The relationship between health literacy and blood sugar control in rural areas among diabetes patients.

Background: Although the relationship between health literacy and glycemic control has been explored in patients with diabetes, little is known about the relationship between different categories of diabetes health literacy and glycemic control in rural areas. Therefore, this study focused on the relationship between different categories of health literacy and glycemic control among diabetic patients in rural areas of Guangxi, China. Objective: To explore the potential profiles of health literacy among rural diabetes patients in Guangxi and investigate their relationship with blood sugar control. Methods: A health literacy questionnaire was administered to 2280 rural diabetes patients in five cities in the Guangxi Zhuang Autonomous Region. Latent profile analysis was conducted to identify potential health literacy profiles. Results: Health literacy among rural diabetes patients in Guangxi could be categorized into high literacy-high functionality and low literacy-low criticality groups. The latent categories of health literacy were associated with blood sugar control, with diabetes patients in the high literacy-high functionality group demonstrating better blood sugar control than those in the low literacy-low criticality group (P < 0.05). Conclusion: Health literacy among rural diabetes patients in Guangxi exhibits heterogeneity. Healthcare professionals should pay attention to patients with low literacy and low criticality in rural areas and develop interventions to enhance their health literacy, thereby improving their blood sugar control.

Application of G-quadruplex targets in gastrointestinal cancers: Advancements, challenges and prospects.

Genomic instability and inflammation are considered to be two enabling characteristics that support cancer development and progression. G-quadruplex structure is a key element that contributes to genomic instability and inflammation. G-quadruplexes were once regarded as simply an obstacle that can block the transcription of oncogenes. A ligand targeting G-quadruplexes was found to have anticancer activity, making G-quadruplexes potential anticancer targets. However, further investigation has revealed that G-quadruplexes are widely distributed throughout the human genome and have many functions, such as regulating DNA replication, DNA repair, transcription, translation, epigenetics, and inflammatory response. G-quadruplexes play double regulatory roles in transcription and translation. In this review, we focus on G-quadruplexes as novel targets for the treatment of gastrointestinal cancers. We summarize the application basis of G-quadruplexes in gastrointestinal cancers, including their distribution sites, structural characteristics, and physiological functions. We describe the current status of applications for the treatment of esophageal cancer, pancreatic cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, and gastrointestinal stromal tumors, as well as the associated challenges. Finally, we review the prospective clinical applications of G-quadruplex targets, providing references for targeted treatment strategies in gastrointestinal cancers.

Sweet potato (Ipomoea batatas) and hyacinth bean (Lablab purpureus) in combination provide greater suppression of mile-a-minute (Mikania micrantha) than either crop alone.

Introduction: In natural systems, diverse plant communities tend to prevent a single species from dominating. Similarly, management of invasive alien plants may be achieved through various combinations of competing species. Methods: We used a de Wit replacement series to compare different combinations of sweet potato (Ipomoea batatas (L.) Lam), hyacinth bean (Lablab purpureus (L.) Sweet) and mile-a-minute (Mikania micrantha Kunth) through measures of photosynthesis, plant growth, nutrient levels in plant tissue and soil, and competitive ability. Results: Cultured alone sweet potato and hyacinth beans exhibited higher total biomass, leafstalk length, and leaf area than mile-a-minute. In mixed culture, either sweet potato or hyacinth bean or both together significantly suppressed the mile-a-minute parameters, i.e., plant height, branch, leaf, adventitious root, and biomass (P<0.05). Based on a significantly lower than 1.0 relative yield of the three plant species in mixed culture, we showed intraspecific competition to be less than interspecific competition. Calculated indices (relative yield, relative yield total, competitive balance index, and change in contribution) demonstrated a higher competitive ability and higher influence of either crop compared to mile-a-minute. The presence of sweet potato and hyacinth bean, especially with both species in combination, significantly reduced (P<0.05) mile-a-minute's net photosynthetic rate (Pn), antioxidant enzyme activities (superoxide dismutase, peroxidase, catalase, and malondialdehyde), chlorophyll content, and nutrient content (N, P, and K). In soil with mile-a-minute in monoculture soil organic matter, total and available N, total and available K, and available P were significantly greater (P<0.05) than in soil with sweet potato grown in monoculture, but less than in soil with hyacinth bean grown in monoculture soil. Nutrient soil content was comparatively reduced for plant mixtures. Plant height, leaf, biomass, Pn, antioxidant enzyme activities, and plant and soil nutrient contents of sweet potato and hyacinth bean tended to be much greater when grown with two crops compared to in mixture with just sweet potato or hyacinth bean. Discussion: Our results suggest that the competitive abilities of both sweet potato and hyacinth bean were greater than that of mile-a-minute, and also that mile-a-minute suppression was significantly improved via a combination of the two crops compared to either sweet potato or hyacinth bean alone.

