1.Clinical and Histopathological Relevance of Helicobacter pylori BabA2 Genotype
Tariq Elhashim ; M. Imad Mustafa Mahmud ; Imad M. Alani
The International Medical Journal Malaysia 2016;15(2):43-49
Introduction: H. pylori BabA is an outer membrane protein that mediates bacterial adherence to the gastric
epithelium, triggers several pathways during the course of infection, and thus contributes to the disease
development. Considering the variability in the presence of BabA coding gene (babA2) among H. pylori
clinical strains, the aim of this study was to assess the relationship between the genotype status of H. pylori
babA2 and the severity of clinical and histopathological outcomes. Methods: Gastric mucosal biopsy
specimens were collected from 30 CLO test-positive patients, 16 with gastritis and 14 with peptic ulcer
disease. Polymerase chain reaction was carried out to detect the presence of H. pylori-specific glmM gene
and BabA coding gene (babA2). Histopathological examination was performed to evaluate the severity of H.
pylori-associated gastric disease according to the Updated Sydney Classification System. Results: The glmM
and babA2 genes were present in 100% and 86.7% of the tested H. pylori strains, respectively. Although
higher degrees of inflammatory activity and H. pylori density were noted in babA2-positive biopsy
specimens, there was no statistically significant association between babA2 genotype status and the severity
of gastric disease. Conclusion: The babA2 genotype status of H. pylori may not be considered as a sole
marker for determining the infection outcomes.
2.Increased levels of multiple forms of dihydrofolate reductase in peripheral blood leucocytes of cancer patients receiving haematopoietic colony-stimulating factors: interim analysis.
M Perwaiz IQBAL ; Ikram A BURNEY ; Fakhra SULTANA ; Naseema MEHBOOBALI ; Tariq SIDDIQUI
Experimental & Molecular Medicine 2000;32(2):84-87
The precise mechanism whereby granulocytes proliferate when haematopoietic colony stimulating factors (CSFs) are used in neutropenic cancer patients is poorly understood. The purpose of this study was to investigate whether these cytokines bring about leucocyte proliferation by increasing the levels of multiple forms of dihydrofolate reductase (DHFR). Blood samples were collected from 36 cancer patients (25 males and 11 females) with chemotherapy-induced neutropenia. One sample of blood from each patient was obtained before therapy either with CSF, such as granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) or with placebo, and another one at the time of resolution of neutropenia. Peripheral blood leucocytes in these blood samples were counted, separated and lysed. From lysates, cytoplasmic samples were prepared and analyzed for active DHFR by a methotrexate-binding assay and for total immunoreactive DHFR by an enzyme linked immunosorbent assay. The increase in total leucocyte count (TLC) was most prominent (P < 0.005) in the CSF group and less so (P < 0.05) in the placebo group. The mean +/- SD concentration values of active DHFR before and after stimulation with GM-CSF found were to be 0.34 +/- 0.4 ng/mg protein and 0.99 +/- 0.82 ng/mg protein, respectively, and in the group treated with G-CSF, 0.24 +/- 0.32 ng/mg protein and 1.18 +/- 2.4 ng/mg protein, respectively. This increase in active DHFR after stimulation with CSF was statistically significant (P <0.05). Similarly, concentration values of immunoreactive but nonfunctional form of DHFR (IRE) were 110 +/- 97 ng/mg protein and 605 +/- 475 ng/mg protein before and after stimulation with GM-CSF, and 115 +/- 165 ng/mg protein and 1,054 +/- 1,095 ng/ mg protein before and after stimulation with G-CSF. This increase in concentration of IRE after stimulation with GM-CSF or G-CSF was statistically significant (P < 0.005). In the control group, there was an increase in the concentration of both active DHFR and IRE after treatment with placebo. However, this was not statistically significant. Resolution of neutropenia was quicker in the groups treated with CSF compared to the control group. Results of this study indicate that colony stimulating factors (G-CSF and GM-CSF) induce white cell proliferation by increasing the levels of multiple forms of DHFR.
