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2.
Pharmacol Res ; 204: 107209, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38740147

RESUMO

Considerable progress has recently been made in cancer immunotherapy, including immune checkpoint blockade, cancer vaccine, and adoptive T cell methods. The lack of effective targets is a major cause of the low immunotherapy response rate in colorectal cancer (CRC). Here, we used a proteogenomic strategy comprising immunopeptidomics, whole exome sequencing, and 16 S ribosomal DNA sequencing analyses of 8 patients with CRC to identify neoantigens and bacterial peptides that can serve as antitumor targets. This study directly identified several personalized neoantigens and bacterial immunopeptides. Immunoassays showed that all neoantigens and 5 of 8 bacterial immunopeptides could be recognized by autologous T cells. Additionally, T cell receptor (TCR) αß sequencing revealed the TCR repertoire of epitope-reactive CD8+ T cells. Functional studies showed that T cell receptor-T (TCR-T) could be activated by epitope pulsed lymphoblastoid cells. Overall, this study comprehensively profiled the CRC immunopeptidome, revealing several neoantigens and bacterial peptides with potential to serve as immunotherapy targets in CRC.


Assuntos
Antígenos de Neoplasias , Neoplasias Colorretais , Imunoterapia , Proteogenômica , Humanos , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Neoplasias Colorretais/genética , Proteogenômica/métodos , Imunoterapia/métodos , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/genética , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Peptídeos/imunologia , Linfócitos T CD8-Positivos/imunologia
3.
Biomed Pharmacother ; 174: 116545, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38603884

RESUMO

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Others and our studies have shown that mechanical stresses (forces) including shear stress and cyclic stretch, occur in various pathological conditions, play significant roles in the development and progression of CVDs. Mitochondria regulate the physiological processes of cardiac and vascular cells mainly through adenosine triphosphate (ATP) production, calcium flux and redox control while promote cell death through electron transport complex (ETC) related cellular stress response. Mounting evidence reveal that mechanical stress-induced mitochondrial dysfunction plays a vital role in the pathogenesis of many CVDs including heart failure and atherosclerosis. This review summarized mitochondrial functions in cardiovascular system under physiological mechanical stress and mitochondrial dysfunction under pathological mechanical stress in CVDs (graphical abstract). The study of mitochondrial dysfunction under mechanical stress can further our understanding of the underlying mechanisms, identify potential therapeutic targets, and aid the development of novel treatments of CVDs.


Assuntos
Doenças Cardiovasculares , Mitocôndrias , Estresse Mecânico , Humanos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Animais , Mitocôndrias/metabolismo
4.
Int J Mol Sci ; 25(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38612472

RESUMO

Birinapant, an antagonist of the inhibitor of apoptosis proteins, upregulates MHCs in tumor cells and displays a better tumoricidal effect when used in combination with immune checkpoint inhibitors, indicating that Birinapant may affect the antigen presentation pathway; however, the mechanism remains elusive. Based on high-resolution mass spectrometry and in vitro and in vivo models, we adopted integrated genomics, proteomics, and immunopeptidomics strategies to study the mechanism underlying the regulation of tumor immunity by Birinapant from the perspective of antigen presentation. Firstly, in HT29 and MCF7 cells, Birinapant increased the number and abundance of immunopeptides and source proteins. Secondly, a greater number of cancer/testis antigen peptides with increased abundance and more neoantigens were identified following Birinapant treatment. Moreover, we demonstrate the existence and immunogenicity of a neoantigen derived from insertion/deletion mutation. Thirdly, in HT29 cell-derived xenograft models, Birinapant administration also reshaped the immunopeptidome, and the tumor exhibited better immunogenicity. These data suggest that Birinapant can reshape the tumor immunopeptidome with respect to quality and quantity, which improves the presentation of CTA peptides and neoantigens, thus enhancing the immunogenicity of tumor cells. Such changes may be vital to the effectiveness of combination therapy, which can be further transferred to the clinic or aid in the development of new immunotherapeutic strategies to improve the anti-tumor immune response.


