Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line.

Nigella sativa is also known for its properties as a traditional herbal healing for many ailments. In this study, the anticancer properties of thyomquinone (TQ), the active ingredient of N. sativa, were studied using ovarian cancer cell line (Caov-3 cells). The anti-proliferative activity of TQ was determined using MTT and the apoptosis was investigated using Flowcytometry and Annexin-V Assays. Multiparameteric cytotoxicity bioassays were used to quantify the changes in cell permeability and mitochondrial membrane potential. Reactive oxygen species (ROS) and apoptosis-involved cell markers were examined to verify cell death mechanism. The MTT-assay showed that TQ induces anti-proliferative activity on Caov-3 with an IC50 of 6.0±0.03 µg/mL, without any cytotoxic activity towards WRL-68 normal hepatocytes. A significant induction of early phase of apoptosis was shown by annexin-V analysis. Treatment of Caov-3 cells with TQ induces decreases in plasma membrane permeability and mitochondrial membrane potential. Visible decrease in the nuclear area was also observed. A significant decrease is observed in Bcl-2 while Bax is down-regulated. TQ-triggered ROS-mediated has found to be associated with Hsp70 dysregulation, an indicator of oxidative injury. We found that TQ induced anti-cancer effect involves intrinsic pathway of apoptosis and cellular oxidative stress. Our results considered collectively indicated that thyomquinone may be a potential agent for ovarian cancer drug development.

Impact of COVID-19 on the use of online mental health services among adults in Riyadh: a cross-sectional study.

OBJECTIVE: Online therapies are licensed online programs designed to aid the use of psychotherapy via the Internet or mobile phone applications by providing effective treatments through digital communication. The number of individuals seeking online therapy has increased during the COVID-19 pandemic. Thus, this study aimed to assess the impact of COVID-19 on the use of online mental health services among Saudi adults in Riyadh. SUBJECTS AND METHODS: The research design was a cross-sectional descriptive study. The data collection tool was an online survey distributed through social media and email. The survey consisted of two parts: a sociodemographic questionnaire and the e-Therapy Attitudes and Process (eTAP). A total of four hundred participants have completed the survey. RESULTS: Most of the respondents had used online therapy for the first time during the COVID-19 pandemic, and most of the users had a relatively positive experience with online interventions for mental health services. CONCLUSIONS: The findings showed that COVID-19 had an impact on the use of online therapy, as it caused an increase in the number of users of these services, and most of the users have found online therapy to be helpful.

Effect of high intensity interval training on arterial stiffness in obese hypertensive women: a randomized controlled trial.

OBJECTIVE: High-intensity interval training (HIIT) has been linked to a lower risk of cardiovascular disease and mortality. The study's overarching goal is to evaluate the impact of HIIT on arterial stiffness in obese hypertensive women. PATIENTS AND METHODS: Sixty obese hypertensive women aged between 40-50 years were randomized to group A (Intervention group, n = 30) or group B (Control group, n = 30). Intervention group received HIIT (4 minutes of cycling at 85-90% of peak HR interspersed with 3-minute active recovery time at 60 - 70% of peak HR, three times per week). Arteriovenous stiffness indicators, the augmentation index corrected for heart rate 75 (AIx@75HR), and oscillometric pulse wave velocity (o-PWV), as well as cardio-metabolic parameters, were assessed before and after 12 weeks of treatment. RESULTS: Finding between-group analysis showed a significant difference in AIx@75HR (95% CI: -8.45 to 0.30) , o-PWV ( 95% CI: -1.14 to 0.15), total cholesterol, (95% CI: -31.25 to -1.12), HDL-cholesterol (95% CI: 8.92 to 0.94), LDL-cholesterol (95% CI: -25.35 to -0.06) , and triglycerides (95% CI: -53.58 to -2.51). CONCLUSIONS: High-intensity interval training for 12 weeks has a favorable effect on arterial stiffness in obese hypertensive women and lowers associated cardio-metabolic risk factors.

Functional analysis of mutations in the ATP loop of the Wilson disease copper transporter, ATP7B.

