The Impact of Hydrogen Inhalation Therapy on Blood Reactive Oxygen Species Levels: A Randomized Controlled Study.

Reactive Oxygen Species (ROS) play a key role in physiological processes. However, the imbalance between ROS and antioxidants in favor of the former causes oxidative stress linked to numerous pathologies. Due to its unique attributes, including distinguished permeability and selective antioxidant capability, molecular hydrogen (H2) has become an essential therapeutic agent. Hydrogen Inhalation Therapy (HIT) has come to light as a promising strategy to counteract oxidative stress. In this randomized controlled study, we aimed to evaluate the effectiveness of HIT in reducing blood ROS levels. 37 participants with elevated ROS levels (d-ROMs value > 350 U.CARR) were enrolled in the study. Participants were divided into test and control groups. The test group participants received HIT, and then their blood ROS levels were measured immediately post-treatment and after 24 hours. Their results were compared to those of the control group participants who did not undergo HIT. The test group demonstrated a significant reduction in blood ROS levels after the treatment. These findings suggested the efficacy of HIT in reducing oxidative stress.

Characterization of a Novel Frameshift Mutation Within the TRPS1 Gene Causing Trichorhinophalangeal Syndrome Type 1 in a Kindred Cypriot Family.

Trichorhinophalangeal syndrome (TRPS) is an extremely rare autosomal dominant multisystem disorder characterized by craniofacial and skeletal abnormalities. Three subtypes of TRPS have been described: TRPS type I, TRPS type II, and TRPS type III. Mutations in the TRPS1 gene can cause both TRPS type I and TRPS type III. Therefore, the genotype-phenotype correlation is crucial to determine the subtype. The current family study from Cyprus involves affected patients from 4 generations who presented with alopecia, unoperated umbilical hernia, caput quadratum, long philtrum, depressed nasal bridge, frontal bossing, pes planus, beaked nose, and some deformities in hands and feet. Sequence analysis of the TRPS1 gene revealed a novel c.2854_2858del (p.Asn952ArgfsTer2) frameshift variant leading to a premature stop codon. To the best of our knowledge, we report here the first case of a Turkish Cypriot family of 4 generations with a novel frameshift mutation leading to truncated protein in the TRPS1 gene causing TRPS type I clinical phenotype. Overall, as the genotype and phenotype correlation in TRPSI is still uncertain and complex, the present outcome can enhance our knowledge of this complicated, rare, and severe genetic disorder.

CCR5-Δ32 gene variant frequency in the Nigerian and Zimbabwean populations living in North Cyprus.

Background: The cystine-cystine chemokine receptor 5 (CCR5) is the primary HIV co-receptor involved in the viral entry process into human cells. The 32 bp deletion variant within the CCR5 gene (CCR5-Δ32) plays a very important role in viral recognition and progression of AIDS. Objective: The current study was aimed at evaluating the CCR5-Δ32 gene variation frequency in Nigerian and Zimbabwean populations residing in Northern Cyprus. Methods: A total number of 211 subjects (103 Nigerians and 108 Zimbabweans) were analyzed. Nigerian population was further analyzed with respect to the three major ethnicities: Igbo, Hausa, and Yoruba. Polymerase Chain Reaction was used to determine the CCR5-Δ32 gene variant status. Results: All studied subjects from both sampling groups were homozygous for the CCR5 wild type gene (CCR5-wt), meaning neither heterozygous nor homozygous genotypes of CCR5-Δ32 gene variant were observed. Conclusion: This study observed the absence of CCR5-Δ32 deletion gene in the Nigeria and Zimbabwean populations living in Northern Cyprus. These populations lack the genetic advantage over HIV infection and may also show a rapid progression towards AIDS. Additionally, these populations could impact the local gene frequency as these two populations interact more and more.

Clinical and molecular evaluation of MEFV gene variants in the Turkish population: a study by the National Genetics Consortium.

Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disorder with recurrent fever, abdominal pain, serositis, articular manifestations, erysipelas-like erythema, and renal complications as its main features. Caused by the mutations in the MEditerranean FeVer (MEFV) gene, it mainly affects people of Mediterranean descent with a higher incidence in the Turkish, Jewish, Arabic, and Armenian populations. As our understanding of FMF improves, it becomes clearer that we are facing with a more complex picture of FMF with respect to its pathogenesis, penetrance, variant type (gain-of-function vs. loss-of-function), and inheritance. In this study, MEFV gene analysis results and clinical findings of 27,504 patients from 35 universities and institutions in Turkey and Northern Cyprus are combined in an effort to provide a better insight into the genotype-phenotype correlation and how a specific variant contributes to certain clinical findings in FMF patients. Our results may help better understand this complex disease and how the genotype may sometimes contribute to phenotype. Unlike many studies in the literature, our study investigated a broader symptomatic spectrum and the relationship between the genotype and phenotype data. In this sense, we aimed to guide all clinicians and academicians who work in this field to better establish a comprehensive data set for the patients. One of the biggest messages of our study is that lack of uniformity in some clinical and demographic data of participants may become an obstacle in approaching FMF patients and understanding this complex disease.