Colorimetric Aptasensor for the Visual and Microplate Determination of Clusterin in Human Urine Based on Aggregation Characteristics of Gold Nanoparticles.

Clusterin has the potential to become the biomarker of multiple diseases, but its clinical quantitative detection methods are limited, which restricts its research progress as a biomarker. A rapid and visible colorimetric sensor for clusterin detection based on sodium chloride-induced aggregation characteristic of gold nanoparticles (AuNPs) was successfully constructed. Unlike the existing methods based on antigen-antibody recognition reactions, the aptamer of clusterin was used as the sensing recognition element. The aptamer could protect AuNPs from aggregation caused by sodium chloride, but clusterin bound with aptamer detached it from AuNPs, thereby inducing aggregation again. Simultaneously, the color change from red in the dispersed state to purple gray in the aggregated state made it possible to preliminarily judge the concentration of clusterin by observation. This biosensor showed a linear range of 0.02-2 ng/mL and good sensitivity with a detection limit of 5.37 pg/mL. The test results of clusterin in spiked human urine confirmed that the recovery rate was satisfactory. The proposed strategy is helpful for the development of label-free point-of-care testing equipment for clinical testing of clusterin, which is cost-effective and feasible.

The bound polyphenols of foxtail millet (Setaria italica) inner shell inhibit breast cancer by promoting lipid accumulation-induced autophagic death.

Foxtail millet is a traditional excellent crop with high nutritional value in the world, belong to cereals. The bran of foxtail millet is rich in polyphenol that has antioxidant, anti-inflammatory, and anti-tumorigenic effects. Previously, we extracted bound polyphenols from the inner shell of foxtail millet bran (BPIS). Here, we report that BPIS specifically induced breast cancer cell death and elevated the autophagy level simultaneously. The addition of an autophagy inhibitor blocked BPIS-induced breast cancer cell death, indicating that excessive autophagy induced cell death. Furthermore, oil red O and BODIPY staining also confirmed that lipids, which are important inducers of autophagy, accumulated in breast cancer cells treated with BPIS. Lipidomics research revealed that glycerophospholipids were the main accumulated lipids induced by BPIS. Further study showed that elevated PCYT1A expression was responsible for glycerophospholipid accumulation, and BPIS contained ferulic acid and p-coumaric acid, which induced PCYT1A expression and breast cancer cell death. Collectively, our results revealed that BPIS resulted in autophagic death by enhancing lipid accumulation in breast cancer cells, and BPIS contains ferulic acid and p-coumaric acid, which provided new insights into developing nutraceuticals and drugs for breast cancer patients.

Probiotics and Prebiotics as Dietary Supplements for the Adjunctive Treatment of Type 2 Diabetes.

In modern lifestyles, high-fat diets and prolonged inactivity lead to more people developing type 2 diabetes (T2D). Based on the modern pathogenesis of T2D, food, and its components have become one of the top concerns for patients. Recent studies have found that dysbiosis and gut-related inflammation are more common in T2D patients. Probiotics and prebiotics play complementary roles in the gut as dietary supplements. Together, they may help improve dysbiosis and intestinal inflammation in people with T2D, increase the production of blood glucose-lowering hormones such as incretin, and help reduce insulin resistance and lower blood glucose. Therefore, changing the dietary structure and increasing the intake of probiotics and prebiotics is expected to become a new strategy for the adjuvant treatment of T2D.

