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Zamani P, Mohammadi H, Mirhoseini SZ. Genome-wide association study and genomic heritabilities for blood protein levels in Lori-Bakhtiari sheep. Sci Rep 2021; 11:23771. [PMID: 34887490 PMCID: PMC8660901 DOI: 10.1038/s41598-021-03290-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 12/01/2021] [Indexed: 01/01/2023] Open
Abstract
Serum protein levels are related to physiological and pathological status of animals and could be affected by both genetic and environmental factors. This study aimed to evaluate genetic variation of serum protein profile in sheep. Blood samples were randomly collected from 96 Lori-Bakhtiari ewes, a heavy meat-type breed. Total protein, albumin, globulin, α1, α2, β and γ globulins and IgG levels were measured in blood serum. The samples were genotyped using the Illumina OvineSNP50 BeadChip. The studied traits adjusted for age, birth type, birth season and estimate of breeding value for body weight were considered as pseudo-phenotypes in genome-wide association analysis. In the GWAS model, the first five principal components were fitted as covariates to correct the biases due to possible population stratification. The Plink, R and GCTA software were used for genome-wide association analysis, construction of Q-Q and Manhattan plots and estimation of genetic variances, respectively. Noticeable genomic heritabilities ± SE were estimated for total and γ globulins (0.868 ± 0.262 and 0.831 ± 0.364, respectively), but other protein fractions had zero or close to zero estimates. Based on the Bonferroni adjusted p values, four QTLs located on 181.7 Mbp of OAR3, 107.7 Mbp of OAR4, 86.3 Mbp of OAR7 and 83.0 Mbp of OAR8 were significantly associated with α1, β, β and γ globulins, respectively. The results showed that the PKP2, IGF2R, SLC22A1 and SLC22A2 genes could be considered as candidate genes for blood serum proteins. The present study showed significant genetic variations of some blood protein fractions.
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Affiliation(s)
- P Zamani
- Department of Animal Science, Faculty of Agriculture, Bu-Ali Sina University, Hamedan, Iran.
| | - H Mohammadi
- Department of Animal Science, Faculty of Agriculture, Bu-Ali Sina University, Hamedan, Iran
| | - S Z Mirhoseini
- Department of Animal Science, Faculty of Agriculture, University of Guilan, Rasht, Iran
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Czumaj A, Śledziński T. Biological Role of Unsaturated Fatty Acid Desaturases in Health and Disease. Nutrients 2020; 12:E356. [PMID: 32013225 PMCID: PMC7071289 DOI: 10.3390/nu12020356] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/20/2020] [Accepted: 01/28/2020] [Indexed: 12/21/2022] Open
Abstract
Polyunsaturated fatty acids (PUFAs) are considered one of the most important components of cells that influence normal development and function of many organisms, both eukaryotes and prokaryotes. Unsaturated fatty acid desaturases play a crucial role in the synthesis of PUFAs, inserting additional unsaturated bonds into the acyl chain. The level of expression and activity of different types of desaturases determines profiles of PUFAs. It is well recognized that qualitative and quantitative changes in the PUFA profile, resulting from alterations in the expression and activity of fatty acid desaturases, are associated with many pathological conditions. Understanding of underlying mechanisms of fatty acid desaturase activity and their functional modification will facilitate the development of novel therapeutic strategies in diseases associated with qualitative and quantitative disorders of PUFA.
