Advances in animal models of chronic heart failure and its applications in traditional Chinese medicine / 中国中药杂志

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.

Effect of MiR-155 Knockout Mediated by Dual sgRNAs on Drug Sensitivity of FLT3-ITD+AML / 中国实验血液学杂志

OBJECTIVE@#Two sgRNAs transfected FLT3-ITD+AML cell line MV411 with different binding sites were introduced into CRISPR/cas9 to obtain MV411 cells with miR-155 gene knockout. To compare the efficiency of miR-155 gene knockout by single and double sgRNA transfection and their effects on cell phenotypes.@*METHODS@#The lentiviral vectors were generated containing either single sgRNA or dual sgRNAs and packaged into lentivirus particles. PCR was conducted to measure gene editing efficiency, and miR-155 expression was evaluated by qPCR. CCK-8 assay was used to evaluate the cell proliferation, and calculate drug sensitivity of cells to adriamycin and quizartinib. Annexin V-APC/7-AAD staining was used to label cell apoptosis induced by adriamycin and quizartinib.@*RESULTS@#In the dual sgRNAs transfected cells, a cleavage band could be observed, meaning the success of gene editing. Compared with the single sgRNA transfected MV411 cells, the expression level of mature miR-155-5p was lower in the dual sgRNA transfected cells. And, dual sgRNA transfected MV411 were more sensitive to adriamycin and quizartinib with lower IC50 and higher apoptosis rate.@*CONCLUSION@#The inhibition rate of miR-155 gene expression transfected by dual sgRNA is higher than that by single sgRNA. Dual sgRNA transfection can inhibit cell proliferation, reverse drug resistance, and induce apoptosis more significantly. Compared with single sgRNA transfection, dual sgRNA transfection is a highly efficient gene editing scheme.

Trace therapeutic substances of traditional Chinese medicine: great resources of innovative drugs derived from traditional Chinese medicine / 中国中药杂志

The traditional Chinese medicine(TCM) contains very complex constituents. Besides the major constituents, there are a large number of unclear trace constituents with novel skeletons and potent bioactivities, which have been regarded as one of the important therapeutic substances and the great resources of innovative drugs derived from TCM. The present review highlighted that the development of the trace therapeutic substances of TCM is closely depends on the advanced technologies for their identification, isolation, structure elucidation, and bioactivity evaluation. Additionally, this paper reviewed the novel trace compounds derived from Chinese herbal medicines which have been published in Organic Letters during 2001-2021, and summarized the important licensed drugs originated from the trace therapeutic substances and the discovery and development of trace therapeutic substances of 8 kinds of Chinese herbal medicines. This review provides references for the research and development of TCM therapeutic substances and innovative drugs.

Bioactive neolignans and lignans from the roots of Paeonia lactiflora / 中国天然药物

Two new neolignans and one new lignan (1-3) were obtained from the roots of Paeonia lactiflora. Their structures were unambiguously elucidated based on extensive spectroscopic analysis, single-crystal X-ray crystallography, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 was a racemic mixture and successfully resolved into the anticipated enantiomers via chiral-phase HPLC. Compound 3 demonstrated moderate inhibitory activity against human carboxylesterase 2A1 (hCES2A1) with an IC50 value of 7.28 ± 0.94 μmol·-1.

A new phenolic acid ester from solid culture of Colletotrichum capsici, an endophytic fungus from Paeonia lactiflora / 中国中药杂志

A new phenolic acid ester, 4'-hydroxyphenylethyl 4,8(R)-dihydroxyphenylpropionate(1), was isolated from an endophytic fungus Colletotrichum capsici of Paeonia lactiflora roots, along with eight known phenolic derivatives, tyrosol(2), 2-(4-hydroxyphenyl) ethyl acetate(3), methyl p-hydroxyphenylacetate(4), methyl m-hydroxyphenylacetate(5), 4-(4-hydroxyphene-thoxy)-4-oxobutanoic acid(6), 4-hydroxyphenethyl methyl succinate(7), trichodenol B(8) and 4-hydroxyphenethyl 2-(4-hydroxyphenyl) acetate(9). Their structures were identified by a combination of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), nuclear magnetic resonance(NMR) spectroscopy, ultraviolet(UV) spectroscopy and electronic circular dichroism(ECD) spectroscopy. Compounds 2-9 were isolated from this fungus for the first time.