Adolescence
;
Adult
;
Cell Division/drug effects
;
Child
;
Female
;
Granulocyte Colony-Stimulating Factor/therapeutic use
;
Granulocyte Colony-Stimulating Factor/pharmacology*
;
Granulocyte Colony-Stimulating Factor/adverse effects
;
Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use
;
Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology*
;
Granulocyte-Macrophage Colony-Stimulating Factor/adverse effects
;
Human
;
Isoenzymes/metabolism
;
Isoenzymes/biosynthesis
;
Leukocyte Count
;
Leukocytes/pathology
;
Leukocytes/enzymology
;
Leukocytes/drug effects
;
Male
;
Middle Age
;
Neoplasms/enzymology
;
Neoplasms/drug therapy
;
Neoplasms/blood*
;
Neutropenia/metabolism*
;
Neutropenia/chemically induce
;
Neutropenia/blood
;
Tetrahydrofolate Dehydrogenase/metabolism*
;
Tetrahydrofolate Dehydrogenase/biosynthesis
3.miR-139 modulates MCPIP1/IL-6 expression and induces apoptosis in human OA chondrocytes.
Mohammad Shahidul MAKKI ; Tariq M HAQQI
Experimental & Molecular Medicine 2015;47(10):e189-
IL-6 is an inflammatory cytokine and its overexpression plays an important role in osteoarthritis (OA) pathogenesis. Expression of IL-6 is regulated post-transcriptionally by MCPIP1. The 3' untranslated region (UTR) of MCPIP1 mRNA harbors a miR-139 'seed sequence', therefore we examined the post-transcriptional regulation of MCPIP1 by miR-139 and its impact on IL-6 expression in OA chondrocytes. Expression of miR-139 was found to be high in the damaged portion of the OA cartilage compared with unaffected cartilage from the same patient and was also induced by IL-1beta in OA chondrocytes. Inhibition of miR-139 decreased the expression of IL-6 mRNA by 38% and of secreted IL-6 protein by 40%. However, overexpression of miR-139 increased the expression of IL-6 mRNA by 36% and of secreted IL-6 protein by 56%. These data correlated with altered expression profile of MCPIP1 in transfected chondrocytes. Studies with a luciferase reporter construct confirmed the interactions of miR-139 with the 'seed sequence' located in the 3' UTR of MCPIP mRNA. Furthermore, miR-139 overexpression increased the catabolic gene expression but expression of anabolic markers remained unchanged. Overexpression of miR-139 also induced apoptosis in OA chondrocytes. Importantly, we also discovered that IL-6 is a potent inducer of miR-139 expression in OA chondrocytes. These findings indicate that miR-139 functions as a post-transcriptional regulator of MCPIP1 expression and enhances IL-6 expression, which further upregulates miR-139 expression in OA chondrocytes. These results support our hypothesis that miR-139-mediated downregulation of MCPIP1 promotes IL-6 expression in OA. Therefore, targeting miR-139 could be therapeutically beneficial in the management of OA.
3' Untranslated Regions
;
Aged
;
*Apoptosis
;
Chondrocytes/*metabolism/pathology
;
Down-Regulation
;
Female
;
Gene Expression Regulation
;
Humans
;
Interleukin-6/*genetics
;
Male
;
MicroRNAs/*genetics
;
Middle Aged
;
Osteoarthritis/*genetics/pathology
;
RNA, Messenger/genetics
;
Ribonucleases/*genetics
;
Transcription Factors/*genetics
;
Up-Regulation
4.The SLC29A3 variant, neutrophilic dermatosis, and hyperferritinemia imitate systemic juvenile idiopathic arthritis in a Saudi child: a case report
Shahad ALANSARI ; Alhanouf ALSALEEM ; Tariq ALZAID ; Maad GALAL ; Noura ALYAHYA ; Sulaiman M AL-MAYOUF
Journal of Rheumatic Diseases 2023;30(2):133-137
Genetic defects of SLC29A3 result in a wide range of syndromic histiocytosis that encompasses H syndrome. Patients with SLC29A3 variants typically have hyperpigmentation, hypertrichosis, hepatosplenomegaly, sensorineural hearing loss, diabetes mellitus, and hypogonadism. Herein, we identify a novel phenotype in a girl presenting with clinical and laboratory findings similar to systemic juvenile arthritis and hyperferritinemia. Exome sequencing identified a homozygous variant in SLC29A3 (NM_018344.5: c.707C>T [p.T236M]). Our patient did not show the cardinal features of the broad spectrum of SLC29A3-related disorders. She demonstrated remarkable improvement in her clinical and laboratory manifestations after starting interleukin-1 blockade (Anakinra). Recent research suggests that SLC29A3-related disorders are accompanied with autoinflammation and autoimmunity due to an overactive inflammasome pathway, which is most likely induced by mitochondrial and lysosomal dysfunction. Hence, our findings may expand the phenotypic features of the SLC29A3 variant. Patients with the SLC29A3 variant and systemic inflammation may benefit from interleukin-1 blockade as a therapeutic option.
