Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome.

Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1ß production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.

De novo podocytopathy following moderna COVID-19 vaccine: A case report and racial disproportionality in adverse effect reports.

In this study, we report a case of de novo minimal change disease shortly after the second dose of the Moderna COVID-19 vaccine. A previously healthy 51-year-old Asian man presented with lower-limb edema and foamy urine 3 days after receiving the second dose of the vaccine. Laboratory data revealed the following: serum creatinine, 0.65 mg/dl; serum albumin, 1.3 g/dl; urine protein-to-creatinine ratio, 15.3 g. A renal biopsy was performed, and minimal change in the disease was confirmed. The patient achieved complete remission in the tenth week after starting treatment with prednisolone (1 mg/kg/day). Ethnic differences may influence the adverse effects of drugs and vaccines. However, there is very limited data to address the influence of ethnic diversity on disease prevalence, clinical presentation, and treatment outcomes in COVID-19 vaccine-associated glomerulonephritis.

Far-infrared protects vascular endothelial cells from advanced glycation end products-induced injury via PLZF-mediated autophagy in diabetic mice.

The accumulation of advanced glycation end products (AGEs) in diabetic patients induces vascular endothelial injury. Promyelocytic leukemia zinc finger protein (PLZF) is a transcription factor that can be activated by low-temperature far-infrared (FIR) irradiation to exert beneficial effects on the vascular endothelium. In the present study, we investigated the influence of FIR-induced PLZF activation on AGE-induced endothelial injury both in vitro and in vivo. FIR irradiation inhibited AGE-induced apoptosis in human umbilical vein endothelial cells (HUVECs). PLZF activation increased the expression of phosphatidylinositol-3 kinases (PI3K), which are important kinases in the autophagic signaling pathway. FIR-induced PLZF activation led to autophagy in HUVEC, which was mediated through the upregulation of PI3K. Immunofluorescence staining showed that AGEs were engulfed by HUVECs and localized to lysosomes. FIR-induced autophagy promoted AGEs degradation in HUVECs. In nicotinamide/streptozotocin-induced diabetic mice, FIR therapy reduced serum AGEs and AGEs deposition at the vascular endothelium. FIR therapy also reduced diabetes-induced inflammatory markers in the vascular endothelium and improved vascular endothelial function. These protective effects of FIR therapy were not found in PLZF-knockout mice. Our data suggest that FIR-induced PLZF activation in vascular endothelial cells protects the vascular endothelium in diabetic mice from AGE-induced injury.

Peroxisome Proliferator-Activated Receptor α Protects Renal Tubular Cells from Gentamicin-Induced Apoptosis via Upregulating Na+/H+ Exchanger NHE1.

Peroxisome proliferator-activated receptor (PPAR)-α is a transcription factor that has been reported to inhibit gentamicin-induced apoptosis in renal tubular cells. However, the antiapoptotic mechanism of PPARα is still unknown. In this study, we found that PPARα overexpression induced Na+/H+ exchanger-1 (NHE1) expression in the rat renal tubular cells NRK-52E. Beraprost, a PPARα ligand, also increased NHE1 expression in the renal tubules in normal mice, but not in PPARα knockout mice. Chromatin immunoprecipitation assays revealed that two PPARα binding elements were located in the rat NHE1 promoter region. Na+/H+ exchanger activity also increased in the PPARα-overexpressed cells. Flow cytometry showed that the PPARα-overexpressed cells were resistant to apoptosis-induced shrinkage. Cariporide, a selective NHE1 inhibitor, inhibited the antiapoptotic effect of PPARα in the gentamicin-treated cells. The interaction between NHE1 and ezrin/radixin/moesin (ERM) and between ERM and phosphatidylinositol 4,5-bisphosphate in the PPARα-overexpressed cells was more than in the control cells. ERM short interfering RNA (siRNA) transfection inhibited the PPARα-induced antiapoptotic effect. PPARα overexpression also increased the phosphoinositide 3-kinase (PI3K) expression, which is dependent on NHE1 activity. Increased PI3K further increased the phosphorylation of the prosurvival kinase Akt in the PPARα-overexpressed cells. Wortmannin, a PI3K inhibitor, inhibited PPARα-induced Akt activity and the antiapoptotic effect. We conclude that PPARα induces NHE1 expression and then recruits ERM to promote PI3K/Akt-mediated cell survival in renal tubular cells. The application of PPARα activation reduces the nephrotoxicity of gentamicin and may expand the clinical use of gentamicin.

[Characteristics of PCBs in a capacitor storage site and an industrial brownfield].

The levels and congener patterns of 28 PCBs compounds were investigated in soil and dust fallout collected in a capacitor storage site and an industrial brownfield, respectively in Sichuan Ziyang Locomotive Factory. The highest concentration of the total PCBs(sigma PCBs =227 502 ng x g(-1)) was found in soil collected from the front gate (unsealed) of the capacitor storage tunnel. Very high levels of sigma PCBs, exceed 10 microg x g(-1), were also found in the dust collected from the window sill of an iron foundry. There were significant positive correlations (P < 0.01) among PCB congener concentration in the storage site and the iron foundry samples. The major contribution to the total content of PCBs in the high contaminated samples was tetrachlorinated biphenyls, followed by tri- and penta-chlorinated biphenyls. Hexa- and higher chlorinated biphenyls contributed more to sigma PCBs in the iron foundry than those in the storage site. The total toxicity equivalents (TEQ) of 12 dioxin-like congeners varied in the range of 75.43-24 027 pg x g(-1) and were much higher than those in soils of e-waste recycling sites. However, PCB126 contribute the most to the TEQ in most cases.

