Unveiling the Anticancer Mechanism of Echinops davuricus: Isolation and Evaluation of AKR1B10 Inhibitors.

Five compounds (1-5), one long-chain fatty acid (1), two thiophenes (2 and 3), one alkaloid (4), and one phenyl ester (5), were isolated from the aerial part of Echinops davuricus. The structures of the products were established by performing detailed nuclear magnetic resonance (NMR) analysis, and the structure of compound 1 was determined via high-resolution electrospray ionization mass spectrometry (HRESIMS) and NMR. Compounds 1, 4, and 5 were isolated from Echinops davuricus for the first time. Based on network pharmacology methods, AKR1B10 was selected as a key anticancer target. Compounds 1 and 5 exhibited significant AKR1B10 inhibitory activities, with IC50 values of 156.0±1.00 and 146.2±1.50 nM, respectively, with epalrestat used as the positive control (81.09±0.61 nM). Additionally, the interactions between the active compounds and AKR1B10 were evaluated via molecular docking. Ultimately, the GO and KEGG enrichment analysis indicated that the key signaling pathways associated with the active compounds may be related to the PI3K-Akt, MAPK, apoptotic, cellular senescence, and TNF signaling pathways and the human diseases corresponding to the targets are cancer. Our study reveals for the first time the anticancer properties of Echinops davuricus and provides a comprehensive understanding of its application in traditional medicine.

Development of AKR1B10 inhibitors from Ajuga nipponensis based on diseases and targets.

Ten compounds (1-10) including one new neoclerodane diterpenoid (1) and nine known compounds were isolated from the whole plants of Ajuga nipponensis. Their structures were established by performing detailed analysis of NMR, the structure of 1 was determined using HRESIMS, 1D and 2D NMR, UV, and IR. Compounds 1 and 4-10 were isolated from Ajuga nipponensis for the first time. And it was the first time to report compounds 9 and 10 as natural products. Based on network pharmacology methods, 45 key targets were selected, which were compounds mapping to diseases. And compounds 2, 3, 7, and a (ajugacumbin B) exhibited excellent AKR1B10 inhibitory activities, with IC50 values of 53.05 ± 0.75, 87.22 ± 0.85, 61.85 ± 0.66, and 85.19±1.02 nM respectively, with Epalrestat used as the positive control (82.09 ± 1.62 nM). Additionally, the interaction between active compounds and AKR1B10 had been discussed according to the molecular docking results. Ultimately, the analysis of GO and KEGG enrichment indicated that the key signaling pathway of the active compounds may be related to prostate cancer. Our study results demonstrate the hypoglycemic and anti-tumor properties of A. nipponensis for the first time, and provide a comprehensive understanding of its application in traditional medicine. Furthermore, this article establishes a reference for further research on the optimized experimental design of novel AKR1B10 inhibitors.

Calcitriol combined with high-calcium and high-phosphorus diet induces vascular calcification model in chronic kidney disease rats.

BACKGROUND: Cardiovascular diseases represent a significant complication arising from chronic kidney disease (CKD). Vascular calcification is an important risk factor for cardiovascular diseases. Reducing vascular calcification is therefore critical to reducing mortality in CKD patients. HYPOTHESIS: This study aims to establish a vascular calcification model in rats with CKD by administering subcutaneous injections of calcitriol in combination with a high-calcium and high-phosphorus diet. METHODS: The rats were divided into the CKD vascular calcification model group (subtotal nephrectomy+ [SNx+]) and the sham-operated control group (subtotal nephrectomy- [SNx-]). The rats in the SNx(+) group were administered high-calcium and high-phosphorus feeds following a 5/6 nephrectomy. Calcitriol (1 µg/kg, three times a week) was injected subcutaneously at weeks 0, 4, 8, and 12 after the operation. Measurements of body weight, urine, serum biochemical indicators and vascular calcification level were conducted in rats. RESULTS: (1) Compared with the SNx(-) group, rats in the SNx(+) group experienced an increase in 24-h urine output, urinary phosphorus, and urinary microprotein excretion, along with the development of severe anemia. Additionally, there was a notable elevation in serum phosphorus, blood urea nitrogen, blood creatinine, fibroblast growth factor 23 (FGF-23), and intact parathyroid hormone levels, accompanied by severe hypoproteinemia at week 12. (2) The results of micro-compuyed tomography (µCT) and alizarin S staining of the thoracic aorta demonstrated an increase in vascular calcification in the SNx(+) group. (3) The expression levels of vascular calcification-related proteins were increased. CONCLUSIONS: The administration of calcitriol combined with a high-calcium and high-phosphorus diet was found to induce vascular calcification in CKD rats, leading to a disturbance in mineral metabolism. Vascular calcification was effectively induced in CKD rats after 12 weeks of modeling, thereby presenting a novel approach for establishing a vascular calcification model in CKD rats, helping to elucidate this clinical condition and its underlying molecular mechanisms.

