Novel strategies to fight Candida species infection

In recent years, there has been a significant increase in the incidence of human fungal infections. The increase in cases of infection caused by Candida species, and the consequent excessive use of antimicrobials, has favored the emergence of resistance to conventional antifungal agents over the past decades. Consequently, Candida infections morbidity and mortality are also increasing. Therefore, new approaches are needed to improve the outcome of patients suffering from Candida infections, because it seems unlikely that the established standard treatments will drastically lower the morbidity of mucocutaneous Candida infections and the high mortality associated with invasive candidiasis. This review aims to present the last advances in the traditional antifungal therapy, and present an overview of novel strategies that are being explored for the treatment of Candida infections, with a special focus on combined antifungal agents, antifungal therapies with alternative compounds (plant extracts and essential oils), adjuvant immunotherapy, photodynamic therapy and laser therapy.Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB’’, Ref. FCOMP-01-0124-FEDER-027462BioHealth – Biotechnology and Bioengineering approaches to improve health quality’’, Ref. NORTE-07-0124-FEDER-000027 co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER

Lion Algorithm-Optimized Long Short-Term Memory Network for Groundwater Level Forecasting in Udupi District, India

Groundwater is a precious natural resource. Groundwater level (GWL) forecasting is crucial in the field of water resource management. Measurement of GWL from observation-wells is the principle source of information about the aquifer and is critical to its evaluation. Most part of the Udupi district of Karnataka State in India consists of geological formations: lateritic terrain and gneissic complex. Due to the topographical ruggedness and inconsistency in rainfall, the GWL in Udupi region is declining continually and most of the open wells are drying-up during the summer. Hence, the current research aimed at developing a groundwater level forecasting model by using hybrid long short-term memory-lion algorithm (LSTM-LA). The historical GWL and rainfall data from an observation well from Udupi district, located in Karnataka state, India, were used to develop the model. The prediction accuracy of the hybrid LSTM-LA model was better than that of the feedforward neural network (FFNN) and the isolated LSTM models. The hybrid LSTM-LA-based forecasting model is promising for a larger dataset

Comparative antibacterial effectiveness of alcohol and herbal based commercially available hand antiseptics

Background: Human skin is a reservoir of numerous microorganisms. Even though hand washing with soap and water alone reduces the microbial load, the complementary uses of hand antiseptics enhance the antimicrobial effect. Aim: To compare the antimicrobial effectiveness of two commercially available hand antiseptics, routinely used in dental practice, after hand washing with antiseptic soap. Method: A clinical trial with cross over design was carried out on 12 health care workers (HCWs). The antibacterial effectiveness of two hand antiseptics (Alcohol based -Sterillium and Herbal Based-Himalaya′s ′Pure Hands′) compared using fingerprint contact sampling on blood agar. Bacterial samples were obtained before and after hand washing (with antiseptic soap) and after hand disinfection. The data was tabulated and analyzed using one way ANOVA and Tukey′s post hoc test for pair-wise comparison. Result: There was a slight decrease in the Colony forming units (CFUs) count following use of antiseptic soap when compared to the baseline values. A statistically significant reduction (p<0.000) in the CFUs count was seen following use of both hand antiseptics but the mean number of CFUs reduction was more in case of alcohol based hand antiseptic(sterillium) than herbal based hand antiseptic(Himalaya′s ′PureHands"). Conclusion: Using alcohol based antiseptic soap before hygienic hand disinfection will provide maximum benefit in reducing the microbial count

Influence of Glycosylation Inhibition on the Binding of KIR3DL1 to HLA-B*57:01

<div><p>Viral infections can affect the glycosylation pattern of glycoproteins involved in antiviral immunity. Given the importance of protein glycosylation for immune function, we investigated the effect that modulation of the highly conserved HLA class I <i>N</i>-glycan has on KIR:HLA interactions and NK cell function. We focused on HLA-B*57:01 and its interaction with KIR3DL1, which has been shown to play a critical role in determining the progression of a number of human diseases, including human immunodeficiency virus-1 infection. 721.221 cells stably expressing HLA-B*57:01 were treated with a panel of glycosylation enzyme inhibitors, and HLA class I expression and KIR3DL1 binding was quantified. In addition, the functional outcomes of HLA-B*57:01 <i>N</i>-glycan disruption/modulation on KIR3DL1ζ⁺ Jurkat reporter cells and primary human KIR3DL1⁺ NK cells was assessed. Different glycosylation enzyme inhibitors had varying effects on HLA-B*57:01 expression and KIR3DL1-Fc binding. The most remarkable effect was that of tunicamycin, an inhibitor of the first step of <i>N</i>-glycosylation, which resulted in significantly reduced KIR3DL1-Fc binding despite sustained expression of HLA-B*57:01 on 721.221 cells. This effect was paralleled by decreased activation of KIR3DL1ζ⁺ Jurkat reporter cells, as well as increased degranulation of primary human KIR3DL1⁺ NK cell clones when encountering HLA-B*57:01-expressing 721.221 cells that were pre-treated with tunicamycin. Overall, these results demonstrate that <i>N</i>-glycosylation of HLA class I is important for KIR:HLA binding and has an impact on NK cell function.</p></div