Environmental behavior of organotin compounds in the coastal environment of Xiamen, China.

In 2006, organotins pollution were investigated in the coastal environment of Xiamen, China. Six species of organotin compounds including tributyltin, triphenyltin and their degradation compounds were quantified in the dissolved and particulate phases of the water, and in the sediment using GC-FPD. The concentrations of organotin compounds ranged from 2.2 to 160 ng (Sn) L(-1) dissolved in the water, 0.14-6.7 ng (Sn) L(-1) in suspended particulate matter and nd approximately 26 ng (Sn) g(-1) (dry weight) in the sediment. The highest concentration of total organotin or tributyltin in water was found in a shipyard and at a station near the inlet of the harbor, indicating fresh inputs of antifouling paints to Xiamen's coastal environment. Organotin speciation was performed on sediment cores to investigate contamination trends over the past ten years in the harbor. The results of (210)Pb dating indicated that Xiamen western harbor suffered contamination during 2000. The environmental behavior of organotins such as the enhancement of the microlayer, partitioning between water/suspended particulate matter and between water/sediment are also discussed in this paper.

Persistent organochlorine pollutants in surface sediments and economic shellfish of Minjiang Estuary-Mazu and Xiamen-Jinmen sea areas.

Samples of surface sediment and shellfish were collected from Minjiang Estuary-Mazu and Xiamen-Jinmen sea areas and were analyzed for hexachlorocyclohexanes (HCHs), dichlorodiphenyl-trichlorophenyl (DDT) and its degraded derivatives dichloro-diphenyl-dichloroethane (DDT) and dichloro-dichlorophenyl-ethylene (DDE), and polychlorinated biphenyls (PCBs) by gas chromatography. Concentration ranges of HCHs, DDTs, and PCBs in the sediments were 0.03-0.48, 1.10-14.3, and ND to 0.76 ng/g dw, respectively; those for shellfish samples were ND to 1.5, 21.5-892, dw and ND-3.7 ng/g dw, respectively. The results showed that the concentrations of such oganochlorine compounds (OCs) in the sediments were usually low as compared with other sea areas and estuaries, and the organochlorines were accumulated in marine bivalve mollusks, particularly in oyster. With respect to the concentrations of HCHs, DDTs, and PCBs in the samples of either sediment or shellfish, DDTs were higher than HCHs and PCBs. The concentrations of OCs in shellfish samples varied with the sampling locations and organism species but were generally higher than those in the sediments. The concentration distributions, compositions, and residue levels of these OCs are extensively discussed and evaluated.

Heavy metals in surface sediments from Minjiang Estuary-Mazu and Xiamen-Jinmen Sea areas.

The concentrations of Cu, Pb, Zn and Cd in surface sediments from Minjiang Estuary-Mazu and Xiamen-Jinmen sea areas of China were investigated during 1995-1996. The concentration ranges of Cu, Pb, Zn and Cd in the Minjiang Estuary-Mazu sea area were 16.4-37.2, 33.4-69.6, 92.1-128, 0.087-0.336 mg/kg(dry wt.), respectively; those for Xiamen-Jinmen sea area were 11.0-24.5, 36. 0-80.3, 77.5-161, 0.135-0.285 mg/kg(dry wt.), respectively. The concentrations and distributions of Cu, Pb, Zn and Cd in surface sediments of Minjiang Estuary-Mazu and Xiamen-Jinmen sea areas were analyzed and evaluated. The results showed that the values of Zn and Pb exceeded those of sediment quality criteria. The average concentration of Cu in Minjiang Estuary-Mazu sea area was higher than that in Xiamen-Jinmen sea area. The obviously higher concentrations of Cu, Pb, Zn and Cd were found at outlets of Minjiang and Jiulong River. From the estuaries to open sea, the concentrations of Cu, Pb, Zn and Cd had a decreasing trend, and then elevated in the sea areas near Mazu and Jinmen, suggesting that Cu, Pb, Zn and Cd in Minjiang Estuary-Mazu and Xiamen-Jinmen sea areas may come from both the mainland and Taiwan of China.

Residue levels of HCHs, DDTs and PCBs in shellfish from coastal areas of east Xiamen Island and Minjiang Estuary, China.

Shellfish samples were collected from the coastal cultivating areas of east Xiamen Island and Minjing Estuary, China and analyzed for hexachlorocyclohexanes (HCHs), DDTs and polychlorinated biphenyls (PCBs) by GC. Concentration ranges of HCHs, DDTs and PCBs in the coastal area of east Xiamen Island were 0.18-345, 75.2-2143 and ND-23 ng g(-1) dry wt., respectively; those for Minjiang Estuary were ND-5.07, 21.5-2396 and ND-6.78 ng g(-1) dry wt., respectively. The results showed that the organochlorines were evidently accumulated in marine bivalve molluscs, particularly in oyster. The concentrations of organocholorine pollutants in shellfish samples varied with the sampling locations, the season of collection and organism species, but were generally higher than those in the sediments. The concentrations of DDTs in the shellfish were high as compared with HCHs and PCBs, so that DDTs can be considered as the typical organochlorines in the survey areas. The residue levels and compositions of HCHs, DDTs and PCBs are discussed.