Unraveling the dynamic mechanisms of natural killer cells in viral infections: insights and implications.

Viruses pose a constant threat to human well-being, necessitating the immune system to develop robust defenses. Natural killer (NK) cells, which play a crucial role in the immune system, have become recognized as vital participants in protecting the body against viral infections. These remarkable innate immune cells possess the unique ability to directly recognize and eliminate infected cells, thereby contributing to the early control and containment of viral pathogens. However, recent research has uncovered an intriguing phenomenon: the alteration of NK cells during viral infections. In addition to their well-established role in antiviral defense, NK cells undergo dynamic changes in their phenotype, function, and regulatory mechanisms upon encountering viral pathogens. These alterations can significantly impact the effectiveness of NK cell responses during viral infections. This review explores the multifaceted role of NK cells in antiviral immunity, highlighting their conventional effector functions as well as the emerging concept of NK cell alteration in the context of viral infections. Understanding the intricate interplay between NK cells and viral infections is crucial for advancing our knowledge of antiviral immune responses and could offer valuable information for the creation of innovative therapeutic approaches to combat viral diseases.

Therapeutic approaches for HTLV-1-associated adult T-cell leukemia/lymphoma: a comprehensive review.

Adult T-cell leukemia/lymphoma (ATLL), an infrequent malignancy resultant from human T-cell lymphotropic virus type I (HTLV-1), exhibits a spectrum of phenotypes, encompassing acute, smoldering, lymphomatous, and chronic variants, each bearing distinct clinical presentations. The preponderant acute manifestation is characterized by hypercalcemia, systemic manifestations, organomegaly, and dermatological eruptions. Conversely, the chronic phenotype is typified by lymphocytosis and/or cutaneous eruptions, while smoldering ATLL assumes an asymptomatic course. Immunocompromise afflicts ATLL patients, heightening their vulnerability to opportunistic infections that frequently intricately intertwine with disease progression. Therefore, an early diagnosis is crucial to manage the disease appropriately. While conventional chemotherapeutic regimens have shown limited success, especially in acute and lymphoma types, recent studies suggest that allogeneic stem cell transplantation might enhance treatment results because it has shown promising outcomes in some patients. Novel therapeutics, such as interferon and monoclonal antibodies, have also shown promise, but more research is needed to confirm their efficacy. Moreover, the identification of biomarkers for ATLL and genetic changes in HTLV-1 infected cells has led to the development of targeted therapies that have shown remarkable success in clinical trials. These targeted therapies have the potential to offer a more personalized approach to the treatment of ATLL. The aim of our review is to elaborate on conventional and novel therapies and the efficiency of mentioned treatments.

Video Scene Detection Using Transformer Encoding Linker Network (TELNet).

This paper introduces a transformer encoding linker network (TELNet) for automatically identifying scene boundaries in videos without prior knowledge of their structure. Videos consist of sequences of semantically related shots or chapters, and recognizing scene boundaries is crucial for various video processing tasks, including video summarization. TELNet utilizes a rolling window to scan through video shots, encoding their features extracted from a fine-tuned 3D CNN model (transformer encoder). By establishing links between video shots based on these encoded features (linker), TELNet efficiently identifies scene boundaries where consecutive shots lack links. TELNet was trained on multiple video scene detection datasets and demonstrated results comparable to other state-of-the-art models in standard settings. Notably, in cross-dataset evaluations, TELNet demonstrated significantly improved results (F-score). Furthermore, TELNet's computational complexity grows linearly with the number of shots, making it highly efficient in processing long videos.

Epidemiology of injuries during Iran wheelchair basketball professional league: predictive risk factors and prevention strategies.

