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INTRODUCTION: Lung cancer is a major global health problem because of its high incidence and mortality. Targeted therapies have transformed treatment of driver-mutated metastatic non-small cell lung cancer (NSCLC). Nevertheless, recent studies demonstrated that cardiovascular disease (CVD) was the second leading cause of mortality in cancer survivors now, management of patients' cardiovascular health during the course of anticancer therapy has become a great challenge faced by the oncologists. Anticancer related cardiovascular (CV) complications are not limited to traditional chemotherapy, but are also increasingly recognized in targeted therapy. CASE REPORT: We present a case of pulmonary embolism (PE) and bradycardia in a 91-year-old NSCLC patient treated with crizotinib for a rare MET Y1003S mutation. To our knowledge, this is the second report to show antitumor response of crizotinib in lung cancer patients with such a rare mutation. However, the patient complained chest tightness and shortness of breath after a month of standard dose crizotinib therapy. Non-invasive examination revealed new onset bradycardia and PE. MANAGEMENT & OUTCOME: Such clinical manifestations were associated with targeted therapy-related CV toxicity, on which the emerging discipline cardio-oncology focused, and a multidisciplinary investigation and treatment was conducted. DISCUSSION: This case highlights the CV adverse events of novel therapies and the current challenges to be tackled in cardio-oncology.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Embolia Pulmonar , Humanos , Idoso de 80 Anos ou mais , Crizotinibe/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Mutação , Bradicardia/induzido quimicamente , Embolia Pulmonar/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversosRESUMO
The least damaging and most economical method to deliver drugs or carriers into the inner ear for treatment of disease is through the middle ear. However, the retention of drug in the middle ear is an obstacle. Here, inspired by the adhesion of mussels, a methacrylate gelatin microspheres (GM) coupling polydopamine (PDA) layer (GM@PDA) with excellent adhesive ability is constructed, and Ebselen liposomes are further loaded into the GM@PDA (GM@PDA@Lipo-Ebselen). The loading capacity of GM@PDA for Ebselen liposomes is 25 ± 1 µg mg-1 microspheres. GM@PDA@Lipo-Ebselen could be injected on round windows membrane (RWM) and tightly adheres to the surface of RWM by PDA, and the microspheres are even still attached to the RWM after 360° rotation and inverted shaking. The in vivo imaging system shows that the adhesive microspheres can prolong the retention of the middle ear cavity for more than 7 days. The hearing of mice in the GM@PDA@Lipo-Ebselen group is significantly recovered, especially on day 14 after noise exposure, and the hearing of each frequency is restored to baseline level. At 32 kHz frequency, the survival of outer hair cells recovers from 48 0± 6% to 93 ± 2%. Therefore, the adhesive and injectable hydrogel microspheres provide a promising strategy for the treatment of hearing loss.
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Orelha Interna , Hidrogéis , Adesivos , Animais , Gelatina , Lipossomos , Camundongos , MicroesferasRESUMO
Oxidative stress plays an important role in the pathogenesis of chronic heart failure (CHF) in many tissues. Increasing evidence suggests that systemic activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling can protect against postinfarct cardiac remodeling by reducing oxidative stress. However, it remains to be elucidated if Nrf2 activation exerts therapeutic effects in the CHF state. Here, we investigated the beneficial hemodynamic effects of bardoxolone methyl (2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester, CDDO-Me), a pharmacological activator of Nrf2, in a rodent model of CHF. Based on echocardiographic analysis, rats at 12 weeks post-myocardial infarction (MI) were randomly split into four groups. CDDO-Me (5 mg/kg, i.p.) was administered daily for another 2 weeks in sham and CHF rats and compared with vehicle treatment. Echocardiographic and hemodynamic analysis suggest that short-term CDDO-Me administration increased stroke volume and cardiac output in CHF rats and decreased left ventricle end-diastolic pressure. Molecular studies revealed that CDDO-Me-induced cardiac functional improvement was attributed to an increase of both Nrf2 transcription and translation, and a decrease of oxidative stress in the noninfarcted areas of the heart. Furthermore, CDDO-Me reduced NF-κB binding and increased Nrf2 binding to the CREB-binding protein, which may contribute to the selective increase of Nrf2 downstream targets, including NADPH Oxidase Quinone 1, Heme Oxygenase 1, Catalase, and Glutamate-Cysteine Ligase Catalytic Subunit, and the attenuation of myocardial inflammation in CHF rats. Our findings suggest that Nrf2 activation may provide beneficial cardiac effects in MI-mediated CHF. SIGNIFICANCE STATEMENT: Chronic heart failure (CHF) is the leading cause of death among the aged worldwide. The imbalance between pro- and antioxidant pathways is a determinant in the pathogenesis of CHF. Systemic activation of Nrf2 and antioxidant protein signaling by bardoxolone methyl may have beneficial effects on cardiac function and result in improvements by enhancing antioxidant enzyme expression and attenuating myocardial inflammation.
