Objective To investigate expression of cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and squamous cell carcinoma antigen (SCC-Ag) in cervical cancer patients with lung metastasis before treatment and their prognostic value. Methods The pretreatment serum expression levels of SCC-Ag and CYFRA21-1 of 72 cervical cancer patients with lung metastasis were measured. Survival rate analysis and Cox proportional hazard model were performed to evaluate the prognostic significance of two pretreatment variables. Results The media survival time (MST) of 72 patients was 14 months, and 38 (52.8 %) patients with pulmonary metastasis occurred in 1 year of treatment. The pretreatment serum SCC-Ag and CYFRA21-1 levels in the patients with tumor diameter over 4 cm or with squamous cell carcinoma were higher than those in the other patients (all P<0.05). The MST in the pretreatment serum CYFRA21-1 positive group (>3.3 mg/L) was higher than that in the negative group (13 months vs 19 months, P< 0.05), and the MST in the SCC-Ag positive group (>1.5 mg/L) was also higher than that in the negative group (14 months vs 21 months, P<0.05). The result of Cox regression analysis showed that the tumor diameter (OR = 11.6, P = 0.01), pretreatment serum SCC-Ag (OR= 4.2, P= 0.01) and CYFRA21-1 (OR= 8.2, P= 0.05) levels were independent prognostic factors of overall survival. Conclusion Pretreatment CYFRA 21-1 and SCC-Ag levels may be considered as useful prognostic indicators for cervical cancer patients with lung metastasis.

Objective To study the effect of Yangfei Huoxue Prescription on ERK1/2 and NFK-B of bleomycin-induced pulmonary fibrosis in rats. Methods All of rats were randomly divided into seven groups and were intratracheally infused with bleomycin to build the model. Sham operation group and model group were given 5‰ CMC, dexamethasone group was given dexarnethasone solution, and each treatment group was given corresponding Chinese medicine mixture. After histological process, the expression of ERK1/2 and NFK-B were examined by SABC immunohistochemical method. Results Expression of ERK1/2 and NFK-B in model group were higher than that in sham operation group (P

Anti-Inflammatory Agents ; therapeutic use ; Antioxidants ; therapeutic use ; Diabetes Mellitus, Type 2 ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Herbal Medicine ; methods ; Humans ; Hypoglycemic Agents ; therapeutic use

The study is aimed to explore the molecular mechanism of the treatment of apocynin in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. 5% DSS was used to mimic the UC model, and 2% apocynin was applied to treat the UC mice. HE staining was used for histopathological evaluation. Chemiluminescence technique was used to measure reactive oxygen species (ROS) production, and the rate of consumption of NADPH inhibited by DPI was detected to determine the NADPH oxidases (NOXs) activity. Western blot was applied to identify the level of p38MAPK phosphorylation, Griess reaction assay to analyze NO production, immunoenzymatic method to determine prostaglandin E2 (PGE2) production, real time RT-PCR and Western blot to identify the expression of iNOS and COX2, and enzyme linked immunosorbent assay to detect inflammatory cytokines TNF-α, IL-6, IFN-γ, IL-1β. Rat neutrophils were separated, and then ROS production, NOXs activity, NO and PGE2 production, NOX1 and p-p38MAPK expression were detected. Compared with the UC group, apocynin decreased ROS over-production and NOXs activity (P < 0.01), reduced p38MAPK phosphorylation, inhibited NO, PGE2 and cytokines production (P < 0.01). Apocynin also decreased NOXs activity and ROS over-production (P < 0.01), inhibited p38MAPK phosphorylation and NOX1 expression, and reduced NO and PGE2 production (P < 0.01) in separated neutrophils from UC mice. Therefore, apocynin could relieve inflammation in DSS-induced UC mice through inhibiting NOXs-ROS-p38MAPK signal pathway, and neutrophils play an important role.
Acetophenones ; pharmacology ; Animals ; Colitis, Ulcerative ; chemically induced ; drug therapy ; Cytokines ; metabolism ; Dextran Sulfate ; Inflammation ; drug therapy ; MAP Kinase Signaling System ; Mice ; NADH, NADPH Oxidoreductases ; metabolism ; Neutrophils ; metabolism ; Rats ; Reactive Oxygen Species ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

