The Impact of Pulmonary Hydatid Cyst Rupture on COVID-19 Symptom Severity.

BACKGROUND: Co-infection with other microorganisms such as parasites in patients with COVID-19 can affect the clinical outcome and require prompt diagnosis and appropriate therapy. CASE PRESENTATION: We present a case of an adult male with chest pain, dyspnea, cough, diplopia, and anorexia who was confirmed to have acute COVID-19 pneumonia. 2 weeks prior to admission, a hydatid lung cyst was identified on examination, but the patient refused surgery. Thoracoabdominal computed tomography (CT) revealed a rupture of the lung hydatid cyst and co-infection with COVID-19. The patient has prescribed a treatment protocol for COVID-19 and albendazole. Despite measures taken to manage severe inflammation and decreasing blood oxygen levels, the patient required admission to the intensive care unit (ICU) and intubation. After approximately 3 weeks of hospitalization, the patient was successfully extubated and discharged uneventfully from the hospital. Oral albendazole was prescribed for follow-up treatment. CONCLUSION: Our case highlights the importance of considering hydatid cysts in the differential diagnosis of patients with COVID-19, especially those living in endemic areas.

Enhancement of targeted therapy in combination with metformin on human breast cancer cell lines.

BACKGROUND: Breast cancer remains a primary global health concern due to its limited treatment options, frequent disease recurrence, and high rates of morbidity and mortality. Thereby, there is a need for more effective treatment approaches. The proposal suggests that the combination of targeted therapy with other antitumoral agents could potentially address drug resistance. In this study, we examined the antitumoral effect of combining metformin, an antidiabetic drug, with targeted therapies, including tamoxifen for estrogen receptor-positive (MCF-7), trastuzumab for HER2-positive (SKBR-3), and antibody against ROR1 receptor for triple-negative breast cancer (MDA-MB-231). METHODS: Once the expression of relevant receptors on each cell line was confirmed and appropriate drug concentrations were selected through cytotoxicity assays, the antitumor effects of both monotherapy and combination therapy on colony formation, migration, invasion were assessed in in vitro as well as tumor area and metastatic potential in ex ovo Chick chorioallantoic membrane (CAM) models. RESULTS: The results exhibited the enhanced effects of tamoxifen when combined with targeted therapy. This combination effectively inhibited cell growth, colony formation, migration, and invasion in vitro. Additionally, it significantly reduced tumor size and metastatic potential in an ex ovo CAM model. CONCLUSIONS: The findings indicate that a favorable strategy to enhance the efficacy of breast cancer treatment would be to combine metformin with targeted therapies.

Modulatory Effects of Hydatid Cyst Fluid on a Mouse Model of Experimental Autoimmune Encephalomyelitis.

The reduced burden of helminth parasites in industrialized countries is probably one of the reasons for the increased prevalence of autoimmune disorders such as multiple sclerosis (MS). The current study aimed to evaluate the potential preventive effects of hydatid cyst fluid (HCF) on the disease severity in an EAE mouse model of MS. EAE-induced mice were treated with HCF before and after EAE induction. An RT-PCR-based evaluation of IFN-γ, IL-1ß, TNF, T-bet, IL-4, GATA3, IL-17, RoRγ, TGF-ß, and FOXP3 expression levels in splenocytes and an ELISA-based analysis of IFN-γ and IL-4 levels in cell culture supernatant of splenocytes were performed. Histopathological examinations of mice during the study were also conducted. The expression levels of T-bet, IL-4, GATA3, TGF-ß, and FOXP3 in EAE + HCF mice were significantly higher compared to EAE + PBS mice. In the EAE + HCF group, the expression levels of IFN-γ, IL-1ß, and TNF were significantly lower than in the EAE + PBS group. The histopathological results showed significantly reduced inflammation and demyelination in EAE + HCF mice compared to EAE + PBS mice. Our study provides proof-of-concept in the EAE mouse model of MS that helminth-derived products such as HCF have a potential prophylactic effect on MS development and present a novel potential therapeutic strategy.

