Photobiomodulation with 630-nm LED Inhibits M1 Macrophage Polarization via STAT1 Pathway Against Sepsis-Induced Acute Lung Injury.

Background: Sepsis-induced acute lung injury (ALI) is a clinical syndrome characterized by excessive uncontrolled inflammation. Photobiomodulation such as light-emitting diode (LED) irradiation has been used to attenuate inflammatory disease. Objective: The protective effect of 630 nm LED irradiation on sepsis-induced ALI remains unknown. The purpose of this study was to investigate the role of 630 nm LED irradiation in sepsis-induced ALI and its underlying mechanism. Methods and results: C57BL/6 mice were performed cecal ligation and puncture (CLP) for 12 h to generate experimental sepsis models. Histopathology analysis showed that alveolar injury, inflammatory cells infiltration, and hemorrhage were suppressed in CLP mice after 630 nm LED irradiation. The ratio of wet/dry weigh of lung tissue was significantly inhibited by irradiation. The number of leukocytes was reduced in bronchoalveolar lavage fluid. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results and enzyme-linked immunosorbent assay showed that 630 nm LED irradiation significantly inhibited the mRNA and protein levels of M1 macrophage-related genes in the lung of CLP-induced septic mice. Meanwhile, LED irradiation significantly inhibited signal transducer and activator of transcription 1 (STAT1) phosphorylation in the lung of septic mice. In vitro experiments showed that 630 nm LED irradiation significantly inhibited M1 genes mRNA and protein expression in THP-1-derived M1 macrophages without affecting the cell viability. LED irradiation also significantly inhibited the level of STAT1 phosphorylation in THP-1-derived M1 macrophages. Conclusions: We concluded that 630 nm LED is promising as a treatment against ALI through inhibiting M1 macrophage polarization, which is associated with the downregulation of STAT1 phosphorylation.

Resource Utilization of Waste Cooking Oil Catalyzed by Na2CO3/ZSM-5.

A catalyst with a simple synthetic process and good catalytic performance was prepared using Na2CO3 as the active component and ZSM-5 as the carrier for the resource utilization of waste cooking oil. The structure of Na2CO3/ZSM-5 was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy, and the effects of parameters such as Na2CO3 loading, catalyst percentage, and reaction time on the yield of fatty acid methyl esters were investigated. The results showed that the conversion of waste cooking oil to fatty acid methyl esters yielded up to 96.89% when the Na2CO3 loading was 35%, the reaction temperature was 65 °C, the reaction time was 2 h, and the catalyst percentage was 1 wt %. The Na2CO3/ZSM-5 catalyst could be used to replace H2SO4 or NaOCH3 in the industrial treatment of waste cooking oil for its resource utilization.

An optimized 3D-printed capsule scaffold utilizing artificial neural network for the targeted delivery of chlorogenic acid to the colon.

Chlorogenic acid (CGA) is an important bioactive polyphenol with extensive biological properties. This study aimed to fabricate an optimized three-dimensional (3D)-printed capsule scaffold and CGA capsules for targeted delivery of hydrophobic CGA to the colon. The optimized printing parameters identified using the neural network model were a temperature of 170 °C, a printing speed of 20 mm/s, and a nozzle diameter of 0.3 mm. The capsules exhibited slow releasing properties of CGA, and the releasing rates of Eudragit®FS 30D-sealed capsules (due to more cracks and voids) were faster than those of Eudragit®S100-sealed capsules. The Ritger-peppas model was the best fitting model to describe the releasing process of CGA from 8 CGA capsules (R2 ≥ 0.98). All CGA capsules exhibited shear-thinning properties with stable sol-gel viscosity at low shear rates. FTIR spectra confirmed the formation of non-covalent bonds between CGA and the sol. Overall, the obtained 3D-printed capsules provided a promising carrier for the targeted delivery of CGA in the development of personalized dietary supplements.

Targeted metabolic reveals different part of maize in polyphenolic metabolites during germination and hypoglycemic activity analysis.

In this study, qualitative and quantitative analyses of phenolic compounds in the maize germinating seed embryo, radicle, and germ were performed at 0, 48, and 96 h post-germination, followed by the evaluation of their hypoglycemic activity. The results revealed the accumulation of 80 phenolics in different parts of germinated maize, of which 47, 48, and 53 were present in the seed embryo, radicle, and germ. After germination 22, 26, and 34 polyphenols were found to differential accumulate in the seed embryo, radicle, and germ. At 96 h post-germination, the content of monomeric phenols in the germ was higher than that in the radicle and seed embryo. Moreover, the inhibitory activity of polyphenols in the germ towards α-glucosidase and α-amylase was higher than that in the radicle and seed embryo. These results indicate that germination can effectively improve the type and content of phenolic compounds in different parts of maize.

