Euphorbia hirta commonly known as Tawa-Tawa is a plant used in folklore medicine in the Philippines for the treatment of dengue. Though, E. hirta has been extensively investigated for numerous bioactivities, limited studies have been conducted on the antidengue activity. Thus, the present study provides a comprehensive review of studies conducted on the antidengue activity of E. hirta. A systematic literature survey was carried out in scientific databases, PubMed®, Scopus, and Google Scholar, for research carried on the antidengue activity of E. hirta. The literature search identified a total of 867 articles: databases PubMed = 6, Scopus SciVerse® = 423, and Google Scholar = 437; one additional article was identified by searching reference lists. Eight full papers were entitled to the review; out of those, two studies focused on ethnobotanical surveys, three on animal experiments, one on human trial, and two on in vitro antiviral activities, and one was computational study. The available evidence conclusively demonstrates the potential of E. hirta against dengue as it holds significant antiviral and platelet increasing activities. However, the number of studies conducted to validate its antidengue activity was found to be inadequate. Hence, well-controlled clinical trials and contemporary pharmacological approaches including activity guided fractionation and elucidation of the mode of action are encouraged to establish the use of E. hirta for dengue.

The objective of this research was to investigate serotype diversity pattern of dengue hemorrhagic fever virus by using real-time-polymerase chain reaction (RT-PCR) method. It was an explorative laboratory research in endemic dengue fever area in South Sulawesi Province, Indonesia, that is, Makassar municipality and Maros and Gowa region. Serological examination was carried out using real-time-polymerase chain reaction (RT-PCR) method to determine the serotype of dengue virus. The data showed that, of 30 patients, 20 patients (66.67%) were from Makassar municipality: 10 patients (33.33%) from Gowa region and 10 patients (33.33%) from Maros region. The serotypes found were DENV-2 and DENV-4 and no DENV-1 and DENV-3 serotypes were found. Makassar municipality and Gowa region have higher infection with serotype DENV-2, that is, 40% of cases compared with Maros, which is 20.0%. Statistical test results showed no significant differences between the three endemic areas. Maros region has the highest infection with serotype DENV-4, that is, 40% of cases compared with Makassar municipality (5.0%) and Gowa region (0%). Statistical test results showed significant differences between the three endemic areas. This result revealed that serotypes obtained in endemic areas of dengue fever in South Sulawesi are DENV-2 and DENV-4 and not serotypes DENV-1 and DENV-3. Makassar municipality has DENV-2 and DENV-4 serotype, infection dominated by DENV-2, while Maros region also has DENV-2 and DENV-4, but DENV-4 is the dominant serotype. Gowa municipality only has DENV-2 serotype infection.

Berberine hydrochloride is an isoquinoline type alkaloid extracted from Berberidaceae, Rutaceae, and other plants. Previous reports have shown that berberine hydrochloride has anti-inflammatory properties. However, the underlying molecular mechanisms remain unclear. In this study, a lipopolysaccharide- (LPS-) induced murine model of mastitis was established to explore the anti-inflammatory action of berberine hydrochloride. Sixty mice that had been lactating for 5-7 days were randomly divided into six groups, including control, LPS, three berberine hydrochloride treatment groups (5, 10, and 20 mg/kg), and a dexamethasone (DEX) (5 mg/kg) group. Berberine hydrochloride was administered intraperitoneally 1 h before and 12 h after LPS-induced mastitis, and all mice were sacrificed 24 h after LPS induction. The pathological and histopathological changes of the mammary glands were observed. The concentrations and mRNA expressions of TNF-α, IL-1β, and IL-6 were measured by ELISA and qRT-PCR. The activation of TLR4 and NF-κB signaling pathways was analyzed by Western blot. Results indicated that berberine hydrochloride significantly attenuated neutrophil infiltration and dose-dependently decreased the secretion and mRNA expressions of TNF-α, IL-1β, and IL-6 within a certain range. Furthermore, berberine hydrochloride suppressed LPS-induced TLR4 and NF-κB p65 activation and the phosphorylation of I-κB. Berberine hydrochloride can provide mice robust protection from LPS-induced mastitis, potentially via the TLR4 and NF-κB pathway.

