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1.
BMC Infect Dis ; 24(1): 673, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969993

ABSTRACT

BACKGROUND: Redondoviridae is a newly discovered virus family linked to oral and respiratory conditions in people, while there is still debate about whether it is also coinfected with other respiratory viruses. This study aimed to determine the frequency of Redondovirus (ReDoV) in nasopharyngeal samples and to investigate any possible links to SARS-CoV-2 infections. METHODS: A polymerase chain reaction (PCR) test was conducted on 731 nasopharyngeal samples from individuals referred to medical centers in Tehran, Iran, for SARS-CoV-2 testing to investigate the prevalence of ReDoV. An oral interview was performed to complete information on dental issues and the individuals' demographics, symptoms, and vaccination history. RESULTS: The prevalence of ReDoV was 25.99%, and 15.26% had a coinfection with SARS-CoV-2. No notable correlation was found regarding ReDoVs and SARS-CoV-2 infections (p > 0.05). Women had a higher ReDoV positivity rate of 18.47% compared to men at 7.52% (p = 0.12), and there was no significant correlation between age groups and ReDoV presence. Nonetheless, a significant association was noted between ReDoVs and dental/gum issues (p < 0.0001, OR: 13.0326). A phylogenetic analysis showed that ReDoVs originated from various human-related clusters. CONCLUSIONS: These results highlight the potential for detecting ReDoVs in nasopharyngeal samples of people with gum or dental issues. Additionally, conducting more ReDoV epidemiological research and proposing oral health as a possible marker for ReDoV infections is important.


Subject(s)
COVID-19 , Humans , Female , Male , Cross-Sectional Studies , Adult , Iran/epidemiology , Middle Aged , Adolescent , Young Adult , Prevalence , COVID-19/epidemiology , COVID-19/virology , Child , Nasopharynx/virology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Coinfection/virology , Coinfection/epidemiology , Aged , Child, Preschool , Infant
2.
Heliyon ; 10(10): e30900, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803943

ABSTRACT

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.

3.
Curr HIV Res ; 22(1): 53-64, 2024.
Article in English | MEDLINE | ID: mdl-38310469

ABSTRACT

BACKGROUND: Human immunodeficiency virus-1 infection still remains a global health threat. While antiretroviral therapy is the primary treatment option, concerns about the emergence of drug-resistance mutations and treatment failure in HIV-infected patients persist. OBJECTIVE: In this study, we investigated the development of drug resistance in HIV-1-infected individuals receiving antiretroviral therapy for 6-10 years. METHODS: In this cross-sectional study, we evaluated 144 people living with HIV-1 who had received antiretroviral therapy for at least 6 years. Plasma specimens were collected, and the HIV-1 viral load and drug-resistance mutations were assessed using molecular techniques. RESULTS: The demographic and epidemiological characteristics of the participants were also analyzed: Twelve [8.3%) of the studied patients showed a viral load over 1000 copies per/mL, which indicates the suboptimal response to antiretroviral therapy. Significant correlations were found between viral load and CD4 count, as well as epidemiological factors, such as vertical transmission, history of imprisonment, and needle stick injuries. Drug resistance mutations were detected in 10 (83.3%) of patients who failed on antiretroviral therapy, with the most common mutations observed against nucleoside reverse transcriptase inhibitors (5 (41.7%)) and non-nucleoside reverse transcriptase inhibitors (9 (75%)). Phylogenetic analysis revealed that 12 patients who failed treatment were infected with CRF35_AD. CONCLUSION: Our study provides important insights into the characteristics and development of drug resistance in HIV-1-infected individuals receiving long-term antiretroviral therapy in Iran. The findings underline the need for regular viral load monitoring, individualized treatment selection, and targeted interventions to optimize treatment outcomes and prevent the further spread of drug-resistant strains.


Subject(s)
Drug Resistance, Viral , HIV Infections , HIV-1 , Mutation , Viral Load , Humans , Male , HIV-1/drug effects , HIV-1/genetics , Female , HIV Infections/drug therapy , HIV Infections/virology , HIV Infections/epidemiology , Iran/epidemiology , Cross-Sectional Studies , Drug Resistance, Viral/genetics , Adult , Middle Aged , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Young Adult , CD4 Lymphocyte Count , Treatment Failure
4.
Health Sci Rep ; 7(2): e1861, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38332929

ABSTRACT

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.

