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The concept of pore space partition has emerged as an effective strategy for developing improved coordination-based supramolecular porous materials with exceptional performance. Herein, we report that a water-soluble self-assembled tetrahedral cage 1 with a partitioned cavity shown excellent performance as a multifunctional extractant. The results show that this unique partitioned cavity can efficiently separate halogenated adamantanes, adamantane isomers, and polycyclic aromatic hydrocarbons. Furthermore, the influence of cavity-partitioned cage 1 on the electrochemical properties of redox-active molecules and electrochemically driven reversible host-guest process has also been demonstrated. The findings offer valuable insights into the design and development of new type of materials with controlled phase separation and tailored electrochemical properties.
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Herein, a series of face-capped (Tr2M3)4L4 (Tr = cycloheptatrienyl cationic ring; M = metal; L = organosulfur ligand) tetrahedral cages 1-3 functionalized with 12 appended crown ether moieties were designed and synthesized. The reversible binding of ammonium cations with peripheral crown ether moieties to adjust internal guest-binding was realized. Combination of a bisammonium linker and cage 3 led to the formation of a supramolecular gel SPN1 via host-guest interactions between the crown ether moieties and ammonium salts. The obtained supramolecular gel exhibited multiple-stimuli responsiveness, injectability, and excellent self-healing properties and could be further developed to a SPN1-based drug delivery system. In addition, the storage modulus of SPN1 was 20 times higher than that of the model gel without Pd-Pd bonded blocks, and SPN1 had better self-healing properties compared with the latter, demonstrating the importance of such cages in improving mechanical strength without losing the dynamic properties of the material. The cytotoxicity in vitro of the drug-loaded (doxorubicin or methotrexate) SPN1 was significantly improved compared to that of free drugs.
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BACKGROUND: A growing number of cytogenetic techniques have been used for prenatal diagnosis. This study aimed to demonstrate the usefulness of karyotyping, BACs-on-Beads (BoBs) assay and single nucleotide polymorphism (SNP) array in prenatal diagnosis during the second trimester based on our laboratory experience. METHODS: A total of 10,580 pregnant women with a variety of indications for amniocentesis were enrolled in this retrospective study between January 2015 and December 2020, of whom amniotic fluid samples were analysed in 10,320 women. The main technical indicators of participants in the three different technologies were summarized, and cases of chromosome abnormalities were further evaluated. RESULTS: The overall abnormality detection rate of karyotyping among all the amniotic fluid samples was 15.4%, and trisomy 21 was the most common abnormality (20.9%). The total abnormality detection rate of the BoBs assay was 5.6%, and the diagnosis rate of microdeletion/microduplication syndromes that were not identified by karyotyping was 0.2%. The detection results of the BoBs assay were 100.0% concordant with karyotyping analysis in common aneuploidies. Seventy (87.5%) cases of structural abnormalities were missed by BoBs assay. The total abnormality detection rate of the SNP array was 21.6%. The detection results of common aneuploidies were exactly the same between SNP array and karyotyping. Overall, 60.1% of structural abnormalities were missed by SNP array. The further detection rate of pathogenic significant copy number variations (CNVs) by SNP was 1.4%. CONCLUSIONS: Karyotyping analysis combined with BoBs assay or SNP array for prenatal diagnosis could provide quick and accurate results. Combined use of the technologies, especially with SNP array, improved the diagnostic yield and interpretation of the results, which contributes to genetic counselling. BoBs assay or SNP array could be a useful supplement to karyotyping.
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Transtornos Cromossômicos , Feminino , Gravidez , Humanos , Transtornos Cromossômicos/diagnóstico , Líquido Amniótico , Variações do Número de Cópias de DNA , Estudos Retrospectivos , Diagnóstico Pré-Natal/métodos , AneuploidiaRESUMO
The outbreaks of fungal diseases in cultured fish have been severe in recent years, which is harmful to the healthy and sustainable development of fish farming. In this study, an investigation was conducted for significant fungal infections of 12 species of fish in four regions in Xinjiang, China, to understand the distribution of local fish fungal pathogens. Twenty-six fungal strains with pathogenicity were isolated, and the challenge experiment showed that eight strains from Changji area had high infection rate to fish eggs. Based on internal transcribed spacer sequence data and molecular analysis, the 26 strains were classified into nine different species of six fungal genera. Phylogenetic analysis showed that all strains were divided into two clades, namely Cluster 1 (contains only the genus Mucor) and Cluster 2 (consists of five small branches), and the distribution of strains from the same region was scattered in two clusters. There is no strict host selectivity for these fungi to infect fish. Mucor sp. are the main fungal pathogen of fish in these four regions, whereas Hypophthalmichthys molitrix and Carassius auratus are two types of fish that were susceptible to pathogen. In addition, the environmental adaptability experiments showed that eight highly pathogenic strains have different adaptability to the environment, and their optimum temperature and pH were 25°C and 7.0, respectively, whereas the concentration of NaCl was negatively correlated with the growth of strains. Therefore, these results indicated that the coinfection of multiple fungal pathogens in a culture region should be considered in the future study.
