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Schistosoma mansoni is an intestinal parasite with one β-class carbonic anhydrase, SmaBCA. We report the sequence enhancing, production, catalytic activity, and inhibition results of the recombinant SmaBCA. It showed significant catalytic activity on CO 2 hydration in vitro with k cat 1.38 × 10 5  s -1 and k cat / K m 2.33 × 10 7 M -1  s -1 . Several sulphonamide inhibitors, from which many are clinically used, showed submicromolar or nanomolar inhibitory effects on SmaBCA. The most efficient inhibitor with a K I of 43.8 nM was 4-(2-amino-pyrimidine-4-yl)-benzenesulfonamide. Other effective inhibitors with K I s in the range of 79.4-95.9 nM were benzolamide, brinzolamide, topiramate, dorzolamide, saccharin, epacadostat, celecoxib, and famotidine. The other tested compounds showed at least micromolar range inhibition against SmaBCA. Our results introduce SmaBCA as a novel target for drug development against schistosomiasis, a highly prevalent parasitic disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is potentially pathogenic and causes severe symptoms; in addition to respiratory syndromes, patients might experience other severe conditions such as digestive complications and liver complications injury. The abnormality in the liver is manifested by hepatobiliary dysfunction and enzymatic elevation, which is associated with morbidity and mortality. The direct cytopathic effect, immune dysfunction, cytokine storm, and adverse effects of therapeutic regimens have a crucial role in the severity of liver injury. According to aging and immune system alterations, cytokine patterns may also change in the elderly. Moreover, hyperproduction of cytokines in the inflammatory response to SARS-CoV-2 can lead to multi-organ dysfunction. The mortality rate in elderly patients, particularly those with other comorbidities, is also higher than in adults. Although the pathogenic effect of SARS-CoV-2 on the liver has been widely studied, the impact of age and immune-mediated responses at different ages remain unclear. This review discusses the association between immune system responses in coronavirus disease 2019 (COVID-19) patients of different ages and liver injury, focusing on cytokine alterations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Aghamohamadi, Shahba, Zarezadeh Mehrabadi, Khorramdelazad, Karimi, Falak and Emameh.)

We report the production and biochemical characterization of an α-carbonic anhydrase (LrhCA) from gram-positive probiotic bacteria Lactobacillus rhamnosus GG. CAs form a family of metalloenzymes that catalyze hydration of CO 2 /interconversion between CO 2 and water to bicarbonate ions and protons. They are divided into eight independent gene families (α, β, γ, δ, ζ, η, θ, and ι). Interestingly, many pathogens have been identified with only β- and/or γ-CAs, which can be targeted with CA-specific inhibitors (CAIs) acting as anti-pathogen drugs. Since it is important to study the potential off-target effects of CAIs for both the human body and its commensal bacteria, we took L. rhamnosus GG as our study subject. To date, only a single α-CA has been identified in L. rhamnosus GG, which was successfully produced and biochemically characterized. LrhCA showed moderate catalytic activity with the following kinetic parameters: k cat of 9.86 × 10 5  s -1 and k cat /K M of 1.41 × 10 7  s -1  M -1 . Moderate inhibition was established with 11 of the 39 studied sulfonamides. The best inhibitors were 5-((4-aminophenyl)sulfonamido)-1,3,4-thiadiazole-2-sulfonamide, 4-(2-hydroxymethyl-4-nitrophenyl-sulfonamidoethyl)-benzenesulfonamide, and benzolamide with K i values of 319 nM, 378 nM, and 387 nM, respectively. The other compounds showed weaker inhibitory effects. The K i of acetazolamide, a classical CAI, was 733 nM. In vitro experiments with acetazolamide showed that it had no significant effect on cell growth in L. rhamnosus GG culture. Several sulfonamides, including acetazolamide, are in use as clinical drugs, making their inhibition data highly relevant to avoid any adverse off-target effects towards the human body and its probiotic organisms. KEY POINTS: • The α-carbonic anhydrase from Lactobacillus rhamnosus GG (LrhCA) is 24.3 kDa. • LrhCA has significant catalytic activity with a kcat of 9.9 × 105 s-1. • Acetazolamide resulted in a marginal inhibitory effect on cell growth., (© 2022. The Author(s).)