BACKGROUND: Very few studies have investigated athletes with disabilities during a long period of competitions, such as a professional league. Also, there are limited findings related to specific mechanisms and risk factors of injury, and prevention strategies in Wheelchair Basketball. Therefore, the objective of this study was to investigate the rate and characteristics of injuries in the 2021-2022 Iran Wheelchair Basketball League and present prevention strategies. METHODS: This retrospective study was conducted after the 2021-2022 (Mar 2021-Sep 2022) competition season. The sample size consists of 36 players, who were randomly selected among 129 players. All the data was processed using SPSS (version 21). RESULTS: 111 injuries were registered, equivalent to 132 per 100 players (95% CI: 100-180) and 8.16 Injuries per 1000 hours of athlete exposure (6.2-9.8). Also, 77.8% occurred during training and 22.2% in competitions. Most injuries affected the fingers and hands (35.13%), and shoulders (22.57%). The most common types of injuries were contusions (30.63%), laceration and skin lesion (23.42%), and muscle spasms (13.51%), in which, half of the injuries were slight (0-1 days), 27.8% (mild 4-7 days), and 22.2% moderate (8-28 days). Also, 66.9% of injuries were new, and 33.1% were recurrent. Most situations and actions leading to injury include quick wheelchair pushing (29.72%), the intense ball hitting (17.14%), and sudden stops or changes of direction of the wheelchair (12.63%). A multiple linear regression analysis (Enter method) demonstrated (R2 Adjusted=0.530) Wheelchair inappropriateness (P=0.015), lack of protective equipment (P=0.028), and previous injury (P=0.003) explained close to 55% of the injury rate. CONCLUSIONS: The injury rate during the league period was higher than the amounts reported from Paralympic games. Prevention strategies should be focused on rethinking athletes' pre-season readiness evaluation, return to play assessments and protection equipment technologies.

Exploring the correlation between progression of human papillomavirus infection towards carcinogenesis and nutrition.

Human papillomavirus (HPV) is a common sexually transmitted virus that can lead to the development of various types of cancer. While there are vaccines available to prevent HPV infection, there is also growing interest in the role of nutrition in reducing the risk of HPV-related cancers in HPV positive patients. Diet and nutrition play a critical role in maintaining overall health and preventing various diseases. A healthy diet can strengthen the immune system, which is essential for fighting off infections, including HPV infections, and preventing the growth and spread of cancer cells. Therefore, following a healthy diet and maintaining a healthy weight are important components of HPV and cancer prevention. This article explores the current scientific evidence on the relationship between nutrition and HPV, including the impact of specific nutrients, dietary patterns, and supplements on HPV infection toward cancer progression.

Investigating the effect of MAP2K1 gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL).

Background and Objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals. Materials and Methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software. Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database. Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.

Possible ameliorative role of Spirulina platensis on coagulation factors, lymphocytopenia, and malnutrition in ICU patients with COVID-19.

Considering the anti-viral effects of Spirulina platensis (Sp), this study investigated the impact of Sp on impaired blood biomarkers of patients hospitalized in the intensive care unit (ICU) with COVID-19. Therefore, 104 patients (aged 48-66; 61.5% male) were randomly assigned to the Sp (daily consumption of 5 g) or placebo group for 2 weeks. Linear regression analysis was employed to assess the differences in blood test results between the control and intervention groups among patients with COVID-19. Our results showed significant differences in certain hematological tests, including a higher level of hematocrit (HCT) and a lower platelet count (PLT) in the intervention group (p < 0.05). The percentage of lymphocytes (Lym%) in serology testing was significantly different between the control and intervention groups (p = 0.03). In terms of biochemical test analyses, Sp supplementation was associated with reduced levels of both blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) (p = 0.01). Furthermore, on day 14, the intervention group displayed significantly higher medians of serum protein, albumin, and zinc compared to the control group (p < 0.05). Additionally, patients supplemented with Sp had a lower BUN-albumin ratio (BAR) (p = 0.01). No immunological and hormonal differences were observed between groups following 2 weeks. Our analysis indicates that Sp supplementation may be effective in regulating some blood test abnormalities associated with COVID-19. This study was registered at ISRCTN as IRCT20200720048139N1.

