Biomechanism of abnormal stress on promoting osteoarthritis of temporomandibular joint through Piezo1 ion channel.

OBJECTIVE: This study aimed to investigate whether flow fluid shear stress (FFSS)-mediated signal transduction affects the function of Piezo1 ion channel in chondrocyte and to further explore the role of mechanical overloading in development of temporomandibular joint osteoarthritis (TMJ OA). METHODS: Immunohistochemical staining was used to determine the expression of Piezo1 in TMJ OA tissue collected from rat unilateral anterior crossbite (UAC) models. Chondrocytes harvested from normal adult SD rats were treated with FFSS (0, 4, 8, 12 dyn/cm2) in vitro. Immunofluorescent staining, real-time polymerase chain reaction, western blotting, flow cytometry and phalloidin assay were performed to detect the changes of cellular morphology as well as the expression of Piezo1 and certain pro-inflammatory and degradative factors in chondrocyte. RESULTS: Immunohistochemical analysis revealed that significantly increased Piezo1 expression was associated with UAC stimulation (p < .05). As applied FFSS escalated (4, 8 and 12 dyn/cm2), the expression levels of Piezo1, ADAMTS-5, MMP-13 and Col-X gradually increased, compared with the non-FFSS group (p < .05). Administering Piezo1 ion channel inhibitor to chondrocytes beforehand, it was observed that expression of ADAMTS-5, MMP-13 and Col-X was substantially decreased following FFSS treatment (p < .05) and the effect of cytoskeletal thinning was counteracted. The activated Piezo1 ion channel enhanced intracellular Ca2+ excess in chondrocytes during abnormal mechanical stimulation and the increased intracellular Ca2+ thinned the cytoskeleton of F-actin. CONCLUSIONS: Mechanical overloading activates Piezo1 ion channel to promote pro-inflammation and degradation and to increase Ca2+ concentration in chondrocyte, which may eventually result in TMJ OA.

Silver-catalyzed P-centered anion nucleophilic addition to isocyanide: access to 2-phosphinoyl indoles/indol-3-ols.

A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and practical synthesis of a wide range of 2-phosphinoyl indole and indol-3-ol derivatives. Unlike the well-documented synthesis of phosphorus-functionalized heterocycles via a P-centered radical, an anionic reactivity profile of phosphine oxides is most likely involved in this domino transformation.

Access to 2-thio/selenoquinolines via domino reaction of isocyanides with sulfur and selenium in water.

A domino reaction of o-alkenylaryl isocyanides with elemental sulfur and selenium in pure water was developed for the efficient and green synthesis of quinoline-2-thione and diquinolyl diselenide derivatives. Mechanistical investigation reveals that intramolecular nucleophilic addition of an alkenyl group to the in situ generated isothio/isoselenocyanate accounts for the formation of a quinoline-ring. Moreover, this transformation is also amendable for the convenient preparation of 2-fluoromethylthio-/seleno-quinolines by a one-pot three-component reaction.

A Flexible and Highly Sensitive Pressure Sense Electrode Based on Cotton Pulp for Wearable Electronics.

Flexible pressure sensors with high sensitivity have great potential applications in wearable electronics. However, it is still a great challenge to prepare sense electrodes with high flexibility, high sensitivity, and high electrochemical performance. Here, we propose a novel and simple method for carbonizing cotton fibers as excellent electrically conductive materials. Moreover, carbonized cotton fiber (CCF) and polydimethylsiloxane (PDMS) were assembled into a flexible sense electrode. The CCF/PDMS electrode shows a high sensitivity of 10.8 kPa-1, a wide response frequency from 0.2-2.0 Hz, and durability over 900 cycles. The combined CCF/PDMS sensors can monitor human movement and pulse vibration, showing the enormous potential for use in wearable device technology. Additionally, the CCF/PDMS can be used as electrodes with a specific capacitance of 332.5 mF cm-2 at a current density of 5 mA cm-2, thanks to their high electrical conductivity and hydrophilicity, demonstrating the promising prospect of flexible supercapacitors.

