[Expression and significance of hypoxia-inducible factor 1α and Bcl-2/adenovirus E1B19kDa-interacting protein 3 in children with traumatic brain injury]. / ç¼ºæ°§è¯±å¯¼å› å­1α、Bcl-2/è ºç— æ¯’E1B19kDa相互作用蛋白3在儿童创伤性脑损伤中的表达及意义.

OBJECTIVES: To dynamically observe the changes in hypoxia-inducible factor 1α (HIF-1α) and Bcl-2/adenovirus E1B19kDa-interacting protein 3 (BNIP3) in children with traumatic brain injury (TBI) and evaluate their clinical value in predicting the severity and prognosis of pediatric TBI. METHODS: A prospective study included 47 children with moderate to severe TBI from January 2021 to July 2023, categorized into moderate (scores 9-12) and severe (scores 3-8) subgroups based on the Glasgow Coma Scale. A control group consisted of 30 children diagnosed and treated for inguinal hernia during the same period, with no underlying diseases. The levels of HIF-1α, BNIP3, autophagy-related protein Beclin-1, and S100B were compared among groups. The predictive value of HIF-1α, BNIP3, Beclin-1, and S100B for the severity and prognosis of TBI was assessed using receiver operating characteristic (ROC) curves. RESULTS: Serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in the TBI group were higher than those in the control group (P<0.05). Among the TBI patients, the severe subgroup had higher levels of HIF-1α, BNIP3, Beclin-1, and S100B than the moderate subgroup (P<0.05). Correlation analysis showed that the serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were negatively correlated with the Glasgow Coma Scale scores (P<0.05). After 7 days of treatment, serum levels of HIF-1α, BNIP3, Beclin-1, and S100B in both non-surgical and surgical TBI patients decreased compared to before treatment (P<0.05). ROC curve analysis indicated that the areas under the curve for predicting severe TBI based on serum levels of HIF-1α, BNIP3, Beclin-1, and S100B were 0.782, 0.835, 0.872, and 0.880, respectively (P<0.05), and for predicting poor prognosis of TBI were 0.749, 0.775, 0.814, and 0.751, respectively (P<0.05). CONCLUSIONS: Serum levels of HIF-1α, BNIP3, and Beclin-1 are significantly elevated in children with TBI, and their measurement can aid in the clinical assessment of the severity and prognosis of pediatric TBI.

Association of Circulating Autophagy Proteins ATG5 and Beclin 1 with Acute Myocardial Infarction in a Case-Control Study.

INTRODUCTION: Acute myocardial infarction (AMI) is a main contributor of sudden cardiac death worldwide. The discovery of new biomarkers that can improve AMI risk prediction meets a major clinical need for the identification of high-risk patients and the tailoring of medical treatment. Previously, we reported that autophagy a highly conserved catabolic mechanism for intracellular degradation of cellular components is involved in atherosclerotic plaque phenotype and cardiac pathological remodeling. The crucial role of autophagy in the normal and diseased heart has been well described, and its activation functions as a pro-survival process in response to myocardial ischemia. However, autophagy is dysregulated in ischemia/reperfusion injury, thus promoting necrotic or apoptotic cardiac cell death. Very few studies have focused on the plasma levels of autophagy markers in cardiovascular disease patients, even though they could be companion biomarkers of AMI injury. The aims of the present study were to evaluate (1) whether variations in plasma levels of two key autophagy regulators autophagy-related gene 5 (ATG5) and Beclin 1 (the mammalian yeast ortholog Atg6/Vps30) are associated with AMI and (2) their potential for predicting AMI risk. METHODS: The case-control study population included AMI patients (n = 100) and control subjects (n = 99) at high cardiovascular risk but without known coronary disease. Plasma levels of ATG5 and Beclin 1 were measured in the whole population study by enzyme-linked immunosorbent assay. RESULTS: Multivariate analyses adjusted on common cardiovascular factors and medical treatments, and receiver operating characteristic curves demonstrated that ATG5 and Beclin 1 levels were inversely associated with AMI and provided original biomarkers for AMI risk prediction. CONCLUSION: Plasma levels of autophagy regulators ATG5 and Beclin 1 represent relevant candidate biomarkers associated with AMI.

