A naturally derived small molecule compound suppresses tumor growth and metastasis in mice by relieving p53-dependent repression of CDK2/Rb signaling and the Snail-driven EMT.

The tumor suppressor protein p53 is central to cancer biology, with its pathway reactivation emerging as a promising therapeutic strategy in oncology. This study introduced LZ22, a novel compound that selectively inhibits the growth, migration, and metastasis of tumor cells expressing wild-type p53, demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53. LZ22's mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein. This interaction disrupted the MDM2-p53 binding, consequently stabilizing p53 by shielding it from proteasomal degradation. LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling pathway. Moreover, LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT, effectively reducing tumor cell migration and distal metastasis. Importantly, LZ22 administration in tumor-bearing mice did not manifest notable side effects. The findings position LZ22 as a structurally unique reactivator of p53, offering therapeutic promise for the management of human cancers with wild-type TP53.

[Effect of nanoparticles of different stiffness combined with menthol/curcumol on mechanical properties of bEnd.3 cells].

This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.

A novel UHPLC-MS/MS method for the determination of four α-dicarbonyl compounds in wine and dynamic monitoring in human urine after drinking.

α-dicarbonyl compounds (α-DCs) serve as potential biomarkers for oxidative stress-related diseases but are difficult to detect.To study the metabolism of carbonyl compounds, we developed a new mass spectrometry probe, 3-benzyl-2-oxo-4λ3-thiazolidine-4-carbohydrazide (BOTC), containing hydrazyl groups for the targeted detection of carbonyl functional groups.In a novel approach, we used BOTC pre-column derivatization with ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to simultaneously detect four kinds of α-DCs in red wine as well as in urine after drinking. The α-DCs were completely separated (R2 ≥ 0.9995), detection was sensitive (detection limit was 12.5-50 fmol), consistent (intraday and interday precision was 0.1-5.7 %), and efficient (average recoveries were 103.3-110.2 %). The method was applied to the analysis of α-DCs in different wines and the dynamic monitoring of transit and excretion in vivo after drinking. Our novel method provides a new strategy for the detection of α-dicarbonyl compounds in red wine and dicarbonyl compounds produced in oxidative stress-related diseases.

Development of a diphenyl sulfide structure derivatization reagent for amino acid enantiomers analysis: Application of dynamic monitoring in human urine after drinking wine.

We developed a novel chiral mass spectrometry derivatization reagent (S)-(3-(4-carboxythiazolidin-3-yl)-3-oxopropyl) diphenylsulfonium (CTOD) with a positively charged sulfur-containing structure for high-sensitivity detection of the chiral resolution of amino acid enantiomers. CTOD reacted with DL-amino acids at 60oC for 60 min to generate the corresponding diastereomers, fifteen chiral amino acid-derived products were separated. Resolution (Rs) values were of the range 1.54-4.36, except Asn 1.07, achieving good separation. A highly sensitive and selective UHPLC-MS/MS method for the simultaneous determination and chiral separation of five chiral amino acids (Pro, Ala, Glu, Asp, and Phe) based on CTOD derivatization was established and applied to the detection of chiral amino acids in different wines. The diastereomeric resolution of the five amino acids was 1.71-5.42, and an excellent linear relationship was obtained in the range of 0.25-500 pmol (R2 ≥0.9993). The detection limit was 0.05-0.25 pmol. The intra- and inter-day precisions were 0.51-5.76% and 0.78-5.18%, respectively, and the average recovery was 90.03-99.99%. In addition, the metabolic concentration of chiral amino acids was monitored after drinking red wine and white wine, and the fitting curve of metabolic concentration was drawn.

Effect of nanoparticles of different stiffness combined with menthol/curcumol on mechanical properties of bEnd.3 cells / 中国中药杂志

This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.

Tao-Hong-Si-Wu decoction improves depressive symptoms in model rats via amelioration of BDNF-CREB-arginase I axis disorders.

