As a new transportation tool, unmanned aerial vehicle (UAV), has a broad application prospect in logistics distribution, especially for mountainous cities with complex terrain. Due to the limited ...delivery conditions of UAV, considering the advantages of traditional vehicle delivery, this paper proposes a joint delivery mode of UAV and vehicle, and designs three steps for the joint delivery problem of single UAV and single vehicle: first, mark all special nodes; Secondly, the route of UAV and vehicle is planned; Finally, the total delivery route is optimized to minimize the total delivery distance. Genetic algorithm and single distribution terminal optimization are used to solve the problem, and the joint delivery in this paper is compared with the traditional vehicle delivery and the independent delivery of UAV and vehicle. The results show that UAV and vehicle can cooperate with each other to complete the delivery of all customer demand nodes, and the joint delivery of UAV and vehicle can effectively reduce the total delivery distance. Finally, the sensitivity analysis of UAV's maximum load, maximum flight distance, relative speed between UAV and vehicle, and road impedance coefficient is carried out. By relaxing the restrictions of UAV, the UAV can deliver more customers at a single time, and it complete the delivery task with vehicles efficiently.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pancreatic cancer, a poor prognosis and high morbidity and mortality cancer, is a malignant tumor occurring in pancreatic exocrine glands. Currently, surgery and gemcitabine (Gem) are commonly used ...to treat pancreatic cancers. However, the high recurrence rate and resistance makes the therapeutic effects still unsatisfied. Apoptosis is comprehensively recognized as one of the major ways of the programmed cell death, refers to the autonomous and orderly death process of cells in order to maintain the stability of the body's environment after receiving a certain signal or stimulation. Currently, it has also been proven to be a promising way for the treatment of pancreatic cancer. Nowadays, some active ingredients from herbal medicine have been reported to be effective for the treatment of pancreatic cancer via inducing cells apoptosis. Therefore, this article reviews the current references regarding anti pancreatic cancer effects of natural products derived from herbal medicines via triggering apoptosis, and summarizes the related potential signal pathways, including death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, MAPK mediated apoptotic pathway, ERS mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other pathways such as JAK-STAT signal pathway, which can lay a certain foundation for the research and development of new natural products against pancreatic cancer.
Backgroud:
Alzheimer’s disease (AD) is a typical neurodegenerative disease, which occurs in the elderly population.
Alpiniae oxyphyllae
Fructus (AOF) is a traditional Chinese medicine that has ...potential therapeutic effect on AD, but the mechanism behind it is unclear.
Methods:
Firstly, the main chemical components of AOF were identified by LC-MS, while the main active ingredients and targets were screened by TCMSP database. At the same time, AD-related target proteins were obtained using Genecards and OMIM databases. PPI was constructed by cross-linking AOF and AD targets, and GO enrichment analysis and KEGG pathway enrichment analysis were performed to identify the relevant biological processes and signaling pathways. Finally, based on the H
2
O
2
-stimulated PC12 cell, flow cytometry, WB and immunofluorescence experiments were performed to verify the protective effect of AOF on AD.
Results:
We identified 38 active ingredients with 662 non-repetitive targets in AOF, of which 49 were potential therapeutic AD targets of AOF. According to the GO and KEGG analysis, these potential targets are mainly related to oxidative stress and apoptosis. The role of AOF in the treatment of AD is mainly related to the PI3K/AKT signaling pathway. Protocatechuic acid and nootkatone might be the main active ingredients of AOF. In subsequent experiments, the results of CCK-8 showed that AOF mitigated PC12 cell damage induced by H
2
O
2
. Kits, flow cytometry, and laser confocal microscopy indicated that AOF could decrease ROS and increase the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), while AOF could also increase mitochondrial membrane potential (MMP), thereby inhibiting apoptosis. Finally, immunofluorescence and WB results showed that AOF inhibited the expression of BAX and caspase-3 in PC12 cells, and promoted the expression of Bcl-2. At the same time, the phosphorylation levels of PI3K and Akt proteins were also significantly increased.
Conclusion:
This study suggests that AOF had the potential to treat AD by suppressing apoptosis induced by oxidative stress via the PI3K/Akt pathway.
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•Molecular mechanisms of PAZ on T2DM was firstly investigated using network pharmacology;•PAZ is beneficial for ameliorating T2DM by reducing oxidative stress and anti-insulin ...resistance;•AMPK/PI3K/AKT signaling is related to the mechanisms of PAZ.
