[Inhibition of Autophagy by 3-MA Increases Oncolysis Effect of VSV in a Murine Model of Cancer].

Vesicular stomatitis virus has been known as a potent antitumor agent because of its selective replication and lysis of tumor cells and immune-stimulating properties. In response to cellular stress and enhanced metabolism, tumor cells activate autophagy, to provide energy for the cells and preventing tumor destruction. Inhibition of autophagy can increase the therapeutic potential of many antitumor methods. This study aimed to check the efficacy of combined VSV and three-methyl adenine (3-MA) in treating a tumor model in mice. TC-1, a line of C57BL/6 mouse lung cells transformed by HPV-16 E7 and E6 oncoproteins, as well as human Ras, were used for experiments. The viability after treatment with the optimized concentration of 3-MA with or without combination with VSV was assessed by MTT. C57BL/6 male mice were injected with TC-1, and after tumor formation, 3-MA and VSV alone or in combination in two different protocols were injected into tumor mice. Tumor size, tumor-specific CTL response, and apoptosis rate were evaluated. The results showed that 3-MA combined with VSV causes more lethality in tumor cells in vitro. In vivo studies also showed that combined VSV and 3-MA treatment inhibits the progression of TC-1 cancer cells with higher efficiency, especially in daily 3-MA treatment along with four doses of VSV injection with four days' intervals. In addition, the rate of apoptosis and cytotoxic T cells activity in the groups injected with 3-MA and the virus were higher than groups receiving each agent alone. In conclusion, the association of VSV with 3-MA increases its oncolysis activity and subsequently more stimulates the immune system against the tumor. This finding suggests a combinational approach for tumor therapy with therapy. Combining oncolytic VSV with 3-MA as an autophagy inhibitor agent can improve the efficacy of tumor treatment. This combination therapy approach enhances apoptosis in tumors as well as T cell cytotoxicity against tumor cells.

Claims and reasons about mild COVID-19 in children.

The elderly form the main risk group in the coronavirus disease 2019 (COVID-19) pandemic, and age is recognized as a major risk factor for the severity of infection and mortality of COVID-19. The severity of the infection in children is milder than in adults. Although the pathophysiology of COVID-19 is not fully understood, several possible factors and mechanisms have been suggested for the lower severity of infection in children.

The prevalence of human bocavirus in <2-year-old children with acute bronchiolitis.

Acute bronchiolitis is one of the most common lower respiratory tract infections in children with less than 2 years of age. Nowadays, molecular methods provide an opportunity to better understand the etiology of bronchiolitis. Several viral agents including Respiratory syncytial virus (RSV), Rhinovirus, Parainfluenza and Human bocavirus (HBoV) are responsible for acute bronchiolitis. There are growing studies on the prevalence of HBoV in patients with bronchiolitis. The present systematic review and meta-analysis were conducted to determine the pooled prevalence of HBoV in the respiratory samples of children with acute bronchiolitis. A literature search was conducted in the databases of PubMed, Scopus and Web of Science to recruit studies reporting the frequency of HBoV in <2-year-old children with acute bronchiolitis from 2005 to 2019. Only studies that used polymerase chain reaction (PCR)-based methods to detect the virus in nasopharyngeal samples were included. A total of 22 studies assessing 6751 cases were analyzed. According to the meta-analysis based on the random-effects model, the overall prevalence of HBoV in children with <2 years old was obtained 13% (95% CI: 0.09-0.17). Additionally, the rates of single (as the sole organism) and mixed (in combination with other viruses) HBoV infections were 4% and 9%, respectively. This study showed a high rate of HBoV detection in children with acute bronchiolitis. This should be considered as part of a diagnostic test panel for respiratory infections in children with bronchiolitis.

Latent toxoplasmosis and human.

Toxoplasmosis is one of the most common parasitic diseases worldwide. Although estimated that one third of the world's population are infected with Toxoplasma gondii, but the most common form of the disease is latent (asymptomatic). On the other hand, recent findings indicated that latent toxoplasmosis is not only unsafe for human, but also may play various roles in the etiology of different mental disorders. This paper reviews new findings about importance of latent toxoplasmosis (except in immunocompromised patients) in alterations of behavioral parameters and also its role in the etiology of schizophrenia and depressive disorders, obsessive-compulsive disorder, Alzheimer's diseases and Parkinson's disease, epilepsy, headache and or migraine, mental retardation and intelligence quotients, suicide attempt, risk of traffic accidents, sex ratio and some possible mechanisms of T. gondii that could contribute in the etiology of these alterations.