Development and validation of a decision tree classification model for the essential hypertension based on serum protein biomarkers.

Background: Essential hypertension (EH) is a key risk factor for cardiovascular disease. However, the etiology of EH is complex and unknown. So far, there is no good protein biomarker for screening EH. The purpose of this study was to discover potential biomarkers for EH by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and establish a decision-tree classification model. Methods: A total of 108 patients with clinically confirmed EH and 105 HC were enrolled in the present study from September 2020 to April 2021 and were randomly divided into the training group and the blind-test group. The serum protein expression profiles were performed using MALDI-TOF MS combined with magnetic beads with weak cation exchange (MB-WCX). The training group, which comprised 54 EH patients and 53 HC, was used to screen the statistically differential protein peaks by SPSS 19.0 and construct a decision-tree classification model by C5.0 algorithms of SPSS Modeler 18.0. All protein peak intensities of samples in the blind-test group, which comprised 54 EH patients and 52 HC, were used to verify the diagnostic capabilities of the model by classification model. Results: EH patients had higher age, systolic and diastolic blood pressures than HC group. The intensities of 60 protein peaks differed significantly between the EH patients and HC. An optimal decision-tree classification model of EH was successfully established with mass-to-charge ratios of 1,326.7, 1,785.3, 4,228.0, and 8,963.8 as differential protein peaks by the software analysis. The decision-tree classification model was able to distinguish between EH patients and HC and had a sensitivity of 94.44%, a specificity of 94.33%, an accuracy of 94.39%, and an area under the receiver operating characteristic (ROC) curve of 0.96. The blind-test results indicated a sensitivity of 87.04%, a specificity of 88.46%, an accuracy of 87.74%, and an area under the ROC curve of 0.928. Conclusions: MALDI-TOF MS combined with MB-WCX can be used to screen for serum differential protein expression profiles in EH patients. The decision-tree classification model based on mass-to-charge ratios of 1,326.7, 1,785.3, 4,228.0, and 8,963.8 could provide a new and reliable method for screening and identifying EH with high sensitivity and specificity.

c-MYC and HIF1α promoter G-quadruplexes dependent metabolic regulation mechanism of berberine in colon cancer.

Background: G-quadruplexes are molecular switches regulating gene transcription. c-MYC and hypoxia-inducible factor 1-alpha (HIF1α) play important roles in cell proliferation, apoptosis, and metabolic regulation in colon cancer. Whether berberine can regulate metabolism by interacting with c-MYC and HIF1α G-quadruplexes in colon cancer needs to be explored. Methods: The binding mode of berberine with c-MYC and HIF1α G-quadruplexes were explored by ultraviolet and visible absorption spectroscopy and fluorescence spectroscopy. Circular dichroism (CD) spectroscopy was performed to evaluate the effects of berberine on the stability of c-MYC and HIF1α G-quadruplexes. After different concentrations of berberine acting on HCT116 cells for 24 h, cell proliferation and apoptosis were detected by MTT assay and flow cytometry; quantitative real-time polymerase chain reaction and western blot were performed to detect mRNA and protein expression of c-MYC and HIF1α; transcriptome sequencing was used to analyze the metabolic pathways. For the effects of berberine on colon cancer mouse model with dose of 50 mg·kg-1 for 14 days, tumor growth were monitored, hematoxylin and eosin staining and immunofluorescence staining were performed to analyze histopathology and protein expression of c-MYC and HIF1α, central carbon metabolism was detected in tumor tissues. Results: The binding ability of berberine with c-MYC G-quadruplex was different to that of berberine with HIF1α G-quadruplex. Both binding modes involved π-π stacking. The stoichiometric ratios were 1:1, 1:3, and 3:1 for berberine with c-MYC G-quadruplex and only 1:1 for berberine with HIF1α G-quadruplex. Temperature had a greater effect on the binding of berberine to c-MYC G-quadruplex. Berberine could improve the thermal stability of both c-MYC and HIF1α G-quadruplexes. Berberine inhibited the gene transcription and protein expression of c-MYC and HIF1α in colon cancer HCT116 cells. In vivo, berberine delayed tumor progression and inhibited the protein expression of c-MYC and HIF1α. Twelve differential metabolites such as decreased adenosine triphosphate were obtained, indicating that berberine could regulate the metabolic pathways of the tricarboxylic acid (TCA) cycle and glycolysis/gluconeogenesis, among others. Conclusions: Berberine may inhibit colon cancer by regulating the TCA cycle and glycolysis/gluconeogenesis based on the interaction with c-MYC and HIF1α G-quadruplexes.

