Search results for: immune gene therapy

Authors: Imran Hashmi, Sipkaduwa Arachchige Sashika Sureni Wickramasooriya

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Gene-drive technology has emerged as a promising tool for disease control by influencing the population dynamics of disease-carrying organisms. Various gene drive mechanisms, derived from global laboratory experiments, aim to strategically manage and prevent the spread of targeted diseases. One prominent strategy involves population replacement, wherein genetically modified mosquitoes are introduced to replace the existing local wild population. To enhance our understanding and aid in the design of effective release strategies, we employ a comprehensive mathematical model. The utilized approach employs agent-based modeling, enabling the consideration of individual mosquito attributes and flexibility in parameter manipulation. Through the integration of an agent-based model and a meta-population spatial approach, the dynamics of gene drive mosquito spreading in a released site are simulated. The model's outcomes offer valuable insights into future population dynamics, providing guidance for the development of informed release strategies. This research significantly contributes to the ongoing discourse on the responsible and effective implementation of gene drive technology for disease vector control.

Keywords: gene drive, agent-based modeling, disease-carrying organisms, malaria

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Authors: Asavasereerat K., Teacharsripaitoon T., Tungyingyong P., Charupongrat S., Noppiboon S. Hochareon L., Kitsuban P.

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Third generation of vaccines is based on gene therapy where DNA is introduced into patients. The antigenic or therapeutic proteins encoded from transgenes DNA triggers an immune-response to counteract various diseases. Moreover, DNA vaccine offers the customization of its ability on protection and treatment with high stability. The production of DNA vaccines become of interest. According to USFDA guidance for industry, the recommended limits for impurities from host cell are lower than 1%, and the active conformation homogeneity supercoiled DNA, is more than 80%. Thus, the purification strategy using two-steps chromatography has been established and verified for its robustness. Herein, pVax1/lacZ, a pre-approved USFDA DNA vaccine backbone, was used and transformed into E. coli strain DH5α. Three purification process parameters including sample-loading flow rate, the salt concentration in washing and eluting buffer, were studied and the experiment was designed using response surface method with central composite face-centered (CCF) as a model. The designed range of selected parameters was 10% variation from the optimized set point as a safety factor. The purity in the percentage of supercoiled conformation obtained from each chromatography step, AIEX and HIC, were analyzed by HPLC. The response data were used to establish regression model and statistically analyzed followed by Monte Carlo simulation using SAS JMP. The results on the purity of the product obtained from AIEX and HIC are between 89.4 to 92.5% and 88.3 to 100.0%, respectively. Monte Carlo simulation showed that the pVAX1/lacZ purification process is robust with confidence intervals of 0.90 in range of 90.18-91.00% and 95.88-100.00%, for AIEX and HIC respectively.

Keywords: AIEX, DNA vaccine, HIC, puification, response surface method, robustness

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Authors: Omar S. Sharaf

Abstract:

The mitochondrial 12s rRNA (mt-12s rDNA) gene for pig-specific was developed to detect material from pork species in different products collected from Jordanian market. The amplification PCR products of 359 bp and 531 bp were successfully amplified from the cyt b gene of pig the amplification product using mt-12S rDNA gene were successfully produced a single band with a molecular size of 456 bp. In the present work, the PCR amplification of mtDNA of cytochrome b has been shown as a suitable tool for rapid detection of pig DNA. 100 samples from different dairy, gelatin and chocolate based products and 50 samples from baby food formula were collected and tested to a presence of any pig derivatives. It was found that 10% of chocolate based products, 12% of gelatin and 56% from dairy products and 5.2% from baby food formula showed single band from mt-12S rDNA gene.

Keywords: halal food, baby infant formula, chocolate based products, PCR, Jordan

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Authors: Ahmed Assem Abd El Rahim

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Background: Mechanical low back pain is serious physical and social health problem. Purpose: To examine impact of shock wave therapy versus intermittent mechanical traction on mechanical LBP, and disabilities. Subjects: 60 mechanical LBP male studied cases years old 20-35 years were assigned randomly into 3 groups, Picked up from Sohag university orthopedic hospital outpatient clinic. Methods: (Study Group) A: 20 studied cases underwent shock wave therapy plus conventional physical therapy. (Study Group) B: twenty studied cases underwent intermittent mechanical traction plus conventional physical therapy. (Control Group) C: 20 patients underwent conventional physical therapy alone. Three sessions were applied weekly for four weeks. Pain was quantified using McGill Pain Questionnaire, Roland Morris Disability Questionnaire was used for measuring disability, and the ROM was evaluated by (BROM) device pre- & post-therapy. Results: Groups (A, B & C) found a reduction in pain & disability & rise in their in flexion and extension ROM after end of 4 weeks of program. Mean values of pain scale after therapy were 15.3, 9.47, and 23.07 in groups A, B, & C. mean values of Disability scale after therapy were 8.44, 4.87, 11.8in groups A, B & C. mean values of ROM of flexion were 25.53, 29.06, & 23.9 in groups A, B & C. mean values of ROM of extension were 11.73, 15.53 & 9.85 in groups A, B & C. studied cases who received intermittent mechanical traction & conventional physical therapy (group B), found reduction in pain & disability & improvement in ROM of flexion & extension value (P<0.001) after therapy program. Conclusion: Shock wave therapy and intermittent mechanical traction, as well as conventional physical treatment, can be beneficial in studied cases with mechanical LBP.

