonists improved VSMC cytoplasmic Ca2+ homeostasis through upregulated NCX1 expression in SHRs, which plays a key role in blood pressure stability and broad cardiovascular benefits.
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Hipertensión , Hipotensión , Ratas , Animales , Presión Sanguínea , Músculo Liso Vascular/metabolismo , Calcio/metabolismo , Calcio/farmacología , Antihipertensivos/metabolismo , Antihipertensivos/farmacología , Péptido 1 Similar al Glucagón/metabolismo , Péptido 1 Similar al Glucagón/farmacología , Ratas Endogámicas WKY , Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/tratamiento farmacológico , Ratas Endogámicas SHR , HomeostasisRESUMEN
BACKGROUND: S100 calcium binding protein A9 (S100A9) is a pro-inflammatory alarmin associated with several inflammation-related diseases. However, the role of S100A9 in lung injury in sepsis has not been fully investigated. Therefore, the present study aimed to determine the role of S100A9 in a lipopolysaccharide (LPS)-induced lung injury murine model and its underlying molecular mechanisms. METHODS: LPS was utilized to induce sepsis and lung injury in C57BL/6 or NOD-like receptor family pyrin domain containing 3 (NLRP3)-/- mice. To investigate the effects of S100A9 blockade, mice were treated with a specific inhibitor of S100A9. Subsequently, lung injury and inflammation were evaluated by histology and enzymelinked immunosorbent assay (ELISA), respectively. Furthermore, western blot analysis and RT-qPCR were carried out to investigate the molecular mechanisms underlying the effects of S100A9. RESULTS: S100A9 was upregulated in the lung tissues of LPS-treated mice. However, inhibition of S100A9 alleviated LPS-induced lung injury. Additionally, S100A9 blockade also attenuated the inflammatory responses and apoptosis in the lungs of LPS-challenged mice. Furthermore, the increased expression of NLRP3 was also suppressed by S100A9 blockade, while S100A9 blockade had no effect on NLRP3-/- mice. In vitro, S100A9 downregulation mitigated LPS-induced inflammation. Interestingly, these effects were blunted by NLRP3 overexpression. CONCLUSION: The results of the current study suggested that inhibition of S100A9 could protect against LPS-induced lung injury via inhibiting the NLRP3 pathway. Therefore, S100A9 blockade could be considered as a novel therapeutic strategy for lung injury in sepsis.
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Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Calgranulina B/biosíntesis , Lipopolisacáridos/toxicidad , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/biosíntesis , Lesión Pulmonar Aguda/prevención & control , Animales , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
Rib fracture is the most common injury in chest trauma. Most of patients with rib fractures were treated conservatively, but up to 50% of patients, especially those with combined injury such as flail chest, presented chronic pain or chest wall deformities, and more than 30% had long-term disabilities, unable to retain a full-time job. In the past two decades, surgery for rib fractures has achieving good outcomes. However, in clinic, there are still some problems including inconsistency in surgical indications and quality control in medical services. Before the year of 2018, there were 3 guidelines on the management of regional traumatic rib fractures were published at home and abroad, focusing on the guidance of the overall treatment decisions and plans; another clinical guideline about the surgical treatment of rib fractures lacks recent related progress in surgical treatment of rib fractures. The Chinese Society of Traumatology, Chinese Medical Association, and the Chinese College of Trauma Surgeons, Chinese Medical Doctor Association organized experts from cardiothoracic surgery, trauma surgery, acute care surgery, orthopedics and other disciplines to participate together, following the principle of evidence-based medicine and in line with the scientific nature and practicality, formulated the Chinese consensus for surgical treatment of traumatic rib fractures (STTRF 2021). This expert consensus put forward some clear, applicable, and graded recommendations from seven aspects: preoperative imaging evaluation, surgical indications, timing of surgery, surgical methods, rib fracture sites for surgical fixation, internal fixation method and material selection, treatment of combined injuries in rib fractures, in order to provide guidance and reference for surgical treatment of traumatic rib fractures.