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Affiliation(s)
- Aleksandra Czumaj
- Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Medical University of Gdansk, Dębinki, 80-211 Gdansk, Poland;
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Protective Role of Terminalia bellirica (Gaertn.) Roxb Fruits Against CCl 4 Induced Oxidative Stress and Liver Injury in Rodent Model. Indian J Clin Biochem 2018; 34:155-163. [PMID: 31092988 DOI: 10.1007/s12291-017-0732-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Accepted: 12/22/2017] [Indexed: 01/14/2023]
Abstract
Abstract The medicinal plant, Terminalia bellirica (Gaertn.) Roxb. is widely used in the traditional Indian system of medicine like Ayurveda for centuries in the treatment of various ailments owing to it's rejuvenating as well as health promoting effects. The present study evaluates protective role of aqueous acetone extract of T. bellirica fruits (AATB) against CCl4 induced liver toxicity in animal model. The liver damage was assessed by liver function markers including ALT, AST, ALP, GGT, LDH, total bilirubin, total protein, albumin, globulin and albumin-globulin ratio. The levels of MDA, ROS, and NO along with the tissue antioxidants were evaluated to assess hepatic oxidative stress and level of lipid peroxidation. Treatment with AATB prior to the exposure of CCl4 significantly reduced the damage when compared to the control rats. The outcome of the present study advocates the traditional use of the plant as ethnic food and health tonic. Graphical Abstract
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Kuriakose J, Lal Raisa H, A V, Eldhose B, M S L. Terminalia bellirica (Gaertn.) Roxb. fruit mitigates CCl 4 induced oxidative stress and hepatotoxicity in rats. Biomed Pharmacother 2017. [PMID: 28651233 DOI: 10.1016/j.biopha.2017.06.080] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
Terminalia bellirica (Gaertn.) Roxb. is a medicinal plant used for the treatment of various ailments in the traditional system of medicine like Ayurveda where it has been prescribed as a rejuvenator and general health tonic. The fruit of the plant is one of the components of the age old ayurvedic formulation-'Triphala'. The present study evaluates curative effect of aqueous acetone extract of Terminalia bellirica fruits (AATB) against CCl4 induced oxidative stress and liver damage in an animal model. Two doses of the fruit extract (200mg/kg body weight and 400mg/kg body weight) were investigated for the beneficial effects. At the end of the treatment, liver function markers (ALT, AST, ALP, GGT, LDH, total bilirubin, total protein, albumin, globulin, albumin-globulin ratio) as well as hepatic oxidative stress markers (SOD, CAT, GSH) were evaluated. Treatment with AATB significantly restored the parameters towards normal level as compared to the elevated biochemical markers in the CCl4 treated animals. Reversal to normal tissue architecture was observed in histological evaluation. The results of AATB (400mg/kg) were found comparable with that of standard drug silymarin in all the parameters. The above findings suggest the therapeutic potential of the plant in alleviating hepatic oxidative stress and tissue damage, hence the traditional use of the plant in this regard stands justified.
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Affiliation(s)
- Jayesh Kuriakose
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala, India
| | - Helen Lal Raisa
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala, India
| | - Vysakh A
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala, India
| | - Binil Eldhose
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala, India
| | - Latha M S
- School of Biosciences, Mahatma Gandhi University, Priyadarshini Hills, Kottayam, Kerala, India.
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Lin Q, Lin ZH, Chen J, Lin JX, Li X, Jiang JR, Ma XK, Wu DH, Chen ZH, Dong M, Wei L, Wang TT, Ruan DY, Lin ZX, Wen JY, Wu XY, Huang MS. Prognostic significance of preoperative albumin-to-globulin ratio in patients with cholangiocarcinoma. Curr Res Transl Med 2017; 65:83-87. [PMID: 28684265 DOI: 10.1016/j.retram.2017.06.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 06/01/2017] [Accepted: 06/02/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND This study aimed to assess the prognostic value of the serum albumin to globulin ratio (AGR) in cholangiocarcinoma patients after surgery. METHODS We retrospectively enrolled 123 cholangiocarcinoma patients who underwent surgical treatment between June 2003 and September2014 at the Third Affiliated Hospital of Sun Yat-sen University. Univariate and multivariate analyses using the Cox regression model were performed to determine the prognostic value of AGR. RESULTS Univariate analysis suggested that AGR was a predictive factor for (overall survival) OS but not for recurrence free survival (RFS). After adjustment for other risk factors, multivariate analysis showed that AGR remained independently associated with OS. The optimal cut-off point for AGR was determined to be 1.44. Kaplan-Meier curves showed that there was a significantly lower mean survival time in the low AGR group compared to the high AGR group. A low AGR was found to be significantly associated with high alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin levels and an advanced American Joint Committee on Cancer TNM stage, but a low hemoglobin level. CONCLUSION In summary, patients with higher AGRs have better outcomes than those with lower AGRs. Preoperative AGR can be a reliable marker for evaluating the prognosis of cholangiocarcinoma patients.