LED irradiation at 630 nm alleviates collagen-induced arthritis in mice by inhibition of NF-κB-mediated MMPs production.

Matrix metallopreteinase (MMP), a family of matrix degrading enzyme, plays a significant role in persistent and irreversible joint damage in rheumatoid arthritis (RA). Photobiomodulatory therapy (PBMT) has become an emerging adjunct therapy for RA. However, the molecular mechanism of PBMT on RA remains unclear. The purpose of this study is to explore the effect of 630 nm light emitting diode (LED) irradiation on RA and its underly molecular mechanism. Arthritis clinic scores, histology analysis and micro-CT results show that 630 nm LED irradiation ameliorates collagen-induced arthritis (CIA) in mice with the reduction of the extents of paw swelling, inflammation and bone damage. 630 nm LED irradiation significantly reduces MMP-3 and MMP-9 levels and inhibits p65 phosphorylation level in the paws of CIA mice. Moreover, 630 nm LED irradiation significantly inhibits the mRNA and protein levels of MMP-3 and MMP-9 in TNF-α-treated MH7A cells, a human synovial cell line. Importantly, 630 nm LED irradiation reduces TNF-α-induced the phosphorylated level of p65 but not alters STAT1, STAT3, Erk1/2, JNK and p38 phosphorylation levels. Immunofluorescence result showed that 630 nm LED irradiation blocks p65 nuclear translocation in MH7A cells. In addition, other MMPs mRNA regulated by NF-κB were also significantly inhibited by LED irradiation in vivo and in vitro. These results indicates that 630 nm LED irradiation reduces the MMPs levels to ameliorate the development of RA by inhibiting the phosphorylation of p65 selectively, suggesting that 630 nm LED irradiation may be a beneficial adjunct therapy for RA.Graphical abstract.

Epigenetic modulation of Drp1-mediated mitochondrial fission by inhibition of S-adenosylhomocysteine hydrolase promotes vascular senescence and atherosclerosis.

AIMS: Vascular senescence, which is closely related to epigenetic regulation, is an early pathological condition in cardiovascular diseases including atherosclerosis. Inhibition of S-adenosylhomocysteine hydrolase (SAHH) and the consequent increase of S-adenosylhomocysteine (SAH), a potent inhibitor of DNA methyltransferase, has been associated with an elevated risk of cardiovascular diseases. This study aimed to investigate whether the inhibition of SAHH accelerates vascular senescence and the development of atherosclerosis. METHODS AND RESULTS: The case-control study related to vascular aging showed that increased levels of plasma SAH were positively associated with the risk of vascular aging, with an odds ratio (OR) of 3.90 (95% CI, 1.17-13.02). Elevated pulse wave velocity, impaired endothelium-dependent relaxation response, and increased senescence-associated ß-galactosidase staining were observed in the artery of SAHH+/- mice at 32 weeks of age. Additionally, elevated expression of p16, p21, and p53, fission morphology of mitochondria, and over-upregulated expression of Drp1 were observed in vascular endothelial cells with SAHH inhibition in vitro and in vivo. Further downregulation of Drp1 using siRNA or its specific inhibitor, mdivi-1, restored the abnormal mitochondrial morphology and rescued the phenotypes of vascular senescence. Furthermore, inhibition of SAHH in APOE-/- mice promoted vascular senescence and atherosclerosis progression, which was attenuated by mdivi-1 treatment. Mechanistically, hypomethylation over the promoter region of DRP1 and downregulation of DNMT1 were demonstrated with SAHH inhibition in HUVECs. CONCLUSIONS: SAHH inhibition epigenetically upregulates Drp1 expression through repressing DNA methylation in endothelial cells, leading to vascular senescence and atherosclerosis. These results identify SAHH or SAH as a potential therapeutic target for vascular senescence and cardiovascular diseases.

Low glycemic index potato biscuits alleviate physio-histological damage and gut dysbiosis in rats with type-2 diabetes mellitus induced by high-sugar and high-fat diet and streptozotocin.

