Asiatic acid ameliorates doxorubicin-induced cardiotoxicity by promoting FPN-mediated iron export and inhibiting ferroptosis.

Doxorubicin (DOX), a common chemotherapeutic agent in cancer therapy, is accompanied by pronounced cardiotoxicity. Ferroptosis has been implicated in the pathogenesis and therapeutics of DOX-induced cardiotoxicity (DIC). Asiatic acid (AA), a pentacyclic triterpene from the Chinese medicinal herb Centella asiatica, displays antioxidant, anti-inflammatory, and antiapoptotic activities. In this study, we investigated the beneficial effects of AA against DOX-induced ferroptosis and cardiotoxicity and the underlying mechanisms. A chronic DIC model was established by challenging mice with DOX (5 mg/kg, i.p.) once per week for 4 weeks. Concurrent with DOX insult, the mice were administered AA (25 mg·kg-1·d-1, i.g.). Cardiac function and mechanical properties of isolated cardiomyocytes were evaluated at the end of treatment. We showed that AA administration preserved cardiac function, significantly reduced cardiac injury, and improved cardiomyocyte contractile function in DIC mice. The beneficial effects of AA were causally linked to the inhibition of DOX-induced ferroptosis both in vivo and in vitro. We revealed that AA attenuated DOX-induced iron accumulation in HL-1 cells by increasing FPN-mediated iron export, in a Nrf2-dependent manner. AA upregulated Nrf2 expression and promoted Nrf2 nuclear translocation in DOX-treated HL-1 cells. Moreover, AA-offered benefits against DOX-induced cardiac dysfunction and ferroptosis were abolished by Nrf2 inhibitor ML385 (30 mg·kg-1·d-1, i.p.) administrated 30 min before AA in DIC mice. Our data favor that AA promotes FPN-mediated iron export to inhibit iron overload and ferroptosis in DIC, suggesting its therapeutic potential in the treatment of DIC.

Generation of a competing endogenous RNA network and validation of BNIP1 expression in the lung of irradiated mice.

BACKGROUND: Radiation-induced lung injury (RILI) is a serious complication of radiation therapy, and it is mediated by long non-coding RNAs (lncRNAs). STUDY DESIGN AND METHODS: Mouse lung tissues were examined using RNA-Seq and RNA-Seq libraries 72 h after the administration of 6 Gy of X-ray irradiation. The target mRNAs were functionally annotated and the target lncRNA-based miRNAs and target miRNA-based mRNAs were predicted after irradiation to establish the lncRNA-miRNA-mRNA ceRNA axis. RESULTS: The analyses showed that relative to unirradiated controls, 323 mRNAs, 114 miRNAs, and 472 lncRNAs were significantly up-regulated following irradiation, whereas 1907 mRNAs, 77 miRNAs, and 1572 lncRNAs were significantly down-regulated following irradiation. Voltage-gated ion channels, trans-membrane receptor protein tyrosine kinases, and vascular endothelial growth factor have all been associated with dysregulated miRNA-mRNA relationships. KEGG pathway analysis of the dysregulated miRNA-mRNA targets revealed involvement in pathways associated with the hedgehog signaling pathway-fly, ErbB signaling, VEGF signaling, axon guidance, and focal adhesion. KEGG analysis of differentially expressed showed enrichment of mRNAs in primary immunodeficiency, the intestinal immune axis for IgA production, hematopoietic cell lineages, systemic lupus erythematosus, and Th1 and Th2 cell differentiation. Finally, the ceRNA network revealed that BNIP1 was a critical mRNA modulated by the most significant upregulation of lncRNA E230013L22Rik. CONCLUSION: In summary, the lncRNA-miRNA-mRNA ceRNA axis of RILI was constructed following irradiation in a mouse model. RNA dysregulation in the early stage of RILI may lead to severe complications at a later stage, with BNIP1 contributing to radiation-induced cellular apoptosis in RILI.

MP-3 microperimeter in early primary open angle glaucoma with a new pattern.

