Melatonin holds a wide range of biological effects, its multi-channel and multi-target impacts on reproductive sys-tem are the basis of pregnancy related rhythm, including conception, the duration of pregnancy and delivery.This paper describes the synthesis of melatonin, the characteristics of melatonin receptors distribution and melatonin′s biological property.It also illuminates the influence of melatonin rhythm on the above-mentioned courses, hoping to provide theory basis for clinical suggestions to modulate rhythm around pregnancy.

Objective: To investigate the mechanism underlying the effects exerted by the Qizhu prescription (QZP) in breast cancer (BC), and the respective targets. Methods: Expression data from the ArrayExpress and The Cancer Genome Atlas (TCGA) were used to identify differentially expressed genes (DEGs) in BC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the DEGs to identify genes involved in protein–protein interactions. Molecular docking was used to explore the dynamic relationship between active molecules and targets. Cell function experiments and animal studies were conducted to evaluate the effects of hub genes and active QZP compounds on BC cell behavior. Results: Among the 25 evaluated BC-related targets of QZP, matrix metalloproteinase-1 (MMP1) and epidermal growth factor receptor (EGFR) exhibited the highest degrees of dysregulation. GO and KEGG enrichment analyses revealed that the anti-BC targets of QZP primarily affected drug responses and pathways in cancer cells. Molecular docking analysis suggested potential interactions between EGFR and quercetin/luteolin, as well as between MMP1 and luteolin/kaempferol/quercetin. Quercetin significantly reduced BC cell proliferation, migration, invasion, and tumor development in vivo. Treatment of BC cells with quercetin decreased the expression or activation of several associated proteins. Conclusion The findings of our study provide new insights into the therapeutic potential of traditional Chinese medicine against BC, with particular reference to QZP.

Twenty-one compounds were isolated from an ethanol extract of Machilus wangchiana by a combination of various chromatographic techniques including column chromatography over silica gel and Sephadex LH-20 and reversed-phase HPLC. Their structures were identified by spectroscopic data analysis including optical rotation, UV, IR, MS, and NMR data. The compounds are categorized as eight butanolides (1-8), eight lignans (9-16), and five terpenoids (17-21). Compound 16 is a new natural product with an uncommon heptanorlignan skeleton. Meanwhile, the unique Ginkgo biloba (maidenhair) metabolites ginkgolides A (19) and ginkgolides B (20) were obtained from this material. In the preliminary assays, compound 5 showed selective inhibitory activities against human stomach cancer cells (BGC-823) and ovary cancer cells (A2780) with IC50 values of 0.13 x 10(-6) and 2.66 x 10(-6) mol x L(-1), respectively. Compounds 8 and 9, at 1 x 10(-5) mol x L(-1), showed inhibitory activities against the release of beta-glucuronidase of the polymorphous nuclear leukocytes induced by platelet activating factor (PAF), with inhibition rates of 60.0% and 54.2%.
Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Humans ; Inhibitory Concentration 50 ; Lauraceae ; chemistry ; Molecular Structure

OBJECTIVETo investigate the chemical constituents of Heteroplexis nicocephala.

METHODThe constituents were isolated by using a combination of various chromatographic techniques including column chromatography over silica gel, Pharmadex LH-20, and C-18, as well as reversed-phase HPLC. Structures of the isolates were identified by spectroscopic data analysis. In vitro cytotoxic, neuroprotective, and anti-inflammatory activities were screened by using cell-based models.

RESULTSeventeen terpenoids were isolated. The structures were identified as two monoterpenoids: (-)-bomyl ferulate(1) and loliolide(2). Seven sesquiterpenoids: 1beta-hydroxy-alpha-cyperone(3) , alpha-rotunol(4), 10alpha-hydroxycadin-4-en-15-al (5), 1-epi-10beta-hydroxycadin-4-en-15-al(6), 10alpha-hydroxyisodauc-3-en-15-al(7), germacrene B(8), and mandassidione(9). Five diterpenoids: 12-epi-bacchotricuneatin A(10), 1-hydroxy-12-epi-bacchotricuneatin A(11), cleroinermin(12), desoxyarticulin(13), and anhydroolearin(14). And three triterpenoids: friedelin (15), ursolic acid(16), and obtusalin(17). In the in vitro assays, 1 showed selective cytotoxic activity against BGC-823, with an IC50 value of 8.00 x 10(-5) mol x L(-1). At a concentration of 1 x 10(-5) mol x L(-1), 12 showed neuroprotective activity against MPP+ induced PC12-syn cell damage, with a relative cell proliferation rate of 104.32% (P < 0.001). 2 exhibited inhibitory activity against the release of beta-glucuronidase from the polymorphous nuclear leukocytes induced by PAF, with an inhibitory rate of 52.7% (P < 0.05) at the same concentration.

CONCLUSIONCompounds 1-17 were obtained from the genus Heteroplexis for the first time. 1 showed selective cytotoxic activity against human gastric cancer cell lines (BGC-823), 12 and 2 showed potent neuroprotective and anti-inflammatory activities, respectively.

