Ossification of posterior atlantoaxial membrane causing spinal stenosis - A case report.

Background: Ossification of the posterior atlantoaxial membrane (PAAM) is a rare cause of spinal cord compression. Case presentation: A 46-year-old woman with rheumatoid arthritis (RA) and a 2-year history of slowly progressive gait disturbance underwent surgery for right knee stiffness and right lower limb mild weakness. A neurologic examination revealed brisk deep tendon reflexes (DTR) and spasticity in her four limbs. A computed tomography (CT) scan revealed spinal stenosis caused by ossification of the PAAM, a rare cause of spinal cord compression. The patient's lower limbs weakness and walking capability were ameliorated post-surgery. Conclusions: Although the exact mechanism of ossification of PAAM remains unclear, chronic mechanical stress as well as persistent atlantoaxial instability may promote the development of the ossification.

A Single-Substrate Biosensor with Spin-Coated Liquid Crystal Film for Simple, Sensitive and Label-Free Protein Detection.

A liquid crystal (LC)-based single-substrate biosensor was developed by spin-coating an LC thin film on a dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (DMOAP)-decorated glass slide. Compared with the conventional sandwiched cell configuration, the simplified procedure for the preparation of an LC film allows the film thickness to be precisely controlled by adjusting the spin rate, thus eliminating personal errors involved in LC cell assembly. The limit of detection (LOD) for bovine serum albumin (BSA) was lowered from 10-5 g/mL with a 4.2-µm-thick sandwiched cell of the commercial LC E7 to 10-7 g/mL with a 4.2-µm-thick spin-coated E7 film and further to 10-8 g/mL by reducing the E7 film thickness to 3.4 µm. Moreover, by exploiting the LC film of the highly birefringent nematic LC HDN in the immunodetection of the cancer biomarker CA125, an LOD comparable to that determined with a sandwiched HDN cell was achieved at 10-8 g/mL CA125 using a capture antibody concentration an order of magnitude lower than that in the LC cell. Our results suggest that employing spin-coated LC film instead of conventional sandwiched LC cell provides a more reliable, reproducible, and cost-effective single-substrate platform, allowing simple fabrication of an LC-based biosensor for sensitive and label-free protein detection and immunoassay.

Liquid crystal-photopolymer composite films for label-free single-substrate protein quantitation and immunoassay.

Conventional liquid crystal (LC)-based biosensing at the LC-glass interface requires the assembly of an LC cell formed by two glass substrates with an LC film sandwiched in between. As most biochemical and clinical assays are performed on a single solid substrate, the feasibility of a single-substrate biodetection platform based on a thin film of LC-photopolymer composite was explored in this study. The LC mixture, consisting of nematic LC, E7 or AY40-006, doped with a small amount (≤ 5 wt%) of a photocurable prepolymer was spin-coated on a glass substrate modified with dimethyloctadecyl[3-trimethoxysilyl)propyl] ammonium chloride (DMOAP), a vertical alignment reagent, followed by irradiation with ultraviolet (UV) light. During the photopolymerization process, the accumulated and polymerized NOA65 at the LC-glass interface weakened the anchoring strength of DMOAP, resulting in a decrease in the pretilt angle of LC and allowing the LC molecules to be more easily disturbed in the presence of biomolecules, compared with vertically aligned LC in the absence of polymerized NOA65. Incorporating NOA65 in the LC film therefore provides a means for signal amplification. When an LC-photopolymer composite film consisting of AY40-006 and 4-wt% NOA65 was exposed to UV at 15 mW/cm2 for 30 s and utilized as the biosensing mesogen, the limits of detection were 1.6 × 10-12 g/ml for the direct detection of bovine serum albumin (BSA) and 2.1 × 10-8 g/ml for the immunoassay of the cancer biomarker CA125, significantly lower than those detected with AY40-006 alone or AY40-006/NOA65 mixture without UV irradiation. The results from this study offer a compelling implication on the biomedical application of LC-photopolymer composites in label-free and single-substrate biodetection.