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Insuficiência Cardíaca/tratamento farmacológico , Fator 2 Relacionado a NF-E2/fisiologia , Ácido Oleanólico/análogos & derivados , Animais , Proteína de Ligação a CREB/metabolismo , Doença Crônica , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Masculino , NF-kappa B/metabolismo , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Ratos , Ratos Sprague-Dawley , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
BACKGROUND: Due to the importance of evidence-based research in plastic surgery, the authors of this study aimed to assess the accuracy of ChatGPT in generating novel systematic review ideas within the field of craniofacial surgery. METHODS: ChatGPT was prompted to generate 20 novel systematic review ideas for 10 different subcategories within the field of craniofacial surgery. For each topic, the chatbot was told to give 10 "general" and 10 "specific" ideas that were related to the concept. In order to determine the accuracy of ChatGPT, a literature review was conducted using PubMed, CINAHL, Embase, and Cochrane. RESULTS: In total, 200 total systematic review research ideas were generated by ChatGPT. We found that the algorithm had an overall 57.5% accuracy at identifying novel systematic review ideas. ChatGPT was found to be 39% accurate for general topics and 76% accurate for specific topics. CONCLUSION: Craniofacial surgeons should use ChatGPT as a tool. We found that ChatGPT provided more precise answers with specific research questions than with general questions and helped narrow down the search scope, leading to a more relevant and accurate response. Beyond research purposes, ChatGPT can augment patient consultations, improve healthcare equity, and assist in clinical decisionmaking. With rapid advancements in artificial intelligence (AI), it is important for plastic surgeons to consider using AI in their clinical practice to improve patient-centered outcomes.
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Ileocolic intussusception is a consideration in young pediatric patients with acute abdominal pain. Meckel's diverticulum is the most common pathologic lead point for intussusception in children and the appendix acting as the lead point is rare. In addition, management guidelines for recurrent ileocolic intussusception (RICI) are lacking. We present two cases of RICI in which the pathological lead point was the appendix. The first patient, a two-year-old with no medical history, had intermittent abdominal pain and non-bloody vomiting for a month. Ultrasound revealed ileocolic intussusception, successfully managed with pneumatic reduction. However, symptoms recurred and a repeat ultrasound showed partial intussusception of the appendix into the cecum. Laparoscopic reduction and appendectomy were then performed. Symptomatic intussusception recurred, and a second laparoscopic reduction with stump appendectomy resolved all symptoms. The second patient, a three-year-old with no medical history, had colicky abdominal pain for 24 hours. Ultrasound revealed ileocolic intussusception that was pneumatically reduced. As pain recurred, laparoscopic reduction and appendectomy were performed, revealing ileocolic intussusception with a dilated appendix as the pathologic lead point. Recurrent ileocolic intussusception (RICI) with the appendix as the lead point is common, but RICI with the appendix as the lead point is rare. These cases demonstrate the role of the appendix as a pathologic lead point, and a review of the literature supports the need for surgical reduction. While enema reduction is the first line for recurrent intussusception, surgical reduction is preferred when a pathological lead point is suspected.