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Tórax Paradójico , Fracturas de las Costillas , Traumatismos Torácicos , China , Consenso , Fijación Interna de Fracturas , Humanos , Fracturas de las Costillas/diagnóstico por imagen , Fracturas de las Costillas/cirugíaRESUMEN
Integrated photonics has the advantages of miniaturization, low cost, and CMOS compatibility, and it provides a stable, highly integrated, and practical platform for quantum key distribution (QKD). While photonic integration of optical components has greatly reduced the overall cost of QKD systems, single-photon detectors (SPDs) have become the most expensive part of a practical QKD system. In order to circumvent this obstacle and make full use of SPDs, we have designed and fabricated a QKD receiver chip for multiple users. Our chip is based on a time-division multiplexing technique and makes use of a single set of SPDs to support up to four users' QKD. Our proof-of-principle chip-based QKD system is capable of producing an average secret key rate of 13.68 kbps for four users with a quantum bit error rate (QBER) as low as 0.51% over a simulated distance of 20 km in fiber. Our result clearly demonstrates the feasibility of multiplexing SPDs for setting QKD channels with different users using photonic integrated chip and may find applications in the commercialization of quantum communication technology.
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BACKGROUND: Blunt cardiac injury (BCI) increases with traffic accidents and is an important cause of death in trauma patients. In particular, for patients who need surgical treatment, the mortality rate is extremely high unless the patient is promptly operated on. This study aimed to explore early recognition and expeditious surgical intervention to increase survival. METHODS: All patients with BCIs during the past 15 years were reviewed, and those who underwent operative treatment were analyzed retrospectively regarding the mechanism of injury, diagnostic and therapeutic methods, and outcome. RESULTS: A total of 348 patients with BCIs accounted for 18.3% of 1903 patients with blunt thoracic injury (BTI). Of 348 patients, 43 underwent operative treatment. The main cause of injury was traffic accidents, with an incidence of 48.8%. Of them, steering wheel injuries occurred in 15 patients. In 26 patients, a preoperative diagnosis was obtained by echocardiography, CT scanning, etc. In the remaining 17, who had to undergo urgent thoracotomy without any preoperative imaging, a definitive diagnosis of BCI was proven during the operation. The volume of preoperative infusion or crystalloid was <1000 ml in 31 cases. Preoperative pericardiocentesis was not used in anyone. In 12 patients, the operation commenced within 1 h. Overall mortality was 32.6%. The death was caused by BCI in 9. CONCLUSIONS: Facing a patient with BTI, a high index of suspicion for BCI must be maintained. To manage those requiring operations, early recognition and expeditious thoracotomy are essential. Preoperatively, limited fluid resuscitation is emphasized. We do not advocate preoperative pericardiocentesis.
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Lesiones Cardíacas/diagnóstico , Lesiones Cardíacas/cirugía , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/cirugía , Accidentes de Tránsito , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ecocardiografía , Urgencias Médicas , Femenino , Lesiones Cardíacas/etiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Toracotomía , Factores de Tiempo , Tomografía Computarizada por Rayos X , Heridas no Penetrantes/etiología , Adulto JovenRESUMEN
BACKGROUND: Adenosine A1 receptor (AA1R) is widely present in the central nervous system, exerting brain protective antiepileptic effects, mainly by binding corresponding G proteins. We evaluated the neuroprotective effects of AA1R on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy in rats. MATERIALS AND METHODS: A total of 60 male SD rats were randomly divided into four groups (n = 15/group): normal control, epilepsy, epilepsy + AA1R antagonist (DPCPX), and epilepsy + AA1R agonist (2-CAdo). An epilepsy model was established through kindling by lithium chloride-pilocarpine. The four groups were observed on days 1, 14, and 30. Pathological and morphological changes of hippocampal neurons were observed by HE staining; apoptosis was detected by TUNEL assay. Caspase-3 and GABA receptor expressions were detected by Western blot. RESULTS: In the hippocampal CA3 area of the epilepsy group, the cellular structure was not neatly arranged, and some neurons were swelling, thick, and incomplete. Compared with the epilepsy group at the same time point, cells in the epilepsy + DPCPX group had an increased distortion, disorganization, edema, cytoplasmic vacuoles, and degeneration. In the epilepsy + 2-CAdo group, cell arrangement was regular and orderly, and structural damages were lessened. Compared with the normal control group at the same time point, the epilepsy group underwent evident neuronal apoptosis, with a significantly higher apoptotic index (AI) (p < 0.05). Compared with the epilepsy group, the neuronal apoptosis of the epilepsy + DPCPX group was boosted, and the AI significantly increased (p < 0.05). The neuronal apoptosis of the epilepsy + 2-CAdo group was inhibited, and the AI significantly decreased (p < 0.05). Compared with the epilepsy group, the caspase-3 expression levels of the epilepsy + DPCPX group on days 14 and 30 were significantly upregulated (p < 0.05), but those of the epilepsy + 2-CAdo group were significantly downregulated (p < 0.05). CONCLUSIONS: AA1R abated cell edema and reduced apoptosis, exerting neuroprotective effects on hippocampal neuronal injury after lithium chloride-pilocarpine-induced epilepsy.
