The main purpose of the present research was to study the anticancer effects of methylwogonin in A375 human malignant melanoma cells by evaluating its effects on apoptosis, DNA fragmentation, cancer cell invasion and the mTOR/PI3K/AKT signalling pathway.

In Taiwan, the herbal formula B401 is considered as a health supplement for middle-aged women that can alleviate sweating, anxiety, and sleep disorders. However, the relevant mechanisms are still unclear. In this study, we evaluated the beneficial effects of the herbal formula B401 therapy in the reproductive regulation of ovariectomised mice. Female ICR mice were randomised into four groups: wild-type (WT) mice with sham treatment, wild-type mice treated with the herbal formula B401, bilateral ovariectomised (OVX) mice with sham treatment, and bilateral ovariectomised mice treated with the herbal formula B401. Mice were orally given the herbal formula B401 at a dose of 30 mg/kg bw/day for 2 weeks. At the end of oral treatment with sham or the herbal formula B401, levels of reactive oxygen species (ROS), calcium, phosphorus, and estradiol-17β in the blood; uterine weight and endometrial thickness; and expressions of estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor (PR), vascular endothelial growth factor (VEGF), and superoxide dismutase 2 (SOD2) in the uterine tissue were examined and then compared among the four groups of mice. We found that OVX mice decreased levels of calcium, phosphorus, and estradiol-17β in the blood, decreased uterine weight and endometrial thickness, and decreased expressions of ERα, ERβ, PR, and SOD2 in the uterine tissue but increased blood ROS levels compared with those of WT mice. In addition, OVX mice with the herbal formula B401 therapy can increase levels of calcium, phosphorus, and estradiol-17β in the blood, increase uterine weight and endometrial thickness, and increase expressions of ERα, ERβ, PR, VEGF, and SOD2 in the uterine tissue but decrease blood ROS levels. Our results may provide reasonable explanation for the reproductive regulation of the herbal formula B401 therapy.

Propolis has been widely used as a dietary supplement for its health benefits, including cardiovascular protective effects. The aim of this study was to investigate the cytoprotective effects of Brazilian green propolis (BP) against oxidized low-density lipoprotein (Ox-LDL) induced human umbilical vein endothelial cells (HUVECs) damage. Our results suggested that treatment with BP rescued Ox-LDL-stimulated HUVECs cell viability losses, which might be associated with its inhibitive effects on the cell apoptosis and autophagy. We also noticed that BP restored Ox-LDL-stimulated HUVECs oxidative stress, by induced antioxidant gene expressions, including Heme oxygenase-1 and its upstream mediator, Nrf2, which were mediated by the activation of the phosphorylation of PI3K/Akt/mTOR. Pretreatment with wortmannin, PI3K/AKT inhibitor, abolished BP induced Nrf2 nuclear translocation and HO-1 level. Our results demonstrated that BP protected HUVECs against oxidative damage partly via PI3K/Akt/mTOR-mediated Nrf/HO-1 pathway, which might be applied into preventing Ox-LDL mediated cardiovascular diseases.

This study aimed to investigate the effect of the n-butanol fraction of Terminalia catappa Linn., (FBuTC) on biofilm of Candida albicans and Candida glabrata, as well as changes in color and roughness of polymethyl methacrylate resin (PMMA). The susceptibility of C. albicans and C. glabrata to FBuTC was evaluated by means of the Minimum Inhibitory and Minimum Fungicidal Concentration (MIC and MFC). PMMA acrylic resin discs (N= 108) were fabricated. For the susceptibility tests, biofilms of C. albicans and C. glabrata were developed on discs for 48 h and immersed in phosphate-saline buffer solution (PBS), 1% sodium hypochlorite (SH 1%), or FBuTC at MIC, 5xMIC, or 10xMIC. For the color and roughness change tests, the discs were immersed in distilled water, SH 1%, or FBuTC in the concentrations of 0.25 mg/mL, 2.5 mg/mL, or 25.0 mg/mL. After 28 days of incubation, color change was evaluated by spectrophotometry and roughness, by using a profilometer. The biofilms were investigated by one-way ANOVA and, the color and roughness changes (two-way ANOVA and the Tukey test; α=0.05). For both MIC and MFC the value of 0.25 mg/mL of FBuTC was observed for the planktonic cells of C. albicans and C. glabrata. Exposure to FBuTC at 10xMIC had a significant effect on the biofilm of C. albicans, showing a reduction in cell counts when compared with PBS, (p=0.001). For the biofilm of C. glabrata, the MIC was sufficient for significantly reducing the cell count (p<0.001). No important changes in color and roughness of the acrylic resin were observed, even after 28 days, irrespective of the concentration of FBuTC used (p >0.05). It could be concluded that the immersion of acrylic resin for dental prosthesis in FBuTC was effective in reducing the biofilms of C. albicans and C. glabrata without evidence of change in roughness and color of this substrate.