Expression of autophagy related genes in peripheral blood cells in Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder and affects dopaminergic neurons. Autophagy often shows a circadian rhythm pattern under physiological conditions across 24 h. Abnormal autophagy and circadian dysfunction are two characteristics of PD. Whether the rhythm of autophagy is altered in PD has not yet been reported. Therefore, in this study, we collected peripheral blood samples at 6:00 h and 18:00 h from PD patients and age-matched controls, and analyzed the mRNA expressions of ULK1, BECN1, LAMP2, AMPK, and SNCA using real-time quantitative PCR. Blood samples analysis found that BECN1 and LAMP2 levels were decreased in patients with PD. Simultaneously, the rhythm of autophagy in PD is not consistent with that in the Control group, which may be a manifestation of the abnormal biological rhythm of PD.

Sestrin2 and Beclin1 levels in Polycystic Ovary Syndrome.

BACKGROUND: Sestrin2 and beclin1 are two newly found proteins that have essential roles in autophagy. This study attempted to evaluate the plasma concentrations of sestrin2 and beclin1 in women with polycystic ovary syndrome (PCOS) and healthy controls and to explore the clinical value of these proteins as novel biomarkers for PCOS. METHODS: In this case-control study, plasma levels of sestrin2 and beclin1, fasting blood sugar (FBS), lipid profile, insulin, and androgens were evaluated in 63 women (31 patients and 32 controls). Sestrin2 and beclin1 levels were determined using enzyme-linked immunosorbent assay (ELISA). Descriptive statistics, correlation coefficients, logistic regression, and ROC curve analyses were used in this study. RESULTS: Plasma sestrin2 levels of the subjects with PCOS (40.74 [24.39-257.70]) were significantly lower than those of healthy subjects (255.78 [25.46-528.66]; p-value = 0.040). ROC curve analysis showed that a cutoff value of 420.5 ng/L had an appropriate sensitivity (83.87%) and specificity (46.88%) for discriminating individuals with and without PCOS, with the area under the curve (95% CI) of 0.648 (0.518 to 0.764), p = 0.036. There were no statistically significant differences between the two groups concerning plasma levels of beclin1, biochemical parameters, blood pressure, and anthropometric features. CONCLUSION: Our findings highlight the dysregulation of sestrin2 as a marker of autophagy in PCOS and its potential usefulness as a novel biomarker for PCOS. Further research is needed to better understand the role of this protein in the pathophysiology of PCOS and its value as a diagnostic tool for the evaluation of PCOS patients.

Beclin1 circulating level as predictor of carotid intima-media thickness in patients with type 2 diabetes mellitus.

ABSTRACT: Type 2 diabetes (T2DM) represents a major risk factor for atherosclerosis that is the underlying cause of most cardiovascular diseases. Identifying reliable predictive biomarkers are needed to improve the long-term outcome in diabetic patients. Autophagy plays a pivotal role in the pathogenesis of atherosclerosis. Beclin1 is a key regulatory protein of autophagy and has been localized in human atherosclerotic lesions. However, the relation of serum level of Beclin1 and atherosclerosis in patients with diabetes has not been clarified yet.To assess the relationship between serum level of Beclin1 and carotid intima-media thickness (CIMT) in patients with T2DM.In this case-control study participants were recruited from tertiary care hospitals in Egypt. The study enrolled 50 patients with T2DM and 25 healthy subjects between January, 2019 and January, 2020. Age, gender, and body mass index were recorded for all subjects. Laboratory works up including glycated hemoglobin, lipid panel, and serum Beclin1 (by enzyme-linked immunosorbent assay) were measured. CIMT was assessed by color Doppler. Comparisons between patients and the control group were done using analysis of variance and Chi-square test. Correlations between CIMT and Beclin1 level and different variables were done using the Pearson correlation coefficient. Receiver operator characteristic curve was constructed with the area under curve analysis performed to detect the best cutoff value of Beclin1 for detection of CIMT > 0.05 cm.The level of Beclin1 in the patient group was significantly lower compared with that in the control group (1.28 ±â€Š0.51 vs 5.24 ±â€Š1.22 ng/dL, P < .001). The level of Beclin1 apparently decreased in the higher CIMT group in T2DM patients. Serum Beclin1 levels were negatively correlated with CIMT (r = -0.762; P < .001), low-density lipoprotein-cholesterol (r = -0.283; P = .04), and triglycerides (r = -0.350; P = .01) but positively correlated with high-density lipoprotein-cholesterol (r = 0.491; P < .001) in patients with T2DM. Beclin1 level >2.2 ng/dL was an accurate predictor of CIMT >0.05 cm with an area under the curve value of 0.997, 93.9% sensitivity, and 100% specificity.Beclin1 levels were negatively correlated with atherosclerotic load in patients with T2DM and it may be considered as a promising diagnostic and therapeutic target.