Characterization of occult hepatitis B infection among Iranian liver transplant recipients.

BACKGROUND: The prevalence of occult hepatitis B infection (OBI) among Iranian liver transplant recipient patients has not been explored yet. The present study aimed to determine the OBI prevalence among Iranian liver transplant recipients. METHODS: This study encompassed 97 patients having undergone liver transplantation due to several clinical backgrounds in the Liver Transplantation Center, Tehran, Iran. After serological evaluation, two different types of PCR methods were applied for amplification of HBV DNA, followed by the direct sequencing of whole hepatitis B virus (HBV) surface genes. RESULTS: At the time of admission, none of the patients were positive for HBsAg. However, 24 (25%), 12 (12.3%), and 5 (5.1%) cases were positive for anti-HBc, hepatitis C virus (HCV), and hepatitis delta virus (HDV) antibodies, respectively. Moreover, two males were positive for OBI (2.1%). Both were positive for anti-HBc and negative for anti-HBs, anti-HCV, and anti-HDV. HBV-related cirrhosis was the underlying reason for their liver transplantation. HBsAg sequences revealed no amino acid substitution. CONCLUSIONS: The prevalence of OBI in the Iranian liver transplantation patients was relatively low. Future longitudinal studies with a larger sample size are suggested to explore the significance of this clinical finding, including the reactivation of cryptic HBV DNA, in liver transplant subjects.

Selective APC-targeting of a novel Fc-fusion multi-immunodominant recombinant protein (tTax-tEnv:mFcγ2a) for HTLV-1 vaccine development.

AIMS: HTLV-1 causes two life-threatening diseases: adult T-cell leukaemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis. Due to the lack of proper treatment, an effective HTLV-1 vaccine is urgently needed. MAIN METHODS: DNA sequences of 11-19 and 178-186 amino acids of HTLV-1-Tax and SP2 and P21 were fused to the mouse-Fcγ2a, or His-tag called tTax-tEnv:mFcγ2a and tTax-tEnv:His, respectively. These constructs were produced in Pichia pastoris, and their immunogenicity and protective properties were assessed in a mouse challenging model with an HTLV-1-MT2 cell line. KEY FINDINGS: The immunogenicity assessments showed significant increase in IFN-γ production in animals receiving tTax-tEnv:mFcγ2a (1537.2 ± 292.83 pg/mL) compared to tTax-tEnv:His (120.28 ± 23.9, p = 0.02). IL-12 production also increased in group receiving tTax-tEnv:mFcγ2a than tTax-tEnv:His group, (23 ± 2.6 vs 1.5 ± 0.6, p = 0.01), respectively. The IFN-γ and IL-12 levels in the Fc-immunised group were negatively correlated with PVL (R = -0.82, p < 0.04) and (R = -0.87, p = 0.05), respectively. While, IL-4 was increased by tTax-tEnv:His (21.16 ± 1.76 pg/mL) compared to tTax-tEnv:mFcγ2a (13.7 ± 1.49, p = 0.019) with a negative significant correlation to PVL (R = -0.95, p = 0.001). SIGNIFICANCE: The mouse challenging assay with tTax-tEnv:mFcγ2a showed 50 % complete protection and a 50 % low level of HTLV-1-PVL compared to the positive control receiving HTLV-1-MT2 (p = 0.001). Challenging experiments for the His-tag protein showed the same outcome (p = 0.002) but by different mechanisms. The Fc-fusion construct induced more robust Th1, and His-tag protein shifted more to Th2 immune responses. Therefore, inducing both T helper responses, but a Th1/Th2 balance in favour of Th1 might be necessary for appropriate protection against HTLV-1 infection, spreading via cell-to-cell contact manner.

Signaling factors potentially associated to the pathogenesis of Adult T-cell leukemia /lymphoma: A network-analysis and novel findings assessment.