Predictive role of impulsivity, anxiety, and depression in the efficacy of intermittent theta burst transcranial magnetic stimulation modalities for treating methamphetamine use disorder: A randomized clinical trial.

INTRODUCTION: Methamphetamine use disorder (MUD) can cause impulsive behavior, anxiety, and depression. Stimulation of the left dorsolateral prefrontal cortex in MUD patients by intermittent theta burst repetitive transcranial magnetic stimulation (iTBS-rTMS) is effective in reducing cravings, impulsive behavior, anxiety, and depression. The purpose of this study was to explore whether these psychological factors helped to predict MUD patients' responses to iTBS-rTMS treatment. METHODS: Fifty MUD patients and sixty healthy subjects matched for general conditions were used as study subjects. The study randomly divided MUD patients into iTBS-rTMS and sham stimulation groups and received 20 sessions of real or sham iTBS-rTMS treatment, and the study collected cue-related evoked craving data before and after treatment. All subjects completed the Barratt Impulsiveness Scale (BIS-11), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: The MUD patients showed significantly higher levels of impulsivity, anxiety, and depression than the healthy subjects. The MUD patients who received the real treatment had significantly lower impulsivity, anxiety, and depression scores, and better treatment effects on cravings than the sham stimulation group. The Spearman rank correlation and stepwise multiple regression analyses showed that the baseline BIS-11 and the reduction rate (RR) of BIS-11 and RR of SDS were positively correlated with the decrease in cravings in the iTBS-rTMS group. ROC curve analysis showed that RR of SDS (AUC = 91.6 %; 95 % CI = 0.804-1.000) had predictive power to iTBS- rTMS therapeutic efficacy, the cutoff value is 15.102 %. CONCLUSIONS: iTBS-rTMS had a good therapeutic effect in MUD patients and the baseline impulsivity, the improved depression and impulsivity were associated with therapeutic effect of iTBS-rTMS. The improved depression had the potential to predict the efficacy of the iTBS-rTMS modality for MUD treatment.

Joint effects of CuO nanoparticles and perfluorooctanoic acid on cabbage (Brassica pekinensis L.).

Coexisting nanoparticles (NPs) may change plant accumulation and toxicity of perfluorooctanoic acid (PFOA) in soil, but research is very scarce. In this study, cabbage (Brassica pekinensis L.) was exposed to single or combined treatments of PFOA (2 mg/kg and 4 mg/kg) and copper oxide NPs (nCuO, 200 mg/kg and 400 mg/kg) for 40 days. At harvest, biomass, photosynthesis index, and nutrient composition of cabbage, as well as plant accumulation of PFOA and Cu, were measured. Results showed that nCuO and PFOA were adverse to cabbage growth by decreasing chlorophyll contents, inhibiting photosynthesis and transpiration, and interfering with the utilization of nutrient components. Besides, they also affected each other's plant utilization and transmission. Especially, nCuO at a high dose (400 mg/kg) significantly increased the transport of coexisting PFOA (4 mg/kg) content (by 124.9% and 118.2%) to cabbage shoots. The interaction mechanism between nCuO and PFOA is unknown, and more research is needed to evaluate their composite phytotoxicity.

Study on brain function of the frontal lobe in patients with functional gastroduodenal disease by near-infrared functional imaging.

