An integrated bioinformatic analysis of microarray datasets to identify biomarkers and miRNA-based regulatory networks in leishmaniasis.

Micro RNAs (miRNAs, miRs) and relevant networks might exert crucial functions during differential host cell infection by the different Leishmania species. Thus, a bioinformatic analysis of microarray datasets was developed to identify pivotal shared biomarkers and miRNA-based regulatory networks for Leishmaniasis. A transcriptomic analysis by employing a comprehensive set of gene expression profiling microarrays was conducted to identify the key genes and miRNAs relevant for Leishmania spp. infections. Accordingly, the gene expression profiles of healthy human controls were compared with those of individuals infected with Leishmania mexicana, L. major, L. donovani, and L. braziliensis. The enrichment analysis for datasets was conducted by utilizing EnrichR database, and Protein-Protein Interaction (PPI) network to identify the hub genes. The prognostic value of hub genes was assessed by using receiver operating characteristic (ROC) curves. Finally, the miRNAs that interact with the hub genes were identified using miRTarBase, miRWalk, TargetScan, and miRNet. Differentially expressed genes were identified between the groups compared in this study. These genes were significantly enriched in inflammatory responses, cytokine-mediated signaling pathways and granulocyte and neutrophil chemotaxis responses. The identification of hub genes of recruited datasets suggested that TNF, SOCS3, JUN, TNFAIP3, and CXCL9 may serve as potential infection biomarkers and could deserve value as prognostic biomarkers for leishmaniasis. Additionally, inferred data from miRWalk revealed a significant degree of interaction of a number of miRNAs (hsa-miR-8085, hsa-miR-4673, hsa-miR-4743-3p, hsa-miR-892c-3p, hsa-miR-4644, hsa-miR-671-5p, hsa-miR-7106-5p, hsa-miR-4267, hsa-miR-5196-5p, and hsa-miR-4252) with the majority of the hub genes, suggesting such miRNAs play a crucial role afterwards parasite infection. The hub genes and hub miRNAs identified in this study could be potentially suggested as therapeutic targets or biomarkers for the management of leishmaniasis.

Evaluation of dose distribution of an intraoperative radiotherapy device using thermoluminescent dosimeters and radiographic films.

Background: To investigate dose distribution of the 5cm spherical applicator of the INTRABEAM™ intraoperative radiation therapy (IORT) device via thermoluminescence dosimeters (TLDs) and Radiographic films. Independent dose distribution assessment of IORT devices is considered important. Several methods are described for this purpose, including TLDs and films. However, Radiographic films are not routinely used. Materials and methods: Twenty TLDs were used for depth dose measuring and evaluating the isotropy in water. Additionally, the isotropy was assessed separately via Radiographic films in air by drawing isodose curves. Results: TLD measurements showed a steep dose decline which the relative average dose of 0.94 at the applicator surface reduced to 0.32, 0.13, and 0.07 at 1, 2, and 3 cm depths in water, respectively. Some remarkable isodose curves prepared using Radiographic films showed forward anisotropy of the 5 cm applicator. Conclusion: A very steep dose decline and approximately isotropic dose distribution of the 5 cm applicator were observed via TLD measurements. Radiographic films showed acceptable potential for drawing dose distribution maps. However, they should be applied in more various radiation setups to be implemented more confidently.

Clinical relevance and therapeutic potential of IL-38 in immune and non-immune-related disorders