Wilson disease (WND) is an autosomal recessive disorder resulting from mutation of ATP7B. Transport of copper by ATP7B from the trans-Golgi of hepatocytes into apical membrane-trafficked vesicles for excretion in the bile is the major means of copper elimination from the body. Although copper is an essential nutrient, homeostasis must be carefully maintained. If homeostasis is disrupted, copper can accumulate within the liver, kidney, cornea, and/or brain. The range of organs affected leads to clinical heterogeneity and difficulty in WND diagnosis. Sequencing of ATP7B is an important adjunct for diagnosis but has led to the discovery of many novel missense variants. Although prediction programs are available, functional characterization is essential for determining the consequence of novel variants. We have tested 12 missense variants localized to the ATP loop of ATP7B and compared three predictive programs (SIFT, PolyPhen, and Align-GVGD). We found p.L1043P, p.G1000R, p.G1101R, p.I1102T, p.V1239G, and p.D1267V deleterious; p.G1176E and p.G1287S intermediate; p.E1173G temperature sensitive; p.T991M and p.I1148T mild; and p.R1228T functioning as wild type. We found that SIFT most often agreed with functional data (92%), compared with PolyPhen (83%) and Align-GVGD (67%). We conclude that variants found to negatively affect function likely contribute to the WND phenotype in patients.

Percutaneous angioplasty and stenting of subclavian arteries before surgical coronary revascularization in a patient with an aberrant right subclavian artery.

An aberrant right subclavian artery occurs in less than 2% of the population. An associated stenosis of the subclavian artery carries a risk of subclavian-coronary steal in patients who undergo coronary revascularization. We report on the case of a 54-year-old man admitted to our hospital for a coronary artery bypass graft (CABG). Angiographic examination revealed bilateral subclavian-artery stenosis with an aberrant right subclavian artery, anomalous origin of the right vertebral artery from the right common carotid artery, and left vertebral-artery occlusion. The patient underwent successful bilateral subclavian angioplasty and stenting.

Association of ADAM33 gene polymorphism and arginase activity with susceptibility to ventilatory impairment in wood dust-exposed workers.

ADAM33 represents an important gene of susceptibility for lung function impairment. This work aimed to evaluate the association between genetic polymorphism of ADAM33 at four single nucleotide polymorphisms (T1, T2, S1, and Q1) and arginase activity with respiratory functions impairment in wood workers. The study was done to compare ventilatory functions and arginase activity of 82 wood workers and 81 controls. Genotyping was determined by using the polymerase chain restriction fragment length polymorphism method. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow rate (PEF) of the workers were significantly reduced compared with the controls. T1 single nucleotide polymorphism (SNP) was associated with obvious decline in the FEV1, FVC, and PEF in wood workers, while T2 SNP was associated with decline in FEV1 and PEF. A significant increase in arginase activity was found in T2 and S1 SNPs of the exposed workers. Increase in duration of exposure was correlated with the decline in ventilatory functions. This inverse correlation was significant for pulmonary function indices in AA and GG genotypes of T1 and T2, respectively. Moreover, significance was detected for FVC and FEV1 in AA and GA genotypes of S1 and Q1. A positive correlation between arginase activity and duration of exposure was found to be significant in GG genotype of S1 SNP. An association between ADAM33 gene polymorphism and impaired lung functions was detected in wood dust-exposed workers. Arginase activity may play an associated important role in increasing this impairment in wood workers.

Effects of airborne Aspergillus on serum aflatoxin B1 and liver enzymes in workers handling wheat flour.

OBJECTIVE: The present work aimed to investigate the relationship between occupational exposure to airborne molds, serum aflatoxin B1 (AFB1), and liver enzymes of workers handling wheat flour. METHODS: The study included 90 bakers, 100 flour milling workers, and 100 controls with no exposure to flour dust. Workplace aspects such as temperature and relative humidity were measured. Airborne fungi were collected and identified. In all subjects included, the serum levels of AFB1, serum albumin (Alb), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were measured. RESULTS: Air temperature and relative humidity were found to be higher in bakeries than in flour mill sections. Airborne Aspergillus species were isolated in dust particles <8 µm in size. The concentration of Aspergillus flavus and Aspergillus niger were higher in bakeries than in the flour mill sections. They were higher in the grinding section than in other mill sections. The serum AFB1-Alb adduct and ALP levels were significantly higher in bakers compared to milling workers (p < 0.0001, p = 0.05), respectively. The liver enzymes AST and ALT were significantly higher among milling workers and bakers than controls (p < 0.05, p < 0.0001), respectively. The duration of exposure was significantly correlated with serum AFB1 in bakers. Moreover, there was significant correlation between serum AFB1, each of ALT and AST levels in bakers. CONCLUSIONS: chronic occupational exposure to high concentrations of Aspergillus in workplaces may cause elevations in serum levels of AFB1 and liver enzymes in workers exposed to flour dust. Hence, worker protection measures should be consistently adopted and enforced at the workplace.