5.Evaluation of zirconia-porcelain interface using X-ray diffraction.
Tariq F ALGHAZZAWI ; Gregg M JANOWSKI
International Journal of Oral Science 2015;7(3):187-195
The aim of this study was to determine if accelerated aging of porcelain veneering had an effect on the surface properties specific to a tetragonal-to-monoclinic transformation (TMT) of zirconia restorations. Thirty-six zirconia samples were milled and sintered to simulate core fabrication followed by exposure to various combinations of surface treatments including as-received (control), hydrofluoric acid (HF), application of liner plus firings, application of porcelain by manual layering and pressing with firing, plus accelerated aging. The quantity of transformed tetragonal to monoclinic phases was analyzed utilized an X-ray diffractometer and one-way analysis of variance was used to analyze data. The control samples as provided from the dental laboratory after milling and sintering process had no TMT (Xm = 0). There was an effect on zirconia samples of HF application with TMT (Xm = 0.8%) and liner plus HF application with TMT (Xm = 8.7%). There was an effect of aging on zirconia samples (no veneering) with significant TMT (Xm = 70.25%). Both manual and pressing techniques of porcelain applications reduced the TMT (manual, Xm = 4.41%, pressing, Xm = 11.57%), although there was no statistical difference between them. It can be concluded that simulated applications of porcelain demonstrated the ability to protect zirconia from TMT after aging with no effect of a liner between different porcelain applications. The HF treatment also caused TMT.
Dental Porcelain
;
chemistry
;
Surface Properties
;
X-Ray Diffraction
;
methods
;
Zirconium
;
chemistry
6.Global Awareness of Myocardial Infarction Symptoms in General Population: a Systematic Review and Meta-Analysis
Akash SHARMA ; Karavadi VIDUSHA ; Harshini SURESH ; Ajan M. J. ; Kavinkumar SARAVANAN ; Madhvi DHAMANIA ; Nisha B ; Rabbanie Tariq WANI
Korean Circulation Journal 2021;51(12):983-996
Background and Objectives:
Knowledge about myocardial Infarction (MI) symptoms is crucial because inadequate awareness ensures direct association with patient delay and adverse health events subsequently.
Methods:
PRISMA guidelines were followed while conducting the systematic review with PROSPERO number CRD42020219802. An electronic search was conducted comprehensively through 5 databases to find those relevant articles systematically. Prevalence was calculated for each typical symptom of MI separately and subgroup analysis according to continent, country, gender and ethnicity was done. Meta-Analysis was conducted by using statistical software R version 3.4.3. A random-effects model was used.
Results:
Studies from 35 different countries with 120,988,548 individuals were included in the final analysis. The prevalence of chest pain awareness was highest, while it was lowest for jaw, back, and neck pain. There was no difference in terms of awareness in males and females. Prevalence of awareness of typical MI symptoms was higher in the Caucasian white, white, and non-Hispanic white groups than in other groups. The prevalence varies from less than 5% in African countries such as Kenya, Tanzania and Asian countries such as Nepal to as high as 90% in Germany.
Conclusions
People are well aware of chest pain as a symptom of MI. However, there is limited knowledge regarding other typical symptoms of MI.
