Evaluation of angiotensin converting enzyme 2 (ACE2), angiotensin II (Ang II), miR-141-3p, and miR-421 levels in SARS-CoV-2 patients: a case-control study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that uses angiotensin converting enzyme 2 (ACE2), a pivotal member of the renin-angiotensin system (RAS), as its cell-entry receptor. Another member of the RAS, angiotensin II (Ang II), is the major biologically active component in this system. There is growing evidence suggesting that serum miRNAs could serve as prognostic biomarkers for SARS-CoV-2 infection and regulate ACE2 expression. Therefore, the aim of this study is to evaluate the changes in the serum levels of sACE2 and Ang II, as well as the expression level of miR-141-3p and miR-421 in SARS-CoV-2 positive and negative subjects. METHODS: In the present study, the serum levels of sACE2 and Ang II were measured in 94 SARS-CoV-2 positive patients and 94 SARS-CoV-2 negative subjects with some symptoms similar to those of SARS-CoV-2 positive patients using the ELISA method. In addition, the expression level of miR-141-3p and miR-421 as ACE2 regulators and biomarkers was evaluated using quantitative real-time PCR (qRT-PCR) method. RESULTS: The mean serum sACE2 concentration in the SARS-CoV-2-positive group was 3.268 ± 0.410 ng/ml, whereas in the SARS-CoV-2 negative group, it was 3.564 ± 0.437 ng/ml. Additionally, the mean serum Ang II level in the SARS-CoV-2 positive and negative groups were 60.67 ± 6.192 ng/L and 67.97 ± 6.837 ng/L, respectively. However, there was no significant difference in the serum levels of sACE2 (P value: 0.516) and Ang II (P value: 0.134) between the SARS-CoV-2 positive and negative groups. Meanwhile, our findings indicated that the expression levels of miR-141-3p and miR-421 in SARS-CoV-2 positive group were significantly lower and higher than SARS-CoV-2 negative group, respectively (P value < 0.001). CONCLUSIONS: Taken together, the results of this study showed that the serum levels of sACE2 and Ang II in SARS-CoV-2 positive and negative subjects were not significantly different, but the expression levels of miR-141-3p and miR-421 were altered in SARS-CoV-2 positive patients which need more investigation to be used as biomarkers for COVID-19 diagnosis.

Effect of curcumin nanoparticles and alcoholic extract of Falcaria vulgaris on the growth rate, biofilm, and gene expression in Pseudomonas aeruginosa isolated from burn wound infection.

PURPOSE: This study aimed to investigate the effect of Curcumin nanoparticles and alcoholic extract of Falcaria vulgaris on the growth rate, biofilm, and gene expression in Pseudomonas aeruginosa isolated from burn wound infection. METHODS: The alcoholic extract of Falcaria vulgaris was purchased from Pasargad Company. Curcumin nanoparticles were synthesized. Antibacterial activity of Curcumin nanoparticles and alcoholic extract of Falcaria vulgaris was investigated by microdilution method alone and in combination. Biofilm inhibitory was investigated by microtitrplate method. Effect of Curcumin nanoparticles and alcoholic extract of Falcaria vulgaris were evaluated on algD gene expression via Real-Time PCR. Cytotoxicity was evaluated by MTT assay on HDF cell line. Then, the data were analyzed using SPSS software. RESULTS: Synthesized Curcumin nanoparticles were approved by Fourier Transform Infrared (FTIR), and Scanning Electron Microscope. The alcoholic extract of Falcaria Vulgaris showed significant antibacterial activity against multidrug resistance (MDR) P. aeruginosa isolates at a concentration of 156.25 µg/mL. Moreover, MIC of the curcumin nanoparticle for isolates was 625 µg/mL. Based on fraction inhibition concentration, synergy, and the additive effect were shown against %7.7, and %93.3 of MDRs, respectively. The sub-MIC concentration of the binary compound reduced biofilms and algD gene expression in P. aeruginosa isolates. The Biological function of HDF cell lines was desirable after the effect of the binary compound. CONCLUSIONS: Regarding our results, this combination can be suggested as a promising agent in terms of biofilm inhibitory and antimicrobial properties.

