Licochalcone A Protects Vaginal Epithelial Cells Against Candida albicans Infection Via the TLR4/NF-κB Signaling Pathway.

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant portion of women worldwide. Licochalcone A (LA), a natural compound with diverse biological activities, holds promise as a protective agent against Candida albicans (C. albicans) infection. This study aims to investigate the potential of LA to safeguard vaginal epithelial cells (VECs) from C. albicans infection and elucidate the underlying molecular mechanisms. To simulate VVC in vitro, VK2-E6E7 cells were infected with C. albicans. Candida albicans biofilm formation, C. albicans adhesion to VK2-E6E7 cells, and C. albicans-induced cell damage and inflammatory responses were assessed by XTT reduction assay, fluorescence assay, LDH assay, and ELISA. CCK-8 assay was performed to evaluate the cytotoxic effects of LA on VK2-E6E7 cells. Western blotting assay was performed to detect protein expression. LA dose-dependently hindered C. albicans biofilm formation and adhesion to VK2-E6E7 cells. Furthermore, LA mitigated cell damage, inhibited the Bax/Bcl-2 ratio, and attenuated the secretion of pro-inflammatory cytokines in C. albicans-induced VK2-E6E7 cells. The investigation into LA's impact on the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway revealed that LA downregulated TLR4 expression and inhibited NF-κB activation in C. albicans-infected VK2-E6E7 cells. Furthermore, TLR4 overexpression partially abated LA-mediated protection, further highlighting the role of the TLR4/NF-κB pathway. LA holds the potential to safeguard VECs against C. albicans infection, potentially offering therapeutic avenues for VVC management.

TBBPS caused necroptosis and inflammation in hepatocytes by blocking PINK1-PARKIN-mediated mitochondrial autophagy.

The widespread use of Tetrabromobisphenol S (TBBPS), as an alternative to tetrabromobisphenol A (TBBPA), has been detected at high frequency in environmental media in recent years, TBBPS can enter the body via the digestive tract and other routes, thus long-term TBBPS exposure may cause adverse health effects. Therefore, it is necessary to evaluate the toxicological effects of TBBPS. In the current work, two cell models of the liver were used (a human-derived cell line THLE-2 and a murine-derived AML12). The liver cells were then exposed to different concentrations of TBBPS. The results of cell proliferation assays showed that TBBPS resulted in a significant attenuation of the proliferative capacity of liver cells. Further results from ELISA and Western-blot assays showed that TBBPS induced an inflammatory response in liver cells by detecting the levels of inflammatory factors, such as TNFα, IL-1ß and IL-6. We also found that TBBPS promoted the necroptosis in liver cells by evaluating the levels of RIP3 and pMLKL, and the use of inhibitors of necroptosis confirmed that the type of cell death induced by TBBPS belongs to necroptosis. Molecular mechanistic studies showed that TBBPS suppressed mitochondrial autophagy mediated by the PINK1-PARKIN signaling pathway, which led to accumulation of damaged mitochondria in THLE-2 and AML12 cells. Subsequently, accumulated ROS activated necroptosis of liver cells. Current toxicological studies suggest that we need to better control and regulate the production and use of TBBPS, the current work provide a reference for studying the toxicology of TBBPS.

Facultative anaerobic conversion of lignocellulose biomass to new bioemulsifier by thermophilic Geobacillus thermodenitrificans NG80-2.

