Preventive effects of interleukin-6 in lipopolysaccharide/d-galactosamine induced acute liver injury via regulating inflammatory response in hepatic macrophages

Lipopolysaccharide/d-Galactosamine (LPS/d-Gal)-induced acute liver injury is characterized by significant inflammatory responses including TNF-α and interleukin-6 (IL-6) and is a widely applied experimental model for inflammation research. TNF-α is critical in the progression of LPS/d-Gal-induced liver injury. However, the role of IL-6 in this model is still unknown. In the present study, we aim to elucidate the involvement of IL-6 in the pathogenesis of acute liver injury induced by LPS/d-Gal in mice and its underlying mechanism. To induce acute liver injury, LPS (50 μg/kg body weight) and d-Gal (400 mg/kg body weight) were injected intraperitoneally in the C57BL/6 mice. The vehicle (saline) or a single dose of recombinant IL-6 (200 μg/kg body weight) was administered 2 h prior to LPS/d-Gal injection. Mice were sacrificed 2 h and 6 h after LPS/d-Gal injection. The results indicated that IL-6 treatment could protect mice from LPS/d-Gal-induced tissue damage, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation, as well as hepatocyte apoptosis and inflammation. Furthermore, in vitro study showed that IL-6 treatment could significantly suppress LPS-triggered expression of proinflammatory cytokines and chemokines, TNF-α, RANTES and MCP-1 in macrophages while promoting the expression of M2 markers, such as Arg-1 and Mrc-1 in macrophages. Taken together, these findings revealed a novel and unexpected role of IL-6 in ameliorating LPS/d-Gal-induced acute liver injury via regulating inflammatory responses in hepatic macrophages.     

Deflazacort alleviate pro-inflammatory cytokines expression,oxidative stress and histopathological alterations in collagen induced arthritis in Wistar rats

ObjectivesGlucocorticoids are important and frequently used class of anti-inflammatory drugs. Deflazacort (DFZ) is a glucocorticoid and an oxazolone derivative of prednisolone. As it has high anti-inflammatory and immunosuppressive potency, we studied inhibitory effect of DFZ on mediators regulating the pro-inflammatory response and oxidative stress induced in arthritis.MethodsFemale Wistar rats were immunized intradermally by collagen type II to induce collagen induced arthritis. Arthritic rats were treated with DFZ orally (6 mg kg⁻¹ body weight) until 28 days after the onset of clinical symptoms of disease. The effect of DFZ treatment in the rats was monitored by clinical scoring, biochemical parameters, immunohistochemistry and histopathological evaluation.ResultsDeflazacort significantly decreased the level of articular elastase, nitric oxide and lipid peroxidation whereas significantly increased the activity of catalase, superoxide dismutase and glutathione. Deflazacort down-regulated expression of pro-inflammatory molecules like TNF-α and COX-2. Histopathological evaluation revealed significant reduction of synovial hyperplasia and cellular infiltration in synovial membrane in DFZ treated group as compared to the diseased group.ConclusionsThis suggests that DFZ significantly down-regulates the expression of pro-inflammatory molecules such as TNF-α and COX-2 and alleviates the oxidative stress which make it a viable therapeutic option for treatment of arthritis.     

Synthesis of stable nanosilver particles (AgNPs) by the proteins of seagrass Syringodium isoetifolium and its biomedicinal properties