Altered serum levels of autophagy proteins Beclin-1 and mTOR in patients with exudative age-related macular degeneration.

Autophagy is a key process in the maintenance of cellular survival and homeostasis. Inhibition of autophagy results in degenerative changes resembling ageing. We wondered if autophagy can contribute to the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate the serum concentrations of two key autophagy regulators, Beclin-1 and mechanistic target of rapamycin (mTOR), in patients with exudative AMD. This retrospective case-control study included 38 patients with exudative AMD and 36 sex- and age-matched controls selected among senile cataract patients. Circulating Beclin-1 and mTOR were assessed using an enzyme-linked immunosorbent assay. The proteins levels were correlated with age, sex, duration of ocular symptoms, as well as angiographic and optical coherence tomography findings. Serum Beclin-1 levels were much lower in patients with AMD than in controls (median, 0.100 ng/ml versus 1.123 ng/ml; p = 0.0033), while mTOR levels did not differ (median, 4.377 ng/ml versus 3.608 ng/ml; p = 0.4522). Participants of the study older than 70 years had lower Beclin-1 levels than younger ones (p = 0.0444). However, this difference was the most evident in patients with AMD (p = 0.0024). Serum mTOR levels increased with age. In patients with AMD, lower mTOR levels were associated with drusen, while higher levels were observed in those with a fibrous scar in the contralateral eye (p = 0.0212). Our findings suggest that circulating Beclin-1 decreases with age and that is downregulated in patients with AMD.

Beclin-1, an autophagy-related protein, is associated with the disease severity of COVID-19.

AIMS: Coronavirus disease 2019 (COVID-19), which is a highly contagious disease, is an ongoing outbreak worldwide with high morbidity and mortality. The approaches targeting the autophagy processes might have promising diagnostic and therapeutic values against Coronavirus infection. Here, we aimed to investigate the relationship of Beclin-1 (BECN1), an autophagy-related protein, with blood parameters and the clinical severity in patients with COVID-19. MATERIALS AND METHODS: We enrolled 108 patients with COVID-19 and 21 healthy controls in this study, from September 2020 to January 2021 and divided all patients into two groups according to the severity of the disease: The non-severe group and the severe group. BECN1 levels and blood parameters were measured with Enzyme-Linked Absorbent Assay and routine techniques, respectively. KEY FINDINGS: Serum BECN1 levels were increased in patients with COVID-19 compared to the healthy controls, and its concentrations were significantly higher in the severe group than in the non-severe group (p < 0.001). BECN1 levels showed a significantly positive correlation with coagulation markers such as D-dimer and Fibrinogen (FIB) and inflammation markers such as C-reactive protein (CRP), Procalcitonin (PCT), Ferritin and biochemical markers such as Blood urea nitrogen and Lactate dehydrogenase (p < 0.001). We detected that areas under the ROC curve for BECN1, D-dimer, FIB, PCT, CRP and Ferritin were 0.8662, 0.9110, 0.8278, 0.9996 and 0.9284, respectively (p < 0.0001). SIGNIFICANCE: BECN1 may serve as a predictive biomarker in evaluating the disease severity of COVID-19. Our data suggest that BECN1 mediated-autophagy modulation might have a promising value in improving the clinical outcomes of COVID-19.

Evaluation of autophagy-related genes in Egyptian systemic lupus erythematosus patients.