Glutathione peroxidase 8 negatively regulates caspase-4/11 to protect against colitis.

Human caspase-4 and its mouse homolog caspase-11 are receptors for cytoplasmic lipopolysaccharide. Activation of the caspase-4/11-dependent NLRP3 inflammasome is required for innate defense and endotoxic shock, but how caspase-4/11 is modulated remains unclear. Here, we show that mice lacking the oxidative stress sensor glutathione peroxidase 8 (GPx8) are more susceptible to colitis and endotoxic shock, and exhibit reduced richness and diversity of the gut microbiome. C57BL/6 mice that underwent adoptive cell transfer of GPx8-deficient macrophages displayed a similar phenotype of enhanced colitis, indicating a critical role of GPx8 in macrophages. GPx8 binds covalently to caspase-4/11 via disulfide bonding between cysteine 79 of GPx8 and cysteine 118 of caspase-4 and thus restrains caspase-4/11 activation, while GPx8 deficiency leads to caspase-4/11-induced inflammation during colitis and septic shock. Inhibition of caspase-4/11 activation with small molecules reduces the severity of colitis in GPx8-deficient mice. Notably, colonic tissues from patients with ulcerative colitis display low levels of Gpx8 and high caspase-4 expression. In conclusion, these results suggest that GPx8 protects against colitis by negatively regulating caspase-4/11 activity.

Sclareol attenuates the development of atopic dermatitis induced by 2,4-dinitrochlorobenzene in mice.

Context: Atopic dermatitis is a common chronic inflammatory skin disease affecting up to 20% of children and 1% of adults worldwide. Treatment of atopic dermatitis include corticosteroids and immunosuppressants, such as calcineurin inhibitors and methotrexate. However, these treatments often bring about adverse effects including skin atrophy, osteoporosis, skin cancer, and metabolic syndrome. Objective: In this study, we evaluated the therapeutic effects and mechanisms of sclareol, a natural diterpene, on atopic dermatitis (AD)-like skin lesions induced by 2,4-dinitrochlorobenzene (DNCB) in mice. Materials and methods: To evaluate the effect of sclareol in vivo model, BALB/c mice were repeatedly injected intraperitoneally with sclareol (50 and 100 mg/kg) in 2,4-dinitrochlorobenzene (DNCB)-induced AD-like murine model. Major assays were enzyme-linked immunosorbent assay, histological analysis, flow cytometry, western blot analysis. Results: Intraperitoneal administration of sclareol (50 and 100 mg/kg) significantly attenuated AD-like symptoms, such as serum IgE levels, epidermal/dermal hyperplasia, and the numbers of infiltrated mast cells. In addition, systemic sclareol treatments reduced local pro-inflammatory cytokine concentrations, including IL-6, IL-1b, TNF-a, IL-4, IFN-g, and IL-17A, on AD-like lesions. Furthermore, we demonstrated that sclareol also suppressed T cell activation and the capability of cytokine productions (IFN-g, IL-4 and IL-17A) in response to DNCB stimulation. By examining the skin homogenate, we found that sclareol inhibited the AD-like severity likely through suppressions of both NF-kB translocation and phosphorylation of the MAP kinase pathway. Discussion and conclusions: Cumulatively, our results indicate that sclareol induced anti-inflammatory effects against the atopic dermatitis elicited by DNCB. Thus, sclareol is worth of being further evaluated for its potential therapeutic benefits for the clinical treatment of AD.

IgG4-related cerebral pseudotumor with perineural spreading along branches of the trigeminal nerves causing compressive optic neuropathy: A case report.

