Novel strategies in HPV­16­related cervical cancer treatment: An in vitro study of combined siRNA-E5 with oxaliplatin and ifosfamide chemotherapy.

BACKGROUND: Cervical cancer, primarily caused by HPV infection, remains a global health concern. Current treatments face challenges including drug resistance and toxicity. This study investigates combining E5-siRNA with chemotherapy drugs, Oxaliplatin and Ifosfamide, to enhance treatment efficacy in HPV-16 positive cervical cancer cells, targeting E5 oncoprotein to overcome limitations of existing therapies. METHODS: The CaSki cervical cancer cell line was transfected with E5-siRNA, and subsequently treated with Oxaliplatin/Ifosfamide. Quantitative real-time PCR was employed to assess the expression of related genes including p53, MMP2, Nanog, and Caspases. Cell apoptosis, cell cycle progression, and cell viability were evaluated using Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, stemness ability was determined through a colony formation assay, and cell motility was assessed by wound healing assay. RESULTS: E5-siRNA transfection significantly reduced E5 mRNA expression in CaSki cells compared to the control group. The MTT assay revealed that monotherapy with E5-siRNA, Oxaliplatin, or Ifosfamide had moderate effects on cell viability. However, combination therapy showed synergistic effects, reducing the IC50 of Oxaliplatin from 11.42 × 10-8 M (45.36 µg/ml) to 6.71 × 10-8 M (26.66 µg/ml) and Ifosfamide from 12.52 × 10-5 M (32.7 µg/ml) to 8.206 × 10-5 M (21.43 µg/ml). Flow cytometry analysis demonstrated a significant increase in apoptosis for combination treatments, with apoptosis rates rising from 11.02 % (Oxaliplatin alone) and 16.98 % (Ifosfamide alone) to 24.8 % (Oxaliplatin + E5-siRNA) and 34.9 % (Ifosfamide + E5-siRNA). The sub-G1 cell population increased from 15.7 % (Oxaliplatin alone) and 18 % (Ifosfamide alone) to 21.9 % (Oxaliplatin + E5-siRNA) and 27.1 % (Ifosfamide + E5-siRNA), indicating cell cycle arrest. The colony formation assay revealed a substantial decrease in the number of colonies following combination treatment. qRT-PCR analysis showed decreased expression of stemness-related genes CD44 and Nanog, and migration-related genes MMP2 and CXCL8 in the combination groups. Apoptosis-related genes Casp-3, Casp-9, and pP53 showed increased expression following combination therapy, while BAX expression increased and BCL2 expression decreased relative to the control. CONCLUSION: The study demonstrates that combining E5-siRNA with Oxaliplatin or Ifosfamide enhances the efficacy of chemotherapy in HPV-16 positive cervical cancer cells. This synergistic approach effectively targets multiple aspects of cancer cell behavior, including proliferation, apoptosis, migration, and stemness. The findings suggest that this combination strategy could potentially allow for lower chemotherapy doses, thereby reducing toxicity while maintaining therapeutic efficacy. This research provides valuable insights into targeting HPV E5 as a complementary approach to existing therapies focused on E6 and E7 oncoproteins, opening new avenues for combination therapies in cervical cancer treatment.

War or peace: Viruses and metastasis.

Metastasis, the dissemination of malignant cells from a primary tumor to secondary sites, poses a catastrophic burden to cancer treatment and is the predominant cause of mortality in cancer patients. Metastasis as one of the main aspects of cancer progression could be strongly under the influence of viral infections. In fact, viruses have been central to modern cancer research and are associated with a great number of cancer cases. Viral-encoded elements are involved in modulating essential pathways or specific targets that are implicated in different stages of metastasis. Considering the continuous emergence of new viruses and the establishment of their contribution to cancer progression, the warfare between viruses and cancer appears to be endless. Here we aimed to review the critical mechanism and pathways involved in cancer metastasis and the influence of viral machinery and various routes that viruses adopt to manipulate those pathways for their benefit.