A new dimeric dehydrocorydaline alkaloid from vinegar-prepared Corydalis yanhusuo / 药学学报

Bidehydrocorydaline A (1), a new dimeric alkaloid of proberberine connected by a methylenedioxy group, was isolated from the vinegar-prepared Corydalis yanhusuo by various chromatographic methods, including column chromatography over macroporous adsorption resin and silica gel, reverse-phase MPLC, and semi-preparative HPLC. Its structure was determined by spectroscopic methods, including UV, IR, HR-ESI-MS, 1D and 2D NMR. Bidehydrocorydaline A (1) showed potent inhibitory activity against LPS-induced NO production in RAW 264.7 macrophages, with an IC50 value of 2.33 ± 0.57 μmol·L-1.

A new dimeric benzylisoquinoline alkaloid from Corydalis yanhusuo / 药学学报

(±)-Bicoryanhunine B (1), a new dimeric benzylisoquinoline alkaloid was isolated from the dried tubers of Corydalis yanhusuo by various chromatographic methods, including silica gel, Sephadex LH-20, reverse phase C18, and semi-preparative HPLC. Its structure was determined by spectroscopic methods, including UV, IR, ESI-MS, HR-ESI-MS and 1D/2D NMR. (±)-Bicoryanhunine B (1) was a moderate PD-1/PD-L1 interaction inhibitor with an IC50 value of 7.80 ± 0.49 μmol·L-1. In addition, 1 exhibited potent inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages with an IC50 value of 4.83 ± 2.21 μmol·L-1.

Bioactive sesquineolignans from the twigs of Litsea cubeba / 中国天然药物

In a continuing search for biological natural products with structure diversity from traditional Chinese herbs, five new sesquineolignans (1-5) were isolated from an ethyl acetate extract of the twigs of Litsea cubeba. Their structures were elucidated based on MS, 1D and 2D NMR spectroscopic data, as well as experimental electronic circular dichroism (ECD) spectra. Compounds 1-5 showed moderate inhibitory effects against LPS-induced NO production in RAW264.7 macrophages, with IC

Identify Myeloid Differentiation-Related MiRNAs Response to ATRA Induction by RNA Sequencing and CRISPR/Cas9 Gene Editing / 中国实验血液学杂志

OBJECTIVE@#To identify differentiation related miRNA and evaluate roles of miRNA during ATRA induced myeloid differentiation.@*METHODS@#The small RNA sequencing was used to analyze differential expressed miRNAs in ATRA induced NB4 cells. Then the several up or down-regulated miRNA were selected as the research candidates. SgRNAs targeting the genome of each miRNA were designed and NB4 cells with inducible expression of Cas9 protein were generated. After transduced sgRNA into NB4/Cas9 cells, the mutation level by PCR and surveyor assay were evaluated. The cell differentiation level was investigated by surface CD11b expression via flow cytometry.@*RESULTS@#A total of 410 mature miRNAs which expressed in NB4 cells were detected out after treated by ATRA, 74 miRNAs were up-regulated and 55 were down-regulated miRNAs with DNA cleavage generated by CRISPR/Cas9 was assayed directly by PCR or surveyor assay, quantitative PCR showed that the expression of miRNA was downregulated, which evaluated that gene edition successfully inhibitied the expression of mature miRNA. MiR-223 knockout showed the myeloid differentation of NB4 significantly inhibitied, while miRNA-155 knockout showed the myeloid differentation of NB4 cells significantly increased.@*CONCLUSION@#CRISPR/Cas9 is a powerful tool for gene editing and can lead to miRNA knockout. Knockouts of miR-223 and miR-155 have shown a differentiation-related phenotype, and the potential mechanism is the integrative regulation of target genes.

Construction and application of pharmacophore model of human carboxylesterase 2 inhibitors / 中国中药杂志

According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 μmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.

