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Aprepitant Promotes Caspase-Dependent Apoptotic Cell Death and G2/M Arrest through PI3K/Akt/NF- κ B Axis in Cancer Stem-Like Esophageal Squamous Cell Carcinoma Spheres
The antagonists of the neurokinin-1 receptor (NK1R) are known for their anti-inflammatory, anxiolytic, antiemetic, and anticancer activities. Aprepitant, a nonpeptide NK1R antagonist, is used in nausea and vomiting, the most common side effects of cancer chemotherapy in patients. It has been established that NK1R activation by substance P (SP), which links cancer promotion and progression to a neurokinin-mediated environment, became one mechanism that corresponds to the mitogenesis of tumor cells. Therefore, this study is aimed at explaining and evaluating the anticancer impacts of aprepitant on esophageal squamous cancer cell (ESCC) spheres by using in vitro experiments, such as resazurin, ROS, annexin-V binding, RT-PCR, and Western blot analysis. As a result, we showed that aprepitant had strong antiproliferative and cytotoxic effects on ESCC cell spheres. Also, aprepitant caused significant G2-M cell cycle arrest depending on concentration increase. Further, exposure of cells to this agent resulted in caspase -8/-9-dependent apoptotic pathway activation by modifying the expression of genes involved in apoptosis. Besides, treatment of the cells by aprepitant abrogates of the PI3K/Akt pathway, as shown by reducing the level of Akt, induces apoptotic cell death. In summary, pharmacological inhibition of NK1R with aprepitant seems to have a significant chance of treating ESCC as a single agent or in conjunction with other chemotherapeutic drugs. © 2021 Hossein Javid et al
Update on Statin Treatment in Patients with Neuropsychiatric Disorders
Statins are widely accepted as first-choice agents for the prevention of lipid-related cardiovascular diseases. These drugs have both anti-inflammatory and anti-oxidant properties, which may also make them effective as potential treatment marked by perturbations in these pathways, such as some neuropsychiatric disorders. In this narrative review, we have investigated the effects of statin therapy in individuals suffering from major depressive disorder (MDD), schizophrenia, anxiety, obsessive-compulsive disorder (OCD), bipolar disorder (BD), delirium, and autism spectrum disorders using a broad online search of electronic databases. We also explored the adverse effects of these drugs to obtain insights into the benefits and risks associated with their use in the treatment of these disorders. Lipophilic statins (including simvastatin) because of better brain penetrance may have greater protective effects against MDD and schizophrenia. The significant positive effects of statins in the treatment of anxiety disorders without any serious adverse side effects were shown in numerous studies. In OCD, BD, and delirium, limitations, and contradictions in the available data make it difficult to draw conclusions on any positive effect of statins. The positive effects of simvastatin in autism disorders have been evaluated in only a small number of clinical trials. Although some studies showed positive effect of statins in some neuropsychiatric disorders, further prospective studies are needed to confirm this and define the most effective doses and treatment durations. © 2021 by the authors. Licensee MDPI, Basel, Switzerland
Correlations of back muscle electromyography and gait analysis data as a basis for exercise prescription in patients with lumbar disc herniation
Introduction. The principles and practice of physical rehabilitation in patients with lumbar disc herniation still remain controversial. The objective of the study was to reveal the correlations of gait pattern changes and muscle (spinal and leg muscles) electromyographic recordings in patients with lumbar disc herniation Methods. A motion capture system was used to analyse gait parameters, including angular measurements of hip, knee, and ankle joints, foot support time, pace rate, and speed. A targeted exercise program with exercises in a shortened position of muscles without exceeding the internal range of contraction was applied to level the values of goniometric data and pace parameters obtained by motion capture. Results. The gait restored owing to the reconditioning of spine and leg muscles, confirmed by the recorded changes in electromyographic data, ensures the irreversible nature of gait improvement. The changes in H-reflex expression and muscle baseline electromyography of spine and leg muscles make up a proper tool that provides a system for periodic evaluation of gait recovery. Conclusions. Targeting the weak muscles helped to identify the causes of gait deviations, revealing an expressed positive (negative) correlation between the targeted muscle strengthening and gait restoration. This confirms the importance of selective targeting and strengthening of the muscles to restore the deviated angles and other gait parameters. © Wroclaw University of Health and Sport Science
Opium use and the risk of head and neck squamous cell carcinoma