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes globally and poses a major concern for human health. This study aimed to investigate the effects on T2DM of low-glycemic index (GI) potato biscuits with oat bran and inulin as functional additives. T2DM was induced in rats by streptozotocin (STZ) and a high-sugar and high-fat diet. The alleviation of T2DM by low-GI potato biscuits at different doses was evaluated based on the analysis of glycolipid levels, histological observations, inflammatory markers, and gut microbiota structure. Compared to wheat biscuits, low-GI potato biscuits resulted in lower postprandial blood glucose levels. After 8 weeks of intervention, fasting blood sugar levels were 16.9% lower in T2DM rats fed high-dose low-GI potato biscuits than in untreated T2DM rats. Moreover, the intervention with low-GI potato biscuits significantly alleviated T2DM-induced pathological damage, glucose and lipid metabolic disorders, and inflammation by reversing the levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, transforming growth factor-ß, interleukin-1ß, interleukin-6 and tumor necrosis factor-α. Moreover, the levels of short-chain fatty acids and gut microbiota structure in T2DM rats were significantly reversed. The abundance of beneficial bacteria (e.g., Bifidobacterium, Lachnoclostridium, Roseburia) in the gut of T2DM rats was significantly increased whereas the abundance of Escherichia-Shigella and Desulfovibrio decreased. The present study revealed that low-GI potato biscuits alleviated damages caused by high-sugar and high-fat diet- and STZ-induced T2DM in rats, as well as reversed disturbances in the gut microbiota. Thus, low-GI potato biscuits are potentially beneficial to T2DM patients.

ST6GAL1 inhibits metastasis of hepatocellular carcinoma via modulating sialylation of MCAM on cell surface.

The poor prognosis of hepatocellular carcinoma (HCC) is mainly because of its high rate of metastasis. Thus, elucidation of the molecular mechanisms underlying HCC metastasis is of great significance. Glycosylation is an important post-translational modification that is closely associated with tumor progression. Altered glycosylation including the altered sialylation resulting from aberrant expression of ß-galactoside α2,6 sialyltransferase 1 (ST6GAL1) has long been considered as an important feature of cancer cells. However, there is limited information on the roles of ST6GAL1 and α2,6 sialylation in HCC metastasis. Here, we found that ST6GAL1 and α2,6 sialylation were negatively correlated with the metastatic potentials of HCC cells. Moreover, ST6GAL1 overexpression inhibited migration and invasion of HCC cells in vitro and suppressed HCC metastasis in vivo. Using a metabolic labeling-based glycoproteomic strategy, we identified a list of sialylated proteins that may be regulated by ST6GAL1. In particular, an increase in α2,6 sialylation of melanoma cell adhesion molecule (MCAM) inhibited its interaction with galectin-3 and decreased its expression on cell surface. In vitro and in vivo analysis showed that ST6GAL1 exerted its function in HCC metastasis by regulating MCAM expression. Finally, we found the relative intensity of sialylated MCAM was negatively correlated with tumor malignancy in HCC patients. Taken together, these results demonstrate that ST6GAL1 may be an HCC metastasis suppressor by affecting sialylation of MCAM on cell surface, which provides a novel insight into the roles of ST6GAL1 in HCC progression and supports the functional complexity of ST6GAL1 in a cancer type- and tissue type-specific manner.

POR overexpression induces tamoxifen-resistance in breast cancer through the STAT1/c-Myc pathway.

Breast cancer is the most common cancer in women worldwide. Although tamoxifen (TAM), a selective estrogen receptor (ER) modulator, is widely used to treat ER-positive breast cancers, resistance to TAM remains a major clinical problem. NADPH-dependent cytochrome P450 reductase (POR) is known to participate in drug metabolism and steroid metabolism. Recent studies showed that high POR expression was correlated with poor outcomes in triple-negative breast cancer (TNBC), and POR might be a prognostic biomarker in TNBC. However, the role of POR in TAM resistance is still elusive. In this study, we found that high POR expression was associated with poor prognosis of ER-positive and TAM-treated breast cancer patients. In addition, COX analysis showed that POR expression was an independent prognostic biomarker for ER-positive as well as TAM-treated breast cancer patients. Furthermore, our results suggested that POR overexpression promoted TAM resistance by activating the STAT1/c-Myc pathway in ER-positive breast cancer cells. Immunohistochemical analysis showed that high POR/STAT1 expression was correlated with poor prognosis in TAM-treated breast cancer patients. Notably, combined treatment with TAM and a specific STAT1 inhibitor Fludarabine was more effective for inhibiting TAM-resistant breast cancer cells. Altogether, our findings suggested that POR overexpression induced TAM resistance through STAT1/c-Myc pathway and might serve as an independent prognostic biomarker in TAM-treated breast cancer patients. Combining TAM and STAT1 inhibitors might be an effective strategy for treating POR-induced TAM-resistant breast cancer.

