Nanoplastic propels diet-induced NAFL to NASH via ER-mitochondrial tether-controlled redox switch.

Nonalcoholic steatohepatitis (NASH) is multifactorial that lifestyle, genetic, and environmental factors contribute to its onset and progression, thereby posing a challenge for therapeutic intervention. Nanoplastic (NP) is emerged as a novel environmental metabolism disruptor but the etiopathogenesis remains largely unknown. In this study, C57BL/6 J mice were fed with normal chow diet (NCD) and high-fat diet (HFD) containing 70 nm polystyrene microspheres (NP). We found that dietary-derived NP adsorbed proteins and agglomerated during the in vivo transportation, enabling diet-induced hepatic steatosis to NASH. Mechanistically, NP promoted liver steatosis by upregulating Fatp2. Furthermore, NP stabilized the Ip3r1, and facilitated ER-mitochondria contacts (MAMs) assembly in the hepatocytes, resulting in mitochondrial Ca2+ overload and redox imbalance. The redox-sensitive Nrf2 was decreased in the liver of NP-exposed mice, which positively regulated miR26a via direct binding to its promoter region [-970 bp to -847 bp and -318 bp to -176 bp]. NP decreased miR26a simultaneously upregulated 10 genes involved in MAMs formation, lipid uptake, inflammation, and fibrosis. Moreover, miR26a inhibition elevated MAMs-tether Vdac1, which promoted the nucleus translocation of NF-κB P65 and Keap1 and functionally inactivated Nrf2, leading to a vicious cycle. Hepatocyte-specific overexpressing miR26a effectively restored ER-mitochondria miscommunication and ameliorated NASH phenotype in NP-exposed and Keap1-overexpressed mice on HFD. The hepatic MAM-tethers/Nrf2/miR26a feedback loop is an essential metabolic switch from simple steatosis to NASH and a promising therapeutic target for oxidative stress-associated liver damage and NASH.

Size-dependent adverse effects of microplastics on intestinal microbiota and metabolic homeostasis in the marine medaka (Oryzias melastigma).

Microplastic (MP) is an emerging environmental pollutant and exposure to MPs has been associated with numerous adverse health outcomes in both wild and laboratory animals. The toxicity of MPs depends on concentration, exposure time, chemical composition and size distribution, but the impacts of particle size remain inconclusive yet. In this study, adult marine medaka (Oryzias melastigma) were exposed to different size of polystyrene MPs (PS-MPs) with concentration of 10 mg/L for 60 days and the growth performance, lipid metabolism, immune parameters and gut microbiome were determined. Results indicated that particle size is a dominant factor causing lipid metabolism disorders and hepatic toxicity in PS-MPs-exposed fish. The bodyweight, adipocyte size and hepatic lipid contents were significantly increased in 200 µm PS-MPs-exposed fish, while 2 and 10 µm PS-MPs-exposed fish exhibited liver injury principally manifested asthepresence oflittlefibrosis and inflammation. Given that larger particles could not enter the circulatory system, the impacts of PS-MPs on intestinal microbial biota homeostasis were further investigated. The results not only showed the characterization of gut microbial communities in Oryzias melastigma, but also indicated that microbial diversity and composition were altered in gut of fish exposed to PS-MPs, in particular 200 µm PS-MPs. The differentially abundant bacterial taxa in PS-MPs-exposed fish mainly belonged to the phylum Verrucomicrobia, Firmicutes and Fusobacteria. And furthermore, increased abundance of Verrucomicrobia and Firmicutes/Bacteroidetes ratio and decreased Fusobacteria were correlated with the increased bodyweight. Intestinal microbiome should play a critical role in regulating host lipid metabolism in fish exposed to lager size of PS-MPs.

