Atopic dermatitis (AD) is a chronic, relapsing, inflammatory dermatosis with a variety of clinical manifestations and difficult to cure. Currently, many AD drug candidates have entered the research and development pipeline. In order to provide technical specifications for the clinical development of AD drugs, the Center for Drug Evaluation of National Medical Products Administration released the "Technical Guidelines for Clinical Trials of Drugs for AD Treatment" (Draft for Comments) in November 2022. Non-clinical pharmacodynamics evaluation is an important research before the drug enters clinical trials. Oxazolone (OXA)- and 2,4-dinitro-fluorobenzene (DNFB)-induced models are the most popular classical hapten-induced AD murine models, but variations of modeling are existing in the methods from different studies, including sensitization sites, haptens' dosages, the period of challenges, and the skin lesions severity evaluation as well. In this study, the investigation of OXA- and DNFB-induced AD murine models with various conditions of modeling was performed to compare the characteristics of hapten-induced AD murine models in the pathological process and severity according to the appearance of AD patients, and the guidance of pharmacodynamics evaluation of AD-therapeutic drugs in clinical trials as well, which may provide a proposal for AD treatment drug candidates in the non-clinical pharmacodynamics evaluation. All animal experiments were approved by the Animal Care & Welfare Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (approval No.: 00007782 and 00007784).

The hypertension is one of chronic vascular diseases, which often implicates multiple tissues causing stroke, cardiac hypertrophy, and renal failure. A growing body of evidence suggests that inflammatory mechanisms are important participants in the pathophysiology of hypertension. In this study, the inflammatory status of these tissues (kidney, liver, heart, and brain) in spontaneously hypertensive rats (SHR) was analyzed and its molecular mechanism was explored. The tissues were dissected from SHR and age-matched control Wistar-Kyoto (WKY) rats to investigate the abundance of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma). mRNA levels were determined by reverse transcription-polymerase chain reaction and protein expression was evaluated by Western blot. To evaluate the oxidative stress of tissues, carbonyl protein content and total antioxidant capacity of tissues were detected by spectrophotometry and ferric reduction ability power (FRAP) method. The results suggest that: (1) Expressions of inflammation-related mediators (IL-1beta, TNFalpha, ICAM-1, iNOS, C/EBPdelta and PPARgamma) in SHR were higher compared with those in WKY rats except no evident increase of IL-1beta mRNA in liver and brain in SHR. (2) Tissues in SHR contained obviously increased carbonyl protein (nmol/mg protein) compared to that in WKY rats (8.93+/-1.08 vs 2.27+/-0.43 for kidney, 2.23+/-0.23 vs 0.17+/-0.02 for heart, 13.42+/-1.10 vs 5.72+/-1.01 for brain, respectively, P<0.05). However, no evident difference in the amount of carbonyl protein in liver was detected between SHR and WKY rats. (3) Total antioxidant capacities of kidney, liver, heart and brain were markedly lower in SHR than that in WKY rats (P<0.05). Thus, the present data reveal a higher inflammatory status in the important tissues in SHR and indicate that inflammation might play a potential role in pathogenesis of hypertension and secondary organ complications.
Animals ; Brain ; metabolism ; pathology ; Cytokines ; genetics ; metabolism ; Hypertension ; pathology ; Inflammation ; pathology ; Interleukin-1beta ; genetics ; metabolism ; Kidney ; metabolism ; pathology ; Male ; Myocardium ; metabolism ; pathology ; Oxidative Stress ; immunology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

Objective To analyze the species of the antibody and immune responsibility in pneumonic plague patients in order to pave the way to screen the new sub-unit of the vaccine to provide the experimental basis. Methods Using the virulence-related protein microarray containing 149 proteins of Yersinia pestis (Y.pestis), the species of the antibody and immune responsibility were analyzed in serum of two pneumonic plague patients in six months after onset. Results Eighty-eight gene coded proteins were detected out the related antibodies except YPMT1.23c, YPMT1.86, YPO0406 and YPO1071 in patient 1. Forty-three antibodies from gene coded protein were analyzed, other forty-nine had not been identified in patient 2. Thirty-nine antibodies were detected in both patients. The proteins YPMT1.81c, YPMT1.84, YPCD1.31c, rw10, YPCD1.28, YPCD1.58, YPMT1.62c, YPO3247-related antibodies increased significantly by 109.96,176.4 ;20.64,17.73 ;16.50,7.16 ;23.51,7.65 ;46.00,25.61 ;4.50,8.24 ;5.98,5.08 ;23.98,4.76 folds, respectively. Conclusions The study on the antibody in pneumonic plague patients helps us to select the potential vaccine candidates, which reveals that eight proteins are the immunity diagnosis targets and the research key of sub-unit vaccine.

OBJECTIVETo observe the regulatory effect of Chinese herbal compound for detoxifying and activating blood circulation on expression of nuclear factor-kappaB (NF-kappaB) and matrix metalloproteinase-9 (MMP-9) in aorta of apolipoprotein E gene knocked-out (ApoE (-/-)) mice.

