A new phenolic compound from Persicaria capitata.

Persicaria capitata was a frequently used Hmong medicinal flora in China. In this study, one new phenolic compound, capitaone A (1) together with 20 known ones, were isolated from the whole herb of P. capitata. Among them, 7 components (4, 9-11, 15-16, 20-21) were discovered from P. capitata for the first time. Their chemical structures were elucidated on the basis of extensive NMR and MS spectrum. Furthermore, three compounds (15, 20, 21) displayed remarkable cytotoxic activities against two human cancer cell lines (A549 and HepG2).

A novel type lavandulyl flavonoid from Sophora flavescens as potential anti-hepatic injury agent that inhibit TLR2/NF-κB signaling pathway.

ETHNOPHARMACOLOGY RELEVANCE: Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens, which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. AIM OF THE STUDY: This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl4)-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. MATERIALS AND METHODS: The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1ß (IL-1ß), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1ß and cyclooxygenase-2 (COX2) in hepatic tissues were detected. RESULTS: The lavandulyl flavonoid (kurarinol A, 1) and the EtOAc extract from S. flavescens showed protective effects on CCl4-injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What's more, we found that treatment with kurarinol A (1) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1ß in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1ß, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. CONCLUSION: These findings demonstrated that the novel compound (kurarinol A, 1) possessed notable hepatoprotective activity against CCl4. It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl4, and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.

Nutritional qualities and antioxidant activity of Pleurotus floridanus grown on composted peach sawdust substrate with different composting time.

Recently, composting cultivation method is widely used in oyster mushroom production. In this study, we focused on the effects of composting processes on nutritional qualities and antioxidant activity of Pleurotus floridanus mushroom fruiting bodies. Three treatments of different composting time (2, 4, and 5 days) were performed with an atmospheric sterilization treatment as the control. The results showed that the pH value, total carbon content, and total nitrogen content of substrate were critical parameters which would significantly affect mushroom qualities and bioactivities. Fruiting bodies of the control demonstrated significantly higher crude protein content, total amino acid content, and essential amino acid content than that of composting treatments. Moreover, fruiting bodies of treatment D4 and D5 manifested significantly higher crude polysaccharide contents. Crude polysaccharide of treatment D4 represented the highest scavenging ability toward both radical 3-ethylbenzthiazoline-6-sulfonic acid (ABTS·+ ) and Hydroxyl radical (OH·). It suggests that composting processes is suitable for oyster mushroom cultivation based on nutritional and antioxidant qualities of fruiting bodies.

Epigallocatechin Gallate Attenuates Gentamicin-Induced Nephrotoxicity by Suppressing Apoptosis and Ferroptosis.

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.

Impacts of composting duration on physicochemical properties and microbial communities during short-term composting for the substrate for oyster mushrooms.

A short-term composting process to prepare substrate is an effective way to cultivate oyster mushrooms (Pleurotus spp.), which can increase the yield of mushrooms and lower the rate of contamination in non-industrialized cultivation. Moreover, it is different from the traditional composting processes for fertilizers and lacks systematic study, such as microbial succession and compost quality. In this study, a series of different tests of composting duration (0, 2, 4 and 5 d) were performed. A composting duration of 4-5 d over 58 °C was suitable for mushroom cultivation based on the biological efficiency (BE) range of 69.76-73.41 % and the contamination rate of 0 %. The content of total carbon (TC) continuously decreased during composting, while the content of total nitrogen (TN) reacted in an opposite matter. The final TN and C/N ratios were 1.89 % and 28/1, respectively, which fell well within the optimal range of nutritional requirements for oyster mushroom cultivation. The composting bacteria were more diverse than the fungal species. Caldibacillus, Thermobispora, Thermopolyspora, Thermobacillus and Ureibacillus were the predominant bacterial genera during the thermophilic stage. Co-occurrence patterns of microbial communities and physicochemical properties were performed using a network analysis, which indicated that bacteria can play more efficient roles than fungi in the degradation of organic matter. The structural equation model showed that composting duration significantly affected bacterial diversity, lignocellulose degradation rates, and BE. The correlations between bioinformatics parameters with composting characters and agronomic traits were determined by the Mantel test and showed that the induction of bacterial diversity over time rapidly activated carbon metabolism during short-term composting. This study provides a new idea of agro-waste composting for mushroom cultivation.

Targeted inhibition of TGF-ß type I receptor by AZ12601011 protects against kidney fibrosis.