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Carpas , Fungos , Animais , China , Fungos/genética , Filogenia , Análise de Sequência de DNA , VirulênciaRESUMO
OBJECTIVE: To describe a method to fabricate donor tooth replica to assist surgeons in preparation of recipient socket during tooth autotransplantation. MATERIALS AND METHODS: A total of 28 compromised molars in 27 patients were transplanted with third molars using computer-aided rapid prototyping (CARP) technique. Surgery time and extra-alveolar time were documented. Postoperatively, the distance between cervix of transplanted tooth and the alveolar wall was measured. The degree of postoperative pain experienced was assessed with visual analog scale at day 1, 3, and 7. RESULTS: From 28 clinical cases, the average extra-alveolar time and surgery time were 2.5 minutes (±1.3) and 44 minutes (±6.8), respectively. Postoperatively, the average distance between cervix of transplanted tooth and the alveolar wall was 0.87 mm (±0.15) at the mesial-cervix, 0.95 mm (±0.17) at the distal-cervix, 0.88 mm (±0.18) at the buccal-cervix, and 0.95 mm (±0.13) at the lingual-cervix. The value of visual analog scale score significantly decreased from day 1 to day 3. CONCLUSIONS: CARP is a reliable technique for fabrication of tooth like surgical replicas in conventional autotransplantation. CLINICAL SIGNIFICANCE: CARP technique minimized extra-oral time, reduced iatrogenic damage, and consequently increased the survival rate of tooth autotransplantation.
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Cirurgia Assistida por Computador , Dente , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Dente Molar , Dente Serotino , Transplante AutólogoRESUMO
Background Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Novel anticancer drugs against gastric cancer are urgently needed. Methods Compound 10 was designed and synthesized via a molecular hybridization strategy based on the natural product formononetin. It was evaluated for their antiproliferative activity against three gastric cancer cell lines (SGC7901, MKN45 and MGC803). Results Derivative 10 displayed potently antiproliferative activity with an IC50 value of 1.07 µM against SGC7901 cells. Derivative 10 could inhibit the growth and migration against gastric cancer SGC7901 cells through the Wnt/ß-Catenin and AKT/mTOR pathways. From the in vivo expremints, it could effectively inhibited SGC7901 xenograft tumor growth in vivo without significant loss of the body weight. Conclusion Derivative 10 is an novel antitumor agent with potential for further clinical applications to treat gastric cancer. Graphical abstract.
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Antineoplásicos Fitogênicos/uso terapêutico , Cumarínicos/uso terapêutico , Isoflavonas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/farmacologia , Humanos , Isoflavonas/química , Isoflavonas/farmacologia , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Serina-Treonina Quinases TOR/metabolismo , Carga Tumoral/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Cases of fetal volvulus without malrotation are extremely uncommon and pose a life-threatening condition of acute abdomen. In cases of inadequate intestinal rotation, the narrowing of the attachment of the mesenteric root can easily cause intestinal torsion and consequent local blood circulation disorders within the intestinal tract, leading to aseptic necrosis and simultaneous intestinal perforation, resulting in meconium peritonitis, ascites, anemia, and potentially fetal death. In ultrasound examinations, it may be the preferred examination method for this disease. Ultrasound physicians should improve their understanding of this disease in prenatal diagnosis, as it has important clinical value for obstetric management and neonatal treatment, thereby potentially improving adverse pregnancy outcomes.