Exosomal miRNAs: the tumor's trojan horse in selective metastasis.

Organs of future metastasis are not passive receivers of circulating tumor cells, but are instead selectively and actively modified by the primary tumor before metastatic spread has even occurred. Tumors orchestrate a pre-metastatic program by conditioning distant organs to create microenvironments that foster the survival and proliferation of tumor cells before their arrival, thereby establishing pre-metastatic niches. Primary tumor-derived exosomes modulate these pre-metastatic niches, generating a permissive environment that facilitates the homing and expansion of tumor cells. Moreover, microRNAs have emerged as a key component of exosomal cargo, serving not only to induce the formation of pre-metastatic niches but also to prime these sites for the arrival and colonization of specific secondary tumor populations. Against this backdrop, this review endeavors to elucidate the impact of tumor-derived exosomal microRNAs on the genesis of their individualized pre-metastatic niches, with a view towards identifying novel means of specifying cancer metastasis and exploiting this phenomenon for cancer immunotherapy.

Expression pattern analysis of the long non-coding RNAs (TINCR, RP11-573D15.8, RP11-156E8.1), and their target genes (AKT1, FOXO1 and MAPK3) in patients with HIV infection, and elite controllers.

Elite controllers (ECs) defined as a small subclass of subjects with HIV capable of controlling human immunodeficiency virus (HIV) replication in the lack of antiretroviral treatment. One class of RNA molecules that serve as vital components in the network of HIV-related transcriptional regulation, are long noncoding RNAs (lncRNAs). The critical part that they take is in transcriptional regulation of HIV through monitoring various cellular signaling pathways. Reportedly, AKT and MAPK signaling pathways serve a crucial role in modulation of HIV infection. In the current investigation, we utilized bioinformatics tools to predict the lncRNAs that have the ability to interact with MAPK3, AKT, and FOXO1. Then, PBMC expression levels of lncRNAs and their target genes (AKT, FOXO1 and MAPK3) measured in the ECs (n = 15), HIV-positive (n = 40) patients and healthy control subjects (n = 40). We found a significant increase and decrease in the level of AKT and FOXO1 expression within the ECs group, respectively than in the HIV + group (P-value <0.0001 and 0.04, respectively). In the ECs group, the level of TINCR and RP11-156E8.1 was overexpressed compared to the HIV + group (P-value: 0.004 and 0.001, respectively). While RP11-573D15.8 level in ECs exhibited a significant suppression in contrast to HIV + group (P-value: 0.02). According to the receiver-operating characteristic (ROC) curve results, AKT and TINCR could serve as useful biomarkers for screening ECs groups from HIV + patients and healthy control groups. Overall, different expression patterns of selected factors and ROC curve results showed these factors could critically contribute to HIV controlling and be considered as diagnostic markers for ECs from HIV + samples.

Viruses and thrombocytopenia.

Thrombocytopenia, characterized by a decrease in platelet count, is a multifaceted clinical manifestation that can arise from various underlying causes. This review delves into the intriguing nexus between viruses and thrombocytopenia, shedding light on intricate pathophysiological mechanisms and highlighting the pivotal role of platelets in viral infections. The review further navigates the landscape of thrombocytopenia in relation to specific viruses, and sheds light on the diverse mechanisms through which hepatitis C virus (HCV), measles virus, parvovirus B19, and other viral agents contribute to platelet depletion. As we gain deeper insights into these interactions, we move closer to elucidating potential therapeutic avenues and preventive strategies for managing thrombocytopenia in the context of viral infections.

A computational approach to design a multiepitope vaccine against H5N1 virus.

Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely challenging. Here, we used an in silico approach to design a multi-epitope vaccine against H5N1 influenza A virus using hemagglutinin (HA) and neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL) were predicted via IEDB, NetMHC-4 and NetMHCII-2.3 respectively. Two adjuvants consisting of Human ß-defensin-3 (HßD-3) along with pan HLA DR-binding epitope (PADRE) have been chosen to induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG and double EAAAK were utilized to link epitopes and adjuvants. This construct encodes a protein having 350 amino acids and 38.46 kDa molecular weight. Antigenicity of ~ 1, the allergenicity of non-allergen, toxicity of negative and solubility of appropriate were confirmed through Vaxigen, AllerTOP, ToxDL and DeepSoluE, respectively. The 3D structure of H5N1 was refined and validated with a Z-Score of - 0.87 and an overall Ramachandran of 99.7%. Docking analysis showed H5N1 could interact with TLR7 (docking score of - 374.08 and by 4 hydrogen bonds) and TLR8 (docking score of - 414.39 and by 3 hydrogen bonds). Molecular dynamics simulations results showed RMSD and RMSF of 0.25 nm and 0.2 for H5N1-TLR7 as well as RMSD and RMSF of 0.45 nm and 0.4 for H5N1-TLR8 complexes, respectively. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) confirmed stability and continuity of interaction between H5N1-TLR7 with the total binding energy of - 29.97 kJ/mol and H5N1-TLR8 with the total binding energy of - 23.9 kJ/mol. Investigating immune response simulation predicted evidence of the ability to stimulate T and B cells of the immunity system that shows the merits of this H5N1 vaccine proposed candidate for clinical trials.

Analyzing the expression pattern of the noncoding RNAs (HOTAIR, PVT-1, XIST, H19, and miRNA-34a) in PBMC samples of patients with COVID-19, according to the disease severity in Iran during 2022-2023: A cross-sectional study.

Background and aims: MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are well-known types of noncoding RNAs (ncRNAs), which have been known as the key regulators of gene expression. They can play critical roles in viral infection by regulating the host immune response and interacting with genes in the viral genome. In this regard, ncRNAs can be employed as biomarkers for viral diseases. The current study aimed to evaluate peripheral blood mononuclear cell (PBMC) ncRNAs (lncRNAs-homeobox C antisense intergenic RNA [HOTAIR], -H19, X-inactive-specific transcript [XIST], plasmacytoma variant translocation 1 [PVT-1], and miR-34a) as diagnostic biomarkers to differentiate severe COVID-19 cases from mild ones. Methods: Candidate ncRNAs were selected according to previous studies and assessed by real-time polymerase chain reaction in the PBMC samples of patients with severe coronavirus disease 2019 (COVID-19) (n = 40), healthy subjects (n = 40), and mild COVID-19 cases (n = 40). Furthermore, the diagnostic value of the selected ncRNAs was assessed by analyzing the receiver-operating characteristic (ROC). Results: The results demonstrated that the expression pattern of the selected ncRNAs was significantly different between the studied groups. The levels of HOTAIR, XIST, and miR-34a were remarkably overexpressed in the severe COVID-19 group in comparison with the mild COVID-19 group, and in return, the PVT-1 levels were lower than in the mild COVID-19 group. Interestingly, the XIST expression level in men with severe COVID-19 was higher compared to women with mild COVID-19. ROC results suggested that HOTAIR and PVT-1 could serve as useful biomarkers for screening mild COVID-19 from severe COVID-19. Conclusions: Overall, different expression patterns of the selected ncRNAs and ROC curve results revealed that these factors can contribute to COVID-19 pathogenicity and can be considered diagnostic markers of COVID-19 severe outcomes.

Oncoviruses: Induction of cancer development and metastasis by increasing anoikis resistance.

The phenomenon of cell death is a vital aspect in the regulation of aberrant cells such as cancer cells. Anoikis is a kind of cell death that occurs when cells get separated from the extracellular matrix. Some cancer cells can inhibit anoikis in order to progress metastasis. One of the key variables that might be implicated in anoikis resistance (AR) is viral infections. The most important viruses involved in this process are Epstein-Barr virus, human papillomavirus, hepatitis B virus, human herpes virus 8, human T-cell lymphotropic virus type 1, and hepatitis C virus. A better understanding of how carcinogenic viruses suppress anoikis might be helpful in developing an effective treatment for virus-associated cancers. In the current study, we review the role of the mentioned viruses and their gene products in anoikis inhibition.