Early warning of hand, foot, and mouth disease transmission: A modeling study in mainland, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a global infectious disease; particularly, it has a high disease burden in China. This study was aimed to explore the temporal and spatial distribution of the disease by analyzing its epidemiological characteristics, and to calculate the early warning signals of HFMD by using a logistic differential equation (LDE) model. METHODS: This study included datasets of HFMD cases reported in seven regions in Mainland China. The early warning time (week) was calculated using the LDE model with the key parameters estimated by fitting with the data. Two key time points, "epidemic acceleration week (EAW)" and "recommended warning week (RWW)", were calculated to show the early warning time. RESULTS: The mean annual incidence of HFMD cases per 100,000 per year was 218, 360, 223, 124, and 359 in Hunan Province, Shenzhen City, Xiamen City, Chuxiong Prefecture, Yunxiao County across the southern regions, respectively and 60 and 34 in Jilin Province and Longde County across the northern regions, respectively. The LDE model fitted well with the reported data (R2 > 0.65, P < 0.001). Distinct temporal patterns were found across geographical regions: two early warning signals emerged in spring and autumn every year across southern regions while one early warning signals in summer every year across northern regions. CONCLUSIONS: The disease burden of HFMD in China is still high, with more cases occurring in the southern regions. The early warning of HFMD across the seven regions is heterogeneous. In the northern regions, it has a high incidence during summer and peaks in June every year; in the southern regions, it has two waves every year with the first wave during spring spreading faster than the second wave during autumn. Our findings can help predict and prepare for active periods of HFMD.

Biocompatible Croconaine Aggregates with Strong 1.2-1.3 µm Absorption for NIR-IIa Photoacoustic Imaging in Vivo.

Although photoacoustic imaging (PAI) in the second near-infrared (NIR-II) region (1.0-1.7 µm) is admired for deeper penetration and higher contrast, few organic NIR-II absorbers are available as exogenous contrast agents in vivo. A1094 belongs to the very few ∼1.1 µm absorbing croconaine dyes that have superior extinction coefficient and tend to form irregular aggregation. In this study, shape-controlled A1094@DSPE-PEG2000 micelles with a J-aggregate core with remarkable 1.2-1.3 µm absorption are fabricated as biocompatible organic agents. Excellent capabilities in photothermal conversion, photostability, and PAI are found in in vitro studies. In vivo PAI of inguinal lymph nodes and in situ glioma pre- and post-resection, all demonstrate high lymph/tumor-targeting efficiency. An ∼4.54 mm deep brain lesion is imaged at 1200 nm with minimized background and increased contrast compared to 970 nm. Overall, we achieved significant bathochromic shift of organic absorbers and expanded their PAI application to the long-wavelength end of the NIR-IIa region.

[Research progress on the type â ¨ secretion system of Porphyromonas gingivalis].

In recent years, the study found that Porphyromonas gingivalis type Ⅸ secretion system (T9SS) is a novel protein secretion system, also known as Por secretion system (PorSS). Unlike the eight protein secretion systems found in the past, the system is a polyprotein complex found only in Bacteroides. The secreted proteins have both N- and C-terminus, where the former includes Sec-dependent type Ⅰ signals peptide, and the latter contains conserved domains (C-terminal conserved domain, CTD). Porphyromonas gingivalis T9SS includes proteins such as intima, outer membrane, cytoplasm, and cell cycle, including at least 34 proteins containing CTD. Porphyromonas gingivalis T9SS is involved in regulating associated virulence factors including gingivin, fimbriae, lipopolysaccharide, HBP35, CPG70 protein and peptidyl-arginine deiminase. These CTD-containing virulence proteins are localized by T9SS and then released to the extracellular domain, thereby destroying periodontal tissue. Therefore, this review summarizes the research progress on the T9SS of Porphyromonas gingivalis.

[Clinical and microbiologic follow-up evaluations after non-surgical periodontal treatment with Nd: YAG laser and scaling and root planning].

OBJECTIVE: Our research aimed to detect the efficacy of non-surgical periodontal treatment with Nd: YAG laser and scaling and root planning (SRP) for chronic periodontitis. METHODS: We recruited chronic periodontitis patients who have more than four teeth with clinical pocket depth of 4-8 mm. These teeth were distributed in four different zones within the oral cavity. Moreover, the teeth were single root teeth and not adjacent to each other. The subordinated teeth were randomized into four groups, as follows: no treatment (C group), simple SRP (SRP group), Nd: YAG laser after SRP treatment (SRP+L group), and SRP after Nd: YAG laser treatment (L+SRP group). The four experimental observation points were as follows: before treatment (baseline) and 1 week, 1 month, and 3 months after treatment. We measured clinical indicators and collected subgingival deposits in the four time points to analyze changes of red complex in periodontitis. RESULTS: The clinical indicators were better in all treatment groups than in the control group. Comparison among treatment groups indicated that the value of bleeding on probing, periodontal probing depth, and clinical attachment loss showed no difference. However, the value of plaque index in SRP+L and L+SRP presented a significant reduction at 3 months after treatment. The percentages of Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola in all treatment groups decreased after clinical treatment, and differences were observed among the treatment groups at different time points. CONCLUSIONS: Non-surgical periodontal treatment with SRP and Nd: YAG laser is not more effective than SRP monotherapy. The sequence of laser treatment and SRP has no significant effect on the treatment. However, SRP with Nd: YAG laser was beneficial for plaque control. Non-surgical periodontal treatment with Nd: YAG laser may be used as an alternative to reduce and control the proliferation of microorganisms in persistent periodontitis, but it still needs further verification.