Research on the main methods of core strength training in sprinters / Pesquisa sobre os principais métodos de treino de força do core em velocistas / Investigación sobre los principales métodos de entrenamiento de fuerza del core en velocistas

ABSTRACT Introduction With the development of increasingly competitive sports, coaches began experimenting with new methods for training athletes. Although among the most explored training methods is core strength training, a set of muscle groups that stabilize the trunk and hips, there are few studies on the effectiveness of this training dedicated to sprinters. Objective This paper investigates the training method of sprinters based on core strength training, studying the method and its influence on athletes' performance. Methods Sixteen athletes with similar technical levels and physical fitness were selected, and professional coaches were invited to test the training samples. The athletes were randomly assigned to the experimental and control group (8 in each). The experimental group received core strength training for eight weeks, while the control group received general training. Results Off-core training affected the ankle joint angle of the support leg and the ankle joint angle of the swing leg (P < 0.01). After eight weeks of training, the performance of both groups improved without considerable differences. The high jump results of the athletes in the experimental group also improved compared to the previous training. Conclusion The physical function of athletes can be improved through core strength training to improve the sprinters' competitive level and technical ability. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução Com o desenvolvimento de esportes cada vez mais competitivos, os treinadores começaram a experimentar novos métodos para a formação de atletas. Embora entre os métodos de treinamento mais explorados encontra-se o treino do core, conjunto de grupos musculares estabilizadores do tronco e quadril, há poucos estudos sobre a efetividade desse treino dedicado a atletas velocistas. Objetivo Este artigo investiga o método de treino de velocistas baseado no treinamento de força do core, estudando o método e a influência no desempenho do atleta. Métodos Foram selecionados 16 atletas com nível técnico e aptidão física similares, treinadores profissionais foram convidados a testar as amostras de treino. Os atletas foram aleatoriamente designados para o grupo experimental e controle (8 em cada). O grupo experimental recebeu treinamento de força do core por 8 semanas, enquanto o grupo controle recebeu treinamento geral. Resultados O treinamento de fora do core teve um efeito no ângulo da articulação do tornozelo da perna de apoio e no ângulo da articulação do tornozelo da perna de balanço (P < 0,01). Após oito semanas de treinamento, o desempenho de ambos grupos melhoraram sem diferenças consideráveis. Os resultados do salto em altura dos atletas do grupo experimental também melhoraram em relação ao treinamento anterior. Conclusão A função física dos atletas pode ser aprimorada através do treinamento de força do core, de modo a melhorar ainda mais o nível competitivo e a capacidade técnica dos velocistas. Nível de evidência II; Estudos terapêuticos - investigação dos desfechos do tratamento.

RESUMEN Introducción Con el desarrollo de deportes cada vez más competitivos, los entrenadores comenzaron a experimentar nuevos métodos para el entrenamiento de los atletas. Aunque entre los métodos de entrenamiento más explorados se encuentra el entrenamiento del core, un conjunto de grupos musculares que estabilizan el tronco y las caderas, hay pocos estudios sobre la eficacia de este entrenamiento dedicado a los atletas velocistas. Objetivo Este artículo investiga el método de entrenamiento de los velocistas basado en el entrenamiento de la fuerza del core, estudiando el método y la influencia en el rendimiento del atleta. Métodos Se seleccionaron dieciséis atletas con un nivel técnico y una aptitud física similares, y se invitó a entrenadores profesionales a probar las muestras de entrenamiento. Los atletas fueron asignados aleatoriamente al grupo experimental y al de control (8 en cada uno). El grupo experimental recibió un entrenamiento del core durante 8 semanas, mientras que el grupo de control recibió un entrenamiento general. Resultados El entrenamiento fuera del core tuvo un efecto sobre el ángulo de la articulación del tobillo de la pierna de apoyo y el ángulo de la articulación del tobillo de la pierna de impulso (P < 0,01). Tras ocho semanas de entrenamiento, el rendimiento de ambos grupos mejoró sin diferencias considerables. Los resultados del salto de altura de los atletas del grupo experimental también mejoraron en relación con el entrenamiento anterior. Conclusión La función física de los atletas velocistas puede mejorarse mediante el entrenamiento del core, con el fin de mejorar aún más su nivel competitivo y su capacidad técnica. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

Strength training on soccer players' kicking stability / Treinamento de força na estabilidade nos chutes dos jogadores de futebol / Entrenamiento de fuerza en la estabilidad de las patadas de los futbolistas