Type 2 diabetes mellitus (T2DM), the main type of diabetes, is a common chronic metabolic disease and a serious health concern worldwide. The aim of this study was to investigate the anti-diabetic effects and underlying mechanisms of pungent substances in Zanthoxylum armatum DC (ZA) fruit (PAZ), which are both edible and medicinal. We firstly investigated the possible molecular mechanisms of the PAZ on T2DM using network pharmacology and online databases. Furthermore, the predicted results were explored by Glucosamine induced AML12 experiments in vitro. After PAZ intervention, ROS levels decreased, MDA levels of oxidative stress indicators decreased, and SOD, GSH, and CAT levels increased compared to the model group. Thus, the pungent agents from the fruits of Z. armatum are beneficial for ameliorating type 2 diabetes mellitus via regulation of AMPK/PI3K/AKT signaling and reducing oxidative stress levels and exerting an anti-insulin resistance effect.
Cancer, a common malignant disease, is one of the predominant causes of diseases that lead to death. Additionally, cancer is often detected in advanced stages and cannot be radically cured. ...Consequently, there is an urgent need for reliable and easily detectable markers to identify and monitor cancer onset and progression as early as possible. Our aim was to systematically review the relevant roles of cathepsin K (CTSK) in various possible cancers in existing studies. CTSK, a well-known key enzyme in the bone resorption process and most studied for its roles in the effective degradation of the bone extracellular matrix, is expressed in various organs. Nowadays, CTSK has been involved in various cancers such as prostate cancer, breast cancer, bone cancer, renal carcinoma, lung cancer and other cancers. In addition, CTSK can promote tumor cells proliferation, invasion and migration, and its mechanism may be related to RANK/RANKL, TGF-β, mTOR and the Wnt/β-catenin signaling pathway. Clinically, some progress has been made with the use of cathepsin K inhibitors in the treatment of certain cancers. This paper reviewed our current understanding of the possible roles of CTSK in various cancers and discussed its potential as a biomarker and/or novel molecular target for various cancers.
Hepatic fibrosis (HF) refers to the pathophysiological process of connective tissue dysplasia in the liver caused by various pathogenic factors. Nowadays, HF is becoming a severe threat to the health ...of human being. However, the drugs available for treating HF are limited. Currently, increasing natural agents derived from traditional Chinese medicines (TCMs) have been found to be beneficial for HF. A systemic literature search was conducted from PubMed, GeenMedical, Sci-Hub, CNKI, Google Scholar and Baidu Scholar, with the keywords of “traditional Chinese medicine,” “herbal medicine,” “natural agents,” “liver diseases,” and “hepatic fibrosis.” So far, more than 76 natural monomers have been isolated and identified from the TCMs with inhibitory effect on HF, including alkaloids, flavones, quinones, terpenoids, saponins, phenylpropanoids, and polysaccharides, etc. The anti-hepatic fibrosis effects of these compounds include hepatoprotection, inhibition of hepatic stellate cells (HSC) activation, regulation of extracellular matrix (ECM) synthesis & secretion, regulation of autophagy, and antioxidant & anti-inflammation, etc. Natural compounds and extracts from TCMs are promising agents for the prevention and treatment of HF, and this review would be of great significance to development of novel drugs for treating HF.
Abstract
Background
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia and insulin resistance. Mung bean sprouts are traditionally considered a “folk” ...hypoglycemic food and their pharmacological effects and underlying mechanisms warrant further investigation.
Purpose
This study aimed to investigate the anti-diabetic effects of the exosomes-like nanoparticles in mung bean sprouts (MELNs) and explore the related molecular mechanisms.
Results
MELNs were isolated using a differential centrifugation-polyethylene glycol (PEG) method, and the identification of MELNs were confirmed by PAGE gel electrophoresis, agarose gel electrophoresis, thin-layer chromatography (TLC), and transmission electron microscopy (TEM). In the high-fat diet/streptozotocin (HFD/STZ) mouse model, MELNs ameliorated the progression of T2DM by increasing oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) results, decreasing the fasting blood glucose level, and reducing the serum triglycerides (TG) and total cholesterol (TC). Histopathological examinations indicated MELNs diminished inflammatory infiltration of hepatocytes and amplified the area of islet B cells. In addition, MELNs decreased the oxidative stress levels in liver tissue and had good biocompatibility. In vitro experiments verified that MELNs improved the viability of glucosamine (GlcN) induced insulin-resistant hepatocytes. Furthermore, this study also revealed that MELNs upregulated GLUT4 & Nrf2 and down-regulated GSK-3β via activating the PI3K/Akt signaling pathway, promoting the production of antioxidant enzymes, such as HO-1 and SOD, to reduce oxidative stress.