Estimating the critical shear stress for incipient particle motion of a cohesive soil slope.

The critical shear stress is a vital reference indicator for soil erosion. Soil erosion will occur when soil slope suffers from a exceed shear stress, and then causing soil loss and destruction of soil structure. In this work, an equation was proposed based on the force equilibrium of a single particle to estimate the critical shear stress for incipient particle motion of a cohesive soil slope. This formula is characterized by its physical significance, and the critical shear stress for incipient slope soil motion can be easily calculated when the soil properties and the slope angle are known. Moreover, the seepage-runoff coupled model and the excess shear stress equation are introduced in this paper. Two parameters, namely the weight of rushed soil particles and the discharge of water, must be measured in the scouring tests. Through linear regression, the tested τc-values were obtained to validate the τc-values calculated by the formula derived from the critical shear stress. In addition, two other formulas were compared with the derived formulas, which considered more parameters with physical significance. Finally, the influence of all parameters on the critical shear stress was analyzed: the porosity of the soil, the specific gravity of the soil and the slope gradient had less influence on the critical shear stress; the critical shear stress was negatively influenced by the particle diameter and positively influenced by the internal friction angle of the soil.

Allelochemicals Identified From Sweet Potato (Ipomoea batatas) and Their Allelopathic Effects on Invasive Alien Plants.

Sweet potato [Ipomoea batatas (L.) Lam] is grown as important cash and food crop worldwide and has been shown to exhibit allelopathic effects on other plants. However, its metabolome has not been studied extensively, particularly with respect to the production of phytotoxic bioactive secondary products. In this study, the chemical composition of petroleum ether extract of sweet potato was characterized, and the morphological and physiological effects of some individual components against four invasive alien weeds Bidens pilosa L., Galinsoga parviflora Cav., Lolium multiflorum Lam., and Phalaris minor Retz. were determined. Twenty-one components were identified by GS-MS, constituting 96.08% of petroleum ether extract in sweet potato. The major components were palmitic acid (PA) (17.48%), ethyl linoleate (EL) (13.19%), linoleic acid (LA) (12.55%), ethyl palmitate (EP) (11.77%), ethyl linolenate (ELL) (8.29%) oleic acid (5.82%), ethyl stearate (4.19%), and 3-methylphenol acetate (3.19%). The five most abundant compounds exhibited strong inhibition activity against the four invasive weeds tested. The highest inhibition rates were seen for LA, followed by PA and EP, respectively. Catalase (CAT), malondialdehyde (MDA), and peroxidase (POD) content of L. multiflorum were increased by the three allelochemicals, i.e., LA, PA and EP, but superoxide dismutase (SOD), chlorophyll-a and chlorophyll-b levels declined. Overall, the combined impact of all five compounds could be quite effective in suppressing the invasive weeds of concern.

Angiogenic markers could predict adverse pregnancy outcomes.