Assuntos
Apresentação de Antígeno , Dipeptídeos , Indóis , Masculino , Animais , Humanos , Terapia Combinada , Modelos Animais de Doenças
5.
Clin Respir J ; 17(4): 320-328, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36740215

RESUMO

BACKGROUND: The potential of artificial intelligence (AI) to predict the nature of part-solid nodules based on chest computed tomography (CT) is still under exploration. OBJECTIVE: To determine the potential of AI to predict the nature of part-solid nodules. METHODS: Two hundred twenty-three patients diagnosed with part-solid nodules (241) by chest CT were retrospectively collected that were divided into benign group (104) and malignant group (137). Intraclass correlation coefficient (ICC) was used to assess the agreement in predicting malignancy, and the predictive effectiveness was compared between AI and senior radiologists. The parameters measured by AI and the size of solid components measured by senior radiologists were compared between two groups. Receiver operating characteristic (ROC) curve was chosen for calculating the Youden index of each quantitative parameter, which has statistical significance between two groups. Binary logistic regression performed on the significant indicators to suggest predictors of malignancy. RESULTS: AI was in moderate agreement with senior radiologists (ICC = 0.686). The sensitivity, specificity and accuracy of two groups were close (p > 0.05). The longest diameter, volume and mean CT attenuation value and the largest diameter of solid components between benign and malignant groups were different significantly (p < 0.001). Logistic regression analysis showed that the longest diameter and mean CT attenuation value and the largest diameter of solid components were indicators for malignant part-solid nodules, the threshold of which were 9.45 mm, 425.0 HU and 3.45 mm, respectively. CONCLUSION: Potential of quantitative parameter measured by AI to predict malignant part-solid nodules can provide a certain value for the clinical management.


Assuntos
Inteligência Artificial , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Curva ROC
6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(11): 1395-1399, 2022 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-36382458

RESUMO

Objective: To establish a classification model based on knee MRI radiomics, realize automatic identification of meniscus tear, and provide reference for accurate diagnosis of meniscus injury. Methods: A total of 228 patients (246 knees) with meniscus injury who were admitted between July 2018 and March 2021 were selected as the research objects. There were 146 males and 82 females; the age ranged from 9 to 76 years, with a median age of 53 years. There were 210 cases of meniscus injury in one knee and 18 cases in both knees. All the patients were confirmed by arthroscopy, among which 117 knees with meniscus tear and 129 knees with meniscus non-tear injury. The proton density weighted-spectral attenuated inversion recovery (PDW-SPAIR) sequence images of sagittal MRI were collected, and two doctors performed radiomics studies. The 246 knees were randomly divided into training group and testing group according to the ratio of 7∶3. First, ITK-SNAP3.6.0 software was used to extract the region of interest (ROI) of the meniscus and radiomic features. After retaining the radiomic features with intraclass correlation coefficient (ICC)>0.8, the max-relevance and min-redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) were used for filtering the features to establish an automatic identification model of meniscus tear. The receiver operator characteristic curve (ROC) and the corresponding area under the ROC curve (AUC) was obtained; the model performance was comprehensively evaluated by calculating the accuracy, sensitivity, and specificity. Results: A total of 1 316-dimensional radiomic features were extracted from the meniscus ROI, and the ICC within the group and ICC between the groups of the 981-dimensional radiomic features were both greater than 0.80. The redundant information in the 981-dimensional radiomic features was eliminated by mRMR, and the 20-dimensional radiomic features were retained. The optimal feature subset was further selected by LASSO, and 8-dimensional radiomic features were selected. The average ICC within the group and the average ICC between the groups were 0.942 and 0.920, respectively. The AUC of the training group was 0.889±0.036 [95% CI (0.845, 0.942), P<0.001], and the accuracy, sensitivity, and specificity were 0.873, 0.869, and 0.842, respectively; the AUC of the testing group was 0.876±0.036 [95% CI (0.875, 0.984), P<0.001], and the accuracy, sensitivity, and specificity were 0.862, 0.851, and 0.845, respectively. Conclusion: The model established by the radiomics method has good automatic identification performance of meniscus tear.


