Polyhydroxyl guaianolide terpenoids as potential NF-кB inhibitors induced cytotoxicity in human gastric adenocarcinoma cell line.

Six new guaiane-type sesquiterpenes (1-6), and one monoterpenoid (7) along with five known analogues (8-12), were isolated from the leaves of Artemisia argyi Lévl et Vant. The new compounds were characterized by the basic analysis of the spectroscopic data (HRMS, 1D and 2D NMR), and the absolute configurations were determined by both calculated electronic circular dichroism and DP4 calculations. The inhibitory effects of 1-12 against human gastric adenocarcinoma (AGS) cells were investigated in vitro, among which 1-3 and 8 showed remarkable cytotoxic activity with IC50 values in the range of 6.69-10.25 µM. The results suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on C-8. In order to rationalize the binding interactions of active compounds with the active site of NF-кB, in silico study was conducted and the results were in complete agreement with the experimental data for cytotoxicity evaluation.

Virtual screening of active compounds from Artemisia argyi and potential targets against gastric ulcer based on Network pharmacology.

Artemisia argyi (AA) is one of the renowned herbs in China often used in the treatment of gastric ulcer (GU). Aiming to predict the active compounds and systematically investigate the mechanisms of Artemisia argyi for GU treatment, the approach of network pharmacology, molecular docking, gene ontology (GO) analysis, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were adopted, respectively, in present study. A total of 13 predicted targets of the 103 compounds in Artemisia argyi were obtained. Sorted by pathogenic mechanisms of targets and structure types of compounds, it was revealed that flavonoids and sesquiterpenes had better performance than monoterpenes. The network analysis showed that Phospholipase a2 (PA21B), Sulfotransferase family cytosolic 2b member 1 (ST2B1), Nitric-oxide synthase, endothelial (NOS3), Gastrin (GAST), neutrophil collagenase (MMP-8), Leukotriene A-4 hydrolase (LKHA4), Urease maturation factor HypB (HYPB), and Periplasmic serine endoprotease DegP (HtrA) were the key targets with intensely interaction. The functional enrichment analysis indicated that AA probably produced the gastric mucosa protection effects by synergistically regulating many biological pathways, such as NF-κB signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, VEGF signaling pathway, and Toll-like receptor signaling pathway, etc. In addition, C73 and C15 might be promising leading compounds with good molecular docking score. As a consequence, this study holistically illuminates the active constituents and mechanisms based on data analysis, which contributes to searching for leading compounds and the development of new drugs for gastric ulcer.

Systems Pharmacological Approach to Investigate the Mechanism of Ohwia caudata for Application to Alzheimer's Disease.

Ohwia caudata (OC)-a traditional Chinese medicine (TCM)-has been reported to have large numbers of flavonoids, alkaloids, and triterpenoids. The previous studies on OC for treating Alzheimer's disease (AD) only focused on single targets and its mechanisms, while no report had shown about the synergistic mechanism of the constituents from OC related to their potential treatment on dementia in any database. This study aimed to predict the bioactive targets constituents and find potential compounds from OC with better oral bioavailability and blood-brain barrier permeability against AD, by using a system network level-based in silico approach. The results revealed that two new flavonoids, and another 26 compounds isolated from OC in our lab, were highly connected to AD-related signaling pathways and biological processes, which were confirmed by compound-target network, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, respectively. Predicted by the virtual screening and various network pharmacology methods, we found the multiple mechanisms of OC, which are effective for alleviating AD symptoms through multiple targets in a synergetic way.

Phytochemical and cytotoxic studies on the roots of Euphorbia fischeriana.