ABSTRACT Introduction: The physical condition of soccer players in sports competitions has improved over the years. The optimal performance of their professional skills in competitive conditions has become essential for victory in soccer matches. Objective: This paper explores the effects of different methods employing strength training on soccer kicking techniques aiming at the set that best enables the accuracy of hits through its stability. Methods: 36 soccer players were randomly divided into the experimental and control groups, with no statistical difference in fitness and the comprehensive ability characteristics of the players. Both subjects were trained for 12 weeks; only the experimental group received the special strength training intervention for stability. The passing score of the curve ball in 20-meter dribbling was measured before and after training. The data were statistically treated. Results: The kicking accuracy of soccer players in the experimental group differed from before the test (P<0.01). There was also a significant difference in kicking accuracy in the control group (P<0.05). The 20-meter arc dribbling scores in the experimental group were statistically significant compared to those before the test (P<0.05). There was no significant difference between the control group and the test scores on curve ball passing scores in 20-meter dribbling (P>0.05). Conclusion: Functional strength methods to achieve the goal of improving kicking accuracy in athletes have been developed. Coaches should pay attention to physical training, an attitude that encourages players to achieve sufficient physical strength for soccer games with their kicking skills. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A condição física dos jogadores de futebol nas competições esportivas tem se aprimorado ao longo dos anos e o desempenho ótimo de suas habilidades profissionais em condições competitivas tornou-se um fator essencial para a vitória nas partidas de futebol. Objetivo: Este artigo explora os efeitos de diferentes métodos empregando o treinamento de força sobre as técnicas de chute de futebol visando o conjunto que melhor capacita a precisão de acertos através de sua estabilidade. Métodos: 36 jogadores de futebol foram divididos aleatoriamente, sem diferença estatística de aptidão física e as características de capacidade abrangente dos jogadores, em grupo experimental e controle. Ambos os grupos de sujeitos foram treinados durante 12 semanas, somente o grupo experimental recebeu a intervenção especial de treinamento de força para estabilidade. A pontuação de passe da bola curva em drible de 20 metros foi medida antes e depois do treino. Os dados foram tratados estatisticamente. Resultados: A precisão do chute dos jogadores de futebol no grupo experimental foi diferente daquela antes do teste (P<0,01). Também houve uma diferença significativa na precisão de chutes no grupo de controle (P<0,05). As pontuações dos dribles de arco de 20 metros no grupo experimental foram estatisticamente significativas em comparação com aquelas antes do teste (P<0,05). Não houve diferença significativa entre o grupo de controle e os resultados do teste na pontuação de passe da bola curva em drible de 20 metros (P>0,05). Conclusão: Métodos de força funcional para alcançar o objetivo de melhorar a precisão de chute nos atletas foram desenvolvidos. Os treinadores devem prestar atenção ao treinamento físico, atitude que incentiva aos jogadores atingirem a força física suficiente para os jogos de futebol com suas habilidades de chute. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La condición física de los futbolistas en las competiciones deportivas ha ido mejorando a lo largo de los años y el rendimiento óptimo de sus habilidades profesionales en condiciones competitivas se ha convertido en un factor esencial para la victoria en los partidos de fútbol. Objetivo: Este trabajo explora los efectos de diferentes métodos que emplean el entrenamiento de la fuerza en las técnicas de pateo de fútbol con el objetivo de encontrar el conjunto que mejor permita la precisión de los golpes a través de su estabilidad. Métodos: Se dividieron aleatoriamente 36 jugadores de fútbol, sin diferencias estadísticas en cuanto a la aptitud física y las características de capacidad integral de los jugadores, en grupo experimental y grupo de control. Ambos grupos de sujetos fueron entrenados durante 12 semanas, sólo el grupo experimental recibió la intervención especial de entrenamiento de fuerza para la estabilidad. Se midió la puntuación del pase de la pelota curva en el regateo de 20 metros antes y después del entrenamiento. Los datos fueron tratados estadísticamente. Resultados: La precisión de las patadas de los futbolistas del grupo experimental fue diferente a la de antes de la prueba (P<0,01). También hubo una diferencia significativa en la precisión de las patadas en el grupo de control (P<0,05). Las puntuaciones del regateo en arco de 20 metros en el grupo experimental fueron estadísticamente significativas en comparación con las anteriores a la prueba (P<0,05). No hubo diferencias significativas entre el grupo de control y las puntuaciones de la prueba en las puntuaciones de los pases de balón curvo en el regateo de 20 metros (P>0,05). Conclusión: Se han desarrollado métodos de fuerza funcional para lograr el objetivo de mejorar la precisión de las patadas en los atletas. Los entrenadores deben prestar atención a la preparación física, una actitud que anima a los jugadores a conseguir la fuerza física suficiente para los partidos de fútbol con sus habilidades de pateo. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Heat Shock Protein Is Associated with Inhibition of Inflammatory Cytokine Production by 630 nm Light-Emitting Diode Irradiation in Fibroblast-Like Synoviocytes Based on RNA Sequencing Analysis.

