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Probiotics, particularly yeasts from the genus Saccharomyces, are valuable for their health benefits and potential as antibiotic alternatives. To be effective, these microorganisms must withstand harsh environmental conditions, necessitating advanced protective technologies such as encapsulation to maintain probiotic viability during processing, storage, and passage through the digestive system. This review and meta-analysis aims to describe and compare methods and agents used for encapsulating Saccharomyces spp., examining operating conditions, yeast origins, and species. It provides an overview of the literature on the health benefits of nutritional yeast consumption. A bibliographic survey was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The meta-analysis compared encapsulation methods regarding their viability after encapsulation and exposure to the gastrointestinal tract. Nineteen studies were selected after applying inclusion/exclusion criteria. Freeze drying was found to be the most efficient for cell survival, while ionic gelation was best for maintaining viability after exposure to the gastrointestinal tract. Consequently, the combination of freeze drying and ionic gelation proved most effective in maintaining high cell viability during encapsulation, storage, and consumption. Research on probiotics for human food and animal feed indicates that combining freeze drying and ionic gelation effectively protects Saccharomyces spp.; however, industrial scalability must be considered. Reports on yeast encapsulation using agro-industrial residues as encapsulants offer promising strategies for preserving potential probiotic yeasts, contributing to the environmental sustainability of industrial processes., Competing Interests: Declarations Conflict of Interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A systematic review and meta-analysis were conducted to compile information on the bioactive potential of peptides derived from cheese whey from various animal sources, including cattle, sheep, goats, buffaloes, and camels. The systematic search yielded 955 results, with the primary reasons for exclusion being studies that did not utilize cheese whey as a product or did not assess key bioactivities such as antioxidant, antihypertensive, antimicrobial, and anti-aging effects. Ultimately, 36 articles met the inclusion criteria. Among the methods used to evaluate the antioxidant potential of protein hydrolysates, the 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay was identified as the most effective. Peptides derived from cheese whey proteins demonstrated antimicrobial activity against both filamentous fungi and bacteria. However, the review revealed a significant gap in studies investigating the anti-aging properties of these peptides. Notably, β-lactoglobulin contains peptide sequences embedded within its three-dimensional structure that may exhibit various bioactive properties. Overall, the findings highlight that cheese whey, irrespective of its animal origin, is a high-value co-product with excellent potential for biotechnological applications, particularly in the production of bioactive peptides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We have analysed the in silico potential of bioactive peptides from cheese whey, the most relevant by-product from the dairy industry, to bind into the active site of collagenase and elastase. The peptides generated from the hydrolysis of bovine β-lactoglobulin with three proteases (trypsin, chymotrypsin, and subtilisin) were docked onto collagenase and elastase by molecular docking. The interaction models were ranked according to their free binding energy using molecular dynamics simulations, which showed that most complexes presented favourable interactions. Interactions with elastase had significantly lower binding energies than those with collagenase. Regarding the interaction site, it was found that four bioactive peptides were positioned in collagenase's active site, while six were found in elastase's active site. Among these, the most we have found one promising collagen-binding peptide produced by chymotrypsin and two for elastase, produced by subtilisin and chymotrypsin. These in silico results can be used as a tool for designing further experiments aiming at testing the in vitro potential of the peptides found in this work., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aims of this work were to optimize the production of Erwinia carotovora l-asparaginase II enzyme in Escherichia coli by different fed-batch cultivation strategies using a benchtop bioreactor and to evaluate the therapeutic potential of the recombinant enzyme against different acute lymphoblastic leukemia cell lines. The highest enzyme activities (∼98,000 U/L) were obtained in cultures using the DO-stat feeding strategy with induction in 18 h of culture. Under these experimental conditions, the maximum values for recombinant l-asparaginase II (rASNase) yield per substrate, rASNase yield per biomass, and productivity were approximately 1204 U/g glucose , 3660 U/g cells , and 3260 U/(L·h), respectively. This condition was efficient for achieving high yields of the recombinant enzyme, which was purified and used in in vitro antileukemic potential tests. Of all the leukemic cell lines tested, RS4;11 showed the highest sensitivity to rASNase, with an IC 50 value of approximately 0.0006 U/mL and more than 70% apoptotic cells. The study demonstrated that the cultivation strategies used were efficient for obtaining high yield and productivity of rASNase with therapeutic potential inasmuch as cytotoxic activity and induction of apoptosis were demonstrated for this protein., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Nutritional status during critical windows in early development can challenge metabolic functions and physiological responses to immune stress in adulthood, such as the systemic inflammation induced by lipopolysaccharide (LPS). The aim of this study was to investigate the long-term effects of post-natal over- and undernutrition on the anorexigenic effect of LPS and its association with neuronal activation in the brainstem and hypothalamus of male rats. Animals were raised in litters of 3 (small - SL), 10 (normal - NL), or 16 (large - LL) pups per dam. On post-natal day 60, male rats were treated with LPS (500 µg/Kg) or vehicle for the evaluation of food intake and c-Fos expression in the area postrema (AP), nucleus of solitary tract (NTS), and paraventricular (PVN), arcuate (ARC), ventromedial (VMH), and dorsomedial (DMH) nuclei of the hypothalamus. SL, NL, and LL animals showed a decreased food consumption after LPS treatment. In under- and normonourished animals, peripheral LPS induced an increase in neuronal activation in the brainstem, PaV, PaMP, and ARC and a decrease in the number of c-Fos-ir neurons in the DMH. Overnourished rats showed a reduced hypophagic response, lower neuron activation in the NTS and PaMP, and no response in the DMH induced by LPS. These results indicate that early nutritional programming displays different responses to LPS, by means of neonatal overnutrition decreasing LPS-mediated anorexigenic effect and neuronal activation in the NTS and hypothalamic nuclei.

Background: Tuberculosis is one of the most significant infectious diseases for global public health. The reallocation of healthcare resources and the restrictions imposed by the COVID-19 pandemic have hindered access to TB diagnosis and treatment. Increases in unfavorable outcomes of the disease have been observed in Brazil. The objective of this study was to analyze the spatial distribution of unfavorable TB treatment outcomes in Brazil before and