Renal fibrosis, a common feature of chronic kidney disease, causes the progressive loss of renal function, in which TGF-ß1 plays a critical role. In this study, we found that expression levels of TGF-ß1 and its receptor 1 (TGF-ßR1) were both significantly increased in obstructive fibrosis kidneys. AZ12601011 is a small molecular inhibitor of TGF-ßR1; however, its therapeutic potential for renal fibrosis remains unclear. During the experiments, AZ12601011 was applied to various models of renal fibrosis followed by unilateral ureteral obstruction (UUO) and ischemia/reperfusion (I/R) in vivo, in addition to renal tubular epithelial cells (TECs) challenged by hypoxia/reoxygenation (H/R) and TGF-ß1in vitro. Our results revealed that AZ12601011 ameliorated renal injuries and fibrosis shown by PAS, HE, and Masson staining, which was consistent with the decrease in Col-1 and α-SMA expression in the kidneys from UUO and I/R mice. Similarly, in vitro data showed that AZ12601011 inhibited the induction of Col-1 and α-SMA in both TECs treated with TGF-ß1 and H/R. In addition, the results of cellular thermal shift assay (CETSA), molecular docking, and western bolt indicated that AZ12601011 could directly bind to TGF-ßR1 and block activation of the downstream Smad3. Taken together, our findings suggest that AZ12601011 can attenuate renal fibrosis by blocking the TGF-ß/Smad3 signaling pathway and it might serve as a promising clinical candidate in the fight against fibrotic kidney diseases.

Emerging therapeutic potential of adeno-associated virus-mediated gene therapy in liver fibrosis.

Liver fibrosis is a wound-healing response that results from various chronic damages. If the causes of damage are not removed or effective treatments are not given in a timely manner, it will progress to cirrhosis, even liver cancer. Currently, there are no specific medical therapies for liver fibrosis. Adeno-associated virus (AAV)-mediated gene therapy, one of the frontiers of modern medicine, has gained more attention in many fields due to its high safety profile, low immunogenicity, long-term efficacy in mediating gene expression, and increasingly known tropism. Notably, increasing evidence suggests a promising therapeutic potential for AAV-mediated gene therapy in different liver fibrosis models, which helps to correct abnormally changed target genes in the process of fibrosis and improve liver fibrosis at the molecular level. Moreover, the addition of cell-specific promoters to the genome of recombinant AAV helps to limit gene expression in specific cells, thereby producing better therapeutic efficacy in liver fibrosis. However, animal models are considered to be powerless predictive of tissue tropism, immunogenicity, and genotoxic risks in humans. Thus, AAV-mediated gene therapy will face many challenges. This review systemically summarizes the recent advances of AAV-mediated gene therapy in liver fibrosis, especially focusing on cellular and molecular mechanisms of transferred genes, and presents prospective challenges.

Insulin-like growth factor binding protein 7 promotes acute kidney injury by alleviating poly ADP ribose polymerase 1 degradation.

The novel biomarker, insulin-like growth factor binding protein 7 (IGFBP7), is used clinically to predict different types of acute kidney injury (AKI) and has drawn significant attention as a urinary biomarker. However, as a secreted protein in the circulation of patients with AKI, it is unclear whether IGFBP7 acts as a key regulator in AKI progression, and if mechanisms underlying its upregulation still need to be determined. Here we found that IGFBP7 is highly expressed in the blood and urine of patients and mice with AKI, possibly via a c-Jun-dependent mechanism, and is positively correlated with kidney dysfunction. Global knockout of IGFBP7 ameliorated kidney dysfunction, inflammatory responses, and programmed cell death in murine models of cisplatin-, kidney ischemia/reperfusion-, and lipopolysaccharide-induced AKI. IGFBP7 mainly originated from kidney tubular epithelial cells. Conditional knockout of IGFBP7 from the kidney protected against AKI. By contrast, rescue of IGFBP7 expression in IGFBP7-knockout mice restored kidney damage and inflammation. IGFBP7 function was determined in vitro using recombinant IGFBP7 protein, IGFBP7 knockdown, or overexpression. Additionally, IGFBP7 was found to bind to poly [ADP-ribose] polymerase 1 (PARP1) and inhibit its degradation by antagonizing the E3 ubiquitin ligase ring finger protein 4 (RNF4). Thus, IGFBP7 in circulation acts as a biomarker and key mediator of AKI by inhibiting RNF4/PARP1-mediated tubular injury and inflammation. Hence, over-activation of the IGFBP7/PARP1 axis represents a promising target for AKI treatment.