Prevalence of Ecto and Gastrointestinal Parasites of Rattus rattus in Mazandaran Province, North of Iran

Objective: Rodents act as reservoir hosts and are an important potential source for many zoonotic pathogens such as parasites, which pose a public health risk to humans. Therefore, it is necessary to investigate the prevalence of parasites among rodents. Methods: A total of 118 Rattus rattus were captured in Mazandaran province, north of Iran, using snap live traps. Various samples were collected from feces and each rat was combed with a fine-tooth comb to extricate any ectoparasite. Fecal specimens were examined by direct wet mounting, formalin-ether concentration, modified acid-fast, and trichrome staining methods. Results: The overall prevalence of gastrointestinal parasites in the examined rats was 75.4%. Cryptosporidium spp. (30.5%) were the most prevalent protozoan, followed by Giardia spp. (20.3%), Entamoeba muris (13.5%), Trichomonas muris (10.1%), and Spironucleus muris (3.3%). Regarding helminths' eggs, Syphacia obvelata (24.5%), Hymenolepis diminuta (10.1%), and Trichuris muris (9.3%) had the highest prevalence, respectively. Furthermore, 3060 ectoparasites collected from 102 rodents were infested with lice (40% Polyplax spp.), mites (33.3%), and flea (16.1% Xenopsylla cheopis and 10.6% Xenopsylla astia). Conclusion: According to the results of this study, the prevalence of ecto and gastrointestinal parasites in the collected rats in the area being studied was remarkably high. Additionally, Rattus rattus can be considered a potential risk to human health.

Serosal membrane tuberculosis in Iran: A comprehensive review of evidences.

Tuberculosis (TB) is among the most common cause of serositis. There are many uncertainties in diagnostic and therapeutic approach to serous membranes tuberculosis. Our aim in the present review is to discuss the regional facilities for timely diagnosis, rapid decision-making and appropriate treatment regarding to serous membranes tuberculosis; with emphasis on situation in Iran. A comprehensive literature searches about the status of serous membranes tuberculosis in Iran were performed in English databases including Google Scholar, Science Direct, Scopus, Pub Med, and Web of Sciences, Persian SID databases, between 2000 and 2021. The main findings of the present review are as follow: a) pleural tuberculosis is more common than pericardial or peritoneal tuberculosis. b) Clinical manifestations are non-specific and so non-diagnostic. c) Smear and culture, PCR and characteristic granulomatous reaction have been used for definitive TB diagnosis by physicians. d) With Adenosine Deaminase Assays and Interferon-Gamma Release Assays in mononuclear dominant fluid, a possible diagnosis of TB is proposed by experienced physicians in Iran. e) In area of endemic for tuberculosis including Iran, a possible diagnosis of TB is enough to begin empirical treatment. f) In patients with uncomplicated tuberculosis serositis, treatment is similar to pulmonary tuberculosis. First line drugs are prescribed unless evidence of MDR-TB is detected. g) The prevalence of drug resistant tuberculosis (MDR-TB) in Iran is between 1% and 6%, and are treated by empirical standardized treatment. h) It is not known whether adjuvant corticosteroids are effective in preventing long term complication. i) Surgery may be recommended for MDR-TB. Tamponade or constrictive pericarditis and intestinal obstruction. In conclusion, it is recommended to consider serosal tuberculosis in patients who have unknown mononuclear dominant effusion and prolonged constitutional symptoms. Experimental treatment with first line anti-TB drugs can be started based on possible diagnostic findings.

Overview of Apoptosis, Autophagy, and Inflammatory Processes in Toxoplasma gondii Infected Cells.

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite. During the parasitic invasion, T. gondii creates a parasitophorous vacuole, which enables the modulation of cell functions, allowing its replication and host infection. It has effective strategies to escape the immune response and reach privileged immune sites and remain inactive in a controlled environment in tissue cysts. This current review presents the factors that affect host cells and the parasite, as well as changes in the immune system during host cell infection. The secretory organelles of T. gondii (dense granules, micronemes, and rhoptries) are responsible for these processes. They are involved with proteins secreted by micronemes and rhoptries (MIC, AMA, and RONs) that mediate the recognition and entry into host cells. Effector proteins (ROP and GRA) that modify the STAT signal or GTPases in immune cells determine their toxicity. Interference byhost autonomous cells during parasitic infection, gene expression, and production of microbicidal molecules such as reactive oxygen species (ROS) and nitric oxide (NO), result in the regulation of cell death. The high level of complexity in host cell mechanisms prevents cell death in its various pathways. Many of these abilities play an important role in escaping host immune responses, particularly by manipulating the expression of genes involved in apoptosis, necrosis, autophagy, and inflammation. Here we present recent works that define the mechanisms by which T. gondii interacts with these processes in infected host cells.

