AIM To optimize the extraction process for total polyphenols from Conioselinum vaginatu(Spreng.)Thell.,make component analysis,and evaluate their anti-oxidant,hypoglycemic activities.METHODS The effects of ultrasound,enzymatic hydrolysis,acid hydrolysis,alcohol extraction and hydrolysis processes on the extraction quantity of total polyphenols were investigated,respectively.With extraction temperature,extraction time,ethanol concetration and liquid-solid ratio as influencing factors,extraction quantity of total polyphenols as an evaluation index,the extraction process was optimized by response surface method.HPLC was adopted in the identification of polyphenolic composition and determination of their contents.Subsequently,total polyphenols' scavenging capacities on DPPH,ABTS,OH free radicals,total reducing power and inhibitory capacity on α-glucosidase were determined.RESULTS The highest extraction quantity of total polyphenols was observable when extraction process was employed.The optimal conditions were determined to be 62 ℃ for extraction temperature,54 min for extraction time,69％for ethanol concentration,and 50∶1 for liquid-solid ratio,the extraction quantity of total polyphenols was(9.51±0.2)mg GAE/g.Seven constituents existed in C.vaginatu,among which ferulic acid demonstrated the highest content,followed by that of myricetin,while D-tryptophan content was the lowest.At the concentration of 7.61 mg/L,total polyphenols displayed the scavenging rates on DPPH,ABTS,OH free radicals of 80.70％,85.97％,28.60％,total reducing power of 0.22,and inhibition rate on α-glucosidase of 77.23％,respectively.CONCLUSION This stable and reliable method can be used for the extraction of total polyphenols from C.vaginatum with strong anti-oxidant,hypoglycemic activities.

Aim To explore the effect of astragalosideⅣ(AS-Ⅳ)on lipopolysaccharide(LPS)-induced po-larization and migration of RAW 264.7 macrophages and the underlying mechanism.Methods 1 mg·L-1 LPS was used to construct cell migration model.Scratch assay was utilized to determine cell migration rate.Immunofluorescence staining was utilized to de-tect the expression and location of F4/80,iNOS and Arg-1.CCK-8 assay was used to determine the viabili-ty of RAW 264.7 cells.Griess assay was used to measure NO content.Molecular docking was used to analyze the interaction between AS-Ⅳ and the core tar-gets such as cGAS and STING protein.Western blot was employed to detect the expression of iNOS,Arg-1,cGAS,STING,NF-κB p65 and p-NF-κB p65 protein.Results AS-Ⅳ significantly inhibited the migration and M1 polarization of RAW 264.7 cells induced by LPS.Moreover,AS-Ⅳ could interact with cGAS and STING protein,especially cGAS.Further Western blot assay showed that AS-Ⅳ significantly downregulated the expression of iNOS,cGAS,STING and p-NF-κB p65 protein.Conclusions AS-Ⅳ could promote mac-rophage M1 to M2 polarization,thereby inhibited mac-rophage migration through restraining the cGAS/STING/NF-κB signaling pathway,which provides a new therapeutic target for AS-Ⅳ to improve the early inflammatory response of AS.

Aim To investigate the effects of SAHA on the expression of P-gp and the pharmacokinetic pa-rameters of its substrate phenytoin sodium in rats under hypoxic environments.Methods Wistar rats were randomly divided into the normioxic group,the hypoxic model group,and the low-,medium-and high-dose vorinostat(SAHA)groups.Liver tissues were col-lected,and the expression levels of P-gp and HDAC5 were detected by Real-time PCR and Western blot.The morphological changes of liver tissues were ob-served by HE staining.Following intragastric adminis-tration of 50 mg·kg-1 phenytoin sodium to each group,blood samples were collected,and the plasma concentration of phenytoin sodium was determined u-sing UFLC-MS/MS to calculate pharmacokinetic pa-rameters.Results Compared with the normoxic group,the expression of HDAC5 in the liver tissues of hypoxia model rats increased,while the expression of P-gp decreased.After SAHA treatment,HDAC5 expression decreased,and P-gp expression increased.Among the SAHA groups,the medium-dose group showed the most significant effect,and HE staining re-sults indicated that this concentration did not cause damage to rat liver tissues.Compared with the normox-ic group,the AUC,Cmax,and T1/2 of phenytoin sodium in hypoxia model rats were significantly raised.After administration of the medium dose of SAHA,the AUC,Cmax,MRT,and T1/2 were significantly reduced,while CLZ/r was significantly increased.Conclusions Un-der hypoxic environments,the expression of P-gp in rat liver tissue is significantly downregulated,leading to increased systemic exposure of phenytoin,reduced clearance,and consequently elevated blood concentra-tions,raising the risk of central nervous system toxici-ty.In contrast,SAHA suppresses HDAC5 expression,thereby activating P-gp transcription and enhancing its efflux function.This results in decreased systemic ex-posure and improved clearance of phenytoin,signifi-cantly reducing drug accumulation in body and ulti-mately lowering the risk of adverse effects.

