A population-based prospective study on obesity-related non-communicable diseases in northern Iran: rationale, study design, and baseline analysis.

Background: Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population. Method: We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009-2010 and carried out the first repeated measurement (RM) after seven years (2016-2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively. Results: We adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18-90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years. Conclusion: The most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran.

Immunogenicity and safety of a quadrivalent recombinant influenza vaccine manufactured in Iran (FluGuard) in volunteers aged 18-60 years: A double-blind, non-inferiority, randomized controlled trial.

BACKGROUND: This study aimed to evaluate the non-inferiority of the FluGuard (a quadrivalent recombinant vaccine manufactured by Nivad Pharmed Salamat Company in Iran) by comparing its immunogenicity and safety with Vaxigrip Tetra (a quadrivalent inactivated vaccine manufactured by Sanofi Pasteur in France). MATERIALS AND METHODS: In this double-blind, randomized controlled trial, eligible volunteers aged 18-60 were randomized to receive either FluGuard or Vaxigrip Tetra vaccines. Immunogenicity was evaluated using the Hemagglutination Inhibition (HAI) assay and reported with the geometric mean titer (GMT), seroprotection, and seroconversion. In addition, vaccine safety was assessed by interviewing participants through phone calls. RESULTS: Out of 110 randomized volunteers, 51 and 53 were entered into the final analysis in the Vaxigrip and FluGuard groups, respectively. Vaxigrip had a higher seroprotection rate for the H1N1 strain compared with FluGuard (98 % vs. 91 %). Besides, FluGuard had higher seroprotection rates for H3N2 (74 % vs. 69 %), B-Yamagata (87 % vs. 84 %), and B-Victoria (66 % vs. 41 %) strains compared with Vaxigrip. In all four strains, FluGuard was non-inferior to Vaxigrip with the upper bounds of the 95 % CI on the ratio of the GMTs < 1.5: H1N1 (1.25), H3N2 (0.94), B-Yamagata (0.62), and B-Victoria (0.59). Furthermore, FluGuard was non-inferior to Vaxigrip with the upper bounds of the 95 % CI on the difference between the seroconversion rates < 10 %: H1N1 (2 %), H3N2 (10 %), B-Yamagata (-10 %), and B-Victoria (-29 %). The prevalence of solicited adverse drug reactions did not differ between groups. Furthermore, participants did not experience serious adverse events. CONCLUSION: Our findings support the non-inferiority of the FluGuard vaccine to the Vaxigrip vaccine regarding immunogenicity and safety. CLINICAL TRIAL REGISTRY: The study protocol was approved by the Iranian Registry of Clinical Trials (IRCT20210901052358N5).

The effects of the LaSota strain of oncolytic Newcastle disease virus vaccine on cervical intraepithelial neoplasia Patients-Clinical cohort study.

BACKGROUND: Cervical cancer is one of the most common malignancies in women, and its treatment has many side effects. Therefore, in this research, the effects of the LaSota strain of oncolytic Newcastle disease virus vaccine on cervical intraepithelial neoplasia (CIN) patients were investigated. METHODS: 15 patients who met the inclusion criteria and diagnosed as CIN II and CIN III were included in the study. The vaccine was injected inside the cervix (neoplasia site) at increasing doses during 21 days, and they were evaluated for adverse events. NDV antibody titer was measured in 90 days and the levels of ki-67 and p16 proteins were studied by immunohistochemistry. Also, the levels of some important inflammatory cytokines in the serum of CIN patients were measured and finally the patients were evaluated according to the final outcomes and the reduction of tumor lesions. RESULTS: Only in the first dose of vaccine some patients showed flu-like symptoms. The accumulation of NDV antibodies started on the 7th day of the study and increased until the 90th day. Administration of LaSota vaccine had no significant effect on the expressions of Ki-67 and p16 proteins. Nevertheless, a decrease in the serum levels of Il-1ß was observed in patients after the administration of the vaccine, but the serum levels of both Il-2 and INF-γ upregulated significantly. Also, vaccine administration had no significant effect in reducing CIN grades and lesions. CONCLUSIONS: In general, we concluded that LaSota strain of NDV vaccine has no therapeutic effectiveness in CIN patients.