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Affiliation(s)
- Q Lin
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China.
| | - Z-H Lin
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - J Chen
- Department of Oncology, Central Hospital of Hengyang, Hengyang, 421001 Hunan, People's Republic of China
| | - J-X Lin
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - X Li
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - J-R Jiang
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - X-K Ma
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - D-H Wu
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - Z-H Chen
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - M Dong
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - L Wei
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - T-T Wang
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - D-Y Ruan
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - Z-X Lin
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - J-Y Wen
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - X-Y Wu
- Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China
| | - M-S Huang
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-sen University, 600, Tianhe Road, 510630 Guangzhou, People's Republic of China.
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Guo T, Yin RX, Lin WX, Wang W, Huang F, Pan SL. Association of the variants and haplotypes in the DOCK7, PCSK9 and GALNT2 genes and the risk of hyperlipidaemia. J Cell Mol Med 2016; 20:243-65. [PMID: 26493351 PMCID: PMC4727555 DOI: 10.1111/jcmm.12713] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Accepted: 09/07/2015] [Indexed: 01/09/2023] Open
Abstract
Little is known about the association between the single nucleotide polymorphisms (SNPs) and haplotypes of the dedicator of cytokinesis 7 (DOCK7), pro-protein convertase subtilisin/kexin type 9 (PCSK9) and polypeptide N-acetylgalactosaminyltransferase 2 (GALNT2) and serum lipid traits in the Chinese populations. This study was to determine the association between nine SNPs in the three genes and their haplotypes and hypercholesterolaemia (HCH)/hypertriglyceridaemia (HTG), and to identify the possible gene-gene interactions among these SNPs. Genotyping was performed in 733 HCH and 540 HTG participants. The haplotype of C-C-G-C-T-G-C-C-G [in the order of DOCK7 rs1168013 (G>C), rs10889332 (C>T); PCSK9 rs615563 (G>A), rs7552841 (C>T), rs11206517 (T>G); and GALNT2 rs1997947 (G>A), rs2760537 (C>T), rs4846913 (C>A) and rs11122316 (G>A) SNPs] was associated with increased risk of HCH and HTG. The haplotypes of C-C-G-C-T-G-C-C-A and G-C-G-T-T-G-T-C-G were associated with a reduced risk of HCH and HTG. The haplotypes of G-C-G-C-T-G-C-C-A and G-C-G-C-T-G-T-C-G were associated with increased risk of HCH. The haplotypes of C-T-G-C-T-G-C-C-G, G-C-A-C-T-G-C-C-G and G-C-G-C-T-G-C-C-A were associated with an increased risk of HTG. The haplotypes of G-C-G-C-T-G-T-C-A and G-C-G-T-T-G-T-C-G were associated with a reduced risk of HTG. In addition, possible inter-locus interactions among the DOCK7, PCSK9 and GALNT2 SNPs were also noted. However, further functional studies of these genes are still required to clarify which SNPs are functional and how these genes actually affect the serum lipid levels.
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Affiliation(s)
- Tao Guo
- Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China
| | - Rui-Xing Yin
- Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China
| | - Wei-Xiong Lin
- Department of Molecular Genetics, Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi, China
| | - Wei Wang
- Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China
| | - Feng Huang
- Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China
| | - Shang-Ling Pan
- Department of Pathophysiology, School of Premedical Sciences, Guangxi Medical University, Nanning, Guangxi, China
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Nazha B, Moussaly E, Zaarour M, Weerasinghe C, Azab B. Hypoalbuminemia in colorectal cancer prognosis: Nutritional marker or inflammatory surrogate? World J Gastrointest Surg 2015; 7:370-377. [PMID: 26730282 PMCID: PMC4691717 DOI: 10.4240/wjgs.v7.i12.370] [Citation(s) in RCA: 119] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Revised: 10/12/2015] [Accepted: 11/10/2015] [Indexed: 02/06/2023] Open
Abstract
Albumin is the single most abundant protein in the human serum. Its roles in physiology and pathology are diverse. Serum albumin levels have been classically thought to reflect the nutritional status of patients. This concept has been challenged in the last two decades as multiple factors, such as inflammation, appeared to affect albumin levels independent of nutrition. In general, cancer patients have a high prevalence of hypoalbuminemia. As such, the role of hypoalbuminemia in patients with colorectal cancer has received significant interest. We reviewed the English literature on the prognostic value of pretreatment albumin levels in colorectal cancer. We also consolidated the evidence that led to the current understanding of hypoalbuminemia as an inflammatory marker rather than as a nutritional one among patients with colorectal cancer.