Assuntos
Imageamento por Ressonância Magnética , Menisco , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Algoritmos , Artroscopia/métodos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
7.
Int J Cosmet Sci ; 44(5): 500-513, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35775143

RESUMO

OBJECTIVES: Translucent skin is an attribute widely appreciated by people in East Asian countries. There have been studies in the literature to describe the phenomenon by means of clinical grading, instrumental measurement and image analysis. However, due to its subjective and complex nature, skin translucency has not been comprehensively and rigorously characterized and modelled, particularly in the Chinese population. This study is to develop a mathematical model that quantitatively describes skin translucency from visual cues objectively measured from the skin. MATERIALS AND METHODS: The study was designed to characterize and model skin translucency by incorporating expert evaluation, panel perception and image analysis of multiple skin visual attributes in one analysis. Faces of 36 Chinese females aged 18-65 years old were evaluated by a dermatologist to obtain clinical translucency scores. Subject pairs were formed with a relatively high and low translucency score in each pair. Their faces were judged in person by 9 panellists in paired-comparison (2-AFC) fashion to pick a 'more translucent skin' from each subject pair. Front-view facial images of the subjects were taken, and multiple colour and other visually perceivable skin attributes were measured using image analysis. Bradley-Terry analysis and multiple regressions were performed to correlate the panel choices of 'more translucent skin' with the objectively measured skin parameters. RESULTS: Multiple skin colour properties affected the panel choices towards translucent skin. Among them skin tone lightness and skin glossiness had positive effects on skin translucency while the hue, colour unevenness, severity of red and dark spots affected it negatively. Subsurface light reflection and skin visual smoothness had some effect but were not statistically significant. A mathematical model was constructed to predict a person's skin translucency from objectively measured skin attributes. CONCLUSION: The subjective property of skin translucency can be characterized and quantified via a comprehensive modelling process involving clinical grading, panel evaluation, image-based measurement of skin attributes and statistical analysis. A novel skin parameter, Skin Translucency Index (STI) was established, which provides a way to measure skin translucency, making it possible to assess treatment efficacy before and after product application.


OBJECTIF: La peau translucide est un attribut largement apprécié dans les pays d'Asie de l'Est. Des études ont été menées dans la littérature pour décrire ce phénomène au moyen d'une classification clinique, d'une mesure instrumentale et d'une analyse d'images. Cependant, en raison de sa nature subjective et complexe, la translucidité de la peau n'a pas été caractérisée et modélisée de manière exhaustive et rigoureuse, en particulier dans la population chinoise. Cette étude vise à développer un modèle mathématique qui décrit quantitativement la translucidité de la peau à partir de repères visuels objectivement mesurés sur la peau. MATÉRIELS ET MÉTHODES: L'étude a été conçue pour caractériser et modéliser la translucidité de la peau en intégrant l'évaluation des experts, les perceptions d'un panel et l'analyse d'images de multiples attributs visuels de la peau dans une seule analyse. Les visages de 36 femmes chinoises âgées de 18 à 65 ans ont été évalués par un dermatologue afin d'obtenir des scores de translucidité clinique. Des paires de sujets ont été formées, chaque paire ayant un score de translucidité relativement élevé et faible. Leurs visages ont été jugés en personne par 9 panellistes en comparaison appariée (2-AFC) pour choisir une « peau plus translucide ¼ pour chaque paire de sujets. Des images des visages des sujets de face ont été prises, et des attributs liés aux couleurs et d'autres attributs cutanés perceptibles visuellement ont été mesurés par une analyse des images. Une analyse de Bradley-Terry et des régressions multiples ont été réalisées pour corréler les choix de « peau plus translucide ¼ par le panel avec les paramètres cutanés mesurés objectivement. RÉSULTATS: Plusieurs propriétés liées à la couleur de peau ont influencé les choix du panel vers une peau translucide. Parmi celles-ci, la pâleur du teint et la brillance de la peau ont eu des effets positifs sur la translucidité de la peau, tandis que la teinte, l'inégalité de la couleur, la sévérité des taches rouges et foncées ont exercé une influence défavorable. La réflexion de la lumière sous la surface et la douceur de la peau perçue visuellement ont eu un certain effet, mais n'étaient pas statistiquement significatives. Un modèle mathématique a été construit pour prédire la translucidité de la peau d'une personne à partir d'attributs cutanés mesurés objectivement. CONCLUSION: La propriété subjective de la translucidité de la peau peut être caractérisée et quantifiée via un processus de modélisation complet comprenant une classification clinique, une évaluation par un panel, une mesure basée sur les images d'attributs cutanés et une analyse statistique. Un nouveau paramètre cutané, l'indice de translucidité de la peau (ITP), a été établi, qui fournit un moyen de mesurer la translucidité de la peau, permettant d'évaluer l'efficacité du traitement avant et après l'application du produit.