Background: Inflammatory cytokine secretion from fibroblast-like synoviocytes (FLS) plays a vital role in the pathological process of rheumatoid arthritis (RA). Photobiomodulation (PBM) has been widely used in the treatment of RA. However, the mechanism of PBM in RA has not been clarified. Objective: In this study, we investigated the underlying mechanism of 630 nm light-emitting diode (LED) irradiation on anti-inflammation using mRNA sequencing analysis. Methods and results: Reverse transcription (RT)-quantitative polymerase chain reaction (RT-qPCR) results showed that 630 nm LED irradiation significantly inhibited interleukin (IL)-1ß, IL-6, and IL-8 mRNA expression in rheumatoid arthritis fibroblast synovial cells (RA-FLS) and MH7A cells. A total of 1730 differentially expressed genes (DEGs) were identified between tumor necrosis factor α (TNF-α)+LED and TNF-α-treated RA-FLS and 1219 DEGs in MH7A cells by mRNA sequencing analysis. A total of 646 intersecting DEGs from the 2 cell models were used for gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Protein-protein interaction (PPI) network of DEGs was used, and 502 nodes and 1452 edges were found. A total of 14 clusters were generated in MCODE, and the top 3 clusters were selected as hub modules. PPI network showed that most of the nodes were DEGs of the heat shock protein (HSP) family. RT-qPCR verified that 630 nm LED irradiation significantly increased HSP70 mRNA expression in FLS. Conclusions: Taken together, our results revealed the correlation between HSP70 and the inhibition of inflammation caused by 630 nm LED irradiation. These findings suggested that HSP may be a novel target of 630 nm LED irradiation to alleviate inflammation in the treatment of RA.

Thematic trends and knowledge structure map of sentinel lymph node biopsy for breast cancer: a bibliometric analysis from 2010 to 2019.

Background: Breast cancer is the leading cancer-related deaths among women. Although great progress has been made in clinical surgical treatment, it is still urgently needed to look for a treatment model with smaller wounds, lower damage, and a better prognosis. Sentinel lymph node biopsy (SLNB) is a minimally invasive technique for breast cancer treatment, which can correctly assess the patients' condition, prognosis, and treatment response. Methods: We performed a PubMed-based bibliometric analysis to investigate publication trends of SLNB in breast cancer and determined the annual distribution of annual publication numbers, countries, authors, languages, journals, and high-frequency major Medical Subject Headings (MeSH) terms. Results: The results showed that the literature on SLNB in breast cancer has shown an upward trend, and stabilized with the most English literature in the past decade at least. The United States was the country with the most publications from 2010 to 2019. M Ahemd was the first-author who had published the most documents related to SLNB in breast cancer since 2010. The most high-frequency main MeSH words were breast neoplasms/pathology, breast neoplasms/surgery and SLNB. Conclusions: Through bicluster analysis, we divided the related articles of SLNB in breast cancer field from 2010 to 2019 into 4 clusters. Among them, indications for SLNB in breast cancer and detection of lymph node metastases and tracking methods for SLNB were considered to be current research hotspots, while assessment of axillary lymph nodes in neoadjuvant chemotherapy and application of SLNB was a potential hotspot.

Higher S-adenosylhomocysteine and lower ratio of S-adenosylmethionine to S-adenosylhomocysteine were more closely associated with increased risk of subclinical atherosclerosis than homocysteine.

Aim: To examine the relationship of C1 metabolites of the methionine cycle with the risk of subclinical atherosclerosis (SA) in the Chinese population. Methods: A total of 2,991 participants aged 45-75 years old were included for data analyses based on the baseline data of the Guangzhou Nutrition and Health Cohort. Three core serum methionine metabolites including serum S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and homocysteine (Hcy) were measured by UPLC-MS/MS. SA was determined by B-mode ultrasound measured carotid intima-media thickness (CIMT) at the common artery and bifurcation segments. Multivariable logistic and linear regression models were performed to estimate the associations of C1 metabolites of the methionine cycle with SA risk or CIMT. Results: After controlling for potential cofounders and other C1 metabolites, in comparison with the lowest quartile, participants in the highest quartile had lower risk of SA by 27.6% (OR = 0.724; 95% CI:0.563-0.93, P trend = 0.007) for SAM and 32.2% (OR = 0.678; 95% CI:0.538-0.855, P trend < 0.001) for SAM/SAH, while increased SA risk by 27.9% (OR = 1.279; 95% CI: 1.065-1.535, P trend < 0.001) for SAH. No significant association was observed for Hcy with SA after further adjustment of SAH and SAM. The results of multivariable linear regression showed similar findings. The highest two standardized coefficients were observed for SAH (ß = 0.104 for CCA and 0.121 for BIF, P< 0.001) and SAM/SAH (ß = -0.071 for CCA and -0.084 for BIF, P< 0.001). Subgroup analyses suggested more evident associations of SAH with SA were observed in participants of higher cardiovascular risk profiles. Conclusion: Our cross-sectional data showed higher serum SAH, but lower SAM/SAH were independently associated with increased risk of SA among the Chinese middle-aged and elderly population.

