Photothermal therapy (PTT) has attracted significant attention due to minimal side effects and high treatment specificity. However, it often requires very high temperature to achieve complete tumor ablation under a single PTT. Such high temperature brings obvious thermal damage and inflammatory response to the body, affecting the therapeutic effect. In recent years, nitric oxide (NO) has been used to significantly inhibit tumor growth and enhance the sensitivity of tumor cells of temperature and drugs, thus enhancing the therapeutic effect. However, compounds as NO donors often have some disadvantages such as poor biocompatibility and untargeted delivery, etc., therefore, this medical application based on NO therapy is limited. In conclusion, the organic combination of NO donors and photothermal agents (PTAs) is expected to overcome the shortcomings of single therapy and achieve the antitumor effect of "1 + 1 > 2". In view of the rapid development of NO combining with PTT in tumor therapy, this review firstly introduces the antitumor mechanisms of different types of NO donors. Then the treatment strategy based on NO combined with PTT is discussed. Finally, the prospects and challenges of this combination therapy strategy in the clinical treatment of cancer are discussed.

To study the pharmacokinetics characteristic of loganin, ferulic acid and stilbene glucoside in rat plasma after oral administration of Bushen Tongluo formula. The plasma samples were treated by using liquid-liquid extraction technique, the concentrations were determined by HPLC-UV. Johnson spherigel C18 column (4.6 mm x 250 mm, 5 μm) was adopted and eluted with the of mobile phase of methanol-water containing 0.01% glacial acetic acid in a gradient mode, with the flow rate at 1.0 mL x min(-1), column temperature at 30 degrees C and injection volume of 10 μL. According to the findings, loganin was determined at 235 nm, ferulic acid and stilbene glucoside were determined at 320 nm, with the sample size of 10 μL. The pharmacokinetic parameters of loganin, ferulic acid and stilbene glucoside were calculated by DAS 2. 0 software as follows: C(max) was (0.369 ± 0.042), (0.387 ± 0.071), (0.233 ± 0.044) mg x L(-1); t(max) was (0.226 ± 0.022), (0.282 ± 0.031), (0.233 ± 0.044) h; t(½β) was (6.89 ± 0.20), (10.73 ± 0.11), (6.93 ± 0.09) h; AUC(0-∞) was (1.91 ± 0.36), (3.22 ± 0.52), (1.52 ± 0.33) mg x h x L(-1); AUCO(0-t) was (1.62 ± 0.33), (2.58 ± 0.43), (1.30 ± 0.30) mg x h x L(-1); CL was (20.2 ± 4.0), (1.39 ± 0.23), (31.7 ± 6.9) L x h(-1) x kg(-1), respectively. The results showed that after the oral administration with Bushen Tongluo formula, loganin, ferulic acid and stilbene glucoside showed concentration-time curves in conformity with the two compartment model, with a rapid absorption, loganin and stilbene glucoside was excreted at a moderate speed, and ferulic acid was excreted slowly (but with the highest bioavailability). Bushen Tongluo formula can main maintain plasma concentration with three administrations everyday and so is suitable to be made into common oral preparation.
Administration, Oral ; Animals ; Biological Availability ; Coumaric Acids ; administration & dosage ; blood ; pharmacokinetics ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; pharmacokinetics ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Iridoids ; administration & dosage ; blood ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; administration & dosage ; blood ; pharmacokinetics

