Induction of hapten-specific tolerance by interleukin 10 in vivo

Interleukin 10 (IL-10) is released during the induction phase of contact sensitivity and was shown in prior functional studies to convert epidermal Langerhans cells (LC) from potent inducers of primary immune responses to specifically tolerizing cells in vitro. To investigate whether IL-10 also subserves the function of a tolerizing agent in vivo ears of BALB/c or C3H mice were injected intradermally with 1-2 micrograms of recombinant mouse (rm)IL-10 8 h before epicutaneous application of 3% trinitrochlorobenzene (TNCB; a contact allergen). As a control, mice were injected with phosphate-buffered saline or IL-10 plus neutralizing amounts of anti-IL-10 mAb. 5 d later, mice were challenged with 1% TNCB on contralateral ears and ear swelling response was measured 24 h later. Whereas control-treated mice showed a normal ear swelling response to epicutaneous challenge (delta mm-2 = 25 +/- 5), ear swelling response of IL-10-treated animals was significantly inhibited (delta mm-2 = 3 +/- 2). Coinjection of IL-10-specific mAb together with rmIL-10 completely abrogated this effect. To differentiate between a state of nonresponsiveness and induction of tolerance by IL-10, mice initially treated with IL-10 and TNCB were resensitized with 3% TNCB in the absence of any treatment after 14 d of rest (group 1). Again mice were challenged 5 d later and ear swelling responses were tested. Whereas control mice treated with allergen alone (group 2) showed a good swelling response (delta mm-2 = 28 +/- 6), IL-10-treated mice (group 1) showed a minimal response towards application of allergen (delta mm-2 = 4 +/- 2). To show that anergy induction by IL-10 was antigen-specific, mice initially treated with IL-10 plus TNCB were exposed to 0.5% dinitrofluorobenzene (DNFB) 14 d later (group 1). After challenge with 0.1% DNFB, IL-10-treated mice showed an ear swelling response (delta mm-2 = 13 +/- 3; group 1) similar to that of control mice only sensitized with DNFB (delta mm-2 = 14 +/- 3; group 3). In an attempt to show the induction of antigen-specific tolerance in these mice in vitro, regional lymph nodes of mice initially treated with TNCB plus IL-10 (group 1) and control-treated mice (groups 2 and 3) were prepared and cultured in the presence of TNBS, dinitrobenzene sulfonate (DNBS), or medium to measure antigen-specific proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Molecular Biomarkers in Peri-Implant Health and Disease: A Cross-Sectional Pilot Study

Background: The aim of this feasibility study was to investigate the concentration level of CCL-20/MIP-3α, BAFF/BLyS, IL-23, RANKL, and Osteoprotegerin in the Peri-Implant Crevicular Fluid (PICF), from patients diagnosed with peri-implant mucositis and peri-implantitis, and to compare them with PICF from patients with healthy implants. Methods: Participants with at least one dental implant with healthy peri-implant tissues, peri-implant mucositis, or peri-implantitis were included. PICF was collected using paper strips from healthy and diseased peri-implant sites (n = 19). Biomarker levels were analyzed using a custom Multiplex ELISA Assay Kit. Results: In comparison to peri-implant health, the peri-implant mucositis group showed an increased concentration of CCL-20 MIP-3α, BAFF/BLyS, IL-23, RANKL, and Osteoprotegerin. The peri-implantitis group had the lowest median concentration of Osteoprotegerin (1963 ng/mL); this group had a similar concentration of RANKL (640.84 ng/mL) when compared to the peri-implant health group. BAFF/BLyS (17.06 ng/mL) showed the highest concentration in the peri-implantitis group. Conclusions: This feasibility study suggests that IL-23 and RANKL may help to elucidate the pathogenesis during the conversion from peri-implant health to peri-implantitis. Further research is required in BAFF/BLyS for the early diagnosis of peri-implantitis.     