Helicobacter pylori chronic gastritis updated Sydney grading in relation to endoscopic findings and H. pylori IgG antibody: diagnostic methods.

Helicobacter pylori (Hp) inhabits the stomach of > 50% of humans and has been established as a major etiological factor in the pathogenesis of chronic gastritis, gastric atrophy, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. The aim of this study was to provide unequivocal information about Hp-associated gastritis grading according to the Sydney grading system and to compare the histopathological features with the endoscopic findings and anti-Hp immunoglobulin (Ig)G serological status. This analytical study was conducted on 157 patients with dyspeptic gastritis. All patients underwent esophagogastroduodenoscopy, and antrum and corpus biopsies were taken. Blood samples were obtained from all participants. Different stains were performed on formalin-fixed, paraffin-embedded tissue blocks that included hematoxylin and eosin and Giemsa stain for histopathological interpretation. The endoscopic findings of gastritis were observed in 120 patients and most of them showed hyperemia (80 patients), whereas seven patients had normal appearing gastric mucosa. Histologically variable numbers of mononuclear inflammatory cellular infiltrates were seen in 150 cases (95.5%). Most of them showed Grade 1 gastritis (80 patients), whereas Grades 2 and 3 were found in 43 and 27 biopsies, respectively. Hp colonization was observed in most of the examined biopsies (93.7%). Hp-IgG seropositivity was found in 80.9% of cases and 19.1% were seronegative. The relationship between endoscopic and histological findings was significant (p < 0.001).

The effect of an oral contraceptive on acid-base balance, blood gases and electrolytes.

PIP: The short-term and long-term effects of an oral contraceptive containing .05 mg ethinyl estradiol and 3 mg norethisterone acetate (Gyn-Anovlar) were studied in 136 women. 106 had taken the contraceptive for periods ranging from 6 months to 8 years. The remainder served as controls. Mean weight of the controls was 60.2 kg; it was 67.4 kg for women using the drug for 2 years, 71.1 kg for those using it for 4 years, and 70.9 kg for those using it 6-8 years. Mean weight change was p less than .05 in all 3 groups of long-term users. All the women were slightly anemic before beginning the contraceptive but mean hemoglobin and mean hematocrit showed statistically significant improvement (p less than .05), especially among women who had taken the drug more than 4 years. No appreciable change was seen in the acid-base status or in the blood gases. No significant differences were found in mean serum sodium, potassium, or calcium. However, blood chlorides were just significant at the 5% level in women who had taken the drug 6-8 years (t=2.01).^ieng

In vitro anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A, a chalcone isolated from Boesenbergia rotunda (L.) (fingerroot).

The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as the sample tested at 20 µg/mL. The toxic effect of BA on different cell types, reported as IC50, yielded 20.22 ± 3.15, 10.69 ± 2.64, 20.31 ± 1.34, 94.10 ± 1.19, and 9.324 ± 0.24 µg/mL for A549, PC3, HepG2, HT-29, and WRL-68, respectively. BA displayed considerable antioxidant activity, when the results of ORAC assay were reported as Trolox equivalents. BA (20 µg/mL) and quercetin (5 µg/mL) were equivalent to a Trolox concentration of 11.91 ± 0.23 and 160.32 ± 2.75 µM, respectively. Moreover, the anti-inflammatory activity of BA was significant at 12.5 to 50 µM and without any significant cytotoxicity for the murine macrophage cell line RAW 264.7 at 50 µM. The significant biological activities observed in this study indicated that BA may be one of the agents responsible for the reported biological activities of B. rotunda crude extract.

In vitro anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A, a chalcone isolated from Boesenbergia rotunda (L.) (fingerroot)

