Assessment of Individual and Mixed Effects of Six Minerals on Thyroid Hormones in Chinese Pregnant Women.

The biosynthesis of thyroid hormones is essential for brain and neurological development. It requires iodine as a key component but is also influenced by other nutrients. Evidence for the combined nutrient status in relation to thyroid hormones during pregnancy is limited. We aimed to investigate the joint associations of iodine, selenium, zinc, calcium, magnesium and iron with maternal thyroid functions in 489 pregnant women from Hangzhou, China. Serum levels of six essential minerals and thyroid function parameters were measured during the first antenatal visit. Linear regression, quantile g-computation and Bayesian kernel machine regression were used to explore the individual and joint relationships between the six minerals and thyroid hormones. Linear regression analyses revealed that calcium was positively associated with free triiodothyronine (FT3). Zinc was positively associated with free thyroxine (FT4). Iodine was negatively associated with thyroid-stimulating hormone (TSH) and positively associated with FT3 and FT4. The quantile g-computation and BKMR models indicated that the joint nutrient concentration was negatively associated with TSH and positively associated with FT3 and FT4. Among the six minerals, iodine contributed most to thyroid function. The findings suggested that maintaining the appropriate concentration of minerals, either as individuals or a mixture, is important for thyroid health during pregnancy.

A deep learning-based drug repurposing screening and validation for anti-SARS-CoV-2 compounds by targeting the cell entry mechanism.

The recent outbreak of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a severe threat to the global public health and economy, however, effective drugs to treat COVID-19 are still lacking. Here, we employ a deep learning-based drug repositioning strategy to systematically screen potential anti-SARS-CoV-2 drug candidates that target the cell entry mechanism of SARS-CoV-2 virus from 2635 FDA-approved drugs and 1062 active ingredients from Traditional Chinese Medicine herbs. In silico molecular docking analysis validates the interactions between the top compounds and host receptors or viral spike proteins. Using a SARS-CoV-2 pseudovirus system, we further identify several drug candidates including Fostamatinib, Linagliptin, Lysergol and Sophoridine that can effectively block the cell entry of SARS-CoV-2 variants into human lung cells even at a nanomolar scale. These efforts not only illuminate the feasibility of applying deep learning-based drug repositioning for antiviral agents by targeting a specified mechanism, but also provide a valuable resource of promising drug candidates or lead compounds to treat COVID-19.

Potato Stu-miR398b-3p Negatively Regulates Cu/Zn-SOD Response to Drought Tolerance.

One of the main impacts of drought stress on plants is an excessive buildup of reactive oxygen species (ROS). A large number of ·OH, highly toxic to cells, will be produced if too much ROS is not quickly cleared. At the heart of antioxidant enzymes is superoxide dismutase (SOD), which is the first antioxidant enzyme to function in the active oxygen scavenging system. To shield cells from oxidative injury, SOD dismutation superoxide anion free radicals generate hydrogen peroxide and molecule oxygen. Cu/Zn SOD is a kind of SOD antioxidant enzyme that is mostly found in higher plants' cytoplasm and chloroplasts. Other studies have demonstrated the significance of the miR398s family of miRNAs in the response of plants to environmental stress. The cleavage location of potato stu-miR398b-3p on Cu/Zn SOD mRNA was verified using RLM-5'RACE. Using the potato variety 'Desiree', the stu-miR398b-3p overexpression mutant was created, and transgenic lines were raised. SOD activity in transgenic lines was discovered to be decreased during drought stress, although other antioxidant enzyme activities were mostly unaltered. Transgenic plants will wilt more quickly than wild-type plants without irrigation. Additionally, this demonstrates that the response of Cu/Zn SOD to drought stress is adversely regulated by potato stu-miR398b-3p.

Insights into the health status of the general population living near an electroplating industry zone: metal elevations and renal impairment.