Adverse pregnancy outcomes (APOs) have been a devastating actuality in clinic. However, the pre-onset risk factors, that correlated with pregnancy failure, including antiphospholipid antibodies (APLs) and angiogenic factors, remain unclear. A retrospective study was performed in this research, and data from 145 pregnant women were collected during their pregnancy. Patients were finally divided into non-APO group (n = 89) and APO group (n = 56) according to their pregnancy outcomes. The associations among their characteristics, laboratory tests, therapies, and outcomes were analyzed. Univariate analysis demonstrated that patients with APOs showed significant prevalence of lupus anticoagulant (LAC) positive (P < 0.001), antiphospholipid syndrome (P = 0.030), and heparin prior to pregnancy (P = 0.041). LAC positive was correlated with shorter gestational age (P = 0.043) and gestational weeks of pre-term delivery (P = 0.011). Increased ratio of soluble vascular endothelial growth factor receptor-1/placental growth factor in pregnancies with APLs was correlated with the APOs and worse neonatal outcomes, including gestational age (P = 0.028), fetal death (P = 0.011), gestational weeks of pre-term delivery (P = 0.002), and birth weight percentile (P = 0.016). Angiogenic markers in pregnancies with APLs were correlated with the incidence of APOs.

Identification of gene biomarkers and immune cell infiltration characteristics in rectal cancer.

BACKGROUND: Compared with colon cancer, the increase of morbidity is more significant for rectal cancer. The current study set out to identify novel and critical biomarkers or features that may be used as promising targets for early diagnosis and treatment monitoring of rectal cancer. METHODS: Microarray datasets of rectal cancer with a minimum sample size of 30 and RNA-sequencing datasets of rectal adenocarcinoma (READ) were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. The method of robust rank aggregation was utilized to integrate differentially expressed genes (DEGs). The protein-protein interaction (PPI) network of the DEGs was structured using the STRING platform, and hub genes were identified using the Cytoscape plugin cytoHubba and an UpSet diagram. R software was employed to perform functional enrichment analysis. Receiver operating characteristic (ROC) curves based on the GEO data and Kaplan-Meier curves based on the TCGA data were drawn to assess the diagnostic and prognostic values of the hub genes. Immune cell infiltration analysis was conducted with CIBERSORT, and the diagnostic value and correlations between prognostic genes and infiltrated immune cells were analyzed by principal component analysis (PCA), ROC curves, and correlation scatter plots. RESULTS: A total of 137 robust DEGs were obtained by integrating datasets in GEO. Twenty-four hub genes, including CHGA, TTR, SAA1, SPP1, MMP1, TGFBI, COL1A1, and PCK1, were identified as a diagnostic gene biomarker group for rectal cancer, and SAA1, SPP1, and SI were identified as potential novel prognostic biomarkers. Functionally, the hub genes were mainly involved in the rectal cancer related interleukin (IL)-17 and proximal tubule bicarbonate reclamation pathways. Twelve sensitive infiltrated immune cells were identified, and were correlated with prognostic genes. CONCLUSIONS: The integrated gene biomarker group combined with immune cell infiltration can effectively indicate rectal cancer.

Identification and validation of xenobiotic metabolism-associated prognostic signature based on five genes to evaluate immune microenvironment in colon cancer.