Expression Pattern of Cholesterol 25-Hydroxylase and Serum Level of 25-Hydroxycholesterol and Relevant Inflammatory Cytokines in Patients with Varying Disease Severity of COVID-19.

Cholesterol 25-hydroxylase (CH25H) and its product 25-hydroxycholesterol (25HC) showed antiviral effects against various viruses in vitro. CH25H expression is regulated in mice by pro-inflammatory cytokine interferons (IFNs) in mice but data on its possible correlation with IFNs in humans are still unclear. We examined gene expression of CH25H, IFN-α, and IFN-ß and serum levels of 25HC in Iranian patients with mild and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Fifty intensive care unit (ICU) patients and outpatients with SARS-CoV-2 and 25 healthy controls were studied. Gene expression of CH25H and relevant inflammatory cytokines was quantified in peripheral blood mononuclear cells by real-time polymerase chain reaction. The expression of CH25H and serum levels of 25HC were significantly higher in ICU patients with SARS-CoV-2. Notably, IFN-α levels increased in healthy controls. However, compared to healthy controls, IFN-ß was considerably higher in outpatients. Finally, statistical analysis shows that no correlation was found between CH25H and IFN-α expression; nevertheless, a lower correlation was found with IFN-ß. The data revealed that CH25H and 25HC levels increase after SARS-CoV-2 infection. In other words, decreased levels of those factors in severe patients compared with mild patients may indicate the importance of their function in controlling the progression of the disease.

An Overview on Anti-COVID-19 Drug Achievements and Challenges Ahead.

The appearance of several coronavirus pandemics/epidemics during the last two decades (SARS-CoV-1 in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019) indicates that humanity will face increasing challenges from coronaviruses in the future. The emergence of new strains with similar transmission characteristics as SARS-CoV-2 and mortality rates similar to SARS-CoV-1 (∼10% mortality) or MERS-CoV (∼35% mortality) in the future is a terrifying possibility. Therefore, getting enough preparations to face such risks is an inevitable necessity. The present study aims to review the drug achievements and challenges in the fight against SARS-CoV-2 with a combined perspective derived from pharmacology, pharmacotherapy, and medicinal chemistry insights. Appreciating all the efforts made during the past few years, there is strong evidence that the desired results have not yet been achieved and research in this area should still be pursued seriously. By expressing some pessimistic possibilities and concluding that the drug discovery and pharmacotherapy of COVID-19 have not been successful so far, this short essay tries to draw the attention of responsible authorities to be more prepared against future coronavirus epidemics/pandemics.

Corrigendum to "Inhibition of HIV-1 replication using the CRISPR/noNLS-Cas9 system as a prophylactic strategy" <[Heliyon 8 (9) (2022) e10483]>.

[This corrects the article DOI: 10.1016/j.heliyon.2022.e10483.].

Genetic diversity and bioinformatic analysis in the L1 gene of HPV genotypes 31, 33, and 58 circulating in women with normal cervical cytology.