AIM: To investigate macular microperimetry in patients with early primary open angle glaucoma (POAG) using a new custom-made pattern, and analyze the characteristics of macular sensitivity. METHODS: This case-control study included 38 patients with POAG, who were divided into pre-perimetric glaucoma (18 eyes of 18 patients), early-stage (20 eyes of 20 patients), and control (20 eyes of 20 patients) groups. All subjects underwent standard 24-2 humphrey visual field test. An MP-3 microperimeter with a new custom-made pattern (28 testing points distributed in four quadrants, covering the central 10° of the retina) was used to evaluate macular sensitivity. Ganglion cell complex (GCC) thicknesses were examined using an RS-3000 Advance OCT system. The features of structure and function were analysed per quadrant. RESULTS: The pre-perimetric glaucoma group had significantly lower inferior hemifield macular sensitivity compared to controls (P<0.05). The early-stage POAG group had significantly lower average, inferior hemifield, inferonasal, and inferotemporal mean sensitivities compared to the pre-perimetric glaucoma group (P<0.05), and lower macular sensitivity in all sectors compared to controls (P<0.05). Regarding GCC thickness, all sectors in the early-stage POAG group became thinner compared to those in controls (P<0.05); whereas all sectors in the early-stage POAG group, except the superonasal quadrant, became thinner compared to those in the pre-perimetric glaucoma group (P<0.05). Macular sensitivity and GCC thickness were significantly associated in each sector. The inferotemporal quadrant had the highest correlation coefficients (0.840). The structure-function relationship for the inferonasal and inferotemporal sectors was stronger compared to the corresponding superior sectors. CONCLUSION: Microperimetry reveals variations in macular sensitivity in patients with early glaucoma earlier than conventional perimetry, particularly in pre-perimetric glaucoma cases in which it might be undetectable by conventional methods. The new custom-made pattern may improve the accuracy of microperimetry by enhancing point arrangement and reducing fatigue effects. Macular sensitivity measured by MP-3 with this pattern shows statistically significant structural and functional associations with the thicknesses of the GCC.

Ticagrelor alleviates pyroptosis of myocardial ischemia reperfusion-induced acute lung injury in rats: a preliminary study.

Pulmonary infection is highly prevalent in patients with acute myocardial infarction undergoing percutaneous coronary intervention. However, the potential mechanism is not well characterized. Myocardial ischemia-reperfusion injury (MIRI) induces acute lung injury (ALI) related to pulmonary infection and inflammation. Recent studies have shown that pyroptosis mediates ALI in several human respiratory diseases. It is not known whether MIRI induces pyroptosis in the lungs. Furthermore, ticagrelor is a clinically approved anti-platelet drug that reduces ALI and inhibits the expression levels of several pyroptosis-associated proteins, but the effects of ticagrelor on MIRI-induced ALI have not been reported. Therefore, we investigated whether ticagrelor alleviated ALI in the rat MIRI model, and its effects on pyroptosis in the lungs. Sprague-Dawley rats were randomly divided into four groups: control, MIRI, MIRI plus low ticagrelor (30 mg/kg), and MIRI plus high ticagrelor (100 mg/kg). Hematoxylin and Eosin (HE) staining was performed on the lung sections, and the HE scores were calculated to determine the extent of lung pathology. The wet-to-dry ratio of the lung tissues were also determined. The expression levels of pyroptosis-related proteins such as NLRP3, ASC, and Cleaved caspase-1 were estimated in the lung tissues using the western blot. ELISA was used to estimate the IL-1ß levels in the lungs. Immunohistochemistry was performed to determine the levels of MPO-positive neutrophils as well as the total NLRP3-positive and Cleaved caspase-1-positive areas in the lung tissues. The lung tissues from the MIRI group rats showed significantly higher HE score, wet-to-dry ratio, and the MPO-positive area compared to the control group, but these effects were attenuated by pre-treatment with ticagrelor. Furthermore, lung tissues of the MIRI group rats showed significantly higher expression levels of pyroptosis-associated proteins, including NLRP3 (2.1-fold, P < 0.05), ASC (3.0-fold, P < 0.01), and Cleaved caspase-1 (9.0-fold, P < 0.01). Pre-treatment with the high-dose of ticagrelor suppressed MIRI-induced upregulation of NLRP3 (0.46-fold, P < 0.05), ASC (0.64-fold, P < 0.01), and Cleaved caspase-1 (0.80-fold, P < 0.01). Immunohistochemistry results also confirmed that pre-treatment with ticagrelor suppressed MIRI-induced upregulation of pyroptosis in the lungs. In summary, our data demonstrated that MIRI induced ALI and upregulated pyroptosis in the rat lung tissues. Pre-treatment with ticagrelor attenuated these effects.