Heavy oil has hindered crude oil exploitation and pollution remediation due to its high density and viscosity. Bioemulsifiers efficiently facilitate the formation and stabilization of oil-in-water emulsions in low concentrations thus eliminating the above bottleneck. Despite their potential benefits, various obstacles had still impeded the practical applications of bioemulsifiers, including high purification costs and poor adaptability to extreme environments such as high temperature and oxygen deficiency. Herein, thermophilic facultative anaerobic Geobacillus thermodenitrificans NG80-2 was proved capable of emulsifying heavy oils and reducing their viscosity. An exocelluar bioemulsifier could be produced by NG80-2 using low-cost lignocellulose components as carbon sources even under anaerobic condition. The purified bioemulsifier was proved to be polysaccharide-protein complexes, and both components contributed to its emulsifying capability. In addition, it displayed excellent stress tolerance over wide ranges of temperatures, salinities, and pHs. Meanwhile, the bioemulsifier significantly improved oil recovery and degradation efficiency. An eps gene cluster for polysaccharide biosynthesis and genes for the covalently bonded proteins was further certificated. Therefore, the bioemulsifier produced by G. thermodenitrificans NG80-2 has immense potential for applications in bioremediation and EOR, and its biosynthesis pathway revealed here provides a theoretical basis for increasing bioemulsifier output.

Genetic and Comparative Genome Analysis of Exiguobacterium aurantiacum SW-20, a Petroleum-Degrading Bacteria with Salt Tolerance and Heavy Metal-Tolerance Isolated from Produced Water of Changqing Oilfield, China.

The genome of Exiguobacterium aurantiacum SW-20 (E. aurantiacum SW-20), a salt-tolerant microorganism with petroleum hydrocarbon-degrading ability isolated from the Changqing Oilfield, was sequenced and analyzed. Genomic data mining even comparative transcriptomics revealed that some genes existed in SW-20 might be related to the salt tolerance. Besides, genes related to petroleum hydrocarbon degradation discovered in genomic clusters were also found in the genome, indicating that these genes have a certain potential in the bioremediation of petroleum pollutants. Multiple natural product biosynthesis gene clusters were detected, which was critical for survival in the extreme conditions. Transcriptomic studies revealed that some genes were significantly up-regulated as salinity increased, implying that these genes might be related to the salt tolerance of SW-20 when living in a high salt environment. In our study, gene clusters including salt tolerance, heavy metal tolerance and alkane degradation were all compared. When the same functional gene clusters from different strains, it was discovered that the gene composition differed. Comparative genomics and in-depth analysis provided insights into the physiological features and adaptation strategies of E. aurantiacum SW-20 in the oilfield environment. Our research increased the understanding of niches adaption of SW-20 at genomic level.

Ursolic acid reduces Adriamycin resistance of human ovarian cancer cells through promoting the HuR translocation from cytoplasm to nucleus.

Ursolic acid (UA) has been shown to suppress various tumor progression, however, its roles in Adriamycin resistance of human ovarian cancer (OC) cells are still unclear. This work aims to investigate the effects of UA on the Adriamycin resistance of human OC cells. Here, we constructed Adriamycin-resistant OC SKOV3-Adr cells and found that UA attenuated Adriamycin resistance in SKOV3-Adr cells. Additionally, UA enhanced Adriamycin sensitivity in the parental SKOV3 and another OC cell line A2780 cells. Mechanistic studies showed that HuR mRNA level was similar between SKOV3 and SKOV3-Adr cells, but the cytoplasmic expression of HuR protein was increased in SKOV3-Adr cells compared with that in SKOV3 cells, and subsequently enhancing the mRNA stability of multidrug resistance gene 1 (MDR1). Moreover, UA had no effects on HuR expression, but promoted the cytoplasm-nucleus translocation of HuR protein, decreased MDR1 mRNA stability and thus reduced MDR1 expression. Furthermore, overexpression of MDR1 rescued the effects of UA on Adriamycin resistance and sensitivity. This work reveals a novel HuR/MDR1 axis responsible for UA-mediated attenuation on Adriamycin resistance in OC cells.

