Long-term hypercaloric diet exacerbates metabolic liver disease in PNPLA3 I148M animals.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a major health burden associated with the metabolic syndrome leading to liver fibrosis, cirrhosis and ultimately liver cancer. In humans, the PNPLA3 I148M polymorphism of the phospholipase patatin-like phospholipid domain containing protein 3 (PNPLA3) has a well-documented impact on metabolic liver disease. In this study, we used a mouse model mimicking the human PNPLA3 I148M polymorphism in a long-term high fat diet (HFD) experiment to better define its role for NAFLD progression. METHODS: Male mice bearing wild-type Pnpla3 (Pnpla3WT ), or the human polymorphism PNPLA3 I148M (Pnpla3148M/M ) were subjected to HFD feeding for 24 and 52 weeks. Further analysis concerning basic phenotype, inflammation, proliferation and cell death, fibrosis and microbiota were performed in each time point. RESULTS: After 52 weeks HFD Pnpla3148M/M animals had more liver fibrosis, enhanced numbers of inflammatory cells as well as increased Kupffer cell activity. Increased hepatocyte cell turnover and ductular proliferation were evident in HFD Pnpla3148M/M livers. Microbiome diversity was decreased after HFD feeding, changes were influenced by HFD feeding (36%) and the PNPLA3 I148M genotype (12%). Pnpla3148M/M mice had more faecal bile acids. RNA-sequencing of liver tissue defined an HFD-associated signature, and a Pnpla3148M/M specific pattern, which suggests Kupffer cell and monocytes-derived macrophages as significant drivers of liver disease progression in Pnpla3148M/M animals. CONCLUSION: With long-term HFD feeding, mice with the PNPLA3 I148M genotype show exacerbated NAFLD. This finding is linked to PNPLA3 I148M-specific changes in microbiota composition and liver gene expression showing a stronger inflammatory response leading to enhanced liver fibrosis progression.

16-membered ring macrolides and erythromycin induce ermB expression by different mechanisms.

BACKGROUND: Ribosome stalling on ermBL at the tenth codon (Asp) and mRNA stabilization are believed to be mechanisms by which erythromycin (Ery) induces ermB expression. Expression of ermB is also induced by 16-membered ring macrolides (tylosin, josamycin and spiramycin), but the mechanism underlying this induction is unknown. METHODS: We introduced premature termination codons, alanine-scanning mutagenesis and amino acid mutations in ermBL and ermBL2. RESULTS: In this paper, we demonstrated that 16-membered ring macrolides can induce ermB expression but not ermC expression. The truncated mutants of the ermB-coding sequence indicate that the regulatory regions of ermB whose expression is induced by Ery and 16-membered ring macrolides are different. We proved that translation of the N-terminal region of ermBL is key for the induction of ermB expression by Ery, spiramycin (Spi) and tylosin (Tyl). We also demonstrated that ermBL2 is critical for the induction of ermB expression by erythromycin but not by 16-membered ring macrolides. CONCLUSIONS: The translation of ermBL and the RNA sequence of the C-terminus of ermBL are critical for the induction of ermB expression by Spi and Tyl.

Bidirectional Role of NLRP3 During Acute and Chronic Cholestatic Liver Injury.

BACKGROUND AND AIMS: Cholestatic liver injury leads to cell death and subsequent inflammation and fibrosis. As shown for primary biliary cholangitis (PBC), the mechanisms and circuits between different cell death pathways leading to disease progression are incompletely defined. Common bile duct ligation (BDL) is a well-established murine model to mimic cholestatic liver injury. Here, we hypothesized that pyroptotic cell death by the Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3 (Nlrp3) inflammasome plays an essential role during human and murine cholestasis. APPROACH AND RESULTS: NLRP3 activation was analyzed in humans with cholestatic liver injury. Wild-type (WT) and Nlrp3-/- mice were subjected to BDL for 2 or 28 days. Chronic cholestasis in humans and mice is associated with NLRP3 activation and correlates with disease activity. Acute BDL in Nlrp3-deficient mice triggered increased inflammation as well as liver injury, associated with stronger apoptotic and necroptotic cell death. In contrast, NLRP3 deletion led to decreased liver injury and inflammation in chronic cholestasis. Moreover, bridging fibrosis was observed in WT, but not in NLRP3 knockout, mice 28 days after BDL. In contrast, lack of NLRP3 expression attenuated kidney injury and fibrosis after acute and chronic BDL. Importantly, administration of MCC950, an NLRP3 small molecule inhibitor, reduced BDL-induced disease progression in WT mice. CONCLUSIONS: NLRP3 activation correlates with disease activity in patients with PBC. NLRP3 has a differential role during acute and chronic cholestatic liver injury in contrast to kidney injury. Disease progression during chronic cholestasis can be targeted through small molecules and thus suggests a potential clinical benefit for humans, attenuating liver and kidney injury.

