Salvianolic Acid B Attenuates Iopromide-Induced Renal Tubular Epithelial Cell Injury by Inhibiting the TLR4/NF-κB/NLRP3 Signaling Pathway.

Postcontrast acute kidney injury (PC-AKI) is directly caused by the use of contrast, indicating a clear causal relationship between the contrast and the injury. Salvianolic acid B (Sal B), a water-soluble compound of Salvia miltiorrhiza, has a potent anti-inflammatory effect. We conducted a study to explore whether the protective effect of Sal B on iopromide-induced injury in human proximal tubular epithelial cells (HK-2 cells) is related to inhibition of the TLR4/NF-κB/NLRP3 signal pathway. The results showed that 100 µmol/L Sal B counteracted the decrease in cell viability, the increase of ROS and the number of apoptotic cells, and the decrease of mitochondrial membrane potential (ΔΨm) induced by iopromide. Molecular docking analysis showed that Sal B binds TLR4 and NLRP3 proteins. Moreover, 100 µmol/L Sal B also decreased the expression of TLR4, NLRP3, ASC, Caspase-1, IL-18, IL-1ß, TNF-α, p-NF-κB, cleaved caspase-3, and the ratio of Bax/Bcl-2 induced by iopromide. TAK-242, a TLR4 antagonist, was added to further explore the mechanism of Sal B. However, the cotreatment group with TAK-242 and Sal B had no significant difference in cell viability and apoptosis rate compared to the treatment group with TAK-242 or Sal B alone. These results indicated that Sal B can inhibit the TLR4/NF-κB/NLRP3 signal pathway, resulting in the alleviation of iopromide-induced HK-2 cell injury.

Effects and Mechanism of Salvianolic Acid B on the Injury of Human Renal Tubular Epithelial Cells Induced by Iopromide.

With the increasing application of medical imaging contrast materials, contrast-induced nephropathy (CIN) has become the third major cause of iatrogenic renal insufficiency. CIN is defined as an absolute increase in serum creatinine levels of at least 0.50 mg/dl or an increase >25% of serum creatinine from baseline after exposure to contrast. In this study, the protective effects of salvianolic acid B (Sal B) were detected in human renal tubular epithelial cells (HK-2) exposed to iopromide. The results showed that different concentrations of Sal B counteract the loss of cell viability induced by iopromide, and reduce cell apoptosis, the reactive oxygen species (ROS) levels, and the levels of endoplasmic reticulum stress (ERS)-related and apoptosis-related proteins such as p-IRE-1α, p-eIF-2α/eIF-2α, p-JNK, CHOP, Bax/Bcl-2, and cleaved caspase-3. In addition, Sal B at a concentration of 100 µmol/L inhibited ERS and reduced cell damage to a similar extent as the ERS inhibitor 4-PBA. Importantly, treatment with Sal B could abolish the injury induced by ERS agonist tunicamycin, increasing cell viability and the mitochondrial membrane potential, as well as significantly reducing ROS levels and the expression of Bax/Bcl-2, cleaved-caspase-3, GRP78, p-eIF2α, p-JNK, and CHOP. These results suggested that the protective effect of Sal B against HK-2 cell injury induced by iopromide may be related to the inhibition of ERS.

Evaluation of ergosterol composition and esterification rate in fungi isolated from mangrove soil, long-term storage of broken spores, and two soils.

Ergosterol is an important fungal-specific biomarker, but its use for fungal biomass estimation is still varied. It is important to distinguish between free and esterified ergosterols, which are mainly located on the plasma membrane and the cytosolic lipid particles, respectively. The present study analyzes free and esterified ergosterol contents in: (1) the fifty-nine strains of culturable fungi isolated from mangrove soil, (2) the broken spores of the fungus Ganoderma lucidum stored in capsule for more than 12 years, and (3) the mangrove soil and nearby campus wood soil samples by high performance liquid chromatography (HPLC). The results show that the contents of free and esterified ergosterols varied greatly in fifty-nine strains of fungi after 5 days of growth, indicating the diversity of ergosterol composition in fungi. The average contents of free and total ergosterols from the fifty-nine strains of fungi are 4.4 ± 1.5 mg/g and 6.1 ± 1.9 mg/g dry mycelia, respectively, with an average ergosterol esterification rate of 27.4%. The present study suggests that the fungi might be divided into two classes, one is fungi with high esterification rates (e.g., more than 27%) such as Nectria spp. and Fusarium spp., and the other is fungi with low esterification rates (e.g., less than 27%) such as Penicillium spp. and Trichoderma spp. Moreover, the ergosterol esterification rate in the spores of G. lucidum is 91.4% with a very small amount of free ergosterol (0.015 mg/g), compared with 41.9% with a higher level of free ergosterol (0.499 mg/g) reported in our previous study in 2007, indicating that free ergosterol degrades more rapidly than esterified ergosterol. In addition, the ergosterol esterification rates in mangrove soil and nearby campus wood soil samples range from 0 to 39.0%, compared with 80% in an old soil organic matter reported in a previous study, indicating the potential relationship between aging degree of fungi or soil and esterification rate. The present study proposes that both free and esterified ergosterols should be analyzed for fungal biomass estimation. When the ergosterol esterification rates in soils are higher, free ergosterol might be a better marker for fungal biomass. It is speculated that the ergosterol esterification rate in soils might contain some important information, such as the age of old-growth forests over time scales of centuries to millennia, besides the senescence degree of fungal mycelia in soils. KEY POINTS: • Fungi might be divided into two classes depending on ergosterol esterification rates. • Ergosterol esterification rate of broken spores stored for long time raised evidently. • Both free and esterified ergosterols should be analyzed for fungal biomass estimate. • Free ergosterol is a better marker for fungal biomass with a high esterification rate.

Geochemical Significance of Biomarkers in the Methane Hydrate-Bearing Sediments from the Shenhu Area, the South China Sea.

Biomarkers from methane hydrate-bearing sediments can provide vital evidence for microbial activities associated with methanogenesis and their relation to the formation of methane hydrates. However, the former mainly focus on intact polar lipids from these microorganisms, and rarely investigate molecular hydrocarbons such as acyclic isoprenoids and hopanes so far. In this work, the composition of biomarkers in the methane hydrate-bearing sediments in cores SH2B and SH7B from the Shenhu area, the South China Sea (SCS) were identified by gas chromatography-mass spectrometry (GC-MS) and comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC×GC-TOFMS). The occurrence of unresolved complex mixtures (UCMs) and 25-norhopane indicate that the organic matters in methane hydrate-bearing sediments underwent a high degree of biodegradation. Although specific biomarkers for methanogens were not identified, the UCMs, 25-norhopane, pristane, phytane, and hopanes can still indicate the microbial activities associated with methanogenesis. These molecular signals suggest that diverse microorganisms, particularly methanogens, were quite vigorous in the methane hydrate-bearing sediments. Further, the biomarkers identified in this study can also be steadily detected from deep oil/gas reservoirs. Considering numerous adjacent oil/gas reservoir systems, fault systems, and mud diapers occurred in the SCS, it can be inferred that microbial activities and deep oil/gas reservoirs may have jointly contributed to the formation of methane hydrate deposits in the SCS.