A cross-sectional study was conducted in 2016 in Zhejiang Province, China, to evaluate the body burdens of metals and metalloids associated with renal dysfunction in populations living near electroplating industries. We recruited 236 subjects and performed physical examinations, determined the blood and urinary levels of arsenic (As), cadmium (Cd), chromium (Cr), manganese (Mn), nickel (Ni), lead (Pb), antimony (Sb), and selenium (Se) by an inductively coupled plasma mass spectrometer (ICP-MS), and measured three renal impairment biomarkers, namely nacetyl-ß-D-glucosaminidase (NAG), retinol-binding protein (RBP), and ß2-microglobulin (BMG). The proportion of abnormal nasal symptoms in the exposure group (10.1%) was much higher than in the control group (0; p < 0.05). The blood and urinary levels of As, Cd, and Se in the exposure group were significantly higher than those in the control group (p < 0.05). The blood levels of Mn and Pb, as well as the urinary levels of Cr and Ni, were significantly higher in the exposure group than in the control group (p < 0.05). The exposure group demonstrated higher levels of NAG, RBP, and BMG than the control group (0.51 vs. 0.14 mg/g creatinine, 12.79 vs. 9.26 IU/g creatinine, and 1.39 vs. 0.78 mg/g creatinine, respectively; p < 0.05). Urinary BMG was positively correlated with urinary Cd levels (r = 0.223, p < 0.05), while urinary RBP was correlated with blood Cd levels (r = 0.151, p < 0.05) and urinary Cd, Cr, Ni, and Se levels (r = 0.220, 0.303, 0.162, and 0.306, respectively; p < 0.05). In conclusion, our study indicated that a population living in the vicinity of electroplating industries had high body burdens of certain metals and metalloids associated with non-negligible renal dysfunction.

Ribosomal DNA copy number associated with blood metal levels in school-age children: A follow-up study on a municipal waste incinerator in Zhejiang, China.

To evaluate the body burdens of heavy metals and explore the impact of environmental metal exposure on ribosomal DNA (rDNA) or mitochondrial DNA (mtDNA) copy number (CN) variation in school-age children living near a municipal waste incinerator (MWI), we conducted a follow-up study in 2019. A total of 146 sixth-grade children from a primary school located 1.2 km away from the MWI were recruited for our study. Metals, including vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), cadmium (Cd), stannum (Sn), stibium (Sb), thallium (Tl), and lead (Pb), were determined by an inductively coupled plasma mass spectrometer method. Real-time qPCR was used to measure the rDNA and mtDNA CN. The blood metal levels followed this order: Zn > Cu > Se > Pb > Mn > Sb > As > Ni > Cd > Co > Cr > Sn > V > Tl. Blood Cr level was significantly correlated with 18 S, 2.5 S, and 45 S CN (ß = -0.25, -0.22, -0.26, p < 0.05); Ni was correlated with 5 S (ß = -0.36, p < 0.01); Cu was correlated with 28 S, 18 S, and 5.8 S (ß = -0.24, -0.24, -0.23, p < 0.05); while Zn was correlated with 18 S, 5.8 S, and 45 S (ß = -0.28, -0.32, -0.26, p < 0.05). In conclusion, school-age children living near the MWI had lower blood metal levels compared to children recruited in 2013, while rDNA CN loss was found to be correlated to several heavy metals in these children.

The Efficacy and Safety of HoLEP for Benign Prostatic Hyperplasia With Large Volume: A Systematic Review and Meta-Analysis.

This meta-analysis was to evaluate the efficacy and safety of holmium laser enucleation of prostate (HoLEP) in the treatment of benign prostatic hyperplasia (BPH) with large volume. PubMed, Embase, and Cochrane Library databases (until March 2022) were used to search related randomized controlled trials. A total of 11 studies including 1,258 patients were involved. HoLEP could significantly decrease the length of hospital stay and accelerate recovery. In subanalysis, HoLEP had better perioperative outcomes than bipolar transurethral resection of the prostate (B-TURP) and bipolar transurethral enucleation of the prostate (BPEP). The improvement in operative time and enucleation time was better in thulium laser enucleation of the prostate (ThuLEP) than HoLEP. In the follow-up period, the HoLEP decreased post-void residual urine (PVR) in short-term intervals and improved patients' maximum flow rate (Qmax) and prostate-specific antigen (PSA) in mid- and long-term intervals. In subanalysis, HoLEP presented significant improvements in Qmax, PSA, and quality of life (QoL) than B-TURP, and HoLEP could also improve Qmax than ThuLEP after 6 months of surgery. The HoLEP reduced the risk of postoperative bleeding compared with other surgeries in safety. In our study, we confirmed the advantages of HoLEP in treating BPH when the prostate size was larger than 80 mL, which indicated that HoLEP could be the best choice for treatment of large volume of prostate.