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Agonistas del Receptor de Adenosina A1/farmacología , Epilepsia/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Hipocampo/patología , Cloruro de Litio/toxicidad , Masculino , Neuronas/patología , Pilocarpina/toxicidad , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Despite significant progress in human medicine, certain diseases remain challenging to promptly diagnose and treat. Hence, the imperative lies in the development of more exhaustive criteria and tools. Tissue and cellular mechanics exhibit distinctive traits in both normal and pathological states, suggesting that "force" represents a promising and distinctive target for disease diagnosis and treatment. Atomic force microscopy (AFM) holds great promise as a prospective clinical medical device due to its capability to concurrently assess surface morphology and mechanical characteristics of biological specimens within a physiological setting. This review presents a comprehensive examination of the operational principles of AFM and diverse mechanical models, focusing on its applications in investigating tissue and cellular mechanics associated with prevalent diseases. The findings from these studies lay a solid groundwork for potential clinical implementations of AFM. RESEARCH HIGHLIGHTS: By examining the surface morphology and assessing tissue and cellular mechanics of biological specimens in a physiological setting, AFM shows promise as a clinical device to diagnose and treat challenging diseases.
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Fenómenos Mecánicos , Humanos , Microscopía de Fuerza Atómica , Estudios ProspectivosRESUMEN
The magnitude of vascular residual stress, an inherent characteristic exclusive to the vasculature, exhibits a strong correlation with vascular compliance, tensile resistance, vascular rigidity, and vascular remodeling subsequent to vascular transplantation. Vascular residual stress can be quantified by evaluating the magnitude of the opening angle within the vascular ring. For decellularized vessels, the vascular ring's opening angle diminishes, consequently reducing residual stress. The decellularization process induces a laxity in the vascular fiber structure within decellularized vessels. To investigate the interrelation between the magnitude of residual stress and the microstructure as well as mechanical properties of elastin and collagen within blood vessels, this study employed fresh blood vessels, stress-relieved vessels, and sections of decellularized blood vessels. Structural scanning and force map experiments on the surface of the sections were conducted using atomic force microscopy (AFM). The findings revealed well-organized arrangements of elastin and collagen within fresh vessels, wherein the regularity of collagen and elastin exhibited variability as residual stress declined. Furthermore, both stress-relieved and decellularized vessel sections exhibited a reduction in the mean Young's modulus to varying extents in comparison to fresh vessels. The validity of our experimental results was further corroborated through finite element simulations. Hence, residual stress assumes a crucial role in upholding the structural stability of blood vessels, and the intricate association between residual stress and the microstructural and micromechanical properties of blood vessels holds significant implications for comprehending the impact of vascular diseases on vascular structure and advancing the development of biomimetic artificial blood vessels that replicate residual stress. RESEARCH HIGHLIGHTS: In this inquiry, we scrutinized the interconnection amid vascular residual stress and the microscale and nanoscale aspects of vascular structure and mechanical function, employing AFM. We ascertained that residual stress assumes a pivotal role in upholding vascular microstructure and mechanical attributes. The experimental outcomes were subsequently validated through finite element simulation.
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Vasos Sanguíneos , Colágeno , Elastina , Microscopía de Fuerza Atómica , Estrés Mecánico , Microscopía de Fuerza Atómica/métodos , Elastina/análisis , Animales , Vasos Sanguíneos/fisiología , Vasos Sanguíneos/ultraestructura , Módulo de Elasticidad , Fenómenos BiomecánicosRESUMEN
BACKGROUND: Multilocular thymic cyst (MTC) is a rare mediastinal lesion which is considered to occur in the process of acquired inflammation. It is usually characterized by well-defined cystic density and is filled with transparent liquid. CASE SUMMARY: We report on a 39-year-old male with a cystic-solid mass in the anterior mediastinum. Computer tomography (CT) imaging showed that the mass was irregular with unclear boundaries. After injection of contrast agent, there was a slight enhancement of stripes and nodules. According to CT findings, it was diagnosed as thymic cancer. CONCLUSION: After surgery, MTC accompanied by bleeding and infection was confirmed by pathological examination. The main lesson of this case was that malignant thymic tumor and MTC of the anterior mediastinum sometimes exhibit similar CT findings. Caution is necessary in clinical work to avoid misdiagnosis.