Three new polyoxygenated bergamotanes from the endophytic fungus Penicillium purpurogenum IMM 003 and their inhibitory activity against pancreatic lipase / 中国天然药物

Purpurolides D-F (1-3), three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system, were isolated from the endophytic fungus Penicillium purpurogenum IMM 003. Their structures were unambiguously elucidated based on extensive spectroscopic data analyses, C NMR chemical shifts calculations coupled with the DP4+ probability method, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 1-3 showed significant inhibitory activity against pancreatic lipase (PL). The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.

Alveolar soft part sarcoma in children: a clinicopathological study of 13 cases / 中华病理学杂志

To investigate the clinicopathological manifestations, molecular genetic, diagnostic histology and differential diagnosis of alveolar soft part sarcoma (ASPS) in children. A total of 13 cases of ASPS diagnosed at Beijing Children's Hospital from August 2009 to November 2018 were collected. HE staining, histochemical staining for PAS and D-PAS, immunohistochemical (IHC) staining for TFE3, INI1 and CD68 and florescence in situ hybridization (FISH) for TFE3 gene translocation were performed. There were four males and nine females, age ranged from 1 year and 2 months to 13 years and 8 months (mean 7.8 years); and four patients were under 5 years old. Histologically, the tumors showed a distinctive and characteristic nested or organoid growth pattern (11 cases) or solid, diffuse growth (2 cases). The tumor cells possessed abundant eosinophilic, or glycogen-rich and clear to vacuolated cytoplasm. The chromatin was relatively dispersed, with prominent and pleomorphic nucleoli; mitotic figures were rare. Vascular invasion was frequently seen. IHC staining showed specific nuclear TFE3 staining. The tumor cells were also positive for INI1,CD68 and vimentin; but were negative for MyoD1, Myogenin, CK and S-100 protein. Seven cases showed PAS and D-PAS staining, with fuchsia acicular or rod-shaped crystals in tumor cytoplasm. Nine cases showed TFE3 break-apart signals by FISH. ASPS is a rare soft tissue sarcoma in children. Compared with ASPA in adults, it has both similarities and unique clinicopathologic characteristics. The diagnosis needs to be confirmed by combining clinical, pathologic, IHC and genetic testing.

Chemical constituents from ethyl acetate soluble extraction of Litsea cubeba / 中国中药杂志

Chemical investigation on the constituents of the ethyl acetate soluble extraction of Litsea cubeba has resulted in the isolation and structure elucidation of thirty compounds, including one sesquiterpene(1), four monoterpenes(2-5), two γ-butyrolactone derivatives(6 and 7), seven tyramine derivatives(8-14), fifteen aromatic compounds(15-29), and one pyrone derivative(30) via various chromatographic techniques and spectroscopic data analysis(MS, IR, 1 D and 2 D NMR). Compounds 1-7, 13 and 14 were obtained from the genus Litsea for the first time.

Research progress of natural non-alkaloids with analgesic activity / 中国中药杂志

Pain is a complex, unpleasant feeling and emotional experience associated with actual or potential tissue damage, and manifests itself in certain autonomous psychological and behavioral responses. The commonly used opioid and non-steroidal anti-inflammatory analgesics(NSAIDs) may cause adverse reactions to the kidney, liver, cardiovascular or gastrointestinal system and cause problems of drug abuse. Therefore, it is necessary to study new analgesic drugs with less side effects and significant analgesic effects. A variety of natural products derived from terrestrial plants, microorganisms, marine organisms and fungi have been an important source of clinical medicines and provide an inexhaustible resource for the development and innovation of modern medicines. Therefore, this paper mainly reviews the natural non-alkaloids with analgesic activity in order to provide reference for the research and development of analgesic drugs derived from natural products.