Keywords: mechanical low back pain, shock wave, mechanical, low back pain

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Authors: Mahmoud Mabrok, Channarong Rodkhum

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Flavobacterium columanre is one of the devastating pathogen that causes noticeable economic losses in freshwater cultured fish. Like other filamentous bacteria, F. columanre tends to aggregate and fluctuate to all kind of media, thus revealing obstacles in recognition of its colonies. Since the molecular typing is the only fundamental tool for rapid and precise detection of this pathgen. The present study developed a species-specific PCR assay based on cslA unique gene of F. columnare. The cslA gene sequences of 13 F. columnare, strains retrieved from gene bank database, were aligned to identify a conserved homologous segment prior to primers design. The new primers yielded amplicons of 287 bp from F. columnare strains but not from relevant or other pathogens, unlike to other published set that showed no specificity and cross-reactivity with F. indicum. The primers were sensitive and detected as few as 7 CFUs of bacteria and 3 pg of gDNA template. The sensitivity was reduced ten times when using tissue samples. These primers precisely defined all field isolates in a double-blind study, proposing their applicable use for field detection.

Keywords: Columnaris infection, cslA gene, Flavobacterium columnare, PCR

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Authors: Kayla Renteria

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This study explored the role animal-assisted psychotherapy (AAP) can play in treating Post-Traumatic Stress Disorder (PTSD) when incorporated into Trauma-informed cognitive behavioral therapy (TF-CBT). A review of the literature was performed to show how incorporating AAP could benefit TF-CBT since this treatment model often presents difficulties, such as client motivation and avoidance of the exposure element of the intervention. In addition, the fluidity of treatment goals during complex trauma cases was explored, as this issue arose in the case study. This study follows the course of treatment of a 12-year-old female presenting with symptoms of PTSD. Treatment consisted of traditional components of the TF-CBT model, with the added elements of AAP to address typical treatment obstacles in TF-CBT. A registered therapy dog worked with the subject in all sessions throughout her treatment. The therapy dog was incorporated into components such as relaxation and coping techniques, narrative therapy techniques, and psychoeducation on the cognitive triangle. Throughout the study, the client’s situation and clinical needs required the therapist to switch goals to focus on current safety and stability. The therapy dog provided support and neurophysiological benefits to the client through AAP during this shift in treatment. The client was assessed quantitatively using the Child PTSD Symptom Scale Self Report for DSM-5 (CPSS-SR-5) before and after therapy and qualitatively through a feedback form given after treatment. The participant showed improvement in CPSS-SR-V scores, and she reported that the incorporation of the therapy animal improved her therapy. The results of this study show how the use of AAP provided the client a solid, consistent relationship with the therapy dog that supported her through processing various types of traumas. Implications of the results of treatment and for future research are discussed.

Keywords: animal-assisted therapy, trauma-focused cognitive behavioral therapy, PTSD in children, trauma treatment

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Authors: Khiara Claudine C. Carbonel, Patricia Joy A. Canapi, Tracy Gabriella M. Canlas, Teresa Zaine C. Canseco, Reena Marie A. Capistrano, Vernon A. Carandang, Carlo G. Ranoco

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Research problem: The main problem of the study was to determine the effect of Projecting the Reflection of the Individual’s Self-esteem (PRIDE) therapy on the level of self-esteem of physically challenged adolescents. Objectives of the Study: The study determined the effect of PRIDE (Projecting the Reflection of the Individuals Self-esteem) therapy on the level of self-esteem among physically challenged adolescents. Methodology: A quasi-experimental study was used which involved 30 randomly-assigned subjects, 15 in the experimental group and 15 in the control group. The Projecting the reflection of the Individuals’ Self-Esteem (PRDIE) therapy was administered to the experimental group. The researchers utilized the Sorensen Self-Esteem test tool as a pretest and posttest questionnaire and yielded a Cronbach’s alpha of .912. Paired T-test was used to analyze the gathered data. Results: The results showed that after the administration of PRIDE therapy, there was an increase on the level of self-esteem. The experimental group had a value of 3.590, which was significant and meant that the level of self-esteem is significantly increased. On the other hand, the control group, had a value of -2.207 which was also significant, therefore, the level of self esteem significantly decreased. Conclusion: the PRIDE Therapy is effective in increasing the level of self-esteem among physically challenged adolescent. Recommendations: The researchers recommend the use of PRIDE Therapy as an intervention in handling physically challenged patients, especially adolescents, in order to enhance their self-esteem. Also, the researchers recommend that nursing students be informed on the efficacy of PRIDE Therapy in enhancing the self-esteem of physically challenged patients. Furthermore, the inclusion of a psychologist during the implementation of PRIDE Therapy, specifically art therapy, to be able to have a more focused interpretation of the drawings and really be able to see the projection of their self-esteem is also recommended.

