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1.
Genet Test Mol Biomarkers ; 28(3): 91-99, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38359386

RESUMO

Background: At present, numerous clinical studies suggest a correlation between inflammatory bowel disease (IBD) and skin cancer. However, some articles present differing views that IBD does not increase the risk of skin cancer. The presence of potential reverse causality and residual confounding is inherent in conventional observational studies. Thus, this study used a two-sample Mendelian randomization (MR) study design to estimate the causal effect of IBD on the risk of skin cancer, including cutaneous malignant melanoma (CMM, also named melanoma skin cancer) and nonmelanoma skin cancer (NMSC). Design: In this study, a two-sample MR analysis was used to estimate the causal effect of IBD on skin cancer outcomes. The inverse-variance weighted (IVW) method was used as the main MR analysis, with multiple sensitivity analyses conducted to assess the robustness of findings. Results: In examining the association between IBD and NMSC, all p-values of the IVW methods were found to be <0.05, providing evidence for a causal effect of IBD on an increased risk of NMSC. However, IVW for IBD on CMM yielded p-values >0.05, indicating no causal relationship between IBD and CMM. These findings were consistent across other MR methods, with no evidence of pleiotropy or heterogeneity. Sensitivity analyses confirmed the robustness of our results. Conclusion: Using MR analysis, we found evidence for a causal effect of genetic liability for IBD on an increased risk of NMSC. However, our study did not find sufficient evidence to support a significant impact of IBD on CMM outcomes.


Assuntos
Doenças Inflamatórias Intestinais , Melanoma , Neoplasias Cutâneas , Humanos , Análise da Randomização Mendeliana , Neoplasias Cutâneas/genética , Melanoma/genética , Doenças Inflamatórias Intestinais/genética , Projetos de Pesquisa , Estudo de Associação Genômica Ampla
2.
J Cancer ; 15(3): 671-684, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38213735

RESUMO

Background: Ginsenoside, the main active constituent of traditional Chinese medicine Ginseng, has been shown to play an important role in the prevention and treatment of cancer. However, the literature as well as the antitumor mechanisms of ginsenosides has not yet been systematically studied. Methods: We screened all relevant literature on ginsenosides and tumors from Web of Science during 2001-2021 and analyzed the extracted terms of these publications by VOSviewer and CiteSpace. DAVID online tool was used to perform Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathways analysis of ginsenoside-related genes. Cytoscape and String software were used to construct the interaction networks of ginsenoside-related genes and corresponding proteins. Results: A total of 919 publications were included in the study. A total of 122 identified keywords were mainly divided into 3 clusters: "pharmacological function research", "functional validation in animal models" and "anti-tumor efficacy and mechanism". The keywords of "oxidative stress" had the strongest citation burst in the past 5 years. A total of 50 genes were identified as ginsenoside-related genes in tumors. They have the function of regulating gene expression and apoptosis, and they are closely related to signaling pathways in cancers. Ginsenoside-related genes form a complex interactional network, in which TP53 and IL-6 are centrally located. Conclusions: We explored and revealed research hotspots related to the ginsenosides and tumors. More precise anti-tumor mechanism research will be promising in the future. TP53 and IL-6 may be the key points to comprehending the anti-tumor mechanism of ginsenosides.

3.
J Transl Med ; 22(1): 92, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263233

RESUMO

BACKGROUND: Recent research increasingly highlights a strong correlation between gut microbiota and the risk of gastrointestinal diseases. However, whether this relationship is causal or merely coincidental remains uncertain. To address this, a Mendelian randomization (MR) analysis was undertaken to explore the connections between gut microbiota and prevalent gastrointestinal diseases. METHODS: Genome-wide association study (GWAS) summary statistics for gut microbiota, encompassing a diverse range of 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla), were sourced from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were gathered from the UK Biobank, FinnGen study, and various extensive GWAS studies. MR analysis was meticulously conducted to assess the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. To validate the reliability of our findings, sensitivity analyses and tests for heterogeneity were systematically performed. RESULTS: The MR analysis yielded significant evidence for 251 causal relationships between genetically predicted gut microbiota and the risk of gastrointestinal diseases. This included 98 associations with upper gastrointestinal diseases, 81 with lower gastrointestinal diseases, 54 with hepatobiliary diseases, and 18 with pancreatic diseases. Notably, these associations were particularly evident in taxa belonging to the genera Ruminococcus and Eubacterium. Further sensitivity analyses reinforced the robustness of these results. CONCLUSIONS: The findings of this study indicate a potential genetic predisposition linking gut microbiota to gastrointestinal diseases. These insights pave the way for designing future clinical trials focusing on microbiome-related interventions, including the use of microbiome-dependent metabolites, to potentially treat or manage gastrointestinal diseases and their associated risk factors.