Isolation, characterization, therapeutic potency, and genomic analysis of a novel bacteriophage vB_KshKPC-M against carbapenemase-producing Klebsiella pneumoniae strains (CRKP) isolated from Ventilator-associated pneumoniae (VAP) infection of COVID-19 patients.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a significant clinical problem, given the lack of therapeutic options. The CRKP strains have emerged as an essential worldwide healthcare issue during the last 10 years. Global expansion of the CRKP has made it a significant public health hazard. We must consider to novel therapeutic techniques. Bacteriophages are potent restorative cases against infections with multiple drug-resistant bacteria. The Phages offer promising prospects for the treatment of CRKP infections. OBJECTIVE: In this study, a novel K. pneumoniae phage vB_KshKPC-M was isolated, characterized, and sequenced, which was able to infect and lyse Carbapenem-resistant K. pneumoniae host specifically. METHODS: One hundred clinical isolates of K. pneumoniae were collected from patients with COVID-19 associated with ventilator-associated acute pneumonia hospitalized at Shahid Beheshti Hospital, Kashan, Iran, from 2020 to 2021. Initially, all samples were cultured, and bacterial isolates identified by conventional biochemical tests, and then the ureD gene was used by PCR to confirm the isolates. The Antibiotic susceptibility test in the disc diffusion method and Minimum inhibitory concentrations for Colistin was done and interpreted according to guidelines. Phenotypic and molecular methods determined the Carbapenem resistance of isolates. The blaKPC, blaNDM, and blaOXA-23 genes were amplified for this detection. Biofilm determination of CRKP isolates was performed using a quantitative microtiter plate (MTP) method. The phage was isolated from wastewater during the summer season at a specific position from Beheshti Hospital (Kashan, Iran). The sample was processed and purified against the bacterial host, a CRKP strain isolated from a patient suffering from COVID-19 pneumoniae and resistance to Colistin with high potency for biofilm production. This isolate is called Kp100. The separated phages were diluted and titration by the double overlay agar plaque assay. The separate Phage is concentrated with 10% PEG and stored at -80 °C until use. The phage host range was identified by the spot test method. The purified phage morphology was determined using a transmission electron microscope. The phage stability tests (pH and temperature) were analyzed. The effect of cationic ions on phage adsorption was evaluated. The optimal titer of bacteriophage was determined to reduce the concentration of the CRKP strain. One-step growth assays were performed to identify the purified phage burst's latent cycle and size. The SDS-PAGE was used for phage proteins analysis. Phage DNA was extracted by chloroform technique, and the whole genome of lytic phage was sequenced using Illumina HiSeq technology (Illumina, San Diego, CA). For quality assurance and preprocessing, such as trimming, Geneious Prime 2021.2.2 and Spades 3.9.0. The whole genome sequence of the lytic phage is linked to the GenBank database accession number. RASTtk-v1.073 was used to predict and annotate the ORFs. Prediction of ORF was performed using PHASTER software. ResFinder is used to assess the presence of antimicrobial resistance and virulence genes in the genome. The tRNAs can-SE v2.0.6 is used to determine the presence of tRNA in the genome. Linear genome comparisons of phages and visualization of coding regions were performed using Easyfig 2.2.3 and Mauve 2.4.0. Phage lifestyles were predicted using the program PHACTS. Phylogenetic analysis and amino acid sequences of phage core proteins, such as the major capsid protein. Phylogenies were reconstructed using the Neighbor-Joining method with 1000 bootstrap repeat. HHpred software was used to predict depolymerase. In this study, GraphPad Prism version 9.1 was used for the statistical analysis. Student's t-test was used to compare the sets and the control sets, and the significance level was set at P ≤ 0.05. RESULTS: Phage vB_KshKPC-M is assigned to the Siphoviridae, order Caudovirales. It was identified as a linear double-stranded DNA phage of 54,378 bp with 50.08% G + C content, had a relatively broad host range (97.7%), a short latency of 20 min, and a high burst size of 260 PFU/cell, and was maintained stable at different pH (3-11) and temperature (45-65 °C). The vB_KshKPC-M genome contains 91 open-reading frames. No tRNA, antibiotic resistance, toxin, virulence-related genes, or lysogen-forming gene clusters were detected in the phage genome. Comparative genomic analysis revealed that phage vB_KshKPC-M has sequence similarity to the Klebsiella phages, phage 13 (NC_049844.1), phage Sushi (NC_028774.1), phage vB_KpnD_PeteCarol (OL539448.1) and phage PWKp14 (MZ634345.1). CONCLUSION: The broad host range and antibacterial activity make it a promising candidate for future phage therapy applications. The isolated phage was able to lyse most of the antibiotic-resistant clinical isolates. Therefore, this phage can be used alone or as a phage mixture in future studies to control and inhibit respiratory infections caused by these bacteria, especially in treating respiratory infections caused by resistant strains in sick patients.

