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Canagliflozin (CAN) regulates intracellular glucose metabolism by targeting sodium-glucose co-transporter 2 (SGLT2) and intracellular glucose metabolism affects inflammation. In this ...study, we hypothesized that CAN might exert anti-inflammatory effects. The anti-inflammatory effects and action mechanisms of CAN were assayed in lipopolysaccharide (LPS)-induced RAW264.7 and THP-1 cells and NIH mice. Results showed that CAN significantly inhibited the production and release of interleukin (IL)-1, IL-6, or tumor necrosis factor-α (TNF-α) in the LPS-induced RAW264.7 and THP-1 cells, and mice. CAN also significantly inhibited intracellular glucose metabolism and 6-phosphofructo-2-kinase (PFK2) expression. CAN increased the levels of sequestosome-1 (SQSTM1/p62), upregulated the ratios of microtubule-associated protein 1A/1B-light chain 3 (LC3) II to I, promoted the formation of LC3 puncta, and enhanced the activities of lysosome. The inhibition of autophagy by 3-methyladenine (3-MA) reversed the effects of CAN on IL-1α levels. Increased autophagy might be associated with increased AMP-activated protein kinase (AMPK) phosphorylation. Interestingly, p62 demonstrated good co-localization with IL-1α and possibly mediated IL-1α degradation. CAN-induced increase in p62 was dependent on the nuclear factor kappa B (NFκB) signaling pathway. These results indicated that CAN might exert anti-inflammatory effects by inhibiting intracellular glucose metabolism and promoting autophagy. Attenuated glucose metabolism by PFK2, increased autophagy flow by AMPK, and increased p62 levels by NFκB might be responsible for the molecular mechanisms of CAN. This drug might serve as a new promising anti-inflammatory drug for acute or chronic inflammatory diseases via independent hypoglycemic mechanisms. This drug might also be used as an important reference for similar drug research and development by targeting intracellular glucose metabolism and autophagy in immune cells.
Abstract
Abnormal H
2
S concentration in coal mine gas is a serious threat to normal mining activities, which has caused serious loss of life and property in many coal mines. This study explores the ...genesis and influencing factors of abnormal H
2
S concentration in coal mine gas, taking the Xishan coal mine in the Fukang mining area as a case study. The H
2
S formation by bacterial sulfate reduction (BSR) is simulated with a bacterial culture experiment and that by thermochemical sulfate reduction (TSR) is simulated with a thermal reduction experiment. The potential for a magmatic genesis is assessed using data regarding the tectonic evolution and history of magma intrusion in the study area. The factors influencing H
2
S formation and enrichment are then analyzed by a comprehensive consideration of the characteristics of coal, the gas composition, the coal seam groundwater geochemistry and other geological factors in the study area. The results show that the study area meets the necessary conditions for the BSR process to operate and that there is widespread BSR derived H
2
S. TSR genesis H
2
S mainly forms in coal fire areas and their vicinity, while there is little contribution from magmatically formed H
2
S. The concentration of H
2
S is negatively correlated with the buried depth of the coal seam, the concentrations of CH
4
, N
2
and CO
2
, and the ash yield; and it is positively correlated with the volatiles yield and total sulfur content. In addition, in areas with abnormally high H
2
S concentration, the concentration of SO
4
2−
is obviously lower, HCO
3
−
+ CO
3
2−
concentration is higher, and the HCO
3
−
/SO
4
2−
value is larger than that in non-anomalous areas. Geologically, H
2
S enrichment is found to be controlled by lithology, tectonism, and hydrogeological conditions. Moreover, the results of predictive modeling show that areas prone to abnormal H
2
S concentration are generally spatially correlated with coal fire areas. In this study, the genetic types of H
2
S and the factors controlling their formation and retention are discussed, producing research results that have guiding significance for the prediction and prevention of the coal mine disasters that arises from abnormal H
2
S concentration.
