Zidovudine and Interferon Alfa based regimens for the treatment of adult T-cell leukemia/lymphoma (ATLL): a systematic review and meta-analysis.

BACKGROUND: ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1 (HTLV-1), is challenging to treat. There is no known treatment for ATLL as of yet. However, it is recommended to use Zidovudine and Interferon Alfa-based regimens (AZT/IFN), chemotherapy, and stem cell transplant. This study aims to review the outcome of patients with different subtypes of ATLL treated with Zidovudine and Interferon Alfa-based regimens. METHODS: A systematic search was carried out for articles evaluating outcomes of ATLL treatment by AZT/IFN agents on human subjects from January 1, 2004, until July 1, 2022. Researchers assessed all studies regarding the topic, followed by extracting the data. A random-effects model was used in the meta-analyses. RESULTS: We obtained fifteen articles on the AZT/IFN treatment of 1101 ATLL patients. The response rate of the AZT/IFN regimen yielded an OR of 67% [95% CI: 0.50; 0.80], a CR of 33% [95% CI: 0.24; 0.44], and a PR of 31% [95% CI: 0.24; 0.39] among individuals who received this regimen at any point during their treatment. Our subgroup analyses' findings demonstrated that patients who received front-line and combined AZT/IFN therapy responded better than those who received AZT/IFN alone. It is significant to note that patients with indolent subtypes of disease had considerably higher response rates than individuals with aggressive disease. CONCLUSION: IFN/AZT combined with chemotherapy regimens is an effective treatment for ATLL patients, and its use in the early stages of the disease may result in a greater response rate.

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.

Parasite-derived microRNAs as a diagnostic biomarker: potential roles, characteristics, and limitations.

MicroRNAs (miRNAs), a subclass of small regulatory RNAs that present from ancient unicellular protozoans to parasitic helminths and parasitic arthropods. MiRNAs' mode of action has attracted wide attention as a result of their unique functional importance. MiRNAs play a role in diverse physiological and pathological processes ranging from organ development, immune function to apoptosis and cancer at the post-transcription gene expression. Thus, miRNAs are known to be targets for clinical treatment and therapy. The discovery of the high stability of circulating miRNA in various types of host body fluids, such as whole blood, serum, plasma, saliva, and urine has increased great interest among researchers in the potential of circulating miRNA as a prognosis/diagnosis of infectious. Some circulating miRNAs biomarkers advanced to clinical applications related to human diseases. However, this idea starts to come only in the fields of infectious disease. The goal of this review is to enhance the current understanding of these molecules and their applicability in the field of medicine. A detailed review of the available literature consulting tools performed in online repositories such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate. This review summarizes an overview of preclinical studies using circulating miRNAs biomarkers against infectious diseases affecting humans. The use of miRNA as a safe and potential tool is encouraging news, considering that until now, guidelines for the use of miRNA in clinical practice are still lacking.

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.