An overview on mRNA-based vaccines to prevent monkeypox infection.

The human monkeypox virus (Mpox) is classified as a member of the Poxviridae family and belongs to the Orthopoxvirus genus. Mpox possesses double-stranded DNA, and there are two known genetic clades: those originating in West Africa and the Congo Basin, commonly known as Central African clades. Mpox may be treated with either the vaccinia vaccination or the therapeutics. Modifying the smallpox vaccine for treating and preventing Mpox has shown to be beneficial because of the strong link between smallpox and Mpox viruses and their categorization in the same family. Cross-protection against Mpox is effective with two Food and Drug Administration (FDA)-approved smallpox vaccines (ACAM2000 and JYNNEOSTM). However, ACAM2000 has the potential for significant adverse effects, such as cardiac issues, whereas JYNNEOS has a lower risk profile. Moreover, Mpox has managed to resurface, although with modified characteristics, due to the discontinuation and cessation of the smallpox vaccine for 40 years. The safety and efficacy of the two leading mRNA vaccines against SARS-CoV-2 and its many variants have been shown in clinical trials and subsequent data analysis. This first mRNA treatment model involves injecting patients with messenger RNA to produce target proteins and elicit an immunological response. High potency, the possibility of safe administration, low-cost manufacture, and quick development is just a few of the benefits of RNA-based vaccines that pave the way for a viable alternative to conventional vaccines. When protecting against Mpox infection, mRNA vaccines are pretty efficient and may one day replace the present whole-virus vaccines. Therefore, the purpose of this article is to provide a synopsis of the ongoing research, development, and testing of an mRNA vaccine against Mpox.

Discordance Therapeutic Protocol of Cystic Echinococcosis With WHO Guideline: A Descriptive Study Based on Liver Ultra-Sonographic Data in North Khorasan Province, Northeastern of Iran.

BACKGROUND: Cystic echinococcosis (CE), a helminth-associated zoonosis caused by Echinococcus granulosus, poses a significant public health problem, particularly in pastoral-rearing regions. The lack of uniform guidelines led to variations in CE management. Based on ultrasound data, the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) classification system categorizes cysts into active, transitional, and inactive groups. This study assesses whether the therapeutic approach from liver human operation cases in North Khorasan province aligns with the WHO-IWGE reference based on ultrasound data. METHODS: The research is based on ultrasound data from liver CE human operation cases collected between 2018 and 2022. This retrospective study investigates the therapeutic protocol for (CE) in North Khorasan Province, Iran, comparing it with the WHO-IWGE guidelines. We collect data from previously registered patients' medical information from our studied area's main CE surgical hospital. Moreover, as the first hospitalized survey in Iran, this study reveals insights into patient demographics, cyst stage prevalence, and treatment modalities. RESULTS: Notably, more than half of the patients were treated for CE1 stage cysts, and CE4 cases, which generally do not require surgery, underwent open surgery. The results suggest a need for adherence to the "watch-and-wait" approach in specific cases. All patients underwent successful surgeries, but we do not have access to follow-up data from patients after discharge. CONCLUSIONS: This descriptive study contributes to understanding the implementation of WHO guidelines in a regional context, shedding light on the challenges and variations in CE management. It seems, retraining courses for surgeons are required to update their knowledge of standard CE diagnostic and treatment methods.

Aggravation of cognitive impairments in the valproic acid-induced animal model of autism in BALB/c mice infected with Toxoplasma gondii.

PURPOSE: Toxoplasmosis is a disease caused by infection with a type of coccidial protozoan parasite called Toxoplasma gondii. The relationship between toxoplasmosis and cognitive disorders in neurodegenerative diseases has been proven. There is also evidence that children born to Toxoplasma-infected mothers are more likely to develop autism. METHODS: In the present study, Toxoplasma-infected pregnant BALB/c mice were given valproic acid to induce autism in their male offspring, and their social behaviors, learning, and memory were examined. Chronic toxoplasmosis was established in BALB/c mice by intraperitoneal injection of cyst form of T. gondii. To induce autism, 600 mg/kg of valproic acid was injected intraperitoneally into mice on the 12.5th day of pregnancy. The behavioral experiments, such as social interaction, novel object recognition, and passive avoidance tasks, were performed on male offspring at 50 days. RESULTS: Toxoplasma and valproic acid during the embryonic period caused social communication deficits and disrupted recognition memory and avoidance memory in offspring. Our findings showed that administering valproic acid to Toxoplasma-infected mothers exacerbates cognitive disorders in their offspring.

Genetic Diversity of Toxoplasma gondii by Serological and Molecular Analyzes in Different Sheep and Goat Tissues in Northeastern Iran.

