Increased Salivary Cytokines and Nitric Oxide Levels in Behçet's Disease: Interleukin-32, a Novel Player in Disease Prognosis.

BACKGROUND: Oral aphthosis is one of the major manifestations of Behçet's disease (BD), a chronic, multisystemic vasculitis. BD etio-pathogenicity related to oral health lack. OBJECTIVE: This study investigated the possible relationships between poor oral hygiene, oral activity, disease severity and saliva's Interleukin (IL)-32, IL-6, IL-10 and nitric oxide (NO) levels in Behçet's patients to determine their role in disease prognosis and their potential therapeutic interest. METHODS: Fifty-six patients with BD (22 orally active; 34 orally inactive) and 31 healthy subjects have been included in our study. Salivary levels of IL-32, IL-6, and IL-10 were measured using ELISA, while NO levels were assessed by modified Griess's method. Oral health status and disease severity scores were recorded for each participant. Kruskal-Wallis test and Spearman's test were performed for statistical analyses. RESULTS: We observed that the tested molecules were increased in BD patients compared to healthy controls (p˂0.05). Moreover, only IL-32 levels were associated with oral activity in patients (p˂0.05). Interestingly, the disease severity score was noted to be correlated positively and significantly with both IL-32 saliva levels (p˂0.01) and plaque index (p˂0.05) in BD patients. Furthermore, IL-32 levels were correlated with plaque index (p˂0.0001). CONCLUSION: Our results suggest that IL-32, IL- 6, IL-10 and NO were increased in saliva during BD. Our study indicated that IL-32 was associated with the genesis of oral ulcers in response to dental plaque. Ultimately, salivary IL-32 may serve as a prognostic biomarker and a possible therapeutic target for managing Behçet's disease severity.

Association between Increased Bcl-2, Fas and FasL Levels and Inflammation Extent in Labial Salivary Glands During Primary Sjögren's Syndrome.

BACKGROUND: Primary Sjögren Syndrome (pSS) is a chronic autoimmune disease characterized by epithelial atrophy, mononuclear infiltration in exocrine glands resulting in the defective function of these glands. In pSS, atrophy of the epithelium is caused by an increased amount of apoptosis. OBJECTIVE: The main aim of this study is to investigate the role of the apoptosis-related factors by studying Bcl-2, Fas and FasL expression in relation to the extent of inflammation as well as the effect of therapy on the expression of these mediators. METHODS: In pSS patients (n=62) documented for their serological and clinical features, Fas, FasL and Bcl-2 plasma levels were assessed using enzyme-linked immunosorbent assays. In the same context, we investigated their expression by immunohistochemistry analysis in the labial salivary glands samples in association with the extent of inflammation. RESULTS: Interestingly, our results indicated that in pSS patients, the plasmatic Bcl-2, Fas and FasL levels, which appeared to be associated with the severity of inflammation and were significantly elevated in comparison to the healthy controls. Moreover, a significant decrease in all these factors was observed in patients after combined corticosteroids-hydroxychloroquine therapy. Importantly, we report a strong positive correlation between Bcl-2 and NO levels. The immunohistochemical staining reveals a strong Bcl-2 expression in infiltrating mononuclear cells and a total absence in the acinar cells. The Bcl-2 level varies according to the severity of pathology. However, the expression of Fas and FasL was less important and predominantly localized in infiltrating mononuclear cells. CONCLUSION: Our current study highlights the involvement of Bcl-2, Fas and FasL in pSS glands injury. These factors may act as useful predictor markers of a clinical course in pSS, suggesting a novel approach in the pSS patients monitoring.

Acoustic radiation-free surface phononic crystal resonator for in-liquid low-noise gravimetric detection.