In vitro evaluation of antiviral activity of Shouchella clausii probiotic strain and bacterial supernatant against herpes simplex virus type 1.

Herpes simplex virus-1 (HSV-1) is an important human neurotropic virus infecting 70% of the world population. Due to the emergence of viral resistance via mutations in HSV-1 genes and some of the adverse effects of antiviral compounds, there is a growing need for safe, novel, and effective therapeutic and preventive strategies. The aim of the present study was to investigate for the first time the potential antiviral activity of Shouchella clausii probiotic strain and bacterial supernatant against HSV-1. The MTT assay was used to determine the possible cytotoxicity of the S. clausii and bacterial supernatant. Vero cells were treated by S. clausii, bacterial supernatant, and HSV-1 under pre-treatment (incubation of Vero cells with S. clausii then HSV-1 inoculation), pre-incubation (mixture of co-incubated HSV-1/S. clausii added to Vero cell), competition (adding HSV-1 and S. clausii into Vero cells simultaneously) and post-treatment (Vero cells inoculated with HSV-1 then incubated with S. clausii) assays. Viral titer reduction (TCID50) and viral DNA relative quantification by real-time PCR were measured in each experimental condition. The results indicated that S. clausii and its supernatant had the greatest inhibitory activity toward HSV-1 in pre-treatment assay. The HSV-1 titer treated with S. clausii, and bacterial supernatant was 3.6 and 2.2 Log10TCID50/mL lower compared to the control (7.66 Log10TCID50/mL). Results showed an antiviral effect of S. clausii and its supernatant. S. clausii could be considered as a novel inhibitor for HSV-1 infection.

Designing a novel fusion protein from Streptococcus agalactiae with apoptosis induction effects on cervical cancer cells.

Cervical cancer remains life-threatening cancer in women around the world. Due to the limitations of conventional treatment approaches, there is an urgent need to develop novel and more efficient strategies against cervical cancer. Therefore, the researchers attend to the alternative anti-cancer compounds like bacterial products. Rib and α are known as surface proteins of Streptococcus agalactiae with immunologic effects. In the present study, we designed a new anti-cancer fusion protein (Rib-α) originating from S. agalactiae with in silico methods, and then, the recombinant gene was cloned in the pET-22 (+) expression vector. The recombinant protein was expressed in E. coli BL21. To purify the expressed protein, we applied the Ni-NTA column. The molecular mechanism by which Rib-α is cytotoxic to cancer cells has been discussed based on MTT, flow cytometry, and real-time PCR methods. The engineered fusion protein suppressed the proliferation of the cancer cells at 180 µg/ml. Cytotoxic assessment and morphological changes, augmentation of apoptotic-related genes, upregulation of caspase-3 mRNA, and flow cytometric analysis confirmed that apoptosis might be the principal mechanism of cell death. According to our findings, Rib-α fusion protein motivated the intrinsic apoptosis pathway. Therefore, it can be an exciting candidate to discover a new class of antineoplastic agents.

Coinfection of torque teno virus (TTV) and human papillomavirus (HPV) in cervical samples of women living in Tehran, Iran.