Objective To explore the correlation between the glucose variability and the severity of acute isolated traumatic brain injury(TBI). Method According to the inclusion/exclusion criteria,a total of 125 cases of acute isolated TBI admitted in Department of Neurosurgery of China Medical University from July 2012 to June 2015 were included. According to Glasgow coma scale(GSC),the patients were divided into five groups including control(GCS 15),mild(GCS 13?14),moderate(GCS 9?12),severe(GCS 6?8),and extra?severe(GCS 3?5)groups. Blood glucose control(including relief of the stress and the application of insulin)were carried out immediately. The average,standard deviation,and variation co?efficient of blood glucose of all groups were recorded at admission,48 hours and 3?7 days after hospitalization. The clinical records and glycemic in?dex were compared among different groups and during different periods,so as to analyze the relationship of the variability of glucose and the duration of hyperglycemia with the severity of TBI and the effects of glycemic intensive care management. Results The results of Kruskal Wallis test and Mann?Whitney Utest showed that the average,standard deviation,and variation coefficient of glucose in the extra?severe group and the severe group were statistically higher than those in the control group(P<0.05)during the same period. Meanwhile,the average,standard deviation,and variation coefficient of glucose at admission,48 hours and 3?7 days after hospitalization were also different among each group(P<0.05). The duration of hy?perglycemia and conscious disturbance in both the extra?severe group and the severe group were longer than those in the control(P<0.05). The analyses using rank correlation indicated that glucose variability,the level and duration of hyperglycemia were positively correlated with the severity of TBI(r>1). Conclusion The glucose variability in acute isolated TBI patients could be considered as the index of the severity of TBI.

OBJECTIVETo synthesize the complex fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) for labeling IgG and investigate the in vitro stability of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG and its biodistribution in mice.

METHODSfac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) was synthesized and its radiochemical purity determined using polyamide membrane chromatography. IgG was directly labeled with fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) and the labeling ratio was determined using chromatography. The stability of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG in human serum albumin and normal saline was evaluated. ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG was injected via the tail vein into 9 mice at the dose of 3.7×10⁴ Bq/100 µl, and SPECT image was obtained at 2, 4 and 12 h after the injection. The mice were sacrificed at these time points to measure the radioactivity and calculate the %ID/g in each organ.

RESULTSFac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) had a radiochemical purity of 82.48% and remained stable in vitro at room temperature within 4 h. The labeling ratio of ⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG was 57.04% with a radiochemical purity exceeding 90%. In the solution of human serum albumin, the labeled IgG maintained a stable radiochemical purity, but in normal saline, its radiochemical purity was lowered to 20% at 24 h. After injection in mice, the labeled IgG was deposited mainly in the liver, spleen, kidneys, and the blood pool showed a sustained radioactivity.

CONCLUSION⁹⁹(m)Tc(CO)₃(H₂O)₃-IgG prepared in this study has good stability in vitro and in vivo in 24 h and shows a biodistribution pattern similar to that of IgG protein in vivo. The intermediate fac-[⁹⁹(m)Tc(CO)₃(H₂O)₃](+) can meet the experimental requirement for labeling monoclonal antibodies and polypeptides.

Animals ; Immunoglobulin G ; administration & dosage ; metabolism ; Mice ; Mice, Inbred Strains ; Organotechnetium Compounds ; pharmacokinetics ; Radiopharmaceuticals ; pharmacokinetics ; Tissue Distribution

Two stable transformed lines containing antisense LeETR1 [corrected] or LeETR2 [corrected] sequences and their hybridized line were investigated to determine the effect of LeETR1 [corrected] and LeETR2 [corrected] specificity in the ethylene receptor family in tomato (Lycopersicon esculentum Mill.) on ethylene signaling. The transgenic line ale1 containing antisense LeETR1 [corrected] displayed shorter length of seedling grown in the dark and adult plant in the light, severe epinastic petiole, and accelerated abscission of petiole explant and senescence of flower explant, compared with its wild type B1. The transgenic line ale2 containing antisense LeETR2 [corrected] also exhibited shorter hypocotyls and slightly accelerated abscission. The phenotypes of cross line dale of LeETR1 [corrected] and LeETR2 [corrected] were close to ale1 in many aspects. These results suggested that LeETR1 [corrected] probably plays a relatively important role in ethylene signaling of tomato growth and development.
Ethylenes ; metabolism ; Gene Silencing ; physiology ; Lycopersicon esculentum ; physiology ; Plant Proteins ; genetics ; metabolism ; Plants, Genetically Modified ; physiology ; RNA, Antisense ; physiology ; Receptors, Cell Surface ; genetics ; metabolism

