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- Liu, Yang, et al.
(författare)
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Association of mitochondrial DNA copy number with chronic kidney disease in older adults
- 2023
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Ingår i: BMC Geriatrics. - : BMC. - 1471-2318. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of chronic kidney disease (CKD). Estimation of mitochondrial DNA copy number (mtDNA-CN) is considered a convenient method for representing mitochondrial function in large samples. However, no study has investigated the association between mtDNA-CN and CKD in older adults with the highest prevalence. The objective is to examine cross-sectional and prospective associations between mtDNA-CN values and CKD risk in older adults to determine whether mtDNA-CN represents a novel potential biomarker for the recognition of CKD risk. Patients and methods In a Chinese community-based cohort of over 65-year-olds, we included 14,467 participants (52.6% females). CKD was defined by eGFR < 60 mL/min/1.73 m(2) or ICD-10 codes (patients = 3831 (26.5%)). Participants had peripheral blood levels of mtDNA-CN calculated from probe intensities of the Axiom CAS Array. Results The risk of CKD prevalence decreased with mtDNA-CN per 1-SD increment, independent of established risk factors for older CKD (odds ratio [OR] per SD 0.90, 95% confidence interval [CI] 0.86, 0.93, P < 0.001), and has comparable strength of association with these established risk factors. Furthermore, the progression of kidney function was stratified according to the worsening of eGFR categories. The risk of kidney function progression to a more severe stage gradually decreased as the mtDNA-CN increased (P trend < 0.001). Non-CKD participants in the highest quartile of mtDNA-CN had a lower risk of developing CKD compared to the lowest quartile within 2 years of follow-up, reducing the risk of CKD by 36% (95% CI 0.42, 0.97; P = 0.037). Conclusions Based on the analysis of the largest sample to date investigating the association between mtDNA-CN and CKD in older adults, higher levels of mtDNA-CN were found to be associated with a lower risk of CKD, suggesting that a reduced level of mtDNA-CN is a potential risk factor for CKD.
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| 2. |
- Liu, Zhaoxu
(författare)
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Somatostatin effects on the proteome of human prostate cancer cells
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The transition of prostate cancer from androgen dependent to the therapy resistant androgen independent state, is a large and persistent problem in the clinical management of prostate cancer. The aim of this thesis was to study somatostatin effects on the proteome of prostate cancer cells, to identify differences in protein expression in androgen dependent and androgen independent prostate cancer cells, and to explore possibilities to enhance the somatostatin receptor expression through pre-treatment with sms, 5-aza and TSA (DNA methylation/HDAC inhibitors). The results may give insight into the feasibility of using somatostatin as a part of the therapy of advanced prostate cancer. Somatostatin (sms) is important in the regulation and physiological control of many organs including the prostate. Sms can inhibit tumor growth and angiogenesis through binding to its specific receptors (SSTRs) transducing growth inhibitory, anti-secretory and apoptotic signals. Because of these properties sms is of interest for the management of prostate cancer and also of other malignancies. Sms is an unstable peptide and therefore more stable sms derivatives have been developed that are suitable for clinical use. Sms and its derivative smsdx (smsdx is a stable long acting glycosylated derivative of natural sms) were incubated with LNCaP and DU145 cells. Proteomic analysis using two-dimensional electrophoresis (2-DE) was performed to determine and compare the effect of the sms and smsdx incubation. Protein expression patterns were analysed with 2-DE and mass spectrometry (MS). Using cDNA obtained from these cell lines, the difference in expression level of SSTR mRNA transcripts before and after sms/smsdx, 5-aza and TSA treatments was analyzed by RT-PCR. Marked quantitative differences were observed in the protein expression profiles in sms/smsdx treated LNCaP and DU145 cells compared to the control cells. One third of the detected proteins were differentially expressed (PRDXs, hnRNPs). Concordance in protein expression patterns were observed between smsdx and sms treated cells with strong agreement between the up/down regulation of proteins. Catalytic mitochondrial and mitochondrial-associated proteins were significantly affected (fold change ~2 or higher). The incubation triggered up-regulation of the catalytic mitochondrial proteins. Apoptotic related proteins were also affected. An increased induction of mRNA expression of all five SSTR subtypes was observed in the LNCaP cells when incubated with sms/smsdx (dose dependent). The results indicate a positive feedback loop between sms and its receptors. Inhibition of DNA methylation and histone acetylation resulted in up regulation of SSTR5 mRNA expression. The results show that smsdx affects important proteins of the proteome in prostate cancer cells both in androgen dependent and in androgen independent prostate cancer cells. Different treatment protocols in terms of derivatives, doses, dose frequency and treatment duration may trigger/enhance effects on proteins involved in the survival/death of the tumor cells. Epigenetic manipulation in combination with sms, might be a possibility to enhance treatment sensibility for somatostatin therapy. Further clinical research on sms is needed to reveal its full potential in the management of prostate cancer.
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| 3. |
- Liu, Zhaoxu, et al.
(författare)
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Somatostatin effects on the proteome of the LNCaP cell-line
- 2007
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 30:5, s. 1173-1179
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Tidskriftsartikel (refereegranskat)abstract
- Some clinical results indicate that somatostatin (sms) might be useful in the treatment of advanced prostate cancer (HRPC). Because of its transient in vivo half-life only more stable derivatives of sms are of interest in this context. Recent studies have shown that natural sms can be conjugated to a carbohydrate (smsdx) with preservation of sms-like effects on the prostatic tumor cell proteome. The present study identifies some of the affected proteins in an effort to elucidate pathways and proteins that might be of importance for the potential usefulness of sms treatment in HRPC. After incubating the LNCaP cell-line with sms14/smsdx, comparative proteomics was used for analysing and identifying affected proteins. Protein expression patterns were analysed with two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Catalytic mitochondrial and mitochondrial-associated proteins were significantly affected (fold change approximately 2 or higher) and they were in general up-regulated. Apoptosis-related proteins were both up-regulated (VDAC1, VDAC2) and down-regulated (PRDX2, TCTP). The fold change was >2 for PRDX2 and <2 for the others. There was a strong agreement between sms and smsdx on the up- and down-regulation of proteins. Sms/smsdx triggered up-regulation of catalytic mitochondrial proteins and seemed to affect apoptosis-related proteins. This could indicate important pathways on which smsdx might be able to curb the progression of HRPC. The results encourage a pending clinical phase II study.
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