Dietary Isoquercetin Ameliorates Bone Loss via Restoration of the Gut Microbiota and Lipopolysaccharide-Triggered Inflammatory Status in Ovariectomy Mice.

Osteoporosis is one of the skeletal degenerative diseases accompanied by bone loss and microstructure disruption. Given that the gut-bone signaling axis highly contributes to bone health, here, dietary isoquercetin (IQ) was shown to effectively improve postmenopausal osteoporosis (PMO) in an ovariectomy (OVX) mouse model through the modulation of the gut-bone cross-talk. An in vivo study showed that OVX induced striking disruption of the microbial community, subsequently causing gut leakage and gut barrier dysfunction. As a result, lipopolysaccharide (LPS)-triggered inflammatory cytokines released from the intestine to bone marrow were determined to be associated with bone loss in OVX mice. Long-term dietary IQ effectively improved microbial community and gut barrier function in the OVX mice and thus markedly improved bone loss and host inflammatory status by repressing the NF-κB signaling pathway. An in vitro study further revealed that IQ treatments dose-dependently inhibited LPS-induced inflammation and partly promoted the proliferation and differentiation of osteoblasts. These results provide new evidence that dietary IQ has the potential for osteoporosis treatment.

Triclocarban exposure aggravates dextran sulfate sodium-induced colitis by deteriorating the gut barrier function and microbial community in mice.

Triclocarban (TCC) is an antibacterial component widely used in personal care products with potential toxicity possessing public health issues. Unfortunately, enterotoxicity mechanisms of TCC exposure remain largely unknown. Using a combination of 16S rRNA gene sequencing, metabolomics, histopathological and biological examinations, this study systematically explored the deteriorating effects of TCC exposure on a dextran sulfate sodium (DSS)-induced colitis mouse model. We found that TCC exposure at different doses significantly aggravated colitis phenotypes including shortened colon length and altered colonic histopathology. Mechanically, TCC exposure further disrupted intestinal barrier function, manifested by significant downregulation of the number of goblet cells, mucus layer thickness and expression of junction proteins (MUC-2, ZO-1, E-cadherin and Occludin). The gut microbiota composition and its metabolites such as short-chain fatty acids (SCFAs) and tryptophan metabolites were also markedly altered in DSS-induced colitis mice. Consequently, TCC exposure markedly exacerbated colonic inflammatory status of DSS-treated mice by activating NF-κB pathway. These findings provided new evidence that TCC could be an environmental hazards for development of IBD or even colon cancer.

Therapeutic effects of isoquercetin on ovariectomy-induced osteoporosis in mice.

Bone marrow mesenchymal stem cells (BMSCs) are non-hematopoietic multipotent stem cells capable of differentiating into mature cells. Isoquercetin, an extract from natural sources, has shown promise as a potential treatment for osteoporosis. To investigate the therapeutic effects of isoquercetin on osteoporosis, bone marrow mesenchymal stem cells (BMSCs) were cultured in vitro, and osteogenesis or adipogenesis was induced in the presence of isoquercetin for 14 days. We evaluated cell viability, osteogenic and adipogenic differentiation, as well as mRNA expression levels of Runx2, Alpl, and OCN in osteoblasts, and mRNA expression levels of Pparγ, Fabp4, and Cebpα in adipocytes. The results showed that isoquercetin dose-dependently increased cell viability and promoted osteogenic differentiation, as evidenced by Alizarin Red and alkaline phosphatase staining and mRNA expression levels of Runx2, Alpl, and OCN in osteoblasts (P < 0.05). In contrast, isoquercetin inhibited adipogenic differentiation and decreased the mRNA expression levels of Pparγ, Fabp4, and Cebpα in adipocytes (P < 0.05). In vivo, isoquercetin treatment increased bone quantity and density in an osteoporosis model mice group, as determined by µCT scanning and immunohistochemistry (P < 0.05). These findings suggest that isoquercetin may have therapeutic potential for osteoporosis by promoting the proliferation and differentiation of BMSCs towards osteoblasts while inhibiting adipogenic differentiation.

Synergistic effect of zero-valent iron and static magnetic field on wastewater purification and bioelectricity generation in electroactive constructed wetlands.

This study investigated the enhancement effect of zero-valent iron and static magnetic field on the pollutant removal and power generation of electroactive constructed wetland. As demonstration, a conventional wetland was systematically modified by introducing zero-valent iron and then a static magnetic field, leading to progressive increases in pollutant (namely NH4+-N and chemical oxygen demand) removal efficiencies. By introducing both zero-valent iron and a static magnetic field, the power density increased four-fold to 9.2 mW/m2 and the internal resistance decreased by 26.7% to 467.4 Ω. Notably, static magnetic field decreased the relative abundance of electrochemically active bacteria (such as Romboutsia), while significantly enhancing species diversity. The permeability of the microbial cell membrane was improved, leading to a reduction in activation loss and internal resistance, thereby enhancing power generation capacity. Results showed that the addition of zero-valent iron and the applied magnetic field were beneficial to the pollutants removal and bioelectricity generation.

A Novel Prenylflavonoid Icariside I Ameliorates Estrogen Deficiency-Induced Osteoporosis via Simultaneous Regulation of Osteoblast and Osteoclast Differentiation.

