Cancer-associated immune cells and their modulation by melatonin.

OBJECTIVES: Rapidly growing evidence suggests that immune cells play a key role in determining tumor progression. Tumor cells are surrounded by a microenvironment composed of different cell populations including immune cells. The cross talk between tumor cells and the neighboring microenvironment is an important factor to take into account while designing tumor therapies. Despite significant advances in immunotherapy strategies, a relatively small proportion of patients have successfully responded to them. Therefore, the search for safe and efficient drugs, which could be used alongside conventional therapies to boost the immune system against tumors, is an ongoing need. In the present work, the modulatory effects of melatonin on different components of tumor immune microenvironment are reviewed. METHODS: A thorough literature review was performed in PubMed, Scopus, and Web of Science databases. All published papers in English on tumor immune microenvironment and the relevant modulatory effects of melatonin were scrutinized. RESULTS: Melatonin modulates macrophage polarization and prevents M2 induction. Moreover, it prevents the conversion of fibroblasts into cancer-associated fibroblasts (CAFs) and prevents cancer cell stemness. In addition, it can affect the payload composition of tumor-derived exosomes (TEXs) and their secretion levels to favor a more effective anti-tumor immune response. Melatonin is a safe molecule that affects almost all components of the tumor immune microenvironment and prevents them from being negatively affected by the tumor. CONCLUSION: Based on the effects of melatonin on normal cells, tumor cells and microenvironment components, it could be an efficient compound to be used in combination with conventional immune-targeted therapies to increase their efficacy.

Natural products against cisplatin-induced male reproductive toxicity: A comprehensive review.

Cisplatin is widely used as one of the most effective anticancer agents in the treatment of some neoplasms. Reproductive toxicity is the most common outcome associated with cisplatin testicular damage. Alternative natural medicines for treating male testicular disorders and infertility have received extensive attention in research. Natural products, medicinal herbs, and their secondary metabolites have been shown as promising agents in the management of testicular damage induced by chemotherapy drugs. This study aimed to review the research related to natural substances that are promising in mitigation of the cisplatin-induced toxicity in the reproductive system. PubMed and Scopus were searched for studies on various natural products for their potential protective property against reproductive toxicity induced by cisplatin from 2000 to 2020. Eligibility was checked based on selection criteria. Fifty-nine articles were included in this review. Mainly in animal studies, several natural agents have positively affected cisplatin-reproductive-toxicity factors, including reactive oxygen species, inflammatory mediators, DNA damage, and activation of the mitochondrial apoptotic pathway. Most of the natural agents were investigated in short-term duration and high doses of cisplatin exposure, considering their antioxidant activity against oxidative stress. Considering antioxidant properties, various natural products might be effective for the management of cisplatin reproductive toxicity. However, long-term recovery of spermatogenesis and management of low-dose-cisplatin toxicity should be considered as well as the bioavailability of these agents before and after treatment with cisplatin without affecting its anticancer activity.

Toxicity of cuprizone a Cu(2+) chelating agent on isolated mouse brain mitochondria: a justification for demyelination and subsequent behavioral dysfunction.

Multiple Sclerosis (MS) is a complex disease with an unknown etiology and no effective cure, despite decades of extensive research that led to the development of several partially effective treatments. In this study we aimed to investigate brain mitochondrial dysfunction in demyelination induced by cuprizone in mice. Cuprizone was used for induction of demyelination in mice through a diet containing 0.2% w/w cuprizone for 5 weeks. Behavioral tests for proving of MS was performed and then mitochondria from brain of animals were isolated and afterwards parameters of mitochondrial dysfunction examined. Results of mitochondrial dysfunction parameters such as mitochondrial swelling, production ROS, collapse of the membrane potential showed that isolated mitochondria from cuprizone treated mice have been damaged compared to those of untreated control mice. It is likely that demyelination induced mitochondrial damage led to increased mitochondrial ROS formation and progression of oxidative damages in neurons. It is suggested that cuprizone which is a Cu(2+) chelating agent causes impairment of electron transport chain (complex IV) and antioxidant system (SOD) in mitochondria leading to decreased ATP production and increased ROS formation.

Anticholinergic drug use in elderly people: A population- based study in Iran.