BACKGROUND: Xenobiotic metabolism plays an important role in the progression of colon cancer; however, little is known about its related biomarkers. This study sought to construct a prognostic model related to xenobiotic metabolism in colon cancer, and further reveal the characteristics of tumor immune microenvironment based on the prognostic model. METHODS: Transcriptome data of 41 normal colon tissues and 473 colon tumor tissues and the clinical features of 452 colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. Data on xenobiotic metabolism genes (XMGs) were obtained from the hallmark xenobiotic metabolism set of the Molecular Signatures Database (MSigDB) and articles. Additionally, data on differential XMGs in colon cancer were acquired for a functional enrichment analysis by R software. An XMG prognostic model was constructed by a Cox regression analysis, and evaluated using Kaplan-Meier survival curves, risk curves, receiver operating characteristic (ROC) curves, and an independent prognostic analysis in a training cohort and validation cohort. Moreover, tumor immune infiltration and negative regulatory immune genes of cancer-immunity cycle (CIC), including immune checkpoints and immune cytokines, were further analyzed between low- and high-risk groups in both the training and validation cohorts. Differences with P value <0.05 were interpreted as statistically significant. RESULTS: A total of 126 differential XMGs were distinguished in the colon cancer data set, which were mainly enriched in the metabolism pathways of drugs and nutrients. There were 5 optimized genes (i.e., CYP2W1, GSTM1, TGFB2, MPP2, and ACOX1) used to construct the prognosis model, which effectively predicted prognosis and had good ROC curves. Between low- and high-risk groups, there were significant differences in abundance for T cells CD4 memory resting and T cells regulatory (Tregs), and expression of PDCD1, LAG3, NOS3, TGFB1, and ICAM1 in the training cohort and validation cohort. CONCLUSIONS: The XMGs in the prognostic model have a good prediction effect on the prognosis of colon cancer patients. The T cells CD4 memory resting, and Tregs, immune checkpoints PDCD1 and LAG3, and CIC negative regulatory immune cytokines NOS3, TGFB1, and ICAM1 are closely associated with xenobiotic metabolism.

Screening of serum protein biomarkers in hemorrhagic cerebral infarction by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology.

BACKGROUND: Serum samples of patients with hemorrhagic cerebral infarction (HCI), cerebral infarction (CI), and healthy controls (HCs) were used to screen statistically different protein peaks as potential biomarkers and to establish a decision tree classification model. METHODS: The serum samples from clinically confirmed patients with HCI and CI from November 2018 to October 2019 were collected, along with those of HCs who visited our hospital during the same period. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with CM10 ProteinChip was used to analyze the differences in serum protein expression profiles of 30 patients with HCI, 32 patients with CI, and 31 HCs in the training group, and a decision tree classification model was established. At the same time, the blind test group (18 patients with HCI, 21 patients with CI, and 17 HCs) was tested by a blind method. RESULTS: Model 1 was successfully established by software analysis with a mass-to-charge ratio of 3,495.2, 8,941.0, and 15,890.4 as a differential protein peak. The sensitivity, specificity, and accuracy of model 1 in distinguishing HCI from HCs were 86.8%, 87.1%, and 86.9%, respectively. After verification of model 1 by the blind test group, the results showed that the sensitivity, specificity, and accuracy were 88.9%, 94.1%, and 91.4%, respectively. The sensitivity, specificity, and accuracy of model 2 with a mass-to-charge ratio of 2,941.3 as a differential protein peak were 86.7%, 75.0%, and 80.6%, respectively. After verification of model 2 by the blind test group, the results showed that the sensitivity, specificity, and accuracy were 83.3%, 90.4%, and 87.2%, respectively. CONCLUSIONS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and CM10 ProteinChip can be used to screen serum protein markers in patients with HCI. Mass-to-charge ratio of 3,495.2, 8,941.0, 15,890.4, and 2,941.3 may be potential protein biomarkers of HCI and used to distinguish HCI patients from HCs and CI.

Delusions of grandeur: Seed count is not a good fitness proxy under individual variation in phenology.

The concept of fitness is central to evolutionary biology, yet it is difficult to define and to measure. In plant biology, fitness is often measured as seed count. However, under an array of circumstances, seed count may be a biased proxy of fitness, for example when individuals vary in allocation to sexual versus asexual reproduction. A more subtle example, but also likely to be important in natural populations, is when interindividual variation in conditions during development results in variation in offspring quality among seed parents. In monocarpic (semelparous) plants, this is expected to result from variation in effective season length experienced among individuals that reach reproductive maturity at different times. Here, we manipulate growing season length to ask whether seed count is an accurate representation of parental fitness in the monocarpic herb Lobelia inflata. Simple seed count suggests a paradoxical fitness advantage under constrained-season length. However, we find that the apparent fitness advantage of a constrained-season length is overridden by low relative per-seed fitness. Furthermore, the fitness deficit in the constrained environment is associated primarily with an accelerating decrease in viability and seedling survival in seeds derived from fruits produced progressively later in the season. In this study, the overall fitness value of a seed under a constrained season is 0.774 of that observed under a long season.