Adult T-cell leukemia/lymphoma (ATLL) is a human T-cell leukemia virus (HTLV) type 1-associated disease of TCD4+ cell transformation. Despite extensive studies on ATLL development and progression, the fundamental processes of HTLV-1 oncogenicity are yet to be understood. This study aimed to integrate high-throughput microarray datasets to find novel genes involved in the mechanism of ATLL progression. For this purpose, five microarray datasets were downloaded from the Gene Expression Omnibus database and then profoundly analyzed. Differentially expressed genes and miRNAs were determined using the MetaDE package in the R software and the GEO2R web tool. The STRING database was utilized to construct the protein-protein interaction network and explore hub genes. Gene ontology and pathway enrichment analysis were carried out by employing the EnrichR web tool. Furthermore, flow cytometry was employed to assess the CD4/CD8 ratio, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm the high-throughput data analysis results. Four miRNAs, including hsa-mir-146, hsa-mir-451, hsa-mir-31, and hsa-mir-125, were among the statistically significant differentially expressed miRNAs between healthy individuals and ATLL patients. Moreover, 924 differentially expressed genes were identified between normal and ATLL samples. Further network analysis highlighted 59 hub genes mainly regulating pathways implicated in viral interferences, immunological processes, cancer, and apoptosis pathways. Among the identified hub genes, RhoA and PRKACB were most considerable in the high-throughput analysis and were further validated by qRT-PCR. The RhoA and PRKACB expression were significantly down-regulated in ATLL patients compared to asymptomatic carriers (p<0.0001 and p=0.004) and healthy subjects (p=0.043 and p=0.002). Therefore, these corresponding miRNAs and proteins could be targeted for diagnosis purposes and designing effective treatments.

Identifying Potential New Gene Expression-Based Biomarkers in the Peripheral Blood Mononuclear Cells of Hepatitis B-Related Hepatocellular Carcinoma.

Objective: The analysis of the gene expression of peripheral blood mononuclear cells (PBMCs) is important to clarify the pathogenesis of hepatocellular carcinoma (HCC) and the detection of suitable biomarkers. The purpose of this investigation was to use RNA-sequencing to screen the appropriate differentially expressed genes (DEGs) in the PBMCs for the HCC. Methods: The comprehensive transcriptome of extracted RNA of PBMC (n = 20) from patients with chronic hepatitis B (CHB), liver cirrhosis, and early stage of HCC (5 samples per group) was carried out using RNA-sequencing. All raw RNA-sequencing data analyses were performed using conventional RNA-sequencing analysis tools. Next, gene ontology (GO) analyses were carried out to elucidate the biological processes of DEGs. Finally, relative transcript abundance of selected DEGs was verified using qRT-PCR on additional validation groups. Results: Specifically, 13, 1262, and 1450 DEGs were identified for CHB, liver cirrhosis, and HCC, when compared with the healthy controls. GO enrichment analysis indicated that HCC is closely related to the immune response. Seven DEGs (TYMP, TYROBP, CD14, TGFBI, LILRA2, GNLY, and GZMB) were common to HCC, cirrhosis, and CHB when compared to healthy controls. The data revealed that the expressions of these 7 DEGs were consistent with those from the RNA-sequencing results. Also, the expressions of 7 representative genes that had higher sensitivity were obtained by receiver operating characteristic analysis, which indicated their important diagnostic accuracy for HBV-HCC. Conclusion: This study provides us with new horizons into the biological process and potential prospective clinical diagnosis and prognosis of HCC in the near future.

A multicenter retrospective study of clinical features, laboratory characteristics, and outcomes of 166 hospitalized children with coronavirus disease 2019 (COVID-19): A preliminary report from Iranian Network for Research in Viral Diseases (INRVD).