Assuntos
Povo Asiático , Pigmentação da Pele , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Pessoa de Meia-Idade , Pele/diagnóstico por imagem , Adulto Jovem
8.
J Cosmet Dermatol ; 21(9): 3986-3992, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34962051

RESUMO

BACKGROUND: Cosmetic products are widely used in daily life and can cause skin reactions. However, to date, few studies have investigated the prevalence and associated factors of skin reactions to different types of cosmetic products using patch test results. OBJECTIVES: To investigate the frequency and associated factors of skin reactions to sunscreens, skin whitening products, and deodorants using patch test results in China. METHODS: This cross-sectional analysis used data collected during 2004-2017 at the Shanghai Skin Disease Hospital, China. Skin reactions were measured using patch tests following internationally standardized protocols. RESULTS: In total, 151 280 patch tests comprising 16 477 cosmetic products conducted in 4029 healthy volunteers were analyzed. The frequencies of skin reactions to different cosmetic products were 1.07%, 1.28%, and 4.41% for sunscreens, skin whitening products, and deodorants, respectively. With increasing age, a higher frequency of reactions to sunscreens in women (p < 0.001) and a lower frequency of reactions to skin whitening products in men (p < 0.05) were observed. In addition, men were more likely to develop skin reactions to deodorants compared to women (p < 0.05). Skin reactions were more frequent in winter (p < 0.05), which was true for different types of cosmetic products. CONCLUSIONS: The frequency of patch testing for different cosmetic products was 1.07-4.41%. The effects of age, sex, and season vary among the different types of cosmetic products. We hope that these findings can offer guidance for a healthy skincare concept.


Assuntos
Cosméticos , Desodorantes , China/epidemiologia , Cosméticos/efeitos adversos , Estudos Transversais , Feminino , Humanos , Masculino , Testes do Emplastro , Protetores Solares/efeitos adversos
9.
J Cosmet Dermatol ; 21(5): 2183-2188, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34240515

RESUMO

BACKGROUND: Patch test, as a helpful tool in clinic diagnosis and safety assessment of cosmetics, is affected by many factors. OBJECTIVES: To investigate the influencing factors of patch test reactions in a highly standardized large-scale dataset of Chinese. METHODS: Patch test data (n = 151,280) from safety assessments of cosmetic products were obtained following internationally standardized patch testing protocols during 2004-2017 in China. RESULTS: The frequency of patch test reactions was 1.45% (2,191/151,280), with majority of the reactions being "score 1" reactions (also known as doubtful reactions, n = 2,075) and a small number being "score 2" reactions (weak reactions, n = 116). Patch test reactions were 67% more frequent in winter (p < 0.001), associated with temperatures (p < 0.001), rather than relative humidity (P:0.29). The frequency of reactions was higher in men than in women (p:0.001), especially in winter. The risk to develop reactions clearly increased with age in women (p < 0.001), but not in men (p:0.14). In women, the frequency of reactions in the old group (≥50 years old) was 30% more than the young group (<30 years old). CONCLUSIONS: The frequency of patch test reactions to cosmetic products was 1.45% in our large-scale study. The influencing factors of patch test include season, sex, and age, which should be considered when conducting and interpreting patch testing.


