Cytotoxic effect of iris germanica l. Rhizomes extract on human melanoma cell line

Background: Melanoma is the leading cause of 80 of skin cancer worldwide due to its high proliferation rate, metastatic nature, and limited effective therapies. Given the rapid increase in its incidence compared to other skin cancers, new therapeutic agents are needed to control the disease. Scientists are interested in medicinal plants due to their anticancer properties. The rhizomes of the Iris germanica L., known as �Irsa�, is one of the herbs used in traditional Persian medicine for the treatment of various skin cancers. Objectives: This study aimed at investigating the cytotoxic effects of Iris germanica on A375 melanoma and AGO-1522 normal human fibroblast cell lines for the first time. Methods: The ethanolic extract was prepared by the maceration method. Cell viability and cytotoxic activities were assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric assay, using annexin V/propidium iodide (PI) staining. Results: IC50 values were estimated for the A375 melanoma and the AGO-1522 normal cell lines. We revealed that the IC50 for the A375 melanoma was 0.0438 mg/mL and for the AGO-1522 normal cell line was 0.8494 mg/mL after 48 hours of treatment. Further-more, flow cytometry analysis illustrated that 0.125 mg/mL of the Iris germanica extract could lead to 55.24 apoptosis of the A375 melanoma cell line. The same concentration of the Iris germanica extracts only lead to 8.76 apoptosis in the AGO-1522 cell line. Conclusions: Iris germanica extract has considerable cytotoxic effects on the human melanoma cell line. Further studies are re-quired to demonstrate the therapeutic effects of Iris germanica on melanoma cancer. © 2021, Author(s)

Analysis of glutathione S-transferase (M1, T1 and P1) gene polymorphisms in Iranian prostate cancer subjects

Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of prostate cancer in various populations. The current study was done with Iranian subjects to evaluate the association of the polymorphism of glutathione S-transferase subtypes (T, M and P) and the susceptibility of prostate cancer in Iranian patients as compared to controls. Blood samples were collected from 65 prostate cancer patients and 65 unrelated health individuals as controls from Milad hospital, Tehran, Iran. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the polymorphism of glutathione S-transferase pi (GSTP1) -313 A/G gene, while multiplex PCR method was utilized to detect the glutathione S-transferase teta (GSTT) 1 and glutathione S-transferase mμ (GSTM) 1 null allele. There was no significant association in the -313 G allele (Val) of GSTP1 gene  olymorphism and prostate cancer risk (odds ratio 0.61, 95% confidence intervals (CI) 0.08 - 4.60, p = 0.627). Moreover, no relationship was found between the polymorphism of GSTT1 (odds ratio 0.66, 95% CI 0.27 - 1.62) and GSTM1 (odds ratio 0.54, 95% CI 0.27 - 1.08) genes and higher risk of prostate cancer among Iranian subjects (p > 0.05). This study showed that either GSTP1-313 G polymorphism or GSTT1 and GSTM1 genes cannot be predisposing risk factors for prostate cancer among Iranian subjects.Key words: Glutathione S-transferase, prostate cancer, polymorphism

Nicotinamide phosphoribosyltransferase knockdown leads to lipid accumulation in HepG2 cells through the SIRT1-AMPK pathway

Objective: Nicotinamide phosphoribosyltransferase (NAMPT), which is responsible for biosynthesis of nicotinamide adenine dinucleotide (NAD), has a regulatory role in cellular metabolism and thus, might be implicated in non-alcoholic fatty liver disease (NAFLD). This study aimed to show how NAMPT down-regulation in liver cells influences lipid metabolism and sirtiun 1 (SIRT1), as the main NAD-dependent deacetylase enzyme. Materials and Methods: In this experimental study, HepG2 cells were transfected with NAMPT siRNA and hepatic triglyceride (TG) content and SIRT1 deacetylase activity were measured by colorimetric and fluorometric methods, respectively. Gene expression of fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP- 1c) was evaluated by real-time polymerase chain reaction (PCR). Total protein level and the phosphorylated form of acetyl-CoA carboxylase (ACC) and AMP-activated protein kinase (AMPK) were also investigated by western blotting. Results: Knockdown of NAMPT significantly promoted the accumulation of TG in HepG2 cells, accompanied by a remarkable decline in SIRT1 deacetylase activity. A significant rise in the gene expression of two key lipogenic factors, FAS and SREBP-1c was also observed. These effects were also accompanied by decreased phosphorylation of ACC and AMPK. On the other hand, treatment of transfected cells with either NAD, as the SIRT1 substrate or resveratrol, as the SIRT1 activator reversed the outcomes. Conclusion: These results demonstrated a protective role for NAMPT against NAFLD and its involvement in the regulation of de novo lipogenesis through the SIRT1/AMPK pathway. © 2020 Royan Institute (ACECR). All rights reserved

