Integrated multi-omics approach revealed cellular senescence landscape.

Cellular senescence is a complex multifactorial biological phenomenon that plays essential roles in aging, and aging-related diseases. During this process, the senescent cells undergo gene expression altering and chromatin structure remodeling. However, studies on the epigenetic landscape of senescence using integrated multi-omics approaches are limited. In this research, we performed ATAC-seq, RNA-seq and ChIP-seq on different senescent types to reveal the landscape of senescence and identify the prime regulatory elements. We also obtained 34 key genes and deduced that NAT1, PBX1 and RRM2, which interacted with each other, could be the potential markers of aging and aging-related diseases. In summary, our work provides the landscape to study accessibility dynamics and transcriptional regulations in cellular senescence. The application of this technique in different types of senescence allows us to identify the regulatory elements responsible for the substantial regulation of transcription, providing the insights into molecular mechanisms of senescence.

IL-17A promotes the progression of Alzheimer's disease in APP/PS1 mice.

BACKGROUND: Alzheimer's disease (AD), which is the most common cause of dementia in elderly individuals, is a progressive neurodegenerative disorder. Neuroinflammation, which is an immune response that is activated by glial cells in the central nervous system, plays an important role in neurodegenerative diseases. Many studies have shown that interleukin-17A (IL-17A) plays an important role in AD, but research on the pathological effects of IL-17A on AD is limited. METHODS: We report the effect of IL-17A on AD progression in APPswe/PS1dE9 (APP/PS1) mice, which are the most widely used AD model mice. The BV2 cell line, which is a microglial cell line derived from C57/BL6 mice, was used to establish a cell model to verify the role of IL-17A in neuroinflammation at the cellular level. The HT22 hippocampal neuronal cell line was used to investigate the relationship between IL-17A and Aß deposition. RESULTS: In this research, we found that IL-17A promotes the progression of AD in the APP/PS1 mouse model. The role of IL-17A in neuroinflammation is related to tumour necrosis factor (TNF)-α. Circulating IL-17A stimulates the secretion of TNF-α by microglia through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signalling pathway, thus exacerbating neuroinflammation. In addition, intraperitoneal injection of IL-17A antibody (IL17Ab) significantly improved the cognitive function of APP/PS1 mice. CONCLUSIONS: IL-17A increased TNF-α levels in the brain and exacerbated neuroinflammation through the TLR4/NF-κB signalling pathway and microglial activation in APP/PS1 mice. Moreover, IL-17A promoted the progression of AD by enhancing neuroinflammation, inhibiting microglial phagocytosis, and promoting the deposition of ß-amyloid 42 in AD model mice.

Severely High Lactic Acid in Severe Pneumonia Patient: a Case Report.

BACKGROUND: Severe pneumonia (SP) is a clinically critical acute disease which has a higher mortality rate among infectious diseases. In this report, a rare case of severe pneumonia with severely high lactic acid (up to 24 mmol/L) and relatively normal pH was analyzed. METHODS: The case was discussed from different angles including acid-base balance disorder, the use of extractor-poreal membrane oxygenation (ECMO), dialysis treatment, circulatory disturbance, and inspection methodology. RESULTS: Hypoxia and dissolution of muscles caused by circulatory disorders may be the cause of the abnormal increase of lactate in this case; while the relatively normal pH may be caused by the dialysis treatment. CONCLUSIONS: Such a high blood gas lactic acid value is extremely rare, and this increase is not due to the limitations of the test method. High lactic acid may not result in the significant decrease of pH when the patient receives continuous systemic treatment.

Multi-sensor integration approach based on hyperspectral imaging and electronic nose for quantitation of fat and peroxide value of pork meat.