Characterizing thalamic and basal ganglia nuclei in medically intractable focal epilepsy by MR fingerprinting.

OBJECTIVES: Magnetic resonance fingerprinting (MRF) is a novel, quantitative, and noninvasive technique to measure brain tissue properties. We aim to use MRF for characterizing normal-appearing thalamic and basal ganglia nuclei in the epileptic brain. METHODS: A three-dimensional (3D) MRF protocol (1 mm3 isotropic resolution) was acquired from 48 patients with unilateral medically intractable focal epilepsy and 39 healthy controls (HCs). Whole-brain T1 and T2 maps (containing T1 and T2 relaxation times) were reconstructed for each subject. Ten subcortical nuclei in the thalamus and basal ganglia were segmented as regions of interest (ROIs), within which the mean T1 and T2 values, as well as their coefficient of variation (CV) were compared between the patients and HCs at the group level. Subgroup and correlation analyses were performed to examine the relationship between significant MRF measures and various clinical characteristics. Using significantly abnormal MRF measures from the group-level analyses, support vector machine (SVM) and logistic regression machine learning models were built and tested with 5-fold and 10-fold cross-validations, to separate patients from HCs, and to separate patients with left-sided and right-sided epilepsy, at the individual level. RESULTS: MRF revealed increased T1 mean value in the ipsilateral thalamus and nucleus accumbens; increased T1 CV in the bilateral thalamus, bilateral pallidum, and ipsilateral caudate; and increased T2 CV in the ipsilateral thalamus in patients compared to HCs (p < .05, false discovery rate [FDR] corrected). The SVM classifier produced 78.2% average accuracy to separate individual patients from HCs, with an area under the curve (AUC) of 0.83. The logistic regression classifier produced 67.4% average accuracy to separate patients with left-sided and right-sided epilepsy, with an AUC of 0.72. SIGNIFICANCE: MRF revealed bilateral tissue-property changes in the normal-appearing thalamus and basal ganglia, with ipsilateral predominance and thalamic preference, suggesting subcortical involvement/impairment in patients with medically intractable focal epilepsy. The individual-level performance of the MRF-based machine-learning models suggests potential opportunities for predicting lateralization.

The mechanism of AMPA receptor subunit GluR1 in electroacupuncture treatment of acute spinal cord injury in rats.

Glutamate excitotoxicity plays a role in spinal cord injury (SCI). This study aimed to explore whether electroacupuncture (EA) improved the functional recovery of spinal cord anterior horn neurons of rats with acute SCI by regulating the GluR1 AMPA subunit in the SCI area. Eighty Sprague-Dawley rats were randomly divided into 5 groups: sham operation, model, AMPA antagonist (DNQX), EA and DNQX + EA group (n = 16/group). The models were obtained by using the modified Allen's impact method. DNQX was given by intrathecal injection 0.5 h after modeling. EA was performed at the "Dazhui" and "Mingmen" acupoints for 30 min at 0.5, 12, and 24 h. The BBB scores were evaluated before modeling and at 6, 24, and 48 h after modeling. Histopathological changes were evaluated. GluR1 expression was evaluated through immunofluorescence and western blot. Compared to the sham group, the BBB scores at 6, 24, and 48 h in the model group were all lower. The BBB scores and histopathological changes in the EA, DNQX and DNQX + EA group were between that of the sham and model group. GluR1 expression in the model group was higher than the sham group. Compared with the model group, the expression of GluR1 protein in the EA, DNQX, and DNQX + EA group was decreased, but similar among the three treatment groups, supporting the histopathological observations. In conclusion, these findings indicated that EA treatment might inhibit GluR1 expression, thus contributing to prevention of secondary nerve injury after primary acute SCI.

Monoterpene indole alkaloids from Melodinus cochinchinensis (Lour.) Merr.

Melodicochinines A - D (1-4), four new monoterpene indole alkaloids (MIAs), along with 21 known ones, were isolated from the stems and twigs of Melodinus cochinchinensis. Their structures were elucidated on the basis of extensive spectroscopic analysis. A ubiquitin-rhodamine 110 assay showed that 11-methyloxytabersonine had potential inhibitory effect against ubiquitin-specific protease 7 (USP7).