Assuntos
Gastroenteropatias , Microbioma Gastrointestinal , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes
4.
Stem Cell Res Ther ; 15(1): 4, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167128

RESUMO

BACKGROUND: TMC1 is one of the most common deafness genes causing DFNA36. Patient-derived human induced pluripotent stem cells (iPSCs) provide an opportunity to modelling diseases. TMC1 p.M418K mutation in human is orthologous to Beethoven mice. Here, we investigated the differentiation, morphology and electrophysiological properties of hair cell-like cells (HC-like cells) derived from DFNA36 patient. METHODS: Inner ear HC-like cells were induced from iPSCs derived from DFNA36 (TMC1 p.M418K) patient (M+/-), normal control (M+/+) and genetic corrected iPSCs (M+/C). Immunofluorescence, scanning electron microscopy and whole-cell patch-clamp were used to study the mechanism and influence of TMC1 p.M418K mutation. RESULTS: In this study we successfully generated HC-like cells from iPSCs with three different genotypes. HC-like cells from M+/- showed defected morphology of microvilli and physiological properties compared to M+/+. HC-like cells from M+/C showed recovery in morphology of microvilli and physiological properties. CONCLUSIONS: Our results indicate that TMC1 p.M418K mutation didn't influence inner ear hair cell differentiation but the morphology of microvilli and electrophysiological properties and gene correction induced recovery. CRISPR/Cas9 gene therapy is feasible in human patient with TMC1 p.M418K mutation.


Assuntos
Perda Auditiva Neurossensorial , Células-Tronco Pluripotentes Induzidas , Humanos , Animais , Camundongos , Células Ciliadas Auditivas/fisiologia , Perda Auditiva Neurossensorial/genética , Mutação/genética , Cabelo , Proteínas de Membrana/genética
5.
Hear Res ; 441: 108919, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043402

RESUMO

Auditory neuropathy spectrum disorder (ANSD) is a hearing impairment involving disruptions to inner hair cells (IHCs), ribbon synapses, spiral ganglion neurons (SGNs), and/or the auditory nerve itself. The outcomes of cochlear implants (CI) for ANSD are variable and dependent on the location of lesion sites. Discovering a potential therapeutic agent for ANSD remains an urgent requirement. Here, 293T stable transfection cell lines and patient induced pluripotent stem cells (iPSCs)-derived auditory neurons carrying the apoptosis inducing factor (AIF) p.R422Q variant were used to pursue a therapeutic regent for ANSD. Nicotinamide adenine dinucleotide (NADH) is a main electron donor in the electron transport chain (ETC). In 293T stable transfection cells with the p.R422Q variant, NADH treatment improved AIF dimerization, rescued mitochondrial dysfunctions, and decreased cell apoptosis. The effects of NADH were further confirmed in patient iPSCs-derived neurons. The relative level of AIF dimers was increased to 150.7 % (P = 0.026) from 59.2 % in patient-neurons upon NADH treatment. Such increased AIF dimerization promoted the mitochondrial import of coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4), which further restored mitochondrial functions. Similarly, the content of mitochondrial calcium (mCa2+) was downregulated from 136.7 % to 102.3 % (P = 0.0024) in patient-neurons upon NADH treatment. Such decreased mCa2+ levels inhibited calpain activity, ultimately reducing the percentage of apoptotic cells from 30.5 % to 21.1 % (P = 0.021). We also compared the therapeutic effects of gene correction and NADH treatment on hereditary ANSD. NADH treatment had comparable restorative effects on functions of ANSD patient-specific cells to that of gene correction. Our findings offer evidence of the molecular mechanisms of ANSD and introduce NADH as a potential therapeutic agent for ANSD therapy.