BACKGROUND: HPV-31, -33, and -58, along with HPV-45 and -52, account for almost 11% of HPV-associated cancers. Our previous studies showed that after HPV-16 and -51, HPV-58 was common and HPV-31 was as frequent as HPV-18 among Iranian women with normal cytology. Hence, in this study, we aimed to investigate the intra-type variations in L1 genes of HPV-58, -31, and -33 to find the predominant lineages circulating in women with normal cytology. METHODS: Complete coding sequencing of the L1 gene was amplified and nucleotide and amino acid sequences were compared to those of the references. The selective pressure on L1 protein and whether the variations of the L1 genes embed in L1 loops, or N-glycosylated sites were also investigated. RESULTS: B1, A, and A1 (sub)lineages were common in the HPV-58, -33, and -31 samples, respectively. Ninety nucleotide mutations were observed. Twenty nine nucleotide changes corresponded to nonsynonymous substitutions in which seventeen mutations were located in L1 loops. Only one codon position in HPV-58 sequences was found as the positive selection. No difference was observed in N-glycosylation sites between reference and understudied amino acid sequences. CONCLUSION: In the current study, we reported, for the first time, the (sub) lineages, amino acid, and genetic diversity in the L1 gene of circulating HPV-58, -33, and -31, in women with normal cytology, in Iran. Such studies can not only have epidemiological values, but also aid to set vaccination programs.

Amlodipine and Diltiazem Significantly Repress Human Rotavirus Infection In Vitro.

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.

The potential importance of autophagy genes expression profile dysregulation and ATG polymorphisms in COVID-19 pathogenesis.

Autophagy is one of the important mechanisms in cell maintenance, which is considered associated with different pathological conditions such as viral infections. In this current study, the expression level and polymorphisms in some of the most important genes in the autophagy flux in COVID-19 patients were evaluated. This cross-sectional study was conducted among 50 confirmed COVID-19 patients and 20 healthy controls. The COVID-19 patients were divided into a severe group and a mild group according to their clinical features. The expression levels of ATG5, ATG16L1, LC3, and BECN1 were evaluated by the 2-∆∆CT method and beta-actin as the internal control. The polymorphisms of the ATG5 (rs506027, rs510432) and ATG16L1 (rs2241880 or T300A) were evaluated by the Sanger sequencing following the conventional PCR. The mean age of the included patients was 58.3 ± 17.9 and 22 (44%) were female. The expression levels of the LC3 were downregulated, while BECN1 and ATG16L1 genes represent an upregulation in COVID-19 patients. The polymorphism analysis revealed the ATG16L1 rs2241880 and AGT5 rs506027 polymorphism frequencies are statistically significantly different between COVID-19 and Healthy controls. The autophagy alteration represents an association with COVID-19 pathogenesis and severity. The current study is consistent with the alteration of autophagy elements in COVID-19 patients by mRNA expression-level evaluation. Furthermore, ATG16L1 rs2241880 and AGT5 rs506027 polymorphisms seem to be important in COVID-19 and are highly suggested for further investigations.

A survey of ORF8 sequence and immunoinformatics features during alpha, delta, and wild type peaks of the SARS-CoV-2 pandemic in Iran.

Background: The Coronavirus disease 2019 (COVID-19) pandemic influences all around the world. The SARS-CoV-2 ORF8 accessory gene represents multiple functions in virus-host interaction. The current study aimed to compare the ORF8 substitutions and epitope features of these substitutions in the various SARS-CoV-2 outbreaks including delta, alpha, and wild type variants in Iran from 2020 to 2022. In addition, we evaluate B cell, HLA I and II epitopes, by in-silico approach to ORF8 binding site prediction. Methods: The samples were collected from patients diagnosed with SARS-CoV-2 infection via a real-time PCR assay. Then, a conventional PCR was carried out for ORF8 mutations analysis and further Sanger sequencing. Possible important alterations in epitope features of the ORF8 were evaluated by epitope mapping. B cell, HLA class I and II epitopes, evaluated by online databases ABCpred, NetMHCpan-4.1, and NetMHCIIpan-3.2, respectively. Results: The current study results could not represent novel variations in seven full-length ORF8 sequences or major ORF8 deletions in 80 evaluated samples. In addition, we could not find any ORF8 A382 during each outbreak of variants. Epitope mapping represents differences between the Alpha and other variants, especially in B cell potential epitopes and HLA I. Conclusion: The immunoinformatic evaluation of ORF8 suggested epitopes represent major differences for the Alpha variant in comparison with other variants. In addition, having mild pathogenesis of the Omicron variant does not seem to be associated with ORF8 alteration by phylogenetic evaluation. Future in-vitro studies for a clear conclusion about the epitope features of ORF8 are required.

