DNA Damage ; DNA Glycosylases ; genetics ; metabolism ; DNA Repair Enzymes ; genetics ; metabolism ; Humans ; Phosphoric Monoester Hydrolases ; genetics ; metabolism

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.

Ginkgo is one of the most successful cases of botanical drugs developed by modern science and technology during the past fifty years all over the world. At present ginkgo has been applied to the prevention and treatment of cardiovascular disease widely, and has good clinical efficacy. Type 2 diabetes has been proved to be the risk equivalents of cardiovascular disease, therefore it has an important scientific significance for looking for more effective drugs of prevention and control of diabetes. To seek more efficient and safe drug from the plant medicine which has the function of regulate blood sugar and improve insulin resistance becomes a hotspot at home and abroad. Basic and clinical studies have shown the ginkgo preparations of Chinese medicine have certain regulation effect on blood sugar and insulin resistance. In this paper, we review the mechanisms and clinical applications of ginkgo preparations on diabetes and its applications during the past 10 years.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Ginkgo biloba ; chemistry ; Humans ; Hypoglycemic Agents ; administration & dosage

In order to investigate the characteristics of transdermal delivery of ferulic acid under the treated of microneedle arrays and the influence on permeability of rat skin capillaries, improved Franz-cells were used in the transdermal delivery experiment with the rat skin of abdominal wall and the length of microneedle arrays, different insertion forces, retention time were studied in the influence of characteristics of transdermal delivery of FA. The amount of FA was determined by HPLC system. Intravenous injection Evans blue and FA was added after microneedle arrays treated. Established inflammation model was built by daubing dimethylbenzene. The amount of Evans blue in the rat skin was read at 590 nm wavelength with a Multiskan Go microplate reader. Compared with passive diffusion group the skin pretreated with microneedle arrays had a remarkable enhancement of FA transport (P <0.01). The accumulation of FA increased with the enhancement of insertion force as to as the increase of retention time. Microneedle arrays with different length had a remarkable enhancement of FA transport, but was not related to the increase of the length. The research of FA on the reduce of permeability of rat skin capillaries indicated that the skin pretreated with microneedle arrays could reduce the content of Evans blue in the skins of rat significantly compared with the untreated group. The permeation rate of ferulic acid transdermal delivery had remarkable increase under the treated of microneedle arrays and the length of microneedle arrays ,the retention time so as to the insertion force were important to the transdermal delivery of ferulic acid.
Administration, Cutaneous ; Animals ; Coumaric Acids ; administration & dosage ; pharmacokinetics ; Male ; Needles ; Rats ; Rats, Sprague-Dawley ; Skin Absorption

Qigui Tongfeng tablet (QLTFT) is a traditional Chinese medicine with good effect for treating gout. Here, network pharmacology method and molecular similarity analysis were utilized to study the effective substance basis and molecular mechanism of the QLTFT on the gout. The similarity to the medicinal compounds is reflected in the Tanimoto coefficient that gives the structural similarity of two compounds. Operationally, similar modifiers were described as pairs of concepts with a similarity score of 0. 500. The results of the molecular similarity analysis suggested that the flavonoids in QLTFT could be new leads for gout. Furthermore, complex biological systems may be represented and analyzed as computable networks. Two important properties of a network were degree and betweenness. Nodes with high degree or high betweenness may play important roles in the overall composition of a network. And the results of network analysis showed that dongbeinine, verticinone-N-oxide, verticine N-oxide, peimine, peiminine, isobaimonidine, dongbeirine, peimisine and simi-arenol which with high degree acted on xanthine dehydrogenase/oxidase, matrix metalloproteinase-9, an arachidonate 5-lipoxygenase-activating protein, tyrosine-protein kinase and etc. Inhibition of these targets can prevent the formation of uric acid, reduce inflammation by uric acid and regulate the body's immune response. Thus, these compounds may be the main effective substance basis. The research results not only reveals its molecular mechanism, but also provide a theoretical basis for the quality control of drugs and clinical application.
Gout ; drug therapy ; Humans ; Medicine, Chinese Traditional ; Pharmacology ; methods ; Tablets ; Technology, Pharmaceutical ; methods

KRAS is one of the most frequently mutated human oncogenes. In spite of mounting efforts on the development of direct or indirect inhibition targeting KRAS, little has been achieved because of insurmountable difficulties, titling KRAS "undruggable". Recently, subtype-specific inhibitors have shown great hope. Some KRAS^G12C inhibitors have entered clinical trials, including adagrasib and sotorasib, and have shown preliminary clinical effectiveness. Experiences from the inhibitors targeting the downstream factors of RAS pathways show that the anticancer activity of these drugs will be limited due to the development of drug resistance. Preclinical studies of KRAS^G12C inhibitors have revealed that the application of these agents might be hampered by the drug resistance issue. The current review aims to describe the current status of KRAS^G12C inhibitors, and discuss the mechanisms underlying KRAS^G12C inhibitor resistance, so as to provide the clues for the combat of drug resistance.