Anti-HIV Agents ; chemistry ; pharmacology ; Anti-Inflammatory Agents ; chemistry ; pharmacology ; Asteraceae ; chemistry ; Cell Line ; Cell Survival ; drug effects ; Diterpenes ; chemistry ; pharmacology ; HIV-1 ; drug effects ; Humans ; Molecular Structure ; Nuclear Magnetic Resonance, Biomolecular ; Sesquiterpenes ; chemistry ; pharmacology ; Terpenes ; chemistry ; pharmacology

Objective:To observe the clinical effects of intraperitoneal perfusion of bevacizumab combined with albumin paclitaxel and carboplatin in the treatment of malignant peritoneal adhesion caused by ovarian cancer.Methods:From January 2016 to December 2020, 54 patients treated in our hospital with malignant peritoneal adhesions caused by ovarian cancer were enrolled in this study. They were randomly divided into experimental group ( n=27) and control group ( n=27) according to the random number table method. The treatment regimen of the experimental group was intravenous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin and bevacizumab. The treatment regimen of the control group was intra-venous infusion of albumin paclitaxel plus intraperitoneal infusion of carboplatin. The treatment was repeated every 21 days, and the therapeutic effect was evaluated every two cycles. The treatment lasted for six cycles. The efficacy and incidence of adverse reactions were compared between the two groups. Results:The remission rate of incomplete malignant bowel obstruction of the experimental group was higher than that of the control group [85.19% (23/27) vs. 59.26% (16/27)], the total effective rate of the experimental group was higher than that of the control group [74.07% (20/27) vs. 44.44% (12/27)], and there were statistically significant differences ( χ2=4.523, P=0.033; χ2=4.909, P=0.027). After treatment, the levels of vascular endothelial growth factor (VEGF) in ascites of the experimental group and the control group were significantly lower than those before treatment [(80.33±1.41) pg/ml vs. (310.45±3.35) pg/ml, t=449.884, P<0.001; (135.68±1.60) pg/ml vs. (310.46±3.09) pg/ml, t=499.281, P<0.001], and after treatment, the VEGF level in the experimental group decreased more significantly than that in the control group ( t=-134.907, P<0.001). Patients in the experimental group and the control group tolerated the treatment well, and there were no significant differences in the incidences of adverse reactions such as hypertension (11.11% vs. 3.70%, χ2=0.270, P=0.603), neutropenia (14.81% vs. 11.11%, χ2<0.001, P>0.999), peripheral neuropathy (3.70% vs. 0, χ2<0.001, P>0.999), diarrhea (7.41% vs. 3.70%, χ2<0.001, P>0.999), nausea (3.70% vs. 0, χ2<0.001, P>0.999), epistaxis (7.41% vs. 0, χ2=0.519, P=0.471) or albuminuria (3.70% vs. 0, χ2<0.001, P>0.999) between the two groups. Conclusion:Intraperitoneal perfusion of bevacizumab combined with chemotherapy is superior to simple chemotherapy in the treatment of malignant peritoneal adhesion caused by ovarian cancer.

OBJECTIVETo investigate the chemical constituents of Heteroplexis micocephal and their bioactivities.

METHODThe constituents were isolated by using a combination of various chromatographic techniques including column chromatography over macroporous adsorbent resin, silica gel, Pharmadex LH-20, and C-18, as well as reversed-phase HPLC. Structures of the isolates were identified by spectroscopic data analysis. In vitro cytotoxic, HIV-1 replication, neuroprotective, and anti-inflammatory activities were screened by using cell-based models.

RESULTThirty-one compounds were obtained. Twelve of them are phenylpropanols, and the structures were elucidated as (+)-(7S,8R)-guaiacylglycerol (1), ferulic acid (2), cinnamate methyl ester (3), 1-eicosanyl 3,4-dihydroxycinnamate (4), morinin B (5), sinapyl diangelate (6), chlorogenic acid (7), 4-O-caffeoylquinic acid (8), 5-O-caffeoylquinic acid (9), 5-O-caffeoylquinic acid methyl ester (10), 1,5-di-O-caffeoylquinic acid (11) and 4,5-di-O-caffeoylquinic acid methyl ester (12). Three lignans, (+)-pinoresinol (13), prinsepiol (14) and (+)-pinoresinol-O-beta-D-glucopyranoside (15). Four acetophenones, 2,4-diacetylanisole (16), espeleton (17), viscidone (18) and 12-hydroxytremetone-12-O-beta-D-glucopyranoside (19). Nine flavones, isosakuranetin (20), hesperetin (21), 3-methoxy-5,7,3',4'-tetrahydroxyflavone (22), acacetin (23), 5-hydroxy-7,4'- dimethoxyflavone (24), 7-methoxy-4',5, 6-trihydroxyflavone (25), 3,3'-dimethylquercetin (26), kaempferol 3-O-rutinoside (27), rutin (28). And three coumarins scopoletin (29), umbelliferone (30) and ayapin (31). Compound 6 and 22 showed selective cytotoxicities against a human stomach cancer cell line(BGC-823) and a human lung cancer cell line (A549) with IC50 values of 3.74 x 10(-5) and 7.17 x 10(-5) mol L(-1), respectively. In addition, Compound 6 showed a potent activity inhibiting HIV-1 replication with an IC50 value of 4.04 x 10(-6) mol L(-1), while 22 showed neuroprotective activity Against the MPP+ induced PC12-syn cell damage, with a relative protection ratio of 105.2% (P < 0.01) at a concentration of 10(-5) mol L(-1). Compound 26 and 31 showed inhibitory activities against the release of beta-glucuronidase of the polymorphous nuclear leukocytes induced by platelet activating factor (PAF), with inhibitory rates of 75.6% (P < 0.001) and 53. 9% (P < 0.01), respectively.