Inhibition of S-adenosylhomocysteine hydrolase induces endothelial senescence via hTERT downregulation.

BACKGROUND AND AIMS: It has been established that endothelial senescence plays a critical role in the development of atherosclerosis. Elevated S-adenosylhomocysteine (SAH) level induced by inhibition of S-adenosylhomocysteine hydrolase (SAHH) is one of the risk factors of atherosclerosis; however, the interplay between endothelial senescence and inhibition of SAHH is largely unknown. METHODS: Human umbilical vein endothelial cells (HUVECs) after serial passage were used. SAHH-specific inhibitor adenosine dialdehyde (ADA) and SAHH siRNA treated HUVECs and SAHH+/-mice were used to investigate the effect of SAHH inhibition on endothelial senescence. RESULTS: HUVECs exhibited distinct senescence morphology as HUVECs were passaged, together with a decrease in intracellular SAHH expression and an increase in intracellular SAH levels. SAHH inhibition by ADA or SAHH siRNA elevated SA ß-gal activity, arrested proliferation, and increased the expression of p16, p21 and p53 in HUVECs and the aortas of mice. In addition, decreased expression of hTERT and reduced occupancy of H3K4me3 over the hTERT promoter region were observed following SAHH inhibition treatment. To further verify the role of hTERT in the endothelial senescence induced by SAHH inhibition, hTERT was overexpressed with a plasmid vector under CMV promoter. hTERT overexpression rescued the senescence phenotypes in endothelial cells induced by SAHH inhibition. CONCLUSIONS: SAHH inhibition induces endothelial senescence via downregulation of hTERT expression, which is associated with attenuated histone methylation over the hTERT promoter region.

S-adenosylhomocysteine induces cellular senescence in rat aorta vascular smooth muscle cells via NF-κB-SASP pathway.

Vascular aging plays an important role in the development and progression of atherosclerosis (AS) , and one-carbon metabolism dysfunction will lead to Vascular Smooth Muscle Cells (VSMCs) senescence, which contributes to vascular senescence. However, the mechanisms underlying the role of VSMCs senescence in AS remain unclear. This study aimed to evaluate S-adenosyl-homocysteine (SAH) as a one-carbon metabolite that affects VSMCs senescence. We treated Rat Aorta Smooth Muscle Cells (RASMCs) with S-adenosylhomocysteine Hydrolase (SAHH) inhibitor, adenosine-2,3-dialdehyde (ADA) and SAHH siRNA to examine the effect of elevated SAH levels on RASMCs phenotypes. SAHH inhibition induced RASMCs senescence, as demonstrated by the manifestation of senescence-associated secretory phenotype in cells and induction of senescence in pre-senescent RASMCs. Furthermore, we found that SAHH inhibition induced CpG island demethylation in the promoter of NF-κB, a molecule that drives the pro-inflammatory response of the cells manifesting the senescence-associated secretory phenotype (SASP). Overall, these findings indicate that the elevated intracellular SAH levels could be targeted to ameliorate vascular aging.

Web Crawling and mRNA Sequencing Analyze Mechanisms of Photobiomodulation.

Background: Photobiomodulation (PBM) is praised as a promising physical therapy, which has many advantages, such as being noninvasive and painless. However, the mechanisms are not fully elucidated. Methods: Using web crawling, mRNA sequence, and bioinformatics analysis, we selected genes, functional annotation, and mechanisms. The expressions of inflammatory cytokines were measured using quantitative real-time PCR (RT-qPCR). Results: A total of 146 human genes and 57 pathways were identified about PBM. The 630 nm light-emitting diode (LED)-stimulated-MH7A cells were sequenced to further analyze the mechanism of PBM. Two thousand nine hundred fifty differentially expressed genes were identified, and the gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to better understand functions and pathways. The 12 pathways were matched with the KEGG results of PBM and MH7A cells. A protein-protein interaction network was performed among genes in 12 pathways, and 10 outstanding proteins were identified. Importantly, the 9 genes were predicted with potential research value. And we also demonstrated that expression of inflammatory factors [interleukin (IL)-6, IL-1ß, IL-8, and matrix metalloproteinase-3 (MMP-3)] was reduced; meanwhile, the expression of anti-inflammatory factor IL-10 was promoted after 630 nm LED. Conclusions: Using web crawling, bioinformatics analysis, and mRNA sequence, we obtained 9 key genes and 12 important pathways about PBM. Importantly, we demonstrated the anti-inflammatory effect of 630 nm LED red light by RT-qPCR.