Background: Toxoplasmosis is a parasitic disease caused by compilation protozoan agent Toxoplasma gondii, leading to significant financial and quality-adjusted life-year losses. Overcooked or raw meat consumption has been a considerable transmission route. The present study was conducted to determine the seropositivity rate of T. gondii in sheep and goats by serological and molecular tests and genotyping of obtained isolates in northeast Iran. Methods: Blood and tissue samples (diaphragm, heart) of 296 animals (including 168 sheep and 128 goats) were collected from the slaughterhouse in Quchan Country from august 2016 to April 2017. Modified agglutination test (MAT) and the PCR method performed to detect parasite DNA on tissues.PCR-RFLP method of GRA6 gene was used to determine the genotype of T. gondii. In addition, sequencing analysis was performed to evaluate the Toxoplasma type strains. Results: Serum positive for MAT results were found in 27.4% of sheep and 23.4% of goats. Positive PCR of B1 gene results in diaphragm and heart tissues of sheep and goats was 47.8% and 26.1%, 40% and 23.3%, respectively. PCR of GRA6 gene results were positive in 10 samples that RFLP technique results using MseI enzyme revealed genotype I. Sequencing and phylogenetic analysis revealed DNA of all samples was closely related to Toxoplasma type I. Conclusion: Concerning the high seropositivity rate of toxoplasmosis, undertaking an appropriate preventive program for reducing the prevalence of T. gondii infection by raw or undercooked meat consumption of livestock is recommended. Our study supports the notion that these animals' consumption of raw and undercooked meat can be a probable source of human toxoplasmosis.

The effect of aging on the epidemiology of blood transfusions in North Khorasan province, Iran.

PURPOSE: Additional knowledge on the epidemiology and recipients of blood transfusions will help health-care managers to estimate the future needs. The study was performed to define the blood transfusion rate based on gender, sex, and clinical features of patients receiving blood products in all hospitals of the North Khorasan province of Iran. METHODS: Data on blood transfusion implementation were extracted from blood bank documents. The data for all patients who received at least one blood product were collected from March 2018 to March 2019. RESULTS: Among blood transfused patients, the highest transfusion rate was for packed red blood cells (PRBC) (47.7%). The two other most frequently used products were fresh frizzed plasma (FFP) (27.2%) and platelets (PLT) (21.9%). The patients in the age group of 51-80 years received the majority of PRBCs and FFPs. Patients aged 21-40 and 61-70 yrs had the highest transfusion rates for PLT. Elderly female patients (57.4%) received more blood products than their male counterparts. The highest blood transfusion rates were among patients with neoplasms, anemia, gastrointestinal bleeding, and gastric diseases. CONCLUSION: The primary Iranian blood recipients were elderly patients. Population aging is associated with an increase in the number of blood recipients and simultaneously declines the blood donors pool. It highlights the need for optimizing the use of blood in hospitals and having better strategies for overcoming the shortage of blood.

Nano amphotericin B: a good anti-leishmanial drug with effect on cathelicidin gene expression.

Protozoan parasites, such as Leishmania major (L. major), remained as a global health problem of the current century. Leishmania major is a major cause of cutaneous leishmaniasis (CL) in developed and developing countries. Traditionally, amphotericin B is prescribed as an alternative drug, while first-line drugs failed. Some active proteins of the innate immune system such as cathelicidins try to inhibit infection Via several proposed mechanisms. Here this research aimed to not only determine the anti-leishmanial activity of nano amphotericin B but also to evaluate which anti-leishmanial drug can induce the cathelicidin gene expression. Both promastigote and amastigote stages of L. major were exposed to various concentrations of nano amphotericin B, amphotericin B and finally compared to glucan time as standard drug for CL treatment. For the gene expression of cathelicidin, macrophages were exposed to the same concentration of anti-leishmanial drugs. The findings demonstrated that nano amphotericin B was more effective at all concentrations than amphotericin B. Additionally, among tested anti-leishmanial drugs, nano amphotericin B has more potency to induce the cathelicidin gene expression in macrophages cells. The findings revealed that nano amphotericin B has potential as an effective anti-leishmanial drug against CL caused by L. major parasites.

Chronic Toxoplasma gondii Infection Potentiates Parkinson's Disease Course in Mice Model.