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Volvo Intestinal , Ultrassonografia Pré-Natal , Humanos , Feminino , Volvo Intestinal/diagnóstico por imagem , Gravidez , Adulto , Doenças Fetais/diagnóstico por imagem , Recém-NascidoRESUMO
OBJECTIVE: To explore dose-effect relationship of biomechanical parameters in treating atlantoaxial joint disorder by slimming manipulation. METHODS: From October 2022 to May 2023, 18 patients with atlantoaxial joint disorders were treated, including 10 males and 8 females;aged from 24 to 27 years old with an average of (25.50±1.10) years old;CT of cervical vertebra showed 16 patients with right side distortion and 2 patients with left side distortion. The mechanical parameters of treatment of atlantoaxial joint disorder by tendon relaxation manipulation were measured by wearing massage manipulation gloves. The magnitude, frequency and mechanical curve of force during tendon relaxation and starting force, pulling force, pulling time and mechanical curve during rehabilitation were quantified, the differences between the affected and contralateral manipulations were compared. RESULTS: The maximum force and frequency of Fengchi(GB20) on the affected side were (19.82±2.02) N and (116.83±14.49) times/min, and opposite side were (13.87±2.19) N and (188.89±16.03) times/min, respectively. There were statistically difference in the maximum force and frequency of both sides (P<0.05). The maximum force and frequency of Quepen (ST12) on the affected side were (14.44±3.27) N and (139.06±28.47) times/min, and those on the opposite side were (9.41±1.38) N and (142.50±28.47) times/min. There was difference in maximum force on both sides (P<0.05). The starting force, turning force and turning time of the affected side were (14.16±5.98) N, (11.56±6.63) N, (0.14±0.03) S, and the contralateral side were (8.94±3.39) N, (8.30±4.64) N, (0.18±0.04) S, respectively. The difference of starting force, turning force and turning time on both sides were statistically significant (P<0.05). CONCLUSION: By applying a light relaxation force on the affected side, the mechanical balance between cervical vertebrae could be restored, and recovery trend of atlantoaxial joint disorder could be strengthened. On this basis, the atlantoaxial odontoid process could be reversed by applying a light rotation force, which reflects the characteristics of high safety of the manipulation.
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Articulação Atlantoaxial , Humanos , Masculino , Feminino , Adulto , Articulação Atlantoaxial/fisiopatologia , Tendões/fisiopatologia , Fenômenos Biomecânicos , Adulto Jovem , Artropatias/fisiopatologia , Artropatias/terapiaRESUMO
BACKGROUND: Radicular cysts are one of the most common odontogenic cystic lesions found in the jaw. Nonsurgical treatment of large radicular cysts is a topic of ongoing debate, and there is still no clear consensus on the most effective therapies. The apical negative pressure irrigation system aspirates the cystic fluid and releases the static pressure in the radicular cyst, representing a minimally invasive approach for decompression. In this case, the radicular cyst was in close proximity to the mandibular nerve canal. We used nonsurgical endodontic treatment with a homemade apical negative pressure irrigation system and the prognosis was good. CASE SUMMARY: A 27-year-old male presented to our Department of General Dentistry with complaints of pain in the mandibular right molar when chewing. The patient had no history of drug allergies or systemic disease. A multidisciplinary management approach was designed and included root canal retreatment with a homemade apical negative pressure irrigation system, deep margin elevation and prosthodontic treatment. According to a 1-year follow-up period, the patient showed a favorable outcome. CONCLUSION: This report reveals that nonsurgical treatment with an apical negative pressure irrigation system may provide new insights into the treatment of radicular cysts.
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PURPOSE: To establish and validate a nomogram model incorporating both liver imaging reporting and data system (LI-RADS) features and contrast enhanced magnetic resonance imaging (CEMRI)-based radiomics for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) falling the Milan criteria. METHODS: In total, 161 patients with 165 HCCs diagnosed with MVI (n = 99) or without MVI (n = 66) were assigned to a training and a test group. MRI LI-RADS characteristics and radiomics features selected by the LASSO algorithm were used to establish the MRI and Rad-score models, respectively, and the independent features were integrated to develop the nomogram model. The predictive ability of the nomogram was evaluated with receiver operating characteristic (ROC) curves. RESULTS: The risk factors associated with MVI (P<0.05) were related to larger tumor size, nonsmooth margin, mosaic architecture, corona enhancement and higher Rad-score. The areas under the ROC curve (AUCs) of the MRI feature model for predicting MVI were 0.85 (95% CI: 0.78-0.92) and 0.85 (95% CI: 0.74-0.95), and those for the Rad-score were 0.82 (95% CI: 0.73-0.90) and 0.80 (95% CI: 0.67-0.93) in the training and test groups, respectively. The nomogram presented improved AUC values of 0.87 (95% CI: 0.81-0.94) in the training group and 0.89 (95% CI: 0.81-0.98) in the test group (P<0.05) for predicting MVI. The calibration curve and decision curve analysis demonstrated that the nomogram model had high goodness-of-fit and clinical benefits. CONCLUSIONS: The nomogram model can effectively predict MVI in patients with HCC falling within the Milan criteria and serves as a valuable imaging biomarker for facilitating individualized decision-making.