RATIONALE: Immunoglobulin G4-related disease (IgG4-RD) is characterized by tumor-like lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4-RD has been described in a variety of organ systems; however, it rarely involves the central nervous system. PATIENT CONCERNS: A 17-year-old woman visited our clinic with a complaint of blurred vision for the past 5 months. She also reported a painless right submandibular mass that had been present for 1 year. Her best-corrected visual acuity (BCVA) was 2.0 LogMAR, with an almost total visual field defect in the right eye. DIAGNOSES: Magnetic resonance imaging (MRI) revealed lobulated parasellar tumors with perineural spreading along branches of the trigeminal nerves causing right optic nerve compression. A craniotomy with tumor removal and submandibular gland biopsy was performed. Histopathological analysis of the tumor revealed stromal fibrosis with atypical lymphoid infiltrations. Histopathological and immunohistochemical analysis of the submandibular gland confirmed the diagnosis of IgG4-RD. INTERVENTIONS: The patient was administered 500mg/d of pulse methylprednisolone for 3 days, 500mg of intravenous rituximab every 2 weeks (for a total of 2 doses), and 500mg of intravenous pulse cyclophosphamide every month (for a total of 3 doses). OUTCOMES: Two months after the initiation of immunosuppressive therapy, the patient's BCVA returned to 0.1 LogMAR with visual field defect recovery. The follow-up MRI showed the almost complete disappearance of the previously contrast-enhanced lesions. LESSONS: Herein, we report a rare case of IgG4-RD presenting as a parasellar tumor and present a review of the related literature. Based on the case report, we propose that aggressive therapy with glucocorticoid, rituximab, and cyclophosphamide may potentially be useful for treating such cases.

Spontaneous resolution of acute gouty arthritis is associated with rapid induction of the anti-inflammatory factors TGFß1, IL-10 and soluble TNF receptors and the intracellular cytokine negative regulators CIS and SOCS3.

OBJECTIVE: The molecular basis for spontaneous resolution of acute gouty arthritis (GA) remains unclear. The hypothesis that extracellular and intracellular mechanisms play roles in resolving acute GA was tested. METHODS: Synovial fluid (SF) levels of transforming growth factor ß1 (TGFß1), interleukin 1 (IL-1) receptor antagonist (IL-1ra), IL-10 and soluble tumour necrosis factor (TNF) receptor I (sTNFRI) and II (sTNFRII) were measured by ELISA in patients with acute GA and osteoarthritis (OA). Monosodium urate (MSU) crystal-stimulated RAW264.7 mouse macrophages were analysed for cytokine inducible SH2-containing protein (CIS) and suppressors of cytokine signalling (SOCS)1-7 mRNA expression by reverse transcription (RT)-PCR. Immunohistochemical analysis, quantitative PCR and immunoblotting were performed to detect CIS and SOCS3 expression in synovial tissue, SF mononuclear cells (SFMCs) from patients with GA and MSU crystal-stimulated monocyte-derived macrophages from healthy donors. CIS overexpression and small interfering RNA-mediated knockdown in RAW264.7 cells were used to investigate the role of CIS in resolving MSU crystal-induced acute inflammation. RESULTS: SF levels of anti-inflammatory molecules TGFß1, IL-1ra, IL-10 and sTNFR-I/II were significantly elevated in GA compared to OA. CIS and SOCS3 were upregulated in the synovium and SFMCs from acute GA and MSU crystal-stimulated monocyte-derived macrophages and RAW264.7 cells. CIS overexpression in RAW264.7 cells attenuated MSU crystal-induced IL-1ß and TNFα but enhanced TGFß1 production via increased binding of signal transducer and activator of transcription 3 (STAT3) to the TGFß1 promoter. Conversely, CIS knockdown reversed the effect of CIS overexpression, resulting in enhanced IL-1ß and TNFα but reduced TGFß1 production in MSU crystal-stimulated RAW264.7 cells. CONCLUSIONS: Increased production of TGFß1, IL-1ra, IL-10 and sTNFR-I/II and upregulation of intracellular CIS and SOCS3 expression are associated with spontaneous resolution of acute GA.