• Korean Journal of Microbiology
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• v.50 no.4
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• pp.281-284
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• 2014

Immune defense responses against Pseudomonas aeruginosa infection play an important role in maintaining homeostasis in the human body. Previously, we reported that expression of the bradykinin receptor (BR) is induced in response to P. aeruginosa infection. However, the factors responsible for the induction was uncertain. Here, we found that the type III secretion system (T3SS) is responsible for the induction of BR expression, and nucleoside diphosphate kinase (Ndk), as a novel T3SS effector, mediates the upregulation. The Ndk-mediated expression of BR was not induced by fliC mutant treatment, indicating the involvement of flagellin, one of the well-known pathogen-associated molecular patterns (PAMPs). Taken together, this study demonstrated that Ndk cooperates with flagella in the development of defense responses against P. aeruginosa infection.

• Journal of Nutrition and Health
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• v.50 no.3
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• pp.217-224
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• 2017

Purpose: Although it is well known thatmortality and morbidity due to cardiovascular diseases are higher in salt-sensitive subjects than in salt-resistant subjects, their underlying mechanisms related to obesity remain unclear. Here, we focused on salt-sensitive gene variants unrelated to monogenic obesity that interacted with sodium intake in humans. Methods: This review was written based on the modified $3^rd$ step of Khans' systematic review. Instead of the literature, subject genes were based on candidate genes screened from our preliminary Genome-Wide Association Study (GWAS). Finally, literature related to five genes strongly associated with salt sensitivity were analyzed to elucidate the mechanism of obesity. Results: Salt sensitivity is a measure of how blood pressure responds to salt intake, and people are either salt-sensitive or salt-resistant. Otherwise, dietary sodium restriction may not be beneficial for everyone since salt sensitivity may be associated with inherited susceptibility. According to our previous GWAS studies, 10 candidate genes and 11 single nucleotide polymorphisms (SNPs) associated with salt sensitivity were suggested, including angiotensin converting enzyme (ACE), ${\alpha}$-adducin1 (ADD1), angiotensinogen (AGT), cytochrome P450 family 11-subfamily ${\beta}$-2 ($CYP11{\beta}$-2), epithelial sodium channel (ENaC), G-protein b3 subunit (GNB3), G protein-coupled receptor kinases type 4 (GRK4 A142V, GRK4 A486V), $11{\beta}$-hydroxysteroid dehydrogenase type-2 (HSD $11{\beta}$-2), neural precursor cell-expressed developmentally down regulated 4 like (NEDD4L),and solute carrier family 12(sodium/chloride transporters)-member 3 (SLC 12A3). We found that polymorphisms of salt-sensitive genes such as ACE, $CYP11{\beta}$-2, GRK4, SLC12A3, and GNB3 may be positively associated with human obesity. Conclusion: Despite gender, ethnic, and age differences in genetics studies, hypertensive obese children and adults who are carriers of specific salt-sensitive genes are recommended to reduce their sodium intake. We believe that our findings can contribute to the prevention of early-onset of chronic diseases in obese children by facilitating personalized diet-management of obesity from childhood to adulthood.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2787-2793
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• 2016

Background: Urinary bladder cancer is a common malignancy in the West and ranks as the $7^{th}$ most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Materials and Methods: Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Results: Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (p<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. Conclusions: We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.54-62
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• 2019

Cis-3-O-p-hydroxycinnamoyl ursolic acid (HCUA), a triterpenoid compound, was purified from Elaeagnus oldhamii Maxim. This traditional medicinal plant has been used for treating rheumatoid arthritis and lung disorders as well as for its anti-inflammation and anticancer activities. This study aimed to investigate the anti-proliferative and apoptotic-inducing activities of HCUA in oral cancer cells. HCUA exhibited anti-proliferative activity in oral cancer cell lines (Ca9-22 and SAS cells), but not in normal oral fibroblasts. The inhibitory concentration of HCUA that resulted in 50% viability was $24.0{\mu}M$ and $17.8{\mu}M$ for Ca9-22 and SAS cells, respectively. Moreover, HCUA increased the number of cells in the sub-G1 arrest phase and apoptosis in a concentration-dependent manner in both oral cancer cell lines, but not in normal oral fibroblasts. Importantly, HCUA induced p53-mediated transcriptional regulation of pro-apoptotic proteins (Bax, Bak, Bim, Noxa, and PUMA), which are associated with mitochondrial apoptosis in oral cancer cells via the loss of mitochondrial membrane potential. HCUA triggered the production of intracellular reactive oxygen species (ROS) that was ascertained to be involved in HCUA-induced apoptosis by the ROS inhibitors YCG063 and N-acetyl-L-cysteine. As a result, HCUA had potential antitumor activity to oral cancer cells through eliciting ROS-dependent and p53-mediated mitochondrial apoptosis. Overall, HCUA could be applicable for the development of anticancer agents against human oral cancer.