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Changes in lake area (water surface area) are often considered accurate and sensitive representations of climate change. However, the role that elevation plays in this dynamic is somewhat unclear; studies remain inconclusive as to whether lake responses are consistent across elevation gradients. Here, we used Landsat and keyhole satellite images to quantify lake area changes from the 1960s to 2020 at different elevations in Central Asia's Tianshan Mountains and relate them to both climatic and anthropogenic factors. The results revealed that all low-elevation lakes showed a decreasing trend, and the total area of all monitored low-elevation lakes was reduced by 18.50 %. The total area of the mid-elevation lakes decreased by 0.16 %, while the total area of the high-elevation glacial lakes increased by 4.35 %. Lakes are recharged by a variety of influxes including glacial meltwater and precipitation. Notably, human activities (urban and agricultural water consumption) were the dominant factors in the shrinkage of low-elevation lakes. Climatic factors were the main driving factors of mid-elevation lake changes, and these lakes appeared to be more sensitive to temperature changes than lakes at other elevations. In addition, significant warming dominated area changes in high-elevation proglacial and unconnected glacial lakes. Overall, those results emphasized that when using lakes to reconstruct paleoclimates or predict lake evolution, it is necessary to consider how elevation gradients and recharge types may affect lake sensitivity to variations in climatic and anthropogenic activity.
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Taurine has been proven in many trials to alleviate the symptoms of metabolic associated fatty liver disease. Here its protective effect for hepatic steatosis and modulation of AMP-activated protein kinase and insulin signaling pathway were investigated. Steatotic HepG2 cell established with oleic acid (0.05 mmol/L), treated with taurine (5 mmol/L), dorsomorphin (10 µmol/L) for 24 h. Sprague Dawley rats were divided into regular and high-fat diet (HFD) groups, and their corresponding taurine (70 or 350 mg/kg BW/d) groups, fed for 8 weeks. In steatotic cell, taurine reduced the TG concentration and SREBP-1c, PPARγ, FAS, ACC, SCD1 protein levels, decreased phosphorylation of mTOR, IRS1 (Ser302), increased phosphorylation of AMPKα, LKB1, PI3K, Akt, ACC. While dorsomorphin eliminated taurine's TG-lowering effect. In HFD-fed rats, taurine reduced liver TG, serum TG, ALT, AST, IL-1ß, IL-4, TNF-α. The effects of taurine on the main factors of fatty acid synthesis were mostly consistent with cell experiments, and the reduction of microRNAs (451, 33, 291b) was aligned with the improvement in LKB1 and AMPK expression in HFD rats. Taurine alleviated steatosis-induced inhibition of IRS1-PI3K-Akt pathway, but suppressed its positively regulated downstream factor mTOR. In parallel, taurine reduced steatosis by activating LKB1-AMPKα pathway via phosphorylation and no-phosphorylation manner, then inhibiting SREBP-1c directly or by suppressing mTOR phosphorylation.
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BACKGROUND: Palato-radicular groove (PRG) is defined as an anomalous formation of teeth. The etiology of PRG remains unclear. The prognosis of a tooth with a PRG is unfavorable. The treatment of combined periodontal-endodontic lesions requires multidisciplinary management to control the progression of bone defects. Some researchers reported cases that had short-term observations. The management of teeth with PRGs is of great clinical significance. However, to date, no case reports have been documented on the use of bone regeneration and prosthodontic treatment for PRGs. CASE SUMMARY: This case reported the management of a 40-year-old male patient with the chief complaint of slight mobility and abscess in the upper right anterior tooth for 15 d and was diagnosed with type II PRG of tooth 12 with combined endodontic-periodontal lesions. The accumulation of plaque and calculus caused primary periodontitis and a secondary endodontic infection. A multidisciplinary management approach was designed that included root canal therapy, groove sealing, a periodontal regenerative procedure, and prosthodontic treatment. During a 2-year follow-up period, a good prognosis was observed. CONCLUSION: This report indicates that bone regeneration and prosthodontic treatment may contribute to the long-term favorable prognosis of teeth with PRGs.