CONTEXT: The traditional Chinese medicine formula Tao-Hong-Si-Wu decoction (TSD), used for treating ischaemic stroke, has the potential to treat depressive disorder (DD). OBJECTIVE: To explore the effective targets of TSD on DD animal models. MATERIALS AND METHODS: Sprague-Dawley (SD) rats were modelled by inducing chronic unpredictable mild stress (CUMS) during 35 days and treated with three dosages of TSD (2.5, 5 and 10 g/kg) or fluoxetine (10 mg/kg) by oral gavage for 14 days. Bodyweight measurements and behavioural tests were performed to observe the effect of TSD on the CUMS animals. A gas chromatography coupled with mass spectrometry (GC-MS)-based metabolomic analysis was conducted to reveal the metabolic characteristics related to the curative effect of TSD. Levels of the proteins associated with the feature metabolites were analysed. RESULTS: Reduced immobile duration and crossed squares in the behavioural tests were raised by 48.6% and 32.9%, on average, respectively, by TSD treatment (ED50=3.2 g/kg). Antidepressant effects of TSD were associated with 13 decreased metabolites and the restorations of ornithine and urea in the serum. TSD (5 g/kg) raised serum serotonin by 54.1 mg/dL but suppressed arginase I (Arg I) by 47.8 mg/dL in the CUMS rats. Proteins on the brain-derived neurotrophic factor (BDNF)-cAMP response element-binding protein (CREB) axis that modulate the inhibition of Arg I were suppressed in the CUMS rats but reversed by the TSD intervention. DISCUSSION AND CONCLUSIONS: TSD improves depression-like symptoms in CUMS rats. Further study will focus on the antidepressant-like effects of effective compounds contained in TSD.

Norlignans and phenolics from genus Curculigo protect corticosterone-injured neuroblastoma cells SH-SY5Y by inhibiting endoplasmic reticulum stress-mitochondria pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The plants of genus Curculigo are divided into the Section Curculigo and the Section Capitulata, which are mainly distributed in southeastern and southwestern China. Various ancient chinese books record that these plants were used as an important herb for tonifying kidney yang. Traditional Chinese medicine often draws on this property to treat depression syndrome. Thus genus Curculigo has potential for the treatment of neurodegenerative diseases (ND). The study showed that phenolics were the main characteristic components of plants in the Section Curculigo, represented by orcinol glucoside and curculigoside; the norlignans, with Ph-C5-Ph as the basic backbone, were the main characteristic components of the Section Capitulata. However, there is a lack of sufficient scientific evidence as to whether these two types of ingredients have neuroprotective effects. AIM OF THE STUDY: To determine the neuroprotective effects of phenolics and norlignans in genus Curculigo on human neuroblastoma cells SH-SY5Y. To discuss their structure-activity relationship and screen for compounds with high activity and neuroprotective effects. To reveal that the amelioration of endoplasmic reticulum (ER) stress by two classes of compounds is mediated by the PERK/eIF2α/ATF4 pathway. MATERIALS AND METHODS: The cytotoxicity of 17 compounds was assayed by MTT. SH-SY5Y cells were damaged by corticosterone (Cort) (200 µM) for 24 h and then co-administered with 17 compounds (0.1-100 µM) and Cort (200 µM) for 24 h. Cell survival was determined by MTT assay. Apoptosis rate, mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) levels were detected using flow cytometry. Intracellular Ca2+ levels were detected using a fluorescent probe. Cellular mitochondrial and ER damage was observed using transmission electron microscopy (TEM). ER stress and apoptotic pathway-related proteins (BiP, CHOP, cleaved caspase-3, cleaved caspase-9, Bax/Bcl-2), and the expression level of PERK/eIF2α/ATF4 pathway was measured via western blot (WB). RESULTS: The experimental data showed that Cort treatment of SH-SY5Y cells resulted in decreased cell survival and increased apoptosis, mitochondrial depolarization, ROS, and intracellular Ca2+ levels. The co-action of 17 compounds and Cort for a period of time significantly increased cell survival. Compounds 3, 7, 12, 13 also reduced apoptosis rate, mitochondrial depolarization, ROS and intracellular Ca2+ levels in the subsequent experiments. In addition, TEM observed that Cort caused mitochondrial and ER damage, and the damage was improved after treatment. WB analysis obtained that Cort increased the expression of apoptotic and ER stress-related proteins and activated pathway expression. However, in the presence of compounds 3, 7, 12, 13, the expression of BiP, CHOP, cleaved caspase-3, cleaved caspase-9, and Bax/Bcl-2 was significantly reduced, and the phosphorylation of PERK and eIF2α and the expression of ATF4 were inhibited. CONCLUSION: This study found that one phenolic (3) and three norlignans (7, 12, 13) from genus Curculigo have significant neuroprotective effects. The results of the structure-activity relationship indicated that the glucosyl polymeric norlignans and the phenolics with benzoic acid as the parent nucleus were more active. The neuroprotective effect of three norlignans is the latest discovery. This finding has important research value in the field of prevention and treatment of neurodegenerative diseases.

