Triple-negative breast cancer accounts for approximately 15-20% of all breast carcinomas and is associated with earlier age of onset, aggressive clinical course, and dismal prognosis. A series of ...1,3-diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1 H-Pyrazole and 1,3-diaryl-5- (3,4,5-trimethoxyphenyl)- 1 H-Pyrazole were evaluated for their anticancer activity against MDA-MB-468, human triple negative breast cancer cell line.
The cytotoxic effects of Pyrazole derivatives on the growth of MDA-MB-468 and AGO1522 were determined using MTT assay. Annexin-V-FITC and PI staining were performed to detect apoptosis and cell cycle distribution using Flow cytometry. The level of Reactive oxygen species (ROS) formation and caspase 3 activity were determined accordingly.
Pyrazole derivatives induced a dose and time-dependent cell toxicity in MDA-MB-468 compared with untreated cells. The results showed that 3-(4-methoxyphenyl)-1-(p-tolyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-Pyrazole (3f) was the most active compound with IC50 values 14.97 μM and 6.45 μM compared with Paclitaxel with IC50 values 49.90 μM and 25.19 μM, after 24 and 48 hours, respectively. Upon treatment with 14.97 μM of 3f after 24 h, the compound induced cell cycle arrest in S phase. 3f provoked apoptosis was accompanied by the elevated level of ROS and increased caspase 3 activity in MDA-MB-468 cells compared with untreated cells.
The overall results of the present study provided evidence for the cytotoxicity of compound 3f against MDA-MB-468 cells in comparison to reference standard, Paclitaxel. It proves that compound 3f can trigger apoptosis through ROS production and caspase 3 activation. These bring supportive data for future investigations that will lead to their use in cancer therapy.
.
Despite newer therapeutic approaches against glioblastoma multiforme (GBM), the severely poor prognosis and treatment resistance are still disadvantages that slow down the patient's recovery process. ...Consistent with the need to develop more effective and optimized therapies to control GBM cell growth, the effects of a new series of tetrahydrobenzo(g)imidazoα-1,2quinolone derivatives on GBM cell growth and the underlying mechanism is investigated in the current study.
U-87MG cell line, glioblastoma multiforme and normal skin fibroblast cell line, AGO1522 were used to study the anticancer effects of 5 derivatives of tetrahydrobenzo(g)imidazoα-1,2quinolone and paclitaxel as a standard drug. The cytotoxic effect on cell growth was assessed using the MTT assay. Annexin V FITC staining and PI staining were applied to detect apoptosis and cell cycle distribution using flow cytometry. The extent of reactive oxygen species (ROS) formation was assessed using the fluorescent probe 7-dichlorofluorescin diacetate and caspase-3 activity using the colorimetric assay kit.
Among the 5 derivatives of tetrahydrobenzo(g)imidazoα-1,2quinolone, the 5c derivative (5-(6-bromo-2-chloroquinolin-3-yl)-9a-hydroxy-8,8-dimethyl-4-Nitro-2,3,5,5a,7,8,9,9a-octahydroimidazoα-1,2quinoline-6(1H)) showed the strongest cytotoxic effect on U-87MG cells in a time and Dose-dependent manner compared to the other derivatives and paclitaxel. The IC50 (11.91 M) of the 5c derivative induced apoptosis accompanied by a significant increase in sub-G1 and super-G2 phases of U-87MG cells. The increased level of cellular ROS and caspase 3 activity after treatment of U-87MG cells with 5c derivative was significant compared to untreated cells.
Our data provide insights into the potent anticancer effects of the 5c-derivative of tetrahydrobenzo(g)imidazoα-1,2quinolone on GBM cells via the caspase-dependent apoptotic pathway, which may merit further attention.
Deep vein thrombosis (DVT) is a common cause of admission to the emergency departments (ED). Doppler ultrasonography of the entire lower limb is the first-line imaging modality. But most EDs do not ...access to full-time radiologists which can lead to delayed diagnosis.
The aim of this study was to evaluate the diagnostic accuracy of three-point compression ultrasonography performed by emergency medicine resident for diagnosis of DVT.
This prospective diagnostic study was carried out at Imam Khomeini Hospital in Sari from March 2018 to November 2018. For all patients with suspected lower extremity DVT, first bedside 3-point compression ultrasound were performed by a third year emergency medicine resident at ED. Then Doppler ultrasonography were performed by a radiologist in the radiology department, as a reference test. Sensitivity, specificity, and positive predictive value of the three-point compression ultrasound performed by emergency medicine resident was calculated.