Review on Approved and Inprogress COVID-19 Vaccines.

The last generation of Coronavirus named COVID-19 is responsible for the recent worldwide outbreak. Concerning the widespread and quick predominance, there is a critical requirement for designing appropriate vaccines to surmount this grave problem. Correspondingly, in this revision, COVID-19 vaccines (which are being developed until March 29th, 2021) are classified into specific and non-specific categories. Specific vaccines comprise genetic-based vaccines (mRNA, DNA), vector-based, protein/recombinant protein vaccines, inactivated viruses, live-attenuated vaccines, and novel strategies including microneedle arrays (MNAs), and nanoparticles vaccines. Moreover, specific vaccines such as BCG, MRR, and a few other vaccines are considered Non-specific. What is more, according to the significance of Bioinformatic sciences in the cutting-edge vaccine design and rapid outbreak of COVID-19, herein, Bioinformatic principles including reverse vaccinology, epitopes prediction/selection and, their further applications in the design of vaccines are discussed. Last but not least, safety, challenges, advantages, and future prospects of COVID-19 vaccines are highlighted.

Diversity identification of KPC- producing Klebsiella pneumoniae using multilocus variable number tandem repeat analysis.

PURPOSE: The current study aimed to determine blaKPC, blaGES, blaVIM, blaNDM, blaOXA-23, and blaOXA-48 genes in clinical strains of Klebsiella pneumoniae isolated in Tehran, Iran to assess genetic diversity using MLVA as a typing method. METHODS: A total of 181 K. pneumoniae isolates were obtained from various clinical samples. CLSI 2018 (clinical and laboratory standards institute) guidelines were used to determine antibiotic susceptibility and the Modified Hodge Test (MHT). To detect blaKPC, blaGES, blaVIM, blaNDM, blaOXA-23, and blaOXA-48, the polymerase chain reaction (PCR) method was used. The MLVA method was used to type K. pneumoniae isolates by using PCR for 8 Variable Number Tandem Repeats (VNTRs). RESULTS: Imipenem was the most effective antibiotic against K. pneumoniae, with 36.5% susceptibility. 100 (55.24%) of the isolates tested positive for KPC, and 30 (30%) tested positive for six genes. Thirty MLVA genotypes were distinguished, and an examination of diversity indexes (DIs) for eight loci revealed that seven different alleles were the most polymorphic, with the highest DI of 0.780. CONCLUSIONS: The present study showed that MLVA could be helpful for typing clinical strains of K. pneumoniae. Our K. pneumoniae isolates are thought to be derived from a small number of clones that have undergone minor genetic changes over time. The results also showed that this method had great potential to differentiate those strains with high phenotypic similarity. The current study has revealed some intriguing facts about K. pneumoniae genetic relatedness in Tehran, Iran.

Dual role of microbiota-derived short-chain fatty acids on host and pathogen.

A growing body of documents shows microbiota produce metabolites such as short-chain fatty acids (SCFAs) as crucial executors of diet-based microbial influence the host and bacterial pathogens. The production of SCFAs depends on the metabolic activity of intestinal microflora and is also affected by dietary changes. SCFAs play important roles in maintaining colonic health as an energy source, as a regulator of gene expression and cell differentiation, and as an anti-inflammatory agent. Additionally, the regulated expression of virulence genes is critical for successful infection by an intestinal pathogen. Bacteria rely on sensing environmental signals to find preferable niches and reach the infectious state. This review will present data supporting the diverse functional roles of microbiota-derived butyrate, propionate, and acetate on host cellular activities such as immune modulation, energy metabolism, nervous system, inflammation, cellular differentiation, and anti-tumor effects, among others. On the other hand, we will discuss and summarize data about the role of these SCFAs on the virulence factor of bacterial pathogens. In this regard, receptors and signaling routes for SCFAs metabolites in host and pathogens will be introduced.