Assuntos
Cosméticos , Dermatite Alérgica de Contato , Adulto , Alérgenos , China/epidemiologia , Cosméticos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes do Emplastro/métodos
10.
Am J Transl Res ; 13(8): 9332-9339, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540050

RESUMO

OBJECTIVE: The aim of this investigation was to determine the influence of anti-tuberculosis (anti-TB) drugs plus cycloserine (CS) on the sputum negative conversion rate, adverse reactions and inflammatory factors in the treatment of multidrug-resistant tuberculosis (MDR-TB). METHODS: Seventy patients with MDR-TB who were referred to Nanjing Hospital Affiliated with Nanjing University of Traditional Chinese Medicine from April 2017 to April 2020 were assigned into the research group (RG; 38 cases) for anti-TB drugs plus CS, and the control group (CG; 32 cases) for conventional anti-TB drugs. The two groups were compared in their sputum negative conversion rate, incidence of adverse reactions, and foci absorption rate after 6, 12 and 24 months of treatment. The levels of inflammatory factors; tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interferon-γ (IFN-γ), both pre- and post-treatment were detected. Also, pre- and post-treatment, pulmonary function (PF) indexes (forced expiratory volume in 1 s/forced vital capacity, FEV1/FVC; FEV1; peak expiratory flow, PEF), and the scores of anxiety and depression (self-rating anxiety/depression scale, SAS/SDS), as well as Pittsburgh Sleep Quality Index (PSQI) were compared. RESULTS: After 6, 12 and 24 months of treatment, the sputum negative conversion rate and foci absorption rate were higher in the RG than in the CG (both P<0.05). The RG presented with fewer adverse reactions, lower TNF-α, IL-6 and IFN-γ levels, higher FEV1, FEV1/FVC and PEF, and lower SAS, SDS and PSQI scores than the CG, post treatment (all P<0.05). CONCLUSIONS: While helping to raise the sputum negative conversion rate, improve prognosis, and reduce adverse reactions, anti-TB drugs plus CS can also inhibit the release of inflammatory factors, improve PF and alleviate negative emotion and sleep disorders.

11.
Photodiagnosis Photodyn Ther ; 36: 102491, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34418549

RESUMO

BACKGROUND AND OBJECTIVES: Androgenetic alopecia (AGA) is one of the most common hair loss disorders. Treatment options for AGA are limited . New therapies for AGA are clinically needed. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is widely applied in diseases involving the pilosebaceous unit. However, limited research has explored the efficacy of ALA-PDT in treating alopecia. Some studies reported hair regrowth after PDT in alopecia areata patients, but the efficacy of ALA-PDT on AGA remains unclear. The objective of this study is to evaluate the efficacy and safety of ALA-PDT for the treatment of AGA. METHODS: A randomized, placebo-controlled, split-scalp clinical study was conducted. Subjects with AGA received six sessions of 5% ALA-PDT on one half of their scalp and the red-light therapy on the other half. The treatments were applied every two weeks for six sessions on each subject. RESULTS: There were 7 subjects enrolled in this study. No significant difference in hair density was observed between the red-light treatment and ALA-PDT treatment. The hair density in the ALA-PDT treated half of the scalp significantly decreased 1 week after the treatment, then it increased, and no statistical difference was found at 12 weeks after the last treatment compared to the baseline. There was no significant improvement in hair growth according to a 7-point scale and the subjects' self-assessments. The main adverse effects in ALA-PDT treatment were mild edema and tolerable pain, and no adverse effect was observed in red-light treatment. CONCLUSIONS: 6 sessions of 5% ALA-PDT did not increase the hair growth of AGA patients, but slightly suppressed the sebum secretion on the scalp. The adverse effects of ALA-PDT were mild, which indicated safety and tolerability of this treatment.


Assuntos
Alopecia em Áreas , Fotoquimioterapia , Alopecia em Áreas/tratamento farmacológico , Ácido Aminolevulínico/efeitos adversos , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/efeitos adversos , Couro Cabeludo , Resultado do Tratamento
12.
Front Cell Dev Biol ; 9: 683448, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262900