Scolicidal and Apoptotic Activities of 5-hydroxy-1, 4-naphthoquinone as a Potent Agent against Echinococcus granulosus Protoscoleces.

Cystic hydatid disease (CHD) is a zoonotic disease with different clinical stages caused by the larval stage of the cestode Echinococcus granulosus. It is important to highlight as a public health problem in various regions of the world. In the current study, the efficacy and apoptotic activity of the liposomal system containing juglone (5-hydroxy-1,4-naphthoquinone) were assessed against protoscoleces (PSCs) in vitro. To this aim, firstly, liposomal vesicles were prepared by the thin-film method. Their physico-chemical features were assessed using Zeta-Sizer and Scanning Electron Microscope (SEM). Subsequently, various concentrations (50, 100, 200, 400, and 800 µg/mL) of juglone nanoliposomes at different exposure times (15, 30, 60, and 120 min) were used against PSCs. Results showed that juglone nanoliposomes at all tested concentrations induced scolicidal effect, however, 800 µg/mL and 400 µg/mL of juglone nanoliposomes could reach 100% mortality in 60 and 120 min, respectively. Additionally, we found that caspase-3 mRNA expression was higher in PSCs treated with juglone nanoliposomes compared to control groups (p < 0.001). Therefore, juglone nanoliposomes are suggested to have a more potent apoptotic effect on PSCs. Generally, optimized doses of juglone nanoliposomes could display significant scolicidal effects. Moreover, further in vivo studies are required to evaluate the efficacy of this nanoliposome.

Development of Optical Biosensor Using Protein A-Conjugated Chitosan-Gold Nanoparticles for Diagnosis of Cystic Echinococcosis.

Human echinococcosis is a serious parasitic diseasethat still affects millions of people in many parts of the world. Since it can offer a critical threat to people's health, it is important to discover a rapid, convenient, and economical method for detection. Herein, we propose a novel point of care assay, namely, an enhanced immuno-dot-blot assay for diagnosis of cystic echinococcosis (hydatidosis). This method is based on the formation of a sandwich complex between a goldnanoprobe (chitosan-gold nanoparticleprotein A) and hydatid cyst antigen (Ag B), which holds anti-Ag B antibodies. Briefly, protein A was conjugated to chitosan-gold nanoparticles via glutaraldehyde chemistry. Then, Ag B was immobilized on the surface of a nitrocellulose membrane, which was followed by the addition of the sera sample and gold nanoprobes. The positive signals were easily detectable by naked eye. The signal intensity of this biosensor was proportional to the concentration of active anti-Echinococcus granulosus antibodies on the surface of the nanoparticles, titer of antibodies in the sera samples, and concentration of Ag B coated on the nitrocellulose membrane. The minimum concentration to use the protein A for conjugation to detect titer of anti-Echinococcus IgGand the concentration of Ag B coated in nitrocellulose membrane were 0.5 and 0.3 mg/mL, respectively. This enhanced immuno-dot-blot assay offers a simple diagnostic technique withoutthe need for expensive equipment for diagnosis of echinococcosis.

The compliance of surgical prophylactic antibiotics with standard protocols in Imam Reza teaching hospital of Birjand, Iran.