OBJECTIVE: functional gastroduodenal disease is the main type of functional gastrointestinal disease in the clinical department of Gastroenterology and psychosomatic medicine at present, which accounts for a large proportion of outpatients in gastroenterology. The main manifestations are epigastric pain, dyspepsia, belching, chronic nausea, and vomiting. The purpose of this study is to explore the changes in brain function in patients with functional gastroduodenal diseases through experiments to reveal the possible central etiology and development process. METHODS: the functional changes of the prefrontal lobe in patients with functional gastroduodenal diseases and normal controls were detected and analyzed by near-infrared brain imaging. At the same time, SCL-90 was used to evaluate the mental health status of patients with functional gastroduodenal diseases and normal controls. The changes in the autonomic nerve system in patients and normal controls were detected and compared by heart rate variability trend chart. RESULTS: the activity of left prefrontal lobe areas s8-d8, s10-d4, s10-d10 and s10-d15 in patients with functional gastroduodenal disease was significantly lower than normal controls (p < 0.05). The SCL-90 scale showed that there were significant differences between patients with functional gastroduodenal disease and normal controls, especially in depression, compulsion, anxiety, somatization, interpersonal sensitivity and hostility (p < 0.05). There was no significant difference in lf/hf values detected by the HRV trend chart (p > 0.05). CONCLUSION: the function of the left frontal lobe is decreased in patients with functional gastroduodenal disease. The autonomic nervous system may be related to the connection system between the brain center and internal organs.

Total flavone of flowers of Abelmoschus manihot (L.) Medic inhibits the expression of adhesion molecules in primary mesenteric arterial endothelial cells and ameliorates dextran sodium sulphate-induced ulcerative colitis in mice.

BACKGROUND: Flowers of Abelmoschus manihot (L.) medic (AM) is a traditional Chinese medicine used to treat chronic nephritis, nephrotic syndrome, diabetic nephropathy, and colonic inflammation. PURPOSE: This study aimed to explore the influence of the total flavone of AM flowers (TFA) on acute ulcerative colitis (UC) and the potential underlying mechanism. METHODS: Efficacy of TFA (30, 60, 120 mg/kg) on UC was evaluated in a dextran sodium sulphate (DSS)-induced colonic inflammatory mouse model by analyzing disease activity index (DAI), histopathological score, colon length, and cytokine expression. Expression levels of critical adhesion molecules and nuclear factor kappa B (NF-κB) were examined by qRT-PCR, Western blotting, or immunofluorescence labeling. Myeloperoxidase activity was examined using ELISA. In vitro THP-1 adhesion assay was used to evaluate monocyte adhesion. RESULTS: TFA significantly reduced DAI score, prevented colon shortening, and ameliorated histological injuries of colons in DSS-treated mice. TFA inhibited the expression of cytokines (IL-1ß and TNF-α) and adhesion molecules (ICAM-1, VCAM-1, and MAdCAM-1) in colon tissues of DSS mice. In vitro studies on mesenteric arterial endothelial cells (MAECs) showed that TFA attenuated TNF-α-induced upregulation of ICAM-1, VCAM-1, and MAdCAM-1, as well as THP-1 cell adhesion to MAECs. TFA also suppressed the phosphorylation and nuclear translocation of NF-κB in MAECs. CONCLUSION: TFA efficaciously ameliorates UC possibly by inhibiting monocyte adhesion through blocking TNF-α-induced NF-κB activation, which in turn suppresses the upregulation of adhesive molecules in colon endothelial cells. Inhibiting the expression of adhesion molecule in MAECs may represent a useful strategy for therapeutic development to treat UC, with TFA being a safe and efficacious therapeutic agent.

Treatment of berberine alleviates diabetic nephropathy by reducing iron overload and inhibiting oxidative stress.

Diabetic nephropathy (DN) has become one of the major fatal factors in diabetic patients. The aim of this study was to elucidate the function and mechanism by which berberine exerts renoprotective effects in DN. In this work, we first demonstrated that urinary iron concentration, serum ferritin and hepcidin levels were increased and total antioxidant capacity was significantly decreased in DN rats, while these changes could be partially reversed by berberine treatment. Berberine treatment also alleviated DN-induced changes in the expression of proteins involved in iron transport or iron uptake. In addition, berberine treatment also partially blocked the expression of renal fibrosis markers induced by DN, including MMP2, MMP9, TIMP3, ß-arrestin-1, and TGF-ß1. In conclusion, the results of this study suggest that berberine may exert renoprotective effects by ameliorating iron overload and oxidative stress and reducing DN.