Assuntos
Fator de Indução de Apoptose , Apoptose , Perda Auditiva Central , NAD , Células Receptoras Sensoriais , Perda Auditiva Central/genética , Perda Auditiva Central/metabolismo , Perda Auditiva Central/fisiopatologia , Apoptose/efeitos dos fármacos , NAD/farmacologia , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos , Células Receptoras Sensoriais/metabolismo , Dimerização , Mitocôndrias/efeitos dos fármacos , Células HEK293 , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial/metabolismo , Cálcio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Calpaína/metabolismo , Ativação Enzimática/efeitos dos fármacos , Genótipo , Humanos , Fator de Indução de Apoptose/genética , Fator de Indução de Apoptose/metabolismo
6.
J Food Sci ; 89(1): 64-80, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37983835

RESUMO

The limited water solubility and bioactivity of lipophilic phytochemicals may be enhanced by delivery systems. Ellagic acid (EA) has antioxidant and anti-inflammatory properties, but low solubility and instability limit its use in the food industry. In this study, the pH-shift method was applied to encapsulate EA with soy protein isolate (SPI). The interaction, encapsulation, and protective potential of the EA-loaded soy SPI complexes (SPI-EA) were investigated. The fluorescence spectra results suggest that the reaction between SPI and EA is spontaneous, with hydrophobic interactions predominating. Binding of EA molecules quenches the intrinsic fluorescence of SPI, mainly static quenching, with a binding site involved in the binding process. The ultraviolet (UV)-visible spectroscopy of the SPI-EA complexes included the characteristic absorption peaks of both SPI and EA, and the scanning electron microscopy images further indicated that the EA had been successfully embedded in SPI. Fourier transform infrared spectroscopy illustrates that EA has significantly changed the secondary structure of the SPI, primarily in the form of a decreased content of α-helix structures and an increased content of ß-sheet and random coil structures. The encapsulation efficiency of EA was concentration-dependent, up to 81.08%. The addition of EA reduces the size of SPI particles (d < 155 nm). In addition, the SPI-EA complex showed up to 81.05% and 96.46% 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity. TGA showed that the degradation temperature of SPI-EA complex could be extended up to 300°C. And by encapsulation of EA, the loss of EA under the action of UV light, heat treatment, and high concentration of salt ion sensitive environment can be reduced. PRACTICAL APPLICATION: Ellagic acid (EA), a natural bioactive with low water solubility and stability, can be enhanced by forming an inclusion complex with soy protein isolate (SPI). SPI-EA complex has broad potential applications in the food, beverage, and pharmaceutical industries. Multiple spectral analyses have contributed to our understanding of the formation and interaction mechanisms of the SPI-EA complex under pH-driven conditions. Stability assays have also aided in the development of dietary resources for EA.


Assuntos
Antioxidantes , Proteínas de Soja , Proteínas de Soja/química , Ácido Elágico , Fenômenos Químicos , Água/química
7.
Sci Rep ; 13(1): 17310, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828051

RESUMO

Aiming at the problem of multi-object detection such as target occlusion and tiny targets in road scenes, this paper proposes an improved YOLOv5 multi-object detection model based on ML-AFP (multi-level aggregation feature perception) mechanism. Since tiny targets such as non-motor vehicle and pedestrians are not easily detected, this paper adds a micro target detection layer and a double head mechanism to improve the detection ability of tiny targets. Varifocal loss is used to achieve a more accurate ranking in the process of non-maximum suppression to solve the problem of target occlusion, and this paper also proposes a ML-AFP mechanism. The adaptive fusion of spatial feature information at different scales improves the expression ability of network model features, and improves the detection accuracy of the model as a whole. Our experimental results on multiple challenging datasets such as KITTI, BDD100K, and show that the accuracy, recall rate and mAP value of the proposed model are greatly improved, which solves the problem of multi-object detection in crowded road scenes.

