Interleukin-6 And Interleukin-10 Polymorphisms In Chronic Lymphoid Leukemia Patients.

OBJECTIVE: A major part of the cytokines secreted from the immune system are interleukins (IL) and their main role is to stimulate the immune system cells. Therefore the genotypic effects of IL-6 and IL-10 on the immune system in CLL were investigated in the study. METHOD: For this purpose 100 patients diagnosed with CLL and 70 healthy individuals with no cancer history were included in the study. Polymorphisms at IL10 and IL 6 promoter regions (1082 A\G and 819 C\T) and IL6 (174 G\C) polymorphisms were analyzed with RT-PCR. Genotype and allele frequencies were directly calculated. RESULT: In 100 CLL patients, 45 wild type AA, 40 AG and 15 mutant type GG genotypes were found for the IL 10 1082 A\G region. Genotypic distribution of IL10 819 C\T region was determined as CC, BT and TT genotypes in 37, 50 and 13 patients, respectively. In IL 6 174 G\C region, GG, GC and CC genotypes were determined in 62, 30 and 8 patients, respectively. There is no statistically significant difference between the CLL patients and control groups in terms of IL10 1082 A\G, 819 C\T and IL 6 174 G/C regions (p> 0.05). As a result of the allele frequency calculation of the IL 10 1082 region, the values obtained were A (0.65), G (0.35) for the patient group and (0.61) and G (0.31) for the control group. 819 region allele frequencies were C (0.57) and T (0.33) in the patient group and C (0.48) and T (0.32) in the control group. The IL6 174 region was calculated as G (0.82), C (0.28) in the patient group and G (0.63), C (0.23) in the control group. Given the number of patients within the limits of this study, IL 10 and IL 6 genotype frequencies do not seem to be statistically related to CLL patients. CONCLUSION: Mutant alleles of all interleukin SNPs were determined at a higher frequency in the patient group as compared to the control group. Therefore, a potential correlation between the SNPs of these interleukins and CLL can be determined in future studies with a higher number of samples.

The severity of COVID-19 in hypertensive patients is associated with mirSNPs in the 3' UTR of ACE2 that associate with miR-3658: In silico and in vitro studies.

The SARS-CoV-2 virus targets the antigen converting enzyme 2 (ACE2) receptor, thus resulting in elevated morbidity and an increased risk of severe and fatal COVID-19 infection in individuals with hypertension and diabetes mellitus. Objectives: This study aimed to identify the association between increased susceptibility and severity in order to evaluate their impact in hypertensive COVID-19 patients using in vitro and in silico models. Methods: We identified 80 miRNA binding sites on ACE2 (for different miRNAs) as well as various 30 SNPs in the miRNA binding sites of the 3' untranslated region (3' UTR) in the ACE2 gene using different online software and tools. From August 2020 to August 2021, a total of 200 nasopharyngeal/mouth swabs samples were collected from Multan, Pakistan. In order to quantify the cDNA of ACE2 and miR-3658 genes, we used Rotor Gene qRT-PCR on hypertensive patients with COVID-19 as well as healthy controls. Results: Interestingly, the binding site of miR-3658 corresponding to the 3' UTR of ACE2 featured three SNPs (rs1457913029, C>T; rs960535757, A>C, G; rs1423809569, C>T), and its genomic sequence featured a single SNP (rs1024225815, C>T) with the same nucleotide variation (rs1457913029, C>T) which potentially increases the severity of COVID-19. Similarly, three other SNPs (rs1557852115, C>G; rs770335293, A>G; rs1024225815, C>T) were also found on the first binding site positions of miR-3658. Our in vitro study found that ACE2 gene expression had an effect on miR-3658 in COVID-19 patients who also had hypertension. In both cases, our analysis demonstrated that the in silico model captured the same biological mechanisms as the in vitro system. Conclusion: The identified SNPs could represent potential informative signatures owing to their position in the splicing site of the ACE2 gene.

Adrenergic blocker terazosin potentially suppresses acetaminophen induced-acute liver injury in animal models via CYP2E1 gene.