Association of HMGB1 levels in synovial fluid with the severity of temporomandibular joint osteoarthritis.

BACKGROUND: HMGB1 usually serves as a damage-associated molecular pattern (DAMP) molecule (also known as alarmin) that regulates the inflammatory and immune responses via different receptors or direct uptake. Numerous studies have reported the association between HMGB1 and inflammatory diseases; however, its role in temporomandibular joint (TMJ) osteoarthritis (OA) has not been elucidated. In this retrospective study, we aimed to investigate HMGB1 levels in the synovial fluid (SF) in patients with TMJOA and TMID, their correlation with TMJOA and TMID severity, and the therapeutic effect of sodium hyaluronate (hyaluronic acid, HA) on TMJOA. METHODS: SF samples were analyzed for 30 patients with TMJ internal derangement (TMJID) and TMJOA, along with visual analog scale (VAS) scores, radiographic stages, and mandibular functional limitations. The SF levels of HMGB1, IL-1ß, IL-18, PGE2, RAGE, TLR4, and iNOS were determined via an enzyme-linked immunosorbent assay. To evaluate the therapeutic effects of HA, pre-treatment and post-treatment clinical symptoms were also compared in patients of the TMJOA group who had received an intra-articular injection of HA. RESULTS: VAS and Jaw Functional Limitation Scale (JFLS) scores were significantly higher in the TMJOA group than in the TMNID group, as were SF levels of HMGB1, TLR4, IL-1ß, IL-18, PGE2, and iNOS. The synovial HMGB1 level was positively correlated with the VAS score (r = 0.5512, p = 0.0016) and mandibular functional limitations (r = 0.4684, p = 0.0054). The cut-off value for the HMGB1 level as a diagnostic biomarker was 986.8 pg/ml. The SF level of HMGB1 yielded an area under the curve value (AUC) of 0.8344 for predicting TMJOA. HA alleviated TMJ disorders by significantly reducing the VAS score and improving the maximum extent of mouth opening in both the TMJID and TMJOA groups (p < 0.05). Moreover, patients in both the TMJID and TMJOA groups exhibited significant improvement in the JFLS score following HA treatment. CONCLUSIONS: Our results indicate that HMGB1 is a potential marker for predicting the severity of TMJOA. Intra-articular HA injection exerts a positive therapeutic effect on TMJOA; however, further investigations are warranted to validate its therapeutic effect in the late phase of visco-supplementation treatment.

A Particleboard Surface Defect Detection Method Research Based on the Deep Learning Algorithm.

Particleboard surface defects have a significant impact on product quality. A surface defect detection method is essential to enhancing the quality of particleboard because the conventional defect detection method has low accuracy and efficiency. This paper proposes a YOLO v5-Seg-Lab-4 (You Only Look Once v5 Segmentation-Lab-4) model based on deep learning. The model integrates object detection and semantic segmentation, which ensures real-time performance and improves the detection accuracy of the model. Firstly, YOLO v5s is used as the object detection network, and it is added into the SELayer module to improve the adaptability of the model to receptive field. Then, the Seg-Lab v3+ model is designed on the basis of DeepLab v3+. In this model, the object detection network is utilized as the backbone network of feature extraction, and the expansion rate of atrus convolution is reduced to the computational complexity of the model. The channel attention mechanism is added onto the feature fusion module, for the purpose of enhancing the feature characterization capabilities of the network algorithm as well as realizing the rapid and accurate detection of lightweight networks and small objects. Experimental results indicate that the proposed YOLO v5-Seg-Lab-4 model has mAP (Mean Average Precision) and mIoU (Mean Intersection over Union) of 93.20% and 76.63%, with a recognition efficiency of 56.02 fps. Finally, a case study of the Huizhou particleboard factory inspection is carried out to demonstrate the tiny detection accuracy and real-time performance of this proposed method, and the missed detection rate of surface defects of particleboard is less than 1.8%.