Disturbances in autophagy are known to be implicated in autoimmune disorders. Many studies have connected polymorphisms in autophagy-related gene 5 (ATG-5) to systemic lupus erythematosus (SLE). Our aim was the determination of the expression level of ATG-5, Beclin-1 and microtubule-associated protein-light chain 3 (LC-3) in Egyptian SLE patients to investigate the impact of disturbances in autophagy genes on the incidence and progression of the disease. Also, we investigated the incidence of single nucleotide polymorphism (SNP) rs573775 in ATG-5 gene among Egyptian SLE patients. Our results showed that the mean levels of Beclin-1, LC-3 and interleukin (IL)-10 transcripts were significantly higher in SLE patients compared to healthy controls. The previous transcripts were positively correlated with SLE Disease Activity Index (SLEDAI). Beclin-1 and LC-3 transcripts were negatively correlated to complement component 3 (C3) levels. Only LC-3 transcripts were negatively correlated to complement component 4 (C4). The rs573775 SNP of ATG-5 with the variant allele was significantly associated with disease susceptibility, conferring a higher risk of SLE development. This variant allele was more prevalent in patients below 30 years, patients with anemia and in patients with anti-double-stranded DNA (dsDNA), confirming the essential role of ATG-5 polymorphism in the susceptibility of Egyptian patients to SLE.

The Significance of Detection of Circulating Tumor Cells and Beclin1 in Peripheral Blood of Patients with Renal Cell Carcinoma.

AIM: In this study, the correlation between the circulating tumor cells (CTCs), clinical and pathological status, Beclin1 expression, and the prognosis of patients with renal cell carcinoma were studied. METHODS: The patients with renal cancer were tested every 3 months for 2 years, and once every 6 months after 2 years by using CanPatrol-ITMCTCs detection technology. The expression of Beclin1 in different types of CTCs was detected. The study investigated the correlation between Beclin1 expression of patients with different gender, age, tumor pathological stage, clinical stage, and postoperative metastasis. RESULTS: A total of 199 renal cancer patients were included in this study, and the patients underwent CTCs testing ranging from 1 to 10 times. There are 936 epithelial CTCs, 2,884 mixed CTCs, and 1,218 interstitial CTCs were detected. The results show that there are statistical differences between the three subtypes (P = 0.001). The cell count of the Beclin1 negative group was statistically significantly higher than that of the positive group among the three subtypes from the first to the fourth test (P < 0.05). The first test results showed that age was negatively correlated with the number of CTCs (r = -0.204, P = 0.004). There are no differences in the overall survival (OS) and disease-free survival (DFS) between the different numbers of CTCs and Beclin1 expression (all P values were > 0.05). CONCLUSION: The expression of Beclin1 in epithelial and mesenchymal renal cell carcinoma reduces the number of CTCs produced. The age of the patient may affect the levels of CTCs in renal cell carcinoma.

lncRNAVNN3 mediated benzene-induced hematotoxicity through promoting autophagy and apoptosis.

The potential toxicity of low-dose benzene exposure to human health has received attention, but the mechanisms of low-dose benzene-induced hematotoxicity remain largely unknown. The purpose of our study was to investigate the relationships between lncRNAVNN3 expression with benzene-induced autophagy and apoptosis in control and benzene-exposed workers. Seventy benzene-exposed workers and seventy non-benzene-exposed healthy workers were recruited. The expression of lncRNAVNN3, serum autophagy-associated and apoptosis-associated proteins were evaluated, and the relationship among them were also analysed. Furthermore, the mechanism of lncRNAVNN3 on autophagy and apoptosis induced by benzene metabolite (1, 4-benzoquinone, 1, 4-BQ) was investigated in vitro. The results showed that the expression of lncRNAVNN3 increased in benzene-exposed workers (p < 0.05). A positive correlation was found between lncRNAVNN3, serum autophagy-associated and apoptosis-associated proteins. In addition, we found that the knockdown of lncRNAVNN3 reduced phosphorylation of beclin1 and Bcl-2, which mediated 1, 4-benzoquinone-induced autophagy and apoptosis. Overall, lncRNAVNN3 mediated 1, 4-benzoquinone-induced autophagy and apoptosis though regulating phosphorylation of beclin1 and Bcl-2, suggesting that lncRNAVNN3 might be a novel early sensitive biomarker of benzene-induced hematotoxicity.

Impact of vitamin D and vitamin D receptor on the trophoblast survival capacity in preeclampsia.