Three-dimensional model construction and wind simulation of different tree species in farmland shelter.

Protective forests are the ecological barriers of oases in arid sand areas and can effectively prevent and control wind and sand hazards. The structural characteristics of individual trees, as the basic unit of protective forests, are the key factors affecting the protective benefits. With the typical leafless tree species of Ulan Buh Desert oasis, i.e., Populus alba var. pyramidalis, Populus nigra var. thevestina, and Populus popularis, as the research objects, and by using the ground-based LiDAR and through computational fluid dynamics (CFD), we fully explored the structural characteristics of individual trees and their surrounding aerodynamic characteristics on the basis of real 3D models. We further established the relationship between structural parameters of individual trees and wind field index. The results showed that combining AdQSM and MeshLab to build tree models had high accuracy. The wind field around the individual trees could be roughly divided into six regions, including the attenuation zone of the windward side of the plant, the acceleration zone at the top of the plant, the eddy zone, the calm zone, the transition zone, and the recovery zone of leeward side of the plant. The pressure field around individual trees showed a gradual change of high pressure on the windward side to low pressure on the leeward side. Horizontally, in the range of 20% to 50% reduction in relative wind speed, the effective protection distances were 0.21H-1.51H, 0.20H-0.91H, and 0.25H-1.64H (H was the corresponding tree height) for P. alba var. pyramidalis, P. nigra var. thevestina, and P. popularis, corresponding to effective protection areas of 18-294, 15-227, and 18-261 m2, respectively. The maximum wind speed decay rate in the vertical direction was at 0.3H height for P. alba var. pyramidalis and P. popularis, and was reflected at 0.5H height for P. nigra var. thevestina. The correlation and stepwise regression analysis of the single tree structure parameters with the wind field indicators clearly indicated that optical porosity and volume porosity dominated the protection effect. Among the wind field factors, the best regression models related to the porous coefficient were screened for three factors, including diameter at breast height, tree surface area, and optical porosity. The regression variables screened for effective protection distance and effective protection area differed among the classes.

Assessment on the declining degree of farmland shelter forest in a desert oasis based on LiDAR and hyperspectrum imagery.

We examined the growth decline and health status of farmland protective forest belt (Populus alba var. pyramidalis and Populus simonii shelterbelts) in Ulanbuh Desert Oasis by using airborne hyperspectral and ground-based LiDAR to collect the hyperspectral images and point cloud data of the whole forest belt respectively. Through correlation analysis and stepwise regression analysis, we constructed the evaluation model of the decline degree of farmland protection forest with the spectral differential value, vegetation index, and forest structure parameters as independent variables and the tree canopy dead branch index of the field survey as dependent variables. We further tested the accuracy of the model. The results showed that the evaluation accuracy of the decline degree of P. alba var. pyramidalis and P. simonii by LiDAR method was better than that by hyperspectral method, and that the evaluation accuracy of the combined LiDAR and hyperspectral method was the highest. Using the LiDAR method, hyperspectral method, the combined method, the optimal model of P. alba var. pyramidalis was all light gradient boosting machine model, with the overall classification accuracy being 0.75, 0.68, 0.80, and Kappa coefficient being 0.58, 0.43, 0.66, respectively. The optimal model of P. simonii was random forest model, random forest model, and multilayer perceptron model, with the overall classification accuracy being 0.76, 0.62, 0.81, and Kappa coefficient being 0.60, 0.34, 0.71, respectively. This research method could accurately check and monitor the decline of plantations.

Biflavonoids from Ginkgo biloba leaves as a novel anti-atherosclerotic candidate: Inhibition potency and mechanistic analysis.