The study assessed the feasibility of merging data acquired from hyperspectral imaging (HSI) and electronic nose (e-nose) to develop a robust method for the rapid prediction of intramuscular fat (IMF) and peroxide value (PV) of pork meat affected by temperature and NaCl treatments. Multivariate calibration models for prediction of IMF and PV using median spectra features (MSF) and image texture features (ITF) from HSI data and mean signal values (MSV) from e-nose signals were established based on support vector machine regression (SVMR). Optimum wavelengths highly related to IMF and PV were selected from the MSF and ITF. Next, recurring optimum wavelengths from the two feature groups were manually obtained and merged to constitute "combined attribute features" (CAF) which yielded acceptable results with (Rc2 = 0.877, 0.891; RMSEC = 2.410, 1.109; Rp2 = 0.790, 0.858; RMSEP = 3.611, 2.013) respectively for IMF and PV. MSV yielded relatively low results with (Rc2 = 0.783, 0.877; RMSEC = 4.591, 0.653; Rp2 = 0.704, 0.797; RMSEP = 3.991, 0.760) respectively for IMF and PV. Finally, data fusion of CAF and MSV was performed which yielded relatively improved prediction results with (Rc2 = 0.936, 0.955; RMSEC = 1.209, 0.997; Rp2 = 0.895, 0.901; RMSEP = 2.099, 1.008) respectively for IMF and PV. The results obtained demonstrate that it is feasible to mutually integrate spectral and image features with volatile information to quantitatively monitor IMF and PV in processed pork meat. Graphical abstract.

E2F1 mediates the downregulation of POLD1 in replicative senescence.

POLD1, the catalytic subunit of DNA Pol δ, plays an important role in DNA synthesis and DNA damage repair, and POLD1 is downregulated in replicative senescence and mediates cell aging. However, the mechanisms of age-related downregulation of POLD1 expression have not been elucidated. In this study, four potential CpG islands in the POLD1 promoter were found, and the methylation levels of the POLD1 promoter were increased in aging 2BS cells, WI-38 cells and peripheral blood lymphocytes, especially at a single site, CpG 36, in CpG island 3. Then, the transcription factor E2F1 was observed to bind to these sites. The binding affinity of E2F1 for the POLD1 promoter was found to show age-related attenuation and was confirmed to be positively regulated by the E2F1 level and negatively regulated by POLD1 promoter methylation. Moreover, cell senescence characteristics were observed in the cells transfected with shRNA-E2F1 and could contribute to the downregulation of POLD1 induced by the E2F1 decline. Collectively, these results indicated that the attenuation of the binding affinity of E2F1 for the POLD1 promoter, mediated by an age-related decline in E2F1 and increased methylation of CpG island 3, downregulates POLD1 expression in aging.

Questionnaire survey on association between preeclampsia and incontinentia pigmenti.

AIM: In this study, a questionnaire survey was conducted to find the relationship between preeclampsia (PE) and incontinentia pigmenti (IP). METHODS: Using a questionnaire survey of 147 women whose children were diagnosed with IP, this study first investigated their clinical manifestations and complications during pregnancy. The manifestations included high blood pressure, proteinuria and edema after 20 weeks of gestation. Women with and without IP were separated into two groups, then analyzed accordingly. RESULTS: There were 45 mothers with IP in the case group and 102 mothers without IP in the control group. IP mothers who were pregnant with an IP fetus were at higher risk for hypertension, proteinuria, and edema during pregnancy as compared with non-IP mothers that carried an IP fetus. Out of these 147 mothers, 8 mothers with IP and 6 mothers without IP presented with new-onset hypertension during pregnancy (P = 0.024)，7 mothers with IP and 4 mothers without IP presented with new-onset proteinuria during pregnancy (P = 0.013)，and 21 IP mothers and 27 non-IP mothers presented with edema during pregnancy (P = 0.016). Although no statistical difference was observed, mothers in the case group were more likely to develop the above three symptoms concurrently (6.7% vs 2.0%; P = 0.168), and were more likely to be diagnosed with PE (8.9% vs 3.9%; P = 0.249). CONCLUSION: Our study revealed that the simultaneous occurrence of IP in the mother and fetus increased the likelihood of clinical manifestations associated with PE during pregnancy.