There is no conclusion about the most important contributor to the upswing of locally advanced colorectal cancer (LACRC) survival.

Recently, alignment-free sequence analysis methods have gained popularity in the field of personal genomics. These methods are based on counting frequencies of short k-mer sequences, thus allowing faster and more robust analysis compared to traditional alignment-based methods.

Introduction  Epidemiological studies focused on prognostic factors associated with laryngeal cancer in the Brazilian population are poorly reported in the literature. Objective  To evaluate the influence of certain risk factors on the survival rates of patients with squamous cell carcinoma (SCC) of the larynx. Methods  This retrospective study was conducted on adult patients who were admitted to the outpatient clinic of the head and neck department in a tertiary care hospital. Evaluation of the influence of risk factors on the survival rates of patients registered in the hospital with laryngeal SCC was performed based on age, sex, initial stage, time of evolution, habits, educational levels and relapse and death. Overall survival (OS), disease-free survival (DFS) and clinical-demographic data were analyzed using the Kaplan-Meier method, Log-rank test and Cox regression. Results  A total of 107 patients with a mean age of 59.8 years (range 19-81) were included in this study. Stages III and IV were associated with decreased DFS ( p  = 0.02) and OS ( p  = 0.02). Smoking patients had a greater period of disease evolution than non-smoking patients ( p  = 0.003). Alcohol consumption in smokers increased the risk of death by 2.8 ( p  = 0.002) compared with non-drinking smokers. Male patients presented lower DFS average when compared with female patients ( p  = 0.04). Conclusion  Our study confirms that male gender, smoking habit combined with alcohol consumption, and advanced stages were strongly associated with poor prognosis.

Introduction  The main modalities of surgical treatment for laryngeal cancer include transoral laser microsurgery (TLM), open preservation surgery, and total laryngectomy (TL). In the elderly, for the presence of comorbidities, the surgical approach more appropriate in many cases remains TL. The use of a stapler for the closure of the esophagus has been introduced to reduce surgical time and postoperative complications such as pharyngocutaneous fistula (PCF). Objective  In the present study, we have evaluated the effectiveness of the use of the horizontal mechanical pharyngoesophageal closure in patients who underwent TL. Methods  This nonrandomized study was performed on consecutive patients with histopathologically proven squamous cell endolaryngeal carcinoma. The TL was performed using a linear stapler to mechanically suture the pharyngotomy using the semiclosed technique. Results  A total of 33 patients underwent TL, and 13 of them underwent neck dissection. A total of 15 patients (45.4%) were ≤70 years old, and 18 were > 70 years old. Analyzing the results in relation to age, patients > 70 years old showed tumors at an earlier stage than those aged ≤70 years old. Furthermore, in this group there was a greater number of patients who had comorbidities ( p  = 0.014). In total, we had 2 (6%) cases of PCF in 6.6% in the group ≤70 years old, and in 5.5% of the group > 70 years old ( p  = 1.00). Conclusions  The use of the stapler for the horizontal closure of the pharyngoesophagectomy in the patients subjected to TL is proven to be useful and safe even when used in elderly patients.