Active constituent of Polygala tenuifolia attenuates cognitive deficits by rescuing hippocampal neurogenesis in APP/PS1 transgenic mice.

BACKGROUND: Alzheimer's disease (AD) is the most common dementia worldwide, and there is still no satisfactory drug or therapeutic strategy. Polygala tenuifolia is a traditional Chinese medicine with multiple neuroprotective effects. In present study, we investigated the effects of three active constituents [3,6'-disinapoyl sucrose (DISS), onjisaponin B (OB) and tenuifolin (TEN)] of Polygala tenuifolia (PT) on the proliferation and differentiation of neural stem cells (NSCs) to identify the potential active constituent of PT promoting hippocampal neurogenesis. METHODS: NSCs were isolated from hippocampi of newborn C57BL/6 mice, and transfected with mutant amyloid precursor protein (APP) gene to establish an AD cell model (APP-NSCs). 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were performed, and the proliferation and differentiation of NSCs were assessed by neurosphere formation assay, 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and immunofluorescence (IF) staining analysis. APP/PS1 transgenic mice were administrated with the potential active constituent DISS for 4 weeks. Morris water maze (MWM), Nissl staining assay and IF staining assays were carried out to evaluate the cognitive function, neural damages and hippocampal neurogenesis, respectively. RESULTS: DISS exerted the optimal ability to strengthen APP-NSCs proliferation and neuronal differentiation, followed by OB and TEN. Furthermore, DISS treatment for 4 weeks strikingly rescued the cognitive deficits, neuronal injures, and neurogenesis disorder in adult APP/PS1 transgenic mice. CONCLUSIONS: Our findings demonstrated that DISS is the constituent of PT that triggers the most potent increase of hippocampal neurogenesis in our mouse model of AD.

SAG-DTA: Prediction of Drug-Target Affinity Using Self-Attention Graph Network.

The prediction of drug-target affinity (DTA) is a crucial step for drug screening and discovery. In this study, a new graph-based prediction model named SAG-DTA (self-attention graph drug-target affinity) was implemented. Unlike previous graph-based methods, the proposed model utilized self-attention mechanisms on the drug molecular graph to obtain effective representations of drugs for DTA prediction. Features of each atom node in the molecular graph were weighted using an attention score before being aggregated as molecule representation. Various self-attention scoring methods were compared in this study. In addition, two pooing architectures, namely, global and hierarchical architectures, were presented and evaluated on benchmark datasets. Results of comparative experiments on both regression and binary classification tasks showed that SAG-DTA was superior to previous sequence-based or other graph-based methods and exhibited good generalization ability.

Summarizing the Effective Herbs for the Treatment of Hypertensive Nephropathy by Complex Network and Machine Learning.

Hypertensive nephropathy is a common complication of hypertension. Traditional Chinese medicine has been used in the clinical treatment of hypertensive nephropathy for a long time, but the commonly used prescriptions have not been summarized, and the basic therapeutic approaches have not been discussed. Based on data from 3 years of electronic medical records of traditional Chinese medicine used at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, a complex network and machine learning algorithm was used to explore the prescribed herbs of traditional Chinese medicine in the treatment of hypertensive nephropathy (HN). In this study, complex network algorithms were used to describe traditional Chinese medicine prescriptions for HN treatment. The Apriori algorithm was used to analyze the compatibility of these treatments with modern medicine. Data on the targets and regulatory genes related to hypertensive nephropathy and the herbs that affect their expression were obtained from public databases, and then, the signaling pathways enriched with these genes were identified on the basis of their participation in biological processes. A clustering algorithm was used to analyze the therapeutic pathways at multiple levels. A total of 1499 prescriptions of traditional Chinese medicines used for the treatment of hypertensive renal damage were identified. Fourteen herbs used to treat hypertensive nephropathy act through different biological pathways: huangqi, danshen, dangshen, fuling, baizhu, danggui, chenpi, banxia, gancao, qumai, cheqianzi, ezhu, qianshi, and niuxi. We found the formulae of these herbs and observed that they could downregulate the expression of inflammatory cytokines such as TNF, IL1B, and IL6 and the NF-κB and MAPK signaling pathways to reduce the renal inflammatory damage caused by excessive activation of RAAS. In addition, these herbs could facilitate the deceleration in the decline of renal function and relieve the symptoms of hypertensive nephropathy. In this study, the traditional Chinese medicine approach for treating hypertensive renal damage is summarized and effective treatment prescriptions were identified and analyzed. Data mining technology provided a feasible method for the collation and extraction of traditional Chinese medicine prescription data and provided an objective and reliable tool for use in determining the TCM treatments of hypertensive nephropathy.