Ionic Reactivity of 2-Isocyanoaryl Thioethers: Access to 2-Halo and 2-Aminobenzothia/Selenazoles.

An ionic cascade insertion/cyclization reaction of thia-/selena-functionalized arylisocyanides has been successfully developed for the efficient and practical synthesis of 2-halobenzothiazole/benzoselenazole derivatives. This synthetic protocol, incorporating a halogen atom when forming the five-membered ring of benzothia/selenazoles, is different from the existing ones, where halogenation of the preformed benzothia/selenazole precursors happens. Additionally, a facile access to 2-aminobenzothiazoles is also achieved by the one-pot cascade reaction of 2-isocyanoaryl thioethers, iodine, and amines.

Immunohistochemical analysis of pyroptosis-related protein expression in IgG4-related sialadenitis.

BACKGROUND: NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3)-induced pyroptosis is involved in the development of a variety of autoimmune diseases, but its role in IgG4-related sialadenitis (IgG4-RS) is unclear. METHODS: Salivary gland tissues from 19 patients with IgG4-RS were designated the experimental group, and peritumoral tissues from 20 patients with benign salivary gland tumours were designated the control group. The cell morphology and fibrosis in the IgG4-RS samples were observed by haematoxylin-eosin (H&E) and Masson trichrome (MT) staining. Immunohistochemical (IHC) staining was used to determine pyroptosis-related proteins (NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD), Caspase-1, GSDMD (gasdermin family members, including digestive dermatin D), interleukin 1ß (IL-1ß), and interleukin 18 (IL-18)) expression levels. RESULTS: Increased lymphoid follicle proliferation, germinal centre plasma cell infiltration, and irregular fibrosis were observed in the experimental group compared with the control group. The NLRP3, ASC, Caspase-1, GSDMD, IL-1ß, and IL-18 levels were significantly higher in the experimental group than in the control group (p < 0.0001). CONCLUSION: This study suggested that pyroptosis-related proteins might be involved in IgG4-RS pathogenesis. However, the specific cellular pathway involved and whether multiple cell death pathways contribute to the occurrence of IgG4-RS still need to be further studied.

A comparative analysis of NLRP3-related inflammatory mediators in synovial fluid in temporomandibular joint osteoarthritis and internal derangement.

BACKGROUND: The nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome signaling pathway is a highlighted topic in the field of inflammation. However, there is little research on the relationship between the NLRP3 inflammasome pathway and temporomandibular joint osteoarthritis (TMJOA). The aim of this study was to examine the expression of inflammatory mediators related to the NLRP3 inflammasome in the synovial fluid of patients with condylar cartilage degeneration and verify the clinical effects of sodium hyaluronic acid (HA) treatment on TMJOA. METHODS: Patients diagnosed with temporomandibular joint internal derangement (TMJID) without condylar defects and TMJOA with condylar defects were divided into two groups. There were thirty patients in each group, and inflammatory mediators related to the NLRP3 inflammasome, including interleukin-1 beta (IL-1ß), IL-18, NLRP3, and cysteinyl aspartate specific proteinase 1 (CASP1), in synovial fluid were measured by enzyme-linked immunosorbent assay (ELISA). Eighteen patients in the TMJOA group were retested after two HA treatments to evaluate the therapeutic effects of HA. RESULTS: IL-1ß, IL-18, NLRP3 and CASP1 were all positive in the two groups, and TMJOA patients with condylar defects had higher expression of these molecules than TMJID patients (P < 0.05). IL-1ß, IL-18, and NLRP3 were decreased after two HA treatments (P<0.05), but there was no significant difference in CASP1 after two HA injections (P = 0.549). CONCLUSIONS: The NLRP3 inflammasome signaling pathway may be involved in condylar degeneration. HA could reduce some inflammatory molecules to alleviate inflammation.