BACKGROUND: Preeclampsia and intra-uterine growth restriction (IUGR) are major health problems during pregnancy affecting both mother and child. Defective placental development and failure of trophoblast differentiation during pregnancy are important aspects in the pathogenesis of both syndromes. Recent studies have shown that autophagy is involved in the trophoblast survival capacity. As vitamin D has a central role in many cellular processes, we studied the relation of vitamin D and autophagy in those processes of preeclampsia and IUGR. METHODS: Serum and placental samples from four groups of cases; normal term, IUGR, early-onset and late-onset preeclampsia, were analyzed for 25(OH)D vitamin D, sFLT1, PGF, LGALS13 in serum and vitamin D receptor (VDR), MAP1LC3B and BECN1 in placental tissues. RESULTS: There was a significant difference in the sFLT1/PGF ratio in preeclamptic cases compared to controls and IUGR. There was a significant difference between these groups in the MAP1LC3B/BECN1 ratio as marker of the trophoblast survival capacity with a significantly reduced ratio in villous trophoblast of early-onset preeclampsia. Maternal vitamin D deficiency was found in all pathological pregnancies combined with significantly reduced staining levels of placental VDR in IUGR. Finally, there was a strong and significant negative correlation between the survival capacity (MAP1LC3B/BECN1) and both maternal vitamin D and placental VDR in the preeclampsia groups. CONCLUSION: Vitamin D and intracellular VDR are strongly related to the trophoblast survival capacity in preeclampsia.

Sitagliptin Protects Cardiac Function by Reducing Nitroxidative Stress and Promoting Autophagy in Zucker Diabetic Fatty (ZDF) Rats.

PURPOSE: The purpose of the study is to identify potential mechanisms involved in the cardiac protective effects of sitagliptin in Zucker diabetic fatty (ZDF) rats. METHODS AND RESULTS: Male non-diabetic lean Zucker rats (Lean) and ZDF rats treated with saline (ZDF) or sitagliptin (ZDF + sita) were used in this study. The blood pressure and lipid profiles were increased significantly in ZDF rats compared with Lean rats. ZDF + sitagliptin rats had decreased systolic blood pressure compared with ZDF rats. Sitagliptin treatment decreased total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Ejection fraction (EF) and fractional shortening (FS) were decreased in ZDF rats, which improved with sitagliptin from 59.8% ± 3.0 and 34.5% ± 3.1 to 66.9% ± 3.4 and 40.9% ± 4.2, respectively. Moreover, the nitroxidative stress level was increased while autophagy levels were decreased in ZDF rats, which was reversed by the administration of sitagliptin. Treatment with sitagliptin or FeTMPyP improved the autophagy level in high-glucose cultured H9c2 cells by increasing autolysosome numbers from 15 ± 4 to 21 ± 3 and 22 ± 3, respectively. We detected a positive correlation between DPP-4 activity and 3-nitrotyrosine levels (r = 0.3903; P < 0.01), a negative correlation between Beclin-1 levels and DPP-4 activity (r = - 0.3335; P < 0.01), and a negative correlation between 3-nitrotyrosine and Beclin-1 levels (r = - 0.3794; P < 0.01) in coronary heart disease patients. CONCLUSIONS: Sitagliptin alleviates diabetes-induced cardiac injury by reducing nitroxidative stress and promoting autophagy. This study indicates a novel target pathway for the treatment of cardiovascular complications in type 2 diabetes mellitus.

Serum level of the autophagy biomarker Beclin-1 in patients with diabetic kidney disease.