Natural selection at work? Vitamin D deficiency rates and rising health problems in young Turkish Cypriot professionals.

OBJECTIVES: Vitamin D is a fat-soluble, prohormone vitamin that is important especially for bone mineralization and skeletal health. In recent years, vitamin D deficiency appeared as a worldwide problem, affecting many people in different ways including the Northern Cypriot population. The deficiency might be caused by the lack of exposure to sunlight, diet low in vitamin D, sedentary lifestyle, and also due to some genetic variations in the vitamin D receptor (VDR) gene. METHODS: In this study, four common VDR polymorphisms and associations with vitamin D deficiency in the Turkish Cypriot population between ages 18-40 and working in office conditions was studied by PCR- RFLP analysis. RESULTS: rs2228570 C>T variant was shown to be significantly associated with low serum vitamin D levels in the studied population. CONCLUSION: Together with the effect of rs2228570 C>T variant in the VDR gene, it is thought that the lifestyle changes in the Turkish Cypriot population might have caused the increased frequency of vitamin D deficiency in the young professionals.

CCR5-Δ32 gene variant frequency in the Turkish Cypriot population.

Recent UNAIDS reports (December 2019) indicate that 37.9 million people have been affected by HIV infection around the globe in 2018, of which 1.7 million are cited as new infections. Human immunodeficiency virus-1 (HIV-1) requires both the CD4 receptor, as the primary receptor, and a chemokine co-receptor to gain entry into the cell. In addition to the WT allele for C-C motif chemokine receptor 5 (CCR5-wt), there is another allele with a 32 bp deletion in the protein coding region (CCR5-Δ32). Individuals who are homozygous for the mutant allele are resistant towards M-tropic HIV infections. In the current study, we aimed to determine the CCR5-Δ32 allele frequency in the Turkish Cypriot population with 326 subjects, 141 men (43.1%) and 185 (56.9%) women. The region of the CCR5 gene containing the Δ32 deletion was amplified using flanking primers. The CCR5 gene Δ32 allele frequency was calculated at 3% and only observed in heterozygous individuals. We hope that our current publication could be a point of dialog between the physicians, the government officials and the public set up a more modern and well-structured HIV screening program in an effort to control and hopefully eliminate HIV from the Turkish Cypriot population.

The determination of the potential anticancer effects of Coriandrum sativum in PC-3 and LNCaP prostate cancer cell lines.

Coriander (Coriandrum sativum L.) is such an herb from the Apiaceae family, used both for its medicinal and nutritional properties for many centuries. In this study, the effects of C. sativum extract on gene expression, viability, colony formation, migration, and invasion of PC-3 and LNCaP prostate cancer cell lines have been investigated. The half maximal inhibitory concentration (IC50 ) dose in PC-3 and LNCaP cells was detected to be 2 and 5 mg/mL at the 24th hour, respectively. C. sativum extracts have been observed to cause a significant decrease in the expression of Akt and Bcl-2 in the PC-3 cells and just Akt in LNCaP cells while increasing in the expression of p53, caspase-9, caspase-10, PTEN, DR5, TRADD, PUMA, and NOXA. DR4 expression was increased in LNCaP cell line but not PC-3, and APAF and BID had increased expression in PC-3 but not the LNCaP cells. Our observations have shown that C. sativum extract decreased colony formation while inhibiting cell invasion and migration. Cell migration was hindered in PC-3 but not the LNCaP cells. In conclusion, this data present a valuable addition to the very limited data available out there on the potential use of C. sativum in prostate cancer treatment.

The Association Between APOA5 Gene Polymorphisms and Plasma Lipids in the Turkish Cypriot Population: A Possible Biomarker for Preventing Cardiovascular Diseases.

Apolipoprotein A5 (APOA5 or APO A-V) polymorphisms have long been reported to be associated with cardiovascular disease and plasma lipid levels. The present study was undertaken to investigate the relationship between the rs662799, rs3135507, and rs2075291 with biochemical parameters in the Turkish Cypriot population. A total of 100 Turkish Cypriot volunteer subjects (53 female and 47 male), with a mean age of 40.8, participated in the study. A basic biochemical analysis, including serum glucose, total serum cholesterol, HDL-C, LDL-C, and triglycerides, was performed for each participant. Genotyping for the APOA5 three polymorphisms was performed by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Biochemical parameters except the low-density lipoprotein cholesterol (LDL-C) were all within the normal limits. LDL-C was found to be slightly elevated in participants according to WHO guidelines. With respect to the genotype and allele distributions of APOA5 rs662799 T>C polymorphism, TT genotypes are more frequent (62%) in the population and the frequency of T allele is 0.78. The TT genotype for APOA5 rs2075291 GA variant is 0.12 for the A allele. No association between the two studied APOA5 polymorphisms (rs662799 and rs3135507) and the biochemical components of glucose, total cholesterol, and triglyceride were observed. On the other hand, a strong statistical association between the high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) clinical parameters and APOA5 rs662799 CC and rs3135507 AA genotypes was found (p = 0.014 and p = 0.017, respectively). APOA5 polymorphisms rs662799 and rs3135507, with the CC and the AA genotypes, respectively, are associated with increased levels of both high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in the Turkish Cypriot population.