Background and Objectives: Torque Teno virus or transfusion-transmitted virus (TTV) is a non-enveloped virus with a single strand circular DNA genome that currently is classified in the Alphatorquevirus genus and the family of Anelloviridae. Unlike other DNA viruses, TTV has an extremely wide genomic diversity. This virus, based on previous studies, infects both healthy people, as well as those who have HCV and human papillomavirus (HPV). This study aimed to evaluate the coinfection of torque teno virus (TTV) and HPV in cervical samples from Iranian women. Materials and Methods: In this case-control study, the fresh cervical cytobrush specimens were collected from 150 women referred to Dena laboratory in Tehran. Viral DNA was extracted from samples. The HPV-DNA was detected and genotyped. Then, nested polymerase chain reaction (Nested PCR) was performed for TTV using specific primers. Results: Among 50 cervical specimens without HPV, 14 were TTV positive (28%); among 50 low-risk HPV cervical specimen, 23 were TTV positive (46%), and from 50 high-risk HPV cervical specimen, 48 were TTV positive (96%). There is a significantly higher prevalence of TTV virus in low-risk and high-risk papillomavirus-infected specimens than in healthy specimens (p 0.0001). Additionally, TTV is more prevalent in samples containing high-risk papillomaviruses than in samples with low-risk papillomaviruses (P = 0.048). Conclusion: The higher prevalence of TTV among people infected with papillomavirus than in non-infected people indicates that both viruses are transmitted by the same mechanism (sexual route). In addition, the prevalence of TTV in samples containing high-risk papillomavirus is significantly higher than that in samples containing low-risk papillomavirus. The presence of papillomaviruses, particularly high-risk types, may be associated with TTV proliferation, which requires further research in the future.

Evaluation of the association between human herpes virus 6 (HHV-6) and Hashimoto's thyroiditis.

Background and Objectives: Hashimoto's thyroiditis is a chronic inflammation and an autoimmune disease of the thyroid gland that causes hypothyroidism. Genetic, internal, and environmental factors are the causes of this disease. Because human herpes viruses such as herpesvirus type 6 (HHV-6) are involved in some autoimmune disorders, they may also play a role in causing this disease. This study aimed to evaluate the association between human herpes virus 6 (HHV-6) with Hashimoto's thyroiditis. Materials and Methods: In the present study, 64 samples of thyroid paraffin tissue including 32 samples of thyroid paraffin tissue of healthy individuals as control, and 32 samples of thyroid paraffin tissue of Hashimoto's thyroiditis patients were taken from the pathology department of Loghman Hakim Hospital in Tehran. A questionnaire collected demographic information of patients. After DNA extraction from the samples, the nested-PCR technique was performed using specific primers for HHV-6. Results: Totally, the HHV6-DNA was found in 34.4% of thyroid tissues of healthy individuals (81.8% female and 18.2% male) and 46.9% of patients with Hashimoto's thyroiditis (73.3% female and 26.7% male). It was found that this difference in virus frequency between the two groups was not statistically significant (P value=0.309). There was also no statistically significant relationship between the prevalence of human herpesvirus type 6 and age or sex. Conclusion: Based on the present study, the number of HHV-6-infected individuals in Hashimoto's patients and controls did not differ significantly; therefore, HHV-6 appears not to be associated with Hashimoto's thyroiditis.

The impact of spike mutated variants of SARS-CoV2 [Alpha, Beta, Gamma, Delta, and Lambda] on the efficacy of subunit recombinant vaccines.

Since the first described human infection with SARS-CoV-2 in December of 2019 many subunit protein vaccines have been proposed for use in humans. Subunit vaccines use one or more antigens suitable for eliciting a robust immune response. However, the major concern is the efficacy of subunit vaccines and elicited antibodies to neutralize the variants of SARS-CoV-2 like B.1.1.7 (Alpha), B.1.351 (Beta) and P1 (Gamma), B.1.617 (Delta) and C.37 (Lambda). The Spike protein (S) is a potential fragment for use as an antigen in vaccine development. This protein plays a crucial role in the first step of the infection process, as it binds to Angiotensin-Converting Enzyme 2 (ACE2) receptor and enters the host cell after binding. Immunization-induced specific antibodies against the receptor binding domain (RBD) may block and effectively prevent virus invasion. The focus of this review is the impact of spike mutated variants of SARS-CoV2 (Alpha, Beta, Gamma, Delta, and Lambda) on the efficacy of subunit recombinant vaccines. To date, a low or no significant impact on vaccine efficacy against Alpha and Delta variants has been reported. Such an impact on vaccine efficacy for Beta, Delta, Gamma, and Lambda variants may be even greater compared to the Alpha variant. Nonetheless, more comprehensive analyses are needed to assess the real impact on vaccine efficacy brought about by SARS-CoV-2 variants.