With the aim of supporting the folk applications of Euphorbia fischeriana, a phytochemical study was performed, which led to the discovery of 9 compounds, including three new ones (1-3) and six known ones (4-9). Their structures were determined by 1D, 2D NMR, and HRESIMS analysis. In the cytotoxic assays on Hep-3B cell line, 2 showed stronger inhibitory effects (IC50 8.1µmol/L) than that of positive control, and 1, 8 and 9 also gave inhibitory effects in a certain degree with IC50 values of 12.5, 12.0 and 18.7µmol/L, respectively. While on A549, the cytotoxic activities of 1 (IC50 11.9µmol/L) and 8 (IC50 9.4µmol/L) were superior to that of 5-Fu, and those of 4 and 9 were moderate with IC50 values of 28.2 and 29.8µmol/L, respectively. In addition, both petroleum ether and dichloromethane extracts showed cytotoxic activities with different degree, while n-butanol extracts had no effect. The results clarified that the low-polarity fractions of E. fischeriana, including triterpenoids, abietane and tigliane-type diterpenoids might be the potential bioactive ingredients which will exert strong antitumor effects.

PTPN22 modulates macrophage polarization and susceptibility to dextran sulfate sodium-induced colitis.

PTPN22, a protein tyrosine phosphatase expressed mainly in hematopoietic cells, has been linked to many autoimmune diseases. A C-to-T single nucleotide polymorphism (SNP) at position 1858 of human PTPN22 cDNA decreases the risk of Crohn's disease. However, the function of PTPN22 and the mechanism by which this SNP reduces the risk of Crohn's disease are poorly understood. We find that PTPN22 is expressed in macrophages. It suppresses M1 macrophage polarization and reciprocally promotes the expression of M2-associated genes. PTPN22-deficient mice develop severe colitis induced by dextran sulfate sodium, and their intestinal macrophages express higher levels of M1 genes but lower levels of M2-associated genes. Furthermore, the protective T allele of the C1858T SNP is associated with attenuated expression of inflammatory cytokines and a higher level of PTPN22 in human M1 macrophages. This T allele-associated aberrant expression of PTPN22 is partly attributed to an autoinhibition mechanism, in which PTPN22 suppresses its own expression in M1 but not M2 macrophages. Our data not only demonstrate a critical role of PTPN22 in regulating macrophage polarization but also provide a molecular explanation for the protective effect of the C1858T SNP in Crohn's disease.

Factors Impacting Fall Severity in Hospitalized Patients: A Retrospective Cohort Study.

Objectives: This retrospective case-controlled study aimed to evaluate the association between the severity of fall-related injuries and fall-risk-increasing drugs (FRIDs) in hospitalized patients. Methods: Data were collected from Changhua Christian Hospital, Taiwan, of all adult inpatients who experienced falls between January 2017 and December 2021, and were divided into two groups based on whether they sustained severe fall-related injuries. Retrospective data that may affect the severity of fall-related injuries and the use of FRIDs were investigated. Results: Among 1231 documented cases of falls, 26 patients sustained severe fall-related injuries. Older patients and those with osteoporosis were more susceptible to more severe injuries from a fall. The use of mobility aids and osteoporosis medications showed protective effects against fall injuries. No significant association was observed between fall-related injuries and comorbidities or FRIDs. Multivariate analysis confirmed the inverse correlation between the use of mobility aids, osteoporosis medications, and fall severity. Patients with osteoporosis exhibited significantly higher odds of sustaining more severe injuries with a fall (odds ratio = 3.02, 95% confidence interval: 1.21-7.53). Conclusions: This study highlights the importance of addressing risk factors associated with fall severity among hospitalized patients. Providing mobility aids to persons at greater risk.

Associations between doses of fall-risk-increasing drugs (FRIDs) and falls of hospitalized patients.

Falls are a serious public health problem in the aging population because of the associated clinical and socioeconomic impact. Although previous studies have investigated fall-risk-increasing drugs (FRIDs), few studies have focused on dosage among adult inpatients. This study aimed to evaluate associations between fall risk and dosage of different FRIDs classes in hospital inpatients. Inpatients who experienced falls at medical or surgical wards of Changhua Christian Hospital from January 2017 to December 2021 were identified and matched by age, sex, and hospital ward to randomly selected controls (four per case). Anonymous patient data were extracted from the hospital medical data repository, including demographic characteristics, comorbidities, fall-risk scores, and drug prescriptions. Medication dosages were computed using the anatomical therapeutic chemical classification and the defined daily dose system of the World Health Organization. A total of 852 cases and 3408 controls were identified as eligible. Reducing the use of CNS-active medications, administering lower doses of sedative-hypnotics, prescribing sufficient dopaminergic anti-Parkinson agents, and using NSAIDs instead of opioids are imperative in preventing falls among hospitalized patients according to the findings in the study.