Acupoint Catgut Embedding as Adjunctive Therapy for Patients With Gallstones.

AIMS OF THIS STUDY: A randomized clinical trial was undertaken to investigate the efficacy of acupoint catgut embedding (ACE) as adjunctive therapy to tauroursodeoxycholic acid (TUDCA) therapy on gallbladder emptying and clinical symptoms in patients with gallstone disease. MATERIALS AND METHODS: Between August 2018 and January 2019, 70 patients with gallstones in our hospital were enrolled in this prospective clinical trial. All the patients were randomly divided into the ACE group (ACE+TUDCA treatment for 8 wk) and the Sham group (Sham ACE+TUDCA treatment for 8 wk). In the ACE group, all the patients were nightly given ACE every 2 weeks, and in 2 groups, every patient took TUDCA 500 mg at bedtime. The parameters about gallbladder emptying were detected by ultrasound before and after the treatment, and the clinical symptom scores were recorded at the same time points. RESULTS: A total of 63 patients with gallstone disease were included in our study, with 33 patients in the ACE group and 30 patients in the Sham group. In the ACE group, the empty volume (EV) and gallbladder ejection fraction (GBEF) were improved after treatment (P<0.05). Almost every symptom score (except symptom 7, P=0.15) and total score were decreased (P<0.05). In the Sham group, the symptom 1, 2, 4, 5 scores, and total score were significantly decreased (P<0.05). Moreover, the residual volume in the ACE group was significantly lower than in the Sham group (P=0.008). The EV and GBEF in the ACE group were higher than that in the Sham group (P<0.05). The score of symptom 6 in the ACE group was lower than that in the Sham group (P=0.008). CONCLUSION: ACE therapy could more effectively improve the gallbladder emptying with a shorter treatment course. Therefore, ACE+TUDCA therapy might be a time-saving treatment for gallstones.

Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis.

OBJECTIVE: There is a striking association between human cholestatic liver disease (CLD) and inflammatory bowel disease. However, the functional implications for intestinal microbiota and inflammasome-mediated innate immune response in CLD remain elusive. Here we investigated the functional role of gut-liver crosstalk for CLD in the murine Mdr2 knockout (Mdr2-/-) model resembling human primary sclerosing cholangitis (PSC). DESIGN: Male Mdr2-/-, Mdr2-/- crossed with hepatocyte-specific deletion of caspase-8 (Mdr2-/- /Casp8∆hepa) and wild-type (WT) control mice were housed for 8 or 52 weeks, respectively, to characterise the impact of Mdr2 deletion on liver and gut including bile acid and microbiota profiling. To block caspase activation, a pan-caspase inhibitor (IDN-7314) was administered. Finally, the functional role of Mdr2-/- -associated intestinal dysbiosis was studied by microbiota transfer experiments. RESULTS: Mdr2-/- mice displayed an unfavourable intestinal microbiota signature and pronounced NLRP3 inflammasome activation within the gut-liver axis. Intestinal dysbiosis in Mdr2-/- mice prompted intestinal barrier dysfunction and increased bacterial translocation amplifying the hepatic NLRP3-mediated innate immune response. Transfer of Mdr2-/- microbiota into healthy WT control mice induced significant liver injury in recipient mice, highlighting the causal role of intestinal dysbiosis for disease progression. Strikingly, IDN-7314 dampened inflammasome activation, ameliorated liver injury, reversed serum bile acid profile and cholestasis-associated microbiota signature. CONCLUSIONS: MDR2-associated cholestasis triggers intestinal dysbiosis. In turn, translocation of endotoxin into the portal vein and subsequent NLRP3 inflammasome activation contribute to higher liver injury. This process does not essentially depend on caspase-8 in hepatocytes, but can be blocked by IDN-7314.