To study the antitumor effect of Xihuang pill (XHP) on the number of Treg cells in the tumor microenvironment of 4T1 breast tumor-bearing mice by PI3K/AKT/AP-1 pathway, a mouse model was established. Flow cytometry (FCM) and immunohistochemistry (IHC) were used to detect the number of Treg cells in the tumor microenvironment; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect the apoptosis of Treg cells in tumor microenvironment. Quantitative real-time PCR (RT-qPCR) was used to detect the mRNA expression of PI3K, AKT, and AP-1 in Treg cells in tumor microenvironment; immunofluorescence (IF) and Western Blot (WB) were used to detect the protein expression of PI3K, AKT, and AP-1 in Treg cells in tumor microenvironment. Compared with the naive control group, the tumor weight in XHP groups decreased significantly (P < 0.05); FCM and IHC results showed that the number of Treg cells in the tumor microenvironment decreased with the dose of XHP groups (P < 0.05); TUNEL staining showed that the number of Treg cells in tumor microenvironment increased with the dose of XHP groups (P < 0.05); RT-qPCR results showed that the mRNA expression of PI3K and AKT in Treg cells decreased with the dose of XHP groups, while RNA expression of AP-1 increased with the dose of XHP groups (P < 0.05); IF and WB results showed that the protein expression of PI3K and AKT in Treg cells decreased with the dose of XHP groups and the protein expression of AP-1 increased with the dose of XHP groups (P < 0.05). The results suggested that XHP decreased the number of Treg cells via inhibiting PI3K and AKT expression and upregulating AP-1 expression in Treg cells and then promoting the apoptosis of Treg cells. Thus, XHP could improve the immunosuppressive state of tumor microenvironment and reverse the immune escape to inhibit tumor growth.

Objective. Panax ginseng is widely used for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of Panax ginseng. This study aimed to investigate the protective effect of Ginsenoside Re on isoproterenol-induced myocardial injury in rats. Methods. Male Wistar rats were orally given Ginsenoside Re (5, 20 mg/kg) daily for 7 days. Isoproterenol was subcutaneously injected into the rats for two consecutive days at a dosage of 20 mg/kg/day (on 6th and 7th day). Six hours after the last isoproterenol injection, troponin T level and creatine kinase-MB (CK-MB) activity were assayed. Histopathological examination of heart tissues was performed. The levels of malondialdehyde (MDA) and glutathione (GSH) in heart tissues were measured. The nuclear factor erythroid 2-related factor 2 (Nrf2) content in nucleus and the proteins of glutathione cysteine ligase catalytic subunit (GCLC) and glutathione cysteine ligase modulatory subunit (GCLM) in heart tissues were assayed by western blotting method. Results. Treatment with Ginsenoside Re at dose of 5, 20 mg/kg reduced troponin T level and CK-MB activity of rats subjected to isoproterenol. The cardioprotective effect of Ginsenoside Re was further confirmed by histopathological examination which showed that Ginsenoside Re attenuated the necrosis and inflammatory cells infiltration. Ginsenoside Re inhibited the increase of MDA content and the decrease of GSH in heart tissues. Moreover, the Nrf2 content in nucleus and the expressions of GCLC and GCLM were significantly increased in the animals treated with Ginsenoside Re. Conclusion. These findings suggested that Ginsenoside Re possesses the property to attenuate isoproterenol-induced myocardial ischemic injury by regulating the antioxidation function in cardiomyocytes.

The purpose of this study was to investigate whether the ingestion of alkaline-reduced water (ARW) is helpful in improving the symptoms of diarrhea-predominant irritable bowel syndrome (IBS).