Natural Products with Activity against Lung Cancer: A Review Focusing on the Tumor Microenvironment.

Lung cancer is one of the most prevalent malignancies worldwide. Despite the undeniable progress in lung cancer research made over the past decade, it is still the leading cause of cancer-related deaths and continues to challenge scientists and researchers engaged in searching for therapeutics and drugs. The tumor microenvironment (TME) is recognized as one of the major hallmarks of epithelial cancers, including the majority of lung cancers, and is associated with tumorigenesis, progression, invasion, and metastasis. Targeting of the TME has received increasing attention in recent years. Natural products have historically made substantial contributions to pharmacotherapy, especially for cancer. In this review, we emphasize the role of the TME and summarize the experimental proof demonstrating the antitumor effects and underlying mechanisms of natural products that target the TME. We also review the effects of natural products used in combination with anticancer agents. Moreover, we highlight nanotechnology and other materials used to enhance the effects of natural products. Overall, our hope is that this review of these natural products will encourage more thoughts and ideas on therapeutic development to benefit lung cancer patients.

Erxian Decoction, a Famous Chinese Medicine Formula, Ameliorate Depression- Like Behavior in Perimenopausal Mice.

AIMS: The present study was performed in order to find out the anti-depression effect of Erxian Decoction in perimenopausal mice. BACKGROUND: Erxian Decoction (EXD) has been used in folk medicine for the treatment of perimenopausal syndrome, but it has not been researched on perimenopausal depression. OBJECTIVE: The present study aimed to evaluate the effect of extraction of Erxian Decoction on perimenopausal depressive mice. METHODS: In this study, female ICR mice were randomly divided into 6 groups: Low, medium and high dose of EXD groups (0.5, 1.5, and 4.5 g/kg), soy isoflavones group (250 mg/kg) and Sham group. The mice in the Sham group received sham surgery (within ovaries), and the others were excised with bilateral ovaries and exerted by 28-day chronic mild unpredictable stimulation for the establishment of a perimenopausal depression model. RESULTS: Behavioral tests showed that EXD could relieve depression symptoms and improve spatial memory in mice. Western blotting showed that EXD significantly up-regulated the expression of brain-derived neurotrophic factor (BDNF) and Bcl-2 in hippocampus and estrogen receptors (ERs) in the uterus and adrenals, protecting hippocampal tissue and antagonizing the symptoms of estrogen deficiency in mice, which was further proved within a uterine morphology test. In addition, EXD reduced the serum levels of follicle-stimulating hormone, luteinizing hormone, and interleukin- 6. CONCLUSION: These results indicated that EXD can regulate hormone secretion and recover hippocampal damage in perimenopausal depressed mice. Besides, it can antagonize the symptoms of ovarian hormone deficiency as well as relieve perimenopausal syndrome.

Simultaneous Determination of Chiral Thiol Compounds and Monitoring of Dynamic Changes in Human Urine after Drinking Chinese Korean Ethnic Rice Wine.

Chinese Korean ethnic rice wine, a traditional fermented wine made from rice or corn, has antioxidant and antihypertensive activities. Although the determination of amino acids and other nutrients in rice wine has been reported, the existence of chiral thiol compounds has not been published in the literature. Therefore, we established a highly sensitive and selective ultrahigh-performance liquid chromatography-high-resolution mass spectrometry method for simultaneous determination and chiral separation of dl-Cys-GSH, dl-Cys-Cys, and dl-Cys-Hcy based on (R)-(5-(3-isothiocyanatopyrrolidin-1-yl)-5-oxopentyl) triphenylphosphonium derivatization. Three thiol diastereomers were completely separated on a YMC Triart C18 (2.0 × 150 mm, 1.9 µm) column with a resolution value (Rs) ≥ 1.52. The correlation coefficients were ≥0.9996, limit of detection was 2.40-7.20 fmol, and mean recoveries were 83.33-98.59%. Furthermore, fitted curves for dynamic changes in three kinds of chiral thiols in 10 human urine samples after drinking rice wine were drawn. Meanwhile, the metabolic changes in d/l-thiol compounds in human urine were investigated.