BACKGROUND: Ginkgo biloba L. is one of the oldest trees on earth, and its leaves have been used since ages as herbal medicine to treat cerebrovascular disorders. It is worth noting that in addition to the widely concerned flavonoids and terpenoids, it also contains various thus far neglected biflavonoids. In fact, biflavonoids are flavonoids consisting of apigenin or its derivatives as monomeric scaffold, and are linked via C-C or C-O-C bond. PURPOSE: Based on the structural similarity of flavonoids, we hypothesized that biflavonoids may play a potential role in the treatment of cerebrovascular diseases. Here, we describe the effectiveness and underlying mechanisms for prevention and treatment of atherosclerosis (AS) by biflavonoids. STUDY DESIGN AND METHODS: Four main biflavonoids in Ginkgo biloba leaves were screened by oleic acid-induced lipid production in HepG2 cells. The non-covalent effects of biflavonoids on the potential targets of atherosclerosis were screened by reverse targeting and molecular dynamics simulation. The interactions between biflavonoids and potential targets were evaluated by an exogenous cell model, which verified the consistency of the simulation results. CONCLUSION: Among all four biflavonoids, ginkgetin significantly inhibited oleic acid-induced lipid production in HepG2 cells and reduced total cholesterol and triglyceride levels. The interaction of ginkgetin with CDK2 through π-alkyl and hydrogen bonds increased the binding of molecules and proteins. Ginkgetin arrested the cells in the G1-S phase, which significantly inhibited abnormal cell growth which closely related to the occurrence and development of atherosclerosis. Biflavonoids could be a promising natural medicine for the treatment of atherosclerosis.

Marking ground glass nodules with pulmonary nodules localization needle prior to video-assisted thoracoscopic surgery.

OBJECTIVES: To evaluate the efficacy and safety of marking ground glass nodules (GGNs) with pulmonary nodules localization needle (PNLN) prior to video-assisted thoracoscopic surgery (VATS). MATERIALS AND METHODS: From June 2020 to February 2021, all patients with GGNs who received CT-guided localization using PNLN before VATS were enrolled. Clinical and imaging data were retrospectively analyzed. RESULTS: A total of 352 consecutive patients with 395 GGNs were included in the study. The mean diameter of GGNs was 0.95 ± 0.48 cm, and the shortest distance from nodules to the pleura was 1.73 ± 0.96 cm. All 395 GGNs were marked using PNLNs. The time required for marking was 7.8 ± 2.2 min. The marking success rate was 99.0% (391/395). The marking failure of four nodules was all due to the unsatisfactory position of PNLNs. No marker dislocation occurred. Marking-related complications included pneumothorax in 63 cases (17.9%), hemorrhage in 34 cases (9.7%), and hemoptysis in 6 cases (1.7%). All the complications were minor and did not need special treatment. Localization and VATS were performed on the same day in 95 cases and on different days in 257 cases. All GGNs were successfully removed by VATS. No patient converted to thoracotomy. Histopathological examination revealed 74 (18.7%) benign nodules and 321 (81.3%) malignant nodules. CONCLUSIONS: It is safe and reliable to perform preoperative localization of GGNs using PNLNs, which can effectively guide VATS to remove GGNs. KEY POINTS: • Preoperative localization of GGNs could effectively guide VATS to remove GGNs. • PNLN was based on the marking principle of hook-wire, through the improvement of its material, specially designed to mark pulmonary nodules. • The application of PNLN to mark GGNs had high success rate, good patient tolerance, and no dislocation. Meanwhile, VATS could be performed 2 to 3 days after marking GGNs with PNLN.