BACKGROUND AND OBJECTIVES: Taking unnecessary or inappropriate prophylactic antibiotics can cause infections with resistant organisms. The present study aimed to investigate administration prophylactic antibiotics in surgery ward and its compliance with standard protocol in Imam Reza teaching hospital of Birjand, Iran. MATERIALS AND METHODS: This descriptive-analytical study was performed to evaluate the pattern of prophylactic antibiotics on patients who underwent surgical operations from October to December 2019. A checklist including demographic information, type of prophylactic antibiotics, dose and duration of using drug, type of surgery, and compliance with standard protocol was used. The validity and reliability of the checklist were evaluated and confirmed prior to the study. All eligible patients were enrolled and the information of the prescribed drugs in the surgical wards was compared with the Schwartz's principles of surgery as standard protocol. RESULTS: Out of a total of 300 patients, 187 (62.3%) were male. Among the patients, 155 (51.7%) cases underwent general surgery, 119 (39.6%) cases orthopedic surgery, and 26 (8.7%) cases neurosurgery. The most popular prescribed antibiotics were cefazolin (170 cases) and ceftriaxone + metronidazole (67 cases). Furthermore, the maximum antibiotic administrations were two days (127 cases) and one day (93 cases). More importantly, 67.7% and 92.3% of the patients were in compliance with the standard protocol in terms of the type and time of administration, respectively. CONCLUSION: Our results showed that duration and route of administrating antibiotics were consistent with the standard protocol, but the type of drugs and indication did not match.

Current situation and future prospects of Echinococcus granulosus vaccine candidates: A systematic review.

Cystic echinococcosis is a worldwide zoonotic disease, represents a threat for livestock and humans, manifests as a quiescent, subclinical and chronic hydatid cyst infection. The disease imposes high expenditures and economic losses in medical and veterinary. Prophylactic vaccination would be one of the effective preventive health care against echinococcosis. During the last decades, many studies have characterized the protective antigens of Echinococcus granulosus and their role in immunization of various animal host species. Herein, we aimed to systematically evaluate and represent the best antigens as possible vaccine candidates for cystic echinococcosis. Data were systematically searched from five databases including ProQuest, PubMed, Scopus, ScienceDirect and Web of Science, up to 1 February 2020. Two reviewers independently screened and assessed data extraction and quality assessment. A total of 47 articles were eligible for inclusion criteria in the current study. The most common antigens used for vaccination against E. granulosus were EG95 and antigen B. Freund's adjuvant and Quil A have been predominantly utilized. In addition, regarding the antigen delivery, animal models, measurement of immune responses and reduction in hydatid cyst have been discussed in the text. The data demonstrated that DNA vaccines with antigen B and recombinant protein vaccines based on EG95 antigen have the best results and elicited protective immune responses.

Toxoplasma gondii surface antigen 1 (SAG1) as a potential candidate to develop vaccine against toxoplasmosis: A systematic review.

Toxoplasma gondii is an intracellular parasite that infects a broad range of animal species and humans. As the main surface antigen of the tachyzoite, SAG1 is involved in the process of recognition, adhesion and invasion of host cells. The aim of the current systematic review study is to clarify the latest status of studies in the literature regarding SAG1-associated recombinant proteins or SAG1-associated recombinant DNAs as potential vaccines against toxoplasmosis. Data were systematically collected from six databases including PubMed, Science Direct, Web of Science, Google Scholar, EBSCO and Scopus, up to 1st of January 2019. A total of 87 articles were eligible for inclusion criteria in the current systematic review. The most common antigens used for experimental cocktail vaccines together with SAG1 were ROP2 and SAG2. In addition, the most parasite strains used were RH and ME49. Freund's adjuvant and cholera toxin have been predominantly utilized. Furthermore, regarding the animal models, route and dose of vaccination, challenge methods, measurement of immune responses and cyst burden have been discussed in the text. Most of these experimental vaccines induce immune responses and have a high degree of protection against parasite infections, increase survival rates and duration and reduce cyst burdens. The data demonstrated that SAG1 antigen has a high potential for use as a vaccine and provided a promising approach for protecting humans and animals against toxoplasmosis.

Genotyping of Echinococcus granulosus isolates from livestock based on mitochondrial cox1 gene, in the Markazi province, Iran.