Age-Related Increase of Insulin-Degrading Enzyme Is Inversely Correlated with Cognitive Function in APPswe/PS1dE9 Mice.

BACKGROUND Insulin-degrading enzyme (IDE) is an important regulator for Ab clearance and diabetes. Although it is indispensable in removing plaques related to onset Alzheimer's disease (AD) and in degrading insulin related to diabetes, there have been few studies on the dynamic level of IDE in different stages of AD. MATERIAL AND METHODS The present study explored the level IDE protein in different stages of APPswe/PS1dE9 mice and their correlations with cognitive decline. The 4-month-old, 10-month-old, and 18-month-old mice were used as the different age stages of mice. Cognitive function was evaluated using the Morris water maze test. We also observed the level of Ab plaques in brain regions of different stages. RESULTS The data revealed that the expression of IDE was dramatically higher than in age-matched wild mice at the age of 10 months and 18 months. In terms of distribution, Aß plaques were deposited mostly in the cortex and hippocampus, especially in 10-month-old and 18-month-old APPswe/PS1dE9 mice. The cognitive function of 4-month-old APPswe/PS1dE9 mice was not significantly differ in spatial learning. However, the cognitive function, both spatial learning and spatial memory, was dramatically lower in 10-month-old and 18-month-old groups. CONCLUSIONS There was a positive correlation between the expression of IDE and spatial memory in 10-month-old and 18-month-old APPswe/PS1dE9 mice. The study of this protein may provide reference values for the further study of IDE in Alzheimer's disease.

[MCT4 reduces glucose metabolism and promotes apoptosis of prostate cancer cells].

OBJECTIVE: To investigate the effect of monocarboxylate transporter 4 (MCT4) on the apoptosis and glucose metabolism of prostate cancer cells. METHODS: We constructed an adenoviral vector containing shRNA-MCT4 and transfected it into the adenocarcinoma cell lines DU145 and PC-3, using the untransfected vector as the blank control and the negative vector as the negative control (shRNA-NC). We determined the MCT4 expression, lactic acid secretion, glucose consumption and apoptosis rate in different groups of cells. RESULTS: After transfection, the expression of MCT4 in the DU145 and PC-3 cells was significantly lower in the shRNA-MCT4 than in the blank control (P = 0.008 and 0.008) and shRNA-NC groups (P = 0.007 and 0.009), and so were the secretion of lactic acid (P = 0.009 and 0.009; P = 0.009 and 0.008) and single-cell glucose consumption (P = 0.007 and 0.007; P = 0.009 and 0.007). The apoptosis rate of the DU145 cells was remarkably higher in the shRNA-MCT4 than in the blank control and shRNA-NC groups (ï¼»22.11 ± 2.68ï¼½% vs ï¼»9.81 ± 1.24ï¼½% and ï¼»10.01 ± 1.46ï¼½%, P = 0.003 and 0.003), and so was that of the PC-3 cells (ï¼»23.38 ± 3.08ï¼½% vs ï¼»10.21 ± 1.58ï¼½% and ï¼»10.91 ± 1.63ï¼½%, P = 0.004 and 0.004). CONCLUSIONS: Inhibiting the expression of MCT4 can interfere with the glucose metabolism and promote the apoptosis of prostate cancer cells. The MCT4 gene is a potential therapeutic target for the treatment of prostate cancer.