Ferulic acid decreases cell viability and colony formation while inhibiting migration of MIA PaCa-2 human pancreatic cancer cells in vitro.

Novel and combinatorial treatment methods are becoming sought after entities in cancer treatment and these treatments are even more valuable for pancreatic cancer. The scientists are always on the lookout for new chemicals to help them in their fight against cancer. In this study, we examine the effects of ferulic acid (FA), a phenolic compound, on gene expression, viability, colony formation and migration/invasion in the cultured MIA PaCa-2 human pancreatic cancer cell. Cytotoxic effects of FA were determined by using trypan blue dye exclusion test and Cell TiterGlo (CTG) assay. IC50 dose in MIA PaCa-2 cells was detected as 500µM/ml at the 72nd hour. Expression profiles of certain cell cycle and apoptosis genes such as CCND1 (cyclin D1),CDK4, CDK6, RB, p21, p16, p53, caspase-3, caspase-9, caspase-8, caspase-10, Bcl-2, BCL-XL,BID, DR4,DR5,FADD,TRADD,PARP, APAF, Bax, Akt, PTEN, PUMA, NOXA, MMP2, MMP9, TIMP1 and TIMP2 were determined by real-time PCR. The effect of FA on cell viability was determined by CellTiter-Glo® Luminescent Cell Viability Assay. Additionally, effects of FA on colony formation and invasion were also investigated. It was observed that FA caused a significant decrease in the expression of CCND1, CDK 4/6, Bcl2 and caspase 8 and 10 in the MIA PaCa-2 cells while causing an increase in the expression of p53, Bax, PTEN caspase 3 and 9. FA was observed to decrease colony formation while inhibiting cell invasion and migration as observed by the BioCoat Matrigel Invasion Chamber guide and colony formation assays. In conclusion, FA is thought to behave as an anti-cancer agent by affecting cell cycle, apoptotic, invasion and colony formation behavior of MIA PaCa-2 cells. Therefore, FA is placed as a strong candidate for further studies aimed at finding a better, more effective treatment approach for pancreatic cancer.

Mesenchymal stem cells, cancer challenges and new directions.

Therapeutic use of multipotent mesenchymal stromal stem cells (MSC) is a promising venue for a large number of degenerative diseases and cancer. Their availability from many different adult tissues, ease of expansion in culture, the ability to avoid immune rejection and their homing ability, are some of the properties of MSCs that make them a great resource for therapy. However, the challenges and risks for cell-based therapies are multifaceted. The blessing of cell culture expansion also comes with a burden. During in vitro expansion, stem cells experience a long replicative history and therefore, become subjected to damage from intracellular and extracellular influences. As previously shown cells that are manipulated to obtain an expanded replicative potential are prone to spontaneous transformation in culture. These manipulations help bypass the naturally built-in controls of the cell that govern the delicate balance between cell proliferation, senescence and carcinogenesis. Because of this, there is a risk for patients receiving stem cells that are in vitro expanded. Whether these cells are genetically engineered or harbouring xenogenic compounds, they cannot truly be considered "safe" unless the cells are closely monitored. In the present communication, we will focus on the therapeutic potential of the human mesenchymal stem cells (hMSC) with special focus on their use in cancer therapy. We will consider different mechanisms, by which stem cells can maintain telomeres and thereby the cell's ability to be expanded in vitro, and also focus on a new therapeutic venue that utilises hMSCs as delivery vehicles in innovative new cancer treatments.

Mesenchymal stem cells as therapeutic delivery vehicles targeting tumor stroma.

The field of stem cell biology continues to evolve by characterization of further types of stem cells and by exploring their therapeutic potential for experimental and clinical applications. Human mesenchymal stem cells (hMSCs) are one of the most promising candidates simply because of their easiness of both ex vivo expansion in culture dishes and genetic manipulation. Despite many extensive isolation and expansion studies, relatively little has been done with regard to hMSCs' therapeutic potential. Although clinical trials using hMSCs are underway, their use in cancer therapy still needs better understanding and in vivo supporting data. The homing ability of hMSCs was investigated by creating a human xenograft model by transplanting an ovarian cancer cell line into immunocompromised mice. Then, genetically engineered hMSC-telo1 cells were injected through the tail vein and the contribution and distribution of hMSCs to the tumor stroma were investigated by immunohistochemistry and PCR specific to the telomerase gene. Results show that exogenously administered hMSCs preferentially home, engraft, and proliferate at tumor sites and contribute to the population of stromal fibroblasts. In conclusion, this study provides support for the capacity of hMSCs to home to tumor site and serve as a delivery platform for chemotherapeutic agents.