Scutellarein attenuates atopic dermatitis by selectively inhibiting transient receptor potential vanilloid 3 channels.

BACKGROUND AND PURPOSE: Atopic dermatitis (AD) is one of the most common chronic inflammatory cutaneous diseases with unmet clinical needs. As a common ingredient found in several medicinal herbs with efficacy on cutaneous inflammatory diseases, Scutellarein (Scu) has been shown to possess anti-inflammatory and anti-proliferative activities. We aimed to evaluate the therapeutic efficacy of Scu against AD and its underlying molecular mechanism. EXPERIMENTAL APPROACH: Efficacy of Scu on AD was evaluated in 2,4-dinitrofluorobenzene (DNFB) and carvacrol-induced dermatitis mouse models. Cytokine mRNA and serum IgE levels were examined using qPCR and ELISA, respectively. Voltage clamp recordings were used to measure currents mediated by transient receptor potential (TRP) channels. In silico docking, site-direct mutagenesis, and covalent modification were used to explore the binding pocket of Scu on TRPV3. KEY RESULTS: Subcutaneous administration of Scu efficaciously suppresses DNFB and carvacrol-induced pruritus, epidermal hyperplasia and skin inflammation in wild type mice but has no additional benefit in Trpv3 knockout mice in the carvacrol model. Scu is a potent and selective TRPV3 channel allosteric negative modulator with an apparent affinity of 1.18 µM. Molecular docking coupled with site-direct mutagenesis and covalent modification of incorporated cysteine residues demonstrate that Scu targets the cavity formed between the pore helix and transmembrane helix S6. Moreover, Scu attenuates endogenous TRPV3 activity in human keratinocytes and inhibits carvacrol-induced proliferative and proinflammatory responses. CONCLUSION AND IMPLICATIONS: Collectively, these data demonstrate that Scu ameliorates carvacrol-induced skin inflammation by directly inhibiting TRPV3, and TRPV3 represents a viable therapeutic target for AD treatment.

Structural characterization and anti-inflammatory activity of a pectin polysaccharide HBHP-3 from Houttuynia cordata.

In this study, a hot buffer soluble Houttuynia cordata polysaccharide (HBHP-3) with a molecular weight of 397.4 kDa was isolated from H. cordata. HBHP-3 was composed of rhamnose, arabinose, glucose, galactose and galacturonic acid with molar ratio of 16.0:12.6:4.6:18.1:15.6. Structural analysis showed that the main chain of HBHP-3 was composed of →2)-α-L-Rhap-(1→, →4)-α-D-GalpA-(1→ and →4)-ß-D-Galp-(1→. There were branched chains of α-L-Araf-(1→, →5)-α-L-Araf-(1→, →4)-α-D-Glcp-(1→, →6)-ß-D-Galp-(1→, ß-D-Galp-(1→ connected to the O-4 positions of →2)-α-L-Rhap-(1→. HBHP-3 effectively inhibited the secretion of NO and the mRNA expression of pro-inflammatory cytokines in a dose-dependent manner in macrophages. HBHP-3 inhibited the phosphorylation of p65 and IκBα proteins as well, illustrating that HBHP-3 exerted its anti-inflammatory activity by inhibiting the activation of NF-κB pathway.

Predictive Role of Executive Function in the Efficacy of Intermittent Theta Burst Transcranial Magnetic Stimulation Modalities for Treating Methamphetamine Use Disorder-A Randomized Clinical Trial.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment. Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls. Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively. Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR2100046954.

Wei Chang An pill regulates gastrointestinal motility in a bidirectional manner.