5.
Virol J ; 20(1): 296, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38093303

ABSTRACT

BACKGROUND: To improve the patient care, public health surveillance, and infection control, it is crucial to identify the presence and frequency of the common respiratory infections in individuals with COVID-19 symptoms but tested negative for SARS-CoV-2. This study aimed to shed light on this during the COVID-19 pandemic in Iran. METHODS: In this cross-sectional study, a total of 1,002 patients with acute respiratory infection who had negative SARS-CoV-2 test results and referred to Valfajr Health Center, the National Collaborating Laboratory of Influenza and COVID-19 National Reference Laboratory at Pasteur Institute of Iran were recruited between January 2020 and January 2022. Nasopharyngeal and oropharyngeal swab samples were collected to detect 17 common respiratory viruses via TaqMan one-step real-time multiplex PCR. Demographic and clinical data of the participants were obtained from their electronic medical records. RESULTS: In total, 218 samples (21.8%) were tested positive for at least one respiratory virus infection. Most of the common investigated respiratory viruses belonged to the years 2020 and 2022. The number of investigated patients in 2021 was few, which highlights the impact of health measures following the COVID-19 pandemic in Iran. Influenza A was the most common virus (5.8%), while adenovirus had the lowest prevalence (0.1%). Although the rate of respiratory virus infection was higher in men (24%) compared to women (19.3%), this difference was not statistically significant (P = 0.069). The prevalence of respiratory viruses had an inverse association with increasing age, with the highest rate (55.6%) observed in the age group below 2 years and the lowest rate (12.7%) in those above 65 years. CONCLUSION: Our findings underscore the significance of adopting a comprehensive approach to respiratory infections detection and management. These results can be employed for the development of syndromic surveillance systems and implementation of the effective infection control measures. Furthermore, the results contribute to better understanding of the dynamics of respiratory viruses, both during pandemic periods and in non-pandemic contexts.


Subject(s)
COVID-19 , Influenza, Human , Respiratory Tract Infections , Male , Humans , Female , Child, Preschool , COVID-19/epidemiology , SARS-CoV-2 , Pandemics , Influenza, Human/epidemiology , Iran/epidemiology , Cross-Sectional Studies , Respiratory Tract Infections/epidemiology
6.
Intervirology ; 66(1): 122-135, 2023.
Article in English | MEDLINE | ID: mdl-37699384

ABSTRACT

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.


Subject(s)
Coinfection , HIV Infections , Hepatitis C , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Hepatitis B virus/genetics , Hepacivirus/genetics , HIV Infections/complications , HIV , Gene Expression Profiling/methods , Biomarkers , Hepatitis C/complications
7.
Turk J Chem ; 47(1): 148-163, 2023.
Article in English | MEDLINE | ID: mdl-37720867

ABSTRACT

Chitosan plays a crucial role in catalysis, environmental remediation, and sustainable chemistry as a renewable and cationic polysaccharide. Chitosan-based metal catalysts are used in a broad range of chemical transformations. In the study, carbon quantum dots (CQDs) were derived from Momordica charantia fruits by microwave irradiation following a green chemistry approach. Three catalysts were designed: Ag(0)-chitosan, Ag(0)-chitosan-M. charantia fruit powder, and Ag(0)-chitosan-CQDs. The catalyst supports were prepared by stabilizing CQDs or M. charantia powder within the polymeric matrix of chitosan beads. Metallic silver particles were anchored onto glutaraldehyde cross-linked chitosan beads from the aqueous solution of silver nitrate. The heterogeneous silver catalysts were used to reduce toxic nitroaromatics (4-nitrophenol, 2-nitroaniline, 1,2-diamino-4-nitrobenzene, 2,4-dinitrophenol). The regeneration of catalysts was also covered. The reused catalysts retained their catalytic activities after ten cycles. The study suggested that presence of CQDs or M. charantia powder could improve the efficiency of the chitosan-based metallic silver catalysts.