• Genes and Genomics
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• v.40 no.12
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• pp.1363-1371
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• 2018

One of the main concerns in biology is extracting sophisticated features from DNA sequence for gene interaction determination, receiving a great deal of researchers' attention. The epigenetic modifications along with their patterns have been intensely recognized as dominant features affecting on gene expression. However, studying sequenced-based features highly correlated to this key element has remained limited. The main objective in this research was to propose a new feature highly correlated to epigenetic modifications capable of classification of genes. In this paper, classification of 34 genes in PPAR signaling pathway associated with muscle fat tissue in human was performed. Using different statistical outlier detection methods, we proposed that 5-mers highly correlated to epigenetic modifications can correctly categorize the genes involved in the same biological pathway or process. Thirty-four genes in PPAR signaling pathway were classified via applying a proposed feature, 5-mers strongly associated to 17 different epigenetic modifications. For this, diverse statistical outlier detection methods were applied to specify the group of thoroughly correlated genes. The results indicated that these 5-mers can appropriately identify correlated genes. In addition, our results corresponded to GeneMania interaction information, leading to support the suggested method. The appealing findings imply that not only epigenetic modifications but also their highly correlated 5-mers can be applied for reconstructing gene regulatory networks as supplementary data as well as other applications like physical interaction, genes prioritization, indicating some sort of data fusion in this analysis.

• Journal of Microbiology and Biotechnology
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• v.29 no.3
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• pp.500-505
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• 2019

Staphylococcus aureus is a round-shaped, gram-positive bacterium that can cause numerous infectious diseases ranging from mild infections such as skin infections and food poisoning to life-threatening infections such as sepsis, endocarditis and toxic shock syndrome. Various antibiotic-resistant strains of S. aureus have frequently emerged, threatening human lives significantly. Despite much research on the genetics of S. aureus, many of its genes remain unknown functionally and structurally. To counteract its toxins and to prevent the antibiotic resistance of S. aureus, our understanding of S. aureus should be increased at the proteomic scale. SAV0927 was first sequenced in an antibiotic resistant S. aureus strain. The gene is a conserved hypothetical protein, and its homologues appear to be restricted to Firmicutes. In this study, we determined the crystal structure of SAV0927 at $2.5{\AA}$ resolution. The protein was primarily dimeric both in solution and in the crystals. The asymmetric unit contained five dimers that are stacked linearly with ${\sim}80^{\circ}$ rotation by each dimer, and these interactions further continued in the crystal packing, resulting in a long linear polymer. The crystal structures, together with the network analysis, provide functional implications for the SAV0927-mediated protein network.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.1
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• pp.69-79
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• 2021

Objective: Poor ovarian response (POR) refers to a subnormal follicular response that leads to a decrease in the quality and quantity of the eggs retrieved after ovarian stimulation during assisted reproductive treatment (ART). The present study investigated the associations of multiple variants of the estrogen receptor 2 (ESR2) and follicle-stimulating hormone receptor (FSHR) genes with POR in infertile Jordanian women undergoing ART. Methods: Four polymorphisms, namely ESR2 rs1256049, ESR2 rs4986938, FSHR rs6165, and FSHR rs6166, were investigated in 60 infertile Jordanian women undergoing ART (the case group) and 60 age-matched fertile women (the control group), with a mean age of 33.60±6.34 years. Single-nucleotide polymorphisms (SNPs) were detected by restriction fragment length polymorphism and then validated using Sanger sequencing. Results: The p-value of the difference between the case and control groups regarding FSHR rs6166 was very close to 0.05 (p=0.054). However, no significant differences were observed between the two groups in terms of the other three SNPs, namely ESR2 rs1256049, ESR2 rs4986938, and FSHR rs6165 (p=0.561, p=0.433, and p=0.696, respectively). Conclusion: The association between FSHR rs6166 and POR was not statistically meaningful in the present study, but the near-significant result of this experiment suggests that statistical significance might be found in a future study with a larger number of patients.