The combined effect of stressful factors (temperature and pH) on the expression of biofilm, stress, and virulence genes in Salmonella enterica ser. Enteritidis and Typhimurium.

Salmonella enterica is a major food borne pathogen that creates biofilm. Salmonella biofilm formation under different environmental conditions is a public health problem. The present study was aimed to evaluate the combined effects of stressful factors (temperature and pH) on the expression of biofilm, stress, and virulence genes in Salmonella Enteritidis and Salmonella Typhimurium. In this study, the effect of temperature (2, 8, 22.5, 37, 43 °C) and pH (2.4, 3, 4.5, 6, 6.6) on the expression of biofilm production genes (adr A, bap A), virulence genes (hil A, inv A) and the stress gene (RpoS) of S. Enteritidis and S. Typhimurium was evaluated. The response surface methodology (RSM) approach was used to evaluate the combined effect of the above factors. The highest expression of adr A, bap A, hil A, and RpoS gene for S. Typhimurium was at 22 °C-pH 4.5 (6.39-fold increase), 37 °C-pH 6 (3.92-fold increase), 37 °C-pH 6 (183-fold increase), and 37 °C-pH 3 (43.8-fold increase), respectively. The inv A gene of S. Typhimurium was decreased in all conditions. The adr A, bap A, hil A, inv A, and RpoS gene of S. Enteritidis had the highest expression level at 8 °C-pH 3 (4.09-fold increase), 22 °C-pH 6 (2.71-fold increase), 8 °C pH 3 (190-fold increase), 22 °C-pH 4.5 (9.21-fold increase), and 8 °C-pH 3 (16.6-fold), respectively. Response surface methodology (RSM) indicated that the temperature and pH had no significant effect on the expression level of adr A, bap A, hil A, Inv A, and RpoS gene in S. Enteritidis and S. Typhimurium. The expression of biofilm production genes (adr A, bap A), virulence genes (hil A, inv A) and the stress gene (RpoS) of S. Enteritidis and S. Typhimurium is not directly and exclusively associated with temperature and pH conditions.

Use of Salmonella Bacteria in Cancer Therapy: Direct, Drug Delivery and Combination Approaches.

Over the years, conventional cancer treatments, such as chemotherapy with only a limited specificity for tumors, have undergone significant improvement. Moreover, newer therapies such as immunotherapy have undergone a revolution to stimulate the innate as well as adaptive immune responses against the tumor. However, it has been found that tumors can be selectively colonized by certain bacteria, where they can proliferate, and exert direct oncolytic effects as well as stimulating the immune system. Bacterial-mediated cancer therapy (BMCT) is now one example of a hot topic in the antitumor field. Salmonella typhimurium is a Gram-negative species that generally causes self-limiting gastroenteritis in humans. This species has been designed and engineered in order to be used in cancer-targeted therapeutics. S. typhimurium can be used in combination with other treatments such as chemotherapy or radiotherapy for synergistic modification of the tumor microenvironment. Considerable benefits have been shown by using engineered attenuated strains for the diagnosis and treatment of tumors. Some of these treatment approaches have received FDA approval for early-phase clinical trials. This review summarizes the use of Salmonella bacteria for cancer therapy, which could pave the way towards routine clinical application. The benefits of this therapy include an automatic self-targeting ability, and the possibility of genetic manipulation to produce newly engineered attenuated strains. Nevertheless, Salmonella-mediated anticancer therapy has not yet been clinically established, and requires more research before its use in cancer treatment.