CONTEXT: Wei Chang An (WCA) is a commercial prescription developed for the coordination of gastrointestinal movement. OBJECTIVE: To investigate the role of WCA in the regulation of diarrhoea and constipation in rats. MATERIAL AND METHODS: The diarrhoea and constipation models were prepared by gavage of Folium senna and diphenoxylate hydrochloride. Rats were randomized equally (n = 6) into the normal group given saline daily, the positive group given Pinaverium Bromide (13.5 mg/kg) or Sennoside A (0.1 mg/kg) and three WCA-treated groups (22, 44, and 88 mg/kg) by gavage daily for 7 consecutive days. The effects of WCA were assessed by a series of faecal symptoms and histopathology. Gastrointestinal parameters were determined by ELISA. The effect of WCA on gastrointestinal tissues was evaluated by strip assay. Expression of ROCK-1 and MLCK was measured by RT-PCR and Western blotting. RESULTS: Data from Bristol stool form scale, diarrhoea index, visceral sensitivity, defaecation time, and intestinal propulsive rate showed that WCA protected rats against diarrhoea and constipation (p < 0.01). The up-regulation of Substance P and 5-hydroxytryptamine in diarrhoea rats and down-regulation of Substance P and vasoactive intestinal polypeptide in constipation rats were inhibited by WCA (p < 0.05). WCA stimulated the gastrointestinal strip contractions but inhibited ACh-induced contractions (p < 0.01). The decreased ROCK-1 and MLCK expression in diarrhoea rats and increased in constipation rats were suppressed by WCA (p < 0.01). CONCLUSIONS: WCA has both antidiarrhea and anti-constipation effects, suggesting its bidirectional role in gastrointestinal modulation, and providing evidence of WCA for irritable bowel syndrome treatment.

Parabacteroides distasonis Alleviates Obesity and Metabolic Dysfunctions via Production of Succinate and Secondary Bile Acids.

We demonstrated the metabolic benefits of Parabacteroides distasonis (PD) on decreasing weight gain, hyperglycemia, and hepatic steatosis in ob/ob and high-fat diet (HFD)-fed mice. Treatment with live P. distasonis (LPD) dramatically altered the bile acid profile with elevated lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) and increased the level of succinate in the gut. In vitro cultivation of PD demonstrated its capacity to transform bile acids and production of succinate. Succinate supplementation in the diet decreased hyperglycemia in ob/ob mice via the activation of intestinal gluconeogenesis (IGN). Gavage with a mixture of LCA and UDCA reduced hyperlipidemia by activating the FXR pathway and repairing gut barrier integrity. Co-treatment with succinate and LCA/UDCA mirrored the benefits of LPD. The binding target of succinate was identified as fructose-1,6-bisphosphatase, the rate-limiting enzyme in IGN. The succinate and secondary bile acids produced by P. distasonis played key roles in the modulation of host metabolism.

Structural Modification of Natural Product Ganomycin I Leading to Discovery of a α-Glucosidase and HMG-CoA Reductase Dual Inhibitor Improving Obesity and Metabolic Dysfunction in Vivo.

It is a great challenge to develop drugs for treatment of metabolic syndrome. With ganomycin I as a leading compound, 14 meroterpene derivatives were synthesized and screened for their α-glucosidase and HMG-CoA reductase inhibitory activities. As a result, a α-glucosidase and HMG-CoA reductase dual inhibitor (( R, E)-5-(4-( tert-butyl)phenyl)-3-(4,8-dimethylnona-3,7-dien-1-yl)furan-2(5 H)-one, 7d) with improved chemical stability and long-term safety was obtained. Compound 7d showed multiple and strong in vivo efficacies in reducing weight gain, lowering HbAlc level, and improving insulin resistance and lipid dysfunction in both ob/ob and diet-induced obesity (DIO) mice models. Compound 7d was also found to reduce hepatic steatosis in ob/ob model. 16S rRNA gene sequencing, SCFA, and intestinal mucosal barrier function analysis indicated that gut microbiota plays a central and causative role in mediating the multiple efficacies of 7d. Our results demonstrate that 7d is a promising drug candidate for metabolic syndrome.

Spatial-temporal functional mapping of language at the bedside with electrocorticography.

OBJECTIVE: To investigate the feasibility and clinical utility of using passive electrocorticography (ECoG) for online spatial-temporal functional mapping (STFM) of language cortex in patients being monitored for epilepsy surgery. METHODS: We developed and tested an online system that exploits ECoG's temporal resolution to display the evolution of statistically significant high gamma (70-110 Hz) responses across all recording sites activated by a discrete cognitive task. We illustrate how this spatial-temporal evolution can be used to study the function of individual recording sites engaged during different language tasks, and how this approach can be particularly useful for mapping eloquent cortex. RESULTS: Using electrocortical stimulation mapping (ESM) as the clinical gold standard for localizing language cortex, the average sensitivity and specificity of online STFM across 7 patients were 69.9% and 83.5%, respectively. Moreover, relative to regions of interest where discrete cortical lesions have most reliably caused language impairments in the literature, the sensitivity of STFM was significantly greater than that of ESM, while its specificity was also greater than that of ESM, though not significantly so. CONCLUSIONS: This study supports the feasibility and clinical utility of online STFM for mapping human language function, particularly under clinical circumstances in which time is limited and comprehensive ESM is impractical.