• Clinical and Experimental Reproductive Medicine
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• v.49 no.3
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• pp.210-214
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• 2022

Objective: Platelet-rich plasma (PRP) therapy has received a considerable attention as an adjunct to fertility treatments, especially in women with very low ovarian reserve and premature ovarian insufficiency. Although recent studies have demonstrated that PRP led to improvements in folliculogenesis and biomarkers of ovarian reserve, the effect of intraovarian PRP administration on embryo genetics has not been studied. Methods: We report a pilot study of patients who had preimplantation genetic testing for aneuploidy (PGT-A) before and then within 3 months following PRP administration. Twelve infertile women with at least one prior failed in vitro fertilization (IVF) cycle underwent ovarian stimulation (cycle 1) with a gentle stimulation protocol and PGT-A performed at the blastocyst stage. Following cycle 1, autologous intraovarian PRP administration was performed. Within 3 months following PRP administration, the patients underwent cycle 2 and produced blastocysts for PGT-A. The percentage of euploid embryos between both cycles was compared. Results: The mean age of all participants was 40.08±1.46 years, and their mean body mass index was 26.18±1.18 kg/m². The number of good-quality embryos formed at the blastocyst stage was similar between cycle 1 and cycle 2 (3.08±0.88 vs. 2.17±0.49, respectively; p=0.11). Among all patients in cycle 1, 3 of 37 embryos were euploid (8.11%) while in cycle 2, 11 out of 28 embryos were euploid (39.28%, p=0.002). Three clinical pregnancies were noted among this patient group. Conclusion: This novel study is the first to present an improvement in the embryo euploidy rate following intraovarian PRP application in infertile women with prior failed IVF cycles. The growth factors present in PRP may exhibit a local paracrine effect that could improve meiotic aberrations in human oocytes and thus improve euploidy rates. Whether PRP improves live birth rates and lowers miscarriage rates remains to be determined in large trials.

• Natural Product Sciences
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• v.28 no.3
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• pp.121-129
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• 2022

Despite considerable efforts, cancer remains an aggressive killer worldwide. Chemotherapeutic drugs that are currently in use lead to destructive side effects and have not succeeded in fulfilling expectations. For centuries, medicinal plants are used for treating various diseases and are also known to have anticancer activity. The main aim of this research was to evaluate antiproliferative activity of saffron, clove, fenugreek, and green tea on Vero and MDA-MB-231 cell lines and to subsequently analyze the effect of these extracts on IRAK-4, TAK1, IKK-alpha, IKK-beta, NF-Kappa B, IRF3, IRF7 genes in Toll Like Receptors (TLRs) pathway. Antiproliferative assay was done by Neutral Red Dye uptake assay. Methanolic extract of green tea was found to be most effective against both cell lines as IC₅₀ was achieved at least concentration of the extract. For molecular studies, MDAMB-231 cells were sensitized with methanolic extract of green tea at same IC₅₀, and RT-PCR was performed to determine the relative expression of genes. Expression of IRAK-4, TAK1, IKK-beta, NF-Kappa B, IRF3 genes was down regulated and IRF7 and IKKalpha was upregulated. Green tea has a potential cytotoxic effect on both cell lines which was demonstrated by its effect on the expression of (TLRs) pathway genes.

• Journal of Genetic Medicine
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• v.20 no.2
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• pp.60-69
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• 2023

Purpose: Despite enzyme replacement therapy (ERT) and/or allogeneic hematopoietic stem cell transplantation, individuals with mucopolysaccharidosis (MPS) I or II often experience significant growth deficiencies. This study aimed to assess the safety and efficacy of recombinant human growth hormone (hGH) treatment in children diagnosed with MPS I or II. Materials and Methods: A total of nine pediatric patients-four with MPS I and five with MPS II-underwent treatment with ERT and hGH at Samsung Medical Center. Results: The mean hGH dose administered was 0.26±0.03 mg/kg/week. In the MPS I group, three patients showed an increase in height Z-score from -4.09±0.83 to -3.68±0.43 after 1 year of hGH treatment, and to -3.10±0.72 by the end of the hGH regimen. In the MPS II group, while the height Z-score of four patients decreased according to standard growth charts, it improved from 1.61±1.79 to 2.71±1.68 based on the disease-specific growth chart through hGH treatment. Two patients discontinued hGH treatment due to lack of efficacy after 22 and 6 months each of treatment, respectively. No new-onset neurological symptoms or necessity for prosthetic or orthopedic surgery were reported during hGH treatment. Conclusion: This study provides insights into the impact of hGH on MPS patients, demonstrating its potential to reverse growth deceleration in some cases. Further research is needed to explore the long-term effects of hGH on changes in body composition, muscle strength, and bone health in this population.