Seed oil of Rosa roxburghii Tratt against non-alcoholic fatty liver disease in vivo and in vitro through PPARα/PGC-1α-mediated mitochondrial oxidative metabolism.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis and hepatocyte injury, is an obesity-induced metabolic dysregulation with few available therapeutic options. Enhancement of the mitochondrial function was considered as an effective treatment for NALFD. Unsaturated fatty acids (UFAs) have been shown to have beneficial effects on metabolic syndrome disease such as hyperlipidemia, coronary artery disease and cardiovascular diseases. The seed oil of Rosa roxburghii Tratt (ORRT) was of high quality in terms of its high amount of unsaturated fatty acids. However, the effects of ORRT on NALFD have not been reported so far. PURPOSE: The study aimed to evaluate the protective effects and molecular mechanism of ORRT for the treatment of NAFLD in vivo and in vitro. METHODS: The beneficial effects, especially improving the mitochondrial function, and the potential mechanism of ORRT on NAFLD were studied both in vivo and in vitro. Lipid levels were determined by triglyceride (TG), total cholesterol (TC), and Oil Red O staining. Oxidative stress and inflammation were assessed by detecting antioxidant enzyme activity, MDA content, and ELISA assay. Blood TG, TC, HDL-c and LDL-c levels were measured in HFD mice. Western blot analyses were used to determine the levels of the protein involved in fatty acid oxidation, oxidative metabolism, and mitochondria biogenesis and function. The mitochondrial membrane potential level was measured by JC-1 staining to teste the effect of ORRT on mitochondrial function in vitro. GW6471 (inhibitor of PPARα) was used to confirm the relationship between PPARα and PGC-1α. RESULTS: ORRT significantly restrained NAFLD progression by attenuating lipid accumulation, oxidative stress and inflammatory response. Furthermore, ORRT upregulated thermogenesis-related gene expressions, such as uncoupling protein 1 (UCP1) and p38 mitogen-activated protein kinase (p38 MAPK). The results showed that the expression of key genes involved in fatty acid oxidation (e.g., CPT-1α, ACADL, PPARα) and in mitochondrial biogenesis and function (e.g., TFAM, NRF1, PGC-1α, and COX IV) was significantly increased. Together with the observed MMP improvement, these findings suggested that ORRT activated the mitochondrial oxidative pathway. Additionally, GW6471 inhibited the ORRT on promoting the expression of PGC-1α, CPT-1α, and ACADL. In conclusion, ORRT possessed the potential to prevent lipid accumulation via the PPARα/PGC-1α signaling pathway, which could be developed as a natural health-promoting oil against NAFLD.

Association between DBP and major adverse cardiovascular events in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND: In patients with stable coronary artery disease, low DBP is associated with an increased risk of myocardial infarction and cardiovascular death, but its association with clinical outcomes in patients with acute myocardial infarction undergoing percutaneous coronary intervention (PCI) is unknown. METHODS: Consecutive patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI from January 2010 to June 2016 were enrolled. The patients were divided into five groups according to the quintiles of DBP at admission. The primary outcome was in-hospital major adverse cardiovascular events (MACE) including all-cause death, stroke, target vessel revascularization, and recurrent myocardial infarction. RESULTS: A total of 2198 patients were enrolled, of whom 157 (7.1%) developed in-hospital MACE. Patients with DBP lower than 60 mmHg was associated with a higher rate of in-hospital MACE (14.8, 7.8, 5.6, 6.1, and 3.8%, P < 0.001) and all-cause death (12.5, 6.4, 4.3, 3.9, and 1.9%, P < 0.001) compared with those with DBP 60-69, 70-79, 80-89, and at least 90 mmHg. Multivariate logistic regression analysis demonstrated that DBP higher than 90 mmHg was a significant predictor of lower risk of in-hospital MACE (OR = 0.16, 95% CI = 0.04-0.61, P = 0.007). Cubic spline models for the association between DBP and MACE did not demonstrate a U-type relationship after adjusting for potential risk factors. During the follow-up, lower DBP was associated with a higher risk of all-cause death (P < 0.0001). CONCLUSION: Lower DBP is independently associated with an elevated risk of in-hospital MACE and follow-up all-cause death.

Ticagrelor and the risk of infections during hospitalization in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Although ticagrelor exerts an antibacterial activity, its effect on infections in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) is unclear. We aimed to assess whether ticagrelor and clopidogrel affect infections in these patients during hospitalization. METHODS: A total of 2116 consecutive patients with STEMI undergoing PCI were divided into the ticagrelor (n = 388) and clopidogrel (n = 1728) groups. The primary outcome was infection onset. Secondary outcomes were in-hospital all-cause death and major adverse cardiovascular and cerebrovascular events (MACCE). Propensity score analyses were conducted to test the robustness of the results. RESULTS: Infections developed in 327 (15.4%) patients. There was no significant difference in infection between both groups (ticagrelor vs. clopidogrel: 13.1% vs. 16.0%, p = 0.164). Patients in the ticagrelor group had lower rates of in-hospital all-cause death and MACCE than patients in the clopidogrel group. Multivariate logistic regression analysis determined that ticagrelor and clopidogrel had a similar preventive effect on infections during hospitalization (adjusted odds ratio [OR] = 1.20; 95% confidence interval [CI] = 0.80-1.78, p = 0.380). Compared to the patients treated with clopidogrel, patients treated with ticagrelor had a slightly lower risk of other outcomes, but no statistical difference. Propensity score analyses demonstrated similar results for infections and other outcomes. CONCLUSIONS: Compared with clopidogrel treatment, ticagrelor treatment did not significantly alter the risk of infections during hospitalization among STEMI patients undergoing PCI, but was associated with a slightly lower risk of in-hospital all-cause death and MACCE.