8.
Arch Iran Med ; 26(2): 69-75, 2023 02 01.
Article in English | MEDLINE | ID: mdl-37543926

ABSTRACT

BACKGROUND: Global real-time monitoring of SARS-CoV-2 variants is crucial to controlling the COVID-19 outbreak. The purpose of this study was to set up a Sanger-based platform for massive SARS-CoV-2 variant tracking in laboratories in low-resource settings. METHODS: We used nested RT-PCR assay, Sanger sequencing and lineage assignment for 930-bp of the SARS-CoV-2 spike gene, which harbors specific variants of concern (VOCs) mutations. We set up our platform by comparing its results with whole genome sequencing (WGS) data on 137 SARS-CoV-2 positive samples. Then, we applied it on 1028 samples from March-September 2021. RESULTS: In total, 125 out of 137 samples showed 91.24% concordance in mutation detection. In lineage assignment, 123 out of 137 samples demonstrated 89.78% concordance, 65 of which were assigned as VOCs and showed 100% concordance. Of 1028 samples screened by our in-house method, 78 distinct mutations were detected. The most common mutations were: S:D614G (21.91%), S:P681R (12.19%), S:L452R (12.15%), S:T478K (12.15%), S:N501Y (8.91%), S:A570D (8.89%), S:P681H (8.89%), S:T716I (8.74%), S:L699I (3.50%) and S:S477N (0.28%). Of 1028 samples, 980 were attributed as VOCs, which include the Delta (B.1.617.2) and Alpha (B.1.1.7) variants. CONCLUSION: Our proposed in-house Sanger-based assay for SARS-CoV-2 lineage assignment is an accessible strategy in countries with poor infrastructure facilities. It can be applied in the rapid tracking of SARS-CoV-2 VOCs in the SARS-CoV-2 pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , Disease Outbreaks , Laboratories , Mutation
9.
Intervirology ; 66(1): 63-76, 2023.
Article in English | MEDLINE | ID: mdl-36882006

ABSTRACT

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.


Subject(s)
COVID-19 , Diabetes Mellitus , MicroRNAs , Humans , Leukocytes, Mononuclear , COVID-19/diagnosis , MicroRNAs/genetics , Biomarkers , Intensive Care Units
11.
Acta Virol ; 67(1): 91-98, 2023.
Article in English | MEDLINE | ID: mdl-36950889

ABSTRACT

Since the emergence of the original Wuhan SARS-CoV-2 strain, several new variants of the virus have emerged. Alpha, Beta, Gamma, Delta and the most recent Omicron variants have been introduced during this pandemic. Several methods including, but not restricted to, allele-specific PCR, ligation with rolling circle amplification and real-time PCR with allele-specific probes are able to detect mutations as low as a single nucleotide polymorphism. High-resolution melting curve analysis is ano-ther technique to assess any mutations in a nucleic acid chain. Confirmed samples with SARS-CoV-2 infection were subjected to variant identification using a de novo-designed HRM assay. In order to select for mutations with the highest effect on Tm of the amplicon, deletion mutations of NSP6 (Del 3675-3677), and S1 (Del 144) were chosen for HRM analysis. HRM analysis for the amplicon of the primer set-1 (NSP6) resulted in Tm differences of -0.39°C, +0.4°C, and -0.6°C between Alpha, Delta, and Omicron variants, respectively, in comparison to the original Wuhan strain. Moreover, HRM analysis of the amplification performed by primer set-2 (S1) led to Tm differences of +0.32°C, -0.26°C, and +0.24°C between Alpha, Delta, and Omicron variants, respectively, in comparison to original Wuhan strain. The test was able to specify each sample to its variant group with more than 90 percent of confidence. The results obtained in this study demonstrate that using a single closed-tube strategy with a HRM-equipped machine, screening new variants of the virus is possible in a fast and reliable way. Keywords: high resolution melting; SARS coronavirus 2; mutation; variant; genotyping.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , Real-Time Polymerase Chain Reaction , Biological Assay , Mutation
13.
Cancer Med ; 12(7): 8629-8638, 2023 04.
Article in English | MEDLINE | ID: mdl-36573460

