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Identification of novel potential drugs and miRNAs biomarkers in lung cancer based on gene co-expression network analysis

  • Sara Hajipour;Sayed Mostafa Hosseini;Shiva Irani;Mahmood Tavallaie
    • Genomics & Informatics
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    • 제21권3호
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    • pp.38.1-38.8
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    • 2023
  • Non-small cell lung cancer (NSCLC) is an important cause of cancer-associated deaths worldwide. Therefore, the exact molecular mechanisms of NSCLC are unidentified. The present investigation aims to identify the miRNAs with predictive value in NSCLC. The two datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEmiRNA) and mRNAs (DEmRNA) were selected from the normalized data. Next, miRNA-mRNA interactions were determined. Then, co-expression network analysis was completed using the WGCNA package in R software. The co-expression network between DEmiRNAs and DEmRNAs was calculated to prioritize the miRNAs. Next, the enrichment analysis was performed for DEmiRNA and DEmRNA. Finally, the drug-gene interaction network was constructed by importing the gene list to dgidb database. A total of 3,033 differentially expressed genes and 58 DEmiRNA were recognized from two datasets. The co-expression network analysis was utilized to build a gene co- expression network. Next, four modules were selected based on the Zsummary score. In the next step, a bipartite miRNA-gene network was constructed and hub miRNAs (let-7a-2-3p, let-7d-5p, let-7b-5p, let-7a-5p, and let-7b-3p) were selected. Finally, a drug-gene network was constructed while SUNITINIB, MEDROXYPROGESTERONE ACETATE, DOFETILIDE, HALOPERIDOL, and CALCITRIOL drugs were recognized as a beneficial drug in NSCLC. The hub miRNAs and repurposed drugs may act a vital role in NSCLC progression and treatment, respectively; however, these results must validate in further clinical and experimental assessments.

분석심리학적 관점으로 고찰한 창조신화 : '알(卵)'의 상징성 중심으로 (Jungian Interpretation of Creation Myths Focused on Egg Symbolism)