[Correlation analysis of Filifactor alocis detection with periodontal status].

OBJECTIVE: The study investigated the epidemiology of Filifactor alocis (F. alocis) in subgingival plaque samples from subjects with different periodontal statuses. The relationship between the prevalence of F. alocis and clinical periodontal parameters was also analyzed. METHODS: Subgingival plaque samples and periodontal data were collected from 68 healthy sites (H groups) in 17 healthy subjects, 64 healthy (G-H group) and 76 diseased sites (G-D group) in 19 patients with chronic gingivitis, and 36 healthy (P-H group) and 56 diseased sites (P-D group) in 14 patients with chronic periodontitis. The plaque samples were analyzed by polymerase chain reaction, and possible correlations between the F. alocis detection rate and the bleeding index, probing depth, or clinical attachment level were determined. RESULTS: The detection levels of F. alocis increased in both healthy and diseased groups. The lowest level at 30.88% (21/68) was noted in the H group, whereas the highest level at 91.07% (51/56) was obtained from the P-D group. A significant correlation was found between the F. alocis detection levels and periodontal disease condition (P < 0.000 1). Further analyses showed that a significant correlation also existed between the detection level of F. alocis and the abnormal clinical periodontal parameters, namely, bleeding index, probing depth, and clinical attachment loss. The odds ratios were 5.26, 8.85, and 11.65, respectively. CONCLUSION: F. alocis was found at increased-levels in subjects with periodontal disease. The presence of F. alocis increases the risk of sites with abnormal clinical periodontal parameters.

[Research progress on the relationship between Porphyromonas gingivalis and oral squamous cell carcinoma].

Substantial evidence supports the relationship between chronic inflammation and cancer development. Numerous studies suggest that chronic inflammatory disease, such as periodontitis, contributes to head and neck squamous cell carcinoma development. Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial regions. Porphyromonas gingivalis, one of the most important pathogens in association with periodontal disease, might have a potential correlation with OSCC. Along with the development of molecular biological techniques, the association between Porphyromonas gingivalis and OSCC has been greatly emphasized in recent years. This review summarizes the association between these variables and the potential mechanisms involved in such relationship.

[Effect of glutaredoxin on oxidative stress of umbilical vein endothelial cell exposed to Porphyromonas gingivalis lipo- polysaccharide].

OBJECTIVE: This study measures the glutaredoxin (Grx) gene and protein expression in umbilical vein endothelial cells upon exposure to Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS). The involvement of the Akt-signaling pathway is also determined. METHODS: EA-hy926 cells were pretreated with 1,000 ng · mL⁻¹ P. gingivalis LPS for 4, 12, 18, and 24 h, and then real-time reverse transcription polymerase chain reaction was employed to detect Grx1 expression. The effect of Grx on Akt activity was investigated using Western blot for the control, LPS (1,000 ng · mL⁻¹ LPS), and carmus- tine (BCNU) groups (1,000 ng · mL⁻¹ LPS, and the EA-hy926 cells were pretreated with 25 µmol · ml⁻¹ BCNU for 30 min). RESULTS: Gene expression of Grx1 significantly increased in LPS group compared with that in the control group. The Grx1 expression reached the peak level in 12 h, and the variation between the expression in 4 and 12 h was significant (P < 0.05). After 12 h, the protein levels of Grx and phosphorylated-Akt (p-Akt) significantly increased in the LPS group (P < 0.05), whereas the BCNU group showed a considerable decrease in both Grx and p-Akt expression levels (P < 0.05). Moreover, a slight difference was observed in the total Akt protein levels in the three groups (P > 0.05). CONCLUSION: Grx expression increased upon exposure of EA-hy926 cells to the LPS. Akt activity could be inhibited by BCNU (a Grx inhibitor), which indicated that Akt might act as a downstream regulator of Grx.