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This study utilized the freeze-drying method to create a chitosan (CS) and polyvinyl alcohol (PVA) sponge. To enhance its antibacterial properties, curcumin and nano silver (Cur@Ag) were added for synergistic antibacterial. After adding curcumin and nano silver, the mechanical properties of the composite sponge dressing (CS-PVA-Cur@Ag) were improved. The porosity of the composite sponge dressing was closed to 80%, which was helpful for drug release, and it had good water absorption and water retention rate. The nano silver diameter was 50-80 nm, which was optimal for killing bacteria. Antibacterial tests usedEscherichia coliandStaphylococcus aureusdemonstrated that little nano silver was required to eliminate bacteria. Finally, in the rat full-thickness skin wound model, the composite sponge dressing can promote wound healing in a short time. In summary, CS-PVA-Cur@Ag wound dressing could protect from bacterial infection and accelerate wound healing. Thus, it had high potential application value for wound dressing.
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Quitosano , Curcumina , Plata , Ratas , Animales , Alcohol Polivinílico , Antibacterianos , Bacterias , AguaRESUMEN
A 46-year-old male sustained severe pe- netrating injury by a sharp instrument to his right upper sternoclavicular junction. The wound tract was from suprasternal notch to mediastinum. Exploratory operation via median sternotomy under general anesthesia found a large mediastinal septum hematoncus, as well as brachiocephalic trunk and left brachiocephalic vein injuries. The perforating vascular wounds were repaired with 5-0 prolene suture. He was recovered uneventfully and discharged 9 days after operation. There was no sequel found during 7 years follow-up.
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Tronco Braquiocefálico/lesiones , Venas Braquiocefálicas/lesiones , Articulación Esternoclavicular/lesiones , Heridas Penetrantes , Tronco Braquiocefálico/cirugía , Venas Braquiocefálicas/cirugía , Humanos , Masculino , Persona de Mediana Edad , Articulación Esternoclavicular/cirugía , Heridas Penetrantes/cirugíaRESUMEN
Dry eye has become an increasingly prevalent public health issue for which there is currently no cure. Manuka honey possesses anti-inflammatory and antioxidant properties that can be used to treat dry eye. The present study aimed to systematically review evidence supporting the treatment of dry eye with manuka honey and quantify this evidence via meta-analysis. Randomised clinical trials that fulfilled the inclusion criteria from database inception until 5 September 2021, were identified through online searches of seven databases, including but not limited to Embase, Medline, and Central. Changes between the point of longest follow-up and baseline subjective symptoms, tear film quality, ocular surface characteristics, adverse events, and compliance were selected for meta-analysis. A total of 288 adult participants with dry eye from five eligible randomised controlled trials were analysed. Compared with the control groups, treatment with manuka honey demonstrated a significant improvement in Ocular Surface Disease Index, Standard Patient Evaluation of Eye Dryness, tear evaporation rate, negative conversion rate of matrix metalloproteinase-9 levels, ocular surface staining, and daily use frequency of lubricant. No serious adverse events were reported, except for temporary stinging and redness, which were generally tolerated. This review found that manuka honey demonstrated promising results for the treatment of dry eye. However, limitations of the included studies and analytical methodology affect the reliability of this conclusion. Therefore, further high-quality randomised clinical trials are required to confirm the efficacy and safety of the use of manuka honey in the treatment of dry eye.