Association of serum methionine metabolites with non-alcoholic fatty liver disease: a cross-sectional study.

BACKGROUND AND PROJECT: Non-alcoholic fatty liver disease (NAFLD) is viewed as the hepatic manifestation of metabolic syndrome. Methionine metabolites have been linked to metabolic syndrome and its related diseases. Whether serum methionine metabolites levels are associated with NAFLD remains unclear. The study aimed to assess the association between methionine metabolites and NAFLD. METHODS: This cross-sectional study included a total of 2814 individuals aged 40-75 years old. All participants underwent anthropometric measurements, laboratory tests, dietary assessment and abdominal ultrasonography. Multivariable logistic regression analysis was performed to estimate the association of methionine metabolites with NAFLD. RESULTS: Overall, 1446 with and 1368 without NAFLD were enrolled in this study. Participants with NAFLD had significantly higher serum S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and homocysteine (Hcy) levels, and a lower S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio than those without NAFLD (all P < 0.001). After adjusting multiple confounders, odds ratios (95% confidence interval) for quartile 4 versus quartile 1 of SAH, Hcy and SAM/SAH ratio were 1.65 (1.27-2.14), 1.63 (1.26-2.12) and 0.63 (0.49-0.83), respectively (all P for trend < 0.01). In addition, serum SAH, Hcy levels and SAM/SAH ratio were significantly correlated with the degree of hepatic steatosis (all P for trend < 0.001). CONCLUSION: Elevated serum SAH, Hcy levels and lower SAM/SAH ratio may be independently associated with the presence of NAFLD in middle-aged and elder Chinese.

Genome-Wide Identification and Gene Expression Analysis of the OTU DUB Family in Oryza sativa.

Ovarian tumor domain (OTU)-containing deubiquitinating enzymes (DUBs) are an essential DUB to maintain protein stability in plants and play important roles in plant growth development and stress response. However, there is little genome-wide identification and analysis of the OTU gene family in rice. In this study, we identified 20 genes of the OTU family in rice genome, which were classified into four groups based on the phylogenetic analysis. Their gene structures, conserved motifs and domains, chromosomal distribution, and cis elements in promoters were further studied. In addition, OTU gene expression patterns in response to plant hormone treatments, including SA, MeJA, NAA, BL, and ABA, were investigated by RT-qPCR analysis. The results showed that the expression profile of OsOTU genes exhibited plant hormone-specific expression. Expression levels of most of the rice OTU genes were significantly changed in response to rice stripe virus (RSV), rice black-streaked dwarf virus (RBSDV), Southern rice black-streaked dwarf virus (SRBSDV), and Rice stripe mosaic virus (RSMV). These results suggest that the rice OTU genes are involved in diverse hormone signaling pathways and in varied responses to virus infection, providing new insights for further functional study of OsOTU genes.

Resveratrol enhances trans-intestinal cholesterol excretion through selective activation of intestinal liver X receptor alpha.

Resveratrol (RSV) is a dietary polyphenol with well-documented cardio-protective activity, but its effects on blood cholesterol levels remain to be established. Due to its poor bioavailability, tissue accumulation of RSV is extremely low except for that in the small intestine. In the present study, we aimed to investigate the dose-dependent effects of RSV on blood cholesterol levels and the involvement of small intestine in the cholesterol-lowering impacts of RSV. Mice were administrated with RSV at various doses with high-fat diet (HFD) or high-fat and high-cholesterol diet (HCD) for 12 weeks. The fecal neutral sterol contents were analyzed, and intestinal perfusion test was performed. An enteric barrier model using Caco-2 cells was established. We observed that RSV reduced blood cholesterol levels in a dose-dependent manner in mice fed with HFD or HCD. Further investigation revealed that RSV administration increased the bile acid pool size but did not affect cholesterol consumption or de novo cholesterol synthesis. Interestingly, RSV promoted trans-intestinal cholesterol excretion (TICE) by 2-fold in the intestinal perfusion test. In addition, RSV upregulated the expressions of ATP-binding cassette sub-family G member 5 or 8 (Abcg5/8) and ATP-binding cassette sub-family B member 1a or 1b (Abcb1a/b) by up to 8 times in the duodenum mucosa but not in the liver. RSV also significantly downregulated the expression of intestinal Niemann-Pick C1-Like 1 (Npc1l1). Knock-down of liver X receptor alpha (LXRα) but not Sirt1 by siRNA significantly blocked RSV-induced cholesterol excretion in Caco-2 cells. In conclusion, RSV could decrease circulating cholesterol levels through enhancing TICE and limiting cholesterol absorption via selective activation of intestinal LXRα.