Autophagy is a major cellular clearance mechanism that maintains cellular survival and homeostasis. Autophagy has a crucial role in the progression of diabetes and kidney diseases. AIMS: To investigate serum concentrations of Beclin-1, a key regulator of autophagy, in patients with diabetic kidney disease (DKD). METHODS: The study included 70 patients with type 2 diabetes and DKD (group 1; 35 patients with estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 and group 2; 35 patients with eGFR < 30 ml/min/1.73 m2) and 20 age- and sex-matched healthy subjects (group 3). Laboratory work up included; glycated hemoglobin (HbA1c), serum creatinine, eGFR using modification of diet in renal disease (MDRD) formula, urine albumin to creatinine ratio (ACR), and serum Beclin-1 measurement. RESULTS: Patients with DKD had significantly lower Beclin-1 levels (2.38 ±â€¯1.46 ng/mL) compared to control group (6.03 ±â€¯1.94 ng/mL; P < 0.001). Moreover, serum Beclin-1 significantly decreased in group 2 (1.43 ±â€¯0.83 ng/mL) compared to group 1 (3.36 ±â€¯1.30 ng/mL; P < 0.001). In univariate analysis, the concentration of Beclin-1 correlated well with eGFR (r = 0.64, P < 0.001), ACR (r = -0.63, P < 0.001), and duration of diabetes (r = -0.43, P < 0.001) but didn't correlate with HbA1c (r = -0.17, P = 0.15). However, ACR was the only significant predictor of Beclin-1 level on performing multiple regression analysis (ß = -0.40, P = 0.01). CONCLUSION: Serum level of Beclin-1 is reduced in patients with DKD. Furthermore, its level is related to the stage of DKD and correlates with the degree of albuminuria.

Correlation of the predisposition of Chinese children to cerebral palsy with nucleotide variation in pri-miR-124 that alters the non-canonical apoptosis pathway.

Cerebral palsy is a group of non-progressive motor impairment syndromes caused by brain lesions during development. Herein, we investigated the relationship between nucleotide variations in a miRNA coding region and the predisposition of Chinese children to cerebral palsy. A total of 233 CP patients and 256 healthy participants were enrolled, and 60 children were selected from each group for plasma miRNA detection. We screened the coding regions of pri-miR-124-1, -2, and -3 using PCR and sequencing. The expression of miR-124 was determined by qRT-PCR. Luciferase assays and Western blots were used to confirm the regulation of target genes by miR-124. The function of miR-124 was further identified in SH-SY5Y cells by detecting cell viability and apoptosis. We revealed that the rare alleles T of rs3802169 and G of rs191727850 were found to be associated with an increased risk of cerebral palsy (OR=3.71, 95% CI 1.74-7.92 and OR=2.18, 95% CI 1.36-3.49, respectively). We further showed that the levels of mature miR-124 were down-regulated by the C-to-T variation in vitro. More importantly, the reduction of miR-124 resulting from the C-to-T change led to the less-efficient inhibition of the target genes ITGB1, LAMC1 and BECN1, which may play important roles during the development of the nervous system. Meanwhile, the reduction in the expression of miR-124 was also related to the increased nuclear translocation of apoptosis-inducing factor (AIF) under oxidative stress, thereby inducing more cell apoptosis. Our results suggest that one functional polymorphism in pri-miR-124-1 might contribute to the genetic predisposition of Chinese children to cerebral palsy by disrupting the production of miR-124, which consequently interfered in the expression and function of the target genes of miR-124.

Expression pattern of HMGB1 and its association with autophagy in acute necrotizing pancreatitis.

High-motility group box protein 1 (HMGB1) has an important role in autophagy; however, its exact role in acute necrotizing pancreatitis (ANP) remains unknown. The present study aimed to investigate the expression pattern of HMGB1 in ANP, and to determine its association with autophagy. Sprague Dawley rats (weight, 350±30 g, n=48) were randomly divided into control (n=12) and experimental (n=36) groups. Experimental rats were retrogradely injected with 5% sodium taurocholate into the biliopancreatic duct to induce ANP. Control rats received an equal amount of saline. Serum amylase levels were used to determine whether the model had been successfully generated. Autophagosomes in pancreatic acinar cells were observed under electron microscopy. The expression levels of HMGB1 and Beclin 1 were detected in pancreatic tissues by western blotting, quantitative polymerase chain reaction and immunohistochemistry. HMGB1 levels were also determined in the serum and in isolated nuclei. The results demonstrated that autophagy was detected at 3 h post­ANP induction; however, HMGB1 expression remained unaltered during the early stage (0­6 h; P>0.05). HMGB1 expression was significantly increased at 12 h, and was still increasing at 24 h (P<0.05). Notably, HMGB1 was increased in the nuclei compared with in the cytoplasm at 3­6 h. Furthermore, serum HMGB1 levels began to increase at 3 h, and reached the highest levels at 24 h in the ANP group. In conclusion, in an ANP model, HMGB1 was initially increased in the nuclei to initiate autophagy. Subsequently, it moved into the cytoplasm, where it interacted with Beclin 1 to enhance autophagy, and HMGB1 was released into the blood, leading to the deterioration of ANP.