Regulation of osteoblast-mediated bone formation and osteoclast-mediated bone resorption is crucial for bone health. Currently, most clinical drugs for osteoporosis treatment such as bisphosphonates are commonly used to inhibit bone resorption but unable to promote bone formation. In this study, we discovered for the first time that icariside I (GH01), a novel prenylflavonoid isolated from Epimedium, can effectively ameliorate estrogen deficiency-induced osteoporosis with enhancement of trabecular and cortical bone in an ovariectomy (OVX) mouse model. Mechanistically, our in vitro results showed that GH01 repressed osteoclast differentiation and resorption through inhibition of RANKL-induced TRAF6-MAPK-p38-NFATc1 cascade. Simultaneously, we also found that GH01 dose-dependently promoted osteoblast differentiation and formation by inhibiting adipogenesis and accelerating energy metabolism of osteoblasts. In addition, both in vitro and in vivo studies also suggested that GH01 is not only a non-toxic natural small molecule but also beneficial for restoration of liver injury in OVX mice. These results demonstrated that GH01 has great potential for osteoporosis treatment by simultaneous regulation of osteoblast and osteoclast differentiation.

Habitats modulate influencing factors shaping the spatial distribution of bacterial communities along a Tibetan Plateau riverine wetland.

The Tibetan Plateau riverine wetland is very sensitive to global climate change. Understanding the mechanisms that maintain the spatial patterns of bacterial communities provides insight into the dominant biogeochemical processes within the plateau riverine wetlands. Nonetheless, the spatial distribution of bacterial communities along these wetlands has rarely been explored. We investigated the spatial patterns of bacterial community within rhizosphere soil, bulk soil, and sediment samples collected along the Yarlung Tsangpo riverine wetland (YTRW), the longest plateau riverine wetland in China. Our results indicated that the diversity of bacterial communities in all three habitats increased significantly along the YTRW. The slope of the linear relationship between distance and bacterial community diversity in sediment was steeper than those for bulk and rhizosphere soils. Furthermore, bacterial communities in all three habitats showed significant distance-decay relationships. A combination of historical factors (geographical distance and climatic factors) and contemporary environmental heterogeneity (edaphic properties) controlled spatial distributions of bacterial communities in all three habitats, although climatic factors were predominant. Climatic factors affected rhizosphere bacterial communities more than those in bulk soil and sediment. Co-occurrence network analysis revealed that the potential interactions between bacterial taxa may decrease along the YTRW. This field investigation highlighted that the climatic factors strongly influenced the spatial distribution of bacterial communities along the YTRW; however, habitat differences among rhizosphere soil, bulk soil, and sediment samples affected the relative importance of climatic factors on spatial distributions of the associated bacterial communities. These findings would improve the understanding of biogeochemical processes in these typical habitats and potential alterations provoked by climate change.

Characterization of triclosan-induced hepatotoxicity and triclocarban-triggered enterotoxicity in mice by multiple omics screening.

Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether, TCS) and triclocarban (3,4,4'-trichloro-carbanilide, TCC) are two antimicrobial agents commonly used for personal care products. Previous studies primarily focused on respective harmful effects of TCS and TCC. In terms of their structural similarities and differences, however, the structure-toxicity relationships on health effects of TCS and TCC exposure remain unclear. Herein, global 1H NMR-based metabolomics was employed to screen the changes of metabolic profiling in various biological matrices including liver, serum, urine, feces and intestine of mice exposed to TCS and TCC at chronic and acute dosages. Metagenomics was also applied to analyze the gut microbiota modulation by TCS and TCC exposure. Targeted MS-based metabolites quantification, histopathological examination and biological assays were subsequently conducted to supply confirmatory information on respective toxicity of TCS and TCC. We found that oral administration of TCS mainly induced significant liver injuries accompanied with inflammation and dysfunction, hepatic steatosis fatty acids and bile acids metabolism disorders; while TCC exposure caused marked intestine injuries leading to striking disruption of colonic morphology, inflammatory status and intestinal barrier integrity, intestinal bile acids metabolism and microbial community. These comparative results provide novel insights into structure-dependent mechanisms of TCS-induced hepatotoxicity and TCC-triggered enterotoxicity in mice.

Aquaculture drives distinct patterns of planktonic and sedimentary bacterial communities: insights into co-occurrence pattern and assembly processes.

Aquaculture would change the environmental condition in the lake ecosystem, affecting the structure and function of the aquatic ecosystem. However, little is known about the underlying mechanisms controlling the distribution patterns of bacterial community respond to aquaculture in water column and sediment. Here, we investigated the composition, co-occurrence patterns, and assembly processes of planktonic and sedimentary bacterial communities (PBC vs. SBC) from an aquaculture-influenced zone of the Eastern Lake Taihu, China. We found that aquaculture activity greatly influenced the diversity and composition of SBC by inducing excess nitrogen into the sediments. Meanwhile, network analysis revealed that aquaculture activity strengthened species interactions within the SBC network but weakened the species interactions within the PBC network. Aquaculture activity also increased the importance of deterministic processes governing the assembly of SBC by heightening the importance of environmental filtering, whereas it decreased the relative importance of deterministic processes within the assembly of PBC. In addition, ecological restoration with macrophytes increased the diversity of PBC and formed a more stable PBC network by increasing the number of network keystones. Overall, our results indicated that aquaculture drove distinct co-occurrence patterns and assembly mechanisms of PBC and SBC. This study has fundamental implications in the lake ecosystem for evaluating the microbially mediated ecological consequences of aquaculture.