8.
Cell Death Dis ; 14(6): 375, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365177

RESUMO

Auditory neuropathy spectrum disorder (ANSD) is a hearing impairment caused by dysfunction of inner hair cells, ribbon synapses, spiral ganglion neurons and/or the auditory nerve itself. Approximately 1/7000 newborns have abnormal auditory nerve function, accounting for 10%-14% of cases of permanent hearing loss in children. Although we previously identified the AIFM1 c.1265 G > A variant to be associated with ANSD, the mechanism by which ANSD is associated with AIFM1 is poorly understood. We generated induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells (PBMCs) via nucleofection with episomal plasmids. The patient-specific iPSCs were edited via CRISPR/Cas9 technology to generate gene-corrected isogenic iPSCs. These iPSCs were further differentiated into neurons via neural stem cells (NSCs). The pathogenic mechanism was explored in these neurons. In patient cells (PBMCs, iPSCs, and neurons), the AIFM1 c.1265 G > A variant caused a novel splicing variant (c.1267-1305del), resulting in AIF p.R422Q and p.423-435del proteins, which impaired AIF dimerization. Such impaired AIF dimerization then weakened the interaction between AIF and coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4). On the one hand, the mitochondrial import of ETC complex subunits was inhibited, subsequently leading to an increased ADP/ATP ratio and elevated ROS levels. On the other hand, MICU1-MICU2 heterodimerization was impaired, leading to mCa2+ overload. Calpain was activated by mCa2+ and subsequently cleaved AIF for its translocation into the nucleus, ultimately resulting in caspase-independent apoptosis. Interestingly, correction of the AIFM1 variant significantly restored the structure and function of AIF, further improving the physiological state of patient-specific iPSC-derived neurons. This study demonstrates that the AIFM1 variant is one of the molecular bases of ANSD. Mitochondrial dysfunction, especially mCa2+ overload, plays a prominent role in ANSD associated with AIFM1. Our findings help elucidate the mechanism of ANSD and may lead to the provision of novel therapies.


Assuntos
Fator de Indução de Apoptose , Cálcio , Células-Tronco Pluripotentes Induzidas , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Criança , Humanos , Recém-Nascido , Fator de Indução de Apoptose/genética , Fator de Indução de Apoptose/metabolismo , Cálcio/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Leucócitos Mononucleares/metabolismo , Mitocôndrias/metabolismo , Neurônios/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial/genética , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial/metabolismo
9.
Front Bioeng Biotechnol ; 11: 1108952, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37122867

RESUMO

Extracellular vesicles (EVs) derived from pleural effusion (PE) is emerging as disease biomarkers. However, the methods for isolation of EVs from PE (pEVs) were rarely studied. In our study, three methods for isolating pEVs of lung cancer patients were compared, including ultracentrifugation (UC), a combination of UC and size exclusion chromatography (UC-SEC) and a combination of UC and density gradient ultracentrifugation (UC-DGU). The subpopulation of pEVs was identified by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Western blotting (WB) and nano-flow cytometry (nFCM). Additionally, the proteomic landscape of pEVs was analyzed by Label-free proteomics. The results showed that, compared with UC and UC-DGU, the UC-SEC method separated pEVs with the highest purity. In the proteomic analysis, on average, 1595 proteins were identified in the pEVs isolated by UC-SEC, much more than pEVs isolated by UC (1222) or UC-DGU (807). Furthermore, approximately 90% of identified proteins in each method were found in the EVs public database ExoCarta. Consistent with this, GO annotation indicated that the core proteins identified in each method were mainly enriched in "extracellular exosome." Many of the top 100 proteins with high expression in each method were suggested as protein markers to validate the presence of EVs in the MISEV2018 guidelines. In addition, combined with lung tissue-specific proteins and vesicular membrane proteins, we screened out and validated several novel protein markers (CD11C, HLA DPA1 and HLA DRB1), which were enriched in pEVs rather than in plasma EVs. In conclusion, our study shows that the method of UC-SEC could significantly improve the purity of EVs and the performance of mass spectrometry-based proteomic profiling in analyzing pEVs. The exosomal proteins CD11C, HLA DPA1 and HLA DRB1 may act as potential markers of pEVs. The proteomic analysis of pEVs provides important information and new ideas for studying diseases complicated with PE.