Conclusion
MELNs mitigated the progression of type 2 diabetes in HFD/STZ mouse model. The underlying molecular mechanism is related to PI3K/Akt/GLUT4/GSK-3β signaling pathway.
The pericarp of Zanthoxylum bungeanum Maxim. (ZBM) (Rutaceae), also called Sichuan pepper, is a famous condiment and herbal medicine existing in China dating back over 2000 years. In this paper, we ...summarized the active compounds and pharmacological effects of ZBM for regulating glucose and lipid metabolism disorders, and also discussed the challenges associated with the drug development of this herbal medicine. So far, more than 100 natural compounds have been reported from ZBM, including amides, volatile oils, flavonoids, etc., and amides and volatile oil are the predominant active components in ZBM. Current investigations suggested ZBM and its active compounds (such as Hydroxy-α-Sanshool, Hydroxy-β-Sanshool) are beneficial for ameliorating glucose and lipid metabolism disorder, such as diabetes, hyperlipidemia, obesity, as well as nonalcoholic fatty liver disease (NAFLD). Although previous research has obtained great achievements, there is still enormous gaps in drug development of this herbal medicine, and future works should be devoted to break through bottlenecks in mechanisms, safety, structure modification, clinical efficacy, modern preparation and quality control. The present review gives a comprehensive understanding of the available works of ZBM regarding its regulating effects on glucose and lipid metabolic disorders, which would be beneficial for the future drug development of ZBM for combating glucose and lipid metabolic disorders.
As the common pathological basis of various cardiovascular diseases, the morbidity and mortality of atherosclerosis (AS) have increased in recent years. Unfortunately, there are still many problems ...in the treatment of AS, and the prevention and treatment of the disease is not ideal. Up to now, the occurrence and development of AS can roughly include endothelial cell dysfunction, vascular smooth muscle cell proliferation, inflammation, foam cell production, and neoangiogenesis. Among them, endothelial dysfunction, as an early event of AS, plays a particularly important role in promoting the development of AS. In addition, oxidative stress occurs throughout the causes of endothelial dysfunction. Some previous studies have shown that flavonoids derived from herbal medicines are typical secondary metabolites. Due to its structural presence of multiple active hydroxyl groups, it is able to exert antioxidant activity in diseases. Therefore, in this review, we will search PubMed, Web of Science, Elesvier, Wliey, Springer for relevant literature, focusing on flavonoids extracted from herbal medicines, and summarizing how they can prevent endothelial dysfunction by inhibiting oxidative stress. Meanwhile, in our study, we found that flavonoid represented by quercetin and naringenin showed superior protective effects both
and
, suggesting the potential of flavonoid compounds in the treatment of AS.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia. The fruits of
Maxim. is a common spice and herbal medicine in China, and hydroxy-α-sanshool (HAS) is the ...most abundant amide in
and reported to have significant hypoglycemic effects. The purpose of this study was to evaluate the ameliorative effects of HAS on T2DM and the potential mechanisms responsible for those effects. An acute toxicity test revealed the median lethal dose (LD50) of HAS is 73 mg/kg. C57BL/6 J mice were fed a high-fat diet and given an intraperitoneal injection of streptozotocin (STZ) to induce T2DM in mice to evaluate the hypoglycemic effects of HAS. The results showed that HAS significantly reduced fasting blood glucose, reduced pathological changes in the liver and pancreas, and increased liver glycogen content. In addition, glucosamine (GlcN)-induced HepG2 cells were used to establish an insulin resistance cell model and explore the molecular mechanisms of HAS activity. The results demonstrated that HAS significantly increases glucose uptake and glycogen synthesis in HepG2 cells and activates the PI3K/Akt pathway in GlcN-induced cells, as well as increases GSK-3β phosphorylation, suppresses phosphorylation of glycogen synthase (GS) and increases glycogen synthesis in liver cells. Furthermore, these effects of HAS were blocked by the PI3K inhibitor LY294002. The results of our study suggest that HAS reduces hepatic insulin resistance and increases hepatic glycogen synthesis by activating the PI3K/Akt/GSK-3β/GS signaling pathway.
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