Development of a Novel Urine Alzheimer-Associated Neuronal Thread Protein ELISA Kit and Its Potential Use in the Diagnosis of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is an age-related chronic degenerative disease that damages the nervous system. A noninvasive and simple method for early detection of AD is extremely important for the diagnosis and prognosis of AD. Thus, we aimed to develop an enzyme-linked immunosorbent assay (ELISA) kit to detect urine Alzheimer-associated neuronal thread protein (AD7C-NTP), and to evaluate its clinical value for the diagnosis of AD. METHODS: Immunogenic AD7C-NTP peptide fragments were synthesized by the solid-phase method and used for immunizing mice or rabbits to generate anti-AD7C-NTP antibodies. The urine AD7C-NTP ELISA kit was then established; the generated mouse anti-AD7C-NTP antibody was used as a capture antibody, the biotin-labeled rabbit anti-AD7C-NTP antibody was used as a detection antibody, and avidin labeled by horseradish peroxidase was used as a substrate. The first morning urine specimens of 121 AD patients and 118 age-matched controls were collected, and the urine AD7C-NTP levels were detected by the above ELISA kit. RESULTS: Mouse and rabbit anti-AD7C-NTP antibody ELISA titer was found to be 1:8,000 and 1:32,000, respectively. A single band with a relative molecular mass of 41 kDa was found in human brain specimens by Western blot assay, which was identified as AD7C-NTP antibody. The urine AD7C-NTP concentration of the AD patients was higher than that of the age-matched controls, the sensitivity was 89.3% and the specificity was 84.7%. CONCLUSIONS: Our study demonstrated that our newly developed urine AD7C-NTP ELISA kit has suggested potential for diagnosing AD in a Chinese population, suggesting it may be a useful diagnostic kit for detecting early AD.

Human POLD1 modulates cell cycle progression and DNA damage repair.

BACKGROUND: The activity of eukaryotic DNA polymerase delta (Pol δ) plays an essential role in genome stability through its effects on DNA replication and repair. The p125 catalytic subunit of Pol δ is encoded by POLD1 gene in human cells. To clarify biological functions of POLD1, we investigated the effects of POLD1 overexpression or downregulation on cell proliferation, cell cycle progression, DNA synthesis and oxidative DNA damage induced by H2O2. METHODS: HEK293 cells were transfected with POLD1 expression plasmid or shRNA, cell proliferation, cell cycle progression, and DNA synthesis in HEK293 cells were analyzed. RESULTS: HEK293 cells were transfected with POLD1 expression plasmid or shRNA. POLD1 downregulation by shRNA suppressed cell proliferation, cell cycle progression, and DNA synthesis in HEK293 cells. However, POLD1 overexpression had no significant effects on these processes. Finally, comet assay showed that POLD1 downregulation led to increased DNA damage. CONCLUSIONS: Our results suggest that human POLD1 plays important role in the regulation of cell cycle progression and DNA damage repair.

[Prevalence and subtype distribution of HPV infection among women in Beijing urban area and their correlation with age].

OBJECTIVE: To investigate the prevalence and subtype distribution of human papillomavirus (HPV) infection and its correlation with age among women in Beijing urban area, and provide some epidemiological evidence for the clinical application of HPV vaccines. METHODS: We collected cervical specimens from 1999 women in the Outpatient Department of our hospital, performed genetyping of HPV-DNA, and analyzed the incidence of HPV infection in different age groups. RESULTS: HPV infection was detected in 502 (25.2%) of the 1999 women patients, with 391 (19.6%) cases of high-risk HPV, which included 326 (83.4%, 326/391) cases of single infection. HPV-16 was the most common type (21.2%, 69/326), followed by HPV-52 (19.3%, 63/326) and HPV-58 (16.0%, 52/326). The prevalence of HPV infection was the highest among the women aged 41 -50 years and the lowest among those over 60 years. CONCLUSION: The subtype- and age-specific distribution of HPV infection among women in Beijing urban area shows an obvious heterogeneity, which deserves due consideration in the clinical application of HPV vaccines.

Myeloid ectopic viral integration site 2 accelerates the progression of Alzheimer's disease.

