Objective:To determine whether the Rb1 of ginsenoside has protective effects on PA induced oxidative stress in endothelial cells.Methods:Established a model of palmitic acid-induced oxidative stress injury in human umbilical vein endothelial cells(HUVECs).Using MTT assay,flow cytometry,fluorescent probe staining,and Western blot analysis to detect whether Rb1 of ginsenoside has effects on the cell viability,apoptosis rate,ROS and NO production,mitochondrial membrane potential,and the expression levels of related proteins.Results:MTT assay and flow cytometry revealed that ginsenoside Rb1 can reduce PA-induced apoptosis in HUVECs(P＜0.05).The mechanism may be related to the following two points:(1)reducing ROS production and increasing NO levels,thereby enhancing the antioxidant capacity of HUVECs;(2)regulating the expression of Bcl-2 family proteins,increasing the BCL-2/Bax ratio(P＜0.05),modulating mitochondrial membrane permeability,reducing cytochrome C release(P＜0.001),and decreasing Caspase protein activation(P＜0.01),thereby attenuating PA-induced apoptosis.Conclusion:After the stimulation with PA,ROS production in human umbilical vein endothelial cells increased while NO content and cell activity decreased,oxidative stress induced apoptosis in cells.By regulating the production of ROS and NOx stabilizing the mitochondrial transmembrane potential,reducing the leakage of cytochrome C,Ginsenoside Rb1 can reduce HUVECs apoptosis induced by PA.

Objective:To determine whether the Rb1 of ginsenoside has protective effects on PA induced oxidative stress in endothelial cells.Methods:Established a model of palmitic acid-induced oxidative stress injury in human umbilical vein endothelial cells(HUVECs).Using MTT assay,flow cytometry,fluorescent probe staining,and Western blot analysis to detect whether Rb1 of ginsenoside has effects on the cell viability,apoptosis rate,ROS and NO production,mitochondrial membrane potential,and the expression levels of related proteins.Results:MTT assay and flow cytometry revealed that ginsenoside Rb1 can reduce PA-induced apoptosis in HUVECs(P＜0.05).The mechanism may be related to the following two points:(1)reducing ROS production and increasing NO levels,thereby enhancing the antioxidant capacity of HUVECs;(2)regulating the expression of Bcl-2 family proteins,increasing the BCL-2/Bax ratio(P＜0.05),modulating mitochondrial membrane permeability,reducing cytochrome C release(P＜0.001),and decreasing Caspase protein activation(P＜0.01),thereby attenuating PA-induced apoptosis.Conclusion:After the stimulation with PA,ROS production in human umbilical vein endothelial cells increased while NO content and cell activity decreased,oxidative stress induced apoptosis in cells.By regulating the production of ROS and NOx stabilizing the mitochondrial transmembrane potential,reducing the leakage of cytochrome C,Ginsenoside Rb1 can reduce HUVECs apoptosis induced by PA.

Ganoderic acid is a class of lanostane-type triterpenoids found in Ganoderma species, and is one of the most important pharmacologically active components in G. lucidum, exhibiting antioxidant, anti-neuropsychiatric, anti-tumor, and immune-enhancing properties. The content of ganoderic acid in G. lucidum is very low, and the traditional extraction process is complex, yielding minimal amounts at high cost. The biosynthetic pathway of G. lucidum triterpenoids(GLTs), including the synthesis of different structural forms of ganoderic acid from lanosterol, as well as the molecular regulatory mechanisms involving key regulatory enzyme genes and their functions, are not yet fully understood. With the continuous development of synthetic biology technologies, there has been a deeper understanding of the biosynthesis and metabolic regulation pathways of ganoderic acid and its derivatives at the molecular level. Research has explored the key regulatory enzyme genes related to ganoderic acid biosynthesis and their functions. Moreover, through the optimization of synthetic biology and culture conditions, large-scale production and preparation of GLTs at the cellular level have been achieved. This paper reviews and analyzes the latest research progress on the biosynthesis pathways and metabolic regulation of GLTs, focusing on the configuration of ganoderic acid and its derivatives, the biosynthetic pathways, key enzyme genes, transcription factors related to ganoderic acid biosynthesis, signal transduction mechanisms, and factors affecting triterpenoid biotransformation. This review is expected to provide a theoretical basis and technical reference for improving the efficient production of triterpenoid pharmacological components and the exploitation and utilization of G. lucidum resources.
Triterpenes/chemistry* ; Reishi/chemistry* ; Biosynthetic Pathways ; Lanosterol

Objective:To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia(AML)cells.Methods:Juglone and AML targets were collected from public databases,and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML.Then wet experiments were performed to verify.AML cell lines including KG-1a,MV-411,THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h.MTT assay was used to detect cell viability and determine the IC50,and the most sensitive cell line was screened for subsequent experiments.Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone.Western blot was performed to check the expression of relevant proteins.Results:Eleven targets were obtained as potential targets for juglone in the treatment of AML,and the top ten significantly enriched pathways were intrinsic pathway of apoptosis,programmed cell death,cytochrome c-mediated apoptotic response,apoptosis,apoptotic factor-mediated response,regulated necrosis,cytokine signaling in immune system,signaling by interleukins,oncogene induced senescence,and signal transduction.The cell viability of KG-1a,MV-411,THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment(r=-0.992,-0.886,-0.956,-0.910).Among them,MOLM-13 was the most sensitive to juglone.The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone(r=0.99).At the same time point,p-RIPK1/RIPK1,p-RIPK3/RIPK3,and p-MLKL/MLK were decreased in each juglone concentration group compared with control group.Conclusion:Juglone inhibits the viability of KG-1a,MV-411,THP-1 and MOLM-13 cells,and induces apoptosis of MOLM-13 cells,the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.