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Wang X, Tang H, Teng M, Li Z, Li J, Fan J, Zhong L, Sun X, Xu J, Chen G, Chen D, Wang Z, Xing T, Zhang J, Huang L, Wang S, Peng X, Qin S, Shi Y, Peng Z. Mapping of hepatic expression quantitative trait loci (eQTLs) in a Han Chinese population. J Med Genet 2014; 51:319-26. [PMID: 24665059 PMCID: PMC3995251 DOI: 10.1136/jmedgenet-2013-102045] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Background Elucidating the genetic basis underlying hepatic gene expression variability is of importance to understand the aetiology of the disease and variation in drug metabolism. To date, no genome-wide expression quantitative trait loci (eQTLs) analysis has been conducted in the Han Chinese population, the largest ethnic group in the world. Methods We performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue samples (n=64). The data were then compared with published eQTL data from a Caucasian population. We then performed correlations between these eQTLs with important pharmacogenes, and genome-wide association study (GWAS) identified single nucleotide polymorphisms (SNPs), in particular those identified in the Asian population. Results Our analyses identified 1669 significant eQTLs (false discovery rate (FDR) < 0.05). We found that 41% of Asian eQTLs were also eQTLs in Caucasians at the genome-wide significance level (p=10−8). Both cis- and trans-eQTLs in the Asian population were also more likely to be eQTLs in Caucasians (p<10−4). Enrichment analyses revealed that trait-associated GWAS-SNPs were enriched within the eQTLs identified in our data, so were the GWAS-SNPs specifically identified in Asian populations in a separate analysis (p<0.001 for both). We also found that hepatic expression of very important pharmacogenetic (VIP) genes (n=44) and a manually curated list of major genes involved in pharmacokinetics (n=341) were both more likely to be controlled by eQTLs (p<0.002 for both). Conclusions Our study provided, for the first time, a comprehensive hepatic eQTL analysis in a non-European population, further generating valuable data for characterising the genetic basis of human diseases and pharmacogenetic traits.
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Affiliation(s)
- Xiaoliang Wang
- Department of General Surgery, Shanghai First People's Hospital, Medical College, Shanghai Jiaotong University, Shanghai, China
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Azab B, Kedia S, Shah N, Vonfrolio S, Lu W, Naboush A, Mohammed F, Bloom SW. The value of the pretreatment albumin/globulin ratio in predicting the long-term survival in colorectal cancer. Int J Colorectal Dis 2013; 28:1629-36. [PMID: 23857599 DOI: 10.1007/s00384-013-1748-z] [Citation(s) in RCA: 104] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/26/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND Low serum albumin was found as a predictor of long-term mortality in colorectal cancer (CRC) patients. Our aim was to evaluate the value of the pretreatment albumin/globulin ratio (AGR) to predict the long-term mortality in CRC patients. METHODS Patients were included if they had comprehensive metabolic panel (CMP) before treatment (surgery or chemotherapy). The albumin/globulin ratio, routinely reported in CMP, is calculated [AGR = Albumin/(Total protein - Albumin)]. Patients were divided into three equal tertiles according to their pretreatment AGR. The primary outcome was cancer-related mortality, which was obtained from our cancer registry database. RESULTS A total of 534 consecutive CRC patients had pretreatment CMP. The 1st AGR tertile had a significant higher 4-year mortality compared to the second and third AGR tertiles (42 vs. 19 and 7 %, p < 0.0001 according to Fisher's exact two-tailed test). In the multivariate model, AGR remained an independent predictor of survival with 75 % decrease in mortality among the highest AGR tertile in comparison to the lowest AGR tertile, p < 0.0001. In the subset of 234 patients with normal serum albumin (albumin of >3.5 g/dl), serum AGR continues to be an independent predictor of cancer-related mortality with an adjusted hazard ratio of the third tertile compared to the first tertile equal to 0.05 (95 % confidence interval 0.01-0.33, p = 0.002). CONCLUSION Low AGR was a strong independent predictor of long-term cancer-specific survival among colorectal cancer patients. Additionally, among the patients with normal albumin (>3.5 g/dl), patients with lower globulins but higher albumin and AGR levels had better survival.
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Affiliation(s)
- Basem Azab
- Department of Surgery, Staten Island University Hospital, 475 Seaview Avenue, Staten Island, NY, 10305, USA,
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