10.
Injury ; 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36966123

RESUMO

BACKGROUND: Observational studies have suggested that osteoarthritis may increase the risk of cardiovascular diseases. However, there is still no high-quality evidence to explain this causal relationship. We conducted a two-sample Mendelian randomization (MR) study to assess the associations of hip arthritis and knee arthritis with 14 types of cardiovascular diseases in the general population. METHOD: Genome-wide association studies for hip arthritis and knee arthritis were obtained from the UK Biobank. Genome-wide association studies of the 14 types of cardiovascular diseases we studied were extracted from the genetic consortia and the FinnGen consortium. Inverse variance weighted (IVW), maximum likelihood, weighted medium, penalized weighted median, and IVW (fixed effects) of MR were applied to a two-sample MR analysis. The mean pleiotropy of genetic variation and sensitivity analysis were used to evaluate the reliability of the results, and the MR-Egger test and leave-one-out method are the core evaluation methods. RESULT: Genetically predicted knee arthritis was causally associated with vein thromboembolism (IVW Odds Ratio (OR): 1.005, 95% Confidence Interval (CI): 0.842-1.199, P = 0.020) and pulmonary embolism (IVW OR: 1.003, 95% CI: 0.841-1.197, P = 0.025). Furthermore, hip arthritis also has a significant impact on cardiovascular diseases and is positively correlated with ischemic stroke (IVW OR: 1.086, 95% CI: 0.910-1.295, P = 0.024), atrial fibrillation (IVW OR: 1.093, 95% CI: 0.917-1.304, P = 0.019), and coronary artery disease (IVW OR: 1.061, 95% CI: 0.890-1.266, P = 0. 0.002). CONCLUSION: Our study suggested that osteoarthritis may increase the risk of vein thromboembolism, pulmonary embolism, ischemic stroke, atrial fibrillation, and coronary artery disease. However, the findings provided no evidence to support that osteoarthritis has a large effect on the risk of cardiovascular diseases that we studied. Further research is needed to clarify the results.

11.
J Zhejiang Univ Sci B ; 24(2): 172-184, 2023 Feb 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36751702

RESUMO

Auditory neuropathy spectrum disorder (ANSD) represents a variety of sensorineural deafness conditions characterized by abnormal inner hair cells and/or auditory nerve function, but with the preservation of outer hair cell function. ANSD represents up to 15% of individuals with hearing impairments. Through mutation screening, bioinformatic analysis and expression studies, we have previously identified several apoptosis-inducing factor (AIF) mitochondria-associated 1 (AIFM1) variants in ANSD families and in some other sporadic cases. Here, to elucidate the pathogenic mechanisms underlying each AIFM1 variant, we generated AIF-null cells using the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and constructed AIF-wild type (WT) and AIF-mutant (mut) (p.|T260A, p.|R422W, and p.|R451Q) stable transfection cell lines. We then analyzed AIF structure, coenzyme-binding affinity, apoptosis, and other aspects. Results revealed that these variants resulted in impaired dimerization, compromising AIF function. The reduction reaction of AIF variants had proceeded slower than that of AIF-WT. The average levels of AIF dimerization in AIF variant cells were only 34.5%|‒|49.7% of that of AIF-WT cells, resulting in caspase-independent apoptosis. The average percentage of apoptotic cells in the variants was 12.3%|‒|17.9%, which was significantly higher than that (6.9%|‒|7.4%) in controls. However, nicotinamide adenine dinucleotide (NADH) treatment promoted the reduction of apoptosis by rescuing AIF dimerization in AIF variant cells. Our findings show that the impairment of AIF dimerization by AIFM1 variants causes apoptosis contributing to ANSD, and introduce NADH as a potential drug for ANSD treatment. Our results help elucidate the mechanisms of ANSD and may lead to the provision of novel therapies.