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Background: Scrubs have become widespread office attire for plastic surgeons. The purpose of this study is to evaluate the public perception of scrub color and style for plastic surgeons. Methods: A crowdsourced survey was performed via MTurk. Respondents were asked to rate images of a surgeon dressed in black, navy, blue, and green scrubs as well as traditional or fitted scrubs. Qualities including representativeness, skill, trustworthiness, knowledge, and compassion were rated on a Likert scale across all images. Analysis of variance and one-sided t test were used to analyze differences in means. Results: In total, 562 responses were collected. For female plastic surgeons, navy and blue scrubs were perceived to be superior to those wearing black for skill, representativeness, trustworthiness, and compassion (P < 0.05). For male plastic surgeons, navy and blue scrubs were superior to black for knowledge, skill, representativeness, trustworthiness, and compassion (P < 0.05). For skill and representativeness, navy was superior to green (P < 0.05). For representativeness, blue was superior to green (P < 0.05). For trustworthiness and compassion, green was superior to black (P < 0.05). Fitted scrubs were significantly preferred (P < 0.05) across all characteristics with the exception of representativeness in the subgroup of male plastic surgeons. Conclusions: Black scrubs are associated with more negative characteristics than navy or blue scrubs, which were found to be the most positively perceived. Fitted scrubs were associated with positive characteristics for both male and female surgeons. The purchase of fitted scrubs may be a worthwhile purchase to maximize the patient-physician relationship.
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Objectives: While the internet provides accessible medical information, often times it does not cater to the average patient's ability to understand medical text at a 6th and 8th grade reading level, per American Medical Association (AMA)/National Institute of Health (NIH) recommendations. This study looks to analyze current online materials relating to posterior cruciate ligament (PCL) surgery and their readability, understandability, and actionability. Methods: The top 100 Google searchs for "PCL surgery" were compiled. Research papers, procedural protocols, advertisements, and videos were excluded from the data collection. The readability was examined using 7 algorithms: the Flesch Reading Ease Score, Gunning Fog, Flesch-Kincaid Grade Level, Coleman-Liau Index, SMOG index, Automated Readability Index and the Linsear Write Formula. Two evaluators assessed Understandability and Actionability of the results with the Patient Educational Materials Assessment Tool (PEMAT). Outcome measures included Reading Grade Level, Reader's age minimum and maximum, Understandability, and Actionability. Results: Of the 100 results, 16 were excluded based on the exclusion criteria. There was a statistically significant difference between the readability of the results from all algorithms and the current recommendation by AMA and NIH. Subgroup analysis demonstrated that there was no difference in readability as it pertained to which page they appeared on Google search. There was also no difference in readability between individual websites versus organizational websites (hospital and non-hospital educational websites). Three articles were at the 8th grade recommended reading level, and all three were from healthcare institutes. Conclusion: There is a discrepancy in readability between the recommendation of AMA/NIH and online educational materials regarding PCL surgeries, regardless of where they appear on Google and across different forums. The understandability and actionability were equally poor. Future research can focus on the readability and validity of video and social media as they are becoming increasingly popular sources of medical information.
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Introduction: Primary ciliary dyskinesia (PCD) is a rare heterogeneous disease caused by abnormalities in motile cilia. In this case report, we first analyzed the clinical and genetic data of a proband who was suspected of having PCD on the basis of her clinical and radiological findings. Methods: Whole-exome sequencing was performed, and a variant in the RSPH4A gene was identified in the proband. Sanger sequencing was used for validation of RSPH4A variants in the proband, her sister, her daughter and her parents. Finally, the phenotypic features of the patient were analyzed, and the current literature was reviewed to better understand the gene variants in PCD related to hearing loss and the clinical manifestations of the RSPH4A variant in PCD. Results: The chief clinical symptoms of this proband included gradual mixed hearing loss, otitis media, anosmia, sinusitis, recurrent cough and infertility. Her DNA sequencing revealed a novel homozygous T to C transition at position 1321 within exon 3 of RSPH4A according to genetic testing results. This variant had never been reported before. The homozygous variant resulted in an amino acid substitution of tryptophan by arginine at position 441 (p.Trp441Arg). The same variant was also found in the proband's sister, and a heterozygous pathogenic variant was identified among immediate family members, including the proband's daughter and parents. Discussion: A literature review showed that 16 pathogenic variants in RSPH4A have been reported. Hearing loss had only been observed in patients with the RSPH4A (c.921+3_6delAAGT) splice site mutation, and the specific type of hearing loss was not described.