Keywords: PRIDE therapy, physically challenged adolescents, self-esteem, art therapy

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Authors: Kirsten B. Hillman

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There is a growing body of qualitative research in adult mental health and music therapy contexts which highlights user perspectives; however, only a very small sub-section of this literature pertains to people with lived experiences of psychological trauma. This paper will provide a meta-synthesis of this existing body of research, with the intention to present a cohesive overview of salient themes in this research and a platform for the under-represented voices of those with lived experience. This synthesis will be contextualised within a broader discussion of ‘Voice’ in trauma and music therapy research, considering its layered meanings: including literal expressive vocalising and musical expression, voicing after experiences of silencing, and the possibilities of experiencing self-determination and agency in therapy after trauma.

Keywords: lived experience, music therapy, trauma, user perspectives

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Authors: Ankita Singh, Chandan Gorain, Amirul I. Mallick

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Successful adherence of the mucosal epithelial cells is the key early step for Campylobacter jejuni pathogenesis (C. jejuni). A set of Surface Exposed Colonization Proteins (SECPs) are among the major factors involved in host cell adherence and invasion of C. jejuni. Among them, constitutively expressed surface-exposed lipoprotein adhesin of C. jejuni, JlpA, interacts with intestinal heat shock protein 90 (hsp90α) and contributes in disease progression by triggering pro-inflammatory response via activation of NF-κB and p38 MAP kinase pathway. Together with its ability to express in the bacterial surface, higher sequence conservation and predicted predominance of several B cells epitopes, JlpA protein reserves its potential to become an effective vaccine candidate against wide range of Campylobacter sps including C. jejuni. Given that chickens are the primary sources for C. jejuni and persistent gut colonization remain as major cause for foodborne pathogenesis to humans, present study explicitly used chickens as model to test the immune-protective efficacy of JlpA protein. Taking into account that gastrointestinal tract is the focal site for C. jejuni colonization, to extrapolate the benefit of mucosal (intragastric) delivery of JlpA protein, a food grade Nisin inducible Lactic acid producing bacteria, Lactococcus lactis (L. lactis) was engineered to express recombinant JlpA protein (rJlpA) in the surface of the bacteria. Following evaluation of optimal surface expression and functionality of recombinant JlpA protein expressed by recombinant L. lactis (rL. lactis), the immune-protective role of intragastric administration of live rL. lactis was assessed in commercial broiler chickens. In addition to the significant elevation of antigen specific mucosal immune responses in the intestine of chickens that received three doses of rL. lactis, marked upregulation of Toll-like receptor 2 (TLR2) gene expression in association with mixed pro-inflammatory responses (both Th1 and Th17 type) was observed. Furthermore, intragastric delivery of rJlpA expressed by rL. lactis, but not the injectable form, resulted in a significant reduction in C. jejuni colonization in chickens suggesting that mucosal delivery of live rL. lactis expressing JlpA serves as a promising vaccine platform to induce strong immune-protective responses against C. jejuni in chickens.

Keywords: chickens, lipoprotein adhesion of Campylobacter jejuni, immuno-protection, Lactococcus lactis, mucosal delivery

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Authors: Mariela González, Zoraide Lugli

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Objective: to determine the relationship between perceived social support and adherence to therapy in patients who have been placed BioEnteric intragastric balloon (BIB). Material and method: 75 obese (56 women and 19 men) between 18 and 65 years (M = 39.29, SD = 11.82), who attended five centers in the city of Caracas, where he carried out this procedure. We used Social Support Scale and treatment adherence behavior respectively. The procedure was contacted the centers and the sample was selected. Subsequently, the inventories were applied before and the month after the before and three months after the balloon set. Results: Show that participants were characterized by moderate levels in the variables. On the other hand, those who perceive that they perceived support from friends are those who report adherence to therapy. Conclusions: From the results, it is suggested promote social support networks, which could be essential to achieve and maintain adherence to therapy in patients with BioEnterics intragastric balloon.

Keywords: BioEnteric intragastric balloon, perceived social support, adherence to therapy, patients

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Authors: Wissem Abdaoui, Nizar M. Mhaidat, Ilhem Mokhtari, Adel Gouri

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Colorectal cancer (CRC) is one of the most common tumors all over the world. Obesity, considered a risk factor of CRC, is characterized by a high level of secreted cytokines from adipose tissue. Among these inflammatory molecules, leptin is considered the key mediator for CRC cancer development and progression by activation of mitogenic and anti apoptotic signaling pathways. Gene expression can be significantly modulated by alterations in DNA methylation patterns. The aim of this study is to investigate the impact of leptin gene methylation on CRC prognosis and sensitivity to chemotherapy. The study involved 70 CRC tissue samples collected from King Abdullah University Hospital (KAUH) from which only 53 was analyzed because of bisulfate fragmentation and low yield of DNA extracted from FFPE tissues. A total of 22 blood samples were collected from healthy volunteers and enrolled as a control group. Leptin promoter methylation was analyzed by methylation specific PCR after bisulfate conversion. Results revealed that the incidence of leptin gene methylation was significantly higher in CRC patients in comparison to that of controls (P < 0.05). The correlation between patient’s demographics and leptin gene methylation was not significant (P < 0.05). However, a significant correlation between leptin gene methylation status and early cancer stages (I, II and III) was found in male but not in female (p < 0.05). Moreover, a significant correlation was found between leptin promoter methylation and early tumor localization T1-2 (p < 0.05). The correlation between epigenetic regulation of leptin and chemosensitivity was not significant. Taken together, these results suggest the possibility to use leptin gene methylation as a biomarker for the evaluation of CRC prognosis and metastasis.