A convenient sampling and noninvasive dried spot method of uric acid in human saliva: Comparison of serum uric acid value and salivary uric acid in healthy volunteers and hyperuricemia patients.

Concentration of uric acid (UA) in serum is one of the markers used to diagnose gout and hyperuricemia. However, serum treatment and storage are cumbersome, and wounds are susceptible to infection. Therefore, a new sampling and analysis method using noninvasive biological samples has been developed, called the dried spot method of UA in human saliva (DSM-UHS). Saliva (5 µL) was dropped on filter paper (a spot with a diameter of 5 mm) containing hypoxanthine (IS) (5 µL) and dried at room temperature for 30 min. The filter paper was immersed in 200 µL of lithium carbonate solution and shaken in a block bath shaker for 5 min at 30 °C. Afterward, the extraction was concentrated and reconstituted with 100 µL of lithium carbonate solution analyzed by HPLC-UV. When comparing the concentration of UA in the human saliva of hyperuricemia patients (HPs) and with that of healthy volunteers (HVs), we observed the concentration of UA was higher in the HPs than in the HVs (p < 0.0001). In addition, the results showed a significant linear relationship between the content of UA in saliva and the content of UA in the serum (r = 0.6243). The content of UA in human saliva could indirectly reflect the content of UA in human serum. Then DSM-UHS could be used to determine the content of UA in the saliva of HVs and HPs. This study provides a new research method and strategy for the determination of human UA content and the clinical prewiring of hyperuricemia.

Evaluation of Anti-Diabetic Potential of Corn Silk in High-Fat Diet/ Streptozotocin-Induced Type 2 Diabetes Mice Model.

BACKGROUND: Corn silk is the elongated stigma of the female flower of Zea mays and traditionally used to treat diabetes mellitus (DM). OBJECTIVE: To investigate the beneficial effects of corn silk extract (CSE) on HFD/STZ-induced diabetic C56BL/6J mice. METHODS: Establishment of a T2DM model through feeding HFD combined with STZ. T2DM was randomly divided into 5 groups: diabetic control mice treated with vehicle (model group, n=10), metformin- treated group (metformin: 150 mg/kg.d, n=10), three CS-treated groups (CS: 300, 600 and 1200 mg/kg.d, n=10). After four weeks of CS treatment, the body weight, FBG, IR, TC, TG, LDL-C, MDA and SOD levels of mice were measured. In addition, the liver tissue was histomorphologically analyzed by HE stain followed a light microscopy observation. RESULTS: 4-week CSE treatment significantly reduced FBG and enhanced the glucose tolerance; improved IR indicated by decreased HOMA-IR and elevated ISI; alleviated hyperlipidemia indicated by decreased TC, TG, LDL-C, and increased HDL-C; reduced oxidative stress by decreased MDA and elevated SOD activity; decreased hepatic lipid accumulation and prevented liver tissue morphological change in T2DM. In addition, CSE treatments effectively prevent the weight gain loss of diabetic mice. CONCLUSION: These results confirmed the traditionally claimed benefits of corn silk on DM, which suggested that the corn silk possessed the anti-diabetic potential and could be further developed as a cheap and plant-derived agent for the treatment of type 2 diabetes mellitus.

Analysis on Quality Transmitting of Substance Benchmarks of Yihuangtang / 中国实验方剂学杂志