The occurrence of Adrenocorticotropic hormone-independent Cushing's syndrome in a woman with the history of papillary thyroid carcinoma: a case report.

BACKGROUND: Thyroid papillary carcinoma is one of the most common endocrine tumors, and it accounts for 85% of thyroid tumors. Adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome is a rare disease. In this case report, we discuss a very rare case of coexistence of papillary thyroid carcinoma and Cushing's syndrome with an adrenal origin. CASE PRESENTATION: The patient was a 33-year-old Iranian/Persian woman with a history of papillary thyroid carcinoma treated with iodine 131 three years ago. She presented with weight gain, amenorrhea, and mood disorders in the last six months. She was diagnosed with an ACTH-independent Cushing's syndrome due to benign adrenal adenoma and underwent laparoscopic adrenalectomy surgery. The symptoms of the syndrome were disappeared after the surgery. CONCLUSIONS: ACTH-independent Cushing's syndrome due to adrenal tumor and papillary thyroid cancer occurs sporadically. The co-occurrence of two endocrine tumors with different origins is rare. It is recommended that the occurrence of other endocrine neoplasms be considered when an endocrine tumor is diagnosed.

Clinical, epidemiological, laboratory, and radiological characteristics of novel Coronavirus (2019-nCoV) in retrospective studies: A systemic review and meta-analysis.

BACKGROUND: In December 2019, a novel pneumonia related to the 2019 coronavirus unexpectedly developed in Wuhan, China. We aimed to review data of the novel Coronavirus (2019-nCoV) by analyzing all the published retrospective studies on the clinical, epidemiological, laboratory, and radiological characteristics of patients with 2019-nCoV. METHODS: We searched in four bibliographic databases PubMed, Scopus, Embase, and Web of Science) for studies March 10, 2020 focused on the clinical, epidemiological, laboratory, and radiological characteristics of patients with 2019-nCoV for meta-analysis. The Newcastle-Ottawa Scale was used to quality assessment, and publication bias was analyzed by Egger's test. In the meta-analysis, a random-effects model with Stata/SE software, v.14.1 (StataCorp, College Station, TX) was used to obtain a pooled incidence rate. RESULTS: Fifty studies were included in this systematic review and meta-analysis with 8815 patients and the mean age was 46 years and 4647 (52.7%) were male. The pooled incidences rate of clinical symptoms were: fever (83%, 95% CI: 0.77, 0.89), cough (59%, 95% CI: 0.48, 0.69), myalgia or fatigue (31%, 95% CI: 0.23, 0.39), sputum production (29%, 95% CI: 0.21, 0.39), and dyspnea (19%, 95% CI: 0.12, 0.26). The pooled incidence rate of acute respiratory distress syndrome (ARDS) was (22%, 95% CI: 0.00, 0.60). CONCLUSION: The results of this systemic review and meta-analysis present a quantitative pooled incidence rate of different characters of 2019-nCoV and has great potential to develop diagnosis and patient's stratification in 2019-nCoV. However, this conclusions of this study still requisite to be warranted by more careful design, larger sample size multivariate studies to corroborate the results of this meta-analysis.

Systemic lupus erythematosus manifestation following COVID-19: a case report.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex and challenging autoimmune disease. Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) is a novel viral agent that can cause a life-threatening respiratory disorder named coronavirus disease 2019 (COVID­19). Association between SARS­CoV­2 and SLE is not clear. We reported the first case of SLE manifestation following COVID-19. CASE PRESENTATION: A 39-year-old Iranian/Persian man with complaints of fever, scaling on the palms of the hands and feet, lower extremity edema, and ankle swelling was referred to Kashan Rheumatology Clinic in 2020. He was infected with SARS-CoV-2 2 months ago. The patient had proteinuria and was positive for SLE laboratory tests. After one week of treatment with prednisolone (30 mg daily) and hydroxychloroquine, paresthesia, proteinuria, and edema continued. The patient was treated with pulse methylprednisolone (1000 mg for three consecutive days), gabapentin, and vitamin B (300 mg daily), which reduced paresthesia. CONCLUSIONS: This is the first case of SLE manifestation following COVID-19. SARS-CoV-2 may produce autoantibodies or develop the clinical features of subclinical SLE.