Hydatidosisis a parasitic disease caused by the larval stage of Echinococcus granulosus with different genotypes, and major complications in vital organs such as liver, lungs and, brain. Also, this parasite can infect animals and cause economic damages. Recently, some investigations indicated that the genetic variation of the parasite affects the antigenic, immunogenic and pathogenic features. Therefore, present study conducted to genotyping of the E. granulosus larva based on mitochondrial cox1 gene in livestock in the endemic areas of Markazi province, Iran. In this study, 49 hydatid cysts samples collected from 36 sheep, 11 goats and 2 cattle from different slaughterhouses of Markazi province in central part of Iran, 2017. The mitochondrial cox1 gene was amplified and genotyping were accomplished using sequence analysis. The sequencing analysis indicated that the main genotype G1 (61%) and G3 (37%) were identified. Also, one of the samples shows similarity with the G2 (2%) genotype. The results showed the statistically significant differences between the genotypes in different livestock (P < 0.05). This study indicated that the main genotypes of E. granulosus in Markazi province are G1 and G3 which are related to dog/sheep strain. Therefore, parasite control in dogs and sheep can reduce the risk of transmission of infection to humans.

A systematic review on the role of GRA proteins of Toxoplasma gondii in host immunization.

Toxoplasma gondii is a widespread obligatory intracellular parasite infecting humans and most of all other warm-blooded animals. Currently there is no any accepted vaccine for prevention of T. gondii infection. Many studies are focused on using of various excretory secretory antigens (ESA); and among them dense granule antigens (GRAs) being involved in parasite survival, virulence and replication processes, are considered as one of the predominant vaccine candidates. The aim of this systematic review is to prepare more comprehensive understanding of these antigens to reduce T. gondii infection in humans and animals. English databases, including PubMed, Science Direct, Google Scholar, Scopus, ISI Web of Science were systematically searched and papers evaluating GRA antigens published until June 2019 were selected. Evaluation of selected publications revealed that GRA4 and GRA7 substantially increased survival time of the experimental animals. It is noticeable that the maximum reduction in cyst burden was observed in BALB/c mice vaccinated with combination of GRA3, GRA7 and M2AP antigens (93.5%). GRA6 and GRA10 have shown high immunogenicity and GRA1 and 2 are important for virulence and induction of immune responses. This review will be helpful for researchers to conduct more effective studies in the field of immunization against T. gondii infection.

Protective efficacy induced by DNA prime and recombinant protein boost vaccination with Toxoplasma gondii GRA14 in mice.

Toxoplasma gondii, the etiological agent of toxoplasmosis, can cause severe or lethal damages in both animals and man. So, tends to develop a more effective vaccine to prevent this disease is extremely needed and would be so prominent. The novel dense granule antigen 14 (GRA14) has been identified as a potential vaccine candidate against T. gondii infection. The aim of this study was evaluation of protective immunity induced by prime/boost vaccination strategy of GRA14 antigen with calcium phosphate (CaPNs) or Aluminum hydroxide (Alum) nano-adjuvants in BALB/c mice. The finding showed that immunization with the prime-boost strategy using plasmid DNA (pcGRA14) and recombinant protein (rGRA14) with nano-adjuvants significantly elicited levels of specific IgG antibodies and cytokines against T. gondii infection. Given that, there were the high levels of total IgG, IgG2a, IFN-γ in mice of rGRA14-CaPNs and pcGRA14 + rGRA14-CaPNs groups, which indicating a Th-1 type response. While immunization of mice with Alum based rGRA14 and pcGRA14 + rGRA14 elicited specific IgG1 and IL-4 levels, which was confirmed a Th-2 type response. Mice immunized with DNA prime-protein boost vaccine with nano-adjuvants produce more vigorous specific lymphoproliferative responses than mice immunized with other antigen formulations. In addition, the CaPNs-based prime-boost vaccine of pcGRA14 + rGRA14 showed the longest survival time in mice and the lowest parasitic load in their brain tissue compared to the other groups. The results obtained in this study show that the use of GRA14 based DNA prime-protein boost vaccination regime with CaPNs can dramatically enhanced both humoral and cellular immune responses. Therefore, this strategy can provide a promising approach to the development of an effective vaccine against T. gondii infection in the future.

Seroprevalence of Toxoplasma gondii infection in cancer patients: A systematic review and meta-analysis.