BACKGROUND: The objectives of this study were to analyze the clinical features and laboratory profiles and risk factors associated with critical illness of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: One hundred and sixty-six coronavirus disease 2019 (COVID-19) Iranian pediatric patients were recruited through a collaborative research network between March and May 2020. Demographics, clinical, laboratory, and radiological results were obtained from patient files. RESULTS: Of 166 patients, 102 (61%) and 64 (39%) were males and females, respectively. Ninety-six (57.8%) and 70 (42.2%), had moderate and severe conditions, respectively. Thirty (18%) of patients died. The common symptoms were fever (73%), cough (54%), and shortness of breath, headache decrease in neutrophil and platelet counts; increase values in lactate dehydrogenase, decrease in the blood pH and HCO3 were significantly associated with the disease severity. 54% and 56% of patients showed abnormal radiographic appearance in Chest X-ray and in chest computed tomography scan, respectively. Sixty-one (36.7%) of patients were referred to intensive care unit (ICU). The coexistence of comorbidity was the main factor associated with ICU admission, shock, arrhythmia, acute kidney injury, acute respiratory distress syndrome, acute cardiac injury, and death. CONCLUSIONS: We describe a higher than previously recognized rate of COVID-19 mortality in Iranian pediatric patients. Epidemiological factors, such as the relatively high case fatality rate in the country and the presence of underlying diseases were the main factors for the high death rate.

The Barriers, Challenges, and Strategies of COVID-19 (SARS-CoV-2) Vaccine Acceptance: A Concurrent Mixed-Method Study in Tehran City, Iran.

Acceptance and willingness to receive the vaccine are among the main factors in the success or failure of a health system in implementing the vaccination program. The present study was conducted in Tehran, the political and economic capital of Iran, to determine the acceptance of the COVID-19 vaccine and identify its associated factors, and explain the most important barriers and acceptance strategies for vaccination. This research was a concurrent quantitative and qualitative mixed-method study. In the quantitative part, 1200 individuals aged more than 18 years were selected from the households in 22 districts of Tehran City, with a multistage stratified cluster sampling method. Two questionnaires were used to evaluate the acceptance of the COVID-19 vaccine and vaccine acceptance determinants. The qualitative content analysis method addressed the influencing factors, as well as challenges and strategies related to the acceptance of the COVID-19 vaccine in four groups of Tehran inhabitants: the elderly, people with underlying diseases, healthcare workers, and the general population. The related data were simultaneously collected by applying in-depth semi-structural interviews and a data analysis process. Furthermore, we used the Graneheim and Lundman method for data analysis. We analyzed the data of 1200 people with a mean (SD) age of 46.4 (11.1) years, and approximately 58% of them were men. The vaccine acceptance was 83.6% (95% CI: 81.3-85.9). Among those who welcomed vaccination, 58% preferred the imported vaccines, 25% the Iranian ones, and 17% both. There was a significant association between the variables of age (adjusted odds ratio [AOR] = 1.72, 95% CI: 1.01-2.93), being single (AOR = 0.54, 95% CI: 0.41-0.91), moderate pharmacotherapy adherence (AOR = 0.58, 95% CI: 0.4-0.85), and the willingness to receive COVID-19 vaccine. Qualitative study after interviewing 45 people from four study groups showed an insufficient social trust in healthcare system officials, pharmaceutical and vaccine production companies; distrust in the effectiveness of the vaccines, concerns about the vaccine adverse effects, being tracked by microchips after vaccination, traditional anti-vaccination movements, the feeling the inessentiality of vaccination, and uncertainty about the fair distribution of the vaccine. These concerns were the main challenges addressed by the study groups. A good proportion of Tehran residents reported their willingness to receive the COVID-19 vaccine. Additionally, they expressed their critical concerns, such as insufficient trust in the healthcare system, vaccine safeties, and adverse effects that were the significant barriers to vaccine acceptance. It seems that conflicts raised by the shortage of vaccines and their import due to the sanctions have led to intense desire and demand in the general population, and especially the elderly, for vaccination. Besides, vaccination phobia in some individuals requires further investigations.