ABSTRACT

BACKGROUND: We evaluated whether patients' initial screening symptoms were related to subsequent utilization of supportive care services and hospitalizations, and whether patient-level demographics, symptoms, hospitalizations, and supportive care service utilization were associated with mortality in primarily low-income, older, Black Veterans with cancer. METHODS: This quality improvement project created collaborative clinics to conduct cancer distress screenings and refer to supportive care services at an urban, VA medical center. All patients completed a distress screen with follow-up screening every 3 months. Supportive care utilization, hospitalization rates, and mortality were abstracted through medical records. Poisson regression models and cox proportional hazard models were utilized. RESULTS: Five hundred and eighty five screened patients were older (m = 72), mostly Black 70% (n = 412), and had advanced cancer 54%. Fifty-eight percent (n = 340) were screened only once with 81% (n = 470) receiving ≥1 supportive care service and 51.5% (n = 297) being hospitalized ≥1 time 18 months following initial screen. Symptom severity was significantly related to number of hospitalizations. Low mood was significantly related to higher supportive services (p < 0.001), but not hospitalizations (p ≥ 0.52). Pain, fatigue, physical function, nutrition, and physical symptoms were significantly associated with more supportive services and hospitalizations (p < 0.01). Twenty percent (n = 168) died; Veterans who were Black, had lower stage cancers, better physical health, and utilized less supportive care services had lower odds of mortality (p ≤ 0.01). CONCLUSION: Individuals with elevated distress needs and those reporting lower physical function utilized more supportive care services and had higher hospitalization rates. Lower physical function, greater supportive care use, higher stage cancer, and being non-Black were associated with higher odds of death.


Subject(s)
Neoplasms , Veterans , Humans , Hospitalization , Depression , Neoplasms/diagnosis , Neoplasms/therapy , Poverty
14.
Recent Adv Antiinfect Drug Discov ; 18(3): 205-214, 2023.
Article in English | MEDLINE | ID: mdl-36345239

ABSTRACT

BACKGROUND: Considering the role of calcium in the replication and morphogenesis of rotaviruses, it is hypothesized that decreased cytosolic calcium levels by using calcium channel blockers can subsequently interfere with rotavirus replication. OBJECTIVE: The present study investigated the effects of two calcium ion channel blockers, amlodipine and diltiazem, against human rotavirus infection. METHODS: Cytotoxic effects of the drugs on MA-104 cells were evaluated using the neutral red assay. The effects of amlodipine and diltiazem at non-toxic concentrations on human rotavirus were examined using cytopathic effect inhibition, TCID50, and real-time PCR assays. RESULTS: The highest inhibitory effect was obtained at concentrations of 0.5 µg/ml of amlodipine and 3 µg/ml of diltiazem, leading to 4.6 and 5.5 logarithmic reductions in infectious rotavirus titer and four- and a five-fold increase in the Ct values compared to the virus control, respectively (p-value < 0.001). Conversely, infectious rotavirus titers were significantly elevated compared to the virus control at concentrations above 0.9 µg/ml of amlodipine and above 25 µg/ml of diltiazem. CONCLUSION: Our study suggests that in addition to cardiovascular diseases, calcium channel blockers at their optimal doses may also be used to treat gastroenteritis caused by rotavirus infection.


Subject(s)
Rotavirus Infections , Rotavirus , Humans , Diltiazem/pharmacology , Calcium Channel Blockers/pharmacology , Amlodipine/pharmacology , Rotavirus Infections/drug therapy
15.
BMC Infect Dis ; 22(1): 730, 2022 Sep 08.
Article in English | MEDLINE | ID: mdl-36076173

ABSTRACT

BACKGROUND: In December 2019, in Wuhan, China, coronavirus disease 2019 (COVID-19) was emerged due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It seems that children and neonates, similar to adult and elderly individuals, are at risk of SARS-CoV-2 infection. However, adequate data are not available about neonates infected with SARS-CoV-2. METHODS: This study evaluated the presence of SARS-CoV-2 infection in neonates born to mothers or relatives with COVID-19. This cross-sectional study was performed on 25,044 consecutive Iranian participants in Tehran, Iran, from January 2020 to August 2020. Viral ribonucleic acid (RNA) was extracted from 500 µl of the oropharyngeal and nasopharyngeal specimens of the participants. The genomic RNA of SARS-CoV-2 was detected by real-time polymerase chain reaction (PCR) assay. RESULTS: Out of all participants, 98 (0.40%) cases were neonates born to mothers or relatives with SARS-CoV-2 infection. Therefore, the current study was performed on these neonates. Out of 98 studied neonates, 6 (6.1%) cases had positive PCR results for SARS-CoV-2 infection. Moreover, among 98 studied neonates' mothers, 25 (25.5%) cases had positive PCR results for SARS-CoV-2 infection. CONCLUSION: The findings of this study demonstrated that the rate of COVID-19 in neonates born to mothers or relatives with SARS-CoV-2 infection in the Iranian population is about 6.1%.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Adult , Aged , COVID-19/epidemiology , Child , Cross-Sectional Studies , Female , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Iran/epidemiology , Mothers , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Prevalence , RNA , SARS-CoV-2/genetics
16.
Heliyon ; 8(9): e10483, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36158108

