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INTRODUCTION: During postherpetic neuralgia (PHN), the cerebral spinal fluid (CSF) possesses the capability to trigger glial activation and inflammation, yet the specific changes in its composition remain unclear. Recent findings from our research indicate elevations of central bone morphogenetic protein 4 (BMP4) during neuropathic pain (NP), serving as an independent modulator of glial cells. Herein, the aim of the present study is to test the CSF-BMP4 expressions and its role in the glial modulation in the process of PHN. METHODS: CSF samples were collected from both PHN patients and non-painful individuals (Control) to assess BMP4 and its antagonist Noggin levels. Besides, intrathecal administration of both CSF types was conducted in normal rats to evaluate the impact on pain behavior, glial activity, and inflammation.; Additionally, both Noggin and STAT3 antagonist-Stattic were employed to treat the PHN-CSF or exogenous BMP4 challenged cultured astrocytes to explore downstream signals. Finally, microglial depletion was performed prior to the PHN-CSF intervention so as to elucidate the microglia-astrocyte crosstalk. RESULTS: BMP4 levels were significantly higher in PHN-CSF compared to Control-CSF (P < 0.001), with a positive correlation with pain duration (P < 0.05, r = 0.502). Comparing with the Control-CSF producing moderate paw withdrawal threshold (PWT) decline and microglial activation, PHN-CSF further exacerbated allodynia and triggered both microglial and astrocytic activation (P < 0.05). Moreover, PHN-CSF rather than Control-CSF evoked microglial proliferation and pro-inflammatory transformation, reinforced iron storage, and activated astrocytes possibly through both SMAD159 and STAT3 signaling, which were all mitigated by the Noggin application (P < 0.05). Next, both Noggin and Stattic effectively attenuated BMP4-induced GFAP and IL-6 upregulation, as well as SMAD159 and STAT3 phosphorylation in the cultured astrocytes (P < 0.05). Finally, microglial depletion diminished PHN-CSF induced astrogliosis, inflammation and endogenous BMP4 expression (P < 0.05). CONCLUSION: Our study highlights the role of CSF-BMP4 elevation in glial activation and allodynia during PHN, suggesting a potential therapeutic avenue for future exploration.
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Astrocitos , Proteína Morfogenética Ósea 4 , Hiperalgesia , Microglía , Neuralgia Posherpética , Animales , Microglía/metabolismo , Astrocitos/metabolismo , Proteína Morfogenética Ósea 4/metabolismo , Masculino , Ratas , Humanos , Anciano , Neuralgia Posherpética/líquido cefalorraquídeo , Neuralgia Posherpética/metabolismo , Femenino , Hiperalgesia/metabolismo , Persona de Mediana Edad , Ratas Sprague-Dawley , Factor de Transcripción STAT3/metabolismo , Proteínas Portadoras/metabolismoRESUMEN
BACKGROUND: BMP7 has been shown to have neuroprotective effects and to alleviate demyelination. However, its role in trigeminal neuralgia (TN) has not been well investigated. The current study aims to determine whether BMP7 plays a role in demyelination, its effects on pain behaviors and mechanism of action in rats with TN. METHODS: We used an infraorbital-nerve chronic-constriction injury (ION-CCI) to establish a rat model of TN. Adeno-associated viruses (AAVs) were injected into the rats to upregulate or downregulate BMP7. The mechanical withdrawal thresholds (MWT) of the injured rats were detected using Von Frey filaments. The changes in expression levels of BMP7 and oligodendrocyte (OL) markers were examined by western blotting, quantitative real-time PCR, immunofluorescence, and transmission electron microscopy. RESULTS: The ION-CCI induced mechanical allodynia, demyelination, and loss of OLs with a reduction of BMP7. Short-hairpin RNA (shRNA)-BMP7 that inhibited BMP7 expression also caused mechanical allodynia, demyelination, and loss of OLs, and its mechanism may be OL apoptosis. Overexpressing BMP7 in the trigeminal spinal subnucleus caudalis(VC) with AAV-BMP7 relieved all three phenotypes induced by the CCI, and its mechanism may be alleviating OLs apoptosis. Two signal pathways associated with apoptosis, STAT3 and p65, were significantly downregulated in the VC after CCI and rescued by BMP7 overexpression. CONCLUSION: BMP7 can alleviate TN by reducing OLs apoptosis and subsequent demyelination. The mechanism behind this protection could be BMP7-mediated activation of the STAT3 and NF-κB/p65 signaling pathway and subsequent decrease in OL apoptosis. Importantly, our study presents clear evidence in support of BMP7 as a possible therapeutic target for the treatment of TN.