  • 김진숙
    • 심성연구
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    • 제27권1_2호
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    • pp.28-70
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    • 2012
  • 본 논문은 창조신화들 중 특히 '알'이 출현하는 창조신화를 중심으로 그 상징성을 살피고, 이를 무의식적인 내용물에서 출현하는 '알'의 모티브와 비교하여 무의식적인 영역에 속하는 창조신화의 상징성을 의식적인 영역에서 이해하려는 것이 그 취지이다. 먼저 창조신화가 원형적인 투사현상으로서 무의식에서 자아가 탄생하는 것과 관련되며 인간의 의식적인 깨달음의 기원에 관한 것이라는 점을 부각하고, 개인사나 인류사에서 새로운 질서를 필요로 할 때 무의식에 의하여 저절로 만들어지는 현상으로서, 자아의 자세에 따라서 새로운 의식의 도약이나 재건의 조짐이 될 수도 있고 무의식이 자아의식으로 침범하게 될 수도 있음을 논한다. 관련문헌으로서 창조신화에서 출현하는 '우주 알'을 우주창생의 원 질료이자 자기의 상징으로 보는 융, 폰 프란츠, 노이만, 하딩, 에딘져의 연구를 소개한다. 창조신화의 분석심리학적인 의미에서 '태초의 혼돈(messa confusa)'은 고태적 동일시(무의식), 유아기의 경험, 혹은 하나 속에 모든 것이 들어있는 우로보로스적인 경험으로서 분리를 해야 하는 과제를 가지고 있다고 보았다. 그러나 장자의 우화에 등장하는 상제(上帝)로서의 혼돈이나, 연금술에서 검은 색의 단계인 니그레도(nigredo)가 가지는 의미에서 볼 때 너무 성급하게 분리해야 하는 것이 아니며 이러한 사실이 임상에서 시사하는 바를 논한다. '천지개벽(분리)'는 객체로부터 주체를 구별할 수 있게 되어 자아가 출현하는 것과 관련이 있고, 의식의 진보가 있을 때 나타난다고 보면서 연금술의 분리과정(separatio)과 연관하였다. '빛'은 의식성의 획득으로 보았고, 자아의 자세에 따라 다른 경험이 될 수도 있음을 논하면서 창조신화의 전 과정이 의식성을 획득해 가는 과정과 동일하다는 것을 에스키모 창조신화를 통하여 소개한다. '알'이 출현하는 창조신화의 분석심리학적 의미에서 먼저 '알'에 대한 확충과, '알'이 출현하는 창조신화들, 그리고 시조 신들의 모체로서의 '알'을 소개하고 '알'이 자기의 상징과 다르지 않음을 논한다. '알'의 상징성을 알의 출현-품기-분리로 보고 '알 출현'의 심리학적인 의미를 창조론적인 싹인 시바점(Shiva bindu), 히라니야가르바(Hyranyagarba), 황금알(태)의 의미와 자궁 또는 '알'의 의미를 가지고 있는 불교의 여래장(如來藏)과 진여(眞如)와 연관하였고, '세계 알'이자 연금술의 용기로서의 메르쿠리우스이자 세계의 창조혼(Geist)의 의미를 가진다고 보았다. '알 품음'의 심리학적 의미는 스스로에게 리비도를 집중하는 타파스(tapas)로서, 발렌티우스(Valentinus) 문헌의 오토파터(autopater)와 그의 내면의 여성성인 엔노이아(ennoia)를 품음으로서 세상을 만드는 것과, 새가 알을 품고 있는 형상인 주역(周易)의 61괘 중부(中孚)가 가지는 의미인 내적인 진실과, 원효의 지관(止觀)사상, 그리고 '밤의 항해'가 가지는 상징적인 의미와 연관하였고, 연금술적으로 메디타치오(meditatio)의 의미를 가지며, 알의 출현과 품음에 고뇌와 고통이 동반됨에 대해서 논한다. '알 분리'의 심리학적 의미는 미망의 껍질을 벗고 시공을 초월하는 태양적, 의식성의 획득으로서 알에서 출현한 초 개인적인 새의 의미를 새로운 인격의 출현으로 보았고, 연금술적으로 분리과정(separatio)와 상승과정(sublimatio)과 연관하였다. '알'과 관련된 임상 자료들을 통하여 '알의 상징성'(알 출현, 품음, 분리)이 피분석자들의 무의식의 자료에서도 같은 맥락으로 나타난다는 점을 부각하면서 알의 상징성에서 보여주는 전 과정이 내(자아, 주체, 분화됨)가 나 아닌 것(무의식, 객체, 미분화됨)으로부터 분리되는 것과 관련되며 인간정신의 전체성을 지향하는 자기실현과정과 다르지 않음을 논하는 것으로 마감한다.

볼바키아 세균에 의한 절지동물 기주의 생식적 변화와 생물적방제 프로그램에 이용 방안 (Wolbachia-mediated Reproductive Alterations in Arthropod Hosts and its use for Biocontrol Program)