7.Adequacy of sigmoidoscopy as compared to colonoscopy for assessment of disease activity in patients of ulcerative colitis: a prospective study
Sameet Tariq PATEL ; Anuraag JENA ; Sanjay CHANDNANI ; Shubham JAIN ; Pankaj NAWGHARE ; Saurabh BANSAL ; Harsh GANDHI ; Rishikesh MALOKAR ; Jay CHUDASAMA ; Prasanta DEBNATH ; Seemily KAHMEI ; Rima KAMAT ; Sangeeta KINI ; Qais Q CONTRACTOR ; Pravin M RATHI
Intestinal Research 2024;22(3):310-318
Background/Aims:
Patients of ulcerative colitis (UC) on follow-up are routinely evaluated by sigmoidoscopy. There is no prospective literature to support this practice. We assessed agreement between sigmoidoscopy and colonoscopy prospectively in patients with disease extent beyond the sigmoid colon.
Methods:
We conducted a prospective observational study at a tertiary care institute for agreement between sigmoidoscopy and colonoscopy. We assessed endoscopic activity using the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and histological activity using the Nancy Index (NI), Robarts Histopathology Index (RHI), and Simplified Geboes Score (SGS).
Results:
Sigmoidoscopy showed a strong agreement with colonoscopy for MES and UCEIS with a kappa (κ) of 0.96 and 0.94 respectively. The misclassification rate for MES and UCEIS was 3% and 5% respectively. Sigmoidoscopy showed perfect agreement (κ = 1.00) with colonoscopy for assessment of the presence of endoscopic activity in the colon using MES ≥ 1 as activity criteria and strong agreement (κ = 0.93) using MES > 1 as activity criteria. Sigmoidoscopy showed strong agreement with colonoscopy for assessment of the presence of endoscopic activity using UCEIS (κ = 0.92). Strong agreement was observed between sigmoidoscopy and colonoscopy using NI (κ = 0.86), RHI (κ = 1.00), and SGS (κ = 0.92) for the detection of histological activity. The misclassification rate for the detection of histological activity was 2%, 0%, and 1% for NI, RHI, and SGS respectively.
Conclusions
Sigmoidoscopy showed strong agreement with colonoscopy for endoscopic and histologic disease activity. Sigmoidoscopy is adequate for assessment of disease activity in patients with UC during follow-up evaluation.
8.Interplay of interleukins (IL6, IL10) and 25 hydroxycholecalciferol in asthmatic subjects with chronic post-COVID condition (PCC)
Jaleel, A. ; Namoos, K. ; Asim, S. ; Uppal, S.S. ; Zaman, S. ; Irfan, H. ; Pervaiz, S. ; Tariq, M. ; Shafique, M.
Tropical Biomedicine 2024;41(No.1):70-77
The study aimed to compare and correlate serum levels of IL-6, 10, and 25-hydroxycholecalciferol
in individuals with asthma with and without post-COVID condition (PCC). The study was designed
to investigate the inflammatory response and serum 25-hydroxycholecalciferol status in asthmatics
with and without PCC. A cross-sectional study of 252 subjects (128 asthmatics and 124 non-asthmatic
subjects) was carried out. Interleukins and 25-hydroxycholecalciferol levels were estimated on ELISA.
The principle findings were that IL-6 and 25-hydroxycholecalciferol levels were significantly increased
(p<0.001), while IL-10 levels were non-significant in asthmatics with PCC compared to those without PCC.
However, 25-hydroxycholecalciferol levels were significantly increased, but no significant change was
observed in IL-6, and IL-10 levels in non-asthmatics with and without chronic PCC. A significant positive
correlation (r = 0.258) was found between 25-hydroxycholecalciferol and IL-6 but a significant negative
correlation (r = -0.227) with IL-10 in asthmatics with PCC. Similarly, a significant negative correlation (r
= -0.285) was found between 25-hydroxycholecalciferol and IL-10 but was non-significant with IL-6 in
asthmatics without PCC. The correlation of 25-hydroxycholecalciferol with IL-10 was significant (0.683),
but IL-6 was non-significant in non-asthmatics with PCC. Multiple regression analysis showed that age,
IL-6, gender, and PCC were significantly related in adjusted values to 25-hydroxycholecalciferol. This
study sheds light on the complex liaison between 25-hydroxycholecalciferol levels and inflammatory
responses in asthmatics, especially those with PCC. The findings suggest that although asthmatics with
PCC maintain sufficient levels of 25-hydroxycholecalciferol, they show a substantial increase in the proinflammatory response. This suggests that PCC exacerbates the pro-inflammatory response in asthma.