METHODSApoE (-/-) mice of 13-week old were divided into two groups and fed with normal diet (Group A) and hyperlipidemic diet (Group B) respectively, the latter was subdivided into 7 groups as Group B1 - 7. Besides, a normal control group was set up with C57BL/6J mice. The drugs used for intervention were polydatin (PD, with 26.6 mg/kg as one dose) for detoxifying and Xiongshao Capsule (XC, with 110 mg/kg as one dose) for activating blood circulation respectively. The intervention was started 19 weeks later by treated Group B1 with PD one dose daily, Group B2 with XC one dose daily, Group B3 with PD and XC each 2 doses daily, Group B4 with PD and XC each one dose daily, Group B5 with PD and XC each half dose daily, Group B6 with lovastatin. To the Group B 7 (as a hyperlipidemia model group) as well as Group A and the normal control group, normal saline was given. After 17 weeks of intervention, the expressions of NF-kappaB and MMP-9 in aorta of mice were determined with immunohistochemical assay.

RESULTSExpressions of NF-kappaB and MMP-9 in aorta and sclerotic plaque were higher in group B7 than those in the normal control group, which were lowered in group B1 - 6 (P < 0.01), and the optimal effect was shown in group B3 (P <0.01).

CONCLUSIONCombined use of Chinese herbal medicine for detoxifying and activating blood circulation could reduce expression of NF-kappaB and MMP-9 in aorta of ApoE (-/-) mice, and the effect of the combination of the two was superior to that of use either of them.

Animals ; Anticholesteremic Agents ; pharmacology ; Aorta ; drug effects ; metabolism ; physiology ; Apolipoproteins E ; genetics ; Blood Flow Velocity ; drug effects ; Capsules ; Drugs, Chinese Herbal ; pharmacology ; Female ; Immunohistochemistry ; Lovastatin ; pharmacology ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Smooth, Vascular ; blood supply ; drug effects ; metabolism ; NF-kappa B ; biosynthesis

The purpose of this paper is to clarify the structure-activity relationship of anti-tumor activity of diosgenin derivatives in vitro. Study has found that diosgenin can inhibit the reproduction of tumor cells by inducing apoptosis and the main target spot of this effect is Bcl-2. Based on the characteristics of pharmacophoric points' of the three-dimensional pharmacophore for Bcl-2 inhibitors, we have docked lots of diosgenin derivatives with Bcl-2, then synthesized 31 compounds of them, finally assessed the anti-tumor activity of the diosgenin derivatives in vitro against A375, A549, HepG-2 and K562. Preliminary studies of SAR have indicated that the aliphatic esters, and aromatic esters of diosgenin without F ring have no anti-tumor activity in vitro. The triazole bromides of diosgenin all achieve fairly good anti-tumor activity in vitro, and those with larger hydrophobic group have the better activity. The stronger is the hydrogen bonding interaction and dipole-dipole interaction of the heterocyclic of diosgenin and diosgenin without F ring and the acid ester of diosgenin without F ring, the better is the activity of derivatives.
Antineoplastic Agents, Phytogenic ; chemical synthesis ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Diosgenin ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; antagonists & inhibitors ; Structure-Activity Relationship

OBJECTIVETo study the chemical constituents from Corallodiscus flabellata.

METHODThe compounds were isolated with macroporous adsorption resin, silica gel column chromatography and identified on the basis of their physiochemical and spectral data.

RESULTSix compounds were obtained and identified as vanillic acid, 3,4-dihydroxyphenylethyl-8-O-beta-D-glucopyranoside, syringic acid, caffeic acid, isoacteoside, ferulic acid.

CONCLUSIONAll the compounds were isolated from this plant for the first time.

Gallic Acid ; analogs & derivatives ; chemistry ; isolation & purification ; Glucosides ; chemistry ; isolation & purification ; Magnoliopsida ; chemistry ; Phenols ; chemistry ; isolation & purification ; Plants, Medicinal ; chemistry ; Vanillic Acid ; chemistry ; isolation & purification

AIMTo study the chemical constituents from Corallodiscus flabellata.

METHODSFresh plant of Corallodiscus flabellata was extracted twice with boiling water, filtered to remove insoluble materials, concentrated under reduced pressure at temperature 55 degrees C to a small volume. The concentrated liquor was subjected to solvent-solvent partitioning using ether, ethyl acetate, and n-butanol (saturated with water). The fraction of ethyl acetate extract was chromatographed over macroporous adsorption resin (Diaion HP-20) eluted with a mixture of H2O and MeOH in increasing MeOH content. Their fractions from resin were repeatedly chromatographed over Sephadex LH-20, Toyopearl HW-40, gel MCI, Gel CHP-20 and silica gel column. Structures of compounds obtained were identified on the basis of their spectral data, hydrolysis and chemical correlation.