Association of IL-17 and IL-23 Gene Variants with Plasma Levels and Risk of Vulvovaginal Candidiasis in a Chinese Han Population.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a common vaginal inflammatory disease in females. The interleukin (IL)-23/IL-17 axis was involved in vaginal inflammation. Nevertheless, the relationship between gene polymorphisms in the IL-23/IL-17 axis and VVC risk is still unexplored. METHODS: We enrolled 217 VCC cases and 326 controls in this study. The genotyping of all polymorphisms was implemented by PCR-RFLP methods. RESULTS: Data indicated that IL-17F gene rs763780, IL-17A gene rs2275913, and IL-23R rs11209026 polymorphisms were linked with an elevated risk of VVC in Chinese ethnicity. Subgroup analyses uncovered that IL-23R rs11209026, IL-17A rs10484879 and IL-17F rs763780 polymorphisms increased the risk of VVC among smokers or individuals with BMI ≥25 kg/m2. Additionally, IL-17F rs763780 polymorphism was shown to increase the risk of recurrent VVC (RVVC). Furthermore, IL-23 and IL-17 serum levels were higher among VVC cases than controls. We also observed that IL-23 and IL-17 gene polymorphisms were related to their serum levels. Receiver operating characteristics (ROC) curve analysis found that IL-17 and IL-23 serum levels were associated with the relapse of VVC. CONCLUSION: In conclusion, this study indicates that polymorphisms in the IL-23/IL-17 axis increase the risk of VVC.

Function of Atg11 in non-selective autophagy and selective autophagy of Candida albicans.

Candida albicans is an important opportunistic pathogenic fungus in the human body. It is a common microbe inhabiting on the mucosa surfaces of healthy individuals, but may cause infections when the host immune system is weak. Autophagy is a "self-eating" process in eukaryotes, which can recover and utilize damaged organelles and misfolded proteins. Here we investigated the role of the autophagy-related protein Atg11 in C. albicans. Deletion of ATG11 led to the defect in growth under the nitrogen starvation condition. Western blotting and GFP localization further revealed that the transport and degradation of Atg8 was blocked in the atg11Δ/Δ mutant under both the nitrogen starvation and hypha-inducing conditions. Moreover, degradation of both Lap41 (the indicator of the cytoplasm-to-vacuole pathway) and Csp37 (the indicator of mitophagy) was also thoroughly suppressed in this mutant under nitrogen starvation. These results indicated that Atg11 plays an essential role in both non-selective and selective autophagy in C. albicans.

The importance of organic matter distribution and extract soil:solution ratio on the desorption of heavy metals from soils.

The lability (mobility and bioavailability) of metals varies significantly with soil properties for similar total soil metal concentrations. We studied desorption of Cu, Ni and Zn, from 15 diverse, unamended soils. These studies included evaluation of the effects of soil:solution extraction ratio and the roles of soil properties on metal desorption. Dcsorption was examined for each metal by computing distribution coefficients (Kd) for each metal in each soil where Kd = [M]soil/[M]solution, Results from soil:solution ratio studies demonstrated that Kd values for the metals tended to increase with increasing soil:solution ratio. This result also held true for distribution of soil organic matter (SOM). Because the soil:solution ratio has a significant effect on measured metal distributions, we selected a high soil:solution ratio to more closely approach natural soil conditions. Copper showed strong affinity to operationally defined dissolved organic matter (DOM). In this study, DOM was operationally defined based on the total organic carbon (TOC) content in 0.45-microm or 0.22-microm filtrates of the extracts. The Kd of Cu correlated linearly (r2 = 0.91) with the Kd of organic matter (Kd-om) where the Kd-om is equal to SOM as measured by Walkley-Black wet combustion and converted to total carbon (TC) by a factor of 0.59. These values representing solid phase TC were then divided by soluble organic carbon as measured by TOC analysis (DOM). The conversion factor of 0.59 was employed in order to construct Kd-om values based on solid phase carbon and solution phase carbon. SOM plays a significant role in the fate of Cu in soil systems. Soil-solution distribution of Ni and Zn, as well as the activity of free Cu2+, were closely related to SOM, but not to DOM. Kd values for Ni, Zn and free Cu2+ in a particular soil were divided by the SOM content in the same soil. This normalization of the Kd values for Ni, Zn, and free Cu2+ to the SOM content resulted in significant improvements in the linear relationships between non-normalized Kd values and soil pH. The semi-empirical normalized regression equations can be used to predict the solubility of Ni and Zn and the activity of free Cu2+ as a function of pH.