Acoustic wave resonators are promising candidates for gravimetric biosensing. However, they generally suffer from strong acoustic radiation in liquid, which limits their quality factor and increases their frequency noise. This article presents an acoustic radiation-free gravimetric biosensor based on a locally resonant surface phononic crystal (SPC) consisting of periodic high aspect ratio electrodes to address the above issue. The acoustic wave generated in the SPC is slower than the sound wave in water, hence it prevents acoustic propagation in the fluid and results in energy confinement near the electrode surface. This energy confinement results in a significant quality factor improvement and reduces frequency noise. The proposed SPC resonator is numerically studied by finite element analysis and experimentally implemented by an electroplating-based fabrication process. Experimental results show that the SPC resonator exhibits an in-liquid quality factor 15 times higher than a conventional Rayleigh wave resonator at a similar operating frequency. The proposed radiation suppression method using SPC can also be applied in other types of acoustic wave resonators. Thus, this method can serve as a general technique for boosting the in-liquid quality factor and sensing performance of many acoustic biosensors.

Dipole states and coherent interaction in surface-acoustic-wave coupled phononic resonators.

Manipulation of mechanical motion at the micro-scale has been attracting continuous attention, leading to the successful implementation of various strategies with potential impact on classical and quantum information processing. We propose an approach based on the interplay between a pair of localised mechanical resonators and travelling surface acoustic waves (SAW). We demonstrate the existence of a two-sided interaction, allowing the use of SAW to trigger and control the resonator oscillation, and to manipulate the elastic energy distribution on the substrate through resonator coupling. Observation of the vectorial structure of the resonator motion reveals the existence of two coupling regimes, a dipole-dipole-like interaction at small separation distance versus a surface-mediated mechanical coupling at larger separation. These results illustrate the potential of this platform for coherent control of mechanical vibration at a resonator level, and reciprocally for manipulating SAW propagation using sub-wavelength elements.

Interferon-ß inhibits inflammatory responses mediators via suppression of iNOS signaling pathway in PBMCs from patients with primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) represents a chronic, systemic autoimmune disorder, characterized by lymphocytic infiltration of exocrine glands, inducing compromised secretory function and tissue destruction. Increasing evidence had revealed that inflammatory mediators, such as nitric oxide (NO) and pro-inflammatory cytokines, are critical in the development and perpetuation of pSS systemic manifestations. In our current study, we aimed to investigate the ex vivo immunomodulatory effect of interferon (IFN)-ß on iNOS expression, as well as on pro-inflammatory (tumor necrosis factor (TNF)-α, interleukin (IL)-6) and immunoregulatory (IL-10) cytokine production. Furthermore, we examined potential associations between the influence of IFN-ß treatment on NO production, and pSS clinical and serological manifestations. METHODS: In 41 pSS patients documented for their clinical and serological features, NO and cytokines levels were measured by the Griess method and enzyme-linked immunosorbent assay, respectively. Inducible nitric oxide synthase expression was analyzed by fluorescence immunostaining assay, using peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and pSS patients. RESULTS: Our results revealed a strong down-modulating effect of IFN-ß in the secretion of pro-inflammatory mediators including TNF-α, IL-6, and NO production. Interestingly, IFN-ß exerts an increase in IL-10 levels. The most suppressive effect exerted by IFN-ß on NO production was importantly reported for patients with neurological manifestation. This immunomodulatory effect of IFN-ß on NO production is highly related to the decrease of inducible nitric oxide synthase (iNOS) expression. CONCLUSION: Our findings highlight a consistent ex vivo inhibitory effect of IFN-ß on pro-inflammatory cytokine production and NO pathway in pSS patients. Our data suggest that IFN-ß could represent a potential candidate for targeting inflammation during pSS.

Cardamonin inhibits pro-inflammatory cytokine production and suppresses NO pathway in PBMCs from patients with primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disorder with a complex pathophysiology primarily affecting exocrine glands, leading to compromised secretory function. Recent studies imply that many inflammatory mediators, such as pro-inflammatory cytokines and nitric oxide, are critical in the development and perpetuation of pSS systemic manifestations. In the current study, we aimed to investigate the ex vivo immunomodulatory effect of cardamonin (C16H14O4), on pro-inflammatory cytokines, TNF-α, IL-6 and inducible nitric oxide synthase (iNOS) expression during pSS. For this purpose, peripheral blood mononuclear cells isolated from pSS patients and healthy controls were cultured with different concentrations of cardamonin. Cytokine levels were measured by ELISA and NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence staining. Our results suggest that cardamonin inhibits TNF-α, IL-6 and NO production and downregulates iNOS expression and NF-κB activation. Collectively, our results highlight the ex vivo immunomodulatory effects of cardamonin on pro-inflammatory cytokine production and NO pathway in pSS patients. Therefore, cardamonin is a potential candidate for controlling inflammation during pSS.