Toxoplasmosis, caused by Toxoplasma gondii, is a great public health concern in cancer patients, which can induce serious pathological effects. This systematic review and meta-analysis was performed to evaluate the worldwide seroprevalence rate of T. gondii infection among cancer patients. A search was conducted on five electronic databases that reported data on T. gondii seroprevalence in cancer patients. The searching process resulted in the inclusion of 57 studies. The results showed that T. gondii had the pooled prevalence of 30.8% in cancer patients using a random-effect model (95% CI: 26.3-35.6). Cancer patients had a higher overall prevalence of T. gondii infection, compared to those without cancer. Furthermore, the odds ratio of toxoplasmosis in cancer patients was 3.1 times, compared to that of controls (95% CI: 2.5-3.8, P < 0.0001). Toxoplasmosis had a higher prevalence in females (40%) than in males (33%). Furthermore, the age group of upper 40 years had the highest prevalence infection rate (30%). In addition, a significant association was also observed between toxoplasmosis infection and year (P < 0.001), type of cancer (P < 0.001), country (P < 0.001), gender (P < 0.001), age (P = 0.006) and diagnostic method (P < 0.001) in cancer patients. Considering the high prevalence of T. gondii infection in cancer patients and its serious outcomes, the researchers are suggested to carry out further studies to prevent and control toxoplasmosis among this population.

miR-20a inhibition using locked nucleic acid (LNA) technology and its effects on apoptosis of human macrophages infected by Toxoplasma gondii RH strain.

Toxoplasma gondii is a ubiquitous and infectious parasite that multiplies in any nucleated cell of warm-blooded animals and humans worldwide. This parasite has intricate mechanisms to reciprocate host-cell apoptosis to exist in the host cell. So far, the details of the parasite interactions with host cells are not well known. MicroRNAs (miRNAs) are one of the small noncoding RNAs that are now considered as a key mechanism of gene regulation. They are important in physiological and pathological processes such as apoptosis. In this study a Real Time quantitative PCR technique was used to evaluate the levels of miR-20a of miRNAs family in human macrophage during T. gondii infection to determine the role of miR-20a in apoptosis. Then, the inhibition of miR-20a function through interaction with transfection of Locked Nucleic Acid (LNA) antisense oligomer was studied. Furthermore, it was examined whether miR-20a is involved in apoptosis of human macrophages with T. gondii infected cells using flow cytometry. We found that miR-20a expression is up-regulated in human macrophages following T. gondii infection. After LNA anti miR-20a oligomer transfection, miR-20a inhibition was evaluated by quantitative reverse transcriptase polymerase chain reaction. Flow cytometry results showed that LNA anti-miR20a oligomer increased apoptosis. In agreement with this result, we found that specific LNA oligonucleotides prevent the functional activity of miR-20a and promotion of human macrophages apoptosis with T. gondii infection by inhibition of this miRNAs gene. Also, the results support the concept that LNA oligomer antisense may be used as a therapeutic implement for blocking detrimental miRNAs overexpressed in infections.

A cross-sectional analysis of intestinal parasitic infections among the general population in north of Iran.

INTRODUCTION: Intestinal parasitic infection (IPIs) is one of the most important health problems in the developing countries. Study on the prevalence of IPIs in various communities is a prerequisite for the development of appropriate control strategies. The aim of this study was to evaluate the prevalence of intestinal parasites among the general population in Mazandaran province, northern Iran. METHODOLOGY: This study was conducted on 4,788 specimens collected from 17 urban areas (2,515 samples) and 34 rural areas (2,273 samples) within January-December 2016. Fecal specimens were examined by direct wet mounting, formalin-ether concentration, modified Ziehl-Neelsen, and trichrome staining methods. RESULTS: The overall infection rate of intestinal parasite was 14.2% (680/ 4,788). Blastocystis hominis and Giardia lamblia were identified as the most frequent parasites. Protozoa, helminths, and polyparasitism (co-infections with two or more parasite species) were observed in 12.3%, 1.03%, and 0.85% of the specimens, respectively. Furthermore, IPIs showed a significant association with household income, place of residence, washing of vegetables, exposure to soil and season (p < 0.05). CONCLUSIONS: Based on the findings, parasitic infections are still a major public health concern in the north of Iran that requires special attention. Therefore, the major key to success in the prevention of IPIs is the execution of some interventions, including patient screening and treatment, public education, and improvement of sanitary conditions.