Amyloid plaques, a major pathological hallmark of Alzheimer's disease (AD), are caused by an imbalance between the amyloidogenic and non-amyloidogenic pathways of amyloid precursor protein (APP). BACE1 cleavage of APP is the rate-limiting step for amyloid-ß production and plaque formation in AD. Although the alteration of BACE1 expression in AD has been investigated, the underlying mechanisms remain unknown. In this study, we determined MEIS2 was notably elevated in AD models and AD patients. Alterations in the expression of MEIS2 can modulate the levels of BACE1. MEIS2 downregulation improved the learning and memory retention of AD mice and decreased the number of amyloid plaques. MEIS2 binds to the BACE1 promoter, positively regulates BACE1 expression, and accelerates APP amyloid degradation in vitro. Therefore, our findings suggest that MEIS2 might be a critical transcription factor in AD, since it regulates BACE1 expression and accelerates BACE1-mediated APP amyloidogenic cleavage. MEIS2 is a promising early intervention target for AD treatment.

Synaptic vesicle glycoprotein 2 A in serum is an ideal biomarker for early diagnosis of Alzheimer's disease.

BACKGROUND: Previous studies have demonstrated that early intervention was the best plan to inhibit the progression of Alzheimer's disease (AD), which relied on the discovery of early diagnostic biomarkers. In this study, synaptic vesicle glycoprotein 2 A (SV2A) was examined to improve the early diagnostic efficiency in AD. METHODS: In this study, biomarker testing was performed through the single-molecule array (Simoa). A total of 121 subjects including cognitively unimpaired controls, amnestic mild cognitive impairment (aMCI), AD and other types of dementia underwent cerebrospinal fluid (CSF) SV2A testing; 430 subjects including health controls, aMCI, AD and other types of dementia underwent serum SV2A, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL) and p-tau217 testing; 92 subjects including aMCI and AD underwent both CSF SV2A and serum SV2A testing; 115 cognitively unimpaired subjects including APOE ε4 carriers and APOE ε4 non-carriers were tested for serum SV2A, GFAP, NfL and p-tau217. Then, the efficacy of SV2A for the early diagnosis of AD and its ability to identify those at high risk of AD from a cognitively unimpaired population were further analyzed. RESULTS: Both CSF and serum SV2A significantly and positively correlated with cognitive performance in patients with AD, and their levels gradually decreased with the progression of AD. Serum SV2A demonstrated excellent diagnostic efficacy for aMCI, with a sensitivity of 97.8%, which was significantly higher than those of NfL, GFAP, and p-tau217. The SV2A-positive rates ranged from 92.86 to 100% in aMCI cases that were negative for the above three biomarkers. Importantly, of all the biomarkers tested, serum SV2A had the highest positivity rate (81.82%) in individuals at risk for AD. CONCLUSIONS: Serum SV2A was demonstrated to be a novel and ideal biomarker for the early diagnosis of AD, which can effectively distinguish those at high risk of AD in cognitively unimpaired populations.

The Interpretation of Mirror Pattern Bands During Oligoclonal Immunoglobulin Isoelectric Focusing Electrophoresis: A Retrospective Study.

OBJECTIVE: Mirror patterns are incidental types that accompany the analysis of the oligoclonal band (OCB) in cerebrospinal fluid (CSF). However, their interpretation remains controversial. In this study, we analyzed all graphic results of mirror patterns from 86 patients to provide an optimal interpretation scheme for mirror patterns. METHODS: Matched CSF and serum specimens were obtained from patients with various neurological disorders that required OCB analysis. A total of 86 patients were screened and serum immunofixation electrophoresis (IFE) was performed in all 86. The interobserver agreement for interpreting mirror patterns by visual inspection was tested. The method agreement between the visual inspection and IFE was also evaluated. The CSF/serum albumin quotient (QALB) was calculated to determine the blood-brain barrier integrity of all patients. RESULTS: Of the 86 patients with mirror patterns, 19.8% (17/86) had typical mirror bands and most (80.2%) had atypical mirror bands. There was a good agreement between the 2 observers in interpreting typical mirror patterns. However, kappa statistics analysis showed poor agreement regarding the interpretation of atypical mirror bands by visual observation alone (kappa value, -0.026 to 0.314 between 2 observers). The disagreement was pronounced between the visual inspection and validation of IFE (kappa value, -0.0238 to 0.176 between the first observer and IFE; -0.322 to 0.118 between the second observer and IFE). The normal QALB rates in the type V groups were significantly higher than those in the type IV group and the positive QALB rates in the type IV were significantly higher than those in the type V. CONCLUSION: Visual inspection to interpret mirror pattern bands is unreliable. Considering the completely different clinical significance between type IV and type V and high risk of potential misinterpretations, it is necessary to perform IFE on all the atypical mirror types to discriminate atypical type IV from atypical type V.