A case for IL-6, IL-17A, and nitric oxide in the pathophysiology of Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune epithelitis characterized by mononuclear cell (MNC) infiltration of the lacrimal and salivary glands (SG), as well as the presence of serum autoantibodies. This condition is a growing public health concern in Algeria. Herein, we sought to determine if the levels of interleukin (IL)-6, IL-17A, and nitric oxide (NO), were correlated with the extent of MNC infiltration. The expression of inducible NO synthase (NOS2) and CD68 was measured in the SG of all patients, but not in those of the normal controls (NCs). We included 44 primary Sjögren's syndrome (pSS) patients and 15 NCs in this study; we found that the expression of NOS2 and CD68 was elevated in all of the SG of SS patients. Additionally, the serum and saliva levels of IL-6, IL-17A, and NO were higher in the pSS patients, compared with the NCs. Furthermore, the NOS2-induced excess NO was associated with the extent of the MNC infiltration, and thereby with tissue injury. It is also important to note that there were correlations between the levels of IL-6, IL-17A, and NO. Such findings indicate that through the effects of NO, IL-17A participates in the pathophysiology of the disease. With the purpose of improving both the diagnosis and prognosis, IL-6, IL-17A, and NO should be assayed in the serum and saliva of patients suspected of SS.

Acoustic wave filter based on periodically poled lithium niobate.

Solutions for the development of compact RF passive transducers as an alternative to standard surface or bulk acoustic wave devices are receiving increasing interest. This article presents results on the development of an acoustic band-pass filter based on periodically poled ferroelectric domains in lithium niobate. The fabrication of periodically poled transducers (PPTs) operating in the range of 20 to 650 MHz has been achieved on 3-in (76.2-mm) 500-µm-thick wafers. This kind of transducer is able to excite elliptical as well as longitudinal modes, yielding phase velocities of about 3800 and 6500 ms(-1), respectively. A new type of acoustic band-pass filter is proposed, based on the use of PPTs instead of the SAWs excited by classical interdigital transducers. The design and the fabrication of such a filter are presented, as well as experimental measurements of its electrical response and transfer function. The feasibility of such a PPT-based filter is thereby demonstrated and the limitations of this method are discussed.

Simultaneous guidance of slow photons and slow acoustic phonons in silicon phoxonic crystal slabs.

We demonstrate theoretically that photons and acoustic phonons can be simultaneously guided and slowed down in specially designed nanostructures. Phoxonic crystal waveguides presenting simultaneous phononic and photonic band gaps were designed in perforated silicon membranes that can be conveniently obtained using silicon-on-insulator technology. Geometrical parameters for simultaneous photonic and phononic band gaps were first chosen for optical wavelengths around 1550 nm, based on the finite element analysis of a perfect phoxonic crystal of circular holes. A plain core waveguide was then defined, and simultaneous slow light and elastic guided modes were identified for some waveguide width. Joint guidance of light and elastic waves is predicted with group velocities as low as c/25 and 180 m/s, respectively.

Full band gap for surface acoustic waves in a piezoelectric phononic crystal.

A plane-wave-expansion method suited to the analysis of surface-acoustic-wave propagation in two-dimensional piezoelectric phononic crystals is described. The surface modes of a square-lattice Y-cut lithium niobate phononic crystal with circular void inclusions with a filling fraction of 63% are identified. It is found that a large full band gap with a fractional bandwidth of 34% exists for surface acoustic waves of any polarization and incidence, coincidentally with the full band gap for bulk waves propagating in the plane of the surface. The excitation of surface acoustic waves by interdigital transducers is discussed.