Danshen (Salvia miltiorrhiza) is a well-known herb in Traditional Chinese Medicine (TCM) for treating cardiovascular diseases, but the underlying mechanism remains to be fully elucidated. Here, we showed that Danshen and its active ingredient rosmarinic acid exhibited antiplatelet effects through the inhibition of ERp57, a member of protein disulfide isomerase (PDI) with potential roles in platelet aggregation. Danshen extract (DSE) exhibited potent inhibitory effects on the platelet aggregation induced by arachidonic acid- (AA-) induced platelet aggregation and the enzymatic activity of ERp57. Rosmarinic acid was identified by virtual screening and molecular docking as one of the hit compounds for ERp57. In line with this, rosmarinic acid displayed significant inhibitory effect on ERp57 activity and inhibited AA-induced platelet aggregation. Taken together, we demonstrated for the first time that DSE and rosmarinic acid displayed inhibitory effects on the catalytic activity of ERp57, providing evidence of the regulatory role of ERp57 underlying the antiplatelet effects of Danshen.

To investigate the relationship of MUC1, MUC5AC, and the syndrome of spleen and stomach, 109 subjects (34 peptic ulcer (PU), 62 chronic gastritis (CG), and 13 healthy volunteers (CON)) were included. All the subjects included were surveyed with questionnaire to classify them into damp-heat syndrome of spleen and stomach (DHSS), spleen-qi deficiency syndrome (SQD), and CON, examined by gastric endoscope, and biopsied. Rapid urease and methylene blue staining (MBS) were performed on every subject to diagnose for Helicobacter pylori (Hp) infection, and both were defined as Hp-positive. Hematoxylin and eosin (HE) staining was performed on every specimen to explore the histomorphology, inflammatory degree, and inflammatory activity of different groups; then Elivision™ plus kit was used to test the expression of MUC1 and MUC5AC. All the results of digital images were reviewed by two experts blindly. The inflammatory degree with Hp infection was higher than those uninfected or CON, but no significant difference was found between DHSS and SQD. And the expressions of MUC5AC with positive Hp was higher than those with negative Hp or CON regardless of the deficiency and solid syndrome of spleen-stomach but not for MUC1. We speculate that the deficiency and solid syndrome of spleen-stomach is a condition like Tai Ji symbol of dynamic equilibrium, showing the higher expression of MUC5AC but no change of MUC1 in the circumstance of Hp infection.

Reverse genetic strategies, such as virus-induced gene silencing, are powerful techniques to study gene function. Currently, there are few tools to study the spatial dependence of the consequences of gene silencing at the cellular level.

Although the cicada wing has a variety of functions and the nanostructure and surface properties of many species have been extensively investigated, there are no reports investigating diversity of nanostructures and wetting properties within a single species collected at locations with different rainfall conditions. In this study, the hydrophobicity and nanostructure dimensions of the forewing surface of Cryptotympana atrata were measured, based on specimens collected from 12 distributions with varying precipitation averages in China and Japan. The relationships among hydrophobicity, nanostructures, and precipitation were analyzed, and the adaption of hydrophobic nanostructures under different wet environments is discussed. The precipitation of locations in the years the samples of C. atrata were collected only has an effect on the diameter and spacing of wing surface nanostructure, and the multiple years of precipitation may have an influence on the basic diameter and spacing, as well as the height of protrusions. The rougher the wing surface, the stronger the hydrophobicity which was observed from samples taken where the rainfall conditions of the collection years are high. To our knowledge, this is one special example providing evidence of hydrophobic nanostructures found on a biological surface of a single species which shows adaption for specific wet environments.