Biofunctional Extracellular Matrix-Polycaprolactone-Hydroxyapatite Scaffold and Synovium Mesenchymal Stem Cells/Chondrocytes for Repairing Cartilage Defects.

Articular cartilage defects and degeneration can be caused by multiple factors, and the current clinical treatment schemes for pathological changes are relatively limited. Engineered cartilage tissue represents an alternative therapy for repairing cartilage defects in regenerative medicine. The scaffold material is considered the framework of tissue engineering; thus, scaffold material selection plays a crucial role in the therapy outcome. Polycaprolactone (PCL)-hydroxyapatite (HA) has been applied as a scaffold material for bone and cartilage tissue engineering with nontoxic, harmless metabolites and proper physical properties. The extracellular matrix (ECM) is mainly composed of collagen and proteoglycan, as well as a large number of growth factors and cytokines, which provide a tissue-specific microenvironment for host cells. Adipose-derived stem cells are pluripotent stem cells, and transforming growth factor-ß3 (TGF-ß3) enables mesenchymal stem cells to promote ECM production. This study, via in vitro and in vivo experiments, elucidated that the synovium mesenchymal stem cells (SMSCs) + chondrocytes + ECM-PCL-HA repair system, which is constructed upon the ECM-PCL-HA scaffold material, exhibits an adequate chondrogenic ability and reparatory effect. Overall, ECM-PCL-HA can be defined as a biofunctional scaffold material. The SMSCs + chondrocytes + ECM-PCL-HA repair system showed good confluency between the new cartilage and the surface, as well as the interface of the adjacent host cartilage. Furthermore, the structure of new cartilage tissue is consistent with adjacency. Thus, it can be used as a preferred plan for articular cartilage defect repair. Impact statement Studies investigating the chondrogenic ability and reparatory effect of the synovium mesenchymal stem cells (SMSCs) + chondrocytes + extracellular matrix (ECM)-polycaprolactone (PCL)-hydroxyapatite (HA) repair system provided a theoretical and practical basis for choosing ECM-PCL-HA as the scaffold material for cartilage tissue engineering. In this study, the transforming growth factor-ß3 (TGF-ß3) gene was introduced into adipose-derived stem cells (ADSCs) using a lentiviral vector to enhance ECM production. The decellularized ADSCs-ECM-PCL-HA acted as a biofunctional scaffold material with suitable physicochemical properties, which was advantageous for SMSC and chondrocyte adhesion and growth. Lastly, the SMSCs + chondrocytes + ECM-PCL-HA repair system showed excellent capability in the flush fusion state of the prosthetic surface and interface.

The value of high-resolution MRI in the diagnosis, efficacy of treatment, and prognosis of central nervous system vasculitis.

AIM OF THE STUDY: To explore the high-resolution magnetic resonance imaging (HR-MRI) characteristics of central nervous system (CNS) vasculitis and to explore the value of HR-MRI in the treatment effect and prognosis evaluation of CNS vasculitis. MATERIAL AND METHODS: During the follow-up of 24 patients diagnosed as CNS vasculitis by the Second Hospital of Hebei Medical University, 3.0T HR-MRI was used for imaging examination and HR-MRI characteristics were analysed. RESULTS: The affected vessel wall of 24 patients showed diffuse uniform centripetal thickening. The HR-MRI examination showed varying degrees of lumen stenosis, including 5 cases (20.8%) involving a single arterial segment, and 19 cases (79.2%) involving multiple arterial segments. And most cases (92.9%) showed grade 2 enhancement of the involved vessel wall. Except for one case involving the basilar artery at the same time, the remaining 23 cases involved only the anterior circulation vessels. We analysed and compared the affected vessels between the relapsed group and the non-relapsed group, and found that the average number of involved vascular segments was 6.5 ±3.4 (3-11) in the relapsed group and 3.5 ±2.1 (1-8) in the non-relapsed group, with a significant difference between the two groups (p = 0.039). CONCLUSIONS: The CNS vasculitis was more likely to involve the anterior circulation vessels. The number of affected vascular segments in the relapsed group of CNS vasculitis was higher than in the non-relapsed group, suggesting that the more vascular segments involved, the more prone to recurrence.