The protective effect of rabeprazole on cisplatin-induced apoptosis and necroptosis of renal proximal tubular cells.

Nephrotoxicity is a major adverse reaction of cisplatin-based chemotherapy. Organic cation transporter 2 (OCT2) which is located on the basement membrane of human proximal renal tubules is responsible for the renal accumulation of cisplatin and its nephrotoxicity. This study aimed to investigate the protective effect of PPIs to CP-induced nephrotoxicity. Three kinds of PPIs including lansoprazole, omeprazole and rabeprazole (Rab) were co-administrated with CP to mice. In addition, OCT2-overexpressed HEK293, HK-2 and A549 cells were co-incubated with CP and PPIs. The results showed that PPIs can attenuate CP-induced increase of CRE, BUN and histological damage of kidney. Among the three PPIs, Rab was found with a superior protective effect. It significantly reduced the accumulation of CP in OCT2-overexpressed HEK293 cells and in the renal cortex tissues of mice, but not in HK-2 cells. Moreover, Rab reduced the expression levels of cleaved-caspase-3, RIPK1, RIPK3, MLKL and p-MLKL and the apoptosis rate of renal tubular cells induced by CP in vivo, but not in HK-2 cells. However, Rab increased the viability of CP-treated cells in a concentration-dependent manner and attenuated CP-induced apoptosis and necroptosis in OCT2 over-expressed HEK293 cells. Finally, we demonstrated that Rab have no influence on the antitumor effect of CP. In conclusion, Rab attenuate CP-induced nephrotoxicity mainly through inhibiting OCT2-mediated CP uptake, without interfering with its anti-tumor property of inducing apoptosis and necroptosis.

Stratifin promotes renal dysfunction in ischemic and nephrotoxic AKI mouse models via enhancing RIPK3-mediated necroptosis.

Stratifin (SFN) is a member of the 14-3-3 family of highly conserved soluble acidic proteins, which regulates a variety of cellular activities such as cell cycle, cell growth and development, cell survival and death, and gene transcription. Acute kidney injury (AKI) is prevalent disorder characterized by inflammatory response, oxidative stress, and programmed cell death in renal tubular epithelial cells, but there is still a lack of effective therapeutic target for AKI. In this study, we investigated the role of SFN in AKI and the underlying mechanisms. We established ischemic and nephrotoxic AKI mouse models caused by ischemia-reperfusion (I/R) and cisplatin, respectively. We conducted proteomic and immunohistochemical analyses and found that SFN expression levels were significantly increased in AKI patients, cisplatin- or I/R-induced AKI mice. In cisplatin- or hypoxia/reoxygenation (H/R)-treated human proximal tubule epithelial cells (HK2), we showed that knockdown of SFN significantly reduced the expression of kidney injury marker Kim-1, attenuated programmed cell death and inflammatory response. Knockdown of SFN also significantly alleviated the decline of renal function and histological damage in cisplatin-caused AKI mice in vivo. We further revealed that SFN bound to RIPK3, a key signaling modulator in necroptosis, to induce necroptosis and the subsequent inflammation in cisplatin- or H/R-treated HK2 cells. Overexpression of SFN increased Kim-1 protein levels in cisplatin-treated MTEC cells, which was suppressed by RIPK3 knockout. Taken together, our results demonstrate that SFN that enhances cisplatin- or I/R-caused programmed cell death and inflammation via interacting with RIPK3 may serve as a promising therapeutic target for AKI treatment.

Circular RNA CREBBP Suppresses Hepatic Fibrosis Via Targeting the hsa-miR-1291/LEFTY2 Axis.

CircRNAs (circRNAs) are commonly dysregulated in a variety of human diseases and are involved in the development and progression of cancer. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high throughput screen revealed changes in many circRNAs in mice with carbon tetrachloride (CCl4)-induced HF. For example, circCREBBP was significantly down-regulated in primary hepatic stellate cells (HSCs) and liver tissue of HF mice induced by CCl4 compared to those in the vehicle group. Overexpression of circCREBBP with AAV8-circCREBBP in vivo prevented CCl4-induced HF worsening by reducing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents, liver hydroxyproline levels, collagen deposition, and levels of pro-fibrosis genes and pro-inflammatory cytokines. Furthermore, in vitro function loss and function gain analysis showed that circCREBBP inhibited HSCs activation and proliferation. Mechanically, circCREBBP acts as a sponge for hsa-miR-1291 and subsequently promotes LEFTY2 expression. In conclusion, our current results reveal a novel mechanism by which circCREBBP alleviates liver fibrosis by targeting the hsa-miR-1291/LEFTY2 axis, and also suggest that circCREBBP may be a potential biomarker for heart failure.