Phylogenetic status of brown trout Salmo trutta populations in five rivers from the southern Caspian Sea and two inland lake basins, Iran: a morphogenetic approach.

Interrelationships, origin and phylogenetic affinities of brown trout Salmo trutta populations from the southern Caspian Sea basin, Orumieh and Namak Lake basins in Iran were analysed from complete mtDNA control region sequences, 12 microsatellite loci and morphological characters. Among 129 specimens from six populations, seven haplotypes were observed. Based on mtDNA haplotype data, the Orumieh and southern Caspian populations did not differ significantly, but the Namak basin-Karaj population presented a unique haplotype closely related to the haplotypes of the other populations (0·1% Kimura two-parameter, K2P divergence). All Iranian haplotypes clustered as a distinct group within the Danube phylogenetic grouping, with an average K2P distance of 0·41% relative to other Danubian haplotypes. The Karaj haplotype in the Namak basin was related to a haplotype (Da26) formerly identified in the Tigris basin in Turkey, to a Salmo trutta oxianus haplotype from the Aral Sea basin, and to haplotype Da1a with two mutational steps, as well as to other Iranian haplotypes with one to two mutational steps, which may indicate a centre of origin in the Caspian basin. In contrast to results of the mtDNA analysis, more pronounced differentiation was observed among the populations studied in the morphological and microsatellite DNA data, except for the two populations from the Orumieh basin, which were similar, possibly due to anthropogenic causes.

Genetic differentiation between two sympatric morphs of the blind Iran cave barb Iranocypris typhlops.

The phylogenetic relationship between two sympatric morphotypes of the Iran cave barb Iranocypris typhlops, and Garra rufa, was investigated by sequencing the cytochrome c oxidase I (coI) region (788 bp) providing the first molecular evidence of their phylogeny. Consistent with their morphological differences, the mean genetic distance between the two forms of I. typhlops was significantly higher than generally reported for intraspecific divergence in freshwater fishes. They were phylogenetically closer to G. rufa than to any other species.

Developing an educational scheme for undergraduate medical Curriculum: the unit of "infertility" as a sample.

OBJECTIVES: To present our first experience in scheme development based on CPC philosophy in Iran. HYPOTHESIS: One of the most important reasons of an obvious gap between medical education and professional expectations (outcomes) encountered by recent medical graduates is due to applying conventional curricula, which rely on hypothetical-deductive reasoning model. The University of Calgary has implemented a new curriculum which is organized according to 125 ways in which patients may present to a physician. In this study we will present our first experience in scheme development based on CPC philosophy in Iran. METHODS: In 2007, research and clinical center for infertility (Yazd University of medical sciences, IRAN), began developing a full module for infertility (lesson plan) with fourteen components based on the new curricular philosophy. We recruited a scheme of infertility according to a specific way. RESULTS: Thus, at the first step of the module creation, a scheme was made as the most important mainstay of presentation module, i.e. a structured scheme that includes all causative diseases of infertility. CONCLUSIONS: Any effort in the organization of knowledge around schemes including in the domain of infertility would be valuable to meet some of the standards of WFME. Also, development of modules, by the teams composed of experts and students, can improve the quality of medical education.

Impaired reproductive function of male rats infected with Toxoplasma gondii.

Toxoplasmosis is one of the classical conditions known to have an adverse effect on female reproductive functions, but a few investigations into male reproductive parameters have been performed. This work was carried out to study the effects of Toxoplasma gondii on reproductive function in male rats. Male rats were infected with the RH strain of T. gondii tachyzoites, and following every 10 days from 10 to 70 postinfection (PI), the percentage of body weight to testis weight ratio as well as epididymal sperm parameters (number, motility, viability, and morphology rates), serum testosterone (ST), intratesticular testosterone (ITT), serum lactate dehydrogenase (SLDH), intratesticular lactate dehydrogenase and fructose in seminal vesicles and coagulating glands were measured. The results of the study showed sperm motility, viability and concentration rates were significantly decreased temporary after infection up to 70 days. Sperm abnormality was also increased during these days. In addition, temporary alteration in ST, ITT, SLDH, intratesticular LDH and fructose in seminal vesicle and coagulating gland was observed PI. These findings suggest that toxoplasmosis can cause impermanent impairment on the reproductive parameters of male rats.