Moreover, the study reveals that asthmatics, whether with or without PCC, display a negative correlation
between 25-hydroxycholecalciferol and the anti-inflammatory response. This emphasizes the main
influence of asthma on the overall inflammatory response. These findings reveal a complex interplay
between vitamin D levels and inflammatory mediators in asthmatic individuals with and without PCC.
9.Antibacterial activity of plant essential oils against indigenously characterized methicillin-resistant Staphylococcus aureus (MRSA)
Ali, T. ; Anjum, A.A. ; Sattar, M.M.K. ; Ali, M.A. ; Kamran, M. ; Tariq, M. ; Manzoor, R.
Tropical Biomedicine 2022;39(No.1):17-25
Plant essential oils were evaluated for antimicrobial activity against Methicillin-resistant
Staphylococcus aureus (MRSA). The isolates (n=03) were procured from Institute of Microbiology,
UVAS Lahore, Pakistan. After biochemical and 16S rRNA gene-based PCR characterization,
accession numbers were retrieved from NCBI i.e. MW344063.1, MW344064.1 and MW344065.1.
These isolates exhibited molecular positivity by multiplex PCR for mecA, coa and eta toxin
genes. Moreover, these isolates exhibited resistance to cefoxitin, ampicillin, amoxicillin,
penicillin, amoxicillin clavulanate, ciprofloxacin, erythromycin and gentamicin. The antibiotic
resistant isolates were evaluated for antimicrobial activity of plant essential oils. The
highest zone of inhibition (mean ZOI±S.D.) was measured for Cinnamomum verum (22.67±1.52
mm) followed by Eucalyptus globulus (18.67±2.51 mm) and Syzygium aromaticum (12.67±2.51 mm).
Lowest mean MIC value (0.33±0.11 mg/mL) was recorded for E. globulus. Eucalyptus globulus was
processed for fractionation by column chromatography and n-hexane, chloroform, n-hexane
+ chloroform and ethyl-acetate fractions were evaluated for antibacterial activity. Lowest
mean MIC (10.04±5.80 mg/mL) was recorded for E. globulus n-hexane fraction. Cell survival
percentage of BHK21 cell line was 51.7% at 54.87mg/mL concentration of E. globulus n-hexane
fraction. Through gas chromatography-mass spectrometry (GC-MS) analysis of n-hexane
fraction, benzene was found abundant (29.9%) as active compound. It was concluded that E.
globulus n-hexane fraction exhibited significantly promising results against MRSA.
10.Potent and conditional redirected T cell killing of tumor cells using Half DVD-Ig.
Philip D BARDWELL ; Matthew M STARON ; Junjian LIU ; Qingfeng TAO ; Susanne SCESNEY ; Gail BUKOFZER ; Luis E RODRIGUEZ ; Chee-Ho CHOI ; Jennifer WANG ; Qing CHANG ; Feng DONG ; Cherrie DONAWHO ; Jieyi WANG ; Christine M GRINNELL ; Edit TARCSA ; Charles HUTCHINS ; Tariq GHAYUR ; Jijie GU
Protein & Cell 2018;9(1):121-129
Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.
Animals
;
Antibodies, Bispecific
;
immunology
;
Antibodies, Monoclonal
;
immunology
;
pharmacokinetics
;
CD3 Complex
;
metabolism
;
Cell Line, Tumor
;
Cytotoxicity, Immunologic
;
ErbB Receptors
;
metabolism
;
Female
;
Humans
;
Lymphocyte Activation
;
immunology
;
Mice, SCID
;
Neoplasms
;
immunology
;
pathology
;
Rats, Sprague-Dawley
;
T-Lymphocytes, Cytotoxic
;
immunology