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BACKGROUND: Limb hemiplegia is one of the common sequelae of stroke. Physical therapy-based rehabilitation training can rapidly improve limb functioning and muscle strength. This study investigated the effect of physical therapy on the recovery of upper limb motor function by employing a literature search and meta-analysis. METHODS: We searched Embase, The Cochrane Central Register of Controlled Trials library, Wiley online library, PubMed, Ovid, and Clinicaltrials.org for randomized controlled trial (RCT) studies and performed an electronic search with the keyword combinations 'physical therapy/rehabilitation' & 'stroke/post-stroke' & 'upper extremity/upper limb'. After screening the literature for inclusion criteria and assessing the risk of bias, Revman 5.4 software was used for the analysis and to obtain forest and funnel plots. RESULTS: A total of 15 RCTs with 1,081 patients were included in the quantitative analysis for this study. The meta-analysis results showed that compared with conventional therapy, physical therapy improved the upper limb Fugl-Meyer Assessment for Upper Extremity (FMA) scores in convalescent stroke patients (MD =7.27, 95% CI: 4.23-10.32, Z=4.68, P<0.00001), and increased the Functional Independence Measure (FIM) scores (MD =18.82, 95% CI: 6.34-31.30, Z=2.96, P=0.003), the Action Research Arm Test (ARAT) scores (MD =8.84, 95% CI: 6.53-11.15, Z=7.50, P<0.00001), and the Box and Block Test (BBT) scores (MD =6.11, 95% CI: 1.18-11.04, Z=2.43, P=0.02) of patients during the rehabilitation period. DISCUSSION: The use of physical therapy-based rehabilitation training in the recovery period for stroke patients with hemiplegia can improve upper limb movement ability, increase muscle strength, reduce limb pain, and improve the quality of life.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Adulto , Humanos , Modalidades de Fisioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações , Reabilitação do Acidente Vascular Cerebral/métodos , Extremidade Superior/fisiologiaRESUMO
OBJECTIVE: To develop a new color matching method in dentistry by application of digital photography. METHODS: Digital photographs were obtained of Vitapan 3D-Master shade guide and natural teeth under the same condition, the L*a*b* values of each digital photography were assessed and analyzed by Photoshop CS4. RESULTS: The Vitapan 3D-Master shade guide was divided into 5 groups, the L* values were similar in each group, but decreased from group 1 to 5. The a* values of L1.5 and L2.5 were minimum, R1.5 and R2.5 were maximum and M1-M3 were intermediate. Compared with Vitapan 3D-Master shade guide, the L*a*b* values of natural teeth were higher. CONCLUSION: Digital photography can basically reflect the color of Vitapan 3D-Master shade guide, and provides a reference for color matching in dentistry.
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Colorimetria/métodos , Fotografia Dentária/métodos , Adulto , Cor , Humanos , Pigmentação em PróteseRESUMO
RATIONAL: Chromobacterium violaceum is a motile gram-negative bacterium. This bacterium commonly grows in tropical or subtropical areas in sewage and can cause opportunistic infections. PATIENT CONCERNS: A 50-year-old Chinese man had a skin ulcer in the middle of his left leg in front of the tibia. The diameter of the wound was 3.0âcm, the exudation was obvious, and necrotic tissue was attached to the wound. One week previously, he was working in a field where he accidentally punctured his left leg. DIAGNOSIS: C violaceum infection was diagnosed as per the results of pathogen culture from the infection site. INTERVENTIONS: He was treated with piperacillin/tazobactam (3.375âg/12âh iv) and levofloxacin (0.5âg/24âh iv) for 5âdays. OUTCOMES: The patient showed good response to therapy and was discharged on day 18 after wound healing. LESSONS: C violaceum rarely infects humans. When an infection is suspected, samples should be immediately sent for microbial culture. Timely treatment on the basis of drug sensitivity test results can prevent further complications.