RESULTSTwo phenylethanoid glycosides (I, II) and three phenolic acids were obtained from the EtOAc fraction of water-extracts. Their structures were identified as 3,4-dihydroxyphenylethanol-8-O-[beta-D-apiofuranosyl (1-->2)]-beta-D-glucopyranoside (I), 3,4-dihydroxyphenylethanol-8-O-[(5-O- Vanilloyl)-beta-D-apiofuranosyl(1-->2)]-beta-D-glucopyranoside (II), vanillic acid (III), syringic acid (IV) and ferulic acid (V).

CONCLUSIONI and II are new compounds. Compounds III, IV and V were isolated from this plant for the first time.

Disaccharides ; chemistry ; isolation & purification ; Drugs, Chinese Herbal ; chemistry ; Magnoliopsida ; chemistry ; Molecular Structure ; Plants, Medicinal ; chemistry ; Vanillic Acid ; chemistry ; isolation & purification

Near-infrared spectroscopy ( NIR ) is widely used in the area of food quantitative and qualitative analysis.Variable selection technique is a critical step of the spectrum modeling with the development of chemometrics.In this study, a novel variable selection strategy, automatic weighting variable combination population analysis (AWVCPA), was proposed.Firstly, binary matrix sampling (BMS) strategy that gives each variable the same chance to be selected and generates different variable combinations, was used to produce a population of subsets to construct a population of sub-models.Then, the variable frequency ( Fre) and partial least squares regression ( Reg) , which were two kinds of information vector ( IVs) were weighted to obtain the value of the contribution of each spectral variables, the influence of two IVs of Rre and Reg was considered to each spectral variable.Finally, it used the exponentially decreasing function ( EDF) to remove the low contribution wavelengths so as to select the characteristic variable.In the case of near infrared spectrum of beer and corn, the prediction model based on partial least squares ( PLS ) was established.Compared with other variable selection methods, the research showed that AWVCPA was the best variable selection strategy in the same situation.It had 72.7% improvement compared AWVCPA-PLS with PLS and the predicted root mean square error (RMSEP) decreased from 0.5348 to 0.1457 on beer dataset.It had 64.7% improvement compared AWVCPA-PLS with PLS and the RMSEP decreased from 0.0702 to 0.0248 on corn dataset.

AIMTo study the chemical constituents of the pine needles of Pinus massoniana lamb..

METHODSVarious chromatographic techniques were used to separate and purify. Their physico-chemical properties and spectral data (UV, IR, MS, 1H-1 H COSY, HMQC, DEPT, HMBC and ORD ect.) were measured for structure elucication.

RESULTSThree compounds were isolated from the n-BuOH fraction of water-extracts. Their structures were identified as massonianoside A (4), massonianoside A: (7S, 8R)-3, 4, 9'-trihydroxyl-3-methyoxyl-7, 8-dihydrobenzofunan-1'-propanolneoligan-9-O-alpha-L-rhamnopyranoside, massonianoside C (5), (7S, 8R)-9,9'-dihydroxyl-3,3'-dimethyoxyl-7,8-dihydrobenzofunan-1'- propanolneoligan-4-O-alpha-L-rhamnopyranoside and cedrusin-4-O-beta-glucoside (6), (7S, 8R)-3',9,9'-trihydroxyl-3-methoxyl-7,8-dihydrobenzofunan-1'- propanolneoligan-4-O-beta-D-glucopyranoside.

CONCLUSIONCompound 4 and 5 are new compounds.

Benzofurans ; chemistry ; isolation & purification ; Glycosides ; chemistry ; isolation & purification ; Molecular Structure ; Pinus ; chemistry ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry

AIMTo study the chemical constituents from Corallodiscus flabellata.

METHODSThe compounds were isolated and purified by macroporous adsorption resin, silica gel column chromatography and identified on the basis of their physiochemical and spectral data.

RESULTSThree phenylethanoid glycosides (I-III) were obtained from the n-BuOH fraction of water-extracts. Their structures were elucidated as 3,4-dihydroxyphenylethanol-8-O-[beta-D-apiofuranosyl (1-->3)]-beta-D-glucopyranoside (I), 3,4-dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-beta-D-apiofuranosyl (1-->3)-beta-D-glucopyranosyl-(1-->6)]-beta-D-glucopyranoside (II) and 3,4-dihydroxyphenylethanol-8-O-[beta-D-apiofuranosyl(1-->3)-beta- D-glucopyranosyl-(1-->6)]-beta-D-glucopyranoside (III).

CONCLUSIONCompounds I, II and III are new compounds.

Caffeic Acids ; chemistry ; isolation & purification ; Disaccharides ; chemistry ; isolation & purification ; Glycosides ; chemistry ; isolation & purification ; Magnoliopsida ; chemistry ; Molecular Structure ; Plants, Medicinal ; chemistry