Objective:To explore the quality transmitting relationship between decoction pieces and substance benchmarks with the fingerprint， index component content and dry extract rate as evaluation indexes， and investigate the key quality attributes of 15 batches of substance benchmarks of Yihuangtang， and establish the quality standard of this substance benchmarks. Method:Fifteen batches of Yihuangtang substance benchmarks freeze-dried powder samples were prepared， the fingerprint and index component content of 15 batches of decoction pieces and substance benchmarks were determined by high performance liquid chromatography （HPLC）， the mobile phase was acetonitrile （A）-0.1% phosphoric acid aqueous solution （B） for gradient elution （0-6 min， 97%B； 6-12 min， 97%-92%B； 12-25 min， 92%-90%B； 25-35 min， 90%-89%B； 35-50 min， 89%-82%B； 50-75 min， 82%-72%B； 75-85 min， 72%-35%B）， the detection wavelength was set at 230 nm， combined the dry extract rate to clarify the attribution of characteristic peaks and the range of similarity with the control chromatogram， the content range and transfer rate range of geniposidic acid and berberine hydrochloride， the dry extract rate range and the variation range of the substance benchmarks. Result:The established HPLC fingerprint had good precision， repeatability and stability， and could be used for the simultaneous determination of decoction pieces and substance benchmarks of Yihuangtang. The similarities between the control chromatogram and fingerprint of substance benchmarks were >0.99. A total of 15 characteristic peaks were assigned， and 8 characteristic peaks were identified by the reference substances， of which 6 were from Phellodendri Chinensis Cortex processed with salt， 1 was from Plantaginis Semen processed with wine， and 1 was from stir-fried Dioscoreae Rhizoma. The content ranges of geniposidic acid and berberine hydrochloride in 15 batches of substance benchmarks of Yihuangtang were 0.10%-0.16% and 0.63%-1.05%， the transfer rate ranges of them were 20.91%-32.65% and 19.60%-29.59%， respectively. The dry extract rate range of the substance benchmarks was 8.45%-9.92%. Conclusion:The quality standard of Yihuangtang substance benchmarks can be preliminarily formulated by the combination of fingerprint， dry extract rate and determination of index component， which can provide the basis for the quality control of Yihuangtang and the development of related preparations.

Force transmission characteristics in a multiple-fulcrum supporting platform with heavy loads.

This study aims to investigate the force transmission characteristics of a multiple-fulcrum supporting platform, and the significance of this paper is to creatively put forward the law of uniform force characteristics of multiple-fulcrum supporting platform with heavy loads and layout reconfiguration methods to realize the law. In this paper, firstly, a force transmission model for the multiple-fulcrum supporting platform has been constructed, the relationship between force transmission characteristics and layout parameters for all fulcrums has been discussed in detail, and the layout law for all fulcrums with the same supporting force has been discovered. Then, layout reconfiguration methods have been proposed to realize the uniform force characteristics of all fulcrums under different types of constraint surfaces (rectangular or square constrained surface, circular constrained surface, and unconstrained surface). Finally, layout reconfiguration methods have been applied to some engineering problems by ADAMS simulation. The simulation results show that the supporting force of all fulcrums in the supporting platform is equal when the layout central point (LCP) of all fulcrums is coincident with the force equivalent point (FEP) of external loads. The results provide theoretical guidance and support for the reconfiguration of multiple-fulcrum supporting platforms that can realize uniform forces among all fulcrums.

Erxian decoction, a famous Chinese medicine formula, antagonizes corticosterone-induced injury in PC12 cells, and improves depression-like behaviours in mice.

Context: In folk medicine, erxian decoction (EXD) is used to treat perimenopausal syndrome in women. It is also used clinically to treat depression, but the mechanism remains unknown.Objectives: To investigate the neuroprotective effect of EXD, and its antidepressant potential.Materials and methods: ICR mice were treated with EXD (0.5, 1.5 and 4.5 g/kg i.g.) and fluoxetine (6.0 mg/kg i.g.) for 10 days. On day 10 of the treatment, depression-like behaviour was induced by reserpine (2.5 mg/kg injected i.p.), and after 24 h of reserpine administration, it was assessed using the tail suspension and forced swimming tests. MTT assay, lactate dehydrogenase test, flow cytometry analysis, Hoechst staining and western blotting were used to assess the apoptosis of PC12 cells. Apoptosis proteins and neurotransmitter were tested in vitro and in vivo, respectively.Results: MTT assay results showed corticosterone prevented cell growth, but EXD at concentrations of 100, 200 and 400 µg/mL restored cell viability (EC50: 204.016 µg/mL). EXD decreased lactate dehydrogenase leakage from 63.48 to 43.60 U/L, and upregulated expression of Bcl-2 while the expression of Bax, caspase-3 and caspase-8 were decreased in vivo and in vitro. Moreover, EXD improved depression-like behaviour in mice, and 4.5 g/kg EXD treatment increased the secretion of serotonin, dopamine and norepinephrine by 67.44, 28.12 and 42.12 pg/mg, respectively, in hypothalamus compared to that of reserpine group.Discussion and conclusions: EXD demonstrated neuroprotective effects and improved depression-like behaviour in mice. Further research should be focussed on the mechanism of the active components in EXD.