Molecular epidemiology and phylogenetic analysis of human T-lymphotropic virus type 1 in the tax gene and it association with adult t-cell leukemia/lymphoma disorders.

BACKGROUND AND OBJECTIVES: Human T-lymphotropic virus type-1 (HTLV-1) belongs to retrovirus family that causes the neurological disorder HTLV-1 adult T-cell leukemia/lymphoma (ATLL). Since 1980, seven subtypes of the virus have been recognized. HTLV-1 is prevalent and endemic in some regions, such as Africa, Japan, South America and Iran as the endemic regions of the HTLV-1 in the Middle East. To study HTLV-1 subtypes and routes of virus spread in Iran, phylogenetic and phylodynamic analyses were performed and for as much as no previous phylogenetic studies were conducted in Tehran, we do this survey. To this purpose, the Tax region of HTLV-1 was used. MATERIALS AND METHODS: In this study 100 samples were collected from blood donors in Tehran. All samples were screened for anti-HTLV-I antibodies by ELISA. Then, genomic DNA was extracted from all positive samples (10 people), and for confirmation of infection, ordinary PCR was performed for both the HBZ and LTR regions. Moreover, the Tax region was amplified and purified PCR products were sequenced and analyzed, and finally, a phylogenetic tree was constructed using Mega X software. RESULTS: Phylogenetic analysis confirmed that isolates from Iran, Japan, Brazil, and Africa are located within the extensive "transcontinental" subgroup A clade of HTLV-1 Cosmopolitan subtype a. The Japanese sequences are the closest to the Iranian sequences and have the most genetic similarity with them. CONCLUSION: Through phylogenetic and phylodynamic analyses HTLV-1 strain in Tehran were characterized in Iran. The appearance of HTLV-1 in Iran was probably happened by the ancient Silk Road which linked China to Antioch.

Comprehensive high-throughput meta-analysis of differentially expressed microRNAs in transcriptomic datasets reveals significant disruption of MAPK/JNK signal transduction pathway in Adult T-cell leukemia/lymphoma.

BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) infection may lead to the development of Adult T-cell leukemia/lymphoma (ATLL). To further elucidate the pathophysiology of this aggressive CD4+ T-cell malignancy, we have performed an integrated systems biology approach to analyze previous transcriptome datasets focusing on differentially expressed miRNAs (DEMs) in peripheral blood of ATLL patients. METHODS: Datasets GSE28626, GSE31629, GSE11577 were used to identify ATLL-specific DEM signatures. The target genes of each identified miRNA were obtained to construct a protein-protein interactions network using STRING database. The target gene hubs were subjected to further analysis to demonstrate significantly enriched gene ontology terms and signaling pathways. Quantitative reverse transcription Polymerase Chain Reaction (RTqPCR) was performed on major genes in certain pathways identified by network analysis to highlight gene expression alterations. RESULTS: High-throughput in silico analysis revealed 9 DEMs hsa-let-7a, hsa-let-7g, hsa-mir-181b, hsa-mir-26b, hsa-mir-30c, hsa-mir-186, hsa-mir-10a, hsa-mir-30b, and hsa-let-7f between ATLL patients and healthy donors. Further analysis revealed the first 5 of DEMs were directly associated with previously identified pathways in the pathogenesis of HTLV-1. Network analysis demonstrated the involvement of target gene hubs in several signaling cascades, mainly in the MAPK pathway. RT-qPCR on human ATLL samples showed significant upregulation of EVI1, MKP1, PTPRR, and JNK gene vs healthy donors in MAPK/JNK pathway. DISCUSSION: The results highlighted the functional impact of a subset dysregulated microRNAs in ATLL on cellular gene expression and signal transduction pathways. Further studies are needed to identify novel biomarkers to obtain a comprehensive mapping of deregulated biological pathways in ATLL.