A growing number of studies reveal that oxidative stress is associated with viral infections or cancer development. However, there are few reports assessing the relationships between oxidative stress, viral infection, and carcinogenesis. The present study analyzed the level of total antioxidant status (TAS) as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in patients with oropharyngeal cancer both Epstein-Barr virus (EBV)-positive and EBV-negative in comparison with the control group. The correlations between these parameters and EBV type (wild-type LMP1 (wt-LMP1) or LMP1 with deletion (del-LMP1)), level of antibodies against EBV, the degree of tumor differentiation, and TNM classification were also investigated. Fresh frozen tumor tissue samples collected from 66 patients with oropharyngeal squamous cell carcinoma were tested using nested PCR assay for EBV DNA detection. Spectrophotometric methods were used to measure TAS values as well as SOD and GPx activities in homogenates of tissue, using diagnostic kits produced by Randox Laboratories. Sera from all individuals were investigated using ELISA method to detect the presence of Epstein-Barr virus capsid antigen (EBVCA) IgM and IgG, Epstein-Barr virus nuclear antigen (EBNA) IgG, and early antigen (EA) IgG antibodies. The level of TAS and activities of antioxidant enzymes (GPx and SOD) were significantly decreased in tissues with oropharyngeal cancer, particularly in EBV-positive cases. In 82.3% of patients, wt-LMP1 was detected. Significantly lower TAS, GPx, and SOD values were stated in patients infected with wild-type EBV. The presence of antibodies against early antigen (anti-EA) was detected in over 80% of patients, which suggests reactivation of EBV infection. The correlation between the degree of tumor differentiation and TN classification, especially in EBV-positive patients, was also observed. Determination of these parameters may be useful in evaluating tumor burden in patients with various stages of oropharyngeal cancer and could be an important prognostic factor. Future studies are needed to understand the role of EBV lytic reactivation induced by oxidative stress.

Curcumin is a biologically active polyphenol that exists in Indian spice turmeric. It has been reported that curcumin exerted anti-inflammatory, anti-oxidant and anti-cancer effects in numerous in vitro and in vivo studies. However, it is not well-understood the molecular mechanism of curcumin for the cancer stem cells and telomerase in colorectal cancer. In this study, compound 19, a nitrogen-containing curcumin analog, was used to treat human colorectal cancer cells. Compound 19 showed a greater anti-proliferative activity than curcumin while displayed no significant toxicity toward normal human colon epithelial cells. Compound 19 exerted anti-inflammatory activities by deactivating STAT3 and NF-κB. In cancer stem cell populations, CD44, Oct-4 and ALDHA1 expressions were abolished upon treating with compound 19. Cancer stem cell biomarkers CD51 and CD133 positive populations were reduced and telomerase activities were decreased with the reduced STAT3 binding to hTERT promoters. This means compound 19 dually inhibits canonical and non-canonical functions of telomerase. Furthermore, compound 19 treatments induced cell cycle arrest at G1 phase and apoptosis. Human apoptosis-related array screening revealed that activated caspase 3, catalase, clusterin and cytochrome C led to apoptosis. Taken together, our data suggest that compound 19 can be a novel therapeutic agent for metastatic colorectal cancer by concurrently targeting STAT3 and NF-κB signaling pathways.

Background: Immunotherapies targeting immune checkpoint proteins CTLA-4, PD-1, and PD-L1 have saved lives, but these therapies have only been effective in some patients. Patients positive for expression of immune checkpoint proteins in the tumor microenvironment show better response to immune checkpoint inhibitors. Consequently, knowledge of which genes are consistently expressed in lymphocytes within the tumor microenvironment can convey potentially effective and complementary new immunotherapy targets. Results: We identified 54 genes that have higher co-expression with the pan T-cell marker CD3E than CTLA4 or PDCD1. In a dataset of 26 patients who received anti-PD-1 therapy, we observed that co-expression between CD3E and PDCD1 was higher among responders than non-responders, supporting our correlation-based approach. Conclusions: The genes highlighted in these analyses, which include CD6, TIGIT, CD96, and SLAMF6, warrant further investigation of their therapeutic potential. Methods: We analyzed and ranked genes that were co-expressed with the pan T-cell marker CD3E in 9,601 human tumors, spanning 31 cancer types. To further identify targets that may be complementary to existing PD-1 therapy, we examined and ranked genes with high CD3E co-expression and relatively low PDCD1 co-expression.