Background: Niemann-Pick disease type C (NPC) is a rare lysosomal neurovisceral storage disease caused by mutations in the NPC 1 (95%) or NPC2 (5%) genes. The products of NPC1 and NPC2 genes play considerable roles in glycolipid and cholesterol trafficking, which could consequently lead to NPC disease with variable phenotypes displaying a broad spectrum of symptoms., Materials: In the present study 35 Iranian NPC unrelated patients were enrolled. These patients were first analysed by the Filipin Staining test of cholesterol deposits in cells for NPC diagnostics. Genomic DNA was extracted from the samples of peripheral blood leukocytes in EDTA following the manufacturer's protocol. All exon-intron boundaries and coding exons of the NPC1gene were amplified by polymerase chain reaction (PCR) using appropriate sets of primers. Thereafter, the products of PCR were sequenced and analysed using the NCBI database ( https://blast.ncbi.nlm.nih.gov/Blast.cgi ). The variants were reviewed by some databases including the Human Gene Mutation Database (HGMD) ( http://www.hgmd.cf.ac.uk/ac/index.php ) and ClinVar ( https://www.ncbi.nlm.nih.gov/clinvar (. Moreover, all the variants were manually classified in terms of the American College of Medical Genetics and Genomics (ACMG) guideline., Results: The sequence analysis revealed 20 different variations, 10 of which are new, including one nonsense mutation (c.406C > T); three small deletions, (c.3126delC, c.2920_2923delCCTG, and c.2037delG); and six likely pathogenic missense mutations, (c.542C > A, c.1970G > A, c.1993C > G, c.2821 T > C, c.2872C > G, and c.3632 T > A). Finally, the pathogenicity of these new variants was determined using the ACMG guidelines., Conclusion: The present study aimed to facilitate the prenatal diagnosis of NPC patients in the future. In this regard, we identified 10 novel mutations, and verified that the majority of them occurred in six NPC1 exons (5, 8, 9, 13, 19, and 21), that should be considered with a high priority for Iranian patients' cost-effective evaluation., (© 2022. The Author(s).)

Leishmaniosis is caused by different species of Leishmania parasites. The available treatments for this disease have not provided strong consistent results yet. The weak response of current chemotherapeutics can be attributed to their deficient effects on stealth parasites inside macrophages, rapid clearance from the site of action, and systemic side effects in high doses. To enhance leishmaniosis vaccine efficacy, it is a valuable strategy to use liposomes as vaccine delivery systems due to combined increase in technological advances and understanding of the immune system. Liposomes that contain and deliver immunostimulators and antigens are now being developed to target diseases that require stimulation of both humoral and cell-mediated immune responses. Hence, using particulate adjuvants, like liposomes for effective delivery to the antigen presenting cells (APCs) is important for improving leishmaniosis vaccine efficacy. This study aimed at reviewing liposomal adjuvants in vaccine development with specific accentuation on their adjuvant mechanism and surface charge. It also examined how specific physicochemical qualities of liposomes and the particle size during formulation design can affect the immune response.

With the increase in CO 2 emissions worldwide and its dire effects, there is a need to reduce CO 2 concentrations in the atmosphere. Alpha-carbonic anhydrases (α-CAs) have been identified as suitable sequestration agents. This study reports the sequence and structural analysis of 15 α-CAs from bacteria, originating from hydrothermal vent systems. Structural analysis of the multimers enabled the identification of hotspot and interface residues. Molecular dynamics simulations of the homo-multimers were performed at 300 K, 363 K, 393 K and 423 K to unearth potentially thermostable α-CAs. Average betweenness centrality ( BC ) calculations confirmed the relevance of some hotspot and interface residues. The key residues responsible for dimer thermostability were identified by comparing fluctuating interfaces with stable ones, and were part of conserved motifs. Crucial long-lived hydrogen bond networks were observed around residues with high BC values. Dynamic cross correlation fortified the relevance of oligomerization of these proteins, thus the importance of simulating them in their multimeric forms. A consensus of the simulation analyses used in this study suggested high thermostability for the α-CA from Nitratiruptor tergarcus . Overall, our novel findings enhance the potential of biotechnology applications through the discovery of alternative thermostable CO 2 sequestration agents and their potential protein design.