Keywords: colorectal cancer, obesity, leptin, DNA methylation, disease prognosis, bisulfate conversion, chemoresistance

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Authors: Elmeida Effendy, Mustafa M. Amin, Nauli Aulia Lubis, P. J. Sirait

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Music therapy may have an effect on mental illnesses. This is a comparative, quasi-experimental study to examine the effect of music therapy added to standard care on Positive Negative Syndrome Scale, Cognitive Function and Quality of Life in female schizophrenic patients. 50 schizophrenic participants who were diagnosed with semistructured MINI ICD-X, were assigned into two groups received pharmacotherapy. Participants were assigned into each group of therapy by using matched allocation method. Music therapy added on to the first group. They received music therapy, using Mozart Sonata four times a week, over a period of six week. Positive and negative symptoms were measured by using Positive and Negative Syndrome Scale (PANSS). Cognitive function were measured by using Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MOCA). All rating scale were administrated by certified skill residents every week after music therapy session. The participants who were received pharmaco-and-music therapy significantly showed greater response than who received pharmacotherapy only. The mean difference of response were -6,6164 (p=0,001) for PANNS, 2,911 (p=0,004) for MMSE, 3,618 (p=0,001) for MOCA, 4,599 (p=0,001) for SF-36. Music therapy have beneficial effects on PANSS, Cognitive Function and Quality of Life in schizophrenic patients.

Keywords: music therapy, rating scale, schizophrenia, symptoms

Procedia PDF Downloads 322

Authors: Canapi Patricia Joy, Canlas Tracy Gabriella, Canseco Teresa, Capistrano Reena Marie, Carandang Vernon, Carbonel Khiara Claudine

Abstract:

Research problem: The main problem of the study was to determine the effect of Projecting the Reflection of the Individual’s Self-esteem (PRIDE) therapy on the level of self-esteem of physically challenged adolescents. Objectives of the Study: The study determined the effect of PRIDE (Projecting the Reflection of the Individuals Self-esteem) therapy on the level of self-esteem among physically challenged adolescents. Methodology: A quasi-experimental study was used which involved 30 randomly-assigned subjects, 15 in the experimental group and 15 in the control group. The Projecting the reflection of the Individuals’ Self-Esteem (PRDIE) therapy was administered to the experimental group. The researchers utilized the Sorensen Self-Esteem test tool as a pretest and posttest questionnaire and yielded a Cronbach’s alpha of .912. Paired T-test was used to analyze the gathered data. Results: The results showed that after the administration of PRIDE therapy, there was an increase on the level of self-esteem. The experimental group had a value of 3.590, which was significant and meant that the level of self-esteem is significantly increased. On the other hand, the control group, had a value of -2.207 which was also significant, therefore, the level of self esteem significantly decreased. Conclusion: the PRIDE Therapy is effective in increasing the level of self-esteem among physically challenged adolescent. Recommendations: The researchers recommend the use of PRIDE Therapy as an intervention in handling physically challenged patients, especially adolescents, in order to enhance their self-esteem. Also, the researchers recommend that nursing students be informed on the efficacy of PRIDE Therapy in enhancing the self-esteem of physically challenged patients. Furthermore, the inclusion of a psychologist during the implementation of PRIDE Therapy, specifically art therapy, to be able to have a more focused interpretation of the drawings and really be able to see the projection of their self-esteem is also recommended.

Keywords: adolescents, PRIDE therapy, physically challenged, self-esteem

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Authors: Saeedeh Salimi, Farzaneh Farajian- Mashhadi, Ehsan Tabatabaei, Mahnaz Shahrakipoor, Minoo Yaghmaei, Mojgan Mokhtari

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Purpose: Estrogen receptor-α (ERα) plays an essential role in the adaptation of increased uterine blood flow during gestation. Therefore ERα gene could be a possible candidate for preeclampsia(PE) susceptibility. In the current study, we aimed to investigate the association of the ERα gene polymorphisms and PE in an Iranian population. Methods: One hundred ninety-two pregnant women with PE and 186 normotensive women were genotyped for ERα gene (PvuII and XbaI) polymorphisms by PCR-RFLP method. Results: The frequency of alleles and genotypes of ERα PvuII and XbaI polymorphisms were not different between PE and normotensive control women. However, higher frequency of GG genotype was observed in women with severe PE compared to mild PE (OR, 1.8 [95% CI, 1.1 to 3]; P = 0.02) and in severe PE compared to normotensive women [OR= 1.8(1.1-3), P=0.02] after adjusting for age, ethnicity and primiparity. Conclusions: The GG genotype of ERα XbaI polymorphism could be a genetic risk factor for PE predisposition.