Chemical constituents and biological activities of Artemisia argyi H.Lév. & vaniot.

Artemisia argyi is a widely distributed and inexpensive plant resource, and study on its chemical compositions and biological activities will provide an important basis for its food applications and pharmaceutical developments. In this study, fourteen known guaiane-type sesquiterpenes (1-14), four known eudesmane-type sesquiterpenes (15-18), two known germacranolide-type sesquiterpenes (19, 20), and eight other types of terpenoids (20-28) were isolated from the leaves of A. argyi by polyamide and ODS CC and HPLC. The structures of all compounds are determined by 1 D NMR (1H-NMR、13C-NMR) and literature comparison. Among them, compounds 1 and 8 were isolated from Chinese folk medicine A. argyi for the first time. Besides, the LPS-induced RAW264.7 cell model has been evaluated the anti-inflammatory activities in vitro by the Griess reagent. The results indicated that the guaianolide sesquiterpenoids obtained from A. argyi have an excellent ability to inhibit NO production, especially Argyin A, a guaianolide sesquiterpenoid with isovaleryloxy substitution.

Accuracy of Pedicle Screw Placement and Four Other Clinical Outcomes of Robotic Guidance Technique versus Computer-Assisted Navigation in Thoracolumbar Surgery: A Meta-Analysis.

BACKGROUND: Robotic guidance (RG) pedicle screw placement has been increasingly used to improve the rate of insertion accuracy. However, the superiority of the RG technique over computer-assisted navigation (CAN) remains debatable. OBJECTIVE: To determine whether the Mazor RG technique is superior to CAN in terms of the rate of insertion accuracy and 4 other clinical indices, namely, intraoperative time, blood loss, complications and revision surgery caused by malposition. METHODS: A search of PubMed, Embase, Cochrane, Web of Science, CNKI, and WanFang was conducted. We mainly aimed to evaluate the accuracy of pedicle screw placement between the Mazor RG and CAN techniques. The secondary objectives were intraoperative time, blood loss, complications, and revision surgery caused by malposition. The meta-analysis was conducted using the RevMan 5.3 and Stata 15.1 software. RESULTS: A randomized controlled trial and 5 comparative cohort studies consisting of 529 patients and 4081 pedicle screws were included in this meta-analysis. The RG technique has a significantly higher accuracy than CAN in terms of optimal (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.85-2.76; P < 0.01) and clinically acceptable (OR, 1.69; 95% CI, 1.22-2.34; P = 0.002) pedicle screw insertions. Furthermore, the RG technique showed significantly less blood loss (mean difference, -42.49; 95% CI, -78.38 to -6.61; P = 0.02) than did the CAN technique but has equivalent intraoperative time (mean difference, 0.75; 95% CI, -5.89 to 7.40; P = 0.82), complications (OR, 0.65; 95% CI, 0.32-1.33, P = 0.24), and revision surgery caused by malposition (OR, 0.46; 95% CI, 0.15-1.43, P = 0.18). CONCLUSIONS: The Mazor RG technique is superior to CAN concerning the accuracy of pedicle screw placement. Thus, the Mazor RG technique is accurate and safe in clinical application.

Population genetic structure and adaptive differentiation of iron walnut Juglans regia subsp. sigillata in southwestern China.

