To investigate the effect of Ginkgo biloba extract (GBE) on lipids accumulation and the progression of atherosclerosis(AS), ApoE-/- mice fed with HFD were injected i.g. with two different doses of GBE (GBE-L 50 mg/(kg·d) or GBE-H 150 mg/(kg·d)) for 9 weeks. The core targets and potential mechanisms of GBE therapy for AS were investigated using network pharmacological target prediction. Subsequently, oxidized low-density lipoprotein (ox-LDL)-induced THP-1 was used to investigate the effect of GBE on foam cell formation through oil red staining and Dil-oxLDL fluorescent staining. The mRNA alterations in cholesterol uptake and efflux receptors were detected by real-time quantitative PCR. Finally, the impact of GBE on the expression of PPARγ as the core target was assessed through Western blot and immunofluorescence. It was found that GBE improved serum lipid profile, reduced necrotic cores and lipid deposition in aortic root plaques, and decreased the level of inflammatory factors in serum of ApoE-/- mice. Moreover, GBE treatment reduced the level of intracellular lipid accumulation and inhibited cholesterol uptake and efflux to alleviate foam cell formation. GBE activated PPARγ to enhance ABCA1/ABCG1-induced cholesterol efflux in THP-1. These results suggest that GBE can suppress lipid accumulation and alleviate foam cell formation by activating PPARγ pathway.

Type 2 diabetes (T2D) is an independent risk factor for cognitive impairment. The dysregulation of hypoxia inducible factor (HIF) signaling in T2D patients results in impaired adaptive responses to hypoxia, thereby accelerating the progression of complications. However, limited knowledge is available regarding its precise function in diabetes-associated cognitive impairment (DACI). Here, elevated HIF-1α levels were observed in brain endothelial cells (ECs) of db/db mice. Functionally, brain ECs-specific knockdown of H if1 a significantly ameliorated T2D-induced memory loss and neuronal damage. Glycolysis in brain ECs was inhibited in this process, as indicated by RNA-seq, leading to decreased hippocampal lactate production through reduced LDHA expression. Notably, T2D patients showed increased cerebrospinal fluid lactate levels, which were strongly associated with their cognitive dysfunction. Intrahippocampal injection of lactate accelerated cognitive dysfunction and impaired adult hippocampal neurogenesis (AHN) in db/db mice. Conversely, reducing hippocampal lactate levels through the intrahippocampal injection of oxamate delayed the onset of memory deficits. Furthermore, asiatic acid was discovered to protect db/db mice from cognitive impairment by decreasing brain endothelial HIF-1α expression and subsequently reducing hippocampal lactate-induced AHN damage. Overall, this study elucidates the inhibiting role played by endothelial HIF-1α-driven lactate in AHN and highlights a potential tactic of targeting HIF-1α in brain ECs for treating cognitive impairment.

In order to investigate the chemical constituents of glycosides in Piper sintenense Hatusima, column chromatographic techniques such as silica gel, ODS, MCI GEL CHP20P, Sephadex LH-20, and semi-preparative high performance liquid chromatography were used to afford nine glycosides from the n-butanol part of the 95% ethanol extract of Piper sintenense Hatusima. Based on the physicochemical properties and NMR data, the above compounds were identified as (2S)-2-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone-2-O-β-D-glucopyranoside (1), 2-phenylethyl β-D-glucopyranoside (2), benzyl α-L-arabinopyranosyl-(1''→6')-β-D-glucopyranoside (3), benzyl β-D-xylopyanosyl-(1''→6')-β-D-glucopyranoside (4), phenethyl β-D-apiofuranosyl-(1''→ 2')-β-D-glucopyranoside(5), salidroside (6), phenethanol β-D-xylopyanosyl-(1''→6')-β-D-glucopyranoside (7), (Z)-hexenyl-O-α-L-arabinopyranosyl-(1''→6')-O-β-D-glucopyranoside (8), (Z)-hexenyl-O-β-D-xylopyanosyl-(1''→6')-O-β-D-glucopyranoside (9). Compound 1 was identified as a new compound, and compounds 3-9 were isolated from the genus Piper for the first time.

Epilepsy, one of the most common neurological diseases, is usually accompanied by anxiety, depression, cognitive disorders and other neuropsychiatric comorbidities. Current therapies are not effective in patients with drug-resistant and psychoneurotic comorbidities, so it is necessary to find new therapeutic approaches to address this challenge. Stem cells have good application basis in epilepsy for their characteristics of self-renewal, multidirectional differentiation, existence in a variety of tissues, participating in tissue regeneration and repair. This review focuses on the research progress of stem cells in epilepsy and epileptic neuropsychiatric comorbidity, in order to provide some references for subsequent clinical application in this field.