BACKGROUND: Toxoplasma gondii is a neuroinvasive protozoa pathogen that could manipulate its intermediate host's behavior. However, the possible link between T. gondii infection and the development of neurodegenerative disorders such as Parkinson's disease (PD) has been proposed, we tested the hypothesis that in chronic toxoplasmosis neuroinflammation, and molecular mediators potentiate behavioral-cognitive impairments in BALB/c mice with PD. METHODS: To establish chronic toxoplasmosis by Tehran strain, cysts of T. gondii were injected intraperitoneally into BALB/c mice in Kerman, Iran in 2019. To induce the PD model, mice (BALB/c) were treated with Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The behavioral experiments such as anxiety and motor coordination were performed using the Open field and Rotarod tests. Additionally, we investigated the contribution of Toxoplasma-induced neuroinflammation, and behavioral-cognitive impairments in the PD mice model. RESULTS: Chronic toxoplasmosis caused PD-like symptoms and induced various behavioral changes in infected BALB/c mice. In T. gondii infected+MPTP treated group, T. gondii infection could potentiate PD in infected mice receiving MPTP and caused remarkable dysfunction in motor coordination and change in anxiety and depression-like behaviors similar or more severe than PD group. CONCLUSION: Chronic T. gondii infection exacerbates pathological progression of PD in BALB/c mice brain by promoting neuroinflammation, and behavioral changes establishing.

Frequency of different genotypes of Giardia duodenalis in slaughtered sheep and goat in east of iran.

Giardia duodenalis is one of the most common and important protozoan parasites of the gastrointestinal tract in humans and animals, especially in developing countries. The purpose of this study was determining prevalence of Giardia genotypes specially zoonosis genotypes in sheep and goat in eastern of iran slaughterers.This cross-sectional study was conducted during April to November 2019. 300 fecal samples were collected from the rectum of sheep and goats. The samples were subjected to DNA extraction after sucrose gradient purification. A fragment of the glutamate dehydrogenase gene (gdh) was amplified by semi-nested PCR and genotype diagnosis was performed by digestion of the secondary PCR product with restriction enzymes RsaI and Nla IV. The prevalence of Giardia was found as (274/300) by the molecular method. Restriction endonuclease digestion of the nested-PCR product showed; among 274 positive isolates, 95 were typed as assemblage E, 15 as assemblage B, 87 assemblage AI, 45 assemblage AII, and 32 assemblege C. In this study, frequency of different assemblages of G. duodenalis was determined in sheep and goats by gdh gene and PCR-RFLP method. Same of other studies, assemblage E was dominant genotype in sheep and goats. Isolation of zoonotic assemblages as AI, AII, and BIII showed that sheep and goats should be considered as a source for human infection.

Murine cathelicidin: as a host defensive response against Leishmania major infection.

Leishmaniasis is a serious global challenge with neither efficacious prophylactic vaccine nor effective and safe therapeutic measures. Cathelicidins, members of antimicrobial peptides family, are small proteins of innate immunity system, which represent a protective barrier against a number of potential pathogens in living organisms. The murine cathelicidin or cathelin-related antimicrobial peptide (CRAMP) is expressed by a variety of cells or tissues, and highly resembles to human cathelicidin (LL-37). It is naturally expressed at a low concentration in adolescent age, but extensively increases during cutaneous infections. Despite its important role, it has less been investigated in parasitic infections. Among all cells, macrophages and skin cells are the two important cells that directly have a relationship with Leishmania major parasites. The present study aimed to show whether cathelicidins protect their hosts following cutaneous leishmaniasis due to L. major parasites. Both in vitro and in vivo models of L. major infection were established by exposing of J744 cell line (murine macrophages) and BALB/c mice with the stationary phase of L. major promastigotes for 24 h and 7 days. The findings revealed that both macrophages and skin cells significantly (p < 0.05) expressed a high level of CRAMP gene and peptide after challenging with L. major parasites. Thus, our data suggest a protective role for cathelicidins against infections caused by L. major parasites. This experimental model could be considered as a novel potential vaccine candidate for planning future control strategy against human leishmaniasis.

Nanosilver Colloid Inhibits Toxoplasma gondii Tachyzoites and Bradyzoites in Vitro.

BACKGROUND: Toxoplasma gondii, the coccidian protozoan parasite with worldwide distribution, is the agent of toxoplasmosis. The disease is life threatening in congenital form and in immunocompromised patients. The present study was carried out in 2016 to evaluate the in vitro effects of nanosilver colloid on tachyzoites and bradyzoites of T. gondii, RH and Tehran strains. METHODS: Different concentrations (5, 10, 20 ppm) of nanosilver colloid were added to tachyzoites of T. gondii, RH strain (type I) and bradyzoites and tissue cysts of T. gondii, Tehran strain (type II) and incubated for 30, 60, 90 and 120 minutes. The mortality rates of tachyzoites and bradyzoites were evaluated by trypan blue dye and MTT assay. Then SEM carried out to show the changes between control and exposed parasites. RESULTS: The greatest mortality rate was seen in 20 ppm concentration and after 120 minutes of exposure. By electron microscopy, the structural changes were seen in tachyzoites of RH and tissue cyst of Tehran strain in comparison with control groups. CONCLUSION: Nanosilver colloid was effective on both tachyzoites and bradyzoites of T. gondii, RH and Tehran strains.