The current in vitro study was designed to investigate the anti-inflammatory, cytotoxic and antioxidant activities of boesenbergin A (BA), a chalcone derivative of known structure isolated from Boesenbergia rotunda. Human hepatocellular carcinoma (HepG2), colon adenocarcinoma (HT-29), non-small cell lung cancer (A549), prostate adenocarcinoma (PC3), and normal hepatic cells (WRL-68) were used to evaluate the cytotoxicity of BA using the MTT assay. The antioxidant activity of BA was assessed by the ORAC assay and compared to quercetin as a standard reference antioxidant. ORAC results are reported as the equivalent concentration of Trolox that produces the same level of antioxidant activity as the sample tested at 20 µg/mL. The toxic effect of BA on different cell types, reported as IC50, yielded 20.22 ± 3.15, 10.69 ± 2.64, 20.31 ± 1.34, 94.10 ± 1.19, and 9.324 ± 0.24 µg/mL for A549, PC3, HepG2, HT-29, and WRL-68, respectively. BA displayed considerable antioxidant activity, when the results of ORAC assay were reported as Trolox equivalents. BA (20 µg/mL) and quercetin (5 µg/mL) were equivalent to a Trolox concentration of 11.91 ± 0.23 and 160.32 ± 2.75 µM, respectively. Moreover, the anti-inflammatory activity of BA was significant at 12.5 to 50 µM and without any significant cytotoxicity for the murine macrophage cell line RAW 264.7 at 50 µM. The significant biological activities observed in this study indicated that BA may be one of the agents responsible for the reported biological activities of B. rotunda crude extract.

Enhancing uncertainty tolerance in modelling creep of ligaments.

The difficulty in performing biomechanical tests and the scarcity of biomechanical experimental databases necessitate extending the current knowledge base to allow efficient modelling using limited data sets. This study suggests a framework to reduce uncertainties in biomechanical systems using limited data sets. The study also shows how sparse data and epistemic input can be exploited using fuzzy logic to represent biomechanical relations. An example application to model collagen fibre recruitment in the medial collateral ligaments during time-dependent deformation under cyclic loading (creep) is presented. The study suggests a quality metric that can be employed to observe and enhance uncertainty tolerance in the modelling process.

Biomechanical study using fuzzy systems to quantify collagen fiber recruitment and predict creep of the rabbit medial collateral ligament.

In normal daily activities, ligaments are subjected to repeated loads, and respond to this environment with creep and fatigue. While progressive recruitment of the collagen fibers is responsible for the toe region of the ligament stress-strain curve, recruitment also represents an elegant feature to help ligaments resist creep. The use of artificial intelligence techniques in computational modeling allows a large number of parameters and their interactions to be incorporated beyond the capacity of classical mathematical models. The objective of the work described here is to demonstrate a tool for modeling creep of the rabbit medial collateral ligament that can incorporate the different parameters while quantifying the effect of collagen fiber recruitment during creep. An intelligent algorithm was developed to predict ligament creep. The modeling is performed in two steps: first, the ill-defined fiber recruitment is quantified using the fuzzy logic. Second, this fiber recruitment is incorporated along with creep stress and creep time to model creep using an adaptive neurofuzzy inference system. The model was trained and tested using an experimental database including creep tests and crimp image analysis. The model confirms that quantification of fiber recruitment is important for accurate prediction of ligament creep behavior at physiological loads.

A clonal derivative of mammary epithelial cell line COMMA-D retains stem cell characteristics of unique morphological and functional heterogeneity.

The COMMA-D cell line derived from mammary epithelial cells of midpregnant mice was shown previously to be heterogeneous as determined by phase-contrast microscopy, immunocytochemical staining, DNA content, and oncogenic potential (K.D. Danielson et al. (1984) Proc. Natl. Acad. Sci. USA 81, 3756; D. Medina et al. (1986) J. Natl. Cancer Inst. 76, 1143). Clonal subpopulations of COMMA-D cells have now been isolated by both transfection and selection using a dominant-selectable gene transfer vector and by limiting dilution. Despite their clonal origin, these subpopulations in many cases retained the heterogeneity of the parental COMMA-D line. Of 18 clonal lines assayed, only 5 were able to express beta-casein mRNA. Pooled populations of G418-resistant cells expressed substantially higher levels of beta-casein mRNA than the clonal lines. One of the expressing clonal lines, BNW-7, was characterized further, using immunocytochemical techniques. Approximately 10% of BNW-7 cells expressed casein under the appropriate hormonal and cell-substratum conditions by indirect immunofluorescent staining. Casein immunoperoxidase staining of BNW-7 cells on floating collagen gels revealed that casein-producing cells were localized in small alveolar structures, which were formed in a non-hormone-dependent fashion. The cells in these alveolar structures were cuboidal with basally located nuclei, expressed keratin intermediate filament proteins preferentially, and comprised approximately 18% of the total cells. Cells elsewhere on the surface of the gel displayed a flattened morphology, and expressed vimentin intermediate filament proteins preferentially. A proportion of COMMA-D cells, therefore, appeared to have some of the characteristics of mammary stem cells, and retained the ability to differentiate and form phenotypically heterogeneous cell populations in vitro.