The effects of deposition time and current density on the electrochemical performance of flexible and high-performance MnO2@PFG composite electrodes.

A novel composite electrode has been fabricated by the direct deposition of MnO2 onto graphene networks surrounding a paper fiber (PFG). The paper fiber between graphene sheets could be used as a flexible substrate for MnO2 nanoparticles, and the microscopic morphologies and electrochemical performances of the MnO2@PFG electrodes were tuned via regulating the deposition current densities and deposition times. 3D graphene on PFG served as a highly conductive backbone with a high surface area for the deposition of the MnO2 nanoparticles, which provided high accessibility to electrolyte ions for shortening the diffusion paths. The MnO2-10-600 s@PFG composite electrode achieved a maximum specific capacitance of 878.6 mF cm-2 with an MnO2 loading mass of 3.62 mg cm-2 (specific capacitance of 187.7 F g-1) at a current density of 0.5 mA cm-2 in a 1 M NaSO4 aqueous solution. Additionally, the MnO2-10-600 s@PFG composite material with the most favorable composite ratio exhibited the highest energy density of 61.01 mW h cm-2, maximum power density of 1249.78 mW cm-2, excellent capacitance retention with no more than 7% capacitance loss after 10 000 cycles and good mechanical flexibility (about 91.06% of its original capacitance after 500 bending times). By combining the electric double layer capacitance of graphene networks with the pseudocapacitance of the MnO2 nanostructures, the flexible electrode showed much enhanced electrochemical capacitance behaviors with robust tolerance to mechanical deformation; thus, it is promising for being woven into textiles for wearable electronics.

Self-assembly of flexible graphene hydrogel electrode based on crosslinked pectin-cations.

Pectin, natural polysaccharide biopolymer, was chelated with cations (Mg2+/Ca2+) to form an interwoven framework. Herein, the graphene hydrogel electrodes were self-assembled by the synergistic effects of pectin-cations. The optimum combination proportion was determined, the Mg2+/Ca2+-pectin matrix cross-linked graphene hydrogel (Mg2+/Ca2+-PGH) electrodes exhibited a large specific capacitance of about 839.2 F g-1 with high coulombic efficiency of 191.8% at a current density of 1 A g-1. The assembled flexible supercapacitor displayed excellent stability (capacitance retention of 98.5% after 2000 charge/discharge cycles) and flexibility (the specific capacitance remained 98.4% of its original value after 500 folding/unfolding cycles). Such flexible and high-performance Mg2+/Ca2+-PGH electrodes are attractive in the field of lightweight, miniature and wearable energy storage devices.

[Logistic regression analysis of risk factors of temporomandibular disorder in undergraduates of Xinjiang Medical University].

PURPOSE: To investigate the prevalence of temporomandibular disorders (TMD) in undergraduates of Xinjiang Medical University and analyse its possible risk factors. METHODS: A sample of 700 medical students included 244 males and 456 females was selected from Xinjiang Medical University and underwent examination of temporomandibular joint, questionnaire survey. Their average age was 20.08±1.457 years. Prevalence of TMD was analyzed, and the possible risk factors associated with the disease were identified by logistic regression analysis with SPSS17.0 software package. RESULTS: The prevalence of TMD was 42.40% in this population. There was no difference between different ethnics. Chewing-side preference, bruxism，orthodontic treatment，tooth extraction，psychological factors，anterior overjet, posterior scissors-bite were the main risk factors which increased the occurrence of TMD. CONCLUSIONS: Poor oral habits, psychological factors and malocclusion were related to the development of TMD.