Effects of High-Intensity Interval Vs. Moderate-Intensity Continuous Training on Body Composition and Gene Expression of ACE2, NLRP3, and FNDC5 in Obese Adults: A Randomized Controlled Trial.

Background: Obesity is considered a multisystem disease associated with higher mortality and morbidity in adults. This study explored the effects of two Moderate-Intensity Continuous Training (MICT) and High-Intensity Interval Training (HIIT) on body composition, maximal oxygen uptake (VO2max), and the gene expression of angiotensin-converting enzyme 2 (ACE2), fibronectin type III domain-containing protein 5 (FNDC5), and NLR family pyrin domain containing 3 (NLRP3) in adults with obesity. Methods: In a randomized controlled trial, 36 obese, inactive subjects (age: 45.16 ± 3.13 yrs.; mean, BW: 112.38 ± 20.1 kg, Height: 1.67 ± 0.07, and BMI: 39.66 ± 6.07 kg/m2) were randomly assigned to one of three groups: HIIT: (n = 12), MICT (n = 12), and control (n = 12). Both exercise groups received 40 min of training per session (three times/week) for eight weeks. Body composition, body fat percentage (BFP), VO2max, and the gene expression of ACE2, and NLRP3, were taken pre- and post-intervention using the qRT-PCR technique. The data were analyzed using SPSS software via parametric (ANOVA and ANCOVA) and non-parametric tests (Mann Whitney U and Kruskal-Wallis). Results: Our results showed that HIIT and MICT protocols could be effective in normalizing body composition measurements and VO2max, but HIIT could reduce body fat percentage (BFP) in obese subjects. Moreover, HIIT and MICT could significantly reduce the gene expression of NLRP3 (p < 0.0001) and ACE2 (p < 0.0001), while increasing the gene expression of FNDC5 (p < 0.0001). There were negative correlations between the gene expression of FNDC5 and NLRP3, as well as ACE2. Furthermore, increased FNDC5 was negatively correlated with BFP (r = 0.392, p < 0.001). Conclusion: Overall, our results indicated that HIIT and MICT protocols had the greatest impact on the gene expression of NLRP3, ACE2, and FNDC5.

Association between Melatonin Value and Interleukins1B, -18, and -33 Levels in Patients with Different Stages of Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Interaction between immune modulators and inflammatory factors is considered as one of the main underlying pathologies of non-alcoholic fatty liver disease (NAFLD). Hence we aimed to assess the association between these cytokines and melatonin. METHODS: We enrolled adult patients diagnosed with fatty liver by ultrasonography in a crosssectional study. All of them underwent Fibroscan evaluation. The subjects who met the inclusion and exclusion criteria for NAFLD were involved. A normal group who did not have NAFLD, viral or non-viral hepatitis, and without a history of pancreatobiliary surgery, bariatric surgery, and intake of any medication that influence the liver was also selected. The participants were categorized into the three following groups: 1) fibrosis>9.1 kPa and steatosis>290 dbm, 2) fibrosis: 6-9.0 kPa and steatosis 240-290 dbm, and 3) normal group with fibrosis<6.0 kPa and steatosis<240 dbm. Laboratory assessment and a questionnaire including demographic, anthropometric, laboratories, and clinical data were completed for each of them. RESULTS: Totally 97 subjects were enrolled in the present study. The mean age of the subjects was 42.2±11.3 years. 60% of them (59 patients) were female. Serum levels of melatonin, interleukin (IL)-1B, IL-18, and IL-33 increased according to the advancing of NAFLD state. Based on multiple linear regression model, melatonin was significantly associated with IL-1B (ß=2.8, P<0.001,95% CI=1.41-4.19), IL-18 (ß=0.018, P=0.0005, 95% CI=0.006-0.03), and IL-33 (ß=0.31, P=0.045, 95% CI=0.008-0.62) after adjustment for other variables. CONCLUSION: Melatonin level has a strong association with these cytokines. This linkage probably influences on the development and progression of NAFLD. Therefore it can be hypothesized that the therapeutic approach that affects this process may have a significant impact.