BACKGROUND: Elderly people are in need of several drugs due to physiological changes and multiple chronic diseases. Studies have shown that anticholinergic drugs can cause cognitive impairment, reduced physical activity, and increased mortality in elderly population. Paying attention to the anticholinergic medication use in older adults can prevent the occurrence of adverse events and increase the quality of health care. This study was conducted to quantify exposure to anticholinergic medicines in older people in Amirkola. METHODS: This study is a part of the comprehensive cohort project that was being conducted from 2011 on the case patients of 60 years and above that referred to the Amirkola Health Center. A total of 1532 individuals were included, of whom 54.9% were men. The drug information was obtained by observing the patient's prescription and self-report questionnaires and collected data were analyzed by SPSS software. Exposure to anticholinergic medications was measured using the drug burden index-anticholinergic (DBI-Ach) and the anticholinergic drug scale (ADS). RESULTS: Among the 1532 elderly people with an average age of 69.21 years, 29% had DBI>0 and 36.3% had ADS>0. Also, there was a significant correlation between DBI and ADS (R=0.758). In addition, there is a significant relationship between sex variable with DBI and ADS (P=0.0001). So, women in comparison with men had higher values of DBI and ADS. CONCLUSION: The findings of this study indicate that anticholinergic exposure is relatively high especially in older women, which posed special precautions to avoid inappropriate prescribing in the elderly.

Neurobehavioral toxicity of triclosan in mice.

Triclosan (TCS) is a broad-spectrum antibacterial compound which is used in many cosmetic products, medical devices and house hold products. Toxicity attributed to TCS has recently become a focus of research. Recent studies showed that TCS can easily migrate into the human brain and animal tissues and cause adverse changes in various target organs. Our knowledge of the neurotoxicity of TCS is largely based on very limited data. In this regard, adult male NMRI mice were administered TCS (1000, 2000, and 4000 mg/kg) by gavage for 14 consecutive days, whereas the control animals were given corn oil. At the end of the exposure, all mice were evaluated for locomotor activity, motor coordination and anxiety behaviors through the use of an open-field test, rotarod test, and elevated-plus maze (EPM) test, and for muscle strength in a grip strength test. A significant change in locomotor activity and coordination was observed in TCS treated mice. In parallel anxiety-like behaviors and muscle strength were affected by TCS. Haematoxylin-eosin staining also showed significant adverse effects in brain tissue of the TCS exposed mice. Based on these results, we conclude that a 14-day TCS exposure resulting in some behavioral disturbances in mice.

Interaction between Cannabinoid Compounds and Capsazepine in Protection against Acute Pentylenetetrazole-induced Seizure in Mice.

The pharmacological interaction between cannabinoidergic system and vanilloid type 1 (TRPV1) channels has been investigated in various conditions such as pain and anxiety. In some brain structure including hippocampus, CB1 and TRPV1 receptors coexist and their activation produces opposite effect on excitability of neurons. In this study, we tested the hypothesis that TRPV1 channel is involved in the modulation of cannabinoid effects on pentylenetetrazole (PTZ)-induced seizure threshold. In single therapy, male mice (n = 10 per group) received either TRPV1 receptor antagonist capsazepine, CB1 receptor agonist ACEA or anandamide reuptake inhibitor VDM11. In combination therapy, mice were treated with either capsazepine-ACEA or capsazepine-VDM11 combination prior to seizure test. Thirty min later, mice were submitted to infusion of PTZ (1%, 0.25 mL/min) into tail vein and the dose of PTZ to induce clonic convulsion was considered as seizure threshold. Administration of capsazepine and ACEA per se produced protective effects against PTZ-induced seizure, while administration of VDM11 per se did not produce such a protection effect. The anticonvulsant actions of both capsazepine and ACEA were attenuated after co-administration of these compounds. Moreover, the anticonvulsant action of capsazepine was attenuated after co-administration with VDM11. The results suggest an interaction between cannabinoidergic system and TRPV1 receptors in protection against acute PTZ-induced seizure in mice.

Patient's Radiation Exposure in Coronary Angiography and Angioplasty: The Impact of Different Projections.

INTRODUCTION: We aimed to determine angiography projections with lower Dose Area Product (DAP) rate by measuring the mean DAP and fluoroscopy times in coronary angiography (CAG) and percutaneous coronary intervention (PCI) and calculating DAP rate in different projections. METHODS: DAP and fluoroscopy times were measured in all employed projections in real-time in 75 patients who underwent CAG or PCI by a single cardiologist in Madani Cardiovascular University Hospital (45 in CAG group and 30 in PCI group). DAP rate was calculated in both groups and in all projections. The projections with highest and lowest DAP rate were determined. RESULTS: Mean DAP was 436.73±315.85 dGy×cm(2) in CAG group and 643.26±359.58 dGy×cm(2) in PCI group. The projection 40° LAO/0° had the highest DAP rate in CAG group (28.98 dGy×cm(2)/ sec) and it was highest in 20° RAO/30° CR in PCI group (29.83 dGy×cm(2)/sec). The latter projection was also the most employed projection in PCI group. CONCLUSION: The amount of radiation dose in this study is in consistent with the previous reports. Specific angiographic projections expose patients to significantly higher radiation and they should be avoided and replaced by less irradiating projections whenever possible.