High-performance MnO2-deposited graphene/activated carbon film electrodes for flexible solid-state supercapacitor.

High theoretical capacitance of MnO2 nanoparticles were successfully electrodeposited on the conductive graphene/activated carbon (GN/AC) composite film, and the urchin type MnO2 microspheres were controlled by adjusting the electro-deposition reaction times. The GN/AC/MnO2-1200s composite electrodes exhibited a maximum specific capacitance of 1231 mF/cm2 (MnO2 loading mass of 7.65 mg/cm2 and the mass specific capacitance of 123 F/g) at a current density of 0.5 mA/cm2. The assembled flexible solid-state symmetric supercapacitor had a good mechanical flexibility (about 88.6% of its original capacitance after 500 bending times) and prominent cycling stability (about 82.8% retention in capacitance over 10000 cycles). More importantly, the device could possess a maximum energy density of 0.27 mW h/cm3 and a maximum power density of 0.02 W/cm3. These results well demonstrate a great potential for applications of GN/AC/MnO2 composite electrodes in flexible energy storage devices.

Rotenone, a mitochondrial respiratory complex I inhibitor, ameliorates lipopolysaccharide/D-galactosamine-induced fulminant hepatitis in mice.

The syntheses of inflammatory mediators are energy-intensive processes and the mitochondria play pivotal roles in supporting these energy-requiring molecular responses. In the present studies, a mitochondrial respiratory complex I inhibitor rotenone was administrated in mice with lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced fulminant liver injury and the prophylactic and therapeutic effects on tissue injury were evaluated. We found that pretreatment with rotenone suppressed the elevation of plasma aminotransferases, alleviated the histopathological abnormalities and improved the survival rate of LPS/D-Gal-challenged mice. Pretreatment with rotenone has no obvious effects on hepatic malondialdehyde (MDA) contents but it significantly inhibited the up-regulation of both hepatic mRNA level and plasma protein level of TNF-α and IL-6. In the rotenone-pretreated group, the elevation of hepatic caspase-3, caspase-8 and caspase-9 activities induced by LPS/D-Gal decreased and rotenone reduced the count of TUNEL-positive apoptotic hepatocytes. In addition, posttreatment with rotenone at 1h after LPS/D-Gal challenge also suppressed the elevation of plasma aminotransferases. These data suggest that mitochondrial complex I inhibition might be a potential approach for the control of inflammation.

Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury.

Metformin is a commonly used anti-diabetic drug with AMP-activated protein kinase (AMPK)-dependent hypoglycemic activities. Recent studies have revealed its anti-inflammatory and anti-oxidative properties. In the present study, the anti-oxidative potential of metformin and its potential mechanisms were investigated in a mouse model with carbon tetrachloride (CCl2)-induced severe oxidative liver injury. Our results showed that treatment with metformin significantly attenuated CCl2-induced elevation of serum aminotransferases and hepatic histological abnormalities. The alleviated liver injury was associated with decreased hepatic contents of oxidized glutathione (GSSG) and malondialdehyde (MDA). In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl4-induced elevation of hepatic H2O2 levels, but it had no obvious effects on the protein level of CAT. We also found that metformin increased the level of phosphorylated AMP-activated protein kinase (AMPK), but treatment with AMPK activator AICAR had no obvious effects on CAT activity. A molecular docking analysis indicated that metformin might interact with CAT via hydrogen bonds. These data suggested that metformin effectively alleviated CCl4-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT.

Protective effects of garcinol in mice with lipopolysaccharide/D-galactosamine-induced apoptotic liver injury.