Parathyroid hormone-related peptide (1-34) promotes tooth eruption and inhibits osteogenesis of dental follicle cells during tooth development.

Dental follicle cells (DFCs) activate and recruit osteoclasts for tooth development and tooth eruption, whereas DFCs themselves differentiate into osteoblasts to form alveolar bone surrounding tooth roots through the interaction with Hertwig's epithelial root sheath (HERS). Also during tooth development, parathyroid hormone-related peptide (PTHrP) is expressed surrounding the tooth germ. Thus, we aimed to investigate the effect of PTHrP (1-34) on bone resorption and osteogenesis of DFCs in vitro and in vivo. In vitro studies demonstrated that DFCs cocultured with HERS cells expressed higher levels of BSP and OPN than the DFCs control group, whereas cocultured DFCs treated with PTHrP (1-34) had lower expressions of ALP, RUNX2, BSP, and OPN than the cocultured DFCs control group. Moreover, we found PTHrP (1-34) inhibited osteogenesis of cocultured DFCs by inactivating the Wnt/ß-catenin pathway. PTHrP (1-34) also increased the expression of RANKL/OPG ratio in DFCs. Consistently, in vivo study found that PTHrP (1-34) accelerated tooth eruption and inhibited alveolar bone formation. Therefore, these results suggest that PTHrP (1-34) accelerates tooth eruption and inhibits osteogenesis of DFCs by inactivating Wnt/ß-catenin pathway.

Inactivation of caspase 8 in liver parenchymal cells confers protection against murine obstructive cholestasis.

BACKGROUND & AIMS: Caspase 8 (CASP8) is the apical initiator caspase in death receptor-mediated apoptosis. Strong evidence for a link between death receptor signaling pathways and cholestasis has recently emerged. Herein, we investigated the role of CASP8-dependent and independent pathways during experimental cholestasis. METHODS: Liver injury was characterized in a cohort of human sera (n = 28) and biopsies from patients with stage IV primary biliary cholangitis. In parallel, mice with either specific deletion of Casp8 in liver parenchymal cells (Casp8Δhepa) or hepatocytes (Casp8Δhep), and mice with constitutive Ripk3 (Ripk3-/-) deletion, were subjected to surgical ligation of the common bile duct (BDL) from 2 to 28 days. Floxed (Casp8fl/fl) and Ripk3+/+ mice were used as controls. Moreover, the pan-caspase inhibitor IDN-7314 was used, and cell death mechanisms were studied in primary isolated hepatocytes. RESULTS: Overexpression of activated caspase 3, CASP8 and RIPK3 was characteristic of liver explants from patients with primary biliary cholangitis. Twenty-eight days after BDL, Casp8Δhepamice showed decreased necrotic foci, serum aminotransferase levels and apoptosis along with diminished compensatory proliferation and ductular reaction. These results correlated with a decreased inflammatory profile and ameliorated liver fibrogenesis. A similar phenotype was observed in Ripk3-/- mice. IDN-7314 treatment decreased CASP8 levels but failed to prevent BDL-induced cholestasis, independently of CASP8 in hepatocytes. CONCLUSION: These findings show that intervention against CASP8 in liver parenchymal cells - specifically in cholangiocytes - might be a beneficial option for treating obstructive cholestasis, while broad pan-caspase inhibition might trigger undesirable side effects. LAY SUMMARY: Loss of caspase 8 - a protein involved in programmed cell death - in liver parenchymal cells protects against experimental cholestasis. Therefore, specific pharmacological intervention against caspase 8 might be a valid alternative for the treatment of obstructive cholestasis in the clinic, whereas broad pan-caspase inhibiting drugs might trigger undesirable side effects.

CX3CR1 is a gatekeeper for intestinal barrier integrity in mice: Limiting steatohepatitis by maintaining intestinal homeostasis.