CT-guided preoperative localization of ground glass nodule: comparison between the application of embolization microcoil and the locating needle designed for pulmonary nodules.

OBJECTIVES: To compare the efficacy and safety of pre-operative localization of ground glass nodule (GGN) using embolization microcoils and the locating needles designed for pulmonary nodules. METHODS: From June 2019 to December 2020, 429 patients who received CT-guided localization of single GGN before video-assisted thoracoscopic surgery (VATS) were enrolled. The diameter and depth of GGNs were 0.84 ± 0.39 cm and 1.66 ± 1.37 cm. Among 429 cases, the first 221 GGNs were marked with microcoils (the microcoil group), and the remaining 208 GGNs were marked with the locating needles designed for pulmonary nodules (the locating needle group). SPSS 17.0 statistical software was used to compare the marking success rate, marking time, marking-related complications between two groups. p values < 0.05 were considered statistically significant. RESULTS: The marking time in the microcoil group was longer than that in the locating needle group (11.1 ± 3.9 vs 8.2 ± 2.0 min, t = -7.87, p = 0.000). The marking success rate in the microcoil group was lower than that in the locating needle group (91.4% vs 98.6%, χ2 = 11.27, p = 0.001). In the microcoil group, marking failures included 16 cases of microcoil dislocation and 3 cases of unsatisfactory microcoil position, while all 3 cases of marking failure in the locating needle group were due to unsatisfactory anchor position. No significant differences in the incidence of total complications (23.1% vs 22.1%), pneumothorax (18.1% vs 19.2%), hemorrhage (9.5% vs 9.1%), and hemoptysis (1.8% vs 1.4%) were observed between the two groups. All the complications were minor and did not need special treatment. Except for one case in the microcoil group, which was converted to thoracotomy, the remaining 428 GGNs were successfully resected by VATS. CONCLUSIONS: It is safe and effective to perform pre-operative localization of GGN using either embolization microcoil or the locating needle designed for pulmonary nodules. The locating needle is superior to microcoil for marking GGN in terms of procedure time and the success rate. The complication rate of both methods is similar. ADVANCES IN KNOWLEDGE: The locating needle designed for pulmonary nodules has recently been used to mark pulmonary nodule. Its structure can effectively avoid dislocation after localization, and the marking process is simple and quick. Compared with localization using microcoil, it takes less time and has higher success rate to mark GGNs using the locating needle. The complication rate of both methods is similar.

Caffeine promotes angiogenesis through modulating endothelial mitochondrial dynamics.

Caffeine induces multiple vascular effects. In this study we investigated the angiogenic effect of physiological concentrations of caffeine with focus on endothelial cell behaviors (migration and proliferation) during angiogenesis and its mitochondrial and bioenergetic mechanisms. We showed that caffeine (10-50 µM) significantly enhanced angiogenesis in vitro, evidenced by concentration-dependent increases in tube formation, and migration of human umbilical vein endothelial cells (HUVECs) without affecting cell proliferation. Caffeine (50 µM) enhanced endothelial migration via activation of cAMP/PKA/AMPK signaling pathway, which was mimicked by cAMP analog 8-Br-cAMP, and blocked by PKA inhibitor H89, adenylate cyclase inhibitor SQ22536 or AMPK inhibitor compound C. Furthermore, caffeine (50 µM) induced significant mitochondrial shortening through the increased phosphorylation of mitochondrial fission protein dynamin-related protein 1 (Drp1) in HUVECs, which increased its activity to regulate mitochondrial fission. Pharmacological blockade of Drp1 by Mdivi-1 (10 µM) or disturbance of mitochondrial fission by Drp1 silencing markedly suppressed caffeine-induced lamellipodia formation and endothelial cell migration. Moreover, we showed that caffeine-induced mitochondrial fission led to accumulation of more mitochondria in lamellipodia regions and augmentation of mitochondrial energetics, both of which were necessary for cell migration. In a mouse model of hindlimb ischemia, administration of caffeine (0.05% in 200 mL drinking water daily, for 14 days) significantly promoted angiogenesis and perfusion as well as activation of endothelial AMPK signaling in the ischemic hindlimb. Taken together, caffeine induces mitochondrial fission through cAMP/PKA/AMPK signaling pathway. Mitochondrial fission is an integral process in caffeine-induced endothelial cell migration by altering mitochondrial distribution and energetics.