Keywords: estrogen receptor-α, polymorphism, gene, preeclampsia

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Authors: Sheikha Turki Alketbi

Abstract:

Objectives: 1. Documenting the spontaneous resolution of AML following the initiation of anti-TB therapy. 2. Presenting an uncommon type of relapse in Acute Myeloid Leukemia. 3. Highlighting the role of immune markers in the diagnosis of Leukemia cutis. 4. Exploring and highlighting the possibility of skin relapse as the exclusive manifestation, even when skin involvement is known secondary manifestation in AML. Background: Spontaneous remission of Acute Myeloid Leukemia (AML) is a rare phenomenon that has only been reported in some case reports, usually following severe infections. Some studies have described the occurrence of tuberculosis (TB) infection with AML, usually after starting chemotherapy. Spontaneous resolution of AML after starting anti TB therapy (ATT), without starting chemotherapy has never been described in the literature. Moreover, Leukemia cutis is another rare skin manifestation of Acute Myeloid Leukemia as a result of infiltration of the skin or subcutaneous tissue by leukemic cells, in which can present during, precedes, after or independently of systemic leukemia. Methods: Here, we present a case of a 13-year-old male who presented with fever, weight loss, lethargy, epistaxis, bruising and dry cough and was later diagnosed with AML. Before initiating leukemia treatment, the patient was tested for TB and was found to have active TB infection. His leukemia treatment was postponed to clear the TB infection and he was commenced on ATT. Two months later, repeat blood film and bone marrow biopsy showed resolution of his AML. The patient remained in remission for 1 month, after which he presented with symmetrical blue purple well-defined round indurated plaques on the chest and thighs. Our differentials were leukemia cutis and Kaposi sarcoma. Results: Skin Biopsy with immune markers done, showed a picture of Acute Myeloid Leukemia. Immunohistochemistry (IHC) showed neoplastic cells diffusely and strongly positive for LCA, CD2, CD31, MPO, CD117, Lysozymes and TDT, and moderately positive for CD34, CD99, CD43 and CD6 And patchy for CD68. Ki67 showed 60% proliferation index. They were negative for the remaining markers. This suggested acute myeloid leukemia (AML). Conclusion: In summary, we present a rare case of TB with AML that resolved after treatment of TB with ATT but relapsed later as leukemia cutis. While skin involvement might occur as a secondary manifestation of AML, Skin relapse could be the only one.

Keywords: Leukemia cutis, Leukemia relapse, Acute Myeloid Leukemia, spontaneous resolution of AML

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Authors: Narayan Moger, Divya B., Preethi Jambagi, Krishnaveni C. K., Apsana M. R., B. R. Patil, Basvaraj Bagewadi

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Salinity is one of the major threats to world food security. Considering the requirement for salt tolerant crop plants in the present study was undertaken to clone and transferred the salt tolerant ectA gene from marine ecosystem into agriculture crop system to impart salinity tolerance. Ectoine is the compatible solute which accumulates in the cell membrane, is known to be involved in salt tolerance activity in most of the Halophiles. The present situation is insisting to development of salt tolerant transgenic lines to combat abiotic stress. In this background, the investigation was conducted to develop transgenic tomato lines by cloning and transferring of ectA gene is an ectoine derivative capable of enzymatic action for the production of acetyl-diaminobutyric acid. The gene ectA is involved in maintaining the osmotic balance of plants. The PCR amplified ectA gene (579bp) was cloned into T/A cloning vector (pTZ57R/T). The construct pDBJ26 containing ectA gene was sequenced by using gene specific forward and reverse primers. Sequence was analyzed using BLAST algorithm to check similarity of ectA gene with other isolates. Highest homology of 99.66 per cent was found with ectA gene sequences of isolates Halomonas elongata with the available sequence information in NCBI database. The ectA gene was further sub cloned into pRI101-AN plant expression vector and transferred into E. coli DH5α for its maintenance. Further pDNM27 was mobilized into A. tumefaciens LBA4404 through tri-parental mating system. The recombinant Agrobacterium containing pDNM27 was transferred into tomato plants through In planta plant transformation method. Out of 300 seedlings, co-cultivated only twenty-seven plants were able to well establish under the greenhouse condition. Among twenty-seven transformants only twelve plants showed amplification with gene specific primers. Further work must be extended to evaluate the transformants at T1 and T2 generations for ectoine accumulation, salinity tolerance, plant growth and development and yield.

Keywords: salinity, computable solutes, ectA, transgenic, in planta transformation

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Authors: Prosper Kudzanai Mushauri

Abstract:

Shock therapy has been used in persons living with depression and deeply depressed persons. It has been used in children also. Shock therapy has been also among its pros believed to improve the quality of life and an effective treatment of depression. The review of the literature on ECT papers have highlighted that benefits to users of ECT are elusive, and iatrogenic harm often occurs showing that the approach will always fall far in comporting to psychological ethics. On the contrary, ECT is known as shock therapy which is the administration of electric shock within the brain; it has been challenged on ethical grounds if it’s proper ethically. From this ethical aperture, it has emerged that relapse rates are approximately higher than 50%, it results in diencephalon disturbances and has also side effects related to cognitive function among other negative effects. It is from these reviewed studies that that ECT should not be viewed as an effective treatment of depression as it does not comport to the mores of psychological ethics.