Associations of autophagy with lung diffusion capacity and oxygen saturation in severe COPD: effects of particulate air pollution.

Although traffic exposure has been associated with the development of COPD, the role of particulate matter <10 µm in aerodynamic diameter (PM10) in the pathogenesis of COPD is not yet fully understood. We assessed the 1-year effect of exposure to PM10 on the pathogenesis of COPD in a retrospective cohort study. We recruited 53 subjects with COPD stages III and IV and 15 healthy controls in a hospital in Taiwan. We estimated the 1-year annual mean levels of PM10 at all residential addresses of the cohort participants. Changes in PM10 for the 1-year averages in quintiles were related to diffusion capacity of the lung for carbon monoxide levels (r=-0.914, P=0.029), changes in the pulse oxygen saturation (ΔSaO2; r=-0.973, P=0.005), receptor for advanced glycation end-products (r=-0.881, P=0.048), interleukin-6 (r=0.986, P=0.002), ubiquitin (r=0.940, P=0.017), and beclin 1 (r=0.923, P=0.025) in COPD. Next, we observed that ubiquitin was correlated with ΔSaO2 (r=-0.374, P=0.019). Beclin 1 was associated with diffusion capacity of the lung for carbon monoxide (r=-0.362, P=0.028), ΔSaO2 (r=-0.354, P=0.032), and receptor for advanced glycation end-products (r=-0.471, P=0.004). Autophagy may be an important regulator of the PM10-related pathogenesis of COPD, which could cause deterioration in the lung diffusion capacity and oxygen saturation.

Tm7sf2 may participate in the healing of burn wounds.

The transmembrane 7 superfamily member 2 (Tm7sf2) gene been reported to be involved in the reduced cholesterol levels of patients with large burn areas. To investigate the importance of Tm7sf2 in the burn wound healing process, a total of 10 Sprague­Dawley rats underwent electrical burns. Blood serum was collected for the culture of HaCaT human keratinocyte cells. Tm7sf2 small interfering RNAs (siRNAs) were prepared and transfected into the normal­ and burn serum­cultured HaCaT cells. Monocyte­endothelial cellular adhesion ability and cell proliferation, as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the levels of autophagy proteins Beclin1 and LC3­II, which were detected by western blot assay and real time­quantitative polymerase chain reaction, and it was identified that Tm7sf2 siRNAs were successfully transfected. Cell proliferation was reduced and monocyte-endothelial cell adhesion increased in the burn serum group compared with the normal serum group (P<0.05). Additionally, the expression levels of Beclin1 and LC3­II were increased, and the addition of siTm7sf2 had a similar effect as the burn serum. Thus, Tm7sf2 may take part in the burn wound healing process by interacting with LC3­II and Beclin1, and targeting Tm7sf2 may have therapeutic benefits.

Altered Blood Gene Expression of Tumor-Related Genes (PRKCB, BECN1, and CDKN2A) in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common of the neurodegenerative diseases. Recent diagnostic criteria have defined a preclinical disease phase during which neuropathological substrates are thought to be present in the brain. There is an urgent need to find measurable alterations in this phase as well as a good peripheral biomarker in the blood. We selected a cohort of 100 subjects (controls = 47; preclinical AD = 11; patients with AD = 42) and analyzed whole blood expression of 20 genes by quantitative polymerase chain reaction. The selected genes belonged to calcium signaling, senescence and autophagy, and mitochondria/oxidative stress pathways. Additionally, two genes associated with an increased risk of developing AD (clusterin (CLU) and bridging integrator 1 (BIN1)) were also analyzed. We detected significantly different gene expressions of BECN1 and PRKCB between the control and the AD groups and of CDKN2A between the control and the preclinical AD groups. Notably, these three genes are also considered tumor suppressor (CDKN2A and BECN1) or tumor promoter (PRKCB) genes. Gene-gene expression Pearson correlations were computed separately for controls and patients with AD. The significant correlations (p < 0.001) were represented in a network analysis with Cytoscape tool, which suggested an uncoupling of mitochondria-related genes in AD group. Whole blood is emerging as a valuable tissue in the study of the physiopathology of AD.