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OBJECTIVE: To investigate the effect of CD8+ CD28- T cells on acute graft-versus-host disease(aGVHD) after haploidentical hematopoietic stem cell transplantation(haplo-HSCT). METHODS: The relationship between absolute count of CD8+ CD28- T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT, and the differences in the incidence rate of chronic graft-versus host disease(cGVHD), infection and prognosis between different CD8+ CD28- T absolute cells count groups were compared. RESULTS: aGVHD occurred in 40 of 60 patients after haplo-HSCT, with an incidence rate of 66.67%. The median occurrence time of aGVHD was 32.5(20-100) days. At 30 days after the transplantation, the absolute count of CD8+ CD28- T cells of aGVHD group was significantly lower than that of non-aGVHD group (P =0.03). Thus the absolute count of CD8+ CD28- T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent. At 30 days after transplantation, the incidence rate of aGVHD in the low cell count group (CD8+ CD28- T cells absolute count < 0.06/µl) was significantly higher than that in the high cell count group (CD8+ CD28- T cells absolute count ≥0.06/µl,P =0.011). Multivariate Cox regression analysis further confirmed that the absolute count of CD8+ CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD, and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group (P =0.015). The incidence of cGVHD, fungal infection, EBV infection and CMV infection were not significantly different between the two groups with different CD8+ CD28- T cells absolute count. The overall survival, non-recurrent mortality and relapse rates were not significantly different between different CD8+ CD28- T cells absolute count groups. CONCLUSION: Patients with delayed CD8+ CD28- T cells reconstitution after haplo-HSCT are more likely to develop aGVHD, and the absolute count of CD8+ CD28- T cells can be used to predict the incidence of aGVHD to some extent. The absolute count of CD8+ CD28- T cells after haplo-HSCT was not associated with cGVHD, fungal infection, EBV infection, and CMV infection, and was also not significantly associated with the prognosis after transplantation.
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Antígenos CD28 , Linfócitos T CD8-Positivos , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Prognóstico , Transplante Haploidêntico , Doença Aguda , Masculino , Feminino , AdultoRESUMO
The pathogenesis of age-related hearing loss (ARHL) remains unclear. OPA1 is the sole fusion protein currently known to be situated in the inner mitochondrial membrane, which is pivotal for maintaining normal mitochondrial function. While it has already been demonstrated that mutations in OPA1 may lead to hereditary deafness, its involvement in the occurrence and development of ARHL has not been previously explored. In our study, we constructed D-gal-induced senescent HEI-OC1 cells and the cochlea of C57BL/6J mice with a mutated SUMOylation site of SIRT3 using CRISPR/Cas9 technology. We found enhanced L-OPA1 processing mediated by activated OMA1, and increased OPA1 acetylation resulting from reductions in SIRT3 levels in senescent HEI-OC1 cells. Consequently, the fusion function of OPA1 was inhibited, leading to mitochondrial fission and pyroptosis in hair cells, ultimately exacerbating the aging process of hair cells. Our results suggest that the dysregulation of mitochondrial dynamics in cochlear hair cells in aged mice can be ameliorated by activating the SIRT3/OPA1 signaling. This has the potential to alleviate the senescence of cochlear hair cells and reduce hearing loss in mice. Our study highlights the significant roles played by the quantities of long and short chains and the acetylation activity of OPA1 in the occurrence and development of ARHL. This finding offers new perspectives and potential targets for the prevention and treatment of ARHL.
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Presbiacusia , Sirtuína 3 , Animais , Camundongos , Acetilação , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/genética , Sirtuína 3/genética , Sirtuína 3/metabolismoRESUMO
There is a relative paucity of literature on abdominal compartment syndrome (ACS) in children compared to adults and even less describing ACS in pediatric oncologic patients. We present this case of ACS in a 14-year-old patient to highlight the acuity of lethal consequences despite swift adequate management. Our patient is a 14-year-old male with a history of non-verbal autism and large synovial sarcoma of the left chest wall. He was admitted for scheduled inpatient chemotherapy and radiation. On day 3 of admission, the patient's clinical condition rapidly deteriorated, and a surgical abdomen was found on the exam. In the operating room (OR), massive gaseous distention of the stomach, small intestines, and colon were noted. A loop of small bowel was under such high pressure that the force of evisceration sheared the bowel from the associated mesentery. Due to the severity of the dilated bowel loops, we could not return the eviscerated bowel back inside the abdomen, which led us to leave the Abthera wound vac as sole coverage. The patient was transferred to the PICU, and medical treatment was aimed toward palliative care. The patient passed away three hours later. This case illustrates the acute and lethal nature of ACS in a less studied population, the pediatric oncologic patient. Prompt detection and treatment of ACS are essential for the management of critically ill pediatric patients, especially in those with space occupying tumors within the abdominal cavity. However, extreme presentations of ACS can have lethal consequences despite swift surgical intervention and adequate management.