RESUMO

Tributyltin oxide (TBTO), an organotin compound, has been demonstrated to have toxic effects on several cell types. Previous research has shown that TBTO impairs mouse denuded oocyte maturation. However, limited information is available on the effects of TBTO exposure on livestock reproductive systems, especially on porcine oocytes in the presence of dense cumulus cells. In the present research, we evaluated the effects of TBTO exposure on porcine oocyte maturation and the possible underlying mechanisms. Porcine cumulus-oocyte complexes were cultured in maturation medium with or without TBTO for 42 h. We found that TBTO exposure during oocyte maturation prevented polar body extrusion, inhibited cumulus expansion and impaired subsequent blastocyst formation after parthenogenetic activation. Further analysis revealed that TBTO exposure not only induced intracellular reactive oxygen species (ROS) accumulation but also caused a loss of mitochondrial membrane potential and reduced intracellular ATP generation. In addition, TBTO exposure impaired porcine oocyte quality by disrupting cellular iron homeostasis. Taken together, these results demonstrate that TBTO exposure impairs the porcine oocyte maturation process by inducing intracellular ROS accumulation, causing mitochondrial dysfunction, and disrupting cellular iron homeostasis, thus decreasing the quality and impairing the subsequent embryonic developmental competence of porcine oocytes.

13.
Theriogenology ; 172: 169-177, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34174755

RESUMO

Asiatic acid is a natural triterpene found in Centella asiatica that acts as an effective free radical scavenger. Our previous research showed that asiatic acid delayed porcine oocyte ageing in vitro and improved preimplantation embryo development competence in vitro; however, the protective effects of asiatic acid against oxidative stress in porcine oocyte maturation are still unclear. Here, we investigated the effects of asiatic acid on porcine oocyte in vitro maturation (IVM) and subsequent embryonic development competence after parthenogenetic activation (PA) and in vitro fertilization (IVF). The results of the present research showed that 10 µM asiatic acid supplementation did not affect the expansion of cumulus cells or polar body extrusion of porcine oocytes, while asiatic acid application significantly increased the subsequent blastocyst formation rate and quality of porcine PA and IVF embryos. Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that induces oxidative stress in porcine oocytes. As expected, asiatic acid supplementation not only decreased intracellular ROS levels but also attenuated H2O2-induced intracellular ROS generation. Further analysis revealed that asiatic acid supplementation enhanced intracellular glutathione production, mitochondrial membrane potential, and ATP generation at the end of IVM. In summary, our results reveal that asiatic acid supplementation exerts beneficial effects on porcine oocytes by regulating oxidative stress during the IVM process and could act as a potential antioxidant in porcine oocytes matured in vitro production systems.


Assuntos
Peróxido de Hidrogênio , Técnicas de Maturação in Vitro de Oócitos , Animais , Blastocisto , Suplementos Nutricionais , Desenvolvimento Embrionário , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oócitos/metabolismo , Estresse Oxidativo , Triterpenos Pentacíclicos , Espécies Reativas de Oxigênio/metabolismo , Suínos
14.
Front Cell Dev Biol ; 9: 673291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34124055

RESUMO

Accumulating evidence indicates that ferroptosis is an iron-dependent form of regulated cell death. This type of iron-dependent programmed cell death is different from traditional forms of regulated cell death, such as apoptosis and autophagy. However, the role of ferroptosis in porcine oocyte maturation and the associated mechanism remain unclear. In the present research, we investigated the effects of ferric ammonium citrate (FAC), a specific ferroptosis inducer, on porcine oocyte meiotic maturation and quality and subsequent embryonic developmental competence. FAC treatment caused obvious accumulation of intracellular ferrous ions in porcine oocytes. At the end of the in vitro maturation (IVM) period, there was a significant decrease in the polar body (PB) extrusion rate and an increase in the percentage of abnormal oocytes in the FAC treatment groups, indicating that iron overload-induced ferroptosis may suppress the meiotic process during porcine oocyte maturation. We also found that after FAC treatment, the subsequent two-cell rate, four-cell rate and blastocyst formation rate were significantly decreased in porcine parthenogenetic activation (PA) embryos, indicating that iron overload-induced ferroptosis decreased porcine oocyte quality. Further analysis revealed that FAC treatment not only enhanced intracellular reactive oxygen species (ROS) generation, decreased intracellular free thiol levels and induced mitochondrial dysfunction but also triggered autophagy in porcine oocytes. Taken together, these findings suggest that iron overload-induced ferroptosis impairs porcine oocyte meiosis and decreases porcine oocyte quality, possibly by increasing oxidative stress, inducing mitochondrial dysfunction and triggering autophagy.