Succession of the microbial communities and function prediction during short-term peach sawdust-based composting.

Short-term composting of raw materials for preparing oyster mushroom cultivation media is widely used in China, and its microbial mechanism needs to be further studied. 11-days' peach sawdust-based composting was performed to evaluate material conversion and microbial succession using physicochemical analysis and 16S rRNA and ITS sequencing. Composting bacteria demonstrated much higher abundance than fungi. Firmicutes, Actinobacteriota, and Proteobacteria were the dominant bacterial phyla, while most of fungal species belonged to Ascomycota. Moisture was the key factor at the beginning, while total nitrogen, temperature, and lignin became main influencing factors for composting maturity. Actinobacteriota, Firmicutes, and Proteobacteria of bacterial phyla, Eurotiomycetes and Sordariomycetes of fungal classes involved in lignocellulosic degradation. Bacterial function prediction analysis showed that carbohydrate metabolism and amino acid metabolism were the main metabolic pathways. These results confer a better understanding of material and microbial succession during short-term composting and also provide valuable utilization in mushroom industry.

Circular RNA circPSD3 alleviates hepatic fibrogenesis by regulating the miR-92b-3p/Smad7 axis.

Recently, circular RNAs (circRNAs) have been frequently reported to be involved in hepatocellular carcinoma (HCC) development and progression. However, the role of circRNAs in hepatic fibrosis (HF) is still unclear. Our previous high-throughput screen revealed changes in many circRNAs in mice with carbon tetrachloride (CCl4)-induced HF. For instance, the expression of circPSD3, a circRNA derived from the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene, was considerably downregulated in primary hepatic stellate cells (HSCs) and liver tissues of mice with CCl4-induced HF compared to those in the vehicle group. In vivo overexpression of circPSD3 using AAV8-circPSD3 arrested the deterioration of CCl4-induced HF as indicated by reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) content, liver hydroxyproline level, collagen deposition, and pro-fibrogenic gene and pro-inflammatory cytokine levels. Moreover, in vitro loss-of-function and gain-of-function analyses suggested that circPSD3 inhibited the activation and proliferation of HSCs. Mechanistically, circPSD3 served as a sponge for miR-92b-3p, subsequently promoting the expression of Smad7. In conclusion, our present findings reveal a novel mechanism by which circPSD3 alleviates hepatic fibrogenesis by targeting the miR-92b-3p/Smad7 axis, and they also indicate that circPSD3 may serve as a potential biomarker for HF.

Advancement and properties of circular RNAs in prostate cancer: An emerging and compelling frontier for discovering.

Prostate cancer (PC) is the most common carcinoma among men worldwide which results in 26% of leading causes of cancer-related death. However, the ideal and effective molecular marker remains elusive. CircRNA, initially observed in plant-infected viruses and Sendai virus in 1979, is generated from pre-mRNA back-splicing and comes in to play by adequate expression. The differential expression in prostate tissues compared with the control reveals the promising capacity in modulating processes including carcinogenesis and metastasis. However, the biological mechanisms of regulatory network in PC needs to systemically concluded. In this review, we enlightened the comprehensive studies on the definite mechanisms of circRNAs affecting tumor progression and metastasis. What's more, we validated the potential clinical application of circRNAs serving as diagnostic and prognostic biomarker. The discussion and analysis in circRNAs will broaden our knowledge of the pathogenesis of PC and further optimize the current therapies against different condition.

LEFTY2 alleviates hepatic stellate cell activation and liver fibrosis by regulating the TGF-ß1/Smad3 pathway.

Activated hepatic stellate cells (HSCs) are the major cell type involved in the deposition of extracellular matrix (ECM) during the development of hepatic fibrosis. In this study, we revealed that left-right determination factor 2 (LEFTY2), one of the proteins belonging to the transforming growth factor-ß (TGF-ß) protein superfamily, was remarkedly decreased in human hepatic fibrosis tissues and in a carbon tetrachloride (CCl4)-induced liver fibrosis mouse model. In addition, TGF-ß1 treatment markedly reduced the level of LEFTY2 in HSCs. Importantly, overexpression of LEFTY2 suppressed the activation and proliferation of HSCs. LEFTY2 inhibited the expression of TGF-ß1-induced fibrosis-associated genes (α-SMA and COL1a1) in human (LX-2) and rat (HSC-T6) HSC cell lines in vitro. Mechanistically, we demonstrated, for the first time, the role of LEFTY2 in inhibiting TGF-ß1/Smad3 signaling, suggesting that there is a mutual antagonism between LEFTY2 and TGF-ß1/Smad3 signaling during liver fibrosis. Similarly, we observed that LEFTY2 has a negative effect on its downstream genes, including c-MYC, CDK4, and cyclin D1, in liver fibrosis. Collectively, our data strongly indicated that LEFTY2 plays an important role in controlling the proliferation and activation of HSCs in the progression of liver fibrosis and this could be a potential therapeutic target for its treatment.