Botanical characteristics, phytochemistry and related biological activities of Rosa roxburghii Tratt fruit, and its potential use in functional foods: a review.

Due to the growing global population, reduction in arable land and effects of climate change, incongruity between food supply and demand has become increasingly severe. Nowadays, with awareness of the elementary nutrients required for human growth, increasing attention is being paid to the health and medical functions of food. Along with increased food production achieved by modern agricultural techniques, underutilised functional foods are an important strategy for solving food security problems and maintaining the nutritional quality of the human diet. Rosa roxburghii Tratt (RRT) is a natural fruit that contains unique functional and nutritional constituents, which are characterised by a high anti-oxidant potential. This review summarises the biological characteristics, chemical composition, health-promoting properties and development status of RRT products to inspire investigations on the use of RRT fruit as a functional food, dietary supplement and pharmaceutical additive. The nutrients and functional ingredients of RRT fruit are described in detail to provide more reference information for nutritionists and pharmacists.

The prevalence of ampicillin-resistant opportunistic pathogenic bacteria undergoing selective stress of heavy metal pollutants in the Xiangjiang River, China.

The emergence of clinically relevant ß-lactam-resistant bacteria poses a serious threat to human health and presents a major challenge for medical treatment. How opportunistic pathogenic bacteria acquire antibiotic resistance and the prevalence of antibiotic-resistant opportunistic pathogenic bacteria in the environment are still unclear. In this study, we further confirmed that the selective pressure of heavy metals contributes to the increase in ampicillin-resistant opportunistic pathogens in the Xiangjiang River. Four ampicillin-resistant opportunistic pathogenic bacteria (Pseudomonas monteilii, Aeromonas hydrophila, Acinetobacter baumannii, and Staphylococcus epidermidis) were isolated on Luria-Bertani (LB) agar plates and identified by 16S rRNA sequencing. The abundance of these opportunistic pathogenic bacteria significantly increased in the sites downstream of the Xiangjiang River that were heavily influenced by metal mining activities. A microcosm experiment showed that the abundance of ß-lactam resistance genes carried by opportunistic pathogenic bacteria in the heavy metal (Cu2+ and Zn2+) treatment group was 2-10 times higher than that in the control. Moreover, heavy metals (Cu2+ and Zn2+) significantly increased the horizontal transfer of plasmids in pathogenic bacteria. Of particular interest is that heavy metals facilitated the horizontal transfer of conjugative plasmids, which may lead to the prevalence of multidrug-resistant pathogenic bacteria in the Xiangjiang River.

Development of fermented chestnut with Bacillus natto: Functional and sensory properties.

Food fermentation can improve food nutritional value and sensory performance, it is considered as an ecofriendly bioprocessing technology. In this work, a fermented natto chestnut food was firstly developed and its active ingredients and functional properties were systematically studied. Through systematic experimental screening, including a single factor experiment and Box-Behnken design, the fermentation parameters of chestnut were optimized and selected. Under the optimal fermentation conditions, fermentation time 56 h, temperature 38 â„ƒ and 5% inoculum concentration, the fibrinolytic activity of the natto-chestnut reached 6479 IU/g. Meanwhile, higher antioxidant activity of the natto-chestnut was obtained due to the increased contents of total phenolic, total flavonoid and VC. In addition, α-glucosidase inhibition activity was also improved in the natto-chestnut. These results indicated that fermented chestnut could be a new dietary supplement with higher quality and better activities for people's health.

Anti-Inflammatory Effects of Neochlorogenic Acid Extract from Mulberry Leaf (Morus alba L.) Against LPS-Stimulated Inflammatory Response through Mediating the AMPK/Nrf2 Signaling Pathway in A549 Cells.