Recent field data showed that lumbar spine fractures occurred more frequently in late model vehicles than early ones in frontal crashes. However, the lumbar spine designs of the current crash test dummies are not accurate in human anatomy and have not been validated against any human/cadaver impact responses. In addition, the lumbar spines of finite element (FE) human models, including GHBMC and THUMS, have never been validated previously against cadaver tests. Therefore, this study developed a detailed FE lumbar spine model and validated it against cadaveric tests. To investigate the mechanism of lumbar spine injury in frontal crashes, effects of changing the coefficient of friction (COF), impact velocity, cushion thickness and stiffness, and cushion angle on the risk of lumbar spine injuries were analyzed based on a Taguchi array of design of experiments. The results showed that impact velocity is the most important factor in determining the risk of lumbar spine fracture (P = 0.009). After controlling the impact velocity, increases in the cushion thickness can effectively reduce the risk of lumbar spine fracture (P = 0.039).

Prolonged and continuous use of contact lenses for as long as 3 or 4 weeks is common in Mexico due to the low socioeconomic status, poor patient education and self-neglect. Furthermore, wearing contact lenses with low oxygen permeability is common due to their low cost. Thus, patients seek ophthalmologic evaluation due to signs and symptoms of overuse such as red eye, discomfort and tearing. In the present study, the effect of wearing soft contact lenses with a low oxygen permeability on the tear fluid composition after 1 day, 1 week and 1 month without removing them was examined. In this prospective clinical trial, several tear fluid biomarkers were measured in 84 non-adapted contact lens wearers (NACLWs), including the pH, electrolytes, osmolarity, pro-inflammatory molecules [interleukin (IL)-8, IL-1β and interferon (IFN)-γ], total protein (TP) levels and enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and alkaline phosphatase (AP)]. The results indicated that the tear pH was significantly decreased after 1 day and 1 week; however, after 1 month of use, the tear pH level returned to the baseline. Tear electrolyte analysis demonstrated a significant decrease in Na+ at 1 day, 1 week and 1 month and Cl- levels at 1 week and 1 month, and a significant increase in Ca2+ at 1 week and 1 month, K+ at 1 day, 1 week and 1 month, IL-8 at 1 week and 1 month, IL-1β only at 1 week and IFN-γ at 1 week and 1 month. Furthermore, the study observed an elevation of TP, AST, LDH and AP levels, however, there were no significant changes in ALT. In conclusion, the current study revealed that continuous wearing of soft contact lenses with low oxygen permeability increase tear fluid proinflammatory cytokine levels and enzymes reflecting tissue damage.

MicroRNA (miR)-423-5p is a potential target for the diagnosis and therapy of heart failure and cancer. The present study aimed to investigate the expression and role of miR-423-5p in ovarian cancer. miR-423-5p expression in ovarian tissues and plasma collected from ovarian cancer patients and healthy volunteers was analyzed by polymerase chain reaction analysis. In addition, a cell proliferation assay, clonogenic assay and Matrigel-based assay were performed to evaluate the role of miR-423-5p in ovarian cancer cells. The results demonstrated that miR-423-5p was downregulated in ovarian cancer tissues and plasma from ovarian cancer patients, compared with healthy individuals. Of note, miR-423-5p expression in ovarian tissues and plasma was demonstrated to be inversely correlated with ovarian cancer progression. Transfection with miR-423-5p efficiently increased miR-423-5p expression in A2780-s and A2780-cp cells, which had low miR-423-5p expression. Ectopic overexpression of miR-423-5p reduced cell proliferation, colony formation and invasion of ovarian cancer cells. In conclusion, the present study indicated that miR-423-5p may serve as a diagnostic indicator and functions as a tumor suppressor in ovarian cancer.