UNLABELLED: Nonalcoholic fatty liver disease is seen as the hepatic manifestation of the metabolic syndrome and represents the most common liver disease in Western societies. The G protein-coupled chemokine receptor CX3CR1 plays a central role in several metabolic syndrome-related disease manifestations and is involved in maintaining intestinal homeostasis. Because diet-induced intestinal dysbiosis is a driver for nonalcoholic fatty liver disease, we hypothesized that CX3CR1 may influence the development of steatohepatitis. In two independent models of diet-induced steatohepatitis (high-fat diet and methionine/choline-deficient diet), CX3CR1 protected mice from excessive hepatic steatosis and inflammation, as well as systemic glucose intolerance. Lack of Cx3cr1 expression was associated with significantly altered intestinal microbiota composition, which was linked to an impaired intestinal barrier. Concomitantly, endotoxin levels in portal serum and inflammatory macrophages in liver were increased in Cx3cr1-/- mice, indicating an increased inflammatory response. Depletion of intestinal microbiota by administration of broad-spectrum antibiotics suppressed the number of infiltrating macrophages and promoted macrophage polarization in liver. Consequently, antibiotic-treated mice demonstrated a marked improvement of steatohepatitis. CONCLUSION: Microbiota-mediated activation of the innate immune responses through CX3CR1 is crucial for controlling steatohepatitis progression, which recognizes CX3CR1 as an essential gatekeeper in this scenario.

Correction of asymmetric facial deformity by contouring: indications and outcomes.

BACKGROUND: Facial asymmetry is usually due to unbalanced development of the lower jaw and zygoma and often results in esthetically unpleasant appearance. However, reasonable and systematic treatment of such an asymmetric face is rarely reported in the literature. This article aims to evaluate the effectiveness of surgical correction of asymmetric facial deformity and discuss their indications. METHODS: From July 2006 to November 2010, a total of 52 patients received contour reshaping procedures to correct their asymmetric faces. Those patients in whom the asymmetric facial deformities were initiated by hypertrophy of the mandible and zygoma without occlusion and temporomandibular joint problem were chosen for this study. The authors performed a modified reduction malarplasty to correct asymmetric middle face and mandibular outer cortex splitting ostectomy, mandibular "V-line" ostectomy, and rotation genioplasty to improve asymmetric lower face depending on individual asymmetric facial characteristics. The effectiveness was then evaluated through cephalometric radiographs, three-dimensional computed tomography, and presurgical and postsurgical standard facial photographs. RESULTS: The postoperative results of all 52 cases showed that the asymmetric face was effectively corrected without serious complications and the harmonious facial contour improved significantly. The final esthetic outcomes were quite satisfactory for both surgeons and patients. CONCLUSIONS: The results indicate that a variety of contouring techniques for facial asymmetric deformity could be carried out based on characteristics of asymmetric face, so as to acquire a symmetric and harmonious face in accordance with facial esthetics.

Surface and interface engineering of BiOCl nanomaterials and their photocatalytic applications.

BiOCl materials have received much attention because of their unique optical and electrical properties. Still, their unsatisfactory catalytic performance has been troubling researchers, limiting the application of BiOCl-based photocatalysts. Therefore, many researchers have studied the adjustment of BiOCl-based materials to enhance photocatalytic efficiency. This review focuses on surface and interface engineering strategies for boosting the photocatalytic performance of BiOCl-based nanomaterials, including forming oxygen vacancy defects, constructing metal/BiOCl, and the fabrication of semiconductor/BiOCl nanocomposites. The photocatalytic applications of the above composites are also concluded in photodegradation of aqueous pollutants, photocatalytic NO removal, photo-induced H2 production, and CO2 reduction. Special emphasis has been given to the modification methods of BiOCl and photocatalytic mechanisms to provide a more detailed understanding for researchers in the fields of energy conversion and materials sciences.

How the root bacterial community of Ficus tikoua responds to nematode infection: enrichments of nitrogen-fixing and nematode-antagonistic bacteria in the parasitized organs.

Plant-parasitic nematodes (PPNs) are among the most damaging pathogens to host plants. Plants can modulate their associated bacteria to cope with nematode infections. The tritrophic plant-nematode-microbe interactions are highly taxa-dependent, resulting in the effectiveness of nematode agents being variable among different host plants. Ficus tikoua is a versatile plant with high application potential for fruits or medicines. In recent years, a few farmers have attempted to cultivate this species in Sichuan, China, where parasitic nematodes are present. We used 16S rRNA genes to explore the effects of nematode parasitism on root-associated bacteria in this species. Our results revealed that nematode infection had effects on both endophytic bacterial communities and rhizosphere communities in F. tikoua roots, but on different levels. The species richness increased in the rhizosphere bacterial communities of infected individuals, but the community composition remained similar as compared with that of healthy individuals. Nematode infection induces a deterministic assembly process in the endophytic bacterial communities of parasitized organs. Significant taxonomic and functional changes were observed in the endophytic communities of root knots. These changes were characterized by the enrichment of nitrogen-fixing bacteria, including Bradyrhizobium, Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, and nematode-antagonistic bacteria, such as Pseudonocardia, Pseudomonas, Steroidobacter, Rhizobacter, and Ferrovibrio. Our results would help the understanding of the tritrophic plant-nematode-bacterium interactions in host plants other than dominant crops and vegetables and would provide essential information for successful nematode management when F. tikoua were cultivated on large scales.