Objective Through construction of a lentiviral expression vector of chemokine receptor 3 (CCR3)RNA interference (RNAi) of mouse,to further study the function of CCR3 gene on eosinophils.Methods Focused on the CCR3 gene sequences,RNAi target sequences were designed,then the target sequences of Oligo DNA were synthesized and annealed to double stranded DNA,which was subsequently connected to pLVX-shRNA2-m vector digested by MluⅠ,Sac Ⅰ,EcoR Ⅰ,Hind m,BamH Ⅰ and Xho Ⅰ,short hairpin RNA lentiviral vectors were constructed.Short hairpin RNA lentiviral vectors were constructed.293T cells and eosinophils were transfected by shRNA lentiviral vector,and virus titer was determined.The expression of the CCR3 gene in eosinophils was identified by quantitative-PCR.Results The lentiviral vector of shRNA-mCCR3-oligonucleotide chain was inserted correctly.Infection efficiency of 293T cells observed under fluorescence microscope was more than 90％,the virus titer was 4 × 108TU/ml.CCR3 interference rate was 86.7％.Conclusion A lentiviral vector of CCR3-gene RNM was constructed successfully by the genetic engineering technology,and it provides a condition for further research in vitro and vivo.

AIMTo study the chemical constituents of the pine needles from Pinus massoniana Lamb..

METHODSVarious chromatographic techniques were used for the separation and purification. The physicochemical properties and spectral data were used to elucidate the structures.

RESULTSThree compounds were isolated from the n-BuOH fraction of water-extracts. The structures were identified as (7S,8R)-4,9'-dihydroxyl-3, 3'-dimethyoxyl-7, 8-dihydrobenzofunan-1'-propanolneolignan-9-O-alpha- L-rhamnopyranoside (massonianoside D, 7), 4,4',9,9'-tetrahydroxyl-3,3'-dimethyoxyl-tetrahydrocyclolignan ((+)-isolariciresinol, 8) and 4,4',9'-trihydroxyl-3,3'-dimethyoxyl-tetrahydrocyclolignan-9-O-beta-D- xylopyranoside (isolariciresinol-9-O-xyloside, 9) on the basis of spectral data (ORD, UV, IR, MS, 1HNMR, 13CNMR, 1H-1HCOSY, HMQC and HMBC etc.).

CONCLUSIONCompound 7 is a new compound, while compounds 8 and 9 were isolated from this plant for the first time.

Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Lignans ; chemistry ; classification ; isolation & purification ; Lignin ; chemistry ; isolation & purification ; Molecular Structure ; Monosaccharides ; chemistry ; isolation & purification ; Naphthols ; chemistry ; isolation & purification ; Pinus ; chemistry ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVETo observe the clinical efficacy and safety of Tiaozhi Yanggan Decoction (TZYGD) in treating non-alcoholic fatty liver.

METHODSOne hundred and thirty-eight patients were enrolled and randomized into two groups according to the random number table in a ratio of 3:1, with 8 cases eventually dropping out. The symptoms, signs, liver function markers, blood lipids, iconographic indices and clinical comprehensive efficacy after a 12-week treatment course were assessed in 101 patients treated with TZYGD in the treated group and 29 patients treated with Thiola in the control group.

RESULTSThe total effective rate in the treated group and the control group was 81.19% and 68.97%, respectively, showing a significant difference between the two groups with the former being significantly higher than the latter (P<0.05). Moreover, the improvements in the symptoms, signs, liver function, blood lipids and iconographic indices in the treated group were favorable with no serious adverse reactions.

CONCLUSIONTZYGD is effective and highly safe in treating non-alcoholic fatty liver.

Adult ; Body Mass Index ; Body Weight ; drug effects ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Fatty Liver ; blood ; drug therapy ; physiopathology ; Female ; Humans ; Lipids ; blood ; Liver ; physiopathology ; Male ; Medicine, Chinese Traditional ; adverse effects ; methods ; Middle Aged ; Phytotherapy ; adverse effects ; Treatment Outcome

BACKGROUNDPrevious investigations indicate that cooks are exposed to polycyclic aromatic hydrocarbons (PAH) from cooking oil fumes (COF). However, Emission of PAH and their carcinogenic potencies from cooking oil fumes sources have not been investigated among cooks.

AIMSTo investigate the urinary excretion of a marker for oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG), in different groups of cooks and different exposure groups, and to study the association between 8-OHdG and 1-hydroxypyrene (1-OHP), a biological marker for PAH exposure.

METHODSUrine samples were collected from different groups of cooks (n = 86) and from unexposed controls (n = 36), all are male with similar age and smoking habits. The health status, occupational history, smoking, and alcohol consumption 24 hours prior to sampling was estimated from questionnaires. The urinary samples were frozen for later analyses of 8-OHdG and 1-OHP by high performance liquid chromatography.

RESULTSExcretion in urine of 8-OHdG were similar for controls (mean 1.2 µmol/mol creatinine, n = 36), and for those who had been in the kitchen room with exhaust hood operation (mean 1.5 µmol/mol creatinine, n = 45). COF exposed cooks without exhaust hood operation had increased excretion of 8-OHdG (mean 2.3 µmol/mol creatinine, n = 18). The difference between this group and the unexposed controls was significant. The urinary levels of ln 1-OHP and ln 8-OHdG were still significantly correlated in a multiple regression analysis.

CONCLUSIONResults indicate that exposure to PAH or possibly other compounds in COF may cause oxidative DNA damage.

Adult ; Air Pollutants, Occupational ; urine ; Cooking ; DNA Damage ; Deoxyguanosine ; analogs & derivatives ; urine ; Humans ; Male ; Occupational Exposure ; Oils ; adverse effects ; Oxidative Stress ; Polycyclic Aromatic Hydrocarbons ; adverse effects ; Surveys and Questionnaires ; Young Adult