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Enfermedades Desmielinizantes , Neuralgia del Trigémino , Ratas , Animales , Neuralgia del Trigémino/tratamiento farmacológico , Hiperalgesia/metabolismo , Ratas Sprague-Dawley , Apoptosis , Oligodendroglía/metabolismoRESUMEN
BACKGROUND: Coagulopathy and massive bleeding are common complications of patients with Stanford type A acute aortic dissection repair, and patients with these complications require many transfusions. Autologous platelet-rich plasma (PRP) is widely used to reduce the need for blood products. In the present study, we aimed to investigate the effects of PRP on blood conservation and the postoperative conditions of patients who underwent aortic arch replacement. METHODS: Patients with aortic dissection undergoing aortic arch replacement were included initially application In all, 837 patients were divided into the PRP and non-PRP groups according to PRP use, whereupon a propensity score match was performed. The data analyzed included patient basic information, intraoperative information, postoperative biochemical examinations, and CTA reports. RESULTS: In total, 610 patients were finally included (305 patients per group). Groups were well balanced after matching. Compared to the non-PRP group, less cryoprecipitate was transfused in the PRP group (10.0 [7.5, 11.0] vs. 10.0 [10.0, 11.5], P = 0.021), while no differences were found in packed RBC, FFP, and platelets between the two groups. Also, the surgery variables showed no differences. After surgery, patients in the PRP group showed higher postoperative serum albumin (36.43±4.20 vs. 35.39±4.40 g/L, P = 0.004) and total protein levels (59.38±6.25 vs. 58.06±7.19 g/L, P = 0.019) than the non-PRP group, but no significant differences in the levels of ALT, AST, Scr, and BUN. CTA reports showed that the proportion of patients with pleural effusion was lower in the PRP group (76.66% vs. 83.99%, OR = 1.59, 95% CI: 1.04-2.45, P = 0.028), while the proportions of pericardial effusion were not significantly different. CONCLUSIONS: PRP application in aortic arch replacement surgery reduced the transfusion of cryoprecipitate, increased the postoperative serum albumin and total protein levels, and reduced the incidence of pleural effusion. No effect of PRP application was found on other postoperative blood indicators and CTA reports.
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Disección Aórtica , Plasma Rico en Plaquetas , Derrame Pleural , Humanos , Aorta Torácica/cirugía , Estudios Retrospectivos , Disección Aórtica/cirugíaRESUMEN
Excessive activation of pro-inflammatory (M1) microglia phenotypes after spinal cord injury (SCI) disrupts tissue repair and increases the risk of secondary SCI. We previously reported that adeno-associated virus (AAV) mediated delivery of bone morphogenetic protein 7 (BMP7) promotes functional recovery after SCI by reducing oligodendrocyte loss and demyelination; however, little is known about the early effects of BMP7 in ameliorating neuroinflammation in the acute SCI phase. Herein, we demonstrate that treatment with recombinant human BMP7 (rhBMP7) suppresses the viability of LPS-induced HMC3 microglia cells and increases the proportion with the M2 phenotype. Consistently, in a rat SCI model, rhBMP7 decreases the activation of microglia and promotes M2 polarization. After rhBMP7 administration, the STAT3 signaling pathway was activated in LPS-induced HMC3 cells and microglia in spinal cord lesions. Furthermore, the levels of TNF-α and IL-1ß were significantly decreased in cell culture supernatants, lesion sites of injured spinal cords, and cerebrospinal fluid circulation after rhBMP7 administration, thus reducing neuron loss in the injured spinal cord and promoting functional recovery after SCI. These results provide insight into the immediate early mechanisms by which BMP7 may ameliorate the inflammation response to secondary SCI.
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Microglía , Traumatismos de la Médula Espinal , Humanos , Ratas , Animales , Microglía/metabolismo , Enfermedades Neuroinflamatorias , Inflamación/metabolismo , Proteína Morfogenética Ósea 7/metabolismo , Proteína Morfogenética Ósea 7/farmacología , Lipopolisacáridos/toxicidad , Traumatismos de la Médula Espinal/patología , Médula Espinal/metabolismo , Factor de Transcripción STAT3/metabolismoRESUMEN
Objective: The aim of this study is to compare the effect of bronchial blockers (BB) and double-lumen tubes (DLT) on patients' postoperative recovery after lung resection. Method: 4,636 patients undergoing lung resection and receiving either BB or DLT intubation were reviewed and matched using the propensity score matching method. The primary outcome was the surgical duration. The secondary outcomes included diagnostic results of postoperative chest X-ray, postoperative oxygenation index, incidence of hypercapnia, hypoxemia and sore throat, chest tube duration, incidence of ICU admission, length of hospital stay and incidence of the 30-day readmission. Results: After matching, 401 patients receiving BB were matched to 3,439 patients receiving DLT. There was no statistical difference on the surgical duration between the two groups (P>0.05). However, compared with the DLT group, patients in the BB group showed more infiltrate especially at the surgery side (14.96% versus 9.07%, P<0.001) based on the chest X-ray, together with higher incidence of ICU admission (5.23% versus 2.61%, P<0.05). Additionally, no statistical differences were found between the two groups about chest tube duration, oxygenation index, incidence of hypercapnia, hypoxemia and sore throat, duration of surgery, hospital stays and 30-day readmission (P>0.05). Conclusions: Compared with the DLT, patients receiving BB technique tend to have increased pulmonary infiltrate (especially the surgery side) and higher incidence of ICU admission at the early post-operative stage, which may have an influence on the patients' recovery.