Scant evidence exists to support the association of opium use with head and neck cancer, limited to the larynx and oral cavity. In a multicenter case-control study�Iran Opium and Cancer study, we recruited 633 cases of head and neck squamous cell carcinoma (HNSCC) (254 lip and oral cavity, 54 pharynx, 327 larynx and 28 other subsites within the head and neck) and 3065 frequency-matched controls from April 2016 to April 2019. Odds ratios (ORs) for opium use and 95 confidence intervals (95 CIs) were obtained using mixed-effects logistic regression because of heterogeneity among centers. The adjusted OR (95 CI) for regular opium use was 3.76 (2.96-4.79) for all HNSCC combined. Strong dose-response effects were observed by frequency or amount of use, and duration of use. Regular opium uses significantly increased the risk of HNSCC of the pharynx, larynx and other subsites within the head and neck with OR (95 CI) of 2.90 (1.40-6.02), 6.55 (4.69-9.13) and 5.95 (2.41-14.71), respectively. The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). Moreover, by the multiplicative interaction scale, the effect of opium use could be varied by cigarette smoking on HNSCC, 8.16 (6.20-10.74). For the first time, the current study showed opium users have an increased risk of several anatomic subsites of HNSCC. © 2020 UIC
Knockdown of TAZ decrease the cancer stem properties of ESCC cell line YM-1 by modulation of Nanog, OCT-4 and SOX2
Cancer stem cells are a rare population in tumors with high metastatic potential and resistance to treatment. Recent strategies in cancer treatment have focused on targeting important signaling pathways that have an important role in maintaining CSC populations. TAZ (transcriptional co-activator with PDZ-binding motif) is a key downstream of the Hippo pathway which plays a fundamental role in the survival of CSCs from different origins, however, no data on the role of TAZ in esophageal cancer are available. Our findings showed that esophageal CSCs enriched from the YM-1 cell line have stemness properties. We found that TAZ was strongly expressed in esophageal CSCs and knockdown of TAZ in esophageal CSCs results in reduced colony formation and cell migration. Moreover, this data indicated that TAZ knockdown reduces the expression of SOX-2, OCT-4, and Nanong in esophageal CSCs. Taken together, the results of the current study suggested that TAZ has a crucial role in the biology of esophageal CSCs. © 202
The effect of group counseling based on self-awareness skill on sexual risk-taking among girl students in Gorgan, Iran: A randomized trial
Background: Sexual puberty in adolescents occurs before their mental and emotional maturity and exposes them to high-risk sexual behaviors. Because sexual risk-taking occurs before adolescents become involved in a sexual relationship, this study was conducted to identify the effect of group counseling based on self-awareness skill on sexual risk-taking among female high school students in Gorgan in order to suggest some preventative measures. Methods: The present parallel study is a randomized field trial conducted on 96 girl students who were studying in grades 10, 11 and 12 of high school with an age range of 14�18 years old. Sampling was done based on a multi-stage process. In the first stage, through the randomized clustering approach, four centers among six health centers were selected. In the second stage, 96 samples were collected through consecutive sampling. Finally, the samples were divided into two intervention and control groups (each one having 48 subjects) through the simple randomized approach. It has to be noted that no blinding was done in the present study. The data were collected using a demographic specifications form and the Iranian Adolescents Risk-Taking Scale (IARS). The consultation sessions based on self-awareness skill were explained to an intervention group through 60-min sessions over 7 weeks. The pretest was conducted for both groups and the posttest was completed 1 week and 1 month after the intervention by the intervention and control groups. Finally, after the loss of follow-up/drop out, a total of 80 subjects remained in the study; 42 subjects in the intervention group and 38 subjects in the control group. Data analyses were done using SPSS v.16 along with the Freidman non-parametric test and the Mann-Whitney and Wilcoxon tests. Results: The results showed that the sexual risk-taking mean scores in the intervention group (10.54 ± 15.64) were reduced by applying 1-week (8.03 ± 12.82) and 1-month (4.91 ± 10.10) follow-ups after the intervention. This reduction was statistically significant (p = 14). However, no statistically significant difference was observed in the control group. Conclusion: Group counseling based on self-awareness skill decreased the sexual risk-taking in girl students of the high school. As prevention is prior to treatment, this method could be proposed as the prevention of high-risk sexual behavior to healthcare centers and educational environments and non-government organizations (NGOs) interacting with adolescents. © 2019 Walter de Gruyter GmbH, Berlin/Boston
Designing hybrid nanofibers based on keratin-poly (vinyl alcohol) and poly (�-caprolactone) for application as wound dressing
In this study, the production of hybrid scaffolds containing keratin/polyvinyl alcohol (Ker/PVA) and poly (�-caproactone) (PCL) for application in skin regeneration has been investigated. In the first step, the extraction of keratin from wool fibers was done, and then electrospinning process was used to fabricate hybrid nanofibers. Ker/PVA blend solution was extruded from one syringe and poly(ε-caprolactone) solution from the other one and hybrid nanofibers were gathered onto a rotary drum collector. The effect of different ratios of Ker/PVA (30:70), (50:50), and (70:30) with PCL were studied on the morphology, hydrophilicity and mechanical features of the scaffolds. The Ker/PVA (50:50)-PCL nanofibers presented an appropriate modulus and mechanical strength similar to the natural skin. These scaffolds possessed high levels of hydrophilicity, which improved cell-scaffold adhesion and increased the growth and proliferation of fibroblast cells. Keratin based nanofibers demonstrated antibacterial characteristic against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. © The Author(s) 2021
Crisis of Breast Cancer in Iran: Focus on Epidemiology and Risk Factors.