ABSTRACT

Globally, it is estimated that 43 million people are living with human immunodeficiency virus type 1 (HIV-1), and there are more than 600,000 acquired immunodeficiency syndrome (AIDS)-related deaths in 2020. The only way to increase the life expectancy of these patients right now is to use combination antiretroviral therapy (cART) for the lifetime. Due to the integration of the HIV-1 DNA in lymphocytes, the replication of the virus can only be reduced by using antiretroviral drugs. If the drug is stopped, the virus will replicate and reduce the number of lymphocytes. In recent years, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease Cas9-mediated genome editing system has been considered, preventing HIV-1 replication by causing DNA double-stranded breaks (DSBs) or disrupting the integrated virus replication by targeting the provirus. In this study, we utilized the CRISPR/Cas9 without the nuclear localization signal sequence (w/o NLS) system to inhibit the VSV-G-pseudotyped HIV-1 replication by targeting the HIV-1 DNA as a prophylactic method. To this end, we designed a multiplex gRNA (guide RNA) cassette to target the pol, env, and nef/long terminal repeat (nef/LTR) regions of the HIV-1 genome and then cloned it in plasmid expressing no-NLS-Cas9 protein as an all-in-one CRISPR/Cas9 vector. Using HIV-1 pseudovirus transduction into HEK-293T cell lines, our results showed that the CRISPR/Cas9-no NLS system disrupts the pseudotyped HIV-1 DNA and significantly (P-value < 0.0001) decreases the p24 antigen shedding and viral RNA load in cell culture supernatants harvested 48h after virus transduction. Although these results revealed the potential of the CRISPR/Cas9-no NLS nuclease system as a prophylactic strategy against HIV-1 infections, due to inefficient impairments of HIV-1 DNA, further studies are required to enhance its effectiveness and application in clinical practice.

17.
Biologicals ; 80: 27-34, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36153188

ABSTRACT

The present study aimed to scrutinize the expression profile of inflammatory-related genes (IFI-16, NOTCH2, CXCL8, and THBS1) from acute to post-acute stage of this infectious epidemic. The current cross-sectional study consisted of 53 acute-phase COVID-19 patients and 53 healthy individuals between February and March 2021. The extraction of total RNA was performed from PBMC specimens and also expression level of selected genes (IFI-16, NOTCH2, CXCL8, and THBS1) was evaluated by real-time PCR. Subsequently, levels of these factors were re-measured six weeks after the acute phase to determine if the levels of chosen genes returned to normal after the acute phase of COVID-19. Receiver operating characteristic (ROC) curve was plotted to test potential of genes as a diagnostic biomarker. The expression levels of inflammatory-related genes were significantly different between healthy and COVID-19 subjects. Besides, a significant higher CXCL8 level was found in the acute-phase COVID-19 compared to post-acute-phase infection which may be able to be considered as a potential biomarker for distinguishing between the acute phases from the post-acute-phase status. Deregulation of the inflammatory-related genes in COVID-19 patients, especially CXCL-8, can be serving as potent biomarkers to manage the COVID-19 infection.


Subject(s)
COVID-19 , Humans , COVID-19/genetics , SARS-CoV-2/genetics , Cross-Sectional Studies , Leukocytes, Mononuclear , Inflammation/genetics , Biomarkers , Receptor, Notch2
18.
J Parasit Dis ; 46(3): 764-770, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36091287

ABSTRACT

Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis with worldwide distribution. This study evaluated actin genotypes of T. vaginalis isolates using PCR-RFLP and sequence analysis in Tehran, Iran. Overall, 850 vaginal samples were collected from women admitted to hospitals affiliated with the Iran University of Medical Sciences in Tehran from 2020-to 2021. The samples were examined by wet mount and cultured. The parasites were harvested, and PCR-RFLP was performed using three endonuclease enzymes of HindII, MseI, and RsaI on all T. vaginalis isolates. Digestion patterns were then compared, and the genotype of these isolates was defined. The PCR products were sequenced. Overall, 12 (1.4%) isolates of T. vaginalis were identified from 850 vaginal samples collected. The most common genotypes were genotype E, seven (58.3%) and genotype G, three (25%), followed by genotype I, two (%16.7), using PCR-RFLP patterns and sequencing. No pattern indicative of mixed infection was found. PCR-RFLP is a proper technique to detect different T. vaginalis isolates, and noticeable polymorphism was found between isolates. Genotype E was the most common genotype in the studied group. The phylogenetic analysis indicated the T. vaginalis genotype E isolates in a distinct group compared to the genotypes G and I that evolved from a common ancestor.

