RESUMO
BACKGROUND: The perforator flap has garnered significant interest since its inception due to its advantage of not needing a vascular network at the deep fascial level. Perforator flaps are commonly utilized in different flap transplant surgeries, and the thigh flap is presently the most widely used perforator flap. Is it possible for the calf to replace the thigh as a more suitable site for harvesting materials? Currently, there is a lack of relevant anatomical research. This study aims to address this question from an anatomical and imaging perspective. METHODS: This study used cadavers to observe the branches and courses of perforators on the calf and the distribution of skin branches using microdissection techniques, digital X-ray photography, and micro-computed tomography techniques. RESULTS: The perforators had three main branches: the vertical cutaneous branch, the oblique cutaneous branch, and the superficial fascial branch. The superficial fascial branch traveled in the superficial fascia and connected with the nearby perforators. The vertical and oblique cutaneous branches entered the subdermal layer and connected with each other to create the subdermal vascular network. CONCLUSIONS: We observed an intact calf cutaneous branch chain between the cutaneous nerve and the perforator of the infrapopliteal main artery at the superficial vein site. Utilizing this anatomical structure, the calfskin branch has the potential to serve as a substitute for thigh skin flap transplantation and may be applied to perforator flap transplantation in more locations.
Assuntos
Cadáver , Perna (Membro) , Retalho Perfurante , Humanos , Retalho Perfurante/irrigação sanguínea , Perna (Membro)/irrigação sanguínea , Perna (Membro)/anatomia & histologia , Masculino , Pele/irrigação sanguínea , Pele/anatomia & histologia , Feminino , Idoso , Microtomografia por Raio-XRESUMO
Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-κB) pathway. Because NF-κB activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-κB activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-κB activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.
Assuntos
Antioxidantes/uso terapêutico , Asma/tratamento farmacológico , Pneumonia/tratamento farmacológico , Silybum marianum , Silimarina/uso terapêutico , Animais , Asma/patologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia/patologia , Silibina , Células Th2/imunologiaRESUMO
AIM: To report a case which keratitis is the first clinical manifestation of COVID-19 that occurred 3d earlier than the common COVID-19 symptoms. METHODS: Regular slit lamp examination, corneal scraping test, and chest computed tomography (CT) were performed for patients with COVID-19 infection. The ophthalmologic treatment included ganciclovir eye drop (50 mg/mL, 6 times/d). The treatment for diarrhea included Guifu Lizhong pills (TID). The antiviral therapy consisted of oseltamivir (75 mg capsule Q12H); therapy preventing bacterial infection consisted of azithromycin (250 mg tablet QD) and moxifloxacin (0.4 g tablet Q12H); and therapy for cough relief and fever prevention consisted of Chinese herbal decoction. RESULTS: A 35-year-old male suddenly suffered pain, photophobia, and tears in his right eye for one day without systemic COVID-19 symptoms. Patient was diagnosed with keratitis, which was seemingly different from common keratitis. Ganciclovir eye drop was initiated. The corneal scraping test for COVID-19 was positive. The chest CT images were abnormal confirming the diagnosis of COVID-19 infection. The antiviral and antibacterial therapies were initiated. Chinese herbal therapy was used for cough relief and fever prevention. After roughly two weeks, patient recovered from COVID-19. CONCLUSION: A new type of keratitis, atypical keratitis, is a clinical manifestation of COVID-19, and this clinical manifestation could appear 3d earlier than fever and cough. The earlier a COVID-19 clinical manifestation is identified, the earlier can a patient be directed to stay at home, and significantly fewer people would be infected.
RESUMO
Macrophages substantially influence the development, progression, and complications of inflammation-driven diseases. Although numerous studies support the critical role of Notch signaling in most inflammatory diseases, there is limited data on the role of Notch signaling in TLR4-induced macrophage activation and interaction of Notch signaling with other signaling pathways in macrophages during inflammation, such as the NF-κB pathway. This study confirmed that stimulation with lipopolysaccharide (LPS), a TLR4 ligand, upregulated Notch1 expression in monocyte/macrophage-like RAW264.7 cells and bone marrow-derived macrophages (BMDMs). LPS also induced increased mRNA expression of Notch target genes Notch1 and Hes1 in macrophages, suggesting that TLR4 signaling enhances activation of the Notch pathway. The upregulation of Notch1, Notch1 intracellular domain (NICD), and Hes1 proteins by LPS treatment was inhibited by DAPT, a Notch1 inhibitor. Additionally, the increased TNF-α, IL-6, and IL-1ß expression induced by LPS was inhibited by DAPT and rescued by jagged1, a Notch1 ligand. Furthermore, suppression of Notch signaling by DAPT upregulated Cylindromatosis (CYLD) expression but downregulated TRAF6 expression, IκB kinase (IKK) α/ß phosphorylation, and subsequently, phosphorylation and degradation of IκB-α, indicating that DAPT inhibited NF-κB activation triggered by TLR-4. Interestingly, DAPT did not inhibit the increased MyD88 expression induced by LPS. Our study findings demonstrate that macrophage stimulation via the TLR4 signaling cascade triggers activation of Notch1 signaling, which regulates the expression patterns of genes involved in pro-inflammatory responses by activating NF-κB. This effect may be dependent on the CYLD-TRAF6-IKK pathway. Thus, Notch1 signaling may provide a therapeutic target against infectious and inflammation-driven diseases.