15.
Aging (Albany NY) ; 13(3): 3353-3367, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33281118

RESUMO

As a pentacyclic triterpene in Centella asiatica, asiatic acid (AA) is a powerful antioxidant with many bioactivities. In the present research, we investigated whether AA has the potential to rescue the decrease in porcine oocyte quality that occurs during in vitro aging (IVA). Mature porcine oocytes were collected and then continuously cultured for an additional 24 h or 48 h with or without AA in maturation medium as an IVA model. The results revealed that AA supplementation reduced the percentage of abnormal aged porcine oocytes during IVA. Furthermore, AA supplementation effectively maintained aged porcine oocyte developmental competence, both parthenogenetic activation and in vitro fertilization. The number of sperm that bound to the zona pellucida on aged porcine oocytes was higher in the AA-supplemented group than in the non-supplemented group. Moreover, AA supplementation not only blocked IVA-induced oxidative stress but also maintained intracellular GSH levels and reduced the percentage of early apoptosis aged porcine oocytes. Mitochondrial functions were disordered during the IVA process. The intracellular ATP levels and mitochondrial membrane potential in aged porcine oocytes were dramatically increased by AA supplementation. Therefore, AA has beneficial effects on porcine oocyte quality and developmental potential maintenance during IVA.


Assuntos
Senescência Celular/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Animais , Antioxidantes , Apoptose/efeitos dos fármacos , Feminino , Técnicas de Maturação in Vitro de Oócitos , Mitocôndrias/efeitos dos fármacos , Suínos
16.
J Evol Biol ; 33(11): 1593-1605, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32929788

RESUMO

Bacteria typically reside in heterogeneous environments with various chemogradients where motile cells can gain an advantage over nonmotile cells. Since motility is energetically costly, cells must optimize their swimming speed and behaviour to maximize their fitness. Here, we investigate how cheating strategies might evolve where slow or nonmotile microbes exploit faster ones by sticking together and hitching a ride. Starting with physical and biological first principles, we computationally study the effects of sticking on the evolution of motility in a controlled chemostat environment. We find that stickiness allows for slow cheaters to dominate when chemoattractants are dispersed at intermediate distances. In this case, slow microbes exploit faster ones until they consume the population, leading to a tragedy of commons. For long races, slow microbes do gain an initial advantage from sticking, but eventually fall behind. Here, fast microbes are more likely to stick to other fast microbes and co-operate to increase their own population. We therefore conclude that whether the nature of the hitchhiking interaction is parasitic or mutualistic, depends on the chemoattractant distribution.


Assuntos
Aderência Bacteriana , Evolução Biológica , Quimiotaxia , Modelos Biológicos , Fatores Quimiotáticos
17.
J Cosmet Dermatol ; 19(8): 2086-2092, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31820565

RESUMO

BACKGROUND: There are increasing cosmetic adverse reactions in China, mostly cosmetic contact dermatitis, with the development of its cosmetics industry. AIMS: To identify the allergens and cosmetics products responsible for cosmetic allergic contact dermatitis (CACD) in Shanghai. METHODS: Five hundred and sixty patients, including 342 suspected CACD patients from dermatological clinic and 218 cosmetics consumers with an allergic history, were patch tested with a cosmetic series (C-1000 series). And 154 patients patched with possible culprit cosmetics. RESULTS: Two hundred and forty-six subjects showed positive reaction to C-1000 series. Clinic patients had much higher positive rate than that of cosmetics consumers. Leading allergens were methylisothiazolinone (MI), methylisothiazolinone + methylchloro-isothiazolinone (MCI/MI), thimerosal, and the positive rates were significantly higher in patients than in cosmetic consumers (P < .001 for all). MCI/MI elicited positive patch test reactions in 73.5% of MI-positive patients. Of those patched with cosmetic products, 19 patients had 31 positive reactions, including 22 skin care products and 5 color decorating. CONCLUSIONS: Preservatives, especially MI, MCI/MI, and thimerosal, were the most common cosmetic allergens, and skin care products occupied the most allergic reaction of CACD. Patch testing is highly recommended for suspected CACD patients. Future comparative investigation with large sample size should benefit cosmetovigilance surveillance.


Assuntos
Cosméticos , Dermatite Alérgica de Contato , China/epidemiologia , Cosméticos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Humanos , Testes do Emplastro , Conservantes Farmacêuticos
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