Urban Open Space Is Associated with Better Renal Function of Adult Residents in New Taipei City.

The purpose of this study is to explore the association between proximity to open space and adult renal function. This was a cross-sectional study. Adult residents of Taipei metropolis were recruited in the analysis. The proximity of each subject to open space was measured using the Geographic Information System. Residents were divided into two groups: with and without chronic kidney disease (CKD). We made univariable comparisons between the two groups. The logistic regression models were used to estimate the odds ratio of CKD. Forest plot was used to examine the effect of interaction between distance to open space and subgroup variable on CKD. A total number of 21,656 subjects with mean age 53.6 years were enrolled in the study. Of the subjects, 2226 (10.28%) had CKD. The mean and standard deviation of distance to open space were 117.23 m and 80.19 m, respectively. Every 100 m distance to open space was associated with an odds ratio of 1.071 for CKD. Subgroup analysis revealed that residents of female, without hypertension, or without impaired fasting glucose (IFG) living more than 200 m from open spaces have greater odds of CKD than those living less than 200 m. Conclusions: Proximity to open space was associated with a lower prevalence of CKD among adults in Taiwan. Such association was enhanced among females and healthy adults without hypertension or impaired fasting glucose (IFG).

Traffic-related air pollution associated with chronic kidney disease among elderly residents in Taipei City.

The associations of air pollution with chronic kidney disease (CKD) have not yet been fully studied. We enrolled 8,497 Taipei City residents older than 65 years and calculated the estimated glomerular filtration rate (eGFR) using the Taiwanese Chronic Kidney Disease Epidemiology Collaboration equation. Proteinuria was assessed via dipstick on voided urine. CKD prevalence and risk of progression were defined according to the KDIGO 2012 guidelines. Land-use regression models were used to estimate the participants' one-year exposures to PM of different sizes and traffic-related exhaust, PM2.5 absorbance, nitrogen dioxide (NO2), and NOx. Generalized linear regressions and logistic regressions were used to examine the associations of one-year air pollution exposures with eGFR, proteinuria, CKD prevalence and risk of progression. The results showed that the interquartile range (IQR) increments of PM2.5 absorbance (0.4 × 10-5/m) and NO2 (7.0 µg/m3) were associated with a 1.07% [95% confidence interval (CI): 0.54-1.57] and 0.84% (95% CI: 0.37-1.32) lower eGFR, respectively; such relationships were magnified in subjects who had an eGFR >60 ml/min/1.73 m2 or who were non-diabetic. Similar associations were also observed for PM10 and PM2.5-10. Two-pollutant models showed that PM10 and PM2.5 absorbance were associated with a lower eGFR. The odd ratios (ORs) of CKD prevalence and risk of progression also increased with exposures to PM2.5 absorbance and NO2. In summary, one-year exposures to traffic-related air pollution were associated with lower eGFR, higher CKD prevalence, and increased risk of CKD progression among the elderly population. Air pollution-related impaired renal function was stronger in non-CKD and non-diabetic subjects.

Association Between Long-term Exposure to Traffic-related Air Pollution and Inflammatory and Thrombotic Markers in Middle-aged Adults.