Simultaneous Hepatitis C Virus Genotyping and Variant Detection in Patients with Thalassemia: A Single-Center Phylogenetic Study.

BACKGROUND: Hepatitis C virus (HCV) genotype distribution is different in various regions. A variety of strategies could be used to detect HCV genotypes and subtypes. The aim of the present study was to introduce a genotyping method by an in-house protocol that could be used to determine HCV drug-resistant variants and phylogeny studies. METHODS: Samples from 91 patients with thalassemia were used for HCV genotyping by Cobas 4800 platform, and 50 cases of 1a, 1b, and 3a genotypes underwent amplification and sequencing of NS5A and NS5B by using consensus primers via conventional reverse transcription-polymerase chain reaction (RT-PCR) method. An ABI 3730xl system used for direct sequencing. Raw sequences were analyzed by popular bioinformatics software MEGA6 and CLC workbench 5. Phylogenetic construction was drawn using 1000 replicates bootstrap by the neighbor-joining method. Multiple sequence alignment (MSA) was performed for mutation detection. RESULTS: Sequencing results of 50 HCV isolates subtypes 1a (31/45), 3a (15/22) and 1b (4/8) NS5A and NS5B genes showed there were 72 NS5A and 105 NS5B mutations. Moreover, 8 resistant associated substitutions (RASs) were identified in nine thalassemia cases by multiple sequence alignment (MSA) protein analysis. The phylogenetic tree construct drew confirmed by the Cobas HCV genotyping results. CONCLUSION: The phylogenetic analysis could be a useful tool for HCV genotyping in case of determining the drug-resistant substitutions; however, it is time-consuming and needs expert analysis and interpretation. This preliminary study in Iranian patients with thalassemia introduces specific conventional RT-PCR to find RASs to direct acting antivirals (DAAs) and subtype determination at the same time.

Idiopathic thrombocytopenic purpura as a hematologic manifestation of COVID-19 infection: A case report.

The hematologic system is one of the vulnerable parts of the human body in coronavirus disease-2019 (COVID-19) infection. Lymphopenia and disseminated intravascular coagulation (DIC) are among the most frequent consequences of COVID-19. Idiopathic thrombocytopenic purpura is one of the common causes of thrombocytopenia in adults. It is defined by thrombocytopenia when platelet counts <105/µl in the absence of anemia and leukopenia. Traditionally, infections, typically viral, have been known as the main culprits of low platelet counts before the involvement of ITP. According to the literature, C virus (HCV), HIV, varicella-zoster virus (VZV), and cytomegalovirus (CMV) are considered secondary causative agents for the development of ITP. In this study, we reported a case that was afflicted with concurrent severe thrombocytopenia diagnosed as ITP and COVID-19 infection.

The role of lovastatin in the attenuation of COVID-19.