The characteristics of fruit ripening and expression of ripening-related genes were investigated in epi, an ethylene overproduction mutant of tomato (Lycopersicon esculentum Mill.). The epi produces apparently more ethylene than its wild type VFN8 at every stage of vegetative and fruit growth and ripening; compared to VFN8, the epi fruit showed higher CO2 evolution, faster descending of chlorophyll, slightly quicker increase of carotenoid and lycopene, and faster reduction in pericarp firmness during maturation and ripening; and the mRNAs of three ripening-related genes including E8, pTOM5 and pTOM6 were at higher levels in epi. The ripening-related characteristics changing of the fruit are consistent with the increase of ethylene production and ripening-related genes expression. These results suggest that epi mutation possibly did not affect the ethylene perception and signaling during fruit ripening, and that the modified characteristics of fruit ripening possibly resulted from the ethylene overproduction and increased expression of ripening-related genes.
Ethylenes ; metabolism ; Fruit ; growth & development ; metabolism ; Gene Expression Regulation, Plant ; physiology ; Hardness ; Lycopersicon esculentum ; growth & development ; metabolism ; Mutation ; Plant Proteins ; metabolism ; Signal Transduction ; physiology

OBJECTIVETo evaluate the clinical efficacy and safety of angong niuhuang pill (ANP) as an adjuvant treatment on moderate or severe neonatal hypoxic-ischemic encephalopathy (NHIE).

METHODSThirty-nine neonates with NHIE in the control group were treated with conventional treatment, and 58 in the treated group were administered orally ANP additionally, and relative indexes were observed.

RESULTSThe improvement of aspects such as recovery of consciousness, muscular tension, and primitive reflex and disappearance of convulsion, in the treated group was better than that in the control group (P < 0.01).

CONCLUSIONANP as an adjuvant treatment has a definite effect on NHIE, it can promote the recovery of patients, decrease the occurrence of sequelae and with high safety, therefore, is a drug feasible for clinical application.

Asphyxia Neonatorum ; complications ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hypoxia-Ischemia, Brain ; drug therapy ; etiology ; Infant, Newborn ; Male ; Phytotherapy

OBJECTIVETo explore cell death and apoptosis in rat hippocampal neurons at different time points after ischemia, hypoxia and reperfusion injury and to elucidate time window characteristics in ischemia neuronal injury.

METHODSHippocampal neurons were obtained from rat embryo and were cultured in vitro. The ischemia and reperfusion of cultured rat hippocampal neurons were simulated by oxygen-glucose deprivation (OGD) and recovery. OGD at different time points (0.25 h to 3.0 h) and then the same recovery (24 h) were prepared. Annexin V-PI staining and flow cytometry examined neuron death and apoptosis at different time after injury.

RESULTSAfter OGD and recovery, both necrosis and apoptosis were observed. At different times after OGD, there were statistically significant differences in neuron necrosis rate (P < 0.05), but not in apoptosis rate (P > 0.05). At recovery, survival rate of hippocampal neurons further decreased while apoptosis rate increased. Furthermore, apoptosis rates of different time differed greatly (P < 0.05). Apoptosis rate gradually increased with significant difference among those of different time points (P < 0.05). However, 2 h after ischemia, apoptosis rate decreased markedly.

CONCLUSIONSApoptosis is an important pathway of delayed neuron death. The therapeutic time window should be within 2 h after cerebral ischemia and hypoxia.