The landscape of extrapulmonary manifestations of human parainfluenza viruses: A systematic narrative review.

Human parainfluenza virus (HPIV) infection is associated with every kind of respiratory tract illnesses, including the common cold, laryngotracheobronchitis (i.e. croup), tracheobronchitis, bronchiolitis, and pneumonia, in both children and adults. Although HPIVs are common respiratory pathogens, there are increasing reports about extrapulmonary manifestations of HPIVs infection. Each of the HPIVs could produce infection of other organs (central nervous system, heart, myocardium, etc.) in all age groups who are either immunocompetent or immunocompromised. This review aimed at summarizing the available data on clinical manifestations of HPIV infection outside the respiratory tract from 1961 to 2020. The findings support the possibility of extrapulmonary infections that were thought to be due to rare host genetic or immunologic defects in infected patients. These findings highlight the fact that extrapulmonary dissemination of HPIV can occur, but the association is not clearly demonstrated. Our data support the hypothesis that HPIV infection is one of the possible causes of these alterations and may even be the direct cause in some cases.

The impact of spike mutated variants of SARS-CoV2 [Alpha, Beta, Gamma, Delta, and Lambda] on the efficacy of subunit recombinant vaccines

ABSTRACT Since the first described human infection with SARS-CoV-2 in December of 2019 many subunit protein vaccines have been proposed for use in humans. Subunit vaccines use one or more antigens suitable for eliciting a robust immune response. However, the major concern is the efficacy of subunit vaccines and elicited antibodies to neutralize the variants of SARS-CoV-2 like B.1.1.7 (Alpha), B.1.351 (Beta) and P1 (Gamma), B.1.617 (Delta) and C.37 (Lambda). The Spike protein (S) is a potential fragment for use as an antigen in vaccine development. This protein plays a crucial role in the first step of the infection process, as it binds to Angiotensin-Converting Enzyme 2 (ACE2) receptor and enters the host cell after binding. Immunization-induced specific antibodies against the receptor binding domain (RBD) may block and effectively prevent virus invasion. The focus of this review is the impact of spike mutated variants of SARS-CoV2 (Alpha, Beta, Gamma, Delta, and Lambda) on the efficacy of subunit recombinant vaccines. To date, a low or no significant impact on vaccine efficacy against Alpha and Delta variants has been reported. Such an impact on vaccine efficacy for Beta, Delta, Gamma, and Lambda variants may be even greater compared to the Alpha variant. Nonetheless, more comprehensive analyses are needed to assess the real impact on vaccine efficacy brought about by SARS-CoV-2 variants.

Prevalence of torque teno virus in healthy individuals and those infected with hepatitis C virus living in Yazd, Iran.

BACKGROUND: Torque teno virus (TTV) is a non-enveloped DNA virus that its role as a helper or causative agent in hepatitis is still unclear. TTV prevalence varies in different regions of the world. This study aimed to determine the prevalence of TTV in healthy individuals and those infected with hepatitis C virus (HCV) living in Yazd city, Iran. METHODS: In this case-control study, 50 healthy subjects and 68 HCV-positive individuals who referred to Yazd hospitals participated in this study. TTV DNA in serum samples were detected by nested polymerase chain reaction (PCR) using specific primers of 5΄-UTR and N22 regions. The genotypes of HCV and TTV were determined by sequencing method. RESULTS: TTV-DNA was detected in 2 out of 50 (4℅) healthy individuals and in 4 out of 68 (5.8℅) HCV-positive persons. There was not a significant correlation between the prevalence of TTV and HCV infection. The most common TTV genotypes among HCV-positive individuals were 3, 17 and 13, respectively. There was not a significant association obtained between HCV genotypes and TTV genotypes. CONCLUSION: The prevalence of TTV in Yazd province was low compared with the other areas of Iran. The prevalence of TTV in HCV infected people was not significantly higher than its rate in uninfected individuals.

P16INK4A Immunohistochemistry as a Gold Standard for Cervical Cancer and Precursor Lesions Screening.