Assuntos
Fator de Indução de Apoptose , NAD , Humanos , Fator de Indução de Apoptose/química , Fator de Indução de Apoptose/genética , Fator de Indução de Apoptose/metabolismo , NAD/metabolismo , Dimerização , Apoptose
12.
Chem Biodivers ; 20(2): e202200658, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36633391

RESUMO

The osmanthus volatile oil was welcomed by consumers even if the high price since the unique and pleasant odor. Meanwhile, the low yield of osmanthus volatile oil restricts industrial production. In this work, an osmanthus volatile oil was obtained by means of a novel ultrasonic-assisted flash extraction method and was compared with the oil from hydrodistillation and supercritical fluid extraction on yield, aroma, and biological activities. The volatile oil obtained from the ultrasonic-assisted flash extraction was obtained with the petroleum ether and got a high yield at 3.51 % within a 40-min process, an increase of nearly 81 % from the single solvent extraction. This oil also showed a high aroma intensity and aroma compound concentration. Meanwhile, the oil also has the highest antioxidant ability but lower antibacterial activity against oil from hydrodistillation. It was considered that this work was helpful for the optimization of the extraction method of osmanthus volatile oil.


Assuntos
Óleos Voláteis , Oleaceae , Odorantes , Solventes
13.
J Sci Food Agric ; 103(1): 185-194, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35842518

RESUMO

BACKGROUND: The encapsulation of flavor and aroma compounds has great potential in foods, while effective preparation in the food industry is still a great challenge. Inspired by leather tanning, tannic acid (TA) was used for deep crosslinking through hydrogen bond-driven assembly on soy protein isolate for encapsulating limonene with a high loading ratio. RESULTS: The added TA changed the protein structure and formed a limonene-loaded microcomplex. The morphology of these microcomplexes changed from smooth to rough, followed by the formation of smooth nanoparticle aggregates, by changing the amount of TA. The encapsulation efficiency and loading ratio were increased from 0.78% and 4.30% to 59.32% and 45.78% after increasing TA from 1.875 to 60 mg mL-1 . The result of confocal laser scanning microscopy indicated that limonene is evenly distributed in microcomplexes. Additionally, the results of thermal stability demonstrated protection of limonene by soy protein-tannic acid microcomplex. CONCLUSION: It is suggested that the added TA improved the encapsulation efficiency and loading ratio. Limonene is loaded in the complex in two ways. The present research provides a new and easy path for the preparation of the non-thermal soy protein aroma carrier. © 2022 Society of Chemical Industry.


Assuntos
Antozoários , Proteínas de Soja , Animais , Limoneno , Proteínas de Soja/química , Taninos/química , Ligação de Hidrogênio
14.
Front Oncol ; 12: 961637, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212414

RESUMO

Tumor microenvironment (TME), which is characterized by hypoxia, widely exists in solid tumors. As a current research hotspot in the TME, hypoxia is expected to become a key element to break through the bottleneck of tumor treatment. More and more research results show that a variety of biological behaviors of tumor cells are affected by many factors in TME which are closely related to hypoxia. In order to inhibiting the immune response in TME, hypoxia plays an important role in tumor cell metabolism and anti-apoptosis. Therefore, exploring the molecular mechanism of hypoxia mediated malignant tumor behavior and therapeutic targets is expected to provide new ideas for anti-tumor therapy. In this review, we discussed the effects of hypoxia on tumor behavior and its interaction with TME from the perspectives of immune cells, cell metabolism, oxidative stress and hypoxia inducible factor (HIF), and listed the therapeutic targets or signal pathways found so far. Finally, we summarize the current therapies targeting hypoxia, such as glycolysis inhibitors, anti-angiogenesis drugs, HIF inhibitors, hypoxia-activated prodrugs, and hyperbaric medicine.