Effect of Ammonium Chloride in addition to standard of care in outpatients and hospitalized COVID-19 patients: A randomized clinical trial.

OBJECTIVE: The COVID-19 pandemic has called an urgent need for drug repurposing to improve the outcome of the disease. Quaternary ammonium compounds have been demonstrated to have antiviral effects and may be of use against SARS-CoV-2 infections. DESIGN: In this double-blind, single-center study, we enrolled patients with positive PCR test and/or CT findings for COVID-19. The participants of each group were randomly assigned to Diphenhydramine Compound (Diphenhydramine + Ammonium Chloride) plus standard of care or to Diphenhydramine alone and standard of care groups. The primary outcome was all-cause mortality within 30 days of randomization. Secondary outcomes include viral burden, clinical status, assessed by a 5-point ordinal scale, and length of stay in hospitalized patients. RESULTS: A total of 120 patients were included in the trial, 60 of which were assigned to the Ammonium Chloride group. The primary endpoint was not statistically different between the two groups (HR: 3.02 (95% CI, 0.57-16.06; p = 0.195)). Recovery time and viral burden were significantly lower in the Ammonium Chloride group, corresponding to an odds ratios of 1.8 (95% CI, 1.15-2.83; p = 0.01) and 7.90 (95% CI, 1.62-14.17; p = 0.014), respectively. CONCLUSION: The findings of this study advocate the careful addition of Ammonium Chloride to standard of care for COVID-19 patients.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) versus adult T-cell leukemia/lymphoma (ATLL).

OBJECTIVES: Human T cell leukemia virus-1 (HTLV-1) infection may lead to one or both diseases including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or adult T cell leukemia lymphoma (ATLL). The complete interactions of the virus with host cells in both diseases is yet to be determined. This study aims to construct an interaction network for distinct signaling pathways in these diseases based on finding differentially expressed genes (DEGs) between HAM/TSP and ATLL. RESULTS: We identified 57 hub genes with higher criteria scores in the primary protein-protein interaction network (PPIN). The ontology-based enrichment analysis revealed following important terms: positive regulation of transcription from RNA polymerase II promoter, positive regulation of transcription from RNA polymerase II promoter involved in meiotic cell cycle and positive regulation of transcription from RNA polymerase II promoter by histone modification. The upregulated genes TNF, PIK3R1, HGF, NFKBIA, CTNNB1, ESR1, SMAD2, PPARG and downregulated genes VEGFA, TLR2, STAT3, TLR4, TP53, CHUK, SERPINE1, CREB1 and BRCA1 were commonly observed in all the three enriched terms in HAM/TSP vs. ATLL. The constructed interaction network was then visualized inside a mirrored map of signaling pathways for ATLL and HAM/TSP, so that the functions of hub genes were specified in both diseases.

Phylogenetic and phylodynamic study of Human T-cell lymphotropic virus Type 1 (HTLV-1) in Iran.

Human T-lymphotropic virus type-1 (HTLV-1) is a retrovirus that causes the neurological disorder HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP) and/or adult T-cell leukemia/lymphoma (ATLL). Iran is one of the endemic regions of the HTLV-1 in the Middle East. To infer the origin of the virus in Iran and to follow the movements of human population and routes of virus spread to this country, phylogenetic and phylodynamic analyses were performed. To this purpose, the long terminal repeat (LTR) region of HTLV-1 was used. New LTR sequences were obtained from 100 blood samples which infected with HTLV-1. Moreover, all Iranian LTR sequences which have been reported so far, were obtained from GenBank database. Sequences were aligned and maximum-likelihood and Bayesian tree topologies were explored. After identification of Iranian specific cluster, molecular-clock and coalescent models were used to estimate time to the most recent common ancestor (tMRCA). Bayesian Skyline Plots (BSP), representing population dynamics HTLV-1 strains back to the MRCA, were estimated using BEAST software. Phylogenetic analysis demonstrated that the Iranian, Kuwaiti, German, Israelite and southern Indian isolates are located within the widespread "transcontinental" subgroup A clade of HTLV-1 Cosmopolitan subtype a. Molecular clock analysis of the Iranian cluster dated back their respective tMRCA to be 1290 AC with a 95% HPD confidence intervals (918, 1517). BSPs indicated a rapid exponential growth rate in the effective number of infections prior the 15th century. Our results support the hypothesis of a multiple introductions of HTLV-1 into Iran with the majority of introductions occurring in prior the 15th century, at the same time the Mongol invasion of Iran. Our results further suggest that HTLV-1 introduction into Iran was facilitated by the commercial/migratory linkage as known as the ancient Silk Road which linked China to Antioch (now in Turkey).