In vitro and in vivo evaluation of drug-eluting microspheres designed for transarterial chemoembolization therapy.

Poly(D,L-lactic acid) biodegradable microspheres, loaded with the drugs cisplatin and/or sorafenib tosylate, were prepared, characterized and studied. Degradation of the microspheres, and release of cisplatin and/or sorafenib tosylate from them, were investigated in detail. Incubation of the drug-carrying microspheres in phosphate buffered saline (pH=7.4) revealed slow degradation. Nevertheless, significant release of cisplatin and sorafenib tosylate from microspheres loaded with both drugs was apparent in vitro; this can be attributed to their porous structure. Supernatants from microspheres loaded with both drugs showed strong toxic effects on cells (i.e. endothelial cells, fibroblast cells and Renca tumor cells) and potent anti-angiogenic effect in the matrigel endothelial tube assay. In vivo anti-tumor effects of the microspheres were also observed, in a Renca tumor mouse model. The poly(D,L-lactic acid) microspheres containing both cisplatin and sorafenib tosylate revealed highest therapeutic efficacy, probably demonstrating that combined local administration of cisplatin and sorafenib tosylate synergistically inhibits tumor growth in situ. In conclusion, this study demonstrates the applicability of biodegradable poly(D,L-lactic acid) microspheres loaded with cisplatin and sorafenib tosylate for local drug delivery as well as the potential of these microspheres for future use in transarterial chemoembolization.

Preparation and structure of drug-carrying biodegradable microspheres designed for transarterial chemoembolization therapy.

Biodegradable poly(D,L-lactic acid) drug-eluting microspheres containing anti-tumor drugs, cisplatin, and sorafenib tosylate have been prepared by the emulsion solvent evaporation method with diameter between 200 and 400 µm. Scanning electron microscopy showed that cisplatin microspheres had smooth surfaces, while sorafenib tosylate microspheres and cisplatin + sorafenib tosylate microspheres were porous at the surface and the pits of the latter were larger than those of the former. Notably, cisplatin + sorafenib tosylate microspheres had a fast drug release rate compared with microspheres containing one drug alone. In vitro cytotoxicity experiments and classical matrigel endothelial tube assay certificated the maintaining bioactivity of cisplatin and sorafenib tosylate released from the microspheres, respectively. This work provides a useful approach for the fabrication of drug-eluting beads used in transarterial chemoembolization.

Inhibition of autophagy via activation of PI3K/Akt pathway contributes to the protection of ginsenoside Rb1 against neuronal death caused by ischemic insults.

Lethal autophagy is a pathway leading to neuronal death caused by transient global ischemia. In this study, we examined the effect of Ginsenoside Rb1 (GRb1) on ischemia/reperfusion-induced autophagic neuronal death and investigated the role of PI3K/Akt. Ischemic neuronal death in vitro was induced by using oxygen glucose deprivation (OGD) in SH-SY5Y cells, and transient global ischemia was produced by using two vessels occlusion in rats. Cellular viability of SH-SY5Y cells was assessed by MTT assay, and CA1 neuronal death was evaluated by Hematoxylin-eosin staining. Autophagic vacuoles were detected by using both fluorescent microscopy in combination with acridine orange (AO) and Monodansylcadaverine (MDC) staining and transmission electronic microscopy. Protein levels of LC3II, Beclin1, total Akt and phosphor-Akt at Ser473 were examined by western blotting analysis. GRb1 inhibited both OGD and transient ischemia-induced neuronal death and mitigated OGD-induced autophagic vacuoles in SH-SY5Y cells. By contrast, PI3K inhibitor LY294002 counteracted the protection of GRb1 against neuronal death caused by either OGD or transient ischemia. LY294002 not only mitigated the up-regulated protein level of phosphor Akt at Ser473 caused by GRb1, but also reversed the inhibitory effect of GRb1 on OGD and transient ischemia-induced elevation in protein levels of LC3II and Beclin1.