Garcinol is a polyisoprenylated benzophenone derivative of Garcinia indica. Recent researches have revealed the antioxidant, anticancer and anti-inflammatory properties of garcinol. In the present study, the pharmacological effects of garcinol in lipopolysaccharide (LPS)-induced hepatic injury in D-galactosamine (D-Gal)-sensitized mice were investigated. We found that treatment with garcinol significantly decreased serum ALT and AST levels in LPS/D-Gal-exposed mice. These were accomplished with improved histological alterations in liver sections and reduced malondialdehyde (MDA) content in liver homogenates. Garcinol significantly reduced the acetylation level of NF-κB, but it had no obvious effects on the elevation of TNF-α or IL-6 in plasma or liver tissue. Garcinol significantly attenuated LPS/D-Gal-induced hepatic apoptosis as evidenced by reduced number of TUNEL-positive cells in liver sections. Our experiments also showed that garcinol markedly suppressed the cleavage of caspase-3 and significantly decreased the activities of caspase-3, -8, and -9 in liver tissues. In addition, garcinol obviously reduced the induction of Bax but did not alter the level of Bcl-2. These results indicated that garcinol might provide protective benefits in LPS/D-Gal-induced liver injury through suppressing apoptosis.

Potential role of catalase in mice with lipopolysaccharide/D-galactosamine-induced fulminant liver injury.

AIM: Lipopolysaccharide (LPS)-induced liver injury in D-galactosamine (D-Gal)-sensitized mice is a well-established animal model widely used in exploring the pathogenesis of fulminant hepatitis. Increasing evidence has indicated that reactive oxygen species (ROS)-induced oxidative injury may be involved in LPS/D-Gal-induced hepatitis. Catalase (CAT) is a major antioxidant enzyme while aminotriazole (ATZ) is commonly used as a CAT inhibitor. In the present study, the effects of ATZ on LPS/D-Gal-induced liver injury were investigated. METHODS: Fuliminant liver injury was induced by intraperitoneal injection of LPS combined with D-Gal, ATZ was administrated 0.5 h prior to LPS/D-Gal challenge. The degree of liver injury, the level of hepatic oxidative stress, the grade of hepatic apoptosis and the survival of experimental animals were determined. RESULTS: Our experimental data showed that treatment with ATZ significantly enhanced LPS/D-Gal-induced elevation of serum aspartate transaminase (AST) and alanine transaminase (ALT), exacerbated the hepatic histopathological abnormality and decreased the survival rate of experimental animals. ATZ inhibited the activity of CAT, increased the content of H2 O2 and the levels of malondialdehyde (MDA) in liver tissues. In addition, treatment with ATZ also enhanced LPS/D-Gal-induced hepatic apoptosis as evidenced by increased caspases activities in liver tissues and increased number of terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells in liver sections. CONCLUSION: These findings suggested that CAT might be involved in the progression of LPS/D-Gal-induced fulminant liver injury.

Negative transcriptional regulation of inflammatory genes by group B3 vitamin nicotinamide.

The water-soluble group B3 vitamin nicotinamide (NAM) is involved in a wide range of physical processes through biosynthetically converted to nicotinamide adenine dinucleotide (NAD(+)). In addition to its pivotal role in energy metabolism, NAD(+) is also the indispensable substrate of poly (ADP-ribose) polymerase-1 (PARP-1) and sirtuin 1 (SIRT1). PARP-1 and SIRT1 may catalyze the posttranslational poly(ADP-ribosyl)ation and acetylation of histones as well as non-histone proteins, such as nuclear factor kappa B and activator protein 1, which play crucial roles in transcriptional regulation of inflammatory genes. The NAD(+)-dependent modifications catalyzed by PARP-1 and SIRT1 liberate NAM, and NAM acts as feedback inhibitor of PARP-1 and SIRT1 through interacting with the enzymes at the binding site for NAD(+). There is increasing evidence that NAM effectively suppresses the expression of inflammatory genes and provides therapeutic benefits in various inflammation-based diseases. The mechanisms underlie the anti-inflammatory properties of NAM might involve the inhibition of PARP-1 and SIRT1.