A simple eco-friendly approach for the hasty synthesis of stable, potent and benign silver nanoparticles (AgNPs) using seagrass, Syringodium isoetifolium was proposed and described here. The UV–Vis, DLS, XRD, AFM, FESEM, EDX and HRTEM analysis highly characterized and confirmed the presence of polydispersed (2–50 nm) spherical and stable AgNPs. FT-IR and phytochemical analysis suggested that the proteins act as reducing and also as capping agent. A hypothetical approach using bioinformatics tools revealed that the Phytochrome B protein of S. isoetifolium might be responsible for the biosynthesis of NPs. Furthermore, biosynthesized AgNPs showed magnificent antibacterial activity against thirteen clinical bacterial pathogens with maximum zone of inhibition of 14.3 ± 0.12 mm due to their smaller size and longer stability even at minimal nanomolar (nM) concentration. In addition, the MIC and MBC values also suggested the same. Moreover, the percentage of haemolysis (8.49 ± 3.10 to 73.34 ± 1.79%) and haemolytic index revealed the satisfactory biocompatibility of AgNPs that showed less/no haemolysis up to 3 nM concentration. Further, the toxicity effect of biosynthesized AgNPs against the brine shrimp, Artemia salina exhibited significantly increasing mortality (13 ± 4.7 to 100%) with LC₅₀ value at 4 nM concentration. Thus, the optical property, crystal structure, size, shape, stability, bactericidal activity, cytotoxicity, and biocompatibility apparently proved that the biologically synthesized AgNPs have typical properties of nanomaterials.     

Antioxidation,anti-inflammation and anti-apoptosis by paeonol in LPS/d-GalN-induced acute liver failure in mice

To evaluate the hepatoprotective effects and potential mechanisms of paeonol (Pae) against acute liver failure (ALF) induced by lipopolysaccharide (LPS)/d-galactosamine (d-GalN) in mice, we examined anti-oxidative, anti-inflammatory and anti-apoptotic activities of Pae. We found that Pae pretreatment markedly reduced the activities of alanine transaminase and aspartate transaminase as well as the histopathological changes induced by LPS/d-GalN. Catalase, glutathione and superoxide dismutase activities increased and reactive oxygen species activity decreased after Pae treatment compared with LPS/d-GalN treatment. Pretreatment with Pae also significantly inhibited the expression levels of iNOS, nitric oxide (NO), COX-2 and prostaglandin E₂ (PGE₂). In addition, Pae administration prevented the phosphorylated expression of IκB kinase, inhibitor kappa B in the nuclear factor-kappa B (NF-κB) signaling pathway, and suppressed the phosphorylated expression of extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase and p38 in the MAPK signaling pathway. Pretreatment with Pae also inhibited hepatocyte apoptosis by reducing the expression of caspases 3, 8, 9, and Bax, and increasing Bcl-2. In total, protective effects of Pae against LPS/d-GalN-induced ALF in mice are attributed to its antioxidative effect, inflammatory suppression in NF-κB and MARK signaling pathways, and inhibition of hepatocyte apoptosis inhibition. Therefore, Pae can be a potential therapeutic agent in attenuating LPS/d-GalN-induced ALF in the future.     

Three-dimensional hydrogel scaffolds facilitate in vitro self-renewal of human skin-derived precursors

Skin-derived precursors (SKPs) are multipotent cells with dermal stem cell properties. These easily available cells possess the capacity to reconstitute the skin in vivo, as well as a broader differentiation potential in vitro, which endows them with great prospects in regenerative medicine. However, the present authors’ group and others previously found that adult human SKPs (hSKPs) expanded deficiently in vitro, which largely counteracted their research and practical values. Taking the physiological micro-environment of hSKPs into consideration, the authors sought to establish a hydrogel scaffold-based three-dimensional (3-D) culture system for hSKPs in the present study. After comparing their morphology, growth characteristics, signature gene expression and differentiation potential in different hydrogels, the present authors found that a chemically defined hyaluronic acid and denatured collagen-based hydrogel system that mimicked the natural niche of hSKPs in the dermis could alleviate hSKP senescence, support hSKP proliferation as spheres, while largely retaining their properties and potential. This study suggested that recapitulating the in vivo stem cell niche by providing them with 3-D extracellular matrix environments could help them achieve better self-renewal in vitro. In addition, the animal-origin-free and biocompatible 3-D hydrogel system will certainly benefit fundamental research and clinical applications of hSKPs in the near future.     