<i>N</i>-glycosylation inhibition increases HLA-B*57:01 surface expression while abrogating KIR3DL1-Fc binding: Anti-HLA-Bw4 antibody staining (A) and KIR3DL1-Fc staining (B) was performed on 221-HLA-B*57:01 cells (221-B57) treated with TUN (+T), CSP (+C), or PBS and untransduced 221 cells (221).

<p>Representative histograms are on left-sided panels and data representing five technical replicates are presented as bar graphs on right-sided panels.</p

TUN treatment HLA-B*57:01 221 cells abrogates binding to KIR3DL1ζ-Jurkat cells: (A) Gating of Jurkat cells by size (SSC = side scatter; FSC = forward scatter), CD3 expression and KIR3DL1 expression (KIR3DL1^-/~/+), (B) CD69 expression of unstimulated and stimulated KIR3DL1-/~/+ Jurkat cells (C) 4.4-fold increase of MFI of CD69 (compared to unstimulated controls) on KIR3DL1ζ+ Jurkat cells coincubated with wildtype 721.221 (221) or cells transfected with HLA-B*08:01/HLA-B*57:01 (221-B57/221-B08) and treated without/with TUN (+T) (n = 10).

<p>TUN treatment HLA-B*57:01 221 cells abrogates binding to KIR3DL1ζ-Jurkat cells: (A) Gating of Jurkat cells by size (SSC = side scatter; FSC = forward scatter), CD3 expression and KIR3DL1 expression (KIR3DL1^-/~/+), (B) CD69 expression of unstimulated and stimulated KIR3DL1-/~/+ Jurkat cells (C) 4.4-fold increase of MFI of CD69 (compared to unstimulated controls) on KIR3DL1ζ+ Jurkat cells coincubated with wildtype 721.221 (221) or cells transfected with HLA-B*08:01/HLA-B*57:01 (221-B57/221-B08) and treated without/with TUN (+T) (n = 10).</p

Glycosylation inhibitor screening and titration: (A) Median fluorescence intensity (MFI) of Bw4 staining of untransfected 221 cells (221) and HLA-B*57:01 transfected 221 cells (B57) treated with a panel of glycosylation inhibitors (n = 2) (B) MFI of KIR-Fc staining of untransfected 221 cells (221) and HLA-B*57:01 transfected 221 cells (B57) treated with a panel of glycosylation inhibitors (n = 2)

<p>Glycosylation inhibitor screening and titration: (A) Median fluorescence intensity (MFI) of Bw4 staining of untransfected 221 cells (221) and HLA-B*57:01 transfected 221 cells (B57) treated with a panel of glycosylation inhibitors (n = 2) (B) MFI of KIR-Fc staining of untransfected 221 cells (221) and HLA-B*57:01 transfected 221 cells (B57) treated with a panel of glycosylation inhibitors (n = 2)</p

Disinhibition of KIR3DL1+ NK cell clones by TUN treatment (A) Gating strategy of NK cell clones by size, CD56, CD16, KIR3DL1 and CD107a expression (B) % of CD107a+ KIR3DL1+ and KIR3DL1- NK cell clones coincubated with wildtype 721.221 (221) or cells transfected with HLA-B*57:01 (221-B57/221-B08) and treated without/with TUN (+T) (n = 3).

<p>Disinhibition of KIR3DL1+ NK cell clones by TUN treatment (A) Gating strategy of NK cell clones by size, CD56, CD16, KIR3DL1 and CD107a expression (B) % of CD107a+ KIR3DL1+ and KIR3DL1- NK cell clones coincubated with wildtype 721.221 (221) or cells transfected with HLA-B*57:01 (221-B57/221-B08) and treated without/with TUN (+T) (n = 3).</p