Research progress of natural alkaloids with analgesic activity / 中国中药杂志

Pain is a protective defense response of the body to harmful stimuli. Long-term pain not only seriously affects the body of the patient and brings great pain to the patient, but also brings huge economic burden to the patient's family and society. It has become one of the most serious problems affecting human health. At present, opioids and non-steroidal anti-inflammatory drugs(NSAIDs) are commonly used as painkillers, but they tend to cause a variety of adverse reactions or risk of addiction. To find and develop new analgesic drugs, which are safer and more effective, has become the hot spot and difficulty in medical research. A variety of alkaloids derived from terrestrial plants, microorganisms, marine organisms and fungi have been an important source of clinical analgesic medicines. Various alkaloids have been proved to have good analgesic effects, such as morphine and the related to opioids, the main analgesic active components from Corydalis Rhizoma and Aconiti Lateralis Radix Praeparata. Here we summarized the research progress of natural alkaloids with analgesic activity, in order to provide reference for the research and development of analgesic drugs based on natural products.

Factors influencing patellar instability in adults with Kaschin-Beck disease and their correlation / 西安交通大学学报(医学版)

Objective To study the correlation of patellar stability with age ,knee Kellgren-Lawrence grading and patellar Wiberg typing of adults with Kaschin-Beck disease (KBD) .Methods Through cross-sectional study , we asked 143 adult patients with KBD from several villages in Gansu Province to receive digital radiographic x-ray (DR) which included lateral slice of knee joint and axis slice of patellar .Meanwhile ,each patient had to undergo patellar stability measurement on the DR film which included some indexes such as Insall index , lateral patellofemoral angle ,sulcus angle ,congruence angle ,lateral migrating ratio of patella ,and patellofemoral index . Then ,all the participants were divided into four groups based on the patella Wiberg typing and three groups based on KBD clinical grading .Last ,we analyzed the correlation of patellar stability with patellar Wiberg typing ,clinical KBD grading ,and Kellgren-Lawrence grading of the patients by Spearman test .Results ① By ANOVA test on the patella Wiberg typing ,lateral patellofemoral angle decreased with increased level of patella Wiberg typing ,but congruence angle ,lateral migrating ratio of patella ,and patellofemoral index were increased with increased level of patella Wiberg typing . P values of the six indexes were all <0 .05 ,which indicated that these differences between groups were significant .By ANOVA test on the KBD clinical grading ,lateral patellofemoral angle decreased with increased level of KBD clinical grading ,but congruence angle ,lateral migrating ratio of patella ,sulcus angle ,and patellofemoral index increased with increased level of KBD clinical grading .Besides that P value of Insall index was>0 .05 , P value of the other five indexes were all <0 .05 ,which indicated these differences between groups were significant .② Spearman test :a strong correlation lay between Wiberg patellar typing and other indexes including age ,lateral patellofemoral angle ,congruence angle ,lateral migrating ratio of patella ,and patellofemoral index ( R=0 .684 ,0 .752 ,0 .582 ,0 .533 ,0 .735 , P< 0 .05) .However ,there was no correlation between Wiberg patellar typing and K-L photographical grading (R=0 .030 ,P>0 .05) .K-L grading was strongly correlated with age (R=0 .782 , P< 0 .05 ) , weakly correlated with lateral migrating ratio of patella ( R = 0 .104 , P> 0 .05 ) , but not correlated with the others ( R < 0 .1 , P> 0 .05 ) . Age was strongly correlated with K-L grading and lateral patellofemoral angle (R=0 .782 ,0 .506 ,P<0 .05) ,moderately correlated with congruence angle ,lateral migrating ratio of patella ,and patellofemoral index (R=0 .403 ,0 .361 ,0 .475 , P< 0 .05) ,but not correlated with Wiberg typing ,sulcus angle ,or Insall index ( R=0 .024 ,0 .074 ,0 .053 , P>0 .05) .Conclusion Patellar Wiberg typing is the key factor which influences latellar stability ;age has a limited influence ,while K-L grading does not affect patellar stability .