Preparation, Physicochemical Characterization, Antimicrobial Effects, Biocompatibility and Cytotoxicity of Co-Loaded Meropenem and Vancomycin in Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles (MSNPs) have been reported as an effective system to co-deliver a variety of different agents to enhance efficiency and improve biocompatibility. This study was aimed at the preparation, physicochemical characterization, antimicrobial effects, biocompatibility, and cytotoxicity of vancomycin and meropenem co-loaded in the mesoporous silica nanoparticles (Van/Mrp-MSNPs). The prepared nanoparticles were explored for their physicochemical features, antibacterial and antibiofilm effects, biocompatibility, and cytotoxicity. The minimum inhibitory concentrations (MICs) of the Van/Mrp-MSNPs (0.12-1 µg/mL) against Staphylococcus aureus isolates were observed to be lower than those of the same concentrations of vancomycin and meropenem. The minimum biofilm inhibitory concentration (MBIC) range of the Van/Mrp-MSNPs was 8-64 µg/mL, which was lower than the meropenem and vancomycin MBICs. The bacterial adherence was not significantly decreased upon exposure to levels lower than the MICs of the MSNPs and Van/Mrp-MSNPs. The viability of NIH/3T3 cells treated with serial concentrations of the MSNPs and Van/Mrp-MSNPs were 73-88% and 74-90%, respectively. The Van/Mrp-MSNPs displayed considerable inhibitory effects against MRSA, favorable biocompatibility, and low cytotoxicity. The Van/Mrp-MSNPs could be a potential system for the treatment of infections.

New Potential MicroRNA Biomarkers in Human Immunodeficiency Virus Elite Controllers, Human Immunodeficiency Virus Infections, and Coinfections with Hepatitis B Virus or Hepatitis C Virus.

INTRODUCTION: This research aimed to evaluate the specific microRNA (miRNA) including miR-17-5p, miRN-140-3p miR-191-5p, miR-200c-3p, and miR-N367 and cellular factors (p21, SDF-1, XCL1, CCL-2, and IL-2) in controlling replication of human immunodeficiency virus (HIV) in ECs. METHODS: The expression of miRNAs was assessed between healthy control groups and patient groups including ART-naïve HIV, HIV ART, ECs, and coinfection (HIV-HBV and HIV-HCV) via real-time PCR technique. Besides, the expression level of the nef gene and cellular factors were assessed by the ELISA method. The differences in the level of cellular factors and selected miRNAs between study groups were analyzed using the Kruskal-Wallis H or one-way ANOVA test. In addition, the potential of selected miRNAs as biomarkers for discriminating study groups was assessed by the receiver-operator characteristic (ROC) curve analysis. RESULTS: Some miRNAs in ECs, HIV ART, and healthy controls have similar expression patterns, whereas a miRNA expression profile of patient groups significantly differed compared to EC and control groups. According to ROC curve analyses, the miR-17-5p, miR-140-3p miR-191-5p, miR-200c-3p, and miR-N367 can be served as biomarkers for discriminating ECs from ART-naïve HIV-infected groups. There was a significant correlation between some miRNAs and cellular factors/the viral load as well. CONCLUSION: This report demonstrated a differentiation in the expression of selected immunological factors and cellular/viral miRNAs in ECs compared to other patient groups. Some miRNAs and cellular factors are involved in the viral replication control, immune response/modulation and can be used as biomarkers for diagnosis of ECs and differentiation with other groups. Differential expression of these miRNAs and cellular factors in different stages of HIV infection can help in finding novel ways for infection control.

Evaluation of expression pattern of cellular miRNAs (let-7b, miR-29a, miR-126, miR-34a, miR-181a-5p) and IL-6, TNF-α, and TGF-ß in patients with pseudoexfoliation syndrome.

Pseudoexfoliation syndrome (PEX) is a critical clinical and biological extracellular matrix systemic disorder. Despite the unknown nature of PEX etiopathogenesis, it is proven to be associated with various genes and factors. The present research focused on analyzing the expression of miR and inflammatory cytokines in PEX. Serum and aqueous humor (AH) were collected prior to cataract surgery or trabeculectomy from 99 participants (64 with PEX glaucoma, and 35 controls). Real-time PCR was used for assessing the expression pattern of some miRNAs namely let-7b, miR-29a, miR-126, miR-34a, and miR-181a-5p. ELISA was carried out to explore the transcription of some inflammatory cytokines such as TGF-ß, TNF-α, and IL-6. The indication of our results was a significant enhancement in the expression of let-7, miR-34a, and miR-181a-5p in PEX in contrast to the control group. Notwithstanding a significant suppression in miR-29a, and miR-126 expression levels in PEX in contrast to the control group. Analysis of ROC curve revealed that miR-29a and miR-34a are able to act as useful markers in order to discriminate the PEX group from the PEX negative subjects which were determined as the control group. According to the results obtained, the mean levels of TGF-ß, TNF-α, and IL-6 upregulated among PEX subjects in contrast to control samples. In conclusion, our findings indicated that the selected cytokines alongside the selected miRNAs could be introduced as a biomarker panel in the diagnosis of PEX.

Paxlovid (Nirmatrelvir/Ritonavir): A new approach to Covid-19 therapy?

Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drug nirmatrelvir can keep SARS-CoV-2 from replicating through inhibiting Mpro. Nirmatrelvir was combined with another HIV protease inhibitor, ritonavir, to create Paxlovid (Nirmatrelvir/Ritonavir). The metabolizing enzyme cytochrome P450 3 A is inhibited by ritonavir to lengthen the half-life of nirmatrelvir, so rintonavir acts as a pharmacological enhancer. Nirmatrelvir exhibits potent antiviral activity against current coronavirus variants, despite significant alterations in the SARS-CoV-2 viral genome. Nevertheless, there are still several unanswered questions. This review summarizes the current literature on nirmatrelvir and ritonavir efficacy in treating SARS-CoV-2 infection, and also their safety and possible side effects.

Evaluation of MicroRNA Expression Pattern (miR-28, miR-181a, miR-34a, and miR-31) in Patients with COVID-19 Admitted to ICU and Diabetic COVID-19 Patients.

INTRODUCTION: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC miRNAs are diagnostic biomarkers to screen the ICU COVID-19 and diabetic COVID-19 subjects. METHODS: Candidate miRNAs were selected through previous studies, and then the PBMC levels of selected miRNAs (miR-28, miR-31, miR-34a, and miR-181a) were measured via quantitative reverse transcription PCR. The diagnostic value of miRNAs was determined by the receiver operating characteristic (ROC) curve. The bioinformatics analysis was utilized to predict the DEM genes and relevant bio-functions. RESULTS: The COVID-19 patients admitted to ICU had significantly greater levels of selected miRNAs compared to non-hospitalized COVID-19 and healthy people. Besides, the mean miR-28 and miR-34a expression levels in the diabetic COVID-19 group were significantly upregulated when compared with the non-diabetic COVID-19 group. ROC analyses demonstrated the role of miR-28, miR-34a, and miR-181a as new biomarkers to discriminate the non-hospitalized COVID-19 group from the COVID-19 patients admitted to ICU samples, and also miR-34a can probably act as a useful biomarker for screening diabetic COVID-19 patients. Using bioinformatics analyses, we found the performance of target transcripts in many bioprocesses and diverse metabolic routes such as the regulation of multiple inflammatory parameters. DISCUSSION: The difference in miRNA expression patterns between the studied groups suggested that miR-28, miR-34a, and miR-181a could be helpful as potent biomarkers for diagnosing and controlling COVID-19.

Virus, Exosome, and MicroRNA: New Insights into Autophagy.