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The c-Jun N-terminal kinase (JNK) pathway is a vital component of the mitogen-activated protein kinase cascade, which regulates cell death and survival. The present study aimed to explore the Spatio-temporal changes in all JNK isoforms in the cochleae of C57/BL6J mice with age-related hearing loss. Changes in the three isoforms of JNKs in the cochleae of an animal model with presbycusis and the senescent HEI-OC1 cell line were tested by immunohistochemistry staining and western blotting. Our results demonstrated that all three JNK isoforms are distributed in the cochleae, and the expression patterns of JNK1, JNK2, and JNK3 differed in hair cells, spiral ganglion neurons, and stria vascularis, with great significance in the cochleae of adult C57BL/6J mice. The levels of JNK1, JNK2, and JNK3 showed various spatio-temporal changes in the aging mice. In a senescent hair cell model, changes in JNK1, JNK2, and JNK3 expression levels were similar to those observed in the cochleae. Our study is the first to show that JNK3 is highly expressed in the hair cells of C57BL/6J mice and further increases in conjunction with age-related hearing loss, suggesting that it may play a more critical role than previously believed in hair cell loss and spiral ganglion degeneration.
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Proteínas Quinases JNK Ativadas por Mitógeno , Presbiacusia , Camundongos , Animais , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Presbiacusia/genética , Camundongos Endogâmicos C57BL , Proteína Quinase 8 Ativada por Mitógeno/genética , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Isoformas de ProteínasRESUMO
Cholesterol is the most abundant sterol molecule in mammalian cells, which not only constitutes the cell membrane but also plays essential roles in the synthesis of important hormones, synapse formation, and cell signal transduction. The effect of hypercholesterolemia on hearing has been studied extensively, and multiple studies have demonstrated that hypercholesterolemia is a risk factor for hearing loss. However, the impact of cholesterol homeostasis within auditory cells on peripheral auditory development and maintenance has not been evaluated in detail. Mutations in certain cholesterol metabolism-related genes, such as NPC1, SERAC1, DHCR7, and OSBPL2, as well as derivatives of cholesterol metabolism-related ototoxic drugs, such as ß-cyclodextrin, can lead to disruptions of cholesterol homeostasis within auditory cells, resulting in hearing loss. This article aims to review the impact of cholesterol homeostasis within auditory cells on the peripheral auditory function from the following two perspectives: (1) changes in cholesterol homeostasis regulatory genes in various hearing loss models; (2) mechanisms underlying the effects of some drugs that have a therapeutic effect on hearing loss via regulating cholesterol homeostasis. This article aims to summarize and analyze the impact of disruption of cellular cholesterol homeostasis within auditory cells on hearing, in order to provide evidence regarding the underlying mechanisms.
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Bone is a hard-connective tissue composed of matrix, cells and bioactive factors with a hierarchical structure, where the matrix is mainly composed of type I collagen and hydroxyapatite. Collagen fibers assembled by collagen are the template for mineralization and make an important contribution to bone formation and the bone remodeling process. Therefore, collagen has been widely clinically used for bone/cartilage defect regeneration. However, pure collagen implants, such as collagen scaffolds or sponges, have limitations in the bone/cartilage regeneration process due to their poor mechanical properties and osteoinductivity. Different forms of collagen-based composites prepared by incorporating natural/artificial polymers or bioactive inorganic substances are characterized by their interconnected porous structure and promoting cell adhesion, while they improve the mechanical strength, structural stability and osteogenic activities of the collagen matrix. In this review, various forms of collagen-based biocomposites, such as scaffolds, sponges, microspheres/nanoparticles, films and microfibers/nanofibers prepared by natural/synthetic polymers, bioactive ceramics and carbon-based materials compounded with collagen are reviewed. In addition, the application of collagen-based biocomposites as cytokine, cell or drug (genes, proteins, peptides and chemosynthetic) delivery platforms for proangiogenesis and bone/cartilage tissue regeneration is also discussed. Finally, the potential application, research and development direction of collagen-based biocomposites in future bone/cartilage tissue regeneration are discussed.