Fecal Microbiota Transplantation Improves Clinical Symptoms of Fibromyalgia: An Open-Label, Randomized, Nonplacebo-Controlled Study.

Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label, randomized, nonplacebo-controlled clinical study. The numerical rating scale scores in the FMT group were slightly lower than the control group at 1 month (P > .05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < .001). Besides, compared with the control group, the Widespread Pain Index, Symptom Severity, Hospital Anxiety and Depression Scale, and Pittsburgh Sleep Quality Index scores were significantly lower in the FMT group at different time points (P < .001). After 6 months of treatment, there was a significant increase in serotonin (5-hydroxytryptamine) and gamma-aminobutyric acid levels (P < .001), while glutamate levels significantly decreased in the FMT group (P < .001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < .05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes in neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: FMT is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.

[Clinical observation of CT guided two needles puncturing crossed through disc for superior hypogastric block to manage intractable pelvic cancer pain].

OBJECTIVE: To observe the feasibility and clinical efficacy of CT guided two needles puncturing crossed through disc for superior hypogastric block with alcohol to manage intractable pelvic cancer pain. METHODS: Thirty-one cases of advanced pelvic cancer suffering from untreatable pain in lower abdomen in our hospital from December 2009 to May 2012 were analyzed, the patients were treated with both sides of superior hypogastric block with absolute alcohol by CT guided two needles puncturing crossed through L5-S1 interlaminar space. Complications during and after the surgery were recorded. To observe and follow-up visual analog scale pain scores (VAS) and the daily oral morphine consumption on just before operation, at 1 week, 1 and 3 months after operation. RESULTS: No case suffered serious complication. A week later of surgery the curative effect of 20 patients: clinical cure in 17 cases, excellent in 14 cases, the effective rate was 100%. Compared with preoperation, The score of VAS on 1 week, 1 and 3 months after the surgery (2.0±0.7, 2.3±0.6, 3.0±0.4) were strikingly lower than before operation (7.7±0.7, P < 0.01); The daily oral dose of morphine of post-operation were significantly decreased in the three time points ((35±17) mg, (42±22) mg and (53±19) mg respectively) than the dose of pre-operation ((201±119)mg, P < 0.01). CONCLUSION: Superior hypogastric block with alcohol with double needles crossed transdiscal approach may be a safe, simple and effective method for relieving the severe pain of advanced pelvic cancer patients.

Recent Advances in Black TiO2 Nanomaterials for Solar Energy Conversion.

Titanium dioxide (TiO2) nanomaterials have been widely used in photocatalytic energy conversion and environmental remediation due to their advantages of low cost, chemical stability, and relatively high photo-activity. However, applications of TiO2 have been restricted in the ultraviolet range because of the wide band gap. Broadening the light absorption of TiO2 nanomaterials is an efficient way to improve the photocatalytic activity. Thus, black TiO2 with extended light response range in the visible light and even near infrared light has been extensively exploited as efficient photocatalysts in the last decade. This review represents an attempt to conclude the recent developments in black TiO2 nanomaterials synthesized by modified treatment, which presented different structure, morphological features, reduced band gap, and enhanced solar energy harvesting efficiency. Special emphasis has been given to the newly developed synthetic methods, porous black TiO2, and the approaches for further improving the photocatalytic activity of black TiO2. Various black TiO2, doped black TiO2, metal-loaded black TiO2 and black TiO2 heterojunction photocatalysts, and their photocatalytic applications and mechanisms in the field of energy and environment are summarized in this review, to provide useful insights and new ideas in the related field.