CONCLUSIONCompounds 1-31 were obtained from the genus Heteroplexis for the first time. Compound 6 and 22 possessed selective cytotoxicities against human cancer cell lines BGC-823 and A549, respectively. In addition, Compound 6 showed a potent activity inhibiting HIV-1 replication while 22 showed neuroprotective activity against the MPP+ induced PC12-syn cell damage. Compound 26 and 31 were potent anti-inflammatory agents.

Animals ; Antiviral Agents ; analysis ; pharmacology ; Cell Line, Tumor ; HIV-1 ; drug effects ; physiology ; Humans ; Myrtaceae ; chemistry ; Neurons ; cytology ; drug effects ; Neuroprotective Agents ; analysis ; pharmacology ; Plant Extracts ; analysis ; pharmacology ; Rats ; Virus Replication ; drug effects

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

To reduce the subjectivity and uncertainty present in the current international methods of drug value pricing when converting value into monetary prices,based on the hedonic pricing theory,it considers the post-negotiation price between manufacturers and payers as a reasonable price reference in the value pricing of Chinese patent medicine.By constructing an indicator system for the characteristics of Chinese patent medicine,it selects and measures the value characteristic variables that affect the price of Chinese patent medicine.It serves as the theoretical foundation and research basis for establishing a Hedonic price model between characteristic price variables and negotiation prices,thereby promoting the enhancement of rationality and objectivity in value-guided pricing of Chinese patent medicine.

BACKGROUND:Cadmium is a common environmental pollutant,which can damage multiple organs and tissues,such as the kidney and bone,but its effect on annulus fibrosus cells in the intervertebral disc has been less reported. OBJECTIVE:To investigate the effect of cadmium chloride on the senescence of annulus fibrosus cells and the role of PI3K/Akt signaling pathway. METHODS:Annulus fibrosus cells from Sprague-Dawley rat intervertebral discs were harvested and passage 3 cells were intervened with different concentrations of cadmium chloride(0,1,5,10,20 μmol/L).Cell viability and proliferation were detected by cell counting kit-8 assay.Transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis were performed on annulus fibrosus cells with or without cadmium chloride addition.Passage 3 annulus fibrosus cells were divided into control group,cadmium chloride group and LY294002 group.Cell proliferation rate was detected by EdU method,positive cell rate was detected by senescence-associated β-galactosidase staining,and expressions of senescence-associated proteins(p16,p21 and p53)and p-Akt at protein and mRNA levels were measured by western blot,RT-PCR and immunofluorescence. RESULTS AND CONCLUSION:5 μmol/L cadmium chloride could inhibit the proliferation of annulus fibrosus cells.Results from the Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis showed that the main signal transduction pathways included PI3K/Akt,cell cycle and p53 signaling pathways,which were related to cell senescence and proliferation.PI3K/Akt signaling pathways with significant differential expression were selected for validation.Compared with the control group,the EdU-positive rate was significantly decreased in the cadmium chloride group(P<0.05),while the β-galactosidase-positive rate,the expression of senescence-associated proteins(p16,p21 and p53)and p-Akt significantly increased(P<0.05).Compared with the cadmium chloride group,the EdU-positive rate and p-Akt expression were significantly decreased in the LY294002 group(P<0.05),while the β-galactosidase-positive rate and the expression of senescence-associated proteins(p16,p21 and p53)significantly increased(P<0.05).To conclude,cadmium chloride can regulate the senescence of annulus fibrosus cells by activating the PI3K/Akt signaling pathway,thereby inducing the occurrence and progression of intervertebral disc degeneration.

WHO Guideline on Country Pharmaceutical Pricing Policies,published in 2020,outlines 10 commonly used pricing methods internationally.However,due to the unique composition of costs for traditional Chinese medicine(TCM),directly applying pricing methods designed for chemical and biological drugs may lead to discrepancies.Currently,in China,drug pricing primarily in-volves internal reference pricing,tender negotiation pricing,promoting the use of quality-assured generic and biosimilar drugs,and centralized procurement.It systematically analyzes various pricing methods and identifies their applicability and underlying reasons concerning the pricing of TCMwithin the medical insurance system.The method of value-based pricing and increasing price transparency has advantages for the pricing regulation of traditional Chinese medicine under medical insurance.