Objective:To investigate the effect of iron overload on the expression of programmed death-1(PD-1)on the surface of T lymphocyte in mice,in order to analyze the mechanism of iron overload inhibiting T cell function.Methods:Flow cytometry was used to detect the labile iron pool(LIP),reactive oxygen species(ROS),and the expression of PD-1 in peripheral blood T cells in mice with iron overload.Results:The mean fluorescence intensity of calcein in T cells of mice in iron overload group was 2 492±311.1,which was significantly lower than 3 136±537.3 in the control group(P＜0.01),suggesting that increased LIP in iron overload group.Compared with the control group,the ratio of CD4/CD8 of peripheral blood T cells was normal or increased in iron overload group.The level of ROS in T cells was 2 452±393.3 in iron overload group,which was significantly increased compared to 1 874±121.8 in the control group(P＜0.001).The expression of PD-1 on the surface of T cells was significantly increased.The percentage of PD-1+cells in CD8+T cells was(12.97±6.92)％and(6.18±2.95)％in iron overload group and control group,respectively(P＜0.05),and that in CD8-T cells was(33.55±15.69)％and(12.51±4.11)％(P＜0.001).Conclusion:The expression of PD-1 on peripheral blood T cells in mice with iron overload is significantly increased,which may be involved in inhibiting T cell effector function.

Objective:To explore the effects of dexmedetomidine (DEX) on postoperative pain, oxidative stress and adverse reactions in patients undergoing radical mastectomy.Methods:A total of 90 patients with breast cancer who received radical surgical treatment in our hospital from Jun. 2022 to Jun. 2023 were prospectively included as research objects and randomly divided into 3 groups with 30 patients in each group. DEX group was applied before, during and after surgery, respectively. The levels of pain visual analogue scale (VAS), Richmonation sedation score (RASS), superoxide dismu-tase (SOD) and malondialdehyde (MDA) were recorded.Results:The recovery time and extubation time in preoperative and intraoperative DEX group were significantly lower than those in postoperative DEX group, and the awakening time and extubation time in preoperative DEX group were significantly lower than those in intraoperative DEX group ( F value was 48.62 and 53.98, respectively, P<0.001). At 1 h, 6 h and 12 h after surgery, the VAS and RASS scores of patients in the preoperative and intraoperative DEX group were significantly lower than those in the postoperative DEX group, compared with those in the intraoperative DEX group. The VAS and RASS scores in the DEX group were significantly decreased ( F value: 62.34, 55.24, 69.26, 36.82, 24.20, 39.97, P<0.001). At 24h after surgery, there was no significant difference in VAS and RASS scores among the three groups ( F value was 0.45 and 0.81, respectively, P value was 0.613 and 0.418). Immediately after surgery, 24 h after surgery, 72 h after surgery, the SOD level of DEX group was significantly higher than that of DEX group before and during surgery ( F value was 29.37, 33.24, 10.35, P<0.001). MDA levels were significantly lower than those in postoperative DEX group ( F value was 30.52, 41.27, 8.26, P<0.001). There was no significant difference in the incidence of postoperative adverse reactions among all groups ( P>0.05) . Conclusion:Preoperative and intraoperative application of DEX can reduce postoperative pain and oxidative stress in breast cancer patients, help patients recover quickly after surgery, and preoperative application is superior to intraoperative application.

Objective To explore the chemical basis of Shenxianshengmai oral liquid.Method UHPLC-Q Exactive Focus MS/MS technology was used to identify the chemical components of Shenxianshengmai oral liquid.The chromatographic separation was performed on a Thermo Accucore aQ C18 column(150 mm×2.1 mm,2.6 μm)with mobile phase gradient elution of 0.1%formic acid aqueous solution(A)and methanol(B)for 0-13 min,5%-60%B;13-27 min,60%-95%B;27-30 min,95%B,the flow rate was 0.3 mL·min-1,and the column temperature was at 30℃.The mass spectrometry was performed by heating electrospray ionization(H-ESI)with positive and negative ion scanning modes.The scanning range was m/z 120-1800,and the collision energies were 30 eV,50 eV and 70 eV.Result A total of 160 components were identified,including 29 flavonoids,24 organic acids,21 alkaloids,19 terpenoids,15 phenylpropanoids,12 saponins and 40 other components.Six chemical constituents(rutin,psoralenoside,isopsoralenoside,psoralen,isopsoralen and bakuchiol)were confirmed by comparison with reference substances.Conclusion In this study,an UHPLC-Q Exactive Focus MS/MS method has been established for accurate,rapid and systematic identification of the constituents in Shenxian Shengmai oral liquid,which provides an important basis for clarifying the chemical basis and quality control.