Autophagy is known as a conserved self-eating mechanism that contributes to cells to degrade different intracellular components (i.e., macromolecular complexes, aggregated proteins, soluble proteins, organelles, and foreign bodies). Autophagy needs formation of a double-membrane structure, which is composed of the sequestered cytoplasmic contents, called autophagosome. There are a variety of internal and external factors involved in initiation and progression of autophagy process. Viruses as external factors are one of the particles that could be associated with different stages of this process. Viruses exert their functions via activation and/or inhibition of a wide range of cellular and molecular targets, which are involved in autophagy process. Besides viruses, a variety of cellular and molecular pathways that are activated and inhibited by several factors (e.g., genetics, epigenetics, and environment factors) are related to beginning and developing of autophagy mechanism. Exosomes and microRNAs have been emerged as novel and effective players anticipated in various stages of autophagy. More knowledge in these pathways and identification of accurate roles of them could help to provide better therapeutic approaches in several diseases such as cancer. We highlighted the roles of viruses, exosomes, and microRNAs in the autophagy processes.

Microfluidics for detection of exosomes and microRNAs in cancer: State of the art.

Exosomes are small extracellular vesicles with sizes ranging from 30-150 nanometers that contain proteins, lipids, mRNAs, microRNAs, and double-stranded DNA derived from the cells of origin. Exosomes can be taken up by target cells, acting as a means of cell-to-cell communication. The discovery of these vesicles in body fluids and their participation in cell communication has led to major breakthroughs in diagnosis, prognosis, and treatment of several conditions (e.g., cancer). However, conventional isolation and evaluation of exosomes and their microRNA content suffers from high cost, lengthy processes, difficult standardization, low purity, and poor yield. The emergence of microfluidics devices with increased efficiency in sieving, trapping, and immunological separation of small volumes could provide improved detection and monitoring of exosomes involved in cancer. Microfluidics techniques hold promise for advances in development of diagnostic and prognostic devices. This review covers ongoing research on microfluidics devices for detection of microRNAs and exosomes as biomarkers and their translation to point-of-care and clinical applications.

The expression patterns of MALAT-1, NEAT-1, THRIL, and miR-155-5p in the acute to the post-acute phase of COVID-19 disease.

INTRODUCTION: One of the hallmarks of COVID-19 is overwhelming inflammation, which plays a very important role in the pathogenesis of COVID-19. Thus, identification of inflammatory factors that interact with the SARS-CoV-2 can be very important to control and diagnose the severity of COVID-19. The aim of this study was to investigate the expression patterns of inflammation-related non-coding RNAs (ncRNAs) including MALAT-1, NEAT-1, THRIL, and miR-155-5p from the acute phase to the recovery phase of COVID-19. METHODS: Total RNA was extracted from Peripheral Blood Mononuclear Cell (PBMC) samples of 20 patients with acute COVID-19 infection and 20 healthy individuals and the expression levels of MALAT-1, NEAT-1, THRIL, and miR-155-5p were evaluated by real-time PCR assay. Besides, in order to monitor the expression pattern of selected ncRNAs from the acute phase to the recovery phase of COVID-19 disease, the levels of ncRNAs were re-measured 6‒7 weeks after the acute phase. RESULT: The mean expression levels of MALAT-1, THRIL, and miR-155-5p were significantly increased in the acute phase of COVID-19 compared with a healthy control group. In addition, the expression levels of MALAT-1 and THRIL in the post-acute phase of COVID-19 were significantly lower than in the acute phase of COVID-19. According to the ROC curve analysis, these ncRNAs could be considered useful biomarkers for COVID-19 diagnosis and for discriminating between acute and post-acute phase of COVID-19. DISCUSSION: Inflammation-related ncRNAs (MALAT-1, THRIL, and miR-150-5p) can act as hopeful biomarkers for the monitoring and diagnosis of COVID-19 disease.

Therapeutic potentials of CRISPR-Cas genome editing technology in human viral infections.