Chemical constituents with cytotoxic and anti-inflammatory activity in Hypericum sampsonii and the antitumor potential under the view of cancer-related inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic inflammation has an important role in the development of cancers. Hypericum sampsonii, known as "Yuanbao Cao", is mainly distributed in the southwest of China. As a folk medicinal plant, "Yuanbao Cao" is traditionally used for treatment of various inflammation-related diseases including swelling, burns, arthritis, and dermatitis, etc. The plant is a promising anticancer herb. However, there is no research on the antitumor potential of this plant from the view of cancer-related inflammation strategy. AIM OF THE STUDY: To explore the H. sampsonii in relation to cancer-related chemical constituents with anti-inflammatory and cytotoxic activity in cancer-related inflammation. MATERIALS AND METHODS: The chemical constituents of H. sampsonii were isolated by repeated chromatography techniques, and their structures were identified mainly by spectroscopic methods and compared to published data. The chemical profile of the herb was analyzed using HPLC. The cytotoxicities of compounds against five cancer cell lines: human melanoma cell (A375), human breast cancer cell (MDA-MB-231), human gastric cancer cell (SGC-7901), human colon cancer cell (SiHa), and human bone marrow neuroblastoma cell (SHSY-5Y), were tested using MTT assay; their anti-inflammatory activities were evaluated by inhibition on NO production in LPS-stimulated RAW 264.7, THP-1 and BV-2 microglial cells. RESULTS: Twenty-five compounds, including four phenols (1-4), two anthraquinonoids (5 and 6), six xanthones (7-12), one benzophenone (13), one phloroglucinol (14), nine flavonoids (15-23), one sterol (24) and one alkaloid (25), were isolated from the EtOH extract of H. sampsonii. Of them, compounds 3, 4, 6, 7, 10-14, 17, 19, 22 and 23 were reported in H. sampsonii for the first time. HPLC analysis showed that flavonoids were the main constituents in the herb. MTT assay revealed that compounds 1, 2, 5-14, 15, 17, 18, 20, 21, 22 and 25 had selective cytotoxic activities (IC50: 7.52-158.90 µM) against tested cancer cells, in which compound 5, 6, 13 and 14 displayed high activities against A375, MDA-MB-231, SiHa and SHSY-5Y. In the screening experiment of anti-inflammatory activity, most compounds (1-2, 5-23) showed considerable high anti-inflammatory activities (IC50: 10.59-42.75 µM), in which compounds 5, 6, 13, 14, and 15 exhibited high anti-inflammatory activities in LPS-stimulated RAW264.7, THP-1 and BV-2 microglial cells. CONCLUSIONS: Compounds 3, 4, 6, 7, 10-14, 17, 19, 22 and 23 were isolated for the first time from H. sampsonii. Compound 5, 6, 13 and 14 displayed high cytotoxic activities against the tested cancer cell lines. Compounds (1-2, 5-23) showed anti-inflammatory activities, of them, compounds 5, 6, 13, 14 and 15 exhibited the high activity. From the view of cancer-related inflammation point, not only the compounds with high cytotoxicity, but those compounds with anti-inflammatory activities, especially the flavonoids, contribute to the antitumor potential of H. sampsonii. The results and viewpoint of present study provide a different insight to better understand the antitumor potential of H. sampsonii, and may also promote the reasonable usage of this folk medical herb.

Endothelial ZEB1 promotes angiogenesis-dependent bone formation and reverses osteoporosis.

Recent interest in the control of bone metabolism has focused on a specialized subset of CD31hiendomucinhi vessels, which are reported to couple angiogenesis with osteogenesis. However, the underlying mechanisms that link these processes together remain largely undefined. Here we show that the zinc-finger transcription factor ZEB1 is predominantly expressed in CD31hiendomucinhi endothelium in human and mouse bone. Endothelial cell-specific deletion of ZEB1 in mice impairs CD31hiendomucinhi vessel formation in the bone, resulting in reduced osteogenesis. Mechanistically, ZEB1 deletion reduces histone acetylation on Dll4 and Notch1 promoters, thereby epigenetically suppressing Notch signaling, a critical pathway that controls bone angiogenesis and osteogenesis. ZEB1 expression in skeletal endothelium declines in osteoporotic mice and humans. Administration of Zeb1-packaged liposomes in osteoporotic mice restores impaired Notch activity in skeletal endothelium, thereby promoting angiogenesis-dependent osteogenesis and ameliorating bone loss. Pharmacological reversal of the low ZEB1/Notch signaling may exert therapeutic benefit in osteoporotic patients by promoting angiogenesis-dependent bone formation.