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Regeneração Óssea , Alicerces Teciduais , Osso e Ossos , Colágeno , Durapatita , Engenharia TecidualRESUMO
With the increase in life expectancy in the global population, aging societies have emerged in many countries, including China. As a common sensory defect in the elderly population, the prevalence of age-related hearing loss and its influence on society are increasing yearly. Metabolic syndrome is currently one of the main health problems in the world. Many studies have demonstrated that metabolic syndrome and its components are correlated with a variety of age-related diseases of the peripheral sensory system, including age-related hearing loss. Both age-related hearing loss and metabolic syndrome are high-prevalence chronic diseases, and many people suffer from both at the same time. In recent years, more and more studies have found that mitochondrial dysfunction occurs in both metabolic syndrome and age-related hearing loss. Therefore, to better understand the impact of metabolic syndrome on age-related hearing loss from the perspective of mitochondrial dysfunction, we reviewed the literature related to the relationship between age-related hearing loss and metabolic syndrome and their components to discern the possible role of mitochondria in both conditions.
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Mitochondria are the powerhouse of the cells. Under physiological conditions, mitochondrial fission and fusion maintain a dynamic equilibrium in the cytoplasm, which is referred to as mitochondrial dynamics. As an important approach to regulating mitochondrial function and quantity, the role of mitochondrial dynamics has been demonstrated in the pathogenesis of various disease models, including brain damage, neurodegeneration, and stress. As the vital organ of the peripheral auditory system, the cochlea consumes a significant amount of energy, and the maintenance of mitochondrial homeostasis is essential for the cochlear auditory capacity. OPA1 functions as both a necessary gene regulating mitochondrial fusion and a pathogenic gene responsible for auditory neuropathy, suggesting that an imbalance in mitochondrial dynamics may play a critical role in hearing loss, but relevant studies are few. In this review, we summarize recent evidence regarding the role of mitochondrial dynamics in the pathogenesis of noise-induced hearing loss (NIHL), drug-induced hearing loss, hereditary hearing loss, and age-related hearing loss. The impacts of impaired mitochondrial dynamics on hearing loss are discussed, and the potential of mitochondrial dynamics for the prevention and treatment of hearing loss is considered.
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Cardiac pressure overload is a crucial risk factor for cardiac hypertrophy and heart failure. Our previous study showed that depletion of the ß3-adrenergic receptor (ADRB3) induced left ventricular diastolic dysfunction via potential regulation of energy metabolism and cardiac contraction. However, the effects of ADRB3 on pressure overload-induced heart failure remain unclear. In the present study, systemic ADRB3-knockout mice suffering from transverse aortic constriction (TAC) surgery were used to identify the effects of ADRB3 on pressure overload-induced heart failure. Compared to wild-type mice, ADRB3 depletion significantly improved the left ventricular ejection fraction, reduced left ventricular posterior wall thickness and interventricular septum thickness, and decreased the area of cardiomyocytes after TAC. RNA sequencing and bioinformatics analysis showed that ADRB3 depletion up-regulated 275 mRNAs and down-regulated 105 mRNAs in mice suffering TAC surgery. GO analysis, GO-tree analysis, and GSEA showed that ADRB3 depletion mainly enhanced the innate immune response of hearts in cardiac pressure overload mice. In addition, pathway analysis and Pathway-Act analysis presented that innate immune response-related pathways, including RIG-I-like receptor signaling pathway, antigen processing and presentation, Toll-like receptor signaling pathway, and cell adhesion molecules, were significantly enriched in ADRB3-KO-TAC mice. Ten hub genes were identified using protein-protein interaction network, MCODE, and cytoHubba analysis. Furthermore, the depletion and activation of ADRB3 validated the effects of ADRB3 on the innate immune response of hearts after TAC. In conclusion, ADRB3 depletion relieves pressure overload-induced cardiac hypertrophy and heart failure, and these effects could be explained by the enhancement of innate immune response.