Drug induced liver injury (DILI) is a global issue and acetaminophen (APAP) is considered as the main cause of this. Due to increasing incidents of DILI, current study attempted to investigate an alternative but better role of terazosin (alpha-adrenergic blocker) in APAP-induced acute liver injury in an animal model using New Zealand rabbits. APAP (1 g/kg of body weight) was given to New Zealand rabbits either with or without terazosin (0.5 mg/kg) and serum was collected after 4 h. Serum alanine transaminase (ALT), alkaline phosphatase (ALP) and ferritin level were determined to analyze the liver functioning of treated rabbits. Furthermore, total cholesterol (TC), total lipids (TL), high-density lipoproteins (HDL), low-density lipoprotein (LDL) and triglycerides (TG) levels were estimated to find any change in lipid profile of the treated animals. Moreover, the urea and creatinine levels assayed the actual renal functionality. To identify any modification in gene expression, qPCR of cytochrome P2E1 (CYP2E1) was performed. Terazosin in combination with APAP enhanced liver functioning by reducing the levels of liver injury markers viz. ALP and ALT, while lipid profile was also lowered by down regulation of TC, TL, LDL and TG with enhanced HDL levels. It caused significant down regulation of expression level of CYP2E1. It is concluded that terazosin has better effects induced on the recovery of normal liver functioning, by improving the liver profile, lipid profile and renal functioning both at tissue and molecular levels.

Global data analysis and risk factors associated with morbidity and mortality of COVID-19.

This review was focused on global data analysis and risk factors associated with morbidity and mortality of coronavirus disease 2019 from different countries, including Bangladesh, Brazil, China, Central Eastern Europe, Egypt, India, Iran, Pakistan, and South Asia, Africa, Turkey and UAE. Male showed higher confirmed and death cases compared to females in most of the countries. In addition, the case fatality ratio (CFR) for males was higher than for females. This gender variation in COVID-19 cases may be due to males' cultural activities, but similar variations in the number of COVID-19 affected males and females globally. Variations in the immune system can illustrate this divergent risk comparatively higher in males than females. The female immune system may have an edge to detect pathogens slightly earlier. In addition, women show comparatively higher innate and adaptive immune responses than men, which might be explained by the high density of immune-related genes in the X chromosome. Furthermore, SARS-CoV-2 viruses use angiotensin-converting enzyme 2 (ACE2) to enter the host cell, and men contain higher ACE2 than females. Therefore, males may be more vulnerable to COVID-19 than females. In addition, smoking habit also makes men susceptible to COVID-19. Considering the age-wise distribution, children and older adults were less infected than other age groups and the death rate. On the contrary, more death in the older group may be associated with less immune system function. In addition, most of these group have comorbidities like diabetes, high pressure, low lungs and kidney function, and other chronic diseases. Due to the substantial economic losses and the numerous infected people and deaths, research examining the features of the COVID-19 epidemic is essential to gain insight into mitigating its impact in the future and preparedness for any future epidemics.

Exonic sequencing and MLH3 gene expression analysis of breast cancer patients.

Breast cancer is the most common cancer in women worldwide. Detection of breast cancer susceptibility genes is an important issue. Also, MLH3 is a DNA mismatch repair gene and mutation in this gene is harmful in different cancers. This study aimed to use exome sequencing to uncover previously undetected breast cancer-predisposing variants. Also, we investigated the MLH3 gene expression of breast cancer patients which can be a breast cancer susceptibility gene. A total of 80 samples including 40 paired normal and cancer tissue samples were collected at Zheen International Hospital, Erbil, Iraq. Exome sequencing was used to identify mutations. Different in silico tools were used to predict the effect of mutation on the structural features or protein function. Real-time PCR was used for assessing the expression of MLH3 in breast cancer patients. We identified 26 variants in breast cancer patients, 22 inherited variants were found in MLH3, CHECK2, BRCA1, BRCA2, BLM, TP53, MSH6, NBN and PTEN genes and 4 somatic variants were found in PALB2, RAD50 and RBM10 genes. It was found that the expression of the MLH3 gene in tumor samples was significantly down-regulated compared with normal tissues. Statistically, high significance was found. The decreased expression of MLH3 was significant in all ranges of ages and all breast cancer types. Also, the expression of MLH3 decreased significantly in patients with breast cancer grades of II and III. In conclusion, MLH3 can be used as a susceptibility gene especially in grades II and III of breast cancer.

Expression patterns of LncRNA-GAS5 and its target APOBEC3C gene through miR-103 in breast cancer patients.