The mounting evidence regarding the pathogenesis of COVID-19 indicated that the cytokine storm has an axial role in the severity of this disease, which may lead to thrombotic complications, acute respiratory distress syndrome (ARDS), and myocardial damage, among other consequences. It has recently been demonstrated that statins are known to have anti-viral, anti-inflammatory, anti-thrombotic, and immunomodulatory features; however, their advantage has not been evaluated in COVID-19. This study aimed to investigate the protective effects of lovastatin in intensive care unit (ICU) patients with COVID-19. The case-control study consists of 284 ICU patients, which classified into three groups as follows: 1) the patients who no received lovastatin as a control (92 patients), 2) patients received 20 mg per day lovastatin (99 patients), and 3) patients received 40 mg per day lovastatin (93 patients). Each group's demographic and clinical parameters, along with CRP, interleukin (IL)-6, IL-8 levels, and mortality rate, were studied in three-time points. The results showed that there was no statistically significant difference between our study groups in terms of age and sex. (P > 0.05). Besides, in patients, receiving lovastatin the CRP, IL-6, IL-8 levels were significantly decreased from T1 to T3 than to the control group. Our results also showed that the use of lovastatin in COVID-19 patients significantly reduced the length of hospitalization in the ICU compared with the control group. In addition, our results showed that the mortality rate in patients receiving lovastatin was lower when compared to the control group; however, this difference was not statistically significant. Since the cytokine storm is a significant factor in the pathology of SARS-CoV-2, our findings highlighted the potential use of lovastatin to mitigate the inflammatory response induced by SARS-CoV-2 infection.

Effect of Baseline Resistance-Associated Substitutions on Thalassemia Patients with Chronic HCV Infection: A Two-Year Follow-Up.

BACKGROUND Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection showed the presence of resistant-associated substitutions (RASs). The aim of the present study was to carry out a follow-up of patients with baseline RASs to report the impact of RASs on DAA therapy outcome. METHODS In a cohort study, we analyzed NS5A and NS5B RASs among nine thalassemia cases by baseline RASs. In a 2-year follow-up, we analyzed viral markers and biochemical and hematological parameters of the participants and their sustained virologic response (SVR). Statistical analyses were performed using SPSS software version 22. RESULTS RASs for HCV subtype 1a included M28V, L31M, and H58P. For subtype 1b: L28M, R30Q, S24F, and C316N. And for subtype 3a: C316S, and S24F. In patients with cirrhosis (n = 5), ALT (p = 0.001) and AST (p = 0.007) levels were significantly reduced after treatment, and creatinine level slightly increased (p = 0.025). However, no significant data was observed in non-cirrhotic patients following the treatment. CONCLUSION The present study did not show any adverse effects of DAA therapy among patients with thalassemia suffering from chronic HCV infection with baseline RASs. Furthermore, reduction in ferritin and liver stiffness levels after DAA therapy could show the efficacy of DAA in such patients.

Melatonin Levels in Patients with Nonalcoholic Fatty Liver Disease Compared with Healthy Individuals according to Fibrosis Level.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide. Studies have shown that melatonin, as a regulatory hormone, is effective in different cell protective pathways. We aimed to compare serum melatonin levels of patients with NAFLD with different stages of fibrosis with that of healthy individuals. METHODS In this cross-sectional study patients, aged >20 years with elevated serum liver enzymes and trance abdominal sonographic diagnosis of fatty liver who met the exclusion criteria for NAFLD were included. The participants were categorized into three groups as follows: 1) severe fibrosis (fibrosis > 9.1 kPa and steatosis > 285 dbm), 2) mild-moderate fibrosis (fibrosis: 6-9.0 kPa and steatosis 240-285), and 3) normal group with fibrosis < 5.8 kPa and steatosis < 240 dbm based on Fibroscan evaluation. Five ml of fasting venous blood was taken from each patient and the control group for laboratory assessment. A questionnaire including demographic, anthropometric, laboratories (serum ALT, AST, triglyceride, total cholesterol and melatonin level), and clinical data was completed for all participants. RESULTS 97 people with a mean±SD age of 42.21 ± 11 years were enrolled. 59 (60.0%) patients were women. we observed that the melatonin levels were increased by advancing fibrosis. Based on control- attenuated parameter results the melatonin levels significantly differed between the healthy individuals and patients with severe steatosis. There was a direct association between increased melatonin levels and liver enzymes. CONCLUSION As a regulatory hormone, melatonin may directly be associated with liver cell injuries. Therefore, considered regulatory substances such as melatonin either diagnostic or therapeutic can improve the patients' outcome.