Neochlorogenic acid (nCGA) is a phenolic compound isolated from mulberry leaf (Morus alba L.), which possesses multiple pharmacological activities containing antioxidant and anti-inflammatory effects. However, the role of nCGA in the treatment of acute pneumonia and the underlying molecular mechanism are still unclear. Hence, the aim of study is to investigate the anti-inflammatory properties of nCGA on LPS-stimulated inflammation in A549 cells. In the present study, results reported that nCGA without cytotoxicity significantly reduced the production of TNF-α, IL-6, and NO, and further suppressed the proteins of iNOS, COX2, TNF-α, IL-6 expression. Furthermore, nCGA also inhibited NF-κB activation and blocked MAPKs signaling pathway phosphorylation. In addition, we found nCGA significantly increased the expression of HO-1 via activating the AMPK/Nrf2 signaling pathway to attenuate the inflammatory response, whereas this protective effect of nCGA was reversed by pre-treatment with compound C (C.C, an AMPK inhibitor). Therefore, all these results indicated that nCGA might act as a natural anti-inflammatory agent for the treatment of acute pneumonia.

A simple and efficient sample preparation for taxanes in Taxus chinensis needles with natural menthol-based aqueous deep eutectic solvent.

Taxanes are natural anticancer constituents, and the sample preparation from matrix normally depends on organochlorine solvents. In this study, green and natural menthol-based aqueous deep eutectic solvent was synthesized and used for sample preparation for taxanes. Five key parameters were optimized and the optimal preparation conditions were as follows: menthol/1-propanol ratio 1:1 (mol/mol), solid-liquid ratio 1:30 g/mL, extraction time 30 min, ultrasonic power 250 W, and water content 80%. Under the above conditions, the total extraction efficiency of seven main taxanes was 1.25- to 1.44-fold to the conventional methods. In addition, a high-performance liquid chromatography method with C18 column was established for quantitation of seven main taxanes in <25 min, which had excellent linearity (R2  > 0.9986), precision (relative standard deviation < 3.00%), repeatability (relative standard deviation < 3.69%), and recovery (90.26-109.00%). This method performed the extraction, and enrichment processes simultaneously, and it had advantages such as high extraction efficiency, simple operation, low cost, and eco-friendliness. This work indicated that the natural menthol-based deep eutectic solvent aqueous could be an excellent alternative to the sample preparation from Taxus or other plants.

Occurrence and distribution of clinical and veterinary antibiotics in the faeces of a Chinese population.

Antibiotics ingested in the human gut may create selective pressure to change the composition of the gut microbiota, which could adversely effect the immune system of the host. However, the occurrence and distribution of antibiotics in the human gut remains unclear. A total population of 180 individuals, across three Chinses regions with different economic development levels, including children, adults, and elders, were sampled in 2017. A total of 19 representative antibiotics, including both clinical and veterinary antibiotics, were investigated in human faeces. While clinical use and prescriptions were the main exposure pathways for children, environmental media were the exposure pathway to adults. In addition, significant differences (P < 0.05) in antibiotic residues in human faeces were observed amongst various economic development levels, where human faeces from underdeveloped areas were mostly associated with higher levels of antibiotics. This study first to investigate the occurrence and distribution of typical antibiotics in the faeces of a Chinese population and thereby provide a reference for the intensive study of the effects and mechanisms of antibiotics on human gut microbiota.

ROS -mediated p53 activation by juglone enhances apoptosis and autophagy in vivo and in vitro.

Juglone (JG) exhibits a broad-spectrum of cytotoxicity against some cancer cells. However, its molecular mechanisms have not been investigated well. Here, the present results showed that JG significantly inhibited tumor growth in vivo. CCK-8 assays, flow cytometric analysis, western blotting and immunohistochemistry revealed that JG effectively inhibited cell proliferation and induced apoptosis through extrinsic pathways. We also observed that JG treatment induced autophagy flux via activiting the AMPK-mTOR signaling pathway. In addition, we found that JG enhanced p53 activation by increasing down-regulation of ubiquitin-mediated degradation. Inhibition of p53 by siRNA attenuated JG-induced cell death and autophagy. Moreover, JG enhanced the generation of hydrogen peroxide (H2O2) and superoxide anion radical (O2• -). Further experiments proved that H2O2 was a major factor since the H2O2 scavenger catalase (CAT) reduced both autophagy and cell death to a greater extent than the O2• - scavenger SOD. Overall, our results illustrated that JG caused apoptosis and autophagy via activating the ROS-mediated p53 pathway in human liver cancer cells in vitro and in vivo, which provided basic scientific evidence that JG serves as a potential anti-cancer agent.