15.
Front Nutr ; 9: 942155, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204379

RESUMO

Background: Observational studies have suggested processed and red meat may increase the risk of cancer. However, the causal effects and direction between them were still unclear. We conducted two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of processed meat and red meat on the risk of nine common types of cancer, namely, lung, ovarian, endometrial, breast, kidney, gastric, prostate, skin, and oropharyngeal cancer. Methods: Genome-wide association studies (GWAS) for processed meat and red meat (pork, beef, and mutton) were obtained from the UK Biobank. GWAS of types of cancer in this study were extracted from the genetic consortia and the FinnGen consortium. The inverse variance weighted (IVW) was carried out as the main method for two-sample MR analysis. Sensitivity analyses were used to assess the robustness of the results. Results: Genetically predicted processed meat intake was causally associated with increased risk of lung cancer (OR [odds ratio] = 1.923, 95% CI = 1.084-3.409, P = 0.025). There is no convincing evidence for the associations between genetically determined processed meat, red meat, and the risk of other cancers we studied. Conclusion: Our results suggested that intake of processed meat may increase the risk of lung cancer. These findings provided no evidence to support that consumption of processed and red meat has a large effect on the risk of other cancers we studied. Further research is needed to clarify the results.

16.
Front Public Health ; 10: 990708, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36187670

RESUMO

Ultrasound, as a common clinical examination tool, inevitably has human errors due to the limitations of manual operation. Artificial intelligence is an advanced computer program that can solve this problem. Therefore, the relevant literature on the application of artificial intelligence in the ultrasonic field from 2011 to 2021 was screened by authors from the Web of Science Core Collection, which aims to summarize the trend of artificial intelligence application in the field of ultrasound, meanwhile, visualize and predict research hotspots. A total of 908 publications were included in the study. Overall, the number of global publications is on the rise, and studies on the application of artificial intelligence in the field of ultrasound continue to increase. China has made the largest contribution in this field. In terms of institutions, Fudan University has the most number of publications. Recently, IEEE Access is the most published journal. Suri J. S. published most of the articles and had the highest number of citations in this field (29 articles). It's worth noting that, convolutional neural networks (CNN), as a kind of deep learning algorithm, was considered to bring better image analysis and processing ability in recent most-cited articles. According to the analysis of keywords, the latest keyword is "COVID-19" (2020.8). The co-occurrence analysis of keywords by VOSviewer visually presented four clusters which consisted of "deep learning," "machine learning," "application in the field of visceral organs," and "application in the field of cardiovascular". The latest hot words of these clusters were "COVID-19; neural-network; hepatocellular carcinoma; atherosclerotic plaques". This study reveals the importance of multi-institutional and multi-field collaboration in promoting research progress.


Assuntos
Inteligência Artificial , COVID-19 , Bibliometria , Humanos , Redes Neurais de Computação , Publicações
17.
Front Cardiovasc Med ; 9: 927120, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119744

RESUMO

Background: Although epidemiological studies have shown a positive relationship between inflammatory bowel disease (IBD) and risk of cardiovascular disease (CVD) outcomes, a solid causal relationship has not been established. Thus, a two-sample Mendelian randomization (MR) study was conducted to explore the potential causal effect between IBD and CVD outcomes. Methods: We performed a two-sample MR analysis to analyze the causal effect of the IBD on CVD outcome by using summary-level genome-wide association studies of European descent. The inverse-variance weighted (IVW) method was used as the main MR analysis, with complementary analyses of MR Egger, maximum likelihood, weighted median, penalized weighted media, simple mode, weighted mode, and MR-PRESSO methods. Multiple sensitivity analyses were used to evaluate the robustness of our results. Results: All P-values were greater than 0.05 in the IVW method, showing no evidence of a causal association between circulating IBD and CVD. Similar results were observed by using other MR methods. No evidence of heterogeneity, pleiotropy, or outlier single-nucleotide polymorphisms was detected. Sensitivity analyses demonstrated the robustness of the results. Conclusion: The findings of this study provided no evidence to support that IBD has a large effect on risk of CVD outcomes, which is in contrast to many previous observational reports. Further studies are needed to determine the potential mechanism of association identified in observational studies.