Persulfidation-induced structural change in SnRK2.6 establishes intramolecular interaction between phosphorylation and persulfidation.

Post-translational modifications (PTMs), including phosphorylation and persulfidation, regulate the activity of SNF1-RELATED PROTEIN KINASE2.6 (SnRK2.6). Here, we report how persulfidations and phosphorylations of SnRK2.6 influence each other. The persulfidation of cysteine C131/C137 alters SnRK2.6 structure and brings the serine S175 residue closer to the aspartic acid D140 that acts as ATP-γ-phosphate proton acceptor, thereby improving the transfer efficiency of phosphate groups to S175 to enhance the phosphorylation level of S175. Interestingly, we predicted that S267 and C137 were predicted to lie in close proximity on the protein surface and found that the phosphorylation status of S267 positively regulates the persulfidation level at C137. Analyses of the responses of dephosphorylated and depersulfidated mutants to abscisic acid and the H2S-donor NaHS during stomatal closure, water loss, gas exchange, Ca2+ influx, and drought stress revealed that S175/S267-associated phosphorylation and C131/137-associated persulfidation are essential for SnRK2.6 function in vivo. In light of these findings, we propose a mechanistic model in which certain phosphorylations facilitate persulfidation, thereby changing the structure of SnRK2.6 and increasing its activity.

Identification of Hypertension Subgroups through Topological Analysis of Symptom-Based Patient Similarity.

OBJECTIVE: To obtain the subtypes of the clinical hypertension population based on symptoms and to explore the relationship between hypertension and comorbidities. METHODS: The data set was collected from the Chinese medicine (CM) electronic medical records of 33,458 hypertension inpatients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between July 2014 and May 2017. Then, a hypertension disease comorbidity network (HDCN) was built to investigate the complicated associations between hypertension and their comorbidities. Moreover, a hypertension patient similarity network (HPSN) was constructed with patients' shared symptoms, and 7 main hypertension patient subgroups were identified from HPSN with a community detection method to exhibit the characteristics of clinical phenotypes and molecular mechanisms. In addition, the significant symptoms, diseases, CM syndromes and pathways of each main patient subgroup were obtained by enrichment analysis. RESULTS: The significant symptoms and diseases of these patient subgroups were associated with different damaged target organs of hypertension. Additionally, the specific phenotypic features (symptoms, diseases, and CM syndromes) were consistent with specific molecular features (pathways) in the same patient subgroup. CONCLUSION: The utility and comprehensiveness of disease classification based on community detection of patient networks using shared CM symptom phenotypes showed the importance of hypertension patient subgroups.

The mechanism of AMPA receptor subunit GluR1 in electroacupuncture treatment of acute spinal cord injury in rats.

Glutamate excitotoxicity plays a role in spinal cord injury (SCI). This study aimed to explore whether electroacupuncture (EA) improved the functional recovery of spinal cord anterior horn neurons of rats with acute SCI by regulating the GluR1 AMPA subunit in the SCI area. Eighty Sprague-Dawley rats were randomly divided into 5 groups: sham operation, model, AMPA antagonist (DNQX), EA and DNQX+EA group (n=16/group). The models were obtained by using the modified Allen's impact method. DNQX was given by intrathecal injection 0.5 h after modeling. EA was performed at the "Dazhui" and "Mingmen" acupoints for 30 min at 0.5, 12, and 24 h. The BBB scores were evaluated before modeling and at 6, 24, and 48 h after modeling. Histopathological changes were evaluated. GluR1 expression was evaluated through immunofluorescence and western blot. Compared to the sham group, the BBB scores at 6, 24, and 48 h in the model group were all lower. The BBB scores and histopathological changes in the EA, DNQX and DNQX+EA group were between that of the sham and model group. GluR1 expression in the model group was higher than the sham group. Compared with the model group, the expression of GluR1 protein in the EA, DNQX, and DNQX+EA group was decreased, but similar among the three treatment groups, supporting the histopathological observations. In conclusion, these findings indicated that EA treatment might inhibit GluR1 expression, thus contributing to prevention of secondary nerve injury after primary acute SCI.

p-MEK expression predicts prognosis of patients with adenocarcinoma of esophagogastric junction (AEG) and plays a role in anti-AEG efficacy of Huaier.