Interleukin-38 (IL-38) is the most recent member of the IL-1 family that acts as a natural inflammatory inhibitor by binding to cognate receptors, particularly the IL-36 receptor. In vitro, animal and human studies on autoimmune, metabolic, cardiovascular and allergic diseases, as well sepsis and respiratory viral infections, have shown that IL-38 exerts an anti-inflammatory activity by modulating the generation and function of inflammatory cytokines (e.g. IL-6, IL-8, IL-17 and IL-36) and regulating dendritic cells, M2 macrophages and regulatory T cells (Tregs). Accordingly, IL-38 may possess therapeutic potential for these types of diseases. IL-38 down-regulates CCR3+ eosinophil cells, CRTH2+ Th2 cells, Th17 cells, and innate lymphoid type 2 cells (ILC2), but up-regulates Tregs, and this has influenced the design of immunotherapeutic strategies based on regulatory cells/cytokines for allergic asthma in future studies. In auto-inflammatory diseases, IL-38 alleviates skin inflammation by regulating γδ T cells and limiting the production of IL-17. Due to its ability to suppress IL-1ß, IL-6 and IL-36, this cytokine could reduce COVID-19 severity, and might be employed as a therapeutic tool. IL-38 may also influence host immunity and/or the components of the cancer microenvironment, and has been shown to improve the outcome of colorectal cancer, and may participate in tumour progression in lung cancer possibly by modulating CD8 tumour infiltrating T cells and PD-L1 expression. In this review, we first briefly present the biological and immunological functions of IL-38, and then discuss the important roles of IL-38 in various types of diseases, and finally highlight its use in therapeutic strategies.

Acid-induced gelation behavior of casein/whey protein solutions assessed by oscillatory rheology.

Gelation process of acid-induced casein gels was studied using response surface method (RSM). Ratio of casein to whey proteins, incubation and heating temperatures were independent variables. Final storage modulus (G') measured 200 min after the addition of glucono-δ-lactone and the gelation time i.e. the time at which G' of gels became greater than 1 Pa were the parameters studied. Incubation temperature strongly affected both parameters. The higher the incubation temperature, the lower was the G' and the shorter the gelation time. Increased heating temperature however, increased the G' but again shortened the gelation time. Increase in G' was attributed to the formation of disulphide cross-linkages between denatured whey proteins and casein chains; whilst the latter was legitimized by considering the higher isoelectric pH of whey proteins. Maximum response (G' = 268.93 Pa) was obtained at 2.7 % w/w, 25 °C and 90 °C for casein content, incubation and heating temperatures, respectively.

Does the diet of Tehranian adults ensure compliance with nutritional targets? Observations from the Tehran Lipid and Glucose Study.

OBJECTIVE: To analyse dietary compliance with WHO/FAO nutritional objectives, identify food subgroups that contribute to discrepancies between dietary intakes and recommendations, and assess food patterns and risk factor profiles at common nutritional targets. DESIGN: The study was a population-based, cross-sectional assessment of the dietary patterns of Tehranian adults. Usual dietary intake was assessed in relation to common nutritional targets of public health (fat, saturated fat, dietary fibre, fruit and vegetables) using a validated FFQ. Metabolic syndrome (MetS) risk factors were diagnosed based on the Iranian-modified diagnostic criteria of the National Cholesterol Education Program Adult Treatment Panel III. SETTING: The Tehran Lipid and Glucose Study (2005-2008). SUBJECTS: A total of 2510 individuals (1121 men and 1389 women), aged between 19 and 70 years. RESULTS: Generally, 68·5 % of total grain ounce-equivalents were derived from refined grains, with rice making up 36·6 % of all grains consumed. Solid fat (61·1 %) contributed more to discretionary energy than did added sugars (38·9 %). There was a twofold difference in fruit and vegetable consumption between the lowest and highest quartile categories of dietary fibre intake. The probability of having MetS was significantly lower in the highest quartile of fibre intake v. the lowest (OR = 0·69, 95 % CI 0·58, 0·84 v. OR = 0·92, 95 % CI 0·80, 1·03; P -trend < 0·001), whereas it was higher in the highest quartile of SFA intake v. the lowest (OR = 0·92, 95 % CI 0·78, 0·98 v. OR = 0·71, 95 % CI 0·62, 0·89; P-trend = 0·01). CONCLUSIONS: Complying with common nutritional targets of public health is inversely associated with MetS risk factors in Tehranian adults. These results may initiate measures for future development of regional food-based dietary guidelines.