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Cardiomegalia/prevenção & controle , Insuficiência Cardíaca/prevenção & controle , Imunidade Inata , Miocárdio/metabolismo , Receptores Adrenérgicos beta 3/deficiência , Animais , Cardiomegalia/imunologia , Cardiomegalia/metabolismo , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Redes Reguladoras de Genes , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Imunidade Inata/genética , Masculino , Camundongos Knockout , Miocárdio/imunologia , Mapas de Interação de Proteínas , Receptores Adrenérgicos beta 3/genética , Transdução de Sinais , Volume Sistólico , Transcriptoma , Função Ventricular Esquerda , Remodelação VentricularRESUMO
Acute and chronic wounds can cause severe physical trauma to patients and also result in an immense socio-economic burden. Thus, wound management has attracted increasing attention in recent years. However, burn wound management is still a major challenge in wound management. Autografts are often considered the gold-standard for burn care, but their application is limited by many factors. Hence, ideal burn dressings and skin substitute dressings are desirable. With the development of biomaterials and progress of tissue engineering technology, some innovative dressings and tissue engineering scaffolds, such as nanofibers, films, foams and hydrogels, have been widely used in the field of biomedicine, especially in wound management. Among them, hydrogels have attracted tremendous attention with their unique advantages. In this review, we discuss the challenges in burn wound management, several crucial design considerations with respect to hydrogels for burn wound healing, and available polymers for hydrogels in burn wound care. In addition, the potential application and plausible prospect of hydrogels are also highlighted.
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Queimaduras , Hidrogéis , Bandagens , Materiais Biocompatíveis , Queimaduras/terapia , Humanos , CicatrizaçãoRESUMO
In situ 3D printing technologies is a new frontier for highly personalized medicine, which requires suitable bioink with rheology, biocompatibility, and gelation kinetics to support the right shape and mechanical properties of the printed construct. To this end, a facile design of thermo/photo dual cure composite hydrogel was proposed using MHBC and soluble collagen in this study. M/C composite hydrogel exhibited rapid thermo-induced sol-gel transition and contraction, tunable mechanical properties, proper microstructure and biodegradability for 3D cell culture, as well as improve cyto-compatibility, all of which were dependent upon the methacrylation degree of MHBC and M/C ratios. The printability of the optimal formulation (3% MHBC/1% collagen) was validated by its mild printing condition, rapid gelation of bioink at 37 °C and simple postprocessing manipulation. Both desirable printability and cyto-compatibility enable M/C composite hydrogel a potential candidate as bioink to be applied for in situ 3D bioprinting.
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Quitosana/análogos & derivados , Colágeno/química , Hidrogéis/química , Impressão Tridimensional , Animais , Plásticos Biodegradáveis/síntese química , Linhagem Celular , Metacrilatos/química , CamundongosRESUMO
Hydrogels have gained great attentions as wound dressing. Binding to the tissue and preventing wound infection were the basic requirements for an "ideal dressing". We employed l-DOPA and ε-Poly-l-lysine to modify thermo-sensitive hydroxybutyl chitosan (HBC) to obtain (l-DOPA) - (ε-Poly-l-lysine)-HBC hydrogels (eLHBC). The eLHBC exhibited an almost 1.5 fold (P < 0.01) increase in wet adhesion strength compared to HBC. Upon the introduction of ε-Poly-l-lysine, eLHBC presented inherent antimicrobial property and prevented wound infection and inflammation response. Bone marrow mesenchymal stem cells (BMSCs) encapsulated in the eLHBC (BMSCs â eLHBC) could secret cytokins and growth factors via paracrine and promote the migration of fibroblast cells. BMSCs â eLHBC enhanced the complete skin-thickness wound healing via promoting collagen deposition and inhibiting infection and inflammation in vivo with wound closure rate being above 99 % after 15 days. The bioinspired, tissue-adhesive eLHBC could serve as advanced wound dressings for facilitating tissue repair and regeneration.