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Síndromes de Ojo Seco , Miel , Adulto , Humanos , Síndromes de Ojo Seco/tratamiento farmacológico , Reproducibilidad de los Resultados , LágrimasRESUMEN
BACKGROUND: S100 calcium-binding protein A9 (S100A9) is a danger-associated molecular pattern molecule that mediates the inflammatory response. Inflammation is essential in aging-related cardiovascular diseases. However, less is known regarding the role of S100A9 in vascular aging. METHODS: S100A9 null mice were used to investigate the role of S100A9 in aging-related pathologies. Artery rings were used to measure the functional characteristics of vascular with a pressurized myograph. Telomere length, Sirtuin activity, oxidative stress, and endothelial nitric oxide synthetase (eNOS) activity were used to elevate vascular senescence. Intraperitoneal glucose tolerance (IPGTT) and insulin sensitivity test (IST) were employed to investigate the effects of S100A9 on insulin resistance. Inflammation response was reflected by the concentration of inflammatory cytokines. The Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) inhibitors were used to identify the downstream molecular mechanisms of S100A9 in aging-induced senescence in endothelial cells. RESULTS: S100A9 expression in vascular increased with aging in mice and humans. Deficiency of S100A9 alleviated vascular senescence in aged mice, as evidenced by increased telomere length, Sirtuin activity, and eNOS activity. Meanwhile, S100A9 knockout improved endothelium-dependent vasodilatation and endothelial continuity in aged mice. Moreover, the increased insulin resistance, oxidative stress, and inflammation were mitigated by S100A9 deletion in aged mice. In vitro, S100A9 induced senescence in endothelial cells, and that effect was blunted by TLR4 but not RAGE inhibitors. CONCLUSION: The present study suggested that S100A9 may contribute to aging-related pathologies and endothelial dysfunction via the TLR4 pathway. Therefore, targeting S100A9/TLR4 signaling pathway may represent a crucial therapeutic strategy to prevent age-related cardiovascular diseases.
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Enfermedades Cardiovasculares , Resistencia a la Insulina , Humanos , Ratones , Animales , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Células Endoteliales/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismo , Calgranulina B/farmacología , Inflamación/genética , Inflamación/metabolismo , Receptor para Productos Finales de Glicación Avanzada/genética , Receptor para Productos Finales de Glicación Avanzada/metabolismoRESUMEN
Background: Sterile inflammation contributes to the pathogenesis of cardiac dysfunction caused by various conditions including pressure overload in hypertension. Mitochondrial DNA (mtDNA) released from damaged mitochondria has been implicated in cardiac inflammation. However, the upstream mechanisms governing mtDNA release and how mtDNA activates sterile inflammation in pressure-overloaded hearts remain largely unknown. Here, we investigated the role of inducible NO synthase (iNOS) on pressure overload-induced cytosolic accumulation of mtDNA and whether mtDNA activated inflammation through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Methods: To investigate whether the cGAS-STING cascade was involved in sterile inflammation and cardiac dysfunction upon pressure overload, cardiomyocyte-specific STING depletion mice and mice injected with adeno-associated virus-9 (AAV-9) to suppress the cGAS-STING cascade in the heart were subjected to transverse aortic constriction (TAC). iNOS null mice were used to determine the role of iNOS in cGAS-STING pathway activation in pressure-stressed hearts. Results: iNOS knockout abrogated mtDNA release and alleviated cardiac sterile inflammation resulting in improved cardiac function. Conversely, activating the cGAS-STING pathway blunted the protective effects of iNOS knockout. Moreover, iNOS activated the cGAS-STING pathway in isolated myocytes and this was prevented by depleting cytosolic mtDNA. In addition, disruption of the cGAS-STING pathway suppressed inflammatory cytokine transcription and modulated M1/M2 macrophage polarization, and thus mitigated cardiac remodeling and improved heart function. Finally, increased iNOS expression along with cytosolic mtDNA accumulation and cGAS-STING activation were also seen in human hypertensive hearts. Conclusion: Our findings demonstrate that mtDNA is released into the cytosol and triggers sterile inflammation through the cGAS-STING pathway leading to cardiac dysfunction after pressure overload. iNOS controls mtDNA release and subsequent cGAS activation in pressure-stressed hearts.
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ADN Mitocondrial , Cardiopatías , Óxido Nítrico Sintasa de Tipo II , Animales , Humanos , Ratones , Citosol/metabolismo , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Cardiopatías/metabolismo , Inflamación/metabolismo , Ratones Noqueados , Mitocondrias/metabolismo , Miocitos Cardíacos/metabolismo , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismoRESUMEN
We aimed to explore the relationships between the plasma expression levels of microRNA (miR)-146a and miR-132 in epileptic patients and cognitive, mental and psychological disorders. Eighty epileptic patients and seventy healthy subjects as controls were evaluated with Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Rating (HAMA) and Hamilton Depression Rating (HAMD) scales, and plasma samples were collected. MiR-146a and miR-132 levels were detected by real-time quantitative PCR. The total incidence rate of cognitive dysfunction, anxiety and depression in epilepsy group was 62.5%. Cognitive dysfunction was correlated positively with educational level, but negatively with disease course, duration and type of administration. The frequency and duration of seizures were positively correlated with anxiety. Depression was correlated negatively with educational level, whereas positively with course of disease and number of used drugs. Epileptic patients had significantly higher miR-146a and miR-132 levels than those of healthy controls. The miR-146a and miR-132 levels of patients with complications were significantly higher than those of cases without complications. Their expressions were correlated negatively with total MoCA scale score, but positively with type of complications. MiR-132 expression was positively correlated with the total scores of HAMA and HAMD scales. Plasma miR-146a and miR-132 expressions increased in epileptic patients, and miR-132 expression reflected the severity of epilepsy and predicted the risks of complications.