Keywords: anterograde amnesia, depression, electroconvulsive therapy, ethics, retrograde amnesia

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Authors: Fahad R. Choudhry., Khadeeja Munawar

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This clinical case presents a 24 years old, Muslim Pakistani girl with a history of conversion disorder. Her symptoms comprised fits, restlessness, numbness in legs, poor coordination and balance, burning during urination and retention. A cognitive-behavioral model was used for conceptualizing her problem and devising a management plan based on cognitive behavioral therapy (CBT) and culturally adapted coping statements. She took 13 therapy sessions and was presented with idiosyncratic case conceptualization. Psychoeducation, coping statements, extinction, verbal challenging, and behavioral activation techniques were practiced in a collaborative way for cognitive restructuring of the client. Focus of terminal sessions was on anger management. The client needed a couple of more sessions in order to help her manage her anger. However, the therapy was terminated on the part of the client after attainment of short term goals. The client reported to have a 75 % improvement in her overall condition and remained compliant throughout the therapy.

Keywords: cognitive behavioral therapy, conversion disorder, female, Muslim, Pakistani

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Authors: Chia-Jung Li, Li-Te Lin, Kuan-Hao Tsui

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The study identifies SPP1 as a potential gene associated with ovarian aging, revealing a significant decline in its expression in aged ovaries. SPP1, also known as osteopontin (OPN), is a multifunctional glycoprotein involved with regulatory proteins and pro-inflammatory immune chemokines. However, its genetic links to ovarian aging have not been extensively explored. Spatial transcriptomic analyses were conducted on ovaries from young and aged female mice, along with a sample from a 73-year-old individual. Additionally, single-cell RNA sequencing analysis was performed to identify associations between SPP1 and key genes. The study focused on crucial genes, including ITGAV, ITGB1, CD44, MMP3, and FN1, with a particular emphasis on the correlation between SPP1 and ITGB1. The findings indicate a significant decline in SPP1 expression in aged ovaries, which was consistent in the 73-year-old sample. Single-cell RNA sequencing unveiled associations between SPP1 and key genes, emphasizing a strong co-expression correlation between SPP1 and ITGB1. While the study provides valuable insights, further research is necessary to understand the broader implications and potential applications of SPP1 in ovarian aging. Translating these findings to clinical settings requires careful consideration. The identification of SPP1 as a gene implicated in ovarian aging opens new avenues for advancing precision medicine and refining treatment strategies for conditions related to ovarian aging.

Keywords: SPP1, ovarian aging, spatial transcriptomic, single-cell RNA sequencing

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Authors: Scott A. Ochsner, Christopher M. Watkins, Apollo McOwiti, David L. Steffen Lauren B. Becnel, Neil J. McKenna

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Understanding signaling by nuclear receptors (NRs) requires an appreciation of their cognate ligand- and tissue-specific transcriptomes. While target gene regulation data are abundant in this field, they reside in hundreds of discrete publications in formats refractory to routine query and analysis and, accordingly, their full value to the NR signaling community has not been realized. One of the mandates of the Nuclear Receptor Signaling Atlas (NURSA) is to facilitate access of the community to existing public datasets. Pursuant to this mandate we are developing a freely-accessible community web resource, Transcriptomine, to bring together the sum total of available expression array and RNA-Seq data points generated by the field in a single location. Transcriptomine currently contains over 25,000,000 gene fold change datapoints from over 1200 contrasts relevant to over 100 NRs, ligands and coregulators in over 200 tissues and cell lines. Transcriptomine is designed to accommodate a spectrum of end users ranging from the bench researcher to those with advanced bioinformatic training. Visualization tools allow users to build custom charts to compare and contrast patterns of gene regulation across different tissues and in response to different ligands. Our resource affords an entirely new paradigm for leveraging gene expression data in the NR signaling field, empowering users to query gene fold changes across diverse regulatory molecules, tissues and cell lines, target genes, biological functions and disease associations, and that would otherwise be prohibitive in terms of time and effort. Transcriptomine will be regularly updated with gene lists from future genome-wide expression array and expression-sequencing datasets in the NR signaling field.

Keywords: target gene database, informatics, gene expression, transcriptomics

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Authors: Wan Liu, Haibo Wang, Cathy Huang, Zhiwu Tan, Zhiwei Chen

Abstract:

The tremendous diversity of HIV-1 has been a major challenge for an effective AIDS vaccine development. Mosaic approach presents the potential for vaccine design aiming for global protection. The mosaic antigen of HIV-1 Gag allows antigenic breadth for vaccine-elicited immune response against a wider spectrum of viral strains. However, the enhancement of immune response using vaccines is dependent on the strategy used. Heterologous prime/boost regimen has been shown to elicit high levels of immune responses. Here, we investigated whether priming using plasmid DNA with electroporation followed by boosting with the live replication-competent modified vaccinia virus vector TianTan (MVTT) combined with the mosaic antigenic sequence could elicit a greater and broader antigen-specific response against HIV-1 Gag in mice. When compared to DNA or MVTT alone, or MVTT/MVTT group, DNA/MVTT group resulted in coincidentally high frequencies of broadly reactive, Gag-specific, polyfunctional, long-lived, and cytotoxic CD8+ T cells and increased anti-Gag antibody titer. Meanwhile, the vaccination could upregulate PD-1+, and Tim-3+ CD8+ T cell, myeloid-derived suppressive cells and Treg cells to balance the stronger immune response induced. Importantly, the prime/boost vaccination could help control the EcoHIV and mesothelioma AB1-gag challenge. The stronger protective Gag-specific immunity induced by a Mosaic DNA/MVTT vaccine corroborate the promise of the mosaic approach, and the potential of two acceptably safe vectors to enhance anti-HIV immunity and cancer prevention.