Southwestern (SW) China is an area of active tectonism and erosion, yielding a dynamic, deeply eroded landscape that influences the genetic structure of the resident populations of plants and animals. Iron walnut (Juglans regia subsp. sigillata) is a deciduous tree species endemic to this region of China and cultivated there for its edible nuts. We sampled 36 iron walnut populations from locations throughout the species' range in SW China and genotyped a total of 765 individuals at five chloroplast DNA regions and 22 nuclear microsatellite loci. Species distribution models were produced to predict the evolution and historical biogeography of iron walnut and to estimate the impacts of climate oscillations and orographic environments on the species' demography. Our results indicated that J. regia subsp. sigillata had relatively low genetic diversity, high interpopulation genetic differentiation, and asymmetric interpopulation gene flow. Based on DIYABC analysis, we identified two lineages of J. sigillata in southwestern China. The lineages (subpopulations) diverge during the last glacial period (~1.34 Ma). Southwestern China was a glacial refuge during the last glacial period, but increasingly colder and arid climates might have fostered the fragmentation of J. regia subsp. sigillata within this refugium. Finally, we found that recent habitat fragmentation has led to a reduction in population connectivity and increased genetic differentiation by genetic drift in isolated populations. Our results support a conclusion that geological and climatic factors since the Miocene triggered the differentiation, evolutionary origin, and range shifts of J. sigillata in the studied region.

A green and facile preparation approach, licochalcone A capped on hollow gold nanoparticles, for improving the solubility and dissolution of anticancer natural product.

This study described a valuable drug delivery system for poorly water-soluble anticancer naturalproduct, licochalcone A, isolated from Glycyrrhiza inflata, loaded on hollow gold nanoparticles by green method to improve solubility and dissolution and maintain its natural pharmacological property. Briefly, the formation of hollow gold nanoparticles involves three steps: preparing of silica nanospheres by Stober method, forming of a thick gold shell around the silica templates and etching of silica particles by HF solution. Hollow gold nanoparticles (HGNPs) and drug loaded hollow gold nanoparticles (L-HGNPs) displayed spherical structure and approximately 200nm in size observed by SEM, XRD, EDS and DSC analysis showed that HGNPs were gold hollow structure and crystalline form. The solubility in aqueous solution of licochalcone A was increased obviously to 488.9 µg/ml, compared with free drugs of 136.1 µg/ml. Another interesting finding is that near-infrared (NIR) irradiation increased the speed of solubility of licochalcone A in aqueous solutions, rather than quantity. In short, the method of nano-delivery system combined with poorly water-soluble drug to improve its solubility and dissolution is worth applying to other natural products in order to increase their opportunities in clinical applications.

[The cardioprotection of estrogen on solated global myocardial ischemia/reperfusion injury in ovariectomized rats].

AIM: To investigated the effect of estrogen on global myocardial ischemia/reperfusion (I/R) injury in ovariectomized (Ovx) rats. METHODS: Sprague-Dawley rats were randomly repartitioned into three groups including sham-operated(Sham), ovariectomized (Ovx), or ovariectomized and then given 17beta-estradiol (Ovx + E2). Hearts were excised, mounted on the Langendorff. After the initial stabilization period, all of the three group hearts were randomly divided into normal perfusion subgroup (Control) and I/R perfusion subgroups. Control, perfused for 60 min after stabilization. I/R perfusion subgroups divided into 10 min I + 30 min R, 20 min I + 30 min R, 30 min I + 0 min R, 30 min I + 5 min R, 30 min I + 15 min R and 30 min I + 30 min R. And then, every group hearts were isolated into the single cardiomyocyte. The cardiomyocytes basal contraction and isoproterenol(ISO) stimulation contraction were measured. The viability and yield of cardiomyocytes were counted. LDH and CK concentrations in coronary effluent were assayed with assay kit. RESULTS: The viability and yield of cardiomyocytes were significantly decreased in the conditions of 30 min ischemia followed by different times of reperfusion. The releases of LDH and CK in coronary effluent were significantly increased in the conditions of 30 min ischemia followed by different times of reperfusion. Except the 10 min and 20 min ischemia, the releases of LDH and CK were significantly increased in Ovx during I/R. Ovx + E2 could abate the heart injury through decreasing the releases of LDH and CK. Besides the control and the 10 min I + 30 min R groups, the myocardial basal and ISO stimulation contraction were higher from Ovx than Sham, and the effect was reversed by Ovx + Ez. CONCLUSION: The results indicate estrogen plays a cardioprotective role in global myocardial ischemia/reperfusion injury in ovariectomized (Ovx) rats.