Overdue treatment and prognostic evaluation lead to low survival rates in patients with lung adenocarcinoma (LUAD). To date, effective biomarkers for prognosis are still required. The aim of the present study was to screen differentially expressed genes (DEGs) as biomarkers for prognostic evaluation of LUAD. DEGs in tumor and normal samples were identified and analyzed for Kyoto Encyclopedia of Genes and Genomes/Gene Ontology functional enrichments. The common genes that are up and downregulated were selected for prognostic analysis using RNAseq data in The Cancer Genome Atlas. Differential expression analysis was performed with 164 samples in GSE10072 and GSE7670 datasets. A total of 484 DEGs that were present in GSE10072 and GSE7670 datasets were screened, including secreted phosphoprotein 1 (SPP1) that was highly expressed and DEGs ficolin 3, advanced glycosylation end-product specific receptor (AGER), transmembrane protein 100 that were lowly expressed in tumor tissues. These four key genes were subsequently verified using an independent dataset, GSE19804. The gene expression model was consistent with GSE10072 and GSE7670 datasets. The dysregulation of highly expressed SPP1 and lowly expressed AGER significantly reduced the median survival time of patients with LUAD. These findings suggest that SPP1 and AGER are risk factors for LUAD, and these two genes may be utilized in the prognostic evaluation of patients with LUAD. Additionally, the key genes and functional enrichments may provide a reference for investigating the molecular expression mechanisms underlying LUAD.

Gastric intestinal metaplasia (IM) induced by bile acid is a precancerous lesion of gastric adenocarcinoma and is associated with the expression of caudal-related homeobox 2 (CDX2). In the present study, the role of farnesoid X receptor (FXR) on the regulation of CDX2 in gastric cells was investigated and the underlying molecular mechanisms were examined. Human gastric cell lines were treated with chenodeoxycholic acid (CDCA) or FXR agonist GW4064. Cells were treated with CDCA in the presence or absence of the FXR antagonist or FXR siRNA transfection. Next, cells were treated with CDCA in the presence or absence of SHP siRNA transfection and FXR, CDX2 and SHP mRNA and protein levels were determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. A chromatin immunoprecipitation assay was performed to examine the relationship between FXR and SHP and the expressions of FXR and CDX2 in gastritis and IM tissues were detected using immunohistochemistry. The results revealed that CDCA was able to induce CDX2 expression, which could be blocked by inhibition or knockdown of FXR. Mechanistically, FXR directly induced the expression of small heterodimer partner (SHP). SHP knockdown significantly decreased CDCA-induced CDX2 expression. ChIP results indicated that FXR could directly bind SHP promoter and promote SHP expression. Finally, immunohistochemistry results demonstrated that the expression levels of CDX2 and FXR in human IM lesions were significantly higher, compared with those in gastritis lesions, and were positively correlated. Collectively, these results revealed that the activation of FXR and sequential direct transcriptional induction of SHP were involved in the expression of CDX2 induced by bile acid in gastric IM lesions.

There are a lot of convincing evidences about the involvement of endothelin pathway proteins in the pathogenesis of atherosclerosis and its fatal complications. In this study, the analysis of a possible association between EDN1 rs5370 and EDNRA rs5335 gene polymorphisms and the risk of large artery stroke (LAS) in a Ukrainian population was conducted. 200 LAS patients and 200 unrelated controls were enrolled in a case-control study. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was used for SNP genotyping. Our results revealed that EDN1 rs5370 polymorphism was associated with LAS development both before and after adjustment for atherosclerosis risk factors (sex, age, body mass index, arterial hypertension, type 2 diabetes mellitus, and smoking). The risk for a LAS incident in rs5370-T allele carriers was 1.6 times higher (CI = 1.066-2.403; P = 0.020) than in subjects with the GG genotype. No link between EDNRA rs5335 and LAS risk in a Ukrainian population was found. The present study indicated that EDN1 rs5370, but not EDNRA rs5335, can be the strong genetic predictor for LAS development in a Ukrainian population.