BACKGROUND: High-risk (HR) Human papillomaviruses (HPVs) are known as the main factors implicated in the pathogenesis of cervical preinvasive and invasive lesions. Therefore, the presence or absence of HR-HPV can be followed for the prognosis of low-grade and high-grade squamous intraepithelial lesions. Since the overexpression of p16INK4a protein depends on the presence of transcriptionally-active HPV, and due to its availability and simple interpretation, it may be considered as a proper marker to diagnose cervical cancer. METHODS: An immunohistochemical analysis of p16INK4a was performed in 72 cervical tissue specimens at Imam Khomeini Complex Hospital (Tehran, Iran) from 2016 to 2018. The performance parameters were calculated and compared using receiving operating characteristics curve (ROC) details. RESULTS: p16INK4a is significantly up-regulated in the cervical cancer samples in comparison with that in normal samples. Moreover, the ROC data showed the potential ability of p16INK4a under determined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. The molecular typing disclosed the attendance of HPV DNA in 44.4% of cases (32/72) with a predominance of HPV type 16. CONCLUSION: The molecular biomarker p16INK4a can be a good candidate for the early diagnosis and prognosis of cervical cancer in HPV-infected patients. Considering the increase in the expression level of p16INK4a in cancer and precancer tissues, p16INK4a may be used for early detection of cervical cancer.

The study of factors associated with pregnancy outcomes in patients with systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease that can lead to unfavorable pregnancy complications in women. This study aimed to evaluate the factors associated with pregnancy outcomes in patients with SLE. RESULTS: Fifty-nine pregnant women with SLE (121 pregnancies) participated in this retrospective cohort study. The mean age of the patients was 33.74 ± 3.80 years (range 21 to 48 years). Fetal loss occurred in 43.8% of pregnancies. The most common laboratory findings in SLE patients were antinuclear antibody (81.4%) and anti-ds DNA positivity (54.2%). High levels of C-reactive protein (CRP) during pregnancy, renal involvement, anti-double-stranded DNA positivity, anti-phospholipid antibody (APA) positivity and younger age at disease onset were significantly correlated with unfavourable pregnancy outcomes. A significant difference was observed between duration of SLE and low birth weight (P = 0.003), pre-eclampsia (P = 0.012) and still birth (P = 0.036). High CRP, APA positivity, anti-dsDNA positivity and kidney involvement were predictors of adverse pregnancy outcomes in SLE patients. Renal involvement increased risk of pregnancy with complication 8.5 times (OR = 8.5, 95% CI 1.396-63.373, P = 0.017). Antiphospholipid syndrome (APS) also was associated with an odds ratio of 5.18 (95% CI 1.681-13.647, P = 0.001).

A Case of Antiphospholipid Syndrome Following Gastric Signet Ring Cell Adenocarcinoma.

BACKGROUND Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by arterial, venous, and small-vessel thrombosis, pregnancy-related morbidity and the presence of antiphospholipid antibodies such as anticardiolipin antibody, and/or anti-beta2-glycoprotein I. In the recent years, APS was observed in patients with solid tumors and the renal cancer, lung carcinoma and breast tumors were the most common tumors linked with APS. CASE REPORT A 53-year-old female presented with pain and pitting edema of left lower extremity that had begun 6 months prior to hospitalization. Deep vein thrombosis (DVT) in the popliteal vein diagnosed by Doppler ultrasonography and the patient was treated with heparin followed by warfarin. Following subdural hematoma, anticoagulant therapy was stopped, and the patient underwent craniotomy. One month later, the patient returned with pain and DVT diagnosed in its right leg. Laboratory tests showed high levels of lupus anticoagulant, IgM and IgG anticardiolipin antibodies. Following a high alkaline phosphatase, diffuse bone marrow involvement was found by whole body bone scan. Looking to find primary tumor, a large infilterable lesion in gastric was seen by endoscopic images, and biopsy histopathology showed a signet ring cell adenocarcinoma. The patient refused chemotherapy and died 6 months after diagnosis. CONCLUSIONS APS is associated with gastric signet ring cell adenocarcinoma.