In bioinformatics, the rapid development of gene sequencing technology has produced an increasing amount of microarray data. This type of data shares the typical characteristics of small sample size ...and high feature dimensions. Searching for biomarkers from microarray data, which expression features of various diseases, is essential for the disease classification. feature selection has therefore became fundemental for the analysis of microarray data, which designs to remove irrelevant and redundant features. There are a large number of redundant features and irrelevant features in microarray data, which severely degrade the classification effectiveness. We propose an innovative feature selection method with the goal of obtaining feature dependencies from a priori knowledge and removing redundant features using spectral clustering. In this paper, the graph structure is firstly constructed by using the gene interaction network as a priori knowledge, and then a link prediction method based on graph neural network is proposed to enhance the graph structure data. Finally, a feature selection method based on spectral clustering is proposed to determine biomarkers. The classification accuracy on DLBCL and Prostate can be improved by 10.90% and 16.22% compared to traditional methods. Link prediction provides an average classification accuracy improvement of 1.96% and 1.31%, and is up to 16.98% higher than the published method. The results show that the proposed method can have full use of a priori knowledge to effectively select disease prediction biomarkers with high classification accuracy.
In the field of genomics and personalized medicine, it is a key issue to find biomarkers directly related to the diagnosis of specific diseases from high-throughput gene microarray data. Feature ...selection technology can discover biomarkers with disease classification information.
We use support vector machines as classifiers and use the five-fold cross-validation average classification accuracy, recall, precision and F1 score as evaluation metrics to evaluate the identified biomarkers. Experimental results show classification accuracy above 0.93, recall above 0.92, precision above 0.91, and F1 score above 0.94 on eight microarray datasets.
This paper proposes a two-stage hybrid biomarker selection method based on ensemble filter and binary differential evolution incorporating binary African vultures optimization (EF-BDBA), which can effectively reduce the dimension of microarray data and obtain optimal biomarkers. In the first stage, we propose an ensemble filter feature selection method. The method combines an improved fast correlation-based filter algorithm with Fisher score. obviously redundant and irrelevant features can be filtered out to initially reduce the dimensionality of the microarray data. In the second stage, the optimal feature subset is selected using an improved binary differential evolution incorporating an improved binary African vultures optimization algorithm. The African vultures optimization algorithm has excellent global optimization ability. It has not been systematically applied to feature selection problems, especially for gene microarray data. We combine it with a differential evolution algorithm to improve population diversity.
Compared with traditional feature selection methods and advanced hybrid methods, the proposed method achieves higher classification accuracy and identifies excellent biomarkers while retaining fewer features. The experimental results demonstrate the effectiveness and advancement of our proposed algorithmic model.
(Lemée and H.Lév.) S.Y.Hu, indigenous to the southern regions of China, is an evergreen tree belonging to the genus Taxus of the Taxaceae family. Owing to its content of various bioactive compounds, ...it exhibits multiple pharmacological activities and has been widely applied in clinical medicine. This article comprehensively discusses the current state of cultivation, chemical constituents, applications in the pharmaceutical field, and the challenges faced by
The paper begins by detailing the ecological distribution of
, aiming to provide an in-depth understanding of its origin and cultivation overview. In terms of chemical composition, the article thoroughly summarizes the extracts and monomeric components of
, unveiling their pharmacological activities and elucidating the mechanisms of action based on the latest scientific research, as well as their potential as lead compounds in new drug development. The article also addresses the challenges in the
research, such as the difficulties in extracting and synthesizing active components and the need for sustainable utilization strategies. In summary,
is a rare species important for biodiversity conservation and demonstrates significant research and application potential in drug development and disease treatment.
In recent years, skin aging has received increasing attention. Many factors affect skin aging, and research has shown that metabolism plays a vital role in skin aging, but there needs to be a more ...systematic review. This article reviews the interaction between skin metabolism and aging from the perspectives of glucose, protein, and lipid metabolism and explores relevant strategies for skin metabolism regulation. We found that skin aging affects the metabolism of three major substances, which are glucose, protein, and lipids, and the metabolism of the three major substances in the skin also affects the process of skin aging. Some drugs or compounds can regulate the metabolic disorders mentioned above to exert anti-aging effects. Currently, there are a variety of products, but most of them focus on improving skin collagen levels. Skin aging is closely related to metabolism, and they interact with each other. Regulating specific metabolic disorders in the skin is an important anti-aging strategy. Research and development have focused on improving collagen levels, while the regulation of other skin glycosylation and lipid disorders including key membrane or cytoskeleton proteins is relatively rare. Further research and development are expected.