Nanotechnology based strategies for HIV-1 and HTLV-1 retroviruses gene detection.

Early detection of retroviruses including human T-cell lymphotropic virus and human immunodeficiency virus in the human body is indispensable to prevent retroviral infection propagation and improve clinical treatment. Until now, diverse techniques have been employed for the early detection of viruses. Traditional methods are time-consuming, resource-intensive, and laborious performing. Therefore, designing and constructing a selective and sensitive diagnosis system to detect serious diseases is highly demanded. Genetic detection with high sensitivity has striking significance for the early detection and remedy of disparate pathogenic diseases. The nucleic acid biosensors are based on the identification of specific DNA sequences in biological samples. Nanotechnology has an important impact on the development of sensitive biosensors. Different kinds of nanomaterials include nanoparticles, nanoclusters, quantum dots, carbon nanotubes, nanocomposites, etc., with different properties have been used to improve the performance of biosensors. Recently, DNA nanobiosensors are developed to provide simple, fast, selective, low-cost, and sensitive detection of infectious diseases. In this paper, the research progresses of nano genosensors for the detection of HIV-1 and HTLV-1 viruses, based on electrochemical, optical, and photoelectrochemical platforms are overviewed.

Phytochemical Composition and Anti-Efflux Pump Activity of Hydroalcoholic, Aqueous, and Hexane Extracts of Artemisia tournefortiana in Ciprofloxacin-Resistant Strains of Salmonella enterica Serotype Enteritidis.

BACKGROUND: The AcrB efflux pump in Salmonella species plays a significant role in the development of antibiotic resistance in ciprofloxacin-resistant Salmonella enteritidis. This study aimed to investigate the anti-efflux pump activity of Artemisia tournefortiana extracts among S. Enteritidis strains. METHODS: The hydroalcoholic, aqueous, and hexanolic extracts of A. tournefortiana were prepared and phytochemical composition of extract was determined using gas chromatography/mass spectrometry (GC/MS) method. After antibiogram, the AcrB efflux pump was detected in ciprofloxacin intermediate and resistant S. enteritidis strains using cartwheel and Polymerase chain reaction (PCR) methods. Finally, minimum inhibitory concentrations (MIC) of extracts against S. enteritidis strains were evaluated. After treatment of S. enteritidis strains with sub-MIC concentrations of extracts, the expression level of AcrB efflux pump gene was evaluated using Real-Time PCR. RESULTS: Phytochemical analysis of extracts using GC/MS method showed that hexadecanoic acid, ethyl ester (30.7%), and cyclopropane,1-(1-hydroxy-1-heptyl)-2-methylene-3-pentyl (17.8%) were the most dominant volatile components volatile compounds in the extract. The results of antibiogram, cartwheel and PCR methods showed that among 20 strains of S. enteritidis that were resistant and intermediate to ciprofloxacin, 16 strains had AcrB efflux pumps. Finally, Real-Time PCR results showed a significant down-regulation of acrB gene in S. enteritidis strains. CONCLUSION: A. tournefortiana had anti-efflux activity and this plant can potentially be used as a natural efflux inhibitor for S. enteritidis strains.