Fasciolosis is considered as an ongoing neglected zoonotic disease in tropical regions of the world, relating to notable financial and public health issues. The current systematic review and meta-analysis was planned to determine the status of fasciolosis among domestic ruminants, including cattle, buffalo, goat, and sheep at the industrial slaughterhouses in Iran, between the years 2000 and 2016. Eight databases, four English and four Persian, were searched. Our findings demonstrated that 2.6% of all inspected livers of slaughtered ruminants were infected with Fasciola spp. during 2000–2016. The mean prevalence of fasciolosis for cattle, buffalo, goat, and sheep was 21%, 4.2%, 2%, and 2.4%, respectively. Additionally, most studies were performed on cattle 25 (39.6%), sheep 24 (38 %), and goat 12 (19%), respectively, and just 2 (3.1%) studies were performed on buffalo. The prevalence of animal fasciolosis has significantly decreased among domestic ruminants in Iran except for cattle. In addition, the prevalence of this disease in Northern and Western regions of the country has remained at hypo-endemic level. The results present updated gathered information on the epidemiology of fasciolosis in domestic ruminants in Iran, and will expand the screening strategies to improve health and reduce economic impacts among farm animals.

Long non-coding RNAs (lncRNAs) are classified as a group of transcripts which regulate various biological processes, such as RNA processing, epigenetic control, and signaling pathways. According to recent studies, lncRNAs are dysregulated in cancer and play an important role in cancer incidence and spreading. There is also an association between lncRNAs and the overexpression of some tumor-associated proteins, including carbonic anhydrases II, IX, and XII (CA II, CA IX, and CA XII). Therefore, not only CA inhibition, but also lncRNA modulation, could represent an attractive strategy for cancer prevention and therapy. Experimental studies have suggested that herbal compounds regulate the expression of many lncRNAs involved in cancer, such as HOTAIR (HOX transcript antisense RNA), H19, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), PCGEM1 (Prostate cancer gene expression marker 1), PVT1, etc. These plant-derived drugs or phytochemicals include resveratrol, curcumin, genistein, quercetin, epigallocatechin-3-galate, camptothcin, and 3,3'-diindolylmethane. More comprehensive information about lncRNA modulation via phytochemicals would be helpful for the administration of new herbal derivatives in cancer therapy. In this review, we describe the state-of-the-art and potential of phytochemicals as modulators of lncRNAs in different types of cancers.

Aim: This study was designed to evaluate the network productions and research collaborations on toxoplasmosis worldwide., Materials and Methods: A bibliometric research was carried out using the Web of Science (WOS) database. The analysis unit was the original research articles about toxoplasmosis published between 2000 and 2016 (17 years)., Results: Totally, 6,550 articles about toxoplasmosis were indexed in the WOS with the following information: (A) 18,410 researchers played a role in drafting the articles; (B) 33 different countries have contributed in the toxoplasmosis studies; (C) the USA was ranked at the first place with 2,162 publications about toxoplasmosis; and (D) "Dubey JP" was compiled and participated in 401 articles from the USA, as the highest number and main core of publications in the toxoplasmosis network., Conclusion: The main focus of the toxoplasmosis research activities in the world was article production in the indexed journals in WOS. Hence, it is necessary to strengthen the collaboration networks to improve the quality of articles. Furthermore, the priority would be the identification of institutions with a higher number of research article productions in WOS, to perform toxoplasmosis collaborative original researches according to the strategic roadmap and scientific plan of each country.