Keywords: DNA/MVTT vaccine, EcoHIV, mosaic antigen, mesothelioma AB1-gag

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Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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Authors: Hager Elsheikh, Matthias Sendler, Juliana Glaubnitz

Abstract:

In pancreatitis, an inflammatory reaction occurs in the pancreatic secretory cells due to premature activation of proteases, leading to pancreatic self-digestion and necrotic cell death of acinar cells. Acute pancreatitis in patients is characterized by a severe immune reaction that could lead to serious complications, such as organ failure or septic shock, if left untreated. Chronic pancreatitis is a recurrence of episodes of acute pancreatitis resulting in a fibro-inflammatory immune response, in which the type 2 immune response is primarily driven by AAMs in the pancreas. One of the most important signaling pathways for M2 macrophage activation is the IL-4/STAT6 pathway. Pancreatic fibrosis is induced by the hyperactivation of pancreatic stellate cells by dysregulation in the inflammatory response, leading to further damage, autodigestion and possibly necrosis of pancreatic acinar cells. The aim of this research is to investigate the effect of STAT6 knockout in disease severity and development of fibrosis wound healing in the presence of different macrophage populations, regulated by the type 2 immune response, after inducing chronic and/or acute pancreatitis in mice models via cerulean injection. We further investigate the influence of the JAK/STAT6 signaling pathway on the balance of fibrosis and regeneration in STAT6 deficient and wild-type mice. The characterization of resident and recruited macrophages will provide insight into the influence of the JAK/STAT6 signaling pathway on infiltrating cells and, ultimately, tissue fibrosis and disease severity.

Keywords: acute and chronic pancreatitis, tissue regeneration, macrophage polarization, Gastroenterology

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Authors: Feng Zhang

Abstract:

Kashin-Beck disease (KBD) is a chronic osteochondropathy. The mechanism of hand growth and development failure of KBD remains elusive now. In this study, we conducted a two-stage genome-wide association study (GWAS) of palmar length-width ratio (LWR) of KBD, totally involving 493 Chinese Han KBD patients. Affymetrix Genome Wide Human SNP Array 6.0 was applied for SNP genotyping. Association analysis was conducted by PLINK software. Imputation analysis was performed by IMPUTE against the reference panel of the 1000 genome project. In the GWAS, the most significant association was observed between palmar LWR and rs2071358 of COL2A1 gene (P value = 4.68×10-8). Imputation analysis identified 3 SNPs surrounding rs2071358 with significant or suggestive association signals. Replication study observed additional significant association signals at both rs2071358 (P value = 0.017) and rs4760608 (P value = 0.002) of COL2A1 gene after Bonferroni correction. Our results suggest that COL2A1 gene was a novel susceptibility gene involved in the growth and development failure of hand of KBD.

Keywords: Kashin-Beck disease, genome-wide association study, COL2A1, hand

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Authors: Wissam Saliba, Mandy Nicholson

Abstract:

Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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Authors: I. A. Farhat

Abstract:

The dynamic economic dispatch (DED) problem is one of the complex, constrained optimization problems that have nonlinear, con-convex and non-smooth objective functions. The purpose of the DED is to determine the optimal economic operation of the committed units while meeting the load demand. Associated to this constrained problem there exist highly nonlinear and non-convex practical constraints to be satisfied. Therefore, classical and derivative-based methods are likely not to converge to an optimal or near optimal solution to such a dynamic and large-scale problem. In this paper, an Artificial Immune System technique (AIS) is implemented and applied to solve the DED problem considering the transmission power losses and the valve-point effects in addition to the other operational constraints. To demonstrate the effectiveness of the proposed technique, two case studies are considered. The results obtained using the AIS are compared to those obtained by other methods reported in the literature and found better.

Keywords: artificial immune system, dynamic economic dispatch, optimal economic operation, large-scale problem

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Authors: Tianjiao Chu, Carla Rios Luci, Christy Maksoudian, Ara Sargsian, Bella B. Manshian, Stefaan J. Soenen

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Nanomaterials have gained high interest in their use as potent anticancer agents. Apart from delivering chemotherapeutic agents in order to reduce off-target effects, molecular agents have also been widely explored. The advances in our understanding of cell biology and cell death mechanisms1 has generated a broad library of potential therapeutic targets by siRNA, mRNA, or pDNA complexes. In the present study, we explore the ability of pDNA-polyplexes to induce tumor-specific necroptosis. This results in a cascade of effects, where immunogenic cell death potentiates anti-tumor immune responses and results in an influx of dendritic cells and cytotoxic T cells, rendering the tumor more amenable to immune checkpoint inhibition. This study aims to explore whether the induction of necroptosis in a subpopulation of tumor cells can be used to potentiate immune checkpoint inhibition studies.