  • 엘라히 로스타미;후세인 마다디;하비브 아바시포르;쉬바 시바라마크리쉬난
    • 한국응용곤충학회지
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    • 제55권2호
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    • pp.177-188
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    • 2016
  • 알파 프로테박테리아(${\alpha}-proteobacterium$)인 볼바키아(Wolbachia) 세균은 절지동물 세포내의 중요한 공생균 중의 하나이다. 그람 음성 세균인 이 공생균은 기주동물의 여러 생물적 과정에 관여하고 있으며, 현재 생물적 방제 수단으로 주목 받고 있다. 볼바키아는 기주 세포의 세포질에 서식하는 세균인데 암컷을 통하여 세대간 전염된다. 볼파키아의 감염 개체 밀도를 높이기 위해 기주의 생식방식을 조작하는 다양한 전략을 발달시켰다. 볼바키아 유전자형 계통은 볼바키아 표면 단백질(WSP)의 고변이영역 아미노산 서열과 복합좌위 서열 타이핑(Multilocus sequence typing, MLST)으로 결정된다. 상이한 유전계통 판별은 wsp, 16S rRNA, ftsZ, gltA, groEL 등 유전자 분자표지를 이용하게 된다.. 이 계통 볼바키아 세균과 그들의 우월한 표현형이 농업해충과 인간의 질병매개 곤충에 대한 방제 프로그램에서 이용 가능성이 고려되고 있다. 볼바키아 표현형들은 세포질불일치(cytoplasmic incompatibility, CI), 단성생식 유도(parthenogenesis induction, PI), 여성화(feminization, F), 수컷치사(male killing, MK) 등을 유발하는 것으로 알려져 있다. 기타 볼바키아 세균의 농업과 위생곤충 방제 프로그램에서 응용 방안을 고찰하였다.

CYP2D6 Genotype and Risk of Recurrence in Tamoxifen Treated Breast Cancer Patients

  • Yazdi, Mohammad Forat;Rafieian, Shiva;Gholi-Nataj, Mohsen;Sheikhha, Mohammad Hasan;Nazari, Tahereh;Neamatzadeh, Hossein
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권15호
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    • pp.6783-6787
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    • 2015
  • Background: Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen exposure, there is considerable controversy regarding the validity of CYP2D6 as a predictor of tamoxifen outcome. Understanding the current state of evidence in this area and its limitations is important for the care of patients who require endocrine therapy for breast cancer. Materials and Methods: A total of 101 patients with breast cancer who received tamoxifen therapy for at least 3 years, were genotyped for common alleles of the CYP2D6 gene by nested-PCR and restriction fragment length polymorphism PCR. Patients were classified as extensive or poor metabolizers (PM) based on CYP2D6*4 alleles in 3 different groups according to the menopause, Her2-neu status, and stage 3. Results: The mean age of the patients with the disease recurrence was $50.8{\pm}6.4$ and in non recurrent patients was $48.2{\pm}6.8$. In this study 63.3% (n=64) patients were extensive metabolizers and 36.6% (n=37) were poor metabolizers. Sixty four of the 101 patients (63.3%) were Her2-neu positive. For tamoxifen-treated patients, no statistically significant difference in rate of recurrence observed between CYP2D6 metabolic variants in stage 3 and post-menopausal patients. However, there was a significant association between CYP2D6 genotype and recurrence in tamoxifen-treated Her2-neu positive patients. Compared with other women with breast cancer, those with Her2-neu positive breast cancer and extensive metabolizer alleles had a decreased likelihood of recurrence. Conclusions: This study for the first time demonstrated significant effects of CYP2D6 extensive metabolizer alleles on risk of recurrence in Her2-neu positive breast cancer patients receiving adjuvant tamoxifen therapy. Therefore, CYP2D6 metabolism, as measured by genetic variation, can be a predictor of breast cancer outcome in Her2-neu positive women receiving tamoxifen.

Glucose-6-phosphate dehydrogenase deficiency does not increase the susceptibility of sperm to oxidative stress induced by H2O2