Early diagnosis of breast cancer can increase the survivability of the patients and the patient's quality of life. There is growing evidence demonstrating the active role of LncRNA-GAS5 and miR-103 in cancer biology. APOBEC enzymes are important players in immunity and may contribute to carcinogenesis. Mutation and expression alteration in the APOBEC gene family was found to have a strong correlation with breast cancer risk. This study aimed to evaluate the expression level of lncRNA-GAS5 and its target APOBEC3C in women with breast cancer through expression evaluation of miR-103. Moreover, the interaction between lncRNA-GAS5 and miR-103 was studied. In the present study, forty paired tumor and normal samples classified based on breast cancer subtypes and clinical features of patients were analyzed using gene expression studies. Immunohistochemical analysis of the gene products was performed to classify tumors. The RNA samples were extracted from breast tissue. Real-time PCR was conducted for APOBEC3C and Lnc-RNA GAS5 expression. In addition, miR-103a miScript Primer Assay was utilized for the expression of miR-103-5p. It was revealed that the expression level of APOBEC3C and lncRNA-GAS5 were significantly down-regulated; however, the miRNA-103 expression level was significantly up-regulated. GAS5 expression was positively correlated with APOBEC3C expression and negatively correlated with miR-103 expression. In conclusion, we observed down-regulation of APOBEC3C and LncRNA-GAS5 and up-regulation of miRNA 103 in breast cancer patients. The expression of GAS5 may provide a new potential treatment target for breast cancer. To clarify the role of these molecules in the cellular signaling pathways, further studies are required.

A novel deletion variant in CLN3 with highly variable expressivity is responsible for juvenile neuronal ceroid lipofuscinoses.

Mutations in CLN3 (OMIM: 607042) are associated with juvenile neuronal ceroid lipofuscinoses (JNCL)-a rare neurodegenerative disease with early retinal degeneration and progressive neurologic deterioration. The study aimed to determine the underlying genetic factors justifying the NCL phenotype in a large Iraqi consanguineous family. Four affected individuals with an initial diagnosis of NCL were recruited. By doing neuroimaging and also pertinent clinical examinations, e.g. fundus examination, due to heterogeneity of neurodevelopmental disorders, the proband was subjected to the paired-end whole-exome sequencing to identify underlying genetic factors. The candidate variant was also confirmed by Sanger sequencing. Various in silico predictions were used to show the pathogenicity of the variant. This study revealed a novel homozygous frameshift variant-NM_000086.2: c.1127del; p.(Leu376Argfs*15)-in the exon 14 of the CLN3 gene as the most likely disease-causing variant. Three out of 4 patients showed bilateral vision loss (< 7 years) and retinal degeneration with macular changes in both eyes. Electroencephalography demonstrated the loss of normal posterior alpha rhythm and also low amplitude multifocal slow waves. Brain magnetic resonance imaging of the patients with a high degree of deterioration showed mild cerebral and cerebellar cortical atrophy, mild ventriculomegaly, thinning of the corpus callosum and vermis, and non-specific periventricular white matter signal changes in the occipital area. The novel biallelic deletion variant of CLN3 was identified that most probably led to JNCL with variable expressivity of the phenotype. This study also expanded our understanding of the clinical and genetic spectrum of JNCL.

The Relevance of SNPs at 3'UTR Region of CASP7 and miR-371b-5p Associated Diseases: A Computational Analysis.

The process of genetically programmed cell death, or apoptosis, plays a crucialrolein cellular homeostasis and gene expression. Disruption of apoptosis may lead to aberrant immune responses, cancer, and neurodegenerative diseases. Single nucleotide polymorphisms (SNPs) present in various microRNA (miRNA) genes and targets being an alteration of miRNA activity resulting in human diseases. Evidence reported that SNPs increase/decrease the effectiveness of the interaction between miRNAs and their target genes associated with diseases. The primary purpose of this study is not only to identify miRSNPs on the CASP7 gene (caspase-7) and SNPs in miRNA genes targeting 3'UTR but also to evaluate the effect of thesegene variations in apoptosis and their associated diseases. We detected 120 miRNAs binding sites and 27 different SNPs in binding sites of miRNA in 3'UTR of the CASP7 gene by ten different online softwares. Interestingly, miR-371b-5p's binding site on CASP7 has an SNP (rs576198588, G/T) on CASP7 3'UTR, and its genomic sequence has an SNP (rs751339395, G/T) at the same nucleotide with rs576198588. Similarly, two other SNPs (rs774879764, C/G rs750389063, C/T) were identified at the first position binding site of miR-371b-5p. Here, miRSNP (rs576198588) at CASP7 3'UTR and SNP (rs751339395) at miR-371b-5p genomic sequence cross-matches at the same site of binding region. Besides, miR-371b-5p targets many apoptosis-related genes (HIP1, TRIAP1, GSKIP, NIN, DAP, CAAP1, XIAP, TMBIM1, TMBIM4, TNFRSF10A, RAD21, AKT1, BAG1, BAG4) even though it had no apoptosis correlated interaction demonstrated formerly. It assures that CASP7 could have a significant consequence on apoptosis through different pathways. Henceforth, this study was representing and signifying an influential connotation among miR-371b-5p and apoptosis via computational exploration and recommended to have better insight.

Novel SARS-CoV-2/COVID-19: Origin, pathogenesis, genes and genetic variations, immune responses and phylogenetic analysis.

In this review, we focused on the origins of the novel coronavirus (SARS-CoV-2), origin, pathogenesis, immune responses, genes and genetic variations, phylogenetic analyses, and potential therapeutic strategies to summarize approaches for developing broadly effective preventions and vaccines to cope COVID-19. Towards the end of 2019, SARS-CoV-2 has emerged in association with the SARS, later was named COVID-19 caused an environment of chaos worldwide and infected a massive number of lives. Since these epidemics or pandemics had spread to 210 countries and territories around the world and 2 international conveyances with 6,467,229 confirmed cases, including, 382,766 deaths, as of June 03, 2020 (https://www.worldometers.info/coronavirus/), hence the World Health Organization declared it as a global Public Health Emergency. There are no clinically approved vaccines or antiviral drugs available for either of new or old corona infections; thus, the development of effective therapeutic and preventive strategies that can be readily available to cope with these strains.

Genetic biomarkers: Potential roles in cancer diagnosis.

Biomarkers are indicators of pathogenic processes, typical biological processes, or pharmacological reactions to a therapy. It has several potential usages in cancer; differential diagnosis, prognosis, risk assessment, therapeutic response, and monitoring of disease progression. Recently, advances in oncomarkers raised significant opportunities for enhancing management of cancer. Chromosomal aberration, molecular impairment and epigenetic alteration might be applied to diagnose and prognose cancer and its epidemiology. Some oncomarkers are specific and highly sensitive for detection. An oncomarker might be used to see how the body reacts to an intervention or a situation. The present study represents a short review about various genetic oncomarkers with diagnostic and prognostic values.

Genomic characterization of a novel SARS-CoV-2.

A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.

Use of Plant Extracts in Alternative Medicine.

Plants provide the oxygen required for maintenance of human life. They are essential for human life in terms of food and health. Thousands of years ago, humans explored the therapeutic power of plants and preferred to benefit from them to live healthily. According to the data of the World Health Organization (WHO), the number of plants used for therapeutic purposes is around 20,000. Since the beginning of using plants for human health, the bioactivity characteristics of the plants have been studied in laboratories. There are various bioactive components in plants, the most important of which are secondary metabolites. It is very important how and by which methods the secondary metabolites of plants are characterized as well as their isolation, proper and effective performance of their extraction process and identification of their various biological activities that might be used in alternative medicine. This review examines the usability of supplementary medical support products after the identification of bioactive characteristics of plants by means of various biochemical and molecular biological methods.

Correction to: Molecular identification of Leishmania spp. isolates causes cutaneous leishmaniasis (CL) in Sanliurfa Province, Turkey, where CL is highly endemic.

In published article (Molecular Identification of Leishmania spp. Isolates Causes Cutaneous Leishmaniasis (CL) in Sanliurfa Province, Turkey, Where CL is Highly Endemic) Table 1 titled "The pH values of yogurts collected from villages in Turkey" doesn't belong to this article.

Molecular identification of Leishmania spp. isolates causes cutaneous leishmaniasis (CL) in Sanliurfa Province, Turkey, where CL is highly endemic.

Cutaneous leishmaniasis (CL) is an important public health problem in Turkey. CL has been most frequently seen in Sanliurfa. There is an expectation of increase in the population of leishmaniasis cases with the influence of Syrian refugees arriving in Turkey. In this study we aimed to diagnosis of CL and identifying of parasite from Leishmania isolates by using ITS 1 PCR RFLP. Samples were collected from 135 CL patients in Sanliurfa. After the specimens were inoculated in medium NNN, the ones which were cultures positive were cultivated in RPMI 1640 followed by PCR-RFLP. Genomic DNA was extracted phenol-chloroform procedure. Samples were examined by using ITS 1 PCR followed by RFLP analysis. Our results indicated that two species, L. tropica (132 samples) and L. major (3 samples), are responsible for cutaneous leishmaniasis in Sanliurfa. Our study is the first scientific study in which it is reported molecular analyses of cutaneous leishmaniasis cases caused by L. major in Sanliurfa in Southestern Anatolia Region. Because CL cases caused by L.major are detected in our study, it is considered that genotyping is important for diagnosis of Leishmania and following change of epidemiology.