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Chromobacterium/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Extremidade Inferior/microbiologia , Úlcera Cutânea/tratamento farmacológico , Pele/microbiologia , Administração Intravenosa , Quimioterapia Combinada , Humanos , Levofloxacino/administração & dosagem , Levofloxacino/uso terapêutico , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/complicações , Combinação Piperacilina e Tazobactam/administração & dosagem , Combinação Piperacilina e Tazobactam/uso terapêutico , Pele/patologia , Resultado do TratamentoRESUMO
BACKGROUND: Hepatic hemolymphangioma is an extremely rare benign congenital malformation composed of cystically dilated lymphatic and blood vessels, and they have nonspecific clinical symptoms and laboratory results. In this study, hepatic hemolymphangioma with multiple hemangiomas in an elderly woman was initially reported and analyzed. CASE SUMMARY: A 61-year-old female patient, with a history of hysterectomy and bilateral adnexectomy, was referred to the hepatobiliary surgery department with the complaint of multiple hepatic hemangiomas that had been diagnosed 2 years prior in a preoperative contrast-enhanced computed tomography (CECT) examination. Upon entering our hospital, no abnormal physical examination and laboratory data were found. The latest CECT revealed a new 7.0 cm × 6.2 cm cystic-solid lesion with multiple internal divisions in segment II of the liver, with delayed CECT enhancement characteristics that presented as solid parts with internal division. On the positron emission tomography (PET)/CT, no significant uptake of 18F-fluorodeoxyglucse was observed. Finally, hepatic hemolymphangioma was confirmed based on the pathological and immunohistochemical results after surgery. At 1-year follow-up, her posthepatectomy evaluation was uneventful, and she had recovered full activity. In addition, no postoperative recurrent or residual lesion was found on CECT imaging. CONCLUSION: Hepatic hemolymphangioma with multiple hemangiomas was reported and observed by CECT and PET/CT imaging.
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3-O-ethyl ascorbic acid (EAA) is an ether-derivative of ascorbic acid, known to inhibit tyrosinase activity, and is widely used in skincare formulations. Nevertheless, the molecular mechanisms underlying the EAA's effects are poorly understood. Here, the anti-melanogenic activity of EAA was demonstrated through Nrf2-mediated α-MSH inhibition in UVA-irradiated keratinocytes (HaCaT) and autophagy induction and inhibition of α-MSH-stimulated melanogenesis in melanocytes (B16F10). EAA pretreatment increased the HaCaT cell viability but suppressed ROS-mediated p53/POMC/α-MSH pathways in UVA-irradiated cells. Further, the conditioned medium from EAA-pretreated and UVA-irradiated HaCaT cells suppressed the MITF-CREB-tyrosinase pathways leading to the inhibition of melanin synthesis in B16F10 cells. EAA treatment increased nuclear Nrf2 translocation via the p38, PKC, and ROS pathways leading to HO-1, γ-GCLC, and NQO-1 antioxidant expression in HaCaT cells. However, Nrf2 silencing reduced the EAA-mediated anti-melanogenic activity, evidenced by impaired antioxidant gene expression and uncontrolled ROS (H202) generation following UVA irradiation. In B16F10 cells, EAA-induced autophagy was shown by enhanced LC3-II levels, AVO formation, Beclin-1 upregulation, and activation of p62/SQSTM1. Further, EAA-induced anti-melanogenic activity was substantially decreased in autophagy inhibitor (3-MA) pretreated or LC3 knockdown B16F10 cells. Notably, transmission electron microscopy data showed increased melanosome-engulfing autophagosomes in EAA-treated B16F10 cells. Moreover, EAA also down-regulated MC1R, TRP-1/-2, tyrosinase expressions, and melanin synthesis by suppressing the cAMP-CREB-mediated MITF expression in B16F10 cells stimulated with α-MSH. In vivo studies on the zebrafish model further confirmed that EAA inhibited tyrosinase expression/activity and endogenous pigmentation. In conclusion, 3-O-ethyl ascorbic acid is an effective skin-whitening agent and could be used as a topical agent for cosmetic purposes.