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Ansiedad/epidemiología , Depresión/epidemiología , Epilepsia/psicología , MicroARNs/sangre , Regulación hacia Arriba , Adulto , Anciano , Estudios de Casos y Controles , Escolaridad , Epilepsia/sangre , Epilepsia/genética , Femenino , Humanos , Masculino , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: The number of patients with bronchial trauma (BT) who survived to hospital admission has increased with the improvement of prehospital care; early diagnosis and treatment should be considered, especially among blunt trauma patients, whose diagnosis is frequently delayed. AIM: To describe the early recognition and surgical management considerations of blunt and penetrating BTs, and to elaborate the differences between them. METHODS: All patients with BTs during the past 15 years were reviewed, and data were retrospectively analyzed regarding the mechanism of injury, diagnostic and therapeutic procedures, and outcomes. According to the injury mechanisms, the patients were divided into two groups: Blunt BT (BBT) group and penetrating BT (PBT) group. The injury severity, treatment procedures, and prognoses of the two groups were compared. RESULTS: A total of 73 patients with BT were admitted during the study period. The proportion of BTs among the entire cohort with chest trauma was 2.4% (73/3018), and all 73 underwent thoracotomy. Polytrauma patients accounted for 81.6% in the BBT group and 22.9% in the PBT group, and the mean Injury Severity Score was 38.22 ± 8.13 and 21.33 ± 6.12, respectively. Preoperative three-dimensional spiral computed tomography (CT) and/or fiberoptic bronchoscopy (FB) were performed in 92.1% of cases in the BBT group (n = 38) and 34.3% in the PBT group (n = 35). In the BBT group, a delay in diagnosis for over 48 h occurred in 55.3% of patients. In the PBT group, 31 patients underwent emergency thoracotomy due to massive hemothorax, and BT was confirmed during the operation. Among them, 22 underwent pulmo-tractotomy for hemostasis, avoiding partial pneumonectomy. In this series, the overall mortality rate was 6.9% (5/73), and it was 7.9% (3/38) and 5.7% (2/35) in the BBT group and PBT group, respectively (P > 0.05). All 68 survivors were followed for 6 to 42 (23 ± 6.4) mo, and CT, FB, and pulmonary function examinations were performed as planned. All patients exhibited normal lung function and healthy conditions except three who required reoperations. CONCLUSION: The difference between blunt and penetrating BTs is obvious. In BBT, patients generally have no vessel injury, and the diagnosis is easily missed, leading to delayed treatment. The main cause of death is ventilation disturbance due to tension pneumothorax early and refractory atelectasis with pneumonia late. However, in PBT, most patients require emergency thoracotomy because of simultaneous vessel trauma and massive hemothorax, and delays in diagnosis are infrequent. The leading cause of death is hemorrhagic shock.
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Decellularization method based on trypsin-digestion is widely used to construct small diameter vascular grafts. However, this method will reduce the opening angle of the blood vessel and result in the reduction of residual stress. Residual stress reduced has an adverse effect on the compliance and permeability of small diameter vascular grafts. To improve the situation, acellular blood vessels were treated with glutaraldehyde and photooxidation crosslinking respectively, and the changes of opening angle, circumferential residual strain of native blood vessels, decellularized arteries and crosslinked blood vessels were measured by means of histological examination, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in this study. The opening angle of decellularized arteries significantly restored after photooxidation crosslinking (P = 0.0216), while that of glutaraldehyde crosslinking blood vessels reduced. The elastic fibers inside the blood vessels became densely rearranged after photooxidation crosslinking. The results of finite element simulation showed that the residual stress increased with the increase of opening angle. In this study, we found at the first time that photooxidation crosslinking method could significantly increase the residual stress of decellularized vessels, which provides biomechanical support for the development of new biomaterials of vascular grafts.