AIM To study the phenylpropanoids from Brandisia hancei Hook.f.and their antioxidant activities.METHODS The extract from B.hancei was isolated and purified by Rp-C18,MCI,semi-preparative HPLC,silica gel and Sephadex LH-20,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The cytotoxicities was determined by MTT method,and the antioxidant activities were determined by DPPH and ABTS+free radical scavenging methods.RESULTS Fifteen phenylpropanoids were isolated and identified as(+)-pinonesinol(1),(-)-medioresinol(2),(-)-syringaresinol(3),buddlenol D(4),(7R,7'R,7″S,8S,8'S,8″S)-4',5″-dihydroxy-3,5,3',4″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol(5),(-)-(7R,7'R,7″R,8S,8'S,8″S)-4',4″-dihydroxy-3,3',3″,5-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineolignan-7″,9″-diol(6),hedyotol A(7),dracunculifoside R(8),acteoside(9),isoacteoside(10),arenarioside(11),isomartynoside(12),curcasinlignan B(13),erythro-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-l-ol(14),citrusin C(15).Compounds 1-4 and 9-10 had no obvious cytotoxicity to HepG2 hepatoma cells.Compounds 1,3,9,10 and 12 had strong scavenging activities against DPPH radicals.Compounds 1-3,9-10,12 and 14 showed strong scavenging activities against ABTS+radical.CONCLUSION Compounds 1-8 and 12-15 are isolated from genus Brandisia for the first time.The phenylpropanoids from B.hancei show strong antioxidant activities.

AIM To analyze the constituents absorbed into blood and brain from Zhishe Tongluo Capsules.METHODS Sixteen rats were randomly assigned into four groups and given intragastric administration(3.1 g/kg),after which the cerebral ischemia-reperfusion injury(MACO)model was established,the blood and brain tissues were collected,and UHPLC-Q Exactive Focus MS/MS was adopted in the identification of prototype constituents.RESULTS Total 70 constituents were identified,20 of which were found in the blood,mainly including flavonoids,tanshinones and Ligusticum chuanxiong phthalides,and 7 of them could enter the brain through blood-brain barrier.Compared with the normal administration group,the MACO administration group demonstrated added constituents absorbed into blood containing 3-hydroxybenzoic acid,calycosin-7-glucoside,curcumenol,senkyunolide B,dihydrotanshinone I and cryptotanshinone;removed constituents absorbed into brain containing puerarin,elemicin,sedanolide,and added those containing salvianolic acid A,senkyunolide I,dihydrotanshinone I in the left brain tissues(infarcted side).CONCLUSION The constituents absorbed into blood and brain from Zhishe Tongluo Capsules,along with the enhanced absorptions of phthalides,quinones and phenols in MACO rats in vivo may be the active substances for treating cerebral infarction.

Objective To investigate the association between the serum creatinine/cystatin C ratio(SCr/Cys C)as a Sarcopenia index(SI)and the incidence of in-hospital adverse events in patients with acute myocardial infarction(AMI)undergoing emergency percutaneous coronary intervention(PCI).Additionally,we evaluate the predictive efficacy of the SI in predicting major adverse cardiovascular events(MACEs)during hospitalization.Methods A total of 306 patients with AMI who underwent emergency PCI in the 904th Hospital of PLA Joint Logistics Support Force from January 2020 to March 2023 were consecutively included in this retrospective analysis.Patients were divided into two groups based on the occurrence of MACEs during hospitalization:MACEs group(n=43)and non-MACEs group(n=263).Clinical characteristics and pre-PCI laboratory test results were collected.Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for MACEs.The predictive performance of SI was assessed using receiver operating characteristic(ROC)curve analysis.Results The incidence of in-hospital MACEs in AMI patients was 14.1%.The results of the independent samples t-test showed that the SI level in MACEs group was significantly lower than that in non-MACEs group,with a statistically significant difference(P<0.001).The results of the multivariate logistic regression analysis suggested that new-onset atrial fibrillation,Killip class 2-4,SI,and TG were independent risk factors for in-hospital adverse events after emergency PCI.The ROC curve results showed that the predictive value of SI(AUC=0.741,95%CI 0.666-0.816)using the SCr/Cys C ratio was superior to that of single Cys C(AUC=0.658,95%CI 0.570-0.746)for predicting post-PCI MACEs,with a statistically significant difference(P<0.05),and the optimal cutoff value for SI was 78.14.After stratifying SI based on the cutoff value,the results of the independent samples t-test showed that compared to the higher SI group,the lower SI group had a higher occurrence of specific adverse events such as heart failure(P<0.001),malignant arrhythmias(P=0.009),and strokes(P=0.003),with statistically significant differences.Conclusions The results highlight SI as an independent risk factor for MACEs during hospitalization after emergency PCI in AMI patients.Furthermore,SI has proven to be an effective prognostic index for patient outcomes.