Medical podcasting in Iran; pilot, implementation and attitude evaluation

Podcasting has become a popular means of transferring knowledge in higher education through making lecture contents available to students at their convenience. Accessing courses on media players provides students with enhanced learning opportunities. Development of teaching methods able to cope with ever-changing nature of medicine is crucial to train the millennium students. Pharmacology education in Tehran University of Medical Sciences has been based on lectures so far; our aim was to implement a pilot study to evaluate the advantages and disadvantages of offering the course contents as podcasts as well as evaluating whether such program can be feasible in our educational program. 46% of students downloaded the podcast according to our download center. 48% favored usage of both internet and DVD-ROM concurrently. Overall 96% of students perceived that podcasting had a positive impact on their learning in pharmacology course. Our results indicate that most of attendants proposed the positive yields of podcasting despite low usage of it, mainly as a pre-class preparing tool.publisher versio

Fatigue-induced changes of impedance and performance in target tracking

Kinematic variability is caused, in part, by force fluctuations. It has been shown empirically and numerically that the effects of force fluctuations on kinematics can be suppressed by increasing joint impedance. Given that force variability increases with muscular fatigue, we hypothesized that joint impedance would increase with fatigue to retain a prescribed accuracy level. To test this hypothesis, subjects tracked a target by elbow flexion and extension both with fatigued and unfatigued elbow flexor and extensor muscles. Joint impedance was estimated from controlled perturbations to the elbow. Contrary to the hypothesis, elbow impedance decreased, whereas performance, expressed as the time-on-target, was unaffected by fatigue. Further analysis of the data revealed that subjects changed their control strategy with increasing fatigue. Although their overall kinematic variability increased, task performance was retained by staying closer to the center of the target when fatigued. In conclusion, the present study reveals a limitation of impedance modulation in the control of movement variability

Force-Field Compensation in a Manual Tracking Task

This study addresses force/movement control in a dynamic “hybrid” task: the master sub-task is continuous manual tracking of a target moving along an eight-shaped Lissajous figure, with the tracking error as the primary performance index; the slave sub-task is compensation of a disturbing curl viscous field, compatibly with the primary performance index. The two sub-tasks are correlated because the lateral force the subject must exert on the eight-shape must be proportional to the longitudinal movement speed in order to perform a good tracking. The results confirm that visuo-manual tracking is characterized by an intermittent control mechanism, in agreement with previous work; the novel finding is that the overall control patterns are not altered by the presence of a large deviating force field, if compared with the undisturbed condition. It is also found that the control of interaction-forces is achieved by a combination of arm stiffness properties and direct force control, as suggested by the systematic lateral deviation of the trajectories from the nominal path and the comparison between perturbed trials and catch trials. The coordination of the two sub-tasks is quickly learnt after the activation of the deviating force field and is achieved by a combination of force and the stiffness components (about 80% vs. 20%), which is a function of the implicit accuracy of the tracking task

Impairment of Gradual Muscle Adjustment during Wrist Circumduction in Parkinson's Disease

Purposeful movements are attained by gradually adjusted activity of opposite muscles, or synergists. This requires a motor system that adequately modulates initiation and inhibition of movement and selectively activates the appropriate muscles. In patients with Parkinson's disease (PD) initiation and inhibition of movements are impaired which may manifest itself in e.g. difficulty to start and stop walking. At single-joint level, impaired movement initiation is further accompanied by insufficient inhibition of antagonist muscle activity. As the motor symptoms in PD primarily result from cerebral dysfunction, quantitative investigation of gradually adjusted muscle activity during execution of purposeful movement is a first step to gain more insight in the link between impaired modulation of initiation and inhibition at the levels of (i) cerebrally coded task performance and (ii) final execution by the musculoskeletal system. To that end, the present study investigated changes in gradual adjustment of muscle synergists using a manipulandum that enabled standardized smooth movement by continuous wrist circumduction. Differences between PD patients (N = 15, off-medication) and healthy subjects (N = 16) concerning the relation between muscle activity and movement performance in these groups were assessed using kinematic and electromyographic (EMG) recordings. The variability in the extent to which a particular muscle was active during wrist circumduction – defined as muscle activity differentiation - was quantified by EMG. We demonstrated that more differentiated muscle activity indeed correlated positively with improved movement performance, i.e. higher movement speed and increased smoothness of movement. Additionally, patients employed a less differentiated muscle activity pattern than healthy subjects. These specific changes during wrist circumduction imply that patients have a decreased ability to gradually adjust muscles causing a decline in movement performance. We propose that less differentiated muscle use in PD patients reflects impaired control of modulated initiation and inhibition due to decreased ability to selectively and jointly activate muscles