A Chinese medicine formula (Jinqi Jiangtang Tablet): A review on its chemical constituents, quality control, pharmacokinetics studies, pharmacological properties and clinical applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes belongs to the category of "Xiao Ke Zheng" in the field of traditional Chinese medicine (TCM) and has been listed as one of the predominant diseases of TCM. Jinqi Jiangtang Tablet (JQJTT), a Chinese medicine formula composed of three herbs (Coptis chinensis, Astragalus membranaceus and Lonicera japonica), is an effective prescription for diabetes proved by randomized, double-blind, placebo-controlled trials. AIM OF THE REVIEW: To analyze systematic and up-to-date classification information on the study of JQJTT, explain the problems existing in the current research of classics formulas, and further propose the solution, providing a reference for future study. MATERIALS AND METHODS: Literatures on JQJTT were collected from a variety of databases, including PubMed, Google Scholar, Science Direct, Wiley, Web of Science, China National Knowledge Infrastructure, and WanFang Data. Information was also collected from books and reports, such as Chinese Pharmacopoeia, Chinese herbal classic books and reports of re-evaluation on post-marketing drugs conducted by companies. RESULTS: There are some problems for JQJTT: the quality control system is not perfect, the pharmacological functional mechanism is not fully explained, and clinical applications need to be reevaluated. A few of research directions for future research are proposed: (i) the chemical quality evaluation combined with bioassay to evaluate quality; (ii) interaction based on gut microbiota in vivo; (iii) the effects of interaction between components of the polypharmacy on pharmacokinetic studies; (iv) interaction mechanism between drugs and endogenous small molecules and biomacromolecules; (v) evidence-based medicine reconfirmation for clinical evaluation. CONCLUSIONS: The recent research status of JQJTT was summarized and analyzed from the aspects of chemical constituents, quality control, pharmacokinetics studies, pharmacological properties and clinical applications. This review takes JQJTT as an example, points out some typical problems and opinions about the TCM formulas, highlights the importance of the secondary development of classical formula, and lays a foundation for the further research.

Effect of CXCR4 silencing with shRNA on MAPK signaling in ovarian cancer.

Our previous study demonstrated that short hairpin RNA (shRNA) targeting of C-X-C chemokine receptor type 4 (CXCR4) significantly inhibited cell proliferation, metastasis and invasion. On the basis of these results, the aim of the present study was to determine the effects of shRNA-CXCR4 silencing on mitogen-activated protein kinase (MAPK) signaling in human SW626 ovarian cancer cells. Following silencing the CXCR4 gene with shRNA, the mRNA expression of apoptosis signal-regulating kinase 1 (ASK1) was determined using the reverse transcription-quantitative polymerase chain reaction, whereas the protein expression of extracellular-signal-regulated kinase (ERK)1/2 and phosphorylated (p)-c-Jun were determined using immunocytochemistry and western blotting. SW626 cells transfected with shRNA-CXCR4 exhibited significantly increased ASK1 mRNA expression (P<0.05), significantly increased p-c-Jun protein expression (P<0.05), and significantly decreased ERK1/2 protein expression (P<0.05). Silencing the CXCR4 gene with shRNA significantly inhibited cell proliferation, promoted cell apoptosis and may be mediated by the MAPK signaling pathway.

Artesunate promotes G2/M cell cycle arrest in MCF7 breast cancer cells through ATM activation.