  • Roshankhah, Shiva;Rostami-Far, Zahra;Shaveisi-Zadeh, Farhad;Movafagh, Abolfazl;Bakhtiari, Mitra;Shaveisi-Zadeh, Jila
    • Clinical and Experimental Reproductive Medicine
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    • 제43권4호
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    • pp.193-198
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    • 2016
  • Objective: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect. G6PD plays a key role in the pentose phosphate pathway, which is a major source of nicotinamide adenine dinucleotide phosphate (NADPH). NADPH provides the reducing equivalents for oxidation-reduction reductions involved in protecting against the toxicity of reactive oxygen species such as $H_2O_2$. We hypothesized that G6PD deficiency may reduce the amount of NADPH in sperms, thereby inhibiting the detoxification of $H_2O_2$, which could potentially affect their motility and viability, resulting in an increased susceptibility to infertility. Methods: Semen samples were obtained from four males with G6PD deficiency and eight healthy males as a control. In both groups, motile sperms were isolated from the seminal fluid and incubated with 0, 10, 20, 40, 60, 80, and $120{\mu}M$ concentrations of $H_2O_2$. After 1 hour incubation at $37^{\circ}C$, sperms were evaluated for motility and viability. Results: Incubation of sperms with 10 and $20{\mu}M\;H_2O_2$ led to very little decrease in motility and viability, but motility decreased notably in both groups in 40, 60, and $80{\mu}M\;H_2O_2$, and viability decreased in both groups in 40, 60, 80, and $120{\mu}M\;H_2O_2$. However, no statistically significant differences were found between the G6PD-deficient group and controls. Conclusion: G6PD deficiency does not increase the susceptibility of sperm to oxidative stress induced by $H_2O_2$, and the reducing equivalents necessary for protection against $H_2O_2$ are most likely produced by other pathways. Therefore, G6PD deficiency cannot be considered as major risk factor for male infertility.

4-Amino-2,3-dimethyl-1-phenyl-3-pyrazoline 또는 4-(4-Methoxybenzylidenimin)thiophenole을 이용한 활성탄에서의 구리의 예비 농축 및 추출 (Preconcentration and Extraction of Copper on Activated Carbon Using 4-Amino-2, 3-dimethyl-1-phenyl-3-pyrazoline or 4-(4-methoxybenzylidenimin) thiophenole)

  • Ghaedi, Mehrorang;Ahmadi, Farshid;Karimi, Hajir;Gharaghani, Shiva
    • 대한화학회지
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    • 제50권1호
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    • pp.23-31
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    • 2006
  • 원자흡수분광법을 사용하여 실제 시료 중의 구리를 예비 농축하고 정량하는데 활성탄 변형법을 사용하였다. 구리 이온을 4-amino-2,3-dimethyl-1-phenyl-3-pyrazoline(ADMPP) 또는 4-(4-methoxybenzylidenimin)thiophenole (MBITP)과 착물을 형성시켜 활성탄에 정량적으로 흡착시키고, 고체상에 흡착된 구리를 소량의 질산을 사용하여 정량적으로 용리시켰다. 최대 회수율을 얻는데 있어서 중요한 pH, 운반체의 양, 흐름속도, 활성탄의 양, 용리제의 종류 및 농도와 같은 파라미터의 영향을 조사하였다. 최적 조건에서 ADMPP와 MBITP를 사용하는 이 방법은 0.05-1.5g mL1 and 0.05-1.2g mL1의 구리 농도 범위에서 각각 상관계수 0.9997 및 0.9994의 선형성을 보이며 검출한계는 1.4 ng mL1 였다. 예비 농축의 농축인자는 310에 이르며 돌파부피는 두 리간드에서 모두 1550 mL였다. 이 방법은 방해 이온에 대한 공차한계와 선택성이 좋아서 수돗물, 샘물, 강물 및 폐수와 같은 실제 시료 중의 구리 함량을 정량하는 데 성공적으로 사용되었다.