Viral infections are a common cause of morbidity worldwide. The emergence of Coronavirus Disease 2019 (COVID-19) has led to more attention to viral infections and finding novel therapeutics. The CRISPR-Cas9 system has been recently proposed as a potential therapeutic tool for the treatment of viral diseases. Here, we review the research progress in the use of CRISPR-Cas technology for treating viral infections, as well as the strategies for improving the delivery of this gene-editing tool in vivo. Key challenges that hinder the widespread clinical application of CRISPR-Cas9 technology are also discussed, and several possible directions for future research are proposed.

MicroRNA let-7 and viral infections: focus on mechanisms of action.

MicroRNAs (miRNAs) are fundamental post-transcriptional modulators of several critical cellular processes, a number of which are involved in host defense mechanisms. In particular, miRNA let-7 functions as an essential regulator of the function and differentiation of both innate and adaptive immune cells. Let-7 is involved in several human diseases, including cancer and viral infections. Several viral infections have found ways to dysregulate the expression of miRNAs. Extracellular vesicles (EV) are membrane-bound lipid structures released from many types of human cells that can transport proteins, lipids, mRNAs, and miRNAs, including let-7. After their release, EVs are taken up by the recipient cells and their contents released into the cytoplasm. Let-7-loaded EVs have been suggested to affect cellular pathways and biological targets in the recipient cells, and can modulate viral replication, the host antiviral response, and the action of cancer-related viruses. In the present review, we summarize the available knowledge concerning the expression of let-7 family members, functions, target genes, and mechanistic involvement in viral pathogenesis and host defense. This may provide insight into the development of new therapeutic strategies to manage viral infections.

Expression levels of miR-22, miR-30c, miR-145, and miR-519d and their possible associations with inflammatory markers among patients with coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of death around the world. Micro-ribonucleic acid (miRNA) can be involved in forming of atherosclerotic plaques, inflammation, cholesterol metabolism, and other mechanisms involved in CAD development. This study aimed to evaluate the expression level of miR-22, miR-30c, miR-145, and miR-519d and their possible association with inflammatory markers among patients with CAD. METHODS: The expression level of miR-22, miR-30c, miR-145, miR-519d, interleukin 6 (IL-6), and transforming growth factor beta (TGF-ß) was determined in peripheral blood mononuclear cells (PBMCs) from 46 patients with CAD and 39 healthy controls using real-time quantitative polymerase chain reaction (qPCR) assay. RESULTS: 53.8% (n = 21) and 52.2% (n = 24) of controls and cases were men, respectively; the mean age was 59.8 ± 7.4 and 57.0 ± 9.8 years, respectively. The miRNA expression pattern of each group showed significantly different expression profiles. In the CAD patients group, miR-22, miR-30c, and miR-145 were down-regulated compared to the control group. On the opposite, miR-519d was up-regulated in patients with CAD compared to the control group. Our results also showed that the expression levels of IL-6 and TGF-ß were up-regulated among patients with CAD compared to the control group. In addition, the expression of miR-145 and miR-519d had a significantly negative and positive correlation with TGF-ß and IL-6, respectively. CONCLUSION: The change in expression levels of miR-22, miR-30c, miR-145, and miR-519d in PBMCs of patients with CAD could be considered as a potential biomarker for CAD.

Oncogenic viruses and chemoresistance: What do we know?

Chemoresistance is often referred to as a major leading reason for cancer therapy failure, causing cancer relapse and further metastasis. As a result, an urgent need has been raised to reach a full comprehension of chemoresistance-associated molecular pathways, thereby designing new therapy methods. Many of metastatic tumor masses are found to be related with a viral cause. Although combined therapy is perceived as the model role therapy in such cases, chemoresistant features, which is more common in viral carcinogenesis, often get into way of this kind of therapy, minimizing the chance of survival. Some investigations indicate that the infecting virus dominates other leading factors, i.e., genetic alternations and tumor microenvironment, in development of cancer cell chemoresistance. Herein, we have gathered the available evidence on the mechanisms under which oncogenic viruses cause drug-resistance in chemotherapy.