Factors influencing the degree of disability in patients with neuromyelitis optica spectrum disorders.

OBJECTIVE: To investigate the factors influencing the degree of disability in patients with neuromyelitis optica spectrum disorder (NMOSD) and provide evidence for disease monitoring and clinical intervention. METHODS: Eighty-four patients with NMOSD at Xuanwu Hospital Capital Medical University were enrolled in this retrospective study. Before treatment, blood was collected from all patients, and their expanded disability status scores were assessed. RESULTS: Of the 84 patients assessed, 66 (78.57%) had an expanded disability status scale score < 7, and 18 (21.43%) had scores ≥ 7. The univariate analysis showed that the total bilirubin (TBil), cerebrospinal fluid albumin (CSF ALB), cerebrospinal fluid immunoglobulin G (CSF IgG), QALB, and QIgG levels in the group with scores ≥ 7 were significantly different from those with scores < 7 (P < 0.05). In addition, Spearman's correlation analysis showed a significant correlation between ALB and expanded disability status scores in patients with NMOSD (P < 0.05), and the multivariate logistic regression analysis showed that TBil was an independent factor influencing the degree of disability in patients with NMOSD (P < 0.05). The receiver operating characteristic curve was constructed using TBil values; the area under the curve of TBil was 0.729 (P < 0.01), and the best cut-off value was 11.015 g/L. Its sensitivity in predicting the severity of disability in NMOSD patients was 51.5% while its specificity was 88.9%. CONCLUSION: TBil is an independent factor that influences the severity of disability in patients with NMOSD. In addition, ALB is closely related to NMOSD severity, and some factors associated with the BBB are significantly increased in severely disabled NMOSD patients.

Downregulation of Krüppel-like factor 14 accelerated cellular senescence and aging.

Aging has been considered as a risk factor in many diseases, thus, comprehensively understanding the cellular and molecular mechanisms of delayed aging is important. Here we investigated whether Krüppel-like factor 14 (KLF14) is a suppressor of cellular senescence and aging. In our research, KLF14 levels significantly decreased not only in the lymphocytes of healthy people but also in the cells and tissues of mice with aging. We performed in vitro and in vivo experiments on cells and mice to reveal the function of KLF14 in aging. KLF14 deficiency facilitates cellular senescence and aging-related pathologies in C57BL/6J mice, whereas KLF14 overexpression attenuates cellular senescence. Mechanistically, KLF14 delays aging by binding to the POLD1 promoter to positively regulate POLD1 expression. Remarkably, cellular senescence mediated by KLF14 downregulation could be alleviated by POLD1 expression. In addition, perhexiline, an agonist of KLF14, could delay cellular senescence and aging-related pathologies in senescence-accelerated P8 mice by inducing POLD1 expression, as perhexiline could enhance the effect of KLF14's transcription activation to POLD1 by elevating the binding level of KLF14 to the POLD1 promoter. Our data indicate that KLF14 might be a critical element in aging by upregulating POLD1 expression, indicating that the activation of KLF14 may delay aging and aging-associated diseases.

Age-dependent down-regulation of DNA polymerase δ1 in human lymphocytes.