Clinical characteristics of COVID-19 in pregnancy: analysis of nine cases / 中华围产医学杂志

Objective@#To evaluate the clinical characteristics and pregnant outcomes of gravidae with COVID-19.@*Methods@#This study involved nine gravidae with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 22 to February 1, 2020. Their clinical data, including epidemiological history, clinical symptoms, laboratory examinations, chest CT, treatment, delivery mode, and pregnancy outcomes, were analyzed retrospectively. Descriptive analysis was applied in this study.@*Results@#(1) Among the nine cases, five were admitted in the third trimester and four in the second trimester. The median incubation period of COVID-19 was 8 (1-14) d. Fever was presented in all cases on admission, and the other commonly seen symptoms were cough (seven cases) and diarrhea (five cases). Other signs and symptoms were also reported, including shortness of breath, myalgia and fatigue (four cases in each), nasal obstruction, pharyngalgia, chest pain, and headache/dizziness (three cases in each), rash (two cases), and chills and expectoration (one case in each). The most common laboratory abnormalities were a decreased number of lymphocytes (seven cases) and elevated C-reactive protein (six cases). Chest CT scans were performed in seven women, and all showed patchy areas or ground-glass opacity in both lungs. Oligohydramnios was detected in only one case at 37+5 weeks, which was 7 d after the diagnosis of COVID-19. (2) All nine cases received empiric antibiotic and antiviral therapy with Chinese medicine as adjuvant treatment. Eight patients required oxygen inhalation, and seven were treated with glucocorticoid. One case received immunotherapy due to worsening conditions. (3) Four of the nine cases had delivered, including three cesarean sections and one spontaneous vaginal preterm birth after premature rupture of membranes, and the mother was transferred to the intensive care unit 2 d after delivery due to acute respiratory distress syndrome. One case was terminated at 26 gestational weeks. Of the four neonates, there were two term and two premature babies, and one preterm babies was small-for-gestational-age. No neonatal asphyxia was observed. Serial real-time quantitative reverse transcription-polymerase chain reaction showed negative results in the detection of 2019-novel coronavirus in all samples obtained from amniotic fluid, umbilical cord blood, neonatal nasopharynx, breast milk, and vagina. Maternal conditions were all stable in all cases, including the four continuing pregnancy, and the terminated ones, except the case mentioned above.@*Conclusions@#There is no distinguishable clinical feature between pregnant and non-pregnant COVID-19 patients. Currently, the evidence for vertical transmission of COVID-19 needs further studies with larger size of examples, but pregnancy may deteriorate COVID-19. Given that COVID-19 may have adverse effects on perinatal outcomes, it's recommended to take positive and effective measures for COVID-19 women in the third trimester.

Clinical characteristics of COVID-19 in pregnancy: analysis of nine cases / 中华围产医学杂志