Cancer is considered as one of the major health concerning issues and causes of death worldwide which could be mainly due to industrialization of human societies in recent years. Considering the high prevalence of breast cancer among various types of malignancies and its impact on women�s health who play a central role in the families as well as the society, the essence of efficient early diagnosis is felt which ultimately helps us in improving women�s health and reducing the incidence of the disease and the mortality rate, likewise. Educating women and promoting their awareness and recommending various breast cancer screening methods at an early stage, with regards to the guidelines available, play an important role as preventive measures. This article reviews the prevalence and epidemiology of breast cancer, its risk factors, and different levels of prevention. © 2021 Ioannina University School of Medicine. All rights reserved
Tigecycline antibacterial activity, clinical effectiveness, and mechanisms and epidemiology of resistance: narrative review
Tigecycline is unique glycylcycline class of semisynthetic antimicrobial agents developed for the treatment of polymicrobial infections caused by multidrug-resistant Gram-positive and Gram-negative pathogens. Tigecycline evades the main tetracycline resistance genetic mechanisms, such as tetracycline-specific efflux pump acquisition and ribosomal protection, via the addition of a glycyclamide moiety to the 9-position of minocycline. The use of the parenteral form of tigecycline is approved for complicated skin and skin structure infections (excluding diabetes foot infection), complicated intra-abdominal infections, and community-acquired bacterial pneumonia in adults. New evidence also suggests the effectiveness of tigecycline for the treatment of severe Clostridioides difficile infections. Tigecycline showed in vitro susceptibility to Coxiella spp., Rickettsia spp., and multidrug-resistant Neisseria gonnorrhoeae strains which indicate the possible use of tigecycline in the treatment of infections caused by these pathogens. Except for intrinsic, or often reported resistance in some Gram-negatives, tigecycline is effective against a wide range of multidrug-resistant nosocomial pathogens. Herein, we summarize the currently available data on tigecycline pharmacokinetics and pharmacodynamics, its mechanism of action, the epidemiology of tigecycline resistance, and its clinical effectiveness. © 2021, Springer-Verlag GmbH Germany, part of Springer Nature
Dietary quality using four dietary indices and lung cancer risk: the Golestan Cohort Study (GCS)
Purpose: The lung cancer incidence in Iran has increased almost ten times over the past three decades. In addition to the known causes such as smoking and certain occupational exposure, dietary quality has been suggested to play a role in lung cancer. We aim to explore the association between dietary pattern and lung cancer risk among a Middle East population. Methods: Data came from Golestan Cohort Study which included 48,421 participants with 136 lung cancer cases diagnosed during a median follow-up of 12 years. Multivariable Cox proportional hazards regression models were used to calculate the HRs and 95 CI of lung cancer risk by tertile of the four dietary index scores�the Health Eating Index (HEI)-2015, the Alternative Health Eating Index (AHEI)-2010, the Alternative Mediterranean Diet (AMED), and the Dietary Approach to Stop Hypertension (DASH)-Fung. Results: A higher DASH-Fung score was inversely associated with risk of lung cancer after adjusting for potential confounders (tertile three vs. tertile one: HR = 0.59 (0.38�0.93); p for trend = 0.07), and pinteraction with smoking was 0.46. Similar findings were observed among current smokers with the HEI-2015 score (tertile three vs. tertile one: HR = 0.22 (0.08�0.60): p for trend < 0.01), and pinteraction between smoking and the HEI-2015 score was 0.03. Conclusion: In the GCS, consuming a diet more closely aligned with the DASH diet was associated with a reduced risk of lung cancer, which appeared to be independent of smoking status. There was also an inverse link between the HEI-2015 score and lung cancer risk among current smokers. Our finding is particularly important for the Middle East population, as diet may play an important role in cancer prevention and overall health. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature