Search results for: pathogenesis

Authors: Wael Khalil, Elias Rahal, Ghassan Matar

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Tooth related infections or commonly named dental infections have been described as the most common causes of tooth loss in adults. These pathologies were mostly periodontitis, pericoronitis, and periapical infection. The involvement of various bacteria in the pathogenesis of these pathologies has been thoroughly mentioned and approved in the literature. However, the variability in the severity and prognosis of these lesions among patients suggests the association of other pathogens, like viruses and fungi, in the pathogenesis of these lesions. Several studies in the literature investigated the association of multiple viruses and fungi with the above-mentioned lesions, yet, a vast controversy was reached concerning this subject.Aim: Our study aims to fill the gap in the literature concerning the contribution of adenovirus, HPV-16, EBV, fungi, and candida in the pathogenesis of periodontitis, pericoronitis, and periapical infection. For this purpose, we utilized the quantitative PCR for pathogen detection in saliva, gingival, and lesions samples of involved subjects. Results: Some of these pathogens appeared to have an association with the investigated dental pathologies, while others showed no contribution to the pathogenesis of these lesions. Further investigation is required in order to identify the subtype of the involved pathogens in these tooth related oral pathology.

Keywords: periodontitis, pericoronitis, dental abscess, PCR, microbiology

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Authors: Dwitya Elvira, Eryati Darwin

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Background: Graves’ disease (GD) is an autoimmune thyroid disease. Imbalance of Th1/Th2 cells and T-regulatory (Treg)/Th17 cells was thought to play pivotal role in the pathogenesis of GD. Treg FoxP3 produced TGF-β to maintain regulatory function, and Th17 cells produced IL-17 as cytokines that were thought in mediating several autoimmune diseases. The aim of this study is to assess the role of IL-17 and TGF-β in the pathogenesis of GD and to investigate its correlation with Thyroid Stimulating Hormone Receptor Antibody (TRAb) and Treg FoxP3 expression. Method: 30 GD patients and 27 age and sex-matched controls were enrolled in this study. Diagnosis of GD was based on clinical and biochemical of GD. Serum IL-17, TGF-β, TRAb, and FoxP3 were measured by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by using SPSS 21.0 (SPSS Inc.). Spearman rank correlation test was used for assessment of correlation. The statistical significance was accepted as P<0.05. Result: There was no significant correlation between IL-17 and TGF-β serum with expression of FoxP3 level in GD, but there was significant correlation between TGF-β and TRAb serum level (P<0.05). Serum levels of IL-17 and TGF-β were found to be elevated in patient group compared to control, where mean values of IL-17 were 14.43±2.15 pg/mL and TGF-β were 10.44±3.19 pg/mL in patients group; and in control group, level of IL-17 were 7.1±1.45 pg/mL and TGF-β were 4.95±1.35 pg/mL. Conclusion: Serum Il-17 and TGF-β were elevated in GD patients that reflect the role of inflammatory and regulatory cytokines activation in pathogenesis of GD. There was significant correlation between TGF-β and TRAb, revealing that Treg cytokines may play a role in pathogenesis of GD.

Keywords: IL-17, TGF-B, FoxP3, TRAb, Graves’ disease

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Authors: Kieren Luellman, Makenzi Rockwell, Eduardo Callegari, Nichole Haag, Chun Wu

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Multiple sclerosis (MS) is an autoimmune disorder that damages the myelin sheath of neurons in the central nervous system. The presence of Acinetobacter bacteria and anti-Acinetobacter antibodies in MS patients has led to the hypothesis that the bacteria may contribute to MS pathogenesis. In this study, the protein sequences of Acinetobacter baumannii were compared to five peptides from three mammalian myelin proteins, i.e., Proteolipid Protein (PLP): PLP 139-151, PLP 178-191, Myelin Basic Protein (MBP): MBP 84-104 and Myelin Oligodendrocyte Glycoprotein (MOG): MOG 35-55 and MOG 92-106 respectively, known to induce experimental autoimmune encephalomyelitis (EAE), a condition similar to MS. We found 11 hits (i.e., with five or more amino acid sequence similarity) in Acinetobacter baumannii, which are identical or similar to PLP139-151, 32 hits to PLP178-191, 35 to MBP 84-104, 41 hits to MOG 35-55 and 26 hits to MOG92-106. In addition, Western blotting was used to assess possible interaction between the bacterial proteins and human anti-MBP, anti-MOG, and anti-PLP antibodies produced in rabbits, corresponding to MBP 84-104, MOG 35-55, and PLP 139-151, respectively. We found that both human Polyclonal anti-MOG antibody and anti-PLP antibody recognized a protein or more proteins of the same molecular mass of around 25 kDa. in Acinetobacter baumannii. The results suggested that this/these protein(s) might potentially serve as antigen(s) to induce anti-MOG antibody and anti-PLP antibody production in mammalian B cells. The proteomic study identified 433 hits, among which the sequence of Acinetobacter baumannii protein 491 subunit A matches a previously published enzyme Acinetobacter 3-Oxoadipate CoA-Transferase, in which a fragment of its peptide was observed to recognize MS patient serum via ELISA method. Our findings might pave the road to understanding one of the pathogenesis mechanisms of MS.

Keywords: multiple sclerosis, pathogenesis, Acinetobacter baumannii, antibody recognition

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Authors: Humberto Foyaca Sibat, Lourdes de Fátima Ibañez Valdés

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Background Cysticercosis (Ct) is a preventable and eradicable zoonotic parasitic disease secondary to a cestode infection by the larva form of pig tapeworm Taenia solium (Ts), mainly seen in people living in developing countries. When the cysticercus is in the brain parenchymal, intraventricular system, subarachnoid space (SAS), cerebellum, brainstem, optic nerve, or spinal cord, then it has named neurocysticercosis (NCC), and the often-clinical manifestations are headache and epileptic seizures/epilepsy among other less frequent symptoms and signs. In this study, we look for a manuscript related to the role played by oligodendrocytes in the pathogenesis of NCC. We review this issue and formulate some hypotheses regarding its role and the role played in the pathogenesis of calcified NCC and epileptic seizures, and secondary epilepsy. Method: We searched the medical literature comprehensively, looking for published medical subject heading (MeSH) terms like "neurocysticercosis", "pathogenesis of neurocysticercosis", "comorbidity in NCC"; OR "oligodendrocytes"; OR "oligodendrocyte precursor cells(OPC/NG2)"; OR "epileptic seizures(ES)/Epilepsy(Ep)/NCC" OR "oligodendrocytes(OLG)/ES/Ep”; OR "calcified NCC/OLG"; OR “OLG Ca2+.” Results: All selected manuscripts were peer-reviewed, and we did not find publications related to OLG/NCC.

Keywords: oligodendrocytes, neurocysticercosis, oligodendrocytes, oligodendrocyte precursor cell, KG2, calcified neurocysticercosis, cellular calcium influx.

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Authors: Hyeon Su Kim, Sungjin Park, Hae Ryung Chang, Hae Rim Jung, Young Zoo Ahn, Yon Hui Kim, Seungyoon Nam

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Ependymoma, one of the most common parenchymal spinal cord tumor, represents 3-6% of all CNS tumor. Especially intracranial ependymomas, which are more frequent in childhood, have a more poor prognosis and more malignant than spinal ependymomas. Although there are growing needs to understand pathogenesis, detailed molecular understanding of pathogenesis remains to be explored. A cancer cell is composed of complex signaling pathway networks, and identifying interaction between genes and/or proteins are crucial for understanding these pathways. Therefore, we explored each ependymoma in terms of differential expressed genes and signaling networks. We used Microsoft Excel™ to manipulate microarray data gathered from NCBI’s GEO Database. To analyze and visualize signaling network, we used web-based PATHOME algorithm and Cytoscape. We show HOX family and NEFL are down-regulated but SCL family is up-regulated in cerebrum and posterior fossa cancers over a spinal cancer, and JAK/STAT signaling pathway and Chemokine signaling pathway are significantly different in the both intracranial ependymoma comparing to spinal ependymoma. We are considering there may be an age-dependent mechanism under different histological pathogenesis. We annotated mutation data of each gene subsequently in order to find potential target genes.

Keywords: systems biology, ependymoma, deg, network analysis

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Authors: Sandeep Pandey, Nimra Habib, Ranjana Singh, Abbas Ali Mahdi

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Leukemia is a malignancy of blood that mainly affects children and young adults; while advancement in the early diagnosis will have the potential to improve the outcome of diseases. A wide range of disease including leukemia shows inflammatory signals in their pathogenesis. In a pilot study conducted in our laboratory, 52 people were screened, of which 26 had leukemia and 26 were free from any kind of malignancy. We performed the estimation of the inflammatory cytokine Interleukin-8 and it was found significantly raised in all the leukemia patients concerning healthy volunteers who participated in the study. Flow cytometry had been performed for the confirmation of leukemia and further genomic, and proteomic, analyses of the sample revealed that IL-8 levels showed a positive correlation in patients with leukemia. The results had shown constitutive secretion of interleukin-8 by leukemia cells. So, our finding demonstrated that IL-8 is considered to have a role in the pathogenesis of leukemia, and quantification of IL-8 levels in leukemia conditions might be more useful and feasible in the clinical setting for the prediction of drug responses where it may represent a putative target for innovative diagnostic toward effective therapeutic approaches. However, further research explorations in this area are needed that include a greater number of patients with all different forms of leukemia, and estimating their IL-8 levels may hold the key for the additional predictive values on the recurrence of leukemia and its prognosis.

Keywords: T-ALL, IL-8, leukemia pathogenesis, cancer therapeutics

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Authors: Lourdes De Fátima Ibañez Valdés, Humberto Foyaca Sibat

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Background: Cysticercosis (Ct) is a preventable and eradicable zoonotic parasitic disease secondary to an infection caused by the larva form of pig tapeworm Taenia solium (Ts), which is mainly seen in people living in developing countries. However, the number of carriers in developed countries increases gradually due to globalization and uncontrolled migration. In this study, we look for the role played by autoimmune innate microglia (Mg) in the pathogenesis of intraparenchymal/subarachnoid neurocysticercosis. (I-SNCC)/ischemic -reperfusion injury (IRI). After reviewing this issue, we formulate some hypotheses regarding to the role of Mg in this process and deliver some novel therapeutic approaches for I- SNCC/IRI. Method: We searched the medical literature comprehensively, looking for published medical subject heading (MeSH) terms like "neurocysticercosis"; "pathogenesis of neurocysticercosis"; "comorbidity in NCC"; OR "I-SNCC"; OR "IRI;" OR "NCC/IS;" OR "Treatment of I-SNCC/IRI;" OR “MPC;” OR “ischemic stroke” OR “subarachnoid neurocysticercosis” OR “racemose neurocysticercosis” Results: All selected manuscripts were peer-reviewed, and we did not find publications related to Mga/I-SNCC/IRI. Comments and concluding remarks: We hypothesized the role played by Mg on the pathogenesis of I-SNCC the role of Mg during the colloid/nodular stage of INCC and racemose NCC and an associated ischemic stroke based on the well-known benefits of Mg polarization.

Keywords: Cysticercosis, neurocysticercosis, microglia activation, apoptosis, pyroptosis, necroptosis, PANoptosis, PANoptosome, infectious vasculitis, ischemic stroke, vascular dementia, racemose neurocysticercosis, subarachnoid neurocysticercosis, extra parenchymal neurocysticercosis

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Authors: Dalia G. Aseel

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The potato (Solanum tubersum, L.) has become one of the major vegetable crops in Egypt and all over the world. Potato leafroll virus(PLRV) was observed on potato plants collected from different governorates in Egypt. Three cultivars, Spunta, Diamont, and Cara, infected with PLRV were collected; RNA was extracted and subjected to Real-Time PCR using the coat protein gene primers. The results showed that the expression of the coat protein was 39.6-fold, 12.45-fold, and 47.43-fold, respectively, for Spunta, Diamont, and Cara cultivars. Differential Display Polymerase Chain Reaction (DD-PCR) using pathogenesis-related protein 1 (PR-1), β-1,3-glucanases (PR-2), chitinase (PR-3), peroxidase (POD), and polyphenol oxidase (PPO) forward primers for pathogenesis-related proteins (PR). The obtained data revealed different banding patterns depending on the viral type and the region of infection. Regarding PLRV, 58 up-regulated and 19 down-regulated genes were detected. Sequence analysis of the up-and down-regulated genes revealed that infected plants were observed in comparison with the healthy control. Sequence analysis of the up-regulated gene was performed, and the encoding sequence analysis showed that the obtained genes include: induced stolen tip protein. On the other hand, two down-regulated genes were identified: disease resistance RPP-like protein and non-specific lipid-transfer protein. In this study, the expressions of PR-1, PR-2, PR-3, POD, and PPO genes in the infected leaves of three potato cultivars were estimated by quantitative real-time PCR. We can conclude that the PLRV-infection of potato plants inhibited the expression of the five PR genes. On the contrary, infected leaves by PLRV elevated the expression of some defense genes. This interaction may also induce and/or suppress the expression of some genes responsible for the plant's defense mechanisms.

Keywords: PLRV, pathogenesis-related proteins (PRs), DD-PCR, sequence, real-time PCR

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Authors: I. Boroňová, J. Bernasovská, J. Kľoc, Z. Tomková, E. Petrejčíková, S. Mačeková, J. Poráčová, M. M. Blaščáková

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Osteoporosis is a common multifactorial disease with a strong genetic component characterized by reduced bone mass and increased risk of fractures. Genetic factors play an important role in the pathogenesis of osteoporosis. The aim of our study was to identify the genotype and allele distribution of T245G polymorphism in OPG gene in Slovak postmenopausal women. A total of 200 unrelated Slovak postmenopausal women with diagnosed osteoporosis and 200 normal controls were genotyped for T245G (rs3134069) polymorphism of OPG gene. Genotyping was performed using the Custom Taqman®SNP Genotyping assays. Genotypes and alleles frequencies showed no significant differences (p=0.5551; p=0.6022). The results of the present study confirm the importance of T245G polymorphism in OPG gene in the pathogenesis of osteoporosis.

Keywords: OPG gene, T245G polymorphism, osteoporosis, T245G polymorphism, real-time PCR

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Authors: Rudzani Manafe, Ezekiel Green

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Brucella, has many different virulence factors that act as a causative agent of brucellosis, depending on the environment and other factors, some factors may play a role more than others during infection and as a result, play a role in becoming a causative agent for pathogenesis. Brucella melitensis and Brucella abortus are considered to be pathogenic to humans. The genetic regularity of nine potential causes of virulence of two Brucella species in Eastern Cape livestock have been examined. A hundred and twenty isolates obtained from Molecular Pathogenesis and Molecular Epidemiology Research Group (MPMERG) were used for this study. All isolates were grown on Brucella agar medium. Nine primer pairs were used for the detection of virB2, virB5, vceC, btpA, btpB, prpA, betB, bpe275, and bspB virulence factors using Polymerase chain reaction (PCR). Approximately 100% was observed for genes BecC and BetB from B. arbotus. While the lowest gene observed was PrpA at 4.6% from B. arbotus. BetB was detected in 34.7%, while virB2 and prpA (0%) were not detected in B. melitensis. The results from this research suggest that most isolates of Brucella have virulence-related genes associated with disease pathogenesis. Finally, our findings showed that Brucella strains in the Eastern Cape Province are extremely virulent as virulence characteristics exist in most strains investigated.

Keywords: putative virulence genes, brucella, polymerase chain reaction, milk

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Authors: Khalda Amr, Noha Eltaweel, Sherif Ismail, Hala Raslan

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Introduction: Osteoarthritis is the most common form of arthritis that involves the wearing away of the cartilage that caps the bones in the joints. While rheumatoid arthritis is an autoimmune disease in which the immune system attacks the joints, beginning with the lining of joints. In this study, we aimed to study the top deregulated miRNAs that might be the cause of pathogenesis in both diseases. Methods: Eight cases were recruited in this study: 4 rheumatoid arthritis (RA), 2 osteoarthritis (OA) patients, as well as 2 healthy controls. Total RNA was isolated from plasma to be subjected to miRNA profiling by NGS. Sequencing libraries were constructed and generated using the NEBNextR UltraTM small RNA Sample Prep Kit for Illumina R (NEB, USA), according to the manufacturer’s instructions. The quality of samples were checked using fastqc and multiQC. Results were compared RA vs Controls and OA vs. Controls. Target gene prediction and functional annotation of the deregulated miRNAs were done using Mienturnet. The top deregulated miRNAs in each disease were selected for further validation using qRT-PCR. Results: The average number of sequencing reads per sample exceeded 2.2 million, of which approximately 57% were mapped to the human reference genome. The top DEMs in RA vs controls were miR-6724-5p, miR-1469, miR-194-3p (up), miR-1468-5p, miR-486-3p (down). In comparison, the top DEMs in OA vs controls were miR-1908-3p, miR-122b-3p, miR-3960 (up), miR-1468-5p, miR-15b-3p (down). The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Six of the deregulated miRNAs (miR-15b, -128, -194, -328, -542 and -3180) had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis. Conclusion: Six of our studied deregulated miRNAs (miR-15b, -128, -194, -328, -542 and -3180) might be highly involved in the disease pathogenesis. Further functional studies are crucial to assess their functions and actual target genes.

Keywords: next generation sequencing, mirnas, rheumatoid arthritis, osteoarthritis

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Authors: David J. Thomson, Joshua C. J. Chew

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Background: Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT) is a rare complication of lithium toxicity that typically causes irreversible cerebellar dysfunction. These patients may require hemodialysis and extensive supports in the intensive care. Methods: A review was performed on the available literature of SILENT with a focus on current pathophysiological hypotheses and advances in treatment. Articles were restricted to the English language. Results: Although the exact mechanism is unclear, CNS demyelination, especially in the cerebellum, was seen on the brain biopsies of a proportion of patients. There is no definitive management of SILENT but instead current management is focused on primary and tertiary prevention – detection of those at risk, and rehabilitation post onset of neurological deficits. Conclusions: This review draws conclusions from a limited amount of available literature, most of which are isolated case reports. Greater awareness of SILENT and further investigation into the risk factors and pathogenesis are required so this serious and irreversible syndrome may be avoided.

Keywords: lithium toxicity, pathogenesis, SILENT, syndrome of irreversible lithium-effectuated neurotoxicity

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Authors: Ashiraliyev SHavkat

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Relevance of the topic: Diabetes mellitus in overweight people development and absence of treatment measures. Objective: to give patients the correct instructions on proper nutrition, to organize a network of preventive and therapeutic measures. Materials and methods: Multidisciplinary Tashkent Medical Academy. As a result of objective observations in patients who applied to the clinic, 28 11 overweight patients had to type 2 diabetes. Diabetesmellituswasdiagnosed. Results: 11.5 mmol / L on an empty stomach in the morning. EDT yes. Pathogenesis: fat content in the diet of patients with diabetes mellitus. Carbohydrate foods make up 60%. Eating disorders and physical inactivity As a result, the accumulation of glucose in the form of fat increases, and this is constantly in the blood, which led to an increase in the number of fatty acids. Clinic: Frequent fasting in 11 patients (hypothalamus). Associated with glucose deficiency), drinking 8-9 liters of water per day of blood in 7 people Systolic pressure 150 diastolic pressures 100. Sensation of ants in 3 people and poor eyesight in 5 people. Conclusion: Explain to patients that nutritional guidelines should be followed. Assign active movement in accordance with the energy entering the body.

Keywords: mellitus, diabetes, pathogenesis, clinic

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Authors: Hala O. El-Mesallamy, Salwa M. Suwailem, Mae M. Seleem

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Visfatin and apelin are two new adipokines that recently gained a special interest in diabetes research. This study was conducted to study the interplay between these two adipokines and their correlation with other inflammatory and biochemical parameters in type 2 diabetic (T2D) postmenopausal women with CAD. Visfatin and apelin were measured by enzyme-linked immunoassay (ELISA). Visfatin was found to be significantly higher in the following groups: T2D patients without CAD, non-obese and obese T2D patients with CAD when compared to control group. Apelin was found to be significantly lower in non-obese and obese T2D patients with CAD when compared to control group. Visfatin and apelin were found to be significantly associated with each other and with other biochemical parameters. The current study provides evidence for the interplay between visfatin and apelin through the inflammatory milieu characteristic of T2D and their possible role in the pathogenesis of CAD complication of T2D.

Keywords: apelin, coronary artery disease, inflammation, type 2 diabetes, visfatin

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Authors: Saha Saradindu, Das Payel, Somdeb BoseDasgupta

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Tuberculosis caused by Mycobacteria tuberculosis is a dreadful disease and more so with the advent of extreme and total drug-resistant species. Mycobacterial pathogenesis is an ever-changing paradigm from phagosome maturation block to phagosomal escape into macrophage cytosol and finally acid tolerance and survival inside the lysosome. Mycobacteria are adept at subverting the host immune response by highjacking host cell signaling and secreting virulence factors. One such virulence factor is a ser/thr kinase; Protein kinase G (PknG), which is known to prevent phagosome maturation. The host substrates of PknG, allowing successful pathogenesis still remain an enigma. Hence we carried out a comparative phosphoproteomic screen and identified a number of substrates phosphorylated by PknG. We characterized some of these substrates in vivo and in vitro and observed that PknG mediated phosphorylation of these substrates leads to reduced TNFa production as well as decreased response to TNFa induced macrophage necroptosis, thus enabling mycobacterial survival and proliferation.

Keywords: mycobacteria, Protein kinase G, phosphoproteomics, necroptosis

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Authors: Saira Baloch, Mohsin Ali Baloch

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Background: Malaria is a potentially life-threatening disease and also a major public health problem in Pakistan. Renal failure is an emerging problem correlated with morbidity and mortality, however can be diagnosed and treated in the early stages. Objectives: To elucidate the biochemical renal parameters in patients with falciparum malaria and comparison with healthy control subjects. Method: 80 patients, who were diagnosed to be affected by falciparum malaria. Detailed history, general physical and systemic examination and necessary pathological, biochemical renal laboratory parameters and investigations were done. Results: Among the 80 patients, 43 were males and 37 were females. All patients were infected with P. falciparum. All patients had increased serum creatinine and urea levels and urine output of less than 400 ml/day were categorized as suffering from renal failure. Conclusion: Patients infected with P. falciparum are at an increased risk of developing renal failure when compared to patients infected with other complications. P. vivax has massive potential to cause life threatening complications and even death. Further research is required to understand the exact pathogenesis of various complications encountered in vivax malaria.

Keywords: falciparum malaria, renal failure, biochemical parameters, pathogenesis

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Authors: J. Vinay , Kusumbati Besra, Niharika Pattnaik, Shivaram Prasad Singh, Manjusha Dixit

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Gallbladder cancer (GBC) is rare but highly malignant cancer; its prevalence is more in certain geographical regions and ethnic groups, which include the Northern and Eastern states of India. Previous studies in India have reported genetic predisposition as one of the risk factors in GBC pathogenesis. Although the matrix metalloproteinase-14 (MMP14) is a well-known modulator of the tumor microenvironment and tumorigenesis and TCGA data also suggests its upregulation yet, its role in the genetic predisposition for GBC is completely unknown. We elucidated the role of MMP14 promoter variants as genetic risk factors and their implications in expression modulation. We screened MMP14 promoter variants association with GBC using Sanger’s sequencing in approximately 300 GBC and 300 control subjects and 26 GBC tissue samples of Indian ethnicity. The immunohistochemistry was used to check the MMP14 protein expression in GBC tissue samples. The role of promoter variants on expression levels was elucidated using a luciferase reporter assay. The variants rs1004030 (p-value = 0.0001) and rs1003349 (p-value = 0.0008) were significantly associated with gallbladder cancer. The luciferase assay in two different cell lines, HEK-293 (p = 0.0006) and TGBC1TKB (p = 0.0036) showed a significant increase in relative luciferase activity in the presence of risk alleles for both the single nucleotide polymorphisms (SNPs). Similarly, genotype-phenotype correlation in patients samples confirmed that the presence of risk alleles at rs1004030 and rs1003349 increased MMP14 expression. Overall, this study unravels the genetic association of MMP14 promoter variants with gallbladder cancer, which may contribute to pathogenesis by increasing its expression.

Keywords: gallbladder cancer, matrix metalloproteinase-14, single nucleotide polymorphism, case control study, genetic association study

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Authors: Mudassar Mohiuddin, Zahid Iqbal

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Introduction: Clostridium perfringens is an important pathogen responsible for causing enteric diseases in both human and animals. The bacteria produce several toxins. These toxins play vital role in the pathogenesis of various fatal enteric diseases and are classified into five types, on the basis of the differential production of Alpha, Beta, Epsilon and Iota toxins. In addition to the so-called major toxins, there are other toxins like beta2 toxin, produced by some strains of C. perfringens which may play a role in the pathogenesis of disease. Aim of the study: In this study a multiplex PCR assay was developed and used for detection of cpb2 gene to identify the Beta2 harboring isolates among different types of C. perfringens. Objectives: The primary objective of this study was to identify the prevalence of β2-toxin gene in local isolates of Clostridium perfringens. Methodology: This was an experimental study. Random sampling technique was used. A total of 97 sheep and goats were included in this study. All were Pakistani local breeds. The samples were collected during the period from Sep, 2014 to Mar, 2015 from selected districts of Punjab province (Pakistan). Faecal samples were cultured in cooked meat media. The identification of Clostridium perfringens was made on the basis of biochemical tests. Multiplex PCR was performed to identify the toxin genes. Results: A total of 43 C. perfringens isolates were genotyped using multiplex PCR assay. The gene encoding C. perfringens β2-toxin (cpb2) was present in more than 50% of the isolates genotyped. However, the prevalence of this gene varied between sheep and goat isolates. Conclusion: The present study suggests the high occurrence of C. perfringens b2-toxin (cpb2) in the local isolates of Pakistan. As β2-toxin is present in both healthy and diseased animals, so further studies are suggested to establish the role of β2-toxin in pathogenesis of the clostridial enteric diseases.

Keywords: beta 2 toxin gene, clostridium perfringens, enteric diseases, goats, multiplex PCR, sheep

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Authors: G. Anjan Babu, G. Sumana, M. Rajasekhar

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Many inherited diseases and non-hereditary disorders are common in the development of renal cystic diseases. Polycystic kidney disease (PKD) is a disorder developed within the kidneys in which grouping of cysts filled with water like fluid. PKD is responsible for 5-10% of end-stage renal failure treated by dialysis or transplantation. New experimental models, application of molecular biology techniques have provided new insights into the pathogenesis of PKD. Researchers are showing keen interest for developing an automated system by applying computer aided techniques for the diagnosis of diseases. In this paper a multi-layered feed forward neural network with one hidden layer is constructed, trained and tested by applying back propagation learning rule for the diagnosis of PKD based on physical symptoms and test results of urinanalysis collected from the individual patients. The data collected from 50 patients are used to train and test the network. Among these samples, 75% of the data used for training and remaining 25% of the data are used for testing purpose. Furthermore, this trained network is used to implement for new samples. The output results in normality and abnormality of the patient.

Keywords: dialysis, hereditary, transplantation, polycystic, pathogenesis

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Authors: Riffat Iqbal, Sidra Ihsan, Andleeb Batool, Maryam Mukhtar

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Glaucoma is a gathering of optic neuropathies described by dynamic degeneration of retinal ganglionic cells. It is clinically and innately heterogenous illness containing a couple of particular forms each with various causes and severities. Primary open-angle glaucoma (POAG) is the most generally perceived kind of glaucoma. This study investigated the genetic association of single nucleotide polymorphisms (SNPs; rs10483727 and rs33912345) at the SIX1/SIX6 locus with primary open-angle glaucoma (POAG) in the Pakistani population. The SIX6 gene plays an important role in ocular development and has been associated with morphology of the optic nerve. A total of 100 patients clinically diagnosed with glaucoma and 100 control individuals of age over 40 were enrolled in the study. Genomic DNA was extracted by organic extraction method. The SNP genotyping was done by (i) PCR based restriction fragment length polymorphism (RFLP) and sequencing method. Significant genetic associations were observed for rs10483727 (risk allele T) and rs33912345 (risk allele C) with POAG. Hence, it was concluded that Six6 gene is genetically associated with pathogenesis of Glaucoma in Pakistan.

Keywords: genotyping, Pakistani population, primary open-angle glaucoma, SIX6 gene

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Authors: Jianli Dong, Fangling Xu, Gengming Huang

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Human endogenous retroviral elements (HERVs) comprise approximately 8% of the human genome. They are thought to be germline-integrated genetic remnants of retroviral infections. Although HERV sequences are highly defective, some, especially the K type (HERV-K), have been shown to be expressed and may have biological activities in the pathogenesis of cancer, chronic inflammation and autoimmune diseases. We found that HERV-K GAG and ENV proteins were strongly expressed in pleomorphic melanoma cells. We also detected a critical role of HERV-K ENV in mediating intercellular fusion and colony formation of melanoma cells. Interestingly, we found that levels of HERV-K GAG and ENV expression correlated with the activation of ERK and loss of p16INK4A in melanoma cells, and inhibition of MEK or CDK4, especially in combination, reduced HERV-K expression in melanoma cells. We also performed a reverse transcription-polymerase chain reaction (RT-PCR) assay using DNase I digestion to remove “contaminating” HERV-K genomic DNA and examined HERV-K RNA expression in plasma samples from HIV-1 infected individuals. We found a covariation between HERV-K RNA expression and CD4 cell counts in HIV-1 positive samples. Although a causal link between HERV-K activation and melanoma development, and between HERV-K activation, HIV-1 infection and CD4 cell count have yet to be determined, existing data support the further research efforts in HERV-K.

Keywords: CD4 cell, HERV-K, HIV-1, melanoma

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Authors: Hala Raslan, Noha Eltaweel, Hanaa Rasmi, Solaf Kamel, May Magdy, Sherif Ismail, Khalda Amr

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Introduction: Rheumatoid arthritis (RA) is an inflammatory, autoimmune disorder with progressive joint damage. Osteoarthritis (OA) is a degenerative disease of the articular cartilage that shows multiple clinical manifestations or symptoms resembling those of RA. Genetic predisposition is believed to be a principal etiological factor for RA and OA. In this study, we aimed to measure the expression of the top deregulated miRNAs that might be the cause of pathogenesis in both diseases, according to our latest NGS analysis. Six of the deregulated miRNAs were selected as they had multiple target genes in the RA pathway, so they are more likely to affect the RA pathogenesis.Methods: Eighty cases were recruited in this study; 45 rheumatoid arthiritis (RA), 30 osteoarthiritis (OA) patients, as well as 20 healthy controls. The selection of the miRNAs from our latest NGS study was done using miRwalk according to the number of their target genes that are members in the KEGG RA pathway. Total RNA was isolated from plasma of all recruited cases. The cDNA was generated by the miRcury RT Kit then used as a template for real-time PCR with miRcury Primer Assays and the miRcury SYBR Green PCR Kit. Fold changes were calculated from CT values using the ΔΔCT method of relative quantification. Results were compared RA vs Controls and OA vs Controls. Target gene prediction and functional annotation of the deregulated miRNAs was done using Mienturnet. Results: Six miRNAs were selected. They were miR-15b-3p, -128-3p, -194-3p, -328-3p, -542-3p and -3180-5p. In RA samples, three of the measured miRNAs were upregulated (miR-194, -542, and -3180; mean Rq= 2.6, 3.8 and 8.05; P-value= 0.07, 0.05 and 0.01; respectively) while the remaining 3 were downregulated (miR-15b, -128 and -328; mean Rq= 0.21, 0.39 and 0.6; P-value= <0.0001, <0.0001 and 0.02; respectively) all with high statistical significance except miR-194. While in OA samples, two of the measured miRNAs were upregulated (miR-194 and -3180; mean Rq= 2.6 and 7.7; P-value= 0.1 and 0.03; respectively) while the remaining 4 were downregulated (miR-15b, -128, -328 and -542; mean Rq= 0.5, 0.03, 0.08 and 0.5; P-value= 0.0008, 0.003, 0.006 and 0.4; respectively) with statistical significance compared to controls except miR-194 and miR-542. The functional enrichment of the selected top deregulated miRNAs revealed the highly enriched KEGG pathways and GO terms. Conclusion: Five of the studied miRNAs were greatly deregulated in RA and OA, they might be highly involved in the disease pathogenesis and so might be future therapeutic targets. Further functional studies are crucial to assess their roles and actual target genes.

Keywords: MiRNAs, expression, rheumatoid arthritis, osteoarthritis

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Authors: Liaqat Ali, Hubert E. Blum, Türkân Sakinc

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Enterococcus faecium is an emerging multidrug-resistant nosocomial pathogen increased dramatically worldwide and causing bacteremia, endocarditis, urinary tract and surgical site infections in immunocomprised patients. The capsular polysaccharides that contribute to pathogenesis through evasion of the host innate immune system are also involved in hindering leukocyte killing of enterococci. The gene cluster (enterococcal polysaccharide antigen) of E. faecalis encoding homologues of many genes involved in polysaccharide biosynthesis. We identified two putative loci with 22 kb and 19 kb which contained 11 genes encoding for glycosyltransferases (GTFs); this was confirmed by using genome comparison of already sequenced strains that has no homology to known capsule genes and the epa-locus. The polysaccharide-conjugate vaccines have rapidly emerged as a suitable strategy to combat different pathogenic bacteria, therefore, we investigated a polysaccharide biosynthesis CapD protein in E. faecium contains 336 amino acids and had putative function for N-linked glycosylation. The deletion/knock-out capD mutant was constructed and complemented by homologues recombination method and confirmed by using PCR and sequencing. For further characterization and functional analysis, in-vitro cell culture and in-vivo a mouse infection models were used. Our ΔcapD mutant shows a strong hydrophobicity and all strains exhibited biofilm production. Subsequently, the opsonic activity was tested in an opsonophagocytic assay which shows increased in mutant compared complemented and wild type strains but more than two fold decreased in colonization and adherence was seen on surface of uroepithelial cells. However, a significant higher bacterial colonialization was observed in capD mutant during animal bacteremia infection. Unlike other polysaccharides biosynthesis proteins, CapD does not seems to be a major virulence factor in enterococci but further experiments and attention is needed to clarify its function, exact mechanism and involvement in pathogenesis of enteroccocal nosocomial infections eventually to develop a vaccine/ or targeted therapy.

Keywords: E. faecium, pathogenesis, polysaccharides, biofilm formation

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Authors: So Youn Park, Yi Sle Lee, Ki Whan Hong, Chi Dae Kim

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The role of metabolism in the pathogenesis of osteoarthritis is an emerging field. Metabolic alterations may be a role in osteoarthritis (OA) pathogenesis, and these changes influence joint destruction via several cytokine. Especially, in OA patients, levels of IL-1β are elevated in the synovial fluid, synovial membrane, subchondral bone, and cartilage. The IL-1β is activated by NLRP3 inflammasomes, and NLRP3 inflammasomes are cytosolic complexes that drive the production of other inflammatory cytokines, including IL-1β. In this study, we examined that SIRT1 suppresses IL-1β through inhibiting NLRP3 inflammasomes and SIRT1 ameliorates osteoarthritis. OA fibroblasts were isolated from synovium of OA patients. IL-1β and NLRP3 were detected in synovium of OA patients by immunohistochemistry. Lipopolysaccharides (LPS) stimulated the expression of active IL-1β mRNA in OA fibroblasts and combination of LPS, and adenosine triphosphate increased more the expression of active IL-1β in OA fibroblasts. The level of IL-1β was measured by western blot and ELISA assay. NLRP3 inflammasomes complex were measured by western blot. SIRT1 did not inhibit expression of NLRP3 inflammasome. So caspase-1, apoptotic speck-like protein containing a caspase recruitment domain (ASC) and NLRP3 protein were expressed in OA fibroblasts. But SIRT1 suppressed activation of IL-1β by inhibiting activity of caspase-1 via NLRP3 inflammasome in OA fibroblasts under LPS plus ATP stimulation. These results suggest that SIRT1 is a modulator of NLRP3 inflammasomes in OA fibroblasts and ameliorate IL-1β, so expression of SIRT1 in OA fibroblast may be a potential strategy for OA inflammation treatment.

Keywords: osteoarthritis, inflammasome, SIRT1, IL-1beta

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Authors: M. Błoch, P. Karpiński, P. Gasperowicz, R. Płoski, A. Lebioda, P. Skiba, A. Rozensztrauch, D. Patkowski, R. Śmigiel

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Introduction: The cause of the isolated form of esophageal atresia has been yet unknown. Objectives: The primary objective of this study was to indicate epigenetic factors which may play an important role in the etiopathogenesis of esophageal atresia. Methods: We recruited a group of 6 pairs of twins, among whom one of the twins developed EA. The selection of such a group for testing allows for excluding external factors (e.g., infections, drugs, toxins) as the cause of the birth defect. The analyzes were performed with the use of genetic material isolated from the whole blood and esophagus tissue of a patient with EA. The reduced representation bisulphite sequencing (RRBS) technique was used to study the change in the genomic imprinting -a change in the expression of genes, which may be the epigenetic cause of EA. Results: In the course of the analyzes, significant hypomethylation and hypermethylation regions were identified. 65 genes with probably increased expression and 65 with decreased expression were selected. These genes have not been marked in literature as possibly pathogenic in esophageal atresia. However, their participation in the pathogenesis of esophageal atresia cannot be clearly excluded. Conclusion: We suggest a role of hypomethylation or hypermethylation of selected genes as one of the possible epigenetic factors in EA pathogenesis. The use of the RRBS technique in the search for the cause of EA is pioneer research; therefore, it seems necessary to extend the research group to new patients with EA. Acknowledgment: The work was supported by the National Science Centre, Poland, under research project 2016/21/N/NZ5/01927.

Keywords: esophageal atresia, epigenetics, embryonic development, surgery, genes expression, twins

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Authors: Aniket Kumar, Jacob Peedicayil

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Major depressive disorder (MDD) is a common and important psychiatric disorder. Several clinical features of MDD suggest an epigenetic basis for its pathogenesis. Since epigenetics (heritable changes in gene expression not involving changes in DNA sequence) may underlie the pathogenesis of MDD, epigenetic drugs such as DNA methyltransferase inhibitors (DNMTi) and histone deactylase inhibitors (HDACi) may be useful for treating MDD. The available literature indexed in Pubmed on preclinical drug trials of epigenetic drugs for the treatment of MDD was investigated. The search terms we used were ‘depression’ or ‘depressive’ and ‘HDACi’ or ‘DNMTi’. Among epigenetic drugs, it was found that there were 3 preclinical trials using HDACi and 3 using DNMTi for the treatment of MDD. All the trials were conducted on rodents (mice or rats). The animal models of depression that were used were: learned helplessness-induced animal model, forced swim test, open field test, and the tail suspension test. One study used a genetic rat model of depression (the Flinders Sensitive Line). The HDACi that were tested were: sodium butyrate, compound 60 (Cpd-60), and valproic acid. The DNMTi that were tested were: 5-azacytidine and decitabine. Among the three preclinical trials using HDACi, all showed an antidepressant effect in animal models of depression. Among the 3 preclinical trials using DNMTi also, all showed an antidepressant effect in animal models of depression. Thus, epigenetic drugs, namely, HDACi and DNMTi, may prove to be useful in the treatment of MDD and merit further investigation for the treatment of this disorder.

Keywords: DNA methylation, drug discovery, epigenetics, major depressive disorder

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Authors: Husham Bayazed

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A growing number of studies indicate that atherosclerotic coronary artery disease (CAD) has a complex pathogenesis that extends beyond cholesterol intimal infiltration. The atherosclerosis process may involve an immune micro-environmental condition driven by local activation of the adaptive and innate immunity arrays, resulting in the formation of atherosclerotic plaques. Therefore, despite the wide usage of lipid-lowering agents, these devastating coronary diseases are not averted either at primary or secondary prevention levels. Many trials have recently shown an interest in the immune targeting of the inflammatory process of atherosclerotic plaques, with the promised improvement in atherosclerotic cardiovascular disease outcomes. This recently includes the immune-modulatory drug “Canakinumab” as an anti-interleukin-1 beta monoclonal antibody in addition to "Colchicine,” which's established as a broad-effect drug in the management of other inflammatory conditions. Recent trials and studies highlight the importance of inflammation and immune reactions in the pathogenesis of atherosclerosis and plaque formation. This provides an insight to discuss and extend the therapies from old lipid-lowering drugs (statins) to anti-inflammatory drugs (colchicine) and new targeted immune-modulatory therapies like inhibitors of IL-1 beta (canakinumab) currently under investigation.

Keywords: atherosclerotic plagues, immune microenvironment, lipid-lowering agents, and immunomodulatory drugs

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Authors: Fatemeh Keshavarz

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Background: Schizophrenia is a disease of the nervous system, and immune system disorders can affect its pathogenesis. Activation of microglia, proinflammatory cytokines, disruption of the blood-brain barrier (BBB) due to inflammation, activation of autoreactive B cells, and consequently the production of autoantibodies against system antigens are among the immune processes involved in neurological diseases. interleukin 32 (IL-32) a proinflammatory cytokine that important player in the activation of the innate and adaptive immune responses. This study aimed to measure the serum level of IL-32 as well as the frequency of autoantibody positivity against several nervous system antigens in patients with schizophrenia. Material and Methods: This study was conducted on 40 patients with schizophrenia and 40 healthy individuals in the control group. Serum IL-32 levels were measured by ELISA. The frequency of autoantibodies against Hu, Ri, Yo, Tr, CV2, Amphiphysin, SOX1, Zic4, ITPR1, CARP, GAD, Recoverin, Titin, and Ganglioside antigens were measured by indirect immunofluorescence method. Results: Serum IL-32 levels in patients with schizophrenia were significantly higher compared to the control group. Autoantibodies were positive in 8 patients for GAD antigen and 5 patients for Ri antigen, which showed a significant relationship compared to the control group. Autoantibodies were also positive in 2 patients for CV2, in 1 patient for Hu, and in 1 patient for CARP. Negative results were reported for other antigens. Conclusion: Our findings suggest that elevated the serum IL-32 level and autoantibody positivity against several nervous system antigens may be involved in the pathogenesis of schizophrenia.

Keywords: schizophrenia, microglia, autoantibodies, IL-32

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Authors: Marissa Dallara, Amalia Ardeljan, Lexi Frankel, Nadia Obaed, Naureen Rashid, Omar Rashid

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Human Cytomegalovirus (HCMV) is a ubiquitous virus that remains latent in approximately 60% of individuals in developed countries. Viral load is kept at a minimum due to a robust immune response that is produced in most individuals who remain asymptomatic. HCMV has been recently implicated in cancer research because it may impose oncomodulatory effects on tumor cells of which it infects, which could have an impact on the progression of cancer. HCMV has been implicated in increased pathogenicity of certain cancers such as gliomas, but in contrast, it can also exhibit anti-tumor activity. HCMV seropositivity has been recorded in tumor cells, but this may also have implications in decreased pathogenesis of certain forms of cancer such as leukemia as well as increased pathogenesis in others. This study aimed to investigate the correlation between cytomegalovirus and the incidence of breast cancer. Methods The data used in this project was extracted from a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to analyze the patients infected versus patients not infection with cytomegalovirus using ICD-10, ICD-9 codes. Permission to utilize the database was given by Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Data analysis was conducted using standard statistical methods. Results The query was analyzed for dates ranging from January 2010 to December 2019, which resulted in 14,309 patients in both the infected and control groups, respectively. The two groups were matched by age range and CCI score. The incidence of breast cancer was 1.642% and 235 patients in the cytomegalovirus group compared to 4.752% and 680 patients in the control group. The difference was statistically significant by a p-value of less than 2.2x 10^-16 with an odds ratio of 0.43 (0.4 to 0.48) with a 95% confidence interval. Investigation into the effects of HCMV treatment modalities, including Valganciclovir, Cidofovir, and Foscarnet, on breast cancer in both groups was conducted, but the numbers were insufficient to yield any statistically significant correlations. Conclusion This study demonstrates a statistically significant correlation between cytomegalovirus and a reduced incidence of breast cancer. If HCMV can exert anti-tumor effects on breast cancer and inhibit growth, it could potentially be used to formulate immunotherapy that targets various types of breast cancer. Further evaluation is warranted to assess the implications of cytomegalovirus in reducing the incidence of breast cancer.

Keywords: human cytomegalovirus, breast cancer, immunotherapy, anti-tumor

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Authors: Somaiya Mateen, Shagufta Moin, Mohammad Owais, Abdul Khan, Atif Zafar

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In rheumatoid arthritis (RA), impaired oxidative metabolism and imbalance between pro-and anti-inflammatory cytokines are responsible for causing inflammation and the degradation of cartilage and bone. The present study was done to evaluate the level and hence the role of reactive oxygen species (ROS) and inflammatory cytokines in the pathogenesis of RA. The present study was performed in the blood of 80 RA patients and 55 age and sex-matched healthy controls. The level of ROS (in 5% hematocrit) and the plasma level of pro-inflammatory cytokines [TNF-α, interleukin-6 (IL-6), IL-22] and anti-inflammatory cytokines (IL-4 and IL-5) were monitored in healthy subjects and RA patients. For evaluating the role of rheumatoid factor (RF) in the pathogenesis of RA, patients were sub-divided on the basis of presence or absence of RF. Reactive species and inflammatory cytokines were correlated with disease activity measure-Disease Activity Score for 28 joints (DAS28). The level of ROS, TNF-α, IL-6 and IL-22 were found to be significantly higher in RA patients as compared to the healthy controls, with the increase being more significant in patients positive for rheumatoid factor and those having high disease severity. On the other hand, a significant decrease in the level of IL-4 and IL-10 were observed in RA patients compared with healthy controls, with the decrease being more prominent in severe cases of RA. Higher ROS (indicative of impaired anti-oxidant defence system) and pro-inflammatory cytokines level in RA patients may lead to the damage of biomolecules which in turn contributes to tissue damage and hence to the development of more severe RA. The imbalance between pro-and anti-inflammatory cytokines may lead to the development of multi-system immune complications. ROS and inflammatory cytokines may also serve as a potential biomarker for assessing the disease severity.

Keywords: rheumatoid arthritis, reactive oxygen species, pro-inflammatory cytokines, anti-inflammatory cytokines

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