An in vivo evaluation of clear aligners for optimal orthodontic force and movement to determine high-efficacy and periodontal-friendly aligner staging.

Objectives: To investigate the effect of aligner displacement on tooth movement and periodontal health to improve the efficiency of aligner treatment and explore the mechanism in vivo. Methods: A two-tooth site was established by a finite element (FE) model to virtually evaluate aligner staging. A randomized controlled experiment was conducted when the tooth sites in beagles were treated with fixed or aligner appliances with different movement and force, and tooth movement and internal structure were recorded during the alignment. After sacrificing five dogs, bone-periodontal ligament (PDL)-tooth specimens were removed and processed to conduct uniaxial compression and tensile tests as well as micro-CT imaging and histological analysis. Results: Three displacements of 0.25, 0.35 and 0.45 mm were obtained from FE analysis and applied in beagles. In general, aligners had poorer performance on movement compared to fixed systems in vivo, but the aligner with a staging of 0.35 mm had the highest accuracy (67.46%) (P < 0.01). Loaded with severe force, fixed sites exhibited tissue damage due to excess force and rapid movement, while aligners showed better safety. The PDL under a 0.35-mm aligner treatment had the highest elastic modulus in the biomechanical test (551.4275 and 1298.305 kPa) (P < 0.05). Conclusions: Compared to fixed appliances, aligners achieve slightly slower movement but better periodontal condition. Aligners with an interval of 0.35 mm have the highest accuracy and best PDL biomechanical and biological capacities, achieving the most effective and safest movement. Even with complexity of oral cavity and lack of evaluation of other factors, these results provide insight into faster displacement as a method to improve the efficacy of aligners.

High-Crystallinity BiOCl Nanosheets as Efficient Photocatalysts for Norfloxacin Antibiotic Degradation.

Semiconductor photocatalysts are essential materials in the field of environmental remediation. Various photocatalysts have been developed to solve the contamination problem of norfloxacin in water pollution. Among them, a crucial ternary photocatalyst, BiOCl, has attracted extensive attention due to its unique layered structure. In this work, high-crystallinity BiOCl nanosheets were prepared using a one-step hydrothermal method. The obtained BiOCl nanosheets showed good photocatalytic degradation performance, and the degradation rate of highly toxic norfloxacin using BiOCl reached 84% within 180 min. The internal structure and surface chemical state of BiOCl were analyzed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman, Fourier transform infrared spectroscopy (FTIR), UV-visible diffuse reflectance (UV-vis), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectra (XPS), and photoelectric techniques. The higher crystallinity of BiOCl closely aligned molecules with each other, which improved the separation efficiency of photogenerated charges and showed high degradation efficiency for norfloxacin antibiotics. Furthermore, the obtained BiOCl nanosheets possess decent photocatalytic stability and recyclability.

The Effects of Ginkgo biloba Extract on Autophagy in Human Macrophages Stimulated by Cigarette Smoke Extract.

OBJECTIVE: To investigate the effects of Ginkgo biloba extract (GBE) on autophagy in human macrophages stimulated by cigarette smoke extract (CSE). METHODS: The human monocyte cell line U937 was cultured in vitro, and phorbol ester (PMA) was added to the cell culture medium to induce differentiation into human macrophages. CSE was prepared by traditional methods for experiments. The cells were divided into four groups: the blank group, the CSE model group, the GBE + CSE group, and the rapamycin + CSE group. Immunofluorescence was used to identify human macrophages, transmission electron microscopy was used to observe the ultrastructure of human macrophages in each group, ELISA was used to measure the amount of IL-6 and IL-10 in the supernatant from each group of cells, the mRNA levels of p62, ATG5, ATG7, and Rab7 were measured by real-time qPCR, and the protein expression levels of p62, ATG5, ATG7, and Rab7 were measured by Western blotting. RESULTS: U937 cells were successfully differentiated into human macrophages after induction with PMA. The CSE model group had many more autophagosomes than the blank group. Compared with the CSE model group, the GBE + CSE group and the rapamycin + CSE group had significantly more autophagolysosomal. Compared with the other groups, the CSE model group had a higher level of IL-6 but a lower level of IL-10 in the supernatant (p < 0.05). Compared with the blank group, the mRNA and protein expression levels of p62 in the CSE model group were significantly decreased, while the mRNA and protein expression levels of ATG5 and ATG7 were significantly increased in the CSE model group (p < 0.05). No difference was found in the mRNA and protein expression levels of Rab7 between the blank group and the CSE model group. Compared with the CSE model group, the IL-6 level in the GBE + CSE group and the rapamycin + CSE group cell culture supernatant decreased significantly, p62 mRNA and protein expression significantly decreased, while ATG5, ATG7, and Rab7 mRNA and protein expression levels were significantly increased (p < 0.05). Moreover, increased LC3-II/LC3-I ratio were also found in the GBE + CSE group and the rapamycin + CSE group compared with the CSE model group. CONCLUSIONS: GBE could promote the fusion of autophagosomes and lysosomes in human macrophages, enhance the autophagy function of human macrophages, and reduce the damaging effect of CSE on the autophagy function of macrophages.