Study on structural conversion of dihydrochelerythrine in different solvents / 中国中药杂志

Dihydrochelerythrine was isolated from the ethanol extract of Corydalis yanhusuo by chromatographic and recrystallization techniques. To our knowledge, this is the first report that dihydrochelerythrine was found to be unstable. The NMR, HPLC, and LC-MS were applied to monitor the structural conversion process of dihydrochelerythrine. The results showed that when dissolved in polar deuteration solvent (e.g., DMSO-₆ & MeOD), dihydrochelerythrine is directly converted to chelerythrine gradually. However, if used non-polar reagent (e.g.,CD₂Cl₂), the sample of dihydrochelerythrine undergoes the formation of pseudobase, chelerythrine, and bimolecular ether then followed by oxidation to oxychelerythrine as the major final product. Which leads to this phenomenon maybe is that the C-6 in dihydrochelerythrine is highly reactive to nucleophiles, and is easily converted to different derivatives in different solvents attributed to the solvent effect. This finding will contribute to the extraction and isolation, bioactivity screening, and quality evaluation of medicinal materials containing dihydrochelerythrine and other similar derivatives.

Chemical constituents from water-soluble extract of dry roots of Paeonia lactiflora / 中国中药杂志

Nineteen compounds were isolated from the water-soluble extract of the dry roots of Paeonia lactiflora by using various chromatographic techniques. Their structures were identified by MS， NMR and other spectroscopic analysis as paeoniflorin(1)， 4--ethylpaeoniflorin(2)， 2'--benzoylpaeoniflorin(3)， benzoylpaeoniflorin(4)， 4"-hydroxy-benzoyloxypaeoniflorin(5)， moudanpioside C(6)， 6'--benzoyl-4"-hydroxy-3"-methoxy-paeoniflorin(7)， paeoniflorin B(8)， 6--benzoylalbiflorin(9)， secoisolariciresinol (10)， (+)-lyoniresinol(11)， dihyrodehydrodiconiferyl alcohol(12)， ()-threo-7，9，9'-trihydroxy-3，3'-dimethoxy-8--4'-neolignan(13)， (+)-neo-olivil (14)， [()-5-methyl-2，3-dihydro-1-benzofuran-3-yl]methanol(15)， 5-hydroxy--hydroxymethyl-6-methyl-2，3-dihydrobenzofuran(16)， (+)-()-2-hydroxy-1-(4-methoxyphenyl)-1-propan-1-one(17)， (+)-(2)-1-(4-hydroxy-3-methoxyphenyl)-2-propanol(18)， (+)-()-()-4-hydroxy-2-nonenoic acid(19). Compounds 15 and 18 are new natural products， while compounds 10， 11， 13， 14， 17 and 19 are isolated from the genus Paeonia for the first time.

Chemical constituents from Fusarium redolens, the endophytic fungus from Edgeworthia chrysantha / 药学学报

A new phomapyrone derivative (1), and 9 known compounds were isolated from the ethyl acetate fraction of solid fermentation of Fusarium redolens, the endophytic fungus from Edgeworthia chrysantha, by using various isolation techniques such as Sephadex LH-20, MCI GEL and Semi pre-HPLC, etc. Their structures were identified by spectroscopic analysis, including MS, UV, CD, specific rotation, IR, 1D and 2D NMR, as (+)-7S-4-deoxy-9-hydroxyphomapyrone C (1), uracil (2), uridine (3), 2'-deoxyuridine (4), adenosine (5), 2'-deoxyadenosine (6), cordysinin B (7), ergosterol (8), ergosta-5α, 8β-epidioxy-6, 22-dien-3β-ol (9), and (22E, 24S)-3α-hydroxy-24-methylcholesta-5, 8, 22-trien-7-one (10).

A new styrene dimer derivative from Litsea greenmaniana / 中国中药杂志

A new styrene dimer derivative has been isolated from the branch of Litsea greenmaniana by column chromatography over silica gel and Sephadex LH-20, as well as semi-preparative HPLC. Its structure was identified by spectroscopic data analysis (MS, UV, IR, 1D and 2D NMR) as (E)-2,4-bis(p-hydroxyphenyl)-2-butenol, named as listeanol. At a concentration of 1×10-5 mol•L⁻¹, compound 1 was inactive in the assays, including cytotoxicity against human tumor cell lines (HCT-8, Bel-7402, BGC-823, A549 and A2780), antioxidant activity in Fe²⁺-cystine-induced rat liver microsomal lipid peroxidation, neuroprotective activity against serum deprivation or glutamate induced neurotoxicity in cultures of PC12 cells, and the inhibitory activity against protein tyrosine phosphatase 1B (PTP1B).