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Faringitis , Procedimientos Quirúrgicos Torácicos , Bronquios , Estudios de Cohortes , Humanos , Hipercapnia/complicaciones , Hipoxia/complicaciones , Intubación Intratraqueal/efectos adversos , Faringitis/etiología , Puntaje de Propensión , Procedimientos Quirúrgicos Torácicos/efectos adversos , Procedimientos Quirúrgicos Torácicos/métodosRESUMEN
BACKGROUND: Cognitive impairment can seriously affect the quality of life of Parkinson's disease (PD) patients. Although numerous studies showed that N200, P300 latency and amplitude are correlated with cognitive functions, there is a sufficient amount of controversial results. Therefore, it is necessary to conduct a meta-analysis of N200, P300 latency and amplitude data of event-related potential (ERP) in PD. METHODS: We systematically searched on PubMed and Web of Science for PD-related ERP studies published before December 2021. Standard mean difference (SMD) and 95% confidence interval (CI) estimates of N200 and P300 components were compared among PD patients, PD dementia (PDD) patients, PD non-dementia (PDND) patient, and healthy control (HC). RESULTS: Our meta-analysis showed prolonged N200 latency at the Fz, Cz electrode sites, prolonged P300 latency at the Fz sites in PD patients, compared to HC; prolonged N200 latency at the Cz, Pz electrode sites in PDND patients, compared to HC; prolonged P300 latency at the Cz site in PDD patients, compared to PDND patients; and reduced P300 amplitude at the Fz electrode site in PDND patients, compared to HC. CONCLUSIONS: N200 and P300 component may be potential electrophysiological biomarkers of early cognitive impairment in PD patients. Future studies are needed to confirm this conclusion. Estimates of N200 and P300 component can be a valuable support for clinicians in diagnosis of early cognitive impairment in PD patients due to the simplicity and non-invasiveness of the procedure.
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Disfunción Cognitiva , Enfermedad de Parkinson , Humanos , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Potenciales Relacionados con Evento P300/fisiología , Potenciales Evocados/fisiología , Calidad de VidaRESUMEN
Monocarboxylate functionalized pillar[5]arene 1 with excellent solubility in organic solvent was prepared. It could be abosorpted on the surface of gold nanorod spontaneously. Then, hybrid supramolecular materials were constructed from 1 stabilized gold nanorods and a linear dinitriles 2 driven by host-guest interaction. Interestingly, the hybrid supramolecular materials show dynamic near-infrared (NIR) and redox dual-responsive reversible properties. 1H nuclear magnetic resonance (NMR) spectra, transmission electron microscopy (TEM), scanning electron microscopy (SEM), optical microscopy, and specific viscosity were used to characterize the obtained materials and the reversible behavior under external stimuli. We suggest that this NIR and redox dual-responsiveness properties would be useful in preparation other smart materials and have potential in vivo applications.
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Inflammation and oxidative stress are two crucial factors mediating liver fibrosis. Stachydrine (STA) is a naturally occurring compound extracted from a medicinal plant Leonuru heterophyllus, which can inhibit the proliferation and induce the apoptosis of breast cancer cells, relieve high glucose-induced endothelial cell senescence and isoproterenol-induced cardiac hypertrophy, and exert antitumor effects. However, its roles in hepatic fibrosis remain largely unknown. We aimed to evaluate the effect of STA on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats and to elucidate the possible mechanisms. STA alleviated the pathological changes caused by CCl4 injection in livers compared to the normal liver. Hematoxylin-eosin staining further showed that STA treatment remarkably improved the liver histology, as evidenced by mitigated hepatic steatosis, necrosis, and fibrotic septa. STA reduced the liver/body weight ratio and the serum levels of aminotransferase, aspartate aminotransferase and alkaline phosphatase. It also significantly decreased collagen deposition and hydroxyproline level. Both mRNA and protein levels of α-SMA, α1(I)-procollagen and fibronectin were decreased by STA compared to those of the model group. STA significantly inhibited the expressions of inflammatory factors interleukin-6 (IL-6), IL-8, IL-1ß, tumor necrosis factor-α, inducible nitric oxide synthase and cyclooxygenase-2. It suppressed oxidative stress by decreasing malondialdehyde level as well as increasing glutathione level and enzymatic activities of superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase. STA also significantly increased the protein expressions of tissue inhibitor of metallopeptidase-1 (TIMP-1) and TIMP-2 but decreased those of matrix metalloproteinase-2 (MMP-2) and MMP-9, indicating excessive basement membrane in the fibrotic liver. Collectively, STA has potent protective effects on the liver, with therapeutic implication for liver fibrosis.