BACKGROUND: Studies evaluating possible associations between long-term exposure to air pollution and inflammatory and thrombotic markers are limited. METHODS: From 2009 to 2011, we monitored hematologic parameters and thrombotic markers in 402 volunteers 35-65 years of age who were recruited as the non-coronary heart disease (CHD) controls in a study of work-related factors and CHD in Taipei. We applied land-use regression models developed by the European Study of Cohorts for Air Pollution Effects to estimate the mean annual exposure of each participant to five air pollutants at their residence in Taipei, namely particulate matter (PM) of diameter <10 µm (PM10) and 2.5 µm (PM2.5), the absorbance of PM2.5 (PM2.5 abs), nitrogen dioxide (NO2), and nitrogen oxide (NOx). RESULTS: The mean annual exposures were 47.82 ± 4.78 µg/m for PM10, 29.08 ± 5.10 µg/m for PM2.5, and 2.04 ± 0.37 (10 m) for PM2.5 abs. Multivariate linear regression analyses showed that the mean percentage (95% confidence interval) of blood monocyte counts increased by 9.08% (1.61%, 16.54%) per 10 µg/m increase in PM10, by 16.28% (6.66%, 25.89%) per 1.0 × 10 m increase in PM2.5 abs, by 8.28% (2.08%, 14.48%) per 20 µg/m increase in NO2, and by 2.84% (1.22%, 4.46%) per 10 µg/m increase in NOx. In addition, each 5 µg/m increase in PM2.5 was associated with 1.97% (0.02%, 3.92%) increases in fibrinogen. CONCLUSIONS: Long-term exposure to traffic-related air pollution is positively associated with subclinical inflammatory and thrombotic markers in middle-aged workers in Taipei.

Associations between Long-Term Particulate Matter Exposure and Adult Renal Function in the Taipei Metropolis.

BACKGROUND: Studies on the effect of air pollutions on kidney diseases are still limited. OBJECTIVE: We aimed to investigate the associations between particulate matter (PM) exposures and renal function among adults. METHODS: We recruited 21,656 adults as participants from 2007 to 2009. The Taiwanese Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to derive the estimated glomerular filtration rate (eGFR). Subjects with an eGFR lower than 60 mL/min/1.73 m2 were defined as having chronic kidney disease (CKD). Land use regression (LUR) models were used to estimate individual exposures to PM with an aerodynamic diameter < 10 µm (PM10), coarse particles (PMCoarse), fine particles (PM2.5), and PM2.5Absorbance. Generalized linear and logistic regression models were used to estimate the associations between PM exposure and renal function. RESULTS: An IQR increase in PM10 (5.83 µg/m3) was negatively associated with eGFR by -0.69 (95% CI: -0.89, -0.48) mL/min/1.73 m2 and positively associated with the prevalence of CKD with adjusted OR = 1.15 (95% CI: 1.07, 1.23). An IQR increase in PMCoarse (6.59 µg/m3) was significantly associated with lower eGFR by -1.07 (95% CI: -1.32, -0.81) mL/min/1.73 m2 and CKD with OR = 1.26 (95% CI: 1.15, 1.38). In contrast, neither outcome was significantly associated with PM2.5 or PM2.5Absorbance. Stratified analyses indicated that associations of CKD with both PM10 and PMCoarse were limited to participants < 65 years of age, and were stronger (for PM10) or limited to (PMCoarse) women. Associations also appeared to be stronger in those without (vs. with) hypertension, and in normal versus overweight participants. CONCLUSIONS: Exposure during the previous year to PM10 and PMCoarse, but not PM2.5 or PM2.5Absorbance, was associated with reduced renal function among Taiwanese adults.

Combining diffusion tensor imaging and gray matter volumetry to investigate motor functioning in chronic stroke.

Motor impairment after stroke is related to the integrity of the corticospinal tract (CST). However, considerable variability in motor impairment remains unexplained. To increase the accuracy in evaluating long-term motor function after ischemic stroke, we tested the hypothesis that combining diffusion tensor imaging (DTI) and gray matter (GM) volumetry can better characterize long-term motor deficit than either method alone in patients with chronic stroke. We recruited 31 patients whose Medical Research Council strength grade was ≤ 3/5 in the extensor muscles of the affected upper extremity in the acute phase. We used the Upper Extremity Fugl-Meyer (UE-FM) assessment to evaluate motor impairment, and as the primary outcome variable. We computed the fractional anisotropy ratio of the entire CST (CSTratio) and the volume of interest ratio (VOIratio), between ipsilesional and contralesional hemispheres, to explain long-term motor impairment. The results showed that CSTratio, VOIratio of motor-related brain regions, and VOIratio in the temporal lobe were correlated with UE-FM. A multiple regression model including CSTratio and VOIratio of the caudate nucleus explained 40.7% of the variability in UE-FM. The adjusted R2 of the regression model with CSTratio as an independent variable was 29.4%, and that of using VOIratio of the caudate nucleus as an independent variable was 23.1%. These results suggest that combining DTI and GM volumetry may achieve better explanation of long-term motor deficit in stroke patients, than using either measure individually. This finding may provide guidance in determining optimal neurorehabilitative interventions.