19.
Int J Immunogenet ; 49(4): 243-253, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35861117

ABSTRACT

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the pathogenesis is unclear. Host genetic background is one of the main factors influencing the patients' susceptibility to several viral infectious diseases. This study aimed to investigate the association between host genetic polymorphisms of two genes, including vitamin D receptor (VDR) and vitamin D binding protein (DBP), and susceptibility to COVID-19 in a sample of the Iranian population. This case-control study enrolled 188 hospitalized COVID-19 patients as the case group and 218 suspected COVID-19 patients with mild signs as the control group. The VDR (rs7975232, rs731236 and rs2228570) and DBP (rs7041) gene single nucleotide polymorphisms (SNPs) were genotyped by Polymerase Chain Reaction Restriction - Fragment Length Polymorphism (PCR-RFLP) method. A significant association between rs2228570 SNP in the VDR gene and the susceptibility of COVID-19 was found between case and control groups. The CT genotype (Heterozygous) of rs2228570 C > T polymorphism showed significant association with a 3.088 fold increased odds of COVID-19 (p < .0001; adjusted OR: 3.088; 95% CI: 1.902-5.012). In addition, a significant association between CC genotype of rs2228570 CT polymorphism and increased odds of COVID-19 in male and female groups (p = .001; adjusted OR: 3.125; 95% CI: 1.630-5.991 and p = .002; adjusted OR: 3.071; 95% CI: 1.485-6.354 respectively) were determined. Our results revealed no significant differences in the frequency of genotype and allele of VDR (rs7975232 and rs731236) and DBP (rs7041) between SARS-CoV-2-infected patients and controls (p > .05). Our results showed that polymorphism of VDR (rs2228570) probably could influence individual susceptibility to COVID-19. The polymorphisms of VDR (rs7975232 and rs731236) and DBP (rs7041) were not associated with SARS-CoV-2 infection susceptibility.


Subject(s)
COVID-19 , COVID-19/genetics , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Iran/epidemiology , Male , Polymorphism, Single Nucleotide , Receptors, Calcitriol/genetics , SARS-CoV-2
20.
J Stroke Cerebrovasc Dis ; 31(9): 106665, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35901588

ABSTRACT

INTRODUCTION: Transient ischaemic attack (TIA) clinics are important for secondary prevention of fatal or disabling stroke. Non-adherence to prescribed medications is an important reason for treatment failure but difficult to diagnose. This study ascertained the utility of a novel biochemical tool in the objective biochemical diagnosis of non-adherence. METHODS: One-hundred consecutive urine samples collected from patients attending the TIA clinic, at a tertiary centre, were analysed for presence or absence of prescribed cardiovascular medications using liquid chromatography-mass spectrometry (LC-MS/MS). Patients were classified as adherent or non-adherent, respectively. Demographic and clinical characteristics were compared between the two cohorts. Univariate regression analyses were performed for individual variables and model fitting was undertaken for significant variables. RESULTS: The mean duration of follow-up from the index event was 31 days [standard deviation (SD): 18.9]. The overall rate of non-adherence for at least one medication was 24%. In univariate analysis, the number of comorbidities [3.4 (SD: 1.9) vs. 2.5 (1.9), P = 0.032] and total number of all prescribed medications [6.0 (3.3) vs 4.4 (2.1), P = 0.032] were higher in the non-adherent group. On multivariate analysis, the total number of medications prescribed correlated with increased non-adherence (odds ratio: 1.27, 95% Confidence Intervals: 1.1-1.5, P = 0.01). CONCLUSIONS: LC-MS/MS is a clinically useful tool for the diagnosis of non-adherence. Nearly a quarter of TIA patients were non-adherent to their cardiovascular medications Addressing non-adherence early may reduce the risk of future disabling cardiovascular events.


Subject(s)
Cardiovascular Agents , Ischemic Attack, Transient , Stroke , Cardiovascular Agents/adverse effects , Chromatography, Liquid/methods , Humans , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/drug therapy , Ischemic Attack, Transient/prevention & control , Secondary Prevention , Stroke/diagnosis , Stroke/drug therapy , Stroke/prevention & control , Tandem Mass Spectrometry/methods
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