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Inflamación/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Metaloendopeptidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Prolina/análogos & derivados , Inhibidores Tisulares de Metaloproteinasas/metabolismo , Animales , Tetracloruro de Carbono/farmacología , Línea Celular , Inflamación/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Masculino , Prolina/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
Antimicrobial peptides have been widely recognized as potential candidates for treating tumor, especially for defending against multidrug-resistant cells. Previously, based on the structure of substance P, we have designed a novel class of hybrid antimicrobial peptide NS, which possesses potent antimicrobial activity against a broad spectrum of bacterial pathogens. In this study, we evaluated its cytotoxicity to tumor cells and studied the possible mechanism of action. We showed that NS could efficiently kill tumor cells by rapidly disrupting the tumor cell membrane and inhibiting the DNA synthesis. In addition, we also found that NS could efficiently deliver plasmids into cells and exhibit high transfection efficiency after the introduction of a stearyl moiety to its N-terminus, like many reported cell-penetrating peptides. Taken together, this study revealed the potential multiple functions of NS, providing fundamental support for further therapeutic application as potential antitumor agent.
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Péptidos Catiónicos Antimicrobianos/farmacología , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Plásmidos/metabolismo , Sustancia P/análogos & derivados , Neoplasias del Cuello Uterino/tratamiento farmacológico , Acilación , Animales , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/metabolismo , Antineoplásicos/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/ultraestructura , Células COS , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Membrana Celular/ultraestructura , Proliferación Celular/efectos de los fármacos , Chlorocebus aethiops , Replicación del ADN/efectos de los fármacos , Femenino , Terapia Genética/métodos , Glioblastoma/metabolismo , Glioblastoma/ultraestructura , Humanos , Plásmidos/uso terapéutico , Señales de Clasificación de Proteína , Transporte de Proteínas , Proteínas Recombinantes/farmacología , Sustancia P/genética , Sustancia P/metabolismo , Sustancia P/farmacología , Transfección/métodos , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/ultraestructuraRESUMEN
Many diseases spread due to the bacterial infections, which cause significant economic and personal losses. Contact with infected surfaces is likely to catch infections. Hence, antimicrobial surfaces play an important role in public sectors that can prevent the spreading of disease and infection. Coatings on contact surfaces have been used to provide antimicrobial function. Copper (Cu), as one of the commonly used metals, has long been known to possess germ-killing properties. However, metallic Cu or Cu coatings have not been widely used for the purposes of antimicrobial due to the heavy weight, relatively high cost, limited corrosion resistance and low compatibility of the metal with substrates of non-metallic materials. We have recently developed a polymer-based coating system containing mixtures of fine particles of Cu and Cu salt, which provides excellent antimicrobial properties. The results indicate that the coating with embedded fine Cu salt showed higher antimicrobial property than the coating with only Cu due to the release of more Cu ions. The elimination of 10(6) bacteria by contacting the polymer-Cu coatings needs 8 h, while contacting with the polymer-CuCl2 coatings took only 20 min to kill the same amount of bacteria. We have also used transmission electron microscopy and synchrotron infrared microscopy technique to study the degradation of bacterial cell membrane to understand the mechanism of the antimicrobial function of Cu coating.
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Materiales Biocompatibles Revestidos/farmacología , Cobre/farmacología , Desinfectantes/farmacología , Polímeros/farmacología , Sales (Química)/farmacología , Bacterias/efectos de los fármacos , Bacterias/ultraestructura , Membrana Celular/efectos de los fármacos , Membrana Celular/ultraestructura , Recuento de Colonia Microbiana , Viabilidad Microbiana/efectos de los fármacos , Microscopía Electrónica de Transmisión , Factores de TiempoRESUMEN
An organocatalytic Michael-Michael cascade for the enantioselective construction of spirocyclopentane bioxindoles was developed in moderate to good yield with good diastereoselectivities and excellent enantioselectivities. The straightforward process, catalyzed by a bifunctional chiral squaramide catalyst, serves as a powerful tool for the enantioselective construction of potentially biological bioxindoles with four contiguous chiral centers, of which two are spiro all-carbon quaternary centers on a single cyclopentane ring.