The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.

Improved Antithrombogenicity of a Poly(lactic acid) Surface Grafted with Chondroitin Sulfate.

For bioabsorbable vascular scaffolds (BVS), thrombosis is an important clinical problem. Poly(lactic acid) (PLA), as a commonly used manufacturing material of BVS, is always facing thrombosis events in the early stage of BVS implantation, because of a lack of anticoagulant properties. Herein, we introduced carboxyl functional groups on the surface of PLA by photooxidation modification and then used NH2-PEG-NH2 as an intermediate to graft chondroitin sulfate (CS) onto PLA. Fourier transform infrared spectroscopy was used to verify the success of each step of the modification, and X-ray photoelectron spectroscopy was used as a further supplement. The methyl of PLA was oxidized to carboxyl by photooxidation, and the hydrophilicity of PLA surface was improved. CS made endothelial cells better adhere to PLA and resisted the adhesion of platelets. The results showed that the surface of PLA grafted with CS embodies the advantages of promoting endothelial cell adhesion and antiplatelet adhesion, providing a broader application prospect for the application of PLA in BVS.

Genome-wide identification and expression analysis of the GSK gene family in Solanum tuberosum L. under abiotic stress and phytohormone treatments and functional characterization of StSK21 involvement in salt stress.

Plant Glycogen Synthase Kinase 3 (GSK3)/SHAGGY-like kinase (GSK) proteins play important roles in modulating growth, development, and stress responses in several plant species. However, little is known about the members of the potato GSK (StGSK) family. Here, nine StGSK genes were identified and phylogenetically grouped into four clades. Gene duplication analysis revealed that segmental duplication contributed to the expansion of the StGSK family. Gene structure and motif pattern analyses indicated that similar exon/intron and motif organizations were found in StGSKs from the same clade. Conserved motif and kinase activity analyses indicated that the StGSKs encode active protein kinases, and they were shown to be distributed throughout whole cells. Cis-acting regulatory element analysis revealed the presence of many growth-, hormone-, and stress-responsive elements within the promoter regions of the StGSKs, which is consistent with their expression in different organs, and their altered expression in response to hormone and stress treatments. Association network analysis indicated that various proteins, including two confirmed BES1 family transcription factors, potentially interact with StGSKs. Overexpression of StSK21 provides enhanced sensitivity to salt stress in Arabidopsis thaliana plants. Overall, these results reveal that StGSK proteins are active protein kinases with purported functions in regulating growth, development, and stress responses.

Identification of the active ingredients from Guangtongxiao decoction in rat bile based on ultra-performance liquid chromatography/Synapt G2 quadrupole time-of-flight tandem mass spectrometry.

OBJECTIVE: To identify the active ingredients and metabolites in rat bile after Guangtongxiao decoction (GTX) had been administered via the rectal route. METHODS: Drug-containing bile samples were collected via a catheter in the bile duct and could be used 5 h after rectal administration. The main active components and their metabolites in rat bile following rectal administration of GTX were identified and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. RESULTS: Positive and negative modes were applied to analyze and identify the chemical ingredients in the bioactive fractions of GTX. Eight peaks were identified by comparison with the standard compounds: berberine hydrochloride, dehydrocorydaline, tetrahydropalmatine, corydaline, magnoflorine, magnolol, obacunone and albiflorin. Furthermore, 60 metabolites were detected in rat bile based on mass-fragmentation behaviors, and 21 metabolites were reported for the first time. CONCLUSION: Our findings provide a solid basis for further pharmacologic and pharmacokinetic studies of GTX.

Epigallocatechin gallate inhibits dimethylhydrazine-induced colorectal cancer in rats.

BACKGROUND: Epigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC. AIM: To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis. METHODS: DMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG. RESULTS: At week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively. CONCLUSION: EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.