Assessment of pregnancy-associated glycoprotein profile in milk for early pregnancy diagnosis in goats

  • Singh, Shiva Pratap;Natesan, Ramachandran;Sharma, Nandini;Goel, Anil Kumar;Singh, Manoj Kumar;Kharche, Suresh Dinkar
    • Animal Bioscience
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    • 제34권1호
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    • pp.26-35
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    • 2021
  • Objective: This study was conducted to assess the level of pregnancy-associated glycoprotein (PAG) in whole and skim milk samples, and its suitability for early pregnancy diagnosis in goats. Methods: A two-step sandwich enzyme-linked immunosorbent assay (ELISA) system for estimation of milk PAG was developed and validated, which employed caprine-PAG specific polyclonal antisera. Whole and skim milk samples (n = 210 each) from fifteen multiparous goats were collected on alternate days from d 10 to d 30, and thereafter weekly till d 51 post-mating. PAG levels in milk samples were estimated by ELISA and the pregnancies were confirmed at d40 post-mating by transrectal ultrasonography (TRUS). Results: The level of PAG in whole and skim milk samples of both pregnant and nonpregnant goats remained below the threshold values until d 24 after mating. Thereafter, PAG concentration in whole and skim milk increased steadily in pregnant goats, whereas it continued below the threshold in non-pregnant does. The PAG profiles in whole and skim milk of pregnant goats were almost similar and exhibited strong positive relationship (r = 0.891; p<0.001). Day 26 post-mating was identified as the first time-point for significantly (p<0.05) higher milk PAG concentration in pregnant goats than to non-pregnant goats. When compared to TRUS examination for pregnancy diagnosis, the accuracy and specificity of PAG ELISA using whole and skim milk samples were 94.5% and 95.4%; and 95.3% and 100%, respectively. The high values of area-under-curve (0.904 [whole milk] and 0.922 [skim milk]), demonstrate outstanding discrimination ability of the milk assays. Among the sampling dates chosen, d 37 post-mating was identified as the best suitable time point for collection of milk samples to detect pregnancy in goats. Conclusion: The PAG concentration in whole and skim milk of goats collected between days 26 and 51 post-breeding can be used for the accurate prediction of pregnancy and may be useful for assisting management decisions in goat flocks.

Anesthetic efficacy of supplemental buccal infiltration versus intraligamentary injection in mandibular first and second molars with irreversible pulpitis: a prospective randomized clinical trial

  • Zargar, Nazanin;Shojaeian, Shiva;Vatankhah, Mohammadreza;Heidaryan, Shirin;Ashraf, Hengameh;Baghban, Alireza Akbarzadeh;Dianat, Omid
    • Journal of Dental Anesthesia and Pain Medicine
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    • 제22권5호
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    • pp.339-348
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    • 2022
  • Background: To compare the anesthetic efficacy of supplemental buccal infiltration (BI) (1.7 ml) versus intraligamentary (IL) injection containing 0.4 ml of 4% articaine with 1:100.000 epinephrine after an inferior alveolar nerve block (IANB) with 1.7 ml 2% lidocaine in the first and second mandibular molars diagnosed with irreversible pulpitis (IP). Methods: One hundred subjects diagnosed with IP of either the mandibular first (n = 50) or second molars (n = 50) and failed profound anesthesia following an IANB were selected. They randomly received either the IL or BI techniques of anesthesia. Pain scores on a 170 mm Heft-Parker visual analog scale were recorded initially, before, and during supplemental injections. Furthermore, pulse rate was measured before and after each supplemental injection. During the access cavity preparation and initial filing, no or mild pain was assumed to indicate anesthetic success. The chi-square test, Mann-Whitney U test, and independent samples t-test were used for the analyses. Results: The overall success rates were 80% in the IL group and 74% in the BI group, with no significant difference (P = 0.63). In the first molars, there was no significant difference between the two techniques (P = 0.088). In the second molars, IL injection resulted in a significantly higher success rate (P = 0.017) than BI. IL injection was statistically more successful (P = 0.034) in the second molars (92%) than in the first molars (68%). However, BI was significantly more successful (P = 0.047) in the first molars (88%) than in the second molars (64%). The mean pulse rate increase was significantly higher in the IL group than in the BI group (P < 0.001). Conclusions: Both the IL and BI techniques were advantageous when used as supplemental injections. However, more favorable outcomes were observed when the second molars received IL injection and the first molars received BI.