Sliding Wear Behavior of a Grey Cast Iron Surface Remelted by TIG

The sliding wear behavior of a grey cast iron surface remelted by tungsten inert gas(TIG)was studied and compared with the unremelted one in the current work.To evaluate the wear behavior a Pin-on-Disk wear test machine was used.Pins which were prepared from the samples with the remelted layers of different thicknesses of 1.2,1.8,2.5 and 3 mm were worn on an AISID3 steel counterface having a hardness of 63HRC under the applied loads of 54,76 and 99 N at a constant sliding velocity of 0.45 m/s.Scanning elect...     

Voltammetric determination of 4-nitrophenol using a modified carbon paste electrode based on a new synthetic crown ether/silver nanoparticles

A novel modified carbon-paste electrode (CPE) with a new synthetic ligand: 6,7,9,10,17,18,19, 20,21, 22-decahydrodibenzo[h,r][1,4,7,11,15]trioxadiazacyclonanodecine-16,23dione(DTD)/Ag nanoparticles (AgNP) was employed for 4-nitrophenol measurement in natural water. Various parameters such as pH, modifier, accumulation time and scan rate were optimized. The proposed electrode showed a good response towards 4-nitrophenol determination. Under the optimized conditions the reduction peak current, showed a good linear relationship with the nitrophenol concentration in the range comprised between 1 × 10^− 6 mol L^− 1 and 1 × 10^− 4 mol L^− 1. The developed electrode was successfully applied for the determination of 4-nitrophenol in water samples.     

Buttermilk as milk powder and whey substitute in compound milk chocolate: Comparative study and optimisation

The aim of this study was to investigate the optimal concentration of milk, whey and buttermilk powder by using mixture design for the formulation of compound milk chocolate. The influence of buttermilk as a milk and whey substitute on the main physicochemical parameters of compound milk chocolate was investigated. The optimisation of the variables indicated that using 35.660% milk powder, 27.957% whey powder and 36.383% buttermilk produced the optimum milk chocolate with the highest desirability without undesirable changes in the quality properties. Chocolates containing equal amounts of buttermilk and milk powder and also equal amounts of whey powder and buttermilk powder demonstrated high consumer acceptability.     

In Silico Molecular Dynamics of Griseofulvin and Its Derivatives Revealed Potential Therapeutic Applications for COVID-19

Treatment options for Coronavirus Disease 2019 (COVID-19) remain limited, and the option of repurposing approved drugs with promising medicinal properties is of increasing interest in therapeutic approaches to COVID-19. Using computational approaches, we examined griseofulvin and its derivatives against four key anti-SARS-CoV-2 targets: main protease, RdRp, spike protein receptor-binding domain (RBD), and human host angiotensin-converting enzyme 2 (ACE2). Molecular docking analysis revealed that griseofulvin (CID 441140) has the highest docking score (–6.8 kcal/mol) with main protease of SARS-CoV-2. Moreover, griseofulvin derivative M9 (CID 144564153) proved the most potent inhibitor with −9.49 kcal/mol, followed by A3 (CID 46844082) with −8.44 kcal/mol against M protease and ACE2, respectively. Additionally, H bond analysis revealed that compound A3 formed the highest number of hydrogen bonds, indicating the strongest inhibitory efficacy against ACE2. Further, molecular dynamics (MD) simulation analysis revealed that griseofulvin and these derivatives are structurally stable. These findings suggest that griseofulvin and its derivatives may be considered when designing future therapeutic options for SARS-CoV-2 infection.     

Tryptophan Metabolism and Gut-Brain Homeostasis

Tryptophan is an essential amino acid critical for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only precursor for the neurotransmitter serotonin, which is vital for the processing of emotional regulation, hunger, sleep, and pain, as well as colonic motility and secretory activity in the gut. Tryptophan catabolites from the kynurenine degradation pathway also modulate neural activity and are active in the systemic inflammatory cascade. Additionally, tryptophan and its metabolites support the development of the central and enteric nervous systems. Accordingly, dysregulation of tryptophan metabolites plays a central role in the pathogenesis of many neurologic and psychiatric disorders. Gut microbes influence tryptophan metabolism directly and indirectly, with corresponding changes in behavior and cognition. The gut microbiome has thus garnered much attention as a therapeutic target for both neurologic and psychiatric disorders where tryptophan and its metabolites play a prominent role. In this review, we will touch upon some of these features and their involvement in health and disease.