, as a globally prevalent evergreen tree, contains a wealth of bioactive components that play a crucial role in the pharmaceutical field.
extracts, defined as a collection of one or more bioactive ...compounds extracted from the genus
spp., have become a significant focus of modern cancer treatment research. This review article aims to delve into the scientific background of
extracts and their considerable value in pharmaceutical research. It meticulously sifts through and compares various advanced extraction techniques such as supercritical extraction, ultrasound extraction, microwave-assisted extraction, solid-phase extraction, high-pressure pulsed electric field extraction, and enzymatic extraction, assessing each technology's advantages and limitations across dimensions such as extraction efficiency, extraction purity, economic cost, operational time, and environmental impact, with comprehensive analysis results presented in table form. In the area of drug formulation design, this paper systematically discusses the development strategies for solid, liquid, and semi-solid dosage forms based on the unique physicochemical properties of
extracts, their intended medical uses, and specific release characteristics, delving deeply into the selection of excipients and the critical technical issues in the drug preparation process. Moreover, the article looks forward to the potential directions of
extracts in future research and medical applications, emphasizing the urgency and importance of continuously optimizing extraction methods and formulation design to enhance treatment efficacy, reduce production costs, and decrease environmental burdens. It provides a comprehensive set of preparation techniques and formulation optimization schemes for researchers in cancer treatment and other medical fields, promoting the application and development of
extracts in pharmaceutical sciences.
With the advancement of living standards in modern society and the emergence of an aging population, an increasing number of people are becoming interested in the topic of aging and anti-aging. An ...important feature of aging is skin aging, and women are particularly concerned about skin aging. In the field of cosmetics, the market share of anti-aging products is increasing year by year. This article reviews the research and development progress of skin aging and related active compounds both domestically and internationally in recent years. The results show that, in terms of the research on skin aging, the popular theories mainly include free radicals and oxidative stress theory, inflammation theory, photoaging theory, and nonenzymatic glycosyl chemistry theory. In terms of research on the active ingredients with anti-aging activities in the skin, there are numerous reports on related products in clinical studies on human subjects, animal experiments, and experimental studies on cell cultures, with a variety of types. Most of the compounds against skin aging are sourced from natural products and their action mechanisms are mainly related to scavenging oxygen free radicals and enhancing antioxidant defenses. This review provides important references for the future research of skin aging and the development of related products. Although there is a great progress in skin aging including related active ingredients, ideal compounds or products are still lacking and need to be further validated. New mechanisms of skin aging, new active ingredients sourced from natural and artificial products, and new pharmaceutical forms including further clinical validations should be further investigated in the future.
The relentless pursuit of effective strategies against skin aging has led to significant interest in the role of bioactive factors, particularly secondary metabolites from natural sources. The ...purpose of this study is to meticulously explore and summarize the recent advancements in understanding and utilization of bioactive factors against skin aging, with a focus on their sources, mechanisms of action, and therapeutic potential. Skin, the largest organ of the body, directly interacts with the external environment, making it susceptible to aging influenced by factors such as UV radiation, pollution, and oxidative stress. Among various interventions, bioactive factors, including peptides, amino acids, and secondary metabolites, have shown promising anti-aging effects by modulating the biological pathways associated with skin integrity and youthfulness. This article provides a comprehensive overview of these bioactive compounds, emphasizing collagen peptides, antioxidants, and herbal extracts, and discusses their effectiveness in promoting collagen synthesis, enhancing skin barrier function, and mitigating the visible signs of aging. By presenting a synthesis of the current research, this study aims to highlight the therapeutic potential of these bioactive factors in developing innovative anti-aging skin care solutions, thereby contributing to the broader field of dermatological research and offering new perspectives for future studies. Our findings underscore the importance of the continued exploration of bioactive compounds for their potential to revolutionize anti-aging skin care and improve skin health and aesthetics.
Taxus × media, belonging to the genus Taxus of the Taxaceae family, is a unique hybrid plant derived from a natural crossbreeding between Taxus cuspidata and Taxus baccata. This distinctive hybrid ...variety inherits the superior traits of its parental species, exhibiting significant biological and medicinal values. This paper comprehensively analyzes Taxus × media from multiple dimensions, including its cultivation overview, chemical composition, and multifaceted applications in the medical field. In terms of chemical constituents, this study delves into the bioactive components abundant in Taxus × media and their pharmacological activities, highlighting the importance and value of these components, including paclitaxel, as the lead compounds in traditional medicine and modern drug development. Regarding its medicinal value, the article primarily discusses the potential applications of Taxus × media in combating tumors, antibacterial, anti-inflammatory, and antioxidant activities, and treating diabetes. By synthesizing clinical research and experimental data, the paper elucidates the potential and mechanisms of its primary active components in preventing and treating these diseases. In conclusion, Taxus × media demonstrates its unique value in biological research and tremendous potential in drug development.
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