Keywords: nanoparticle, MLKL, necroptosis, immunotherapy

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Authors: Fei Xu, Guofan Zhang, Xiao Liu

Abstract:

Many major marine invertebrate phyla are characterized by indirect development. These animals transit from planktonic larvae to benthic adults via settlement and metamorphosis, which has many advantages for organisms to adapt marine environment. Studying the biological process of metamorphosis is thus a key to understand the origin and evolution of indirect development. Although the mechanism of metamorphosis has been largely studied on their relationships with the marine environment, microorganisms, as well as the neurohormones, little is known on the gene regulation network (GRN) during metamorphosis. We treated competent oyster pediveligers with epinephrine, which was known to be able to effectively induce oyster metamorphosis, and analyzed the dynamics of gene and proteins with transcriptomics and proteomics methods. The result indicated significant upregulation of protein synthesis system, as well as some transcription factors including Homeobox, basic helix-loop-helix, and nuclear receptors. The result suggested the GRN complexity of the transition stage during oyster metamorphosis.

Keywords: indirect development, gene regulation network, protein synthesis, transcription factors

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Authors: Han-Qin Zheng, Yi-Fan Chiang-Hsieh, Chia-Hung Chien, Wen-Chi Chang

Abstract:

As the most important non-vascular plants, algae have many research applications, including high species diversity, biofuel sources, adsorption of heavy metals and, following processing, health supplements. With the increasing availability of next-generation sequencing (NGS) data for algae genomes and transcriptomes, an integrated resource for retrieving gene expression data and metabolic pathway is essential for functional analysis and systems biology in algae. However, gene expression profiles and biological pathways are displayed separately in current resources, and making it impossible to search current databases directly to identify the cellular response mechanisms. Therefore, this work develops a novel AlgaePath database to retrieve gene expression profiles efficiently under various conditions in numerous metabolic pathways. AlgaePath, a web-based database, integrates gene information, biological pathways, and next-generation sequencing (NGS) datasets in Chlamydomonasreinhardtii and Neodesmus sp. UTEX 2219-4. Users can identify gene expression profiles and pathway information by using five query pages (i.e. Gene Search, Pathway Search, Differentially Expressed Genes (DEGs) Search, Gene Group Analysis, and Co-Expression Analysis). The gene expression data of 45 and 4 samples can be obtained directly on pathway maps in C. reinhardtii and Neodesmus sp. UTEX 2219-4, respectively. Genes that are differentially expressed between two conditions can be identified in Folds Search. Furthermore, the Gene Group Analysis of AlgaePath includes pathway enrichment analysis, and can easily compare the gene expression profiles of functionally related genes in a map. Finally, Co-Expression Analysis provides co-expressed transcripts of a target gene. The analysis results provide a valuable reference for designing further experiments and elucidating critical mechanisms from high-throughput data. More than an effective interface to clarify the transcript response mechanisms in different metabolic pathways under various conditions, AlgaePath is also a data mining system to identify critical mechanisms based on high-throughput sequencing.

Keywords: next-generation sequencing (NGS), algae, transcriptome, metabolic pathway, co-expression

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Authors: Anida Causevic-Ramosevac, Sabina Semiz

Abstract:

The aim of this study was to investigate the association of four single nucleotide polymorphisms (SNPs) - rs673548, rs693 in ApoB gene, rs1800775 in CETP gene and rs4846914 in GALNT2 gene with parameters of type 2 diabetes (T2D) and diabetic dyslipidemia in the population of Bosnia and Herzegovina (BH). Materials and methods: Our study involved 352 patients with T2D and 156 healthy subjects. Biochemical and anthropometric parameters were measured in all participants. DNA was extracted from the peripheral blood for the purpose of genetic testing. Polymorphisms in ApoB (rs673548, rs693), CETP (rs1800775) and GALNT2 (rs4846914) genes were analyzed by using Sequenom IPLEX platform. Results: Our results demonstrated significant associations for rs180075 polymorphism in CETP gene with levels of fasting insulin (p = 0.020; p = 0.027; p = 0.044), triglycerides (p = 0.046) and ALT (p = 0.031) activity in control group. In group of diabetic patients, results showed a significant association of rs673548 in ApoB gene with levels of fasting insulin (p = 0.008), HOMA-IR (p = 0.013), VLDL-C (p = 0.037) and CRP (p = 0.029) and rs693 in ApoB gene with BMI (p = 0.025), systolic blood pressure (p = 0.027), fasting insulin (p = 0.037) and HOMA-IR (p = 0.023) levels. Significant associations were also observed for rs1800775 in CETP gene with triglyceride (p = 0.023) levels and rs4846914 in GALNT2 gene with HbA1C (p = 0.013) and triglyceride (p = 0.043) levels. Conclusion: In conclusion, this is the first study that examined the impact of variations of candidate genes on a wide range of metabolic parameters in BH population. Our results suggest an association of variations of ApoB, CETP and GALNT2 genes with specific markers of T2D and dyslipidemia. Further studies would be needed in order to confirm these genetic effects in other ethnic groups as well.

Keywords: ApoB, CETP, dyslipidemia, GALNT2, type 2 diabetes

Procedia PDF Downloads 220