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Melaninas , Melanoma Experimental , Animais , Ácido Ascórbico , Autofagia , Linhagem Celular Tumoral , Queratinócitos , Melanócitos , Melanoma Experimental/tratamento farmacológico , Fator 2 Relacionado a NF-E2/genética , Peixe-Zebra , alfa-MSHRESUMO
Pterostilbene (Pt) is a natural polyphenol found in blueberries and several grape varieties. Pt's pharmacological importance was well documented. Nevertheless, the depigmenting effects are not demonstrated. We evaluated the Pt's depigmenting effects through autophagy induction in B16F10 cells and inhibition of UVA (3 J/cm2)-irradiated α-MSH in keratinocyte HaCaT cells via Nrf2-mediated antioxidant pathways. Pt (2.5-5µM) attenuated ROS production and downregulated the POMC/α-MSH pathway in HaCaT cells. The conditioned medium-derived from UVA-irradiated HaCaT pretreated with Pt suppressed melanogenesis in B16F10 through MITF-CREB-tyrosinase pathway downregulation. Interestingly, Pt-induced HaCaT autophagy was revealed by enhanced LC3-II accumulation, p62/SQSTM1 activation, and AVO formation. Pt significantly decreased melanosome gp100 but increased LC3-II levels in HaCaT cells exposed to B16F10-derived melanin. Pt activated and facilitated the Nrf2 antioxidant pathway in HaCaT cells leading to increased HO-1, γ-GCLC, and NQO-1 antioxidant protein expression. ERK, AMPK, and ROS pathways mediate the Nrf2 activation. However, Nrf2 knockdown suppressed Pt's antioxidant ability leading to uncontrolled ROS and α-MSH levels after UVA-irradiation suggested the essentiality of the Nrf2 pathway. Moreover, in α-MSH-stimulated B16F10 cells, Pt (10-30 µM) downregulated the MC1R, MITF, tyrosinase, TRP-1/-2, and melanin expression. Further, Pt showed potent anti-melanogenic effects through autophagy induction mechanism in B16F10 cells, verified by increased LC3-II/p62 levels, AVO formation, and Beclin-1/Bcl-2 ratio, decreased ATG4B levels and PI3K/AKT/mTOR pathway. Transmission electron microscopy provided direct evidence by showing autophagosomes engulfing melanosomes following Pt treatment in α-MSH-stimulated B16F10 cells. Moreover, Pt-induced anti-melanogenic activity through the downregulation of CREB-MITF pathway-mediated TRP-1/-2, tyrosinase expressions, melanosome formation, and melanin synthesis was substantially reversed due to 3-MA (autophagy inhibitor) pretreatment or LC3 silencing in B16F10 cells. In vivo results also confirmed that Pt-inhibited tyrosinase expression/activity and endogenous pigmentation in the zebrafish model. Therefore, pterostilbene is a potent skin-whitening and antioxidant agent and could be used in skin-whitening formulations as a topical applicant.
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Fator 2 Relacionado a NF-E2 , alfa-MSH , Animais , Antioxidantes , Autofagia , Linhagem Celular Tumoral , Queratinócitos , Melaninas , Melanócitos , Fosfatidilinositol 3-Quinases , Estilbenos , Peixe-ZebraRESUMO
OBJECTIVE: To investigate the effect of pH value and fluoride ions on the corrosion resistance of pure Ti and Ni-Cr-Ti alloy in the artificial saliva. METHODS: Electrochemical technique was used to measure the electric potential of corrosion (Ecorr), current density of corrosion (Icorr) and polarization resistance (Rp) of pure titanium and Ti-Ni-Cr alloy in the artificial saliva with different pH value and fluoride concentrations. After electrochemical analysis, microstructure and phase diffraction were examined by FSEM. RESULTS: With the lower pH value, the Ecorr and Icorr of pure titanium and Ti-Ni-Cr alloy increased, the Rp decreased, there was a significant difference (P<0.05). The Ecorr and Icorr increased markedly, the Rp significantly reduced in the artificial saliva containing 0.2% NaF (P<0.01). FSEM showed that pure titanium and Ti-Ni-Cr alloy surface corrosion, pure titanium in the artificial saliva containing 0.2% NaF was most serious. CONCLUSION: Lower pH value decreases the corrosion resistance of pure titanium and Ti-Ni-Cr alloy and the artificial saliva containing fluoride ions decreases the corrosion resistance of pure titanium.