Of the 72 patients enrolled in our study, 50% of the patients were male, with an average age of 36±19 years. The mean of patient admission time to perform ultrasonography by an emergency medicine resident and radiologist were 14.05±19 and 216±140.1 minutes, respectively. The two groups had a statistically significant difference (P<0.0001). In ultrasonography performed by emergency medicine resident and doper ultrasonography by radiologist, 91.67% and 36.1% of patients were diagnosed with DVT, respectively. Although the ultrasonography performed by emergency medicine resident has a relatively low sensitivity (53.8%), it has a good specificity (85.7%). The positive and negative predictive value was 70 and 75%, respectively.
Although the results of this study indicate insufficient sensitivity of bedside three-point compression ultrasound performed by emergency medicine resident in diagnosis of lower limb DVT, the specificity, positive and negative predictive values and positive likelihood ratio were almost appropriate.
Background and Aim: Growth differentiation factor 15 (GDF15) is a cytokine with anti-inflammatory effects, which the influences of acute and chronic exercise on it are not clearly known. Therefore, ...the aim of the present meta-analysis was to determine the effect of the acute and chronic exercise on circulating GDF15. Methods: To extract original articles published in Farsi and English language journals, a comprehensive search was conducted in PubMed, Web of Science, Scopus, Magiran, Noormags and SID databases until December 22, 2022. Two separate meta-analyses were performed to calculate the effect size of standardized mean difference (SMD) and 95% confidence interval for the acute and chronic effects of exercise on GDF15. Results: A total of 18 studies including 551 subjects were included in the meta-analysis. The results showed that acute exercise activity leads to a significant increase in GDF15 P=0.001, (1.65 to 0.80 CI: 1.23), while chronic exercise activity had no significant effect on GDF15 P=0.24, (0.96 to 0.24-CI: 0.35). Conclusion: Exercise leads to a transient and short-term increase in GDF15, which may contribute to the beneficial metabolic effects of exercise.
The aim of this study is to evaluate the preventive effects of carvedilol on doxorubicin-induced cardiotoxicity.
In this trial, 70 female patients with breast cancer who were candidates to receive ...doxorubicin were enrolled, from which 30 were selected randomly to receive carvedilol 6.25 mg daily during chemotherapy, with the rest receiving placebo as the control group. Both groups were evaluated 1 week before and 1 week after chemotherapy by measuring the left ventricular ejection fraction and strain/strain rate.
Data analysis showed that the case group presented no significant reduction in strain and strain-rate parameters after intervention, while there was a significant reduction in these parameters in the control group (all p values <0.001). Also, the mean differences of strain parameters in the case group were significantly less than in the control group in all evaluated heart walls (basal septal strain, p = 0.005, basal lateral strain, p = 0.001, basal inferior strain, p < 0.001, and basal anterior strain, p < 0.001); the same was true for the strain-rate parameters (the p values for basal septal, basal lateral, basal inferior and basal anterior strain rate were 0.037, 0.037, 0.002 and <0.001, respectively).
This study shows that carvedilol can prevent doxorubicin-induced cardiotoxicity. Whether this prophylaxis should be considered as the preferred method needs further investigation.
Cancer is one of the leading causes of death worldwide, and natural agents have shown some promise in fighting it. Thus, the present study tried to evaluate the healing potential of an equal ...combination of olive and sesame extract (MOS) against the colorectal cancerous lesions that were induced by dimethylhydrazine (DMH) in male rats and also compare the anticarcinogenic potential of the MOS and vitamin E with each other. Therefore, the mixture of equal olive and sesame extract (MOS) was used as the main treatment, alongside vitamin E as a parallel treatment. This study examined the red blood cell (RBC) and white blood cell (WBC) levels, biochemical indices, lactate dehydrogenase (LDH), C-reactive protein (CRP), total protein (TP), creatine kinase (CPK), albumin, and the colon tissue pathology, as well as the level of protein expression of the adenomatous polyposis coli (APC), proliferating cell nuclear antigen (PCNA), carcinoembryonic antigen (CEA), and platelet-derived growth factor (PDGF). Also, the tissue stress markers including total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD) were analyzed. Overall, the results represented a significant reduction in the congestion, mitotic index, inflammation, and cell destruction in the MOS group compared to the DMH group. In terms of the oxidative stress level, a significant increase was observed in the DMH group in comparison with the DMH-MOS group (P<0.05), and the MOS significantly increased TAC level (P<0.05). Furthermore, the DMH+MOS-exposed group exhibited a significantly lower expression of the PCNA, CEA, and PDGF proteins than those of the DMH group. Overall, the MOS showed that it can effectively prevent DMH-induced colon lesions. This mixture, as a strong antioxidant agent, can be clinically applied for preventing and treating colorectal cancer, the effectiveness of which is higher than that of vitamin E.