A new classification for female infertility.

Infertility is defined as the inability of a couple to conceive after 12 months of regular, unprotected intercourse. However infertility is a clinical presentation and not a disease. Thus to be able to offer a new classification, it is necessary to apply a clinical presentation (philosophy) suggested by the University of Calgary in 1991. In recent years several classification algorithms have been proposed which apply key predictors of clinical, imaging, or morphological types to determine the diseases that can cause infertility. On the other hand, an algorithm is a product of an expert's mind after many years of practice and experience, which is too difficult to understand by a medical student. However there has not been any simple schematic classification based on a logical justification applying integration of etiologies with basic science to break down etiologies into categories, subcategories and disease classes of this clinical presentation. Because etiology has also become an important criterion for the characterization of causes of infertility, a classification proposal is presented here that attempts to include all relevant (basic science) features of the causative diseases of this clinical presentation.

The role of nitric oxide in bradycardia of rats with obstructive cholestasis.

Nitric oxide (NO) has an important role in controlling heart rate and contributes to the cholinergic antagonism of the positive chronotropic response to adrenergic stimulation. Based on evidence of NO overproduction in cholestasis and also on the existence of bradycardia in cholestatic subjects, this study aimed to evaluate the chronotropic effect of epinephrine in isolated atria of cholestatic rats and determine whether alterations in epinephrine-induced chronotropic responses of cholestatic rats are corrected after systemic inhibition of NO synthase (NOS) with N(G)-nitro-L-arginine (L-NNA). Male Sprague-Dawley rats were used. Cholestasis was induced by surgical ligation of the bile duct under general anesthesia and sham-operated animals were considered as control. The animals were divided into three groups, which received either L-arginine (200 mg/kg/day), L-NNA (10 mg/kg/day) or saline. One week after the operation, a lead II ECG was recorded from the animals, then spontaneously beating atria were isolated and chronotropic responses to epinephrine were evaluated in a standard oxygenated organ bath. The results showed that plasma gamma-glutamyl transpeptidase and alanine aminotransferase activity was increased by bile-duct ligation, and that L-aginine treatment partially, but significantly, prevented the elevation of these markers of liver damage. The results showed that heart rate of cholestatic animals was significantly less than that of sham-operated control rats in vivo and this bradycardia was corrected with daily administration of L-NNA. The basal spontaneous beating rate of atria in cholestatic animals was not significantly different from that of sham-operated rats in vitro. Meanwhile, cholestasis induced a significant decrease in chronotropic effect of epinephrine. These effects were corrected by daily administration of L-NNA. Surprisingly L-arginine was as effective as L-NNA and increased the chronotropic effect of epinephrine in cholestatic rats but not in sham-operated animals. Systemic NOS inhibition corrected the decreased chronotropic response to adrenergic stimulation in cholestatic rats, and suggests an important role for NO in the pathophysiology of heart rate complications in cholestatic subjects. The opposite effect of chronic L-arginine administration in cholestasis and in control rats could be explained theoretically by an amelioration of cholestasis-induced liver damage by chronic L-arginine administration in bile duct-ligated rats.

N(G)-nitro-L-arginine methylester is protective against ethanol-induced gastric damage in cholestatic rats.

In this study the effect of nitric oxide (NO) synthesis inhibition on ethanol-induced gastric damage was evaluated in bile duct-ligated, sham-operated and unoperated rats. The animals were injected intraperitoneally with saline, L-arginine (200 mg/kg) or N(G)-nitro-L-arginine methylester (L-NAME) in doses of 5, 15 and 30 mg/kg, 30 min before ethanol administration. The animals were killed 1 h after ethanol administration and their stomachs were removed for measurement of gastric mucosal damage. The results showed that L-NAME significantly enhanced the development of gastric mucosal lesions in sham-operated and unoperated rats, while in bile duct-ligated animals, L-NAME decreased and L-arginine enhanced the potentiation of ethanol-induced gastric mucosal damage. The plasma level of nitrite and nitrate was also measured and was significantly higher in bile duct-ligated rats than in control groups. The results suggest that inhibition of NO synthase with L-NAME has different effects on ethanol-induced gastric damage in cholestatic groups and in normal rats and that these effects can be explained by overproduction of NO in bile duct-ligated animals.