Transglutaminase 2 (TG2), a multifunctional protein, is reported in regulating the cancer stem cell (CSC) phenotype in various cancers. Our previous work suggested the link between TG2 and Epithelial-Mesenchymal Transition (EMT) in colorectal cancer (CRC). Here we demonstrate the importance of TG2 in CSC development in human CRC cell lines HCT116 and SW620. CRC spheroid cells showed increased CSC characteristics over their monolayer cells with increased expression of CD44 and over expression of Oct3/4, Sox2 and Nanog. They also showed increased EMT and invasiveness, and enhanced expression of TG2. TG2 inhibition by its selective inhibitor 1-155 reduced both spheroid formation and invasive potential of the spheroid cells. β-catenin, a mediator of stem cell maintenance, was overexpressed in the spheroid cells and could be attenuated by TG2 inhibition. Spheroid cells possessed increased angiogenesis stimulating ability via overexpression of Vascular Endothelial Growth Factor (VEGF). Increased VEGF was present in the culture media from spheroid cells when compared to monolayer cultures which could be reduced by selective inhibition by 1-155. Stemness and malignancy in the colorectal spheroid cells was associated with increased TG2, EMT, β-catenin and VEGF. Here we demonstrate that inhibiting TG2 reduces both stemness and angiogenic stimulating activity in CRC.

The nicotine content of cigarettes plays a key role in the pathogenesis of kidney disease. Harmine is a harmal-derived alkaloid with antioxidant properties. This study was designed to evaluate the effects of harmine against nicotine-induced damage to the kidneys of mice.

Tobacco use in pregnancy is linked with various negative health effects. The aim of this study was to examine the prevalence of maternal tobacco use during pregnancy and sociodemographic and health correlates.

We aimed to explore the association between resting heart rate (RHR) and the severity and complexity of atherosclerosis in coronary artery disease (CAD).

The cell membrane contains a highly interactive glycan surface on a scaffold of proteins and lipids. Sialic acids are negatively charged monosaccharides, and the proteins that bind to sialic acids play an important role in maintaining the integrity and collective functions of this interactive space. Sialic acid binding proteins are not readily identified and have nearly all been discovered empirically. In this research, we developed a proximity labeling method to characterize proteins with oxidation by localized radicals produced in situ. The sites of oxidation were identified and quantified using a standard proteomic workflow. In this method, a clickable probe was synthesized and attached to modified sialic acids on the cell membrane, which functioned as a catalyst for the localized formation of radicals from hydrogen peroxide. The proteins in the sialic acid environment were labeled through amino acid oxidation, and were categorized into three groups including sialylated proteins, non-sialylated proteins with transmembrane domains, and proteins that are associated with the membrane with neither sialylated nor transmembrane domains. The analysis of the last group of proteins showed that they were associated with binding functions including carbohydrate binding, anion binding, and cation binding, thereby revealing the nature of the sialic acid-protein interaction. This new tool identified potential sialic acid-binding proteins in the extracellular space and proteins that were organized around sialylated glycans in cells.

The aim of this study was to evaluate the most commonly used body composition tools in clinical practice, such as anthropometry and electrical bioimpedance, and compare it with deuterium oxide.

Atrial fibrillation leads to increased risk of systemic embolism and stroke. To decrease these adverse events, anticoagulation is routinely prescribed. Nonvitamin K anticoagulants like apixaban and rivaroxaban are becoming popular and being used more frequently nowadays. We here compare the efficacy and safety of apixaban with those of warfarin.

Caesarean section is one of the most commonly performed major surgeries in obstetric practice intended to save the mother and child and in turn reduce maternal and perinatal mortality. The steadily increasing global rate of caesarean section has become one of the most debated topics in maternity care. This study identified the factors that influence women's choice of elective cesarean sections in the Duayaw Nkwanta Hospital.

Osteopenia and osteoporosis are common conditions in the United States. The health consequences of low bone density can be dire, from poor surgical outcomes to increased mortality rates following a fracture.