A randomized,double-blind,multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D

This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D plus either SMC021 tablets (0.8 mg/d) or placebo for 36 months. The primary endpoint was the proportion of patients with a new vertebral fracture.The two groups were well balanced at baseline with regards to demographic and clinical data. No effect of SMC021 on preventing new vertebral fractures was observed, nor was any effect seen on new hip or non-vertebral fractures. Women receiving SMC021 had a mean 1.02% (± 0.12%) increase in lumbar spine bone mineral density (BMD) compared with a mean 0.18% (± 0.12%) increase in the placebo group by the end of the study (p < 0.0001). Similarly, small increases in BMD were observed at the femoral neck and hip in both groups. Levels of the biomarkers of bone turnover, urinary CTX-I and CTX-II, were 15% lower in the SMC021 group than in the placebo arm at 12 and 24 months, but not at 36 months. No change in quality of life between groups, assessed by the Qualeffo-14 questionnaire, was observed in either group between baseline and month 36. Pharmacokinetics analysis confirmed exposure to SMC021, but the drug levels were markedly lower than expected.Approximately 92% of subjects in each treatment group experienced an adverse event (AE), the majority of which were mild or moderate in intensity. AEs associated with SMC021 were primarily of gastrointestinal origin and included nausea, vomiting and abdominal pain, as well as hot flushes which were the reason for the slightly higher drop-out rate in the active treatment arm compared to placebo. The number of severe AEs was low in both groups. Thirty-five deaths were reported but none were considered treatment-related.Due to the lack of efficacy in preventing fractures, the development of the orally formulated calcitonin was terminated despite the promising results in earlier studies.     

Mesenteric desmoid fibromatosis with necrosis resembling sarcoma

Intra-abdominal desmoid fibromatosis is a benign but locally aggressive myofibroblastic neoplasm with no capacity to metastasize. Typical examples show an unremarkable homogeneous gross appearance with infiltrative borders and bland histology that pose little difficulty to the pathologist. Characteristically, fibromatoses lack worrisome features such as necrosis, hemorrhage and cavitation, which are usually seen in potentially higher grade tumors particularly gastrointestinal stromal tumor and other soft tissue sarcomas. Differentiating between these lesions is particularly important for prognostic and therapeutic implications. Herein a case of mesenteric desmoid fibromatosis in a 54-year-old woman is described, which demonstrated a pseudosarcomatous appearance both on radiology and gross examination because of the presence of central cavitation and necrosis.     

Filarial nematode infection in eclectus parrots (Eclectus roratus) in Taiwan

A total of 166 psittacines belonging to 22 species were received by the Animal Hospital of National Pingtung University of Science &; Technology (NPUST) from 2013 to 2015. Only eclectus parrots (Eclectus roratus) were identified as hosts for microfilariae. All eclectus parrots were adult birds and had been kept in Taiwan for more than three years. The relevance of filariae to eclectus parrots is evident as indicated by the 35.7% (5/14) infection rate. At necropsy, adult filarial nematodes 57–75?mm in length and 0.4–0.7?mm in width were found in the hepatic veins. The microfilariae were 170–230?μm in length. Histopathological examination confirmed that eggs and larvae were observed in the ovaries and uteri of female filariae. These nematodes were closely related to an unidentified Filaria sp. (KJ612514.1) as indicated by polymerase chain reaction (PCR) analysis and phylogenetic analysis of nucleotide sequences from 18S ribosomal DNA gene (18S rDNA), mitochondrial cytochrome c oxidase subunit 1 (COX1) gene, and internal transcribed spacers 1-5.8S ribosomal DNA gene (ITS 1-5.8S rDNA). However, structurally the filarial nematodes were similar to that of the Pelecitus sp. Eclectus parrot species are important pet birds and are highly traded, resulting in high uncertainty of the origin of the parasite infection. This study is the first of its kind to report the presence and potential impact of filarial nematode infection on eclectus parrots, suggesting parasite inspection prior to the international trade of these pet birds.