18.
Molecules ; 27(13)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35807305

RESUMO

Essential oils have long been used to fight infections and treat various diseases. Peppermint (Mentha × piperita L.) is an herbal medicine that has been widely used in daily life since ancient times, and it has a wide range of applications in food, cosmetics, and medicine. Mint oil is refreshing because of its cool and comfortable smell; therefore, it is often used in ethnopharmacological studies. The present study investigated the effects of peppermint essential oil in electroencephalographic activity response to various visual stimuli. The electroencephalographic changes of participants during peppermint essential oil inhalation under white, red, and blue colour stimulations were recorded. A rapid Fourier transform analysis was used to examine the electroencephalograph power spectra of the various microstates induced by inhaling the oils. Peppermint essential oil had various effects on the brain when subjected to different visual stimuli. Alpha waves increased in the prefrontal area in the white-sniffing group, which facilitated learning and thinking. In the blue-sniffing group, the changes were less pronounced than those in the red group, and the increased alpha wave activity in the occipital area was more controlled, indicating that the participants' visual function increased in this state. Based on EEG investigations, this is the first study to indicate that vision influences the effects of peppermint essential oils. Hence, the results of this study support the use of essential oils in a broader context to serve as a resource for future studies on the effects of different types of essential oils.


Assuntos
Mentha , Óleos Voláteis , Eletroencefalografia , Humanos , Mentha piperita , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Olfato
19.
Front Oncol ; 12: 810774, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35515122

RESUMO

Background: Pancreatic cancer (PC) is a serious disease with high mortality. The tumor microenvironment plays a key role in the occurrence and development of PC. The purpose of this study is to analyze trends by year, country, institution, journal, reference and keyword in publications on the PC microenvironment and to predict future research hotspots. Methods: The Web of Science Core Collection was used to search for publications. We analyzed the contributions of various countries/regions, institutes, and authors and identified research hotspots and promising future trends using the CiteSpace and VOSviewer programs. We also summarized relevant completed clinical trials. Results: A total of 2,155 papers on the PC microenvironment published between 2011 and 2021 were included in the study. The number of publications has increased every year. The average number of citations per article was 32.69. The USA had the most publications, followed by China, and a total of 50 influential articles were identified through co-citation analysis. Clustering analysis revealed two clusters of keywords: basic research and clinical application. The co-occurrence cluster analysis showed glutamine metabolism, carcinoma-associated fibroblasts, oxidative phosphorylation as the highly concerned research topics of basic research in recently. The three latest hot topics in clinical application are liposomes, endoscopic ultrasound and photodynamic therapy. Conclusion: The number of publications and research interest have generally increased, and the USA has made prominent contributions to the study of the tumor microenvironment of PC. The current research hotspots mainly focus on energy metabolism in the hypoxic tumor microenvironment, cancer associated fibroblasts in regulating the tumor microenvironment, accurate diagnosis, drug delivery and new treatments.

20.
Food Chem ; 390: 133182, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35561505

RESUMO

In the present study, soy protein isolate was modified by tannic acid and used as a stabilizer for Pickering emulsions loaded with aroma compounds. The nanoparticles with tannic acid concentrations above 2 mg/mL were found to show great antioxidant properties. Essential oils, aroma compounds, and flavours can be stabilized by nanoparticles to form Pickering emulsions with a droplet diameter of<600 nm. E-nose analysis shows that nanoparticles provide outstanding protective functionalities for the 6 essential oils at 37 °C for 30 days. Further study of limonene and citral indicates that the nanoparticles afford nearly 60% protection against loss with a tannic acid concentration of 10 mg/mL. Furthermore, the nanoparticles also maintain the aroma of the beverages and lengthen the five-day shelf life. Overall, this research provides a sustainable, low-cost, and quickly prepared stabilizer for aroma compounds in foods.


Assuntos
Nanopartículas , Óleos Voláteis , Bebidas , Emulsões , Odorantes , Tamanho da Partícula , Proteínas de Soja , Taninos
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