Animals ; Apoptosis ; physiology ; Brain Ischemia ; pathology ; Cell Death ; physiology ; Cell Hypoxia ; Cells, Cultured ; Disease Models, Animal ; Female ; Fetus ; cytology ; Flow Cytometry ; Hippocampus ; pathology ; Neurons ; pathology ; Pregnancy ; Pregnancy, Animal ; Probability ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; pathology ; Sensitivity and Specificity ; Time Factors

Aim To explore the effect of Klotho (KL) gene transfection on the apoptosis of MC3T3-E1 osteo-blasts induced by dexamethasone(DEX). Methods MC3T3-E1 osteoblasts were transfected by recombinant adenovirus containing KL gene(Ad-KL) and recombi-nant adenovirus containing green fluorescent protein (GFP) gene(Ad-GFP). The apoptosis model was con-structed. The transfection efficiency of Ad-KL and Ad-GFP in cells were observed using inverted fluorescent microscope, and the level of KL mRNA and protein was detected by qPCR and Western blot,respectively. The cell viability after different concentrations of DEX acting on the cells and the viability of every research group were determined by cell counting kit-8 (CCK-8) assay. The apoptotic rate was evaluated by flow cytom-etry. The level of mRNA and protein was analyzed by qPCR and Western blot, respectively. The level of caspase-9 protein was detected by immunofluorens-cence assay. Results Cells were transfected by Ad-KL and Ad-GFP successfully. KL group and KL +DEX group had higher level of KL mRNA and protein than that in other groups. The optimum concentration of DEX was 2.0 mmol·L-1. When DEX acting on the cells, the cells viability decreased and apoptotic rate increased obviously in DEX group and GFP + DEX group. The level of Bax mRNA and protein presented a upward trend in DEX group and GFP +DEX group, while the level of Bcl-2 mRNA and protein was oppo-site. But after KL transfecting MC3T3-E1 osteoblasts, the markers described above in KL group had more dramatic improvement than in DEX group and KL +DEX group. Conclusions High-dosage DEX can in-duce the apoptosis of MC3T3-E1 osteoblasts, and the pro-apoptosis effect of high-dosage DEX in MC3T3-E1 osteoblasts can be suppressed by up-regulating KL gene expression level, suggesting that the glucocorticoid-in-duced osteoporosis might be improved by up-regulating KL gene expression level, and it may be a new target for the treatment of latrogenic osteoporosis induced by high-dosage glucocorticoid in clinic.

OBJECTIVE Non-alcoholic fatty liver disease(NAFLD) encompasses a series of patho-logic changes ranging from steatosis to steatohepatitis,which may progress to cirrhosis and hepatocel-lular carcinoma.The purpose of this study was to determine whether Ganoderma lucidum polysaccha-ride peptide (GLPP) has therapeutic effect on NAFLD. METHODS ob/ob mouse model and ApoC3 transgenic mouse model were used for exploring the effect of GLPP on NAFLD. Key metabolic path-ways and enzymes were identified by metabolomics combining with KEGG and PIUmet analyses and key enzymes were detected by Western blotting. Hepatosteatosis models of HepG2 cells and primary hepatocytes were used to further confirm the therapeutic effect of GLPP on NAFLD. RESULTS GLPP administrated for a month alleviated hepatosteatosis, dyslipidemia, liver dysfunction and liver insulin resistance. Pathways of glycerophospholipid metabolism, fatty acid metabolism and primary bile acid biosynthesis were involved in the therapeutic effect of GLPP on NAFLD. Detection of key enzymes revealed that GLPP reversed low expression of CYP7A1,CYP8B1,FXR,SHP and high expression of FGFR4 in ob/ob mice and ApoC3 mice. Besides, GLPP inhibited fatty acid synthesis by reducing the expression of SREBP1c, FAS and ACC via a FXR-SHP dependent mechanism. Additionally, GLPP reduced the accumulation of lipid droplets and the content of TG in HepG2 cells and primary hepato-cytes induced by oleic acid and palmitic acid. CONCLUSION GLPP significantly improves NAFLD via regulating bile acid synthesis dependent on FXR-SHP/FGF pathway, which finally inhibits fatty acid synthesis,indicating that GLPP might be developed as a therapeutic drug for NAFLD.