Bi/Mn-Doped BiOCl Nanosheets Self-Assembled Microspheres toward Optimized Photocatalytic Performance.

Doping engineering of metallic elements is of significant importance in photocatalysis, especially in the transition element range where metals possess empty 'd' orbitals that readily absorb electrons and increase carrier concentration. The doping of Mn ions produces dipole interactions that change the local structure of BiOCl, thus increasing the specific surface area of BiOCl and the number of mesoporous distributions, and providing a broader platform and richer surface active sites for catalytic reactions. The combination of Mn doping and metal Bi reduces the forbidden bandwidth of BiOCl, thereby increasing the absorption in the light region and strengthening the photocatalytic ability of BiOCl. The degradation of norfloxacin by Bi/Mn-doped BiOCl can reach 86.5% within 10 min. The synergistic effect of Mn doping and Bi metal can change the internal energy level and increase light absorption simultaneously. The photocatalytic system created by such a dual-technology combination has promising applications in environmental remediation.

Construction of 2D/2D Mesoporous WO3/CeO2 Laminated Heterojunctions for Optimized Photocatalytic Performance.

Photocatalytic elimination of antibiotics from the environment and drinking water is of great significance for human health. However, the efficiency of photoremoval of antibiotics such as tetracycline is severely limited by the prompt recombination of electron holes and slow charge migration efficacy. Fabrication of low-dimensional heterojunction composites is an efficient method for shortening charge carrier migration distance and enhancing charge transfer efficiency. Herein, 2D/2D mesoporous WO3/CeO2 laminated Z-scheme heterojunctions were successfully prepared using a two-step hydrothermal process. The mesoporous structure of the composites was proved by nitrogen sorption isotherms, in which sorption-desorption hysteresis was observed. The intimate contact and charge transfer mechanism between WO3 nanoplates and CeO2 nanosheets was investigated using high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy measurements, respectively. Photocatalytic tetracycline degradation efficiency was noticeably promoted by the formation of 2D/2D laminated heterojunctions. The improved photocatalytic activity could be attributed to the formation of Z-scheme laminated heterostructure and 2D morphology favoring spatial charge separation, confirmed by various characterizations. The optimized 5WO3/CeO2 (5 wt.% WO3) composites can degrade more than 99% of tetracycline in 80 min, achieving a peak TC photodegradation efficiency of 0.0482 min-1, which is approximately 3.4 times that of pristine CeO2. A Z-scheme mechanism is proposed for photocatalytic tetracycline by from WO3/CeO2 Z-scheme laminated heterojunctions based on the experimental results.

Colitis ameliorates cholestatic liver disease via suppression of bile acid synthesis.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree. The majority of PSC patients suffer from concomitant inflammatory bowel disease (IBD), which has been suggested to promote disease development and progression. However, the molecular mechanisms by which intestinal inflammation may aggravate cholestatic liver disease remain incompletely understood. Here, we employ an IBD-PSC mouse model to investigate the impact of colitis on bile acid metabolism and cholestatic liver injury. Unexpectedly, intestinal inflammation and barrier impairment improve acute cholestatic liver injury and result in reduced liver fibrosis in a chronic colitis model. This phenotype is independent of colitis-induced alterations of microbial bile acid metabolism but mediated via hepatocellular NF-κB activation by lipopolysaccharide (LPS), which suppresses bile acid metabolism in-vitro and in-vivo. This study identifies a colitis-triggered protective circuit suppressing cholestatic liver disease and encourages multi-organ treatment strategies for PSC.