In order to investigate the feasibility of the extract from Cyclocarya paliurus as an additive in cigarettes,the volatile aromatic components were analyzed by gas chromatography-ion mobility spectrometry(GC-IMS),and C.paliurus extract was pyrolyzed to simulate cigarette smoking by TGA-GC/MS.The cracking products of C.paliurus were analyzed in a nitrogen environment,and the possible cracking mechanism of the products was reasonably speculated.The results showed that aldehydes,alcohols,and ketones were the primary volatile aroma components of the C.paliurus extract,comprising 62.28%of the total aroma components.The cracking products of C.paliurus extract varied greatly under different temperature conditions.A total of 79 compounds were identified at 200,360,and 440℃,among which 24 aromatic components were clearly identified as having significant effects on cigarette style,including aldehydes,ketones,alcohols,phenols,furans,benzene series,and other natural aromatic substances.Among them,phenols containing a high concentration are mainly formed by compounds containing the structure of guaiacol unit and eugenol unit by side chain cleavage,demethylation,demethoxylation,dehydration,etc.Furan and its derivatives are mainly formed by glycosides or glycoside compounds by breaking glucoside bonds and dehydration.

Chemical constituents of n-butanol part of ethanol extract from the leaves of Cyclocarya paliurus (Batalin) Iljinskaja were studied.Eight glycosides were separated and purified by silica gel, MCI, ODS, Sephadex LH-20 column chromatography and semi-preparative high-performance liquid chromatography.Based on the physicochemical properties and spectral data, these compounds were 3-ethyl-4-methyl-pentyl ester-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (1), juglanoside E (2), (4S)-α-terpineol-8-O-α-L-arabinofuranosyl-(1→6)-β-D-glucopyranoside (3), (4S)-α-terpineol-8-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside (4), eugenyl-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside (5), kaempferol-3-O-β-D-glucuronopyranosyl methylester (6), kaempferol-3-O-β-D-glucuronopyranoside (7), and quercetin-3-O-β-D-glucuronopyranoside (8).Among them, compound 1 was a new compound, and compounds 2-6 were isolated from the genus Cyclocarya for the first time.

In order to explore the therapeutic effects and preliminary mechanism of gypenosides (GP) on hypercholesterolemia, as well as the protective effect on liver injury induced by high-dose simvastatin and high cholesterol diet (HCD), the hypercholesterolemia model of golden hamster was established by high cholesterol diet. The experimental animals were divided into blank group, model group, GP low and high dose groups (60 mg/kg, 120 mg/kg), simvastatin group (10 mg/kg), and GP high dose combined with simvastatin group (120 mg/kg + 10 mg/kg).The efficacy was investigated through dynamic monitoring serum cholesterol and liver function related indexes after drug treatment of 14 and 23 days. The results showed that GP could significantly reduce the levels of serum low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), increase the level of serum high density lipoprotein cholesterol (HDL-C), and reduce the secretion of PCSK9. It is suggested that GP has a good therapeutic effect on HCD diet-induced hypercholesterolemia hamsters, which may be related to its inhibition of PCSK9 secretion. In addition, GP can significantly ameliorate liver damage caused by HCD diet and high-dose simvastatin. These findings provide a scientific basis and useful reference for the combination of GP and statins to reduce toxicity and increase efficacy.

Chemical constituents from the air dried parts of Cichorium glandulosum were studied. The chemical constituents of C. glandulosum were separated and purified by means of silica gel, Sephadex-LH 20, ODS column chromatography and semi-preparative high performance liquid chromatography. The structure was elucidated by physicochemical characteristics and spectral data. One new flavonoid glycoside was isolated from C. glandulosum, and identified as quercetin-3-O-［6″-O-(3-ethoxy-1, 3-dioxopropyl)］-β-D-glucopyranoside(1).

Purpose: RIOK1 has been proved to play an important role in cancer cell proliferation and migration in various types of cancers—such as colorectal and gastric cancers. However, the expression of RIOK1 in breast cancer (BC) and the relationship between RIOK1 expression and the development of BC are not well characterized. In this study, we assessed the expression of RIOK1 in BC and evaluated the mechanisms underlying its biological function in this disease context. Materials and Methods: We used immunohistochemistry, western blot and quantitative real-time polymerase chain reaction to evaluate the expression of RIOK1 in BC patients. Then, knockdown or overexpression of RIOK1 were used to evaluate the effect on BC cells in vitro and in vivo. Finally, we predicted miR-204-5p could be a potential regulator of RIOK1. Results: We found that the expression levels of RIOK1 were significantly higher in hormone receptor (HR)–negative BC patients and was associated with tumor grades (p=0.010) and p53 expression (p=0.008) and survival duration (p=0.011). Kaplan-Meier analysis suggested a tendency for the poor prognosis. In vitro, knockdown of RIOK1 could inhibit proliferation, invasion, and induced apoptosis in HR-negative BC cells and inhibited tumorigenesis in vivo, while overexpression of RIOK1 promoted HR-positive tumor progression. MiR-204-5p could regulate RIOK1 expression and be involved in BC progression. Conclusion These findings indicate that RIOK1 expression could be a biomarker of HR-negative BC, and it may serve as an effective prognostic indicator and promote BC progression.

The theories of pathophysiology come from experimental research,and experimental teaching is an important part of pathophysiology course.Experimental teaching can cultivate the abilities of independent thinking and comprehensive analysis in students,improve their practical skills,and enhance their understanding and application of theoretical knowledge.However,teaching reform should be carried out due to the drawbacks of current pathophysiological experimental teaching.With the teaching idea centered on learning,the quality of pathophysiological experimental teaching can be enhanced by rational arrangement of experimental courses,optimization of teaching contents,and comprehensive application of various teaching models,so as to effectively improve the level of theoretical knowledge and comprehensive practical ability among students.