Identification by using MALDI-TOF mass spectrometry of lactic acid bacteria isolated from non-commercial yogurts in southern Anatolia, Turkey.

Yogurt is a dairy product obtained by bacterial fermentation of milk. Commercial yogurts are produced using standard starters while, in the production of non-commercial yogurt, the microbiota is quite different since yogurts are used as starter for years. To determine the final characteristics of the fermented product it is necessary to know the biochemical properties of the starter cultures, such as acidity, aroma and flavor. This can only be achieved by identifying and characterizing the bacteria in starter cultures. In our study, 208 non-commercial yogurt samples were collected from 9 different locations in Anatolia, southern Turkey. Their pH and lactic acid bacteria profiles were analyzed. Isolated bacteria were identified by MALDI-TOF MS (matrix-assisted laser sesorption-ionization time-of-flight, mass spectrometry), which is a fast and reliable method for identification of bacterial isolates compared to classical laboratory methods. In this study, 41% of the isolates were identified by using this method, which is 99.9% and 34.0% confidence. The isolates contained two genera (Enterococcus and Lactobacillus) and four species. Afterwards, the four lactic acid bacteria were characterized physiologically and biochemically and we found that they differed from lactic acid bacteria used in commercial yogurt production. [Int Microbiol 20(1): 25-30 (2017)].

Identification by using MALDI-TOF mass spectrometry of lactic acid bacteria isolated from non-commercial yogurts in southern Anatolia, Turkey

Yogurt is a dairy product obtained by bacterial fermentation of milk. Commercial yogurts are produced using standard starters while, in the production of non-commercial yogurt, the microbiota is quite different since yogurts are used as starter for years. To determine the final characteristics of the fermented product it is necessary to know the biochemical properties of the starter cultures, such as acidity, aroma and flavor. This can only be achieved by identifying and characterizing the bacteria in starter cultures. In our study, 208 non-commercial yogurt samples were collected from 9 different locations in Anatolia, southern Turkey. Their pH and lactic acid bacteria profiles were analyzed. Isolated bacteria were identified by MALDI-TOF MS (matrix-assisted laser sesorption-ionization time-of-flight, mass spectrometry), which is a fast and reliable method for identification of bacterial isolates compared to classical laboratory methods. In this study, 41% of the isolates were identified by using this method, which is 99.9% and 34.0% confidence. The isolates contained two genera (Enterococcus and Lactobacillus) and four species. Afterwards, the four lactic acid bacteria were characterized physiologically and biochemically and we found that they differed from lactic acid bacteria used in commercial yogurt production (AU)

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Antitumoral effect of a selective Rho-kinase inhibitor Y-27632 against Ehrlich ascites carcinoma in mice.

BACKGROUND: The Rho proteins and Rho-kinase (ROCK) enzymes are responsible for signal transduction, and cause cell permeability, contractility, differentiation, migration, proliferation or apoptosis depending on cell types. All of these functions are vital for cancer initiation and progression. In this study, the preventive and protective effects of a selective ROCK inhibitor Y-27632 against Ehrlich ascites carcinoma in Swiss albino mice were investigated. METHODS: Adult male albino mice were divided into five equal groups, and Y-27632 (0.1, 1, and 10 mg/kg) was given to groups as two steps; before (pre-carcinoma) and after inoculation of carcinoma cell suspensions (post-carcinoma). At the end of the experiments (at day 15), cardiac blood samples, the ascitic fluid, and intestinal specimens were collected for histopathology and biochemical investigation. RESULTS: Significant decreases in the body weight and immunostaining scores in small and large intestine for ROCK2, preservation of serum glutathione (GSH) levels, and an increase in tumor level of nitric oxide were recorded in groups pretreated with Y-27632. However, treatment with Y-27632 after tumor inoculation did not affect body weight and ROCK2 immunostaining scores, increased serum MDA levels, and decreased GSH levels. CONCLUSIONS: This is the first study on the effectiveness of Y-27632 in this experimental tumor model. Our findings provided direct evidence for ROCK involvement in tumor development. These data suggest that pretreatment with Y-27632 has a protective effect against tumor formation.