Objective To evaluate the clinical characteristics and pregnant outcomes of gravidae with COVID-19. Methods This study involved nine gravidae with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 22 to February 1, 2020. Their clinical data, including epidemiological history, clinical symptoms, laboratory examinations, chest CT, treatment, delivery mode, and pregnancy outcomes, were analyzed retrospectively. Specimens of maternal vaginal swab were collected in six pregnant women, and the specimens of amniotic fluid, cord blood, neonatal throat swab and breast milk samples were collected in four pregnant women who had a delivery during our study. All samples were tested for the existence of COVID-19. Descriptive analysis was applied in this study. Results (1) Among the nine cases, five were admitted in the third trimester and four in the second trimester. The median incubation period of COVID-19 was 8 (1-14) d. Fever was presented in all cases on admission, and the other commonly seen symptoms were cough (seven cases) and diarrhea (five cases). Other signs and symptoms were also reported, including shortness of breath, myalgia and fatigue (four cases in each), nasal obstruction, pharyngalgia, chest pain, and headache/dizziness (three cases in each), rash (two cases), and chills and expectoration (one case in each). The most common laboratory abnormalities were a decreased number of lymphocytes (seven cases) and elevated C-reactive protein (six cases). Chest CT scans were performed in seven women, and all showed patchy areas or ground-glass opacity in both lungs. Oligohydramnios was detected in only one case at 37 +5 weeks, which was 7 d after the diagnosis of COVID-19. (2) All nine cases received empiric antibiotic and antiviral therapy with Chinese medicine as adjuvant treatment. Eight patients required oxygen inhalation, and eight were treated with glucocorticoid. Six cases received immunotherapy. (3) Four of the nine cases had delivered, including three cesarean sections and one spontaneous vaginal preterm birth after premature rupture of membranes, and the mother was transferred to the intensive care unit 2 d after delivery due to acute respiratory distress syndrome. One case was terminated at 26 gestational weeks. Of the four neonates, there were two term and two premature babies, and one preterm baby was small-for-gestational-age. No neonatal asphyxia was observed. Serial real-time quantitative reverse transcription-polymerase chain reaction showed negative results in the detection of 2019-novel coronavirus in all samples obtained from amniotic fluid, umbilical cord blood, neonatal nasopharynx, breast milk, and vagina. Maternal conditions were all stable in all cases, including the four continuing pregnancy, and the terminated ones, except the case mentioned above. Conclusions There is no distinguishable clinical feature between pregnant and non-pregnant COVID-19 patients. So far, there is no evidence for vertical transmission or worsening perinatal outcome in mothers and babies.

Clinical characteristics of COVID-19 in pregnancy: analysis of nine cases / 中华围产医学杂志

Objective:To evaluate the clinical characteristics and pregnant outcomes of gravidae with COVID-19.Methods:This study involved nine gravidae with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 22 to February 1, 2020. Their clinical data, including epidemiological history, clinical symptoms, laboratory examinations, chest CT, treatment, delivery mode, and pregnancy outcomes, were analyzed retrospectively. Specimens of maternal vaginal swab were collected in six pregnant women, and the specimens of amniotic fluid, cord blood, neonatal throat swab and breast milk samples were collected in four pregnant women who had a delivery during our study. All samples were tested for the existence of COVID-19. Descriptive analysis was applied in this study.Results:(1) Among the nine cases, five were admitted in the third trimester and four in the second trimester. The median incubation period of COVID-19 was 8 (1-14) d. Fever was presented in all cases on admission, and the other commonly seen symptoms were cough (seven cases) and diarrhea (five cases). Other signs and symptoms were also reported, including shortness of breath, myalgia and fatigue (four cases in each), nasal obstruction, pharyngalgia, chest pain, and headache/dizziness (three cases in each), rash (two cases), and chills and expectoration (one case in each). The most common laboratory abnormalities were a decreased number of lymphocytes (seven cases) and elevated C-reactive protein (six cases). Chest CT scans were performed in seven women, and all showed patchy areas or ground-glass opacity in both lungs. Oligohydramnios was detected in only one case at 37 +5 weeks, which was seven days after the diagnosis of COVID-19. (2) All nine cases received empiric antibiotic and antiviral therapy with Chinese medicine as adjuvant treatment. Eight patients required oxygen inhalation, and eight were treated with glucocorticoid. Six cases received immunotherapy. (3) Four of the nine cases had delivered, including three cesarean sections and one spontaneous vaginal preterm birth after premature rupture of membranes, and the mother was transferred to the intensive care unit two days after delivery due to acute respiratory distress syndrome. One case was terminated at 26 gestational weeks. Of the four neonates, there were two term and two premature babies, and one preterm baby was small-for-gestational-age. No neonatal asphyxia was observed. Serial real-time quantitative reverse transcription-polymerase chain reaction showed negative results in the detection of 2019-novel coronavirus in all samples obtained from amniotic fluid, umbilical cord blood, neonatal nasopharynx, breast milk, and vagina. Maternal conditions were all stable in all cases, including the four continuing pregnancy, and the terminated ones, except the case mentioned above. Conclusions:There is no distinguishable clinical feature between pregnant and non-pregnant COVID-19 patients. So far, there is no evidence for vertical transmission or worsening perinatal outcomes in mothers and babies.