A series of tacrine-phenol-bifendate hybrids (7a-7e, 8a-8e) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs) with low hepatotoxicity. All the compounds had potent ChEs inhibitory activity with half-inhibitory concentration (IC₅₀) values at the nanomolar range. Compound 8d exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC₅₀ value of 156.39 nmol·L^-1 and compound 7b showed the most potent inhibition for butyrylcholinesterase with IC₅₀ value of 16.33 nmol·L^-1. Kinetic and molecular modeling studies showed that 8d targeted both the catalytic active site and the peripheral anionic site of AChE. In addition, these compounds showed low toxicity to hepatocytes, and compound 8d did not increase the level of reactive oxygen species in HepG2 cells.

OBJECTIVE To compare the efficacy and safety of lacosamide （LCM） and carbamazepine （CAR） as monotherapy in the treatment of adult patients with newly diagnosed epilepsy. METHODS By methods of retrospective analysis， 84 adult patients with newly diagnosed epilepsy， were admitted to the Department of Neurology， Huaihe Hospital of Henan University during Sept. 2020-Jun. 2022， were divided into the control group （40 cases， receiving CAR treatment） and the observation group （44 cases， receiving LCM treatment） according to different medication regimens. Total response rate， epilepsy seizure frequency， blood lipid levels， and the occurrence of adverse events （AEs） of patients were compared between the 2 groups. RESULTS In the first month after treatment， there was no statistically significant difference in the total response rate between the observation group （63.64%） and the control group （55.00%， P＞0.05）； the frequency of epilepsy seizure in both groups was significantly reduced compared to before treatment （P＜0.05）， but there was no statistically significant difference between 2 groups （P＞0.05）. In the third month after treatment， the total response rate of the observation group （90.91%） was significantly higher than control group （67.50%， P＜0.05）； the frequencies of epilepsy seizure in both groups were significantly reduced compared to before treatment， and the observation group was significantly lower than the control group （P＜0.05）. In the third month after treatment， the levels of total cholesterol （TC）， triglyceride （TG） and low-density lipoprotein cholestrol （LDL-C） in the control group and the level of LDL-C in the observation group were significantly higher than before treatment， and the levels of TC， TG and LDL-C in the observation group were significantly lower than those in the control group （P＜0.05）. There was no statistically significant difference in the incidence of AEs between the observation group （15.91%） and the control group （17.50%， P＞0.05）. CONCLUSIONS Both LCM and CAR have certain effects in the treatment of newly diagnosed epilepsy in adults， which can reduce the frequency of epilepsy seizure in patients and have comparable safety. Meanwhile， LCM has better long-term efficacy than CAR in treating newly diagnosed epilepsy in adults， and its impact on the patient’s blood lipid is smaller than CAR.

A novel series of bis-nicotine derivatives (3a-3i) were designed, synthesized and evaluated as bivalent anti-Alzheimer's disease agents. The pharmacological results indicated that compounds 3e-3i inhibited both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in the micromolar range (IC50, 2.28-117.86 micromol x L(-1) for AChE and 1.67-125 micromol x L(-1) for BChE), which was at the same potency as rivastigmine. A Lineweaver-Burk plot and molecular modeling study showed that these derivatives targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds could significantly inhibit the self-induced Abeta aggregation with inhibition activity (11.85%-62.14%) at the concentration of 20 micromol x L(-1).
Acetylcholinesterase ; metabolism ; Amyloid beta-Peptides ; antagonists & inhibitors ; metabolism ; Binding Sites ; Butyrylcholinesterase ; metabolism ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Nicotine ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology

Treatment with the combination of Chinese herbs and cytotoxic chemotherapies showed a higher survival rate in clinical trials. In this report, the results demonstrated that the tanshinone II A, a key component of Salvia miltiorrhiza bunge, when it is combined with the cytotoxic drug cisplatin showed synergistic antitumor effects on human prostate cancer PC3 cells and LNCaP cells in vitro. Antiproliferative effects were detected with MTT assay. Cell cycle distribution and apoptosis were detected by flow cytometer. Protein expression was detected by Western blotting. The intracellular concentration of cisplatin was detected by high performance liquid chromatography. The results demonstrated that tanshinone II A significantly enhanced the antiproliferative effects of cisplatin on human prostate cancer PC3 cells and LNCaP cells with the increase of the intracellular concentration of cisplatin. These effects were correlated with cell cycle arrested at S phase and cell apoptosis. The apoptosis might be achieved through death receptor pathway and mitochondrial pathway. Furthermore, the Bcl-2 family members were also involved in this apoptotic process. Collectively, these results indicated that the combination of tanshinone II A and cisplatin had a better treatment effect in vitro not only on androgen-dependent LNCaP cells but also on androgen-independent PC3 cells.
Androgens ; metabolism ; Antineoplastic Agents ; pharmacology ; Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cisplatin ; pharmacology ; Diterpenes, Abietane ; isolation & purification ; pharmacology ; Drug Synergism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Humans ; Male ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Prostatic Neoplasms ; metabolism ; pathology ; Salvia miltiorrhiza ; chemistry

This study is to investigate the antitumor activity of ophiopogonin B (OP-B). MTT assay, flow cytometric analysis, acridine orange staining, Lyso-Tracker Red staining and HeLa-GFP-LC3 transfect cells assay were used to detect the proliferation activity, apoptosis and autophagy of HeLa cells. The results showed that OP-B exerted potent antiproliferative activity on HeLa cells, the cell growth inhibition effect of OP-B was not due to apoptosis and OP-B could induce autophagy of HeLa cells. OP-B also induced the protein expression up-regulation of Beclin-1 and promoted LC3 I transformation LC3 II, which were representative proteins of autophagy. Furthermore, 3-MA, an inhibitor of autophagy, not only inhibited OP-B-mediated autophagy but also almost completely reversed the antiproliferative effect of OP-B, suggesting that the growth inhibition effect of OP-B was autophagy dependent. Western blotting demonstrated that OP-B inhibited the phosphorylation of Akt and its' downstream vital protein, such as mTOR and p70S6K. In addition, OP-B also induced the protein expression up-regulation of PTEN, which is a negative regulation protein for Akt/mTOR signaling pathway. However, OP-B did not affect the protein expression of total Akt. Collectively, the antitumor effects of OP-B were autophagy-dependent via repression Akt/mTOR signaling pathway. Therefore, OP-B is a prospective inhibitor of Akt/mTOR and may be used as an alternative compound to treat cervical carcinoma.
Adenine ; analogs & derivatives ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; drug effects ; Beclin-1 ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; HeLa Cells ; Humans ; Membrane Proteins ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Ophiopogon ; chemistry ; PTEN Phosphohydrolase ; metabolism ; Phosphorylation ; Plants, Medicinal ; chemistry ; Proto-Oncogene Proteins c-akt ; metabolism ; Ribosomal Protein S6 Kinases, 70-kDa ; metabolism ; Saponins ; pharmacology ; Signal Transduction ; drug effects ; Spirostans ; pharmacology ; TOR Serine-Threonine Kinases ; metabolism ; Up-Regulation

OBJECTIVETo establish the three-dimensional model of human permanent premolars based on Micro-computed tomography (Micro-CT) data, and evaluate the efficiency quantitatively of two different instrumentations for root canal retreatment.

METHODSForty extracted permanent premolars for the reason of orthodontic treatment were collected, prepared by using ProTaper Ni-Ti files and filled by cold gutta pertscha lateral condensation technique. The subjects were scanned by Micro-CT. Forty teeth were randomly divided into two groups and retreated by K-Flexo files and ProTaper Universal retreatment system respectively. Then all subjects were scanned again, and the mean percentage of remaining filling materials and the scores of remaining filling materials presented in upper, middle and apical 1/3 of the canal were calculated.

RESULTSMean percentage of the remaining filling materials by K-Flexo files was lower than that by ProTaper Universal retreatment system (P=0.005). The scores demonstrated that K-Flexo files had greater efficiency than ProTaper Universal retreatment system when retreating the apical 1/3 of canal (P<0.05).

CONCLUSIONThis study shows that both techniques could not remove filling materials completely.

Dental Alloys ; Dental Pulp Cavity ; Gutta-Percha ; Humans ; Nickel ; Retreatment ; Root Canal Filling Materials ; Root Canal Preparation ; Root Canal Therapy ; Titanium ; X-Ray Microtomography