Aging progress and degeneracy of functional activity are mainly attributed to the decreased DNA repair potential. DNA polymerase (pol) δ activity plays an essential role in genome stability by virtue of its crucial DNA replication and repair capacity. To order to clarify the role of DNA pol δ in aging progression, we firstly examined the expressions of its catalytic subunit named DNA pol δ1 in human lymphocytes at different age stages, respectively, and then observed the effect of diseases on DNA pol δ1 in vivo and of nutriture on its expressions in 2BS cells in vitro. Blood samples from the healthy subjects and patients with diabetes mellitus and coronary heart disease were collected, respectively, for analysis of transcription and protein expressions of DNA pol δ1 by RT-PCR and western blot. 2BS cells of PD30 and PD47 were incubated in both normal medium and other mediums of different nutritures for verifying the differential expressions of DNA pol δ1. Results showed that the mRNA expression of DNA pol δ1 decreased substantially with age and the protein levels were well consistent with gene levels. Furthermore, there were no significant differences in DNA pol δ1 expressions between the groups of healthy individuals and the age matched patients. In addition, DNA pol δ1 gene expression levels were not affected by nutritional status in vitro. Our findings collectively confirmed that the down-regulations of DNA pol δ1 are age-related and have little bearing on diseases and nutritures. DNA pol δ1 has great potential for a new biomarker of aging.

The effect of aging on the DNA damage and repair capacity in 2BS cells undergoing oxidative stress.

Aging is associated with a reduction in the DNA repair capacity under oxidative stress. However, whether the DNA damage and repair capacity can be a biomarker of aging remains controversial. In this study, we demonstrated two cause-and-effect relationships, the one is between the DNA damage and repair capacity and the cellular age, another is between DNA damage and repair capacity and the level of oxidative stress in human embryonic lung fibroblasts (2BS) exposed to different doses of hydrogen peroxide (H2O2). To clarify the mechanisms of the age-related reduction in DNA damage and repair capacity, we preliminarily evaluated the expressions of six kinds of pivotal enzymes involved in the two classical DNA repair pathways. The DNA repair capacity was observed in human fibroblasts cells using the comet assay; the age-related DNA repair enzymes were selected by RT-PCR and then verified by Western blot in vitro. Results showed that the DNA repair capacity was negatively and linearly correlated with (i) cumulative population doubling (PD) levels only in the group of low concentration of hydrogen peroxide treatment, (ii) with the level of oxidative stress only in the group of young PD cells. The mRNA expression of DNA polymerase δ1 decreased substantially in senescent cells and showed negative linear-correlation with PD levels; the protein expression level was well consistent with the mRNA level. Taken together, DNA damage and repair capacity can be a biomarker of aging. Reduced expression of DNA polymerase δ1 may be responsible for the decrease of DNA repair capacity in senescent cells.

Carbonic anhydrases III and IV autoantibodies in rheumatoid arthritis, systemic lupus erythematosus, diabetes, hypertensive renal disease, and heart failure.

In the present study, the CA III and IV autoantibodies, CA activity, antioxidant enzymes and cytokines in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), diabetes, hypertensive renal disease, and heart failure were investigated. The anti-CA III antibody titers in patients with RA, SLE, and type 1 diabetes (T1D) were significantly higher than that in control groups (P < 0.05). The anti-CA IV antibody titers in patients with RA, SLE, type 1 diabetic nephropathy (T1DN), and heart failure were significantly higher than that in control groups (P < 0.05) while anti-CA IV antibody could suppress the total CA activity. The SOD and GPx levels in patients with RA, SLE, and T1DN were significantly lower than that in control groups (P < 0.05). IL-6, IL-17, IFN-γ, and TNF-α levels were significantly higher in SLE group compared with the control group (P < 0.05). Weak but significant correlations were found between anti-CA III antibodies and ESR in RA (r = 0.403, P = 0.013) and SLE patients (r = 0.397, P = 0.007). These results suggested that the generation of CA III and IV autoantibodies, antioxidant enzymes, and cytokines might influence each other and CA autoantibodies might affect the normal physiology function of CA.