Numerous studies have shown that depression is main-ly associated with the abnormal expression of connexin 43(Cx43)in astrocytes(Astro)and its mediated dysfunction of gap junction(GJ).However,the molecular mechanism of post-translational modifications targeting Cx43 to regulate neuroin-flammation-associated depression is still unclear.Post-transla-tional modifications of Cx43 mainly include phosphorylation of specific amino acid sites by PKC,PKA,PKG,MAPK and PTK,and protein degradation of Cx43 through the K48/K63 polyubiq-uitylation and deubiquitination pathways,which ultimately lead to protein degradation through K48/K63 polyubiquitination and deubiquitination.These modifications are ultimately involved in the regulation of neuroinflammatory responses through the associ-ation of GJ function.In this paper,we systematically review the role of Cx43 post-translational modifications in neuroinflamma-tion,with the aim of further exploring the potential application of targeting these modifications to modulate the inflammatory re-sponse mechanism in improving depressive symptoms.

The telomere structure in the cell nucleus is crucial for maintaining the stability and functions of chromosomes.Telomerase is a ribonucleoprotein reverse transcriptase,which catalyzes the elongation of telomeres using its own RNA as a template,thereby counteracting the shortening of telomeres caused by chromosome replication and cell division.Due to its overexpression in over 85％of malignant tumor cells,telomerase has emerged as a highly promising biomarker and a novel target for cancer therapy.In recent years,given the importance of precise quantification of telomerase activity in guiding medical diagnosis and treatment strategies,researchers have developed various high-performance telomerase detection techniques.Among these,electrochemical biosensing technique has cause much attention due to its high sensitivity,operational convenience,rapid response,and ease of miniaturization.This paper focused on the latest advances in electrochemical sensing technique for detection of telomerase activity,aiming to provide inspiration for designing novel telomerase activity detection strategies by elucidating three unique properties of telomerase primer extension products.

Objective To explore the correlation between the actual age and the pulp chamber volume(PCV)and pulp dentinal index(PDI)of the right first molars based on cone beam computed tomog-raphy(CBCT)technology,and to construct an accurate and convenient model for age estimation.Methods CBCT image data of 1 857 Han adults(883 males and 974 females)from the Department of Stomatology,Affiliated Hospital of North Sichuan Medical College were collected.The data were di-vided into training and validation sets at a ratio of 8∶2.A total of 1 485 training samples were used to construct the age estimation model,and 372 samples were used to validate the accuracy of the model.The Mimics 21.0 software was used to measure the PCV and calculate the PDI of the right first molars.Their correlations with age and the differences between different sexes and tooth positions were analyzed.Results Both the PCV and the PDI of the first molars showed strong negative correla-tions with the actual age(r values ranged from 0.82 to 0.89).The differences in PCV and PDI be-tween different sexes and tooth positions were statistically significant(P<0.05).The age estimation model based on PDI was superior to that based on PCV.The model based on the PDI values of the two right first molars(y=73.72-44.15 x3-28.27 x4,where x3 and x4 are the PDI values of the right maxil-lary and mandibular first molars,respectively)was the best,with the R2 of 0.79 and the mean abso-lute error of 4.90 years.Conclusion Both PCV and PDI of the first molars are effective indicators for age estimation.The age estimation model based on the PDI is more convenient and accurate than that based on the PCV,providing a more effective method for age estimation in forensic practice.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

AIM To establish the quantitative models for gallic acid,mononucleoside,loganin,resveratrol,and rhein in Yishen Xiezhuo Mixture.METHODS HPLC was adopted in the content determination of various effective components,after which the near-infrared spectroscopy(NIRS)data were collected in 128 batches of samples and pretreatment was conducted,competitive adaptive reweighting sampling(CARS)algorithm was used for screening wavelength,partial least square method(PLS)regression analysis was performed.RESULTS There were no significant differences between the predicted values obtained by PLS models and measured values obtained by HPLC for various effective components(P＞0.05).CONCLUSION The quantitative models established by NIRS combined with chemometrics display good predictive performance,which can be used for the rapid determination of effective components in Yishen Xiezhuo Mixture,and provide a reference for the rapid monitoring of other traditional Chinese medicine preparations in production processes.