Assuntos
NF-kappa B , Receptor 4 Toll-Like , Humanos , Quinase I-kappa B/metabolismo , Inflamação/metabolismo , Ligantes , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , NF-kappa B/metabolismo , Inibidores da Agregação Plaquetária/metabolismo , Inibidores da Agregação Plaquetária/farmacologia , Receptor Notch1/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Fator 6 Associado a Receptor de TNF/farmacologia , Receptor 4 Toll-Like/genéticaRESUMO
The effects of asiaticoside (AS) on allergic responses mediated by mast cells were investigated. AS showed no obvious cytotoxicity on RPMCs (rat peritoneal mast cells). AS reduced the intracellular calcium in RPMCs and deprived the histamine release and degranulation. AS also decreased the generation of antigen-induced tumor necrosis factor α, interleukin (IL)-4, IL-8, and IL-1ß in RBL-2H3 cells sensitized by IgE. The suppression of AS on pro-inflammatory cytokines was related with the activation of the intracellular FcεRI and the inhibition of the nuclear factor-κB signaling pathway. In addition, AS disabled the phosphorylation of antigen-induced Syk, Lyn, Gab2, and PLCγ1, thus suppressing the downstream Akt phosphorylation and MAPKs pathways. It also increased HO-1 and Nrf2 expression time dependently. In summary, we demonstrate that AS suppresses the allergic inflammation mediated by mast cells and this effect might be mediated by FcεRI-dependent signaling pathways.
Assuntos
Hipersensibilidade/diagnóstico por imagem , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Triterpenos/administração & dosagem , Animais , Degranulação Celular/efeitos dos fármacos , Células Cultivadas , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Interleucina-8/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Establishing therapeutic agents for the treatment of allergic diseases is an important focus of human health research. Sesamin, a lignan in sesame oil, exhibits a diverse range of pharmacological properties. However, to the best of our knowledge, the effect of sesamin on mast cellmediated allergic responses has not yet been investigated. Thus, the aim of the present study was to investigate the effect of sesamin on mast cellmediated allergic responses and the underlying mechanisms by which it produces this effect. In rats, oral administration of sesamin inhibited passive cutaneous anaphylaxis. Sesamin exposure attenuated immunoglobulin Einduced histamine release from rat peritoneal mast cells, which was indicated to be mediated by the modulation of intracellular calcium. In human mast cells, sesamin reduced the stimulatory effects of phorbol 12myristate 13acetate and calcium ionophore A23187 on the production and secretion of proinflammatory cytokines, including tumor necrosis factorα and interleukin6. The inhibitory effect of sesamin on proinflammatory cytokine production was dependent on nuclear factor κlightchainenhancer of activated B cells (NFκB) and p38 mitogenactivated protein kinase (MAPK). The present study demonstrates that sesamin inhibits mast cellderived inflammatory allergic reactions by blocking histamine release, and proinflammatory cytokine production and secretion. In addition, the findings indicate that the effect of sesamin is mediated by its effect on p38 MAPK/NFκB signaling. Furthermore, the in vivo and in vitro antiallergic effects of sesamin reported in the present study suggest that it is a promising therapeutic agent for the treatment of inflammatory allergic diseases.
Assuntos
Dioxóis/farmacologia , Hipersensibilidade/imunologia , Lignanas/farmacologia , Mastócitos/imunologia , NF-kappa B/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , 2,4-Dinitrofenol/farmacologia , Animais , Cálcio/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Ativação Enzimática/efeitos dos fármacos , Liberação de Histamina/efeitos dos fármacos , Humanos , Imunoglobulina E/imunologia , Mediadores da Inflamação/metabolismo , Masculino , Mastócitos/citologia , Camundongos Endogâmicos ICR , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Peritônio/citologia , Ratos Sprague-DawleyRESUMO
Allergic asthma is a chronic inflammatory disease that is regulated by coordination of T-helper type 2 cell cytokines and inflammatory signaling molecules. Ginsenoside Rh2 (G-Rh2) is an active component of ginseng with anti-inflammatory and anti-tumor effects. The aim of the present study was to determine the inhibitory effects of G-Rh2 on allergic airway inflammation in a murine model of asthma, in which mice develop the following pathophysiological features of asthma: Increased abundance of inflammatory cells; increased levels of interleukin-4 (IL-4), IL-5 and IL-13; decreased abundance of interferon gamma in the bronchoalveolar lavage fluid and lung tissue; increased total and ovalbumin (OVA)-specific immunoglobulin E (IgE) levels in the serum; increased airway hyperresponsiveness (AHR); and activation of nuclear factor kappa B (NF-κB) in lung tissue. In the asthmatic mice, administration of G-Rh2 markedly reduced peribronchiolar inflammation, recruitment of airway inflammatory cells, cytokine production, total and OVA-specific IgE levels and AHR. G-Rh2 administration inhibited NF-κB activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation induced by OVA inhalation. These results suggested that G-Rh2 attenuates allergic airway inflammation by regulating NF-κB activation and p38 MAPK phosphorylation. The present study identified the molecular mechanisms of action of G-Rh2, which supported the potential use of G-Rh2 to prevent and/or treat asthma and other airway inflammatory disorders.
Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Asma/imunologia , Ginsenosídeos/uso terapêutico , Pulmão/efeitos dos fármacos , NF-kappa B/imunologia , Animais , Asma/sangue , Asma/patologia , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Interleucina-13/imunologia , Interleucina-4/imunologia , Interleucina-5/imunologia , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/sangue , Ovalbumina/imunologiaRESUMO
Vascular endothelial growth factor (VEGF) is supposed to contribute to the pathogenesis of allergic airway disease. VEGF expression is regulated by a variety of stimuli such as nitric oxide, growth factors, and hypoxia-inducible factor-1 alpha (HIF-1α). Recently, inhibition of the mammalian target of rapamycin (mTOR) has been shown to alleviate cardinal asthmatic features, including airway hyperresponsiveness, eosinophilic inflammation, and increased vascular permeability in asthma models. Based on these observations, we have investigated whether mTOR is associated with HIF-1α-mediated VEGF expression in allergic asthma. In studies with the mTOR inhibitor rapamycin, we have elucidated the stimulatory role of a mTOR-HIF-1α-VEGF axis in allergic response. Next, the mechanisms by which mTOR is activated to modulate this response have been evaluated. mTOR is known to be regulated by phosphoinositide 3-kinase (PI3K)/Akt or protein kinase C-delta (PKC δ) in various cell types. Consistent with these, our results have revealed that suppression of PKC δ by rottlerin leads to the inhibition of PI3K/Akt activity and the subsequent blockade of a mTOR-HIF-1α-VEGF module, thereby attenuating typical asthmatic attack in a murine model. Thus, the present data indicate that PKC δ is necessary for the modulation of the PI3K/Akt/mTOR signaling cascade, resulting in a tight regulation of HIF-1α activity and VEGF expression. In conclusion, PKC δ may represent a valuable target for innovative therapeutic treatment of allergic airway disease.
Assuntos
Asma/complicações , Asma/tratamento farmacológico , Hipersensibilidade/complicações , Proteína Quinase C-delta/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Asma/metabolismo , Asma/patologia , Líquido da Lavagem Broncoalveolar , Linhagem Celular , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Ovalbumina/efeitos adversos , Fosfatidilinositol 3-Quinases/metabolismo , Fosfoproteínas/metabolismo , Proteína Quinase C-delta/deficiência , Proteína Quinase C-delta/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/genética , Serina-Treonina Quinases TOR/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
AIM: To study the inhibition of tumor angiogenesis by 5,2,4´-trihydroxy-6,7,5´-trimethoxyflavone (TTF1) isolated from an extract of herbal medicine Sorbaria sorbifolia. METHODS: Angiogenic activity was assayed using the chick embryo chorioallantoic membrane (CAM) method. Microvessel density (MVD) was determined by staining tissue sections immunohistochemically for CD34 using the Weidner capillary counting method. The mRNA and protein levels of vascular endothelial growth factor (VEGF), vascular endothelialgrowth factor receptor 2 (VEGFR2, Flk-1/KDR), basic fibroblast growth factor (bFGF), cyclo-oxygenase (COX)-2 and hypoxia-inducible factor (HIF)-1α were detected by quantitative real-time polymerase chain reaction and Western blotting analysis. RESULTS: The TTF1 inhibition rates for CAM were 30.8%, 38.2% and 47.5% with treatment concentrations of 25, 50 and 100 µg/embryo × 5 d, respectively. The inhibitory rates for tumor size were 43.8%, 49.4% and 59.6% at TTF1 treatment concentrations of 5, 10, and 20 µmol/kg, respectively. The average MVD was 14.2, 11.2 and 8.5 at treatment concentrations of 5 µmol/kg, 10 µmol/kg and 20 µmol/kg TTF1, respectively. The mRNA and protein levels of VEGF, KDR, bFGF, COX-2 and HIF-1α in mice treated with TTF1 were significantly decreased. CONCLUSION: TTF1 can inhibit tumor angiogenesis, and the mechanism may be associated with the down-regulation of VEGF, KDR, bFGF, HIF-1α and COX-2.