Luminal B breast cancers (BC) have a more aggressive behavior associated with a higher rate of tumor relapse and worse prognosis compared to luminal A tumors. In this study, we evaluated the involvement of specific epithelial-to-mesenchymal transition- (EMT-) and immune-related pathways in the dissemination of luminal B BC cells. The expression of 42 EMT- and immune-related genes was evaluated in matched sentinel lymph nodes (SLNs) analyzed by the one-step nucleic acid amplification assay (OSNA) and primary tumors of 40 luminal B BC patients by gene array and immunohistochemistry. The results were validated in an independent group of 150 luminal B tumors by immunohistochemistry and immunofluorescence and using gene expression data from 315 luminal B BC patients included in the Metabric dataset. We found that the expression of CXCR4 (p = 3.28E - 02) and CD163 (p = 6.92E - 03) was significantly upregulated in SLNs of recurrent luminal B BC patients. Luminal B primary tumors overexpressing CXCR4 were characterized by an increased expression of vimentin and a high content of CD163-positive macrophages. Bioinformatics analysis confirmed the correlation of CXCR4 with CXCL12, VIM, and CD163 expression and LN involvement. Our results suggest that the upregulation of the CXCR4/CXCL12 pathway and the presence of protumor macrophages in the primary tumor and SLNs sustain the aggressiveness of an important subgroup of luminal B BC.

Metabolic pathway disturbances associated with drug-induced liver injury remain unsatisfactorily characterized. Diagnostic biomarkers for hepatotoxicity have been used to minimize drug-induced liver injury and to increase the clinical safety. A metabolomics strategy using rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS) analyses and multivariate statistics was implemented to identify potential biomarkers for hydrazine-induced hepatotoxicity. The global serum and urine metabolomics of 30 hydrazine-treated rats at 24 or 48 h postdosing and 24 healthy rats were characterized by a metabolomics approach. Multivariate statistical data analyses and receiver operating characteristic (ROC) curves were performed to identify the most significantly altered metabolites. The 16 most significant potential biomarkers were identified to be closely related to hydrazine-induced liver injury. The combination of these biomarkers had an area under the curve (AUC) > 0.85, with 100% specificity and sensitivity, respectively. This high-quality classification group included amino acids and their derivatives, glutathione metabolites, vitamins, fatty acids, intermediates of pyrimidine metabolism, and lipids. Additionally, metabolomics pathway analyses confirmed that phenylalanine, tyrosine, and tryptophan biosynthesis as well as tyrosine metabolism had great interactions with hydrazine-induced liver injury in rats. These discriminating metabolites might be useful in understanding the pathogenesis mechanisms of liver injury and provide good prospects for drug-induced liver injury diagnosis clinically.

Factors that contribute to swelling and trismus are complex, and they are originated by surgical trauma. The aim of the present study was to determine whether clinical and radiographic factors could predict the level of swelling and trismus after lower third molar surgery, through longitudinal approach.

Although gemcitabine is the standard chemotherapy treatment for advanced pancreatic cancer, its benefits are quite limited due to prevalent chemoresistance, and the mechanism underlying gemcitabine chemoresistance remains unclear. Currently, Nrf2 has been deemed as a significant contributor to gemcitabine chemoresistance in pancreatic cancer. Brusatol is a unique inhibitor of the Nrf2 pathway, and in previous studies, we determined that brusatol exhibits the effects of growth inhibition and proapoptosis in pancreatic cancer cells. Due to these data, we speculate that brusatol can reverse gemcitabine-induced Nrf2 activation and propose that it can enhance gemcitabine efficacy in treating pancreatic cancer. In this study, we first proved that brusatol can effectively inhibit the Nrf2 signalling pathway and increase ROS accumulation in pancreatic cancer cells. Next, we demonstrated that brusatol can abrogate gemcitabine-induced Nrf2 activation in pancreatic cancer cells. In addition, we discovered that brusatol potentiates gemcitabine-induced growth inhibition and apoptosis in human pancreatic cancer cells. In nude mice with PANC-1 xenografts, treatment with a combination of brusatol and gemcitabine considerably reduced in vivo tumour growth compared with control treatment or treatment with either brusatol or gemcitabine alone. Immunohistochemical staining also showed that Nrf2 expression levels were reduced in brusatol-treated xenograft tumour tissues. In summary, our results suggest that brusatol is capable of enhancing the antitumour effects of gemcitabine in both pancreatic cancer cells and PANC-1 xenografts via suppressing the Nrf2 pathway.