Full text
Available for:
DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
SARS-CoV-2 as a new global threat has affected global population for one year. Despite the great effort to eradicate this infection, there are still some challenges including different viral ...presentation, temporal immunity in infected individuals and variable data of viral shedding. We studied 255 COVID-19 suspected individuals to assess the viral shedding duration and also the antibody development against SARS-CoV-2 among the cases. Real Time RT-PCR assay was applied to determine the virus presence and SARS-CoV-2 antibodies were evaluated using SARS-CoV-2 IgM and IgG kits. 113 patients were confirmed for COVID-19 infection. The patients were followed until negative PCR achieved. The median viral shedding among studied population was obtained 34.16 (±17.65) days which was not significantly associated with age, sex and underlying diseases. Shiver and body pain were found in prolonged form of the infection and also patients who had gastrointestinal problems experienced longer viral shedding. Moreover, IgG was present in 84% of patients after 150 days. According to this data, the median viral shedding prolongation was 34.16 days which indicates that 14 days isolation might not be enough for population. In addition, IgG profiling indicated that it is persistent in a majority of patients for nearly 6 months which has brought some hopes in vaccine efficacy and application.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective: The systemic risk is the risk of a crisis in the financial sector and its transmission to the economy. Due to the importance of social damage caused by the financial crisis, it is ...necessary to pay attention to the systemic risk and its factors. The purpose of the present study is to investigate the effects of strength of corporate governance mechanisms on systemic risk for financial institutions listed on Tehran Stock Exchange.
Methods: In order to study the subject, after extracting the data of 42 financial institutions listed in the Tehran Stock Exchange during the period 1390-1394, combined data and multivariate regression model are used to test the research hypotheses. The strength of corporate governance is scored by applying TOPSIS technique based on the five criteria that as follows: percentage of institutional ownership, major shareholders and managerial investors, board size and the percentage of non-executive members of the board. The systemic risk is measured bases on the marginal expected shortfall (MES) and the expected shortfall of capital (SRISK).
Results: The effects of strength of corporate governance mechanisms on (MES) and (SRISK) as two indicators of systemic risk is not accepted, because it has a significant level above 5%. Also, the significant level of control variables (Size) and (Capital Ratio) indicates that larger financial institutions (with higher assets) and higher capital ratio, have greater role in the systemic risk.
Conclusion: The research findings show that the strength of corporate governance mechanisms does not have significant effect on the financial institutions' systemic risk.
Treatment of leishmaniasis by conventional synthetic compounds has faced a serious challenge worldwide. This study was performed to evaluate the effect and modes of action of aromatic Turmerone on ...the Leishmania major intra-macrophage amastigotes, the causative agent of zoonotic cutaneous leishmaniasis in the Old World. In the findings, the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Turmerone plus meglumine antimoniate (Glucantime®; MA) than MA alone, especially at 50 µg/mL. In addition, Turmerone demonstrated no cytotoxicity as the selectivity index (SI) was 21.1; while it induced significant apoptosis in a dose-dependent manner on L. major promastigotes. In silico molecular docking analyses indicated an affinity of Turmerone to IL-12, with the MolDock score of − 96.8 kcal/mol; which may explain the increased levels of Th1 cytokines and decreased level of IL-10. The main mechanism of action is more likely associated with stimulating a powerful antioxidant and promoting the immunomodulatory roles in the killing of the target organism.
Display omitted
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Green-synthesized nanobiomaterials, for instance silver nanoparticles (AgNPs), can be engineered as smart nanomedicine platforms for diagnostic and therapeutic purposes of various disorders, ...including infectious diseases and cancer. In the present study, the Pimpinella anisum aqueous seed extract was applied for the phytofabrication of AgNPs. Several analytical instrumental techniques were applied for the characterization of AgNPs involving UV-visible spectroscopy, field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS), Fourier transmission infrared (FT-IR) spectroscopy, and X-ray diffraction (XRD). The nanoparticles (NPs) were formed with spherical morphology with an average hydrodynamic diameter of 65.40 nm. Furthermore, the biogenic AgNPs exhibited significant antibacterial activity against the reference strain of Escherichia coli (ATCC 25922) and eleven pathogenic E. coli isolates. Interestingly, the minimum inhibitory concentration (MIC) of AgNPs and gentamicin were found to be 4 and 8 μg mL −1 against E. coli (ATCC 25922), respectively. More interestingly, the AgNPs significantly inhibited the biofilm formation against all tested isolates, whereas gentamicin exhibited lower potency for inhibition of bacterial biofilms at the studied concentrations. The interaction of AgNPs with isolated bacterial plasmid and genomic DNA represented the genotoxic effect of these NPs. The AgNPs also exhibited 82.44 ± 1.43% DPPH inhibition, 67.65 ± 4.78% glucose uptake inhibition by Saccharomyces cerevisiae , and 71.43 ± 4.92% alpha-amylase inhibition at a concentration of 1 mg mL −1 . Moreover, the AgNPs showed significant anticoagulant activity at 1 mg mL −1 compared to saline ( P < 0.05).
PDF