BACKGROUND: Recent studies have revealed that artesunate (ART) has clear anti-tumor activity, suggesting that it could be a good candidate chemotherapeutic agent. In this study, we researched the inhibitory effect of ART on MCF7 cells and explored the possible mechanisms. METHODS: MTT assay was used to detect the effect of ART on the proliferation of MCF7 cells. Crystal violet staining was used to observe morphological and quantitative changes. Flow cytometry was used to detect the cell cycle of the drug-acting MCF7 cells. In addition, western blotting was used to detect the drug influence on expression of the ATM, phospho-ATM(S1981), H2AX, γH2AX(S139), CHK2 and phospho-CHK2(T68), cdc25C, and phospho-cdc25C(S216). RESULTS: In the experimental groups, the proliferation of MCF7 cells was inhibited in a dose-dependent manner and the original cell morphology was lost. The number of G2/M phase cells in the experimental groups increased significantly, and the expression of DNA damage response-associated proteins was significantly increased, such as phospho-ATM(S1981), γH2AX(S139), phospho-CHK2(T68), and phospho-cdc25C(S216). CONCLUSIONS: ART can inhibit cell proliferation and promote G2/M arrest in MCF7 cells through ATM activation and the ensuing "ATM-Chk2-Cdc25C" pathway, thus implicating ART as a novel candidate for breast cancer chemotherapy.

Transplantation of mesenchymal stem cells modulated Cx43 and Cx45 expression in rats with myocardial infarction.

At present, little is known about the influence of mesenchymal stem cell (MSC) transplantation on connexin43 (Cx43) and connexin45 (Cx45) remodeling in the ischemic heart. In this study, we investigated the effect of MSC transplantation on Cx43 and Cx45 remodeling in the ischemic heart. Wistar rats were subjected to left anterior descending artery ligation to induce myocardial infarction (MI) and then randomly allocated to receive an intramyocardial injection of PBS (MI group) or 5-azacytidine-induced MSCs (MSCs group). Histological examination and western blotting were performed 4 weeks after cell transplantation. We found that the MSCs exhibited plasticity by differentiating into cardiomyocyte-like cells. Gap junction remodeling after MI was characterized by a decrease in Cx43 expression and an increase in Cx45 expression. MSC transplantation modulated the MI-induced abnormalities by up-regulating Cx43 and down-regulating Cx45 expression. MSCs exhibited plasticity by differentiating into cardiomyocyte-like cells and modulated abnormal Cx43 and Cx45 remodeling following MI.

MicroRNA-208a-3p contributes to connexin40 remolding in human chronic atrial fibrillation.

Previous studies have demonstrated that connexin40 (Cx40) remolding is involved in atrial fibrillation (AF). GJA5 encoding Cx40 is a potential target mRNA of microRNA-208a-3p (miR-208a-3p), as indicated by preliminary bioinformatics analyses. However, the exact effect of miR-208a-3p on Cx40 in human chronic AF has remained elusive. The present study demonstrated the role of miR-208a-3p in human chronic AF and further investigated the effect of miR-208a-3p on Cx40 expression. A total of 19 patients with AF and 18 patients with sinus rhythm (SR) were enrolled. The AC16 cell line was treated with miR-208a-3p inhibitor or mimics. The miR-208a-3p in right atrial appendage (RAA) tissues of patients was measured by in situ hybridization and reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Furthermore, the expression of Cx40 in the RAA of patients and in AC16 cells treated with miR-208a-3p inhibitor or mimics were detected by RT-qPCR and western blot analysis. A luciferase assay was performed to confirm whether Cx40 was directly targeted by miR-208a-3p. The miR-208a-3p levels in patients with AF were significantly increased compared with those in patients with SR. Conversely, the Cx40 protein levels were significantly decreased and lateralization of Cx40 was observed in patients with AF. miR-208a-3p inhibitor led to a significant upregulation of the protein expression of Cx40 in AC16 cells, while miR-208a-3p mimics led to a significant downregulation. However, the luciferase assay demonstrated that GJA5 was not a direct target gene of miR-208a-3p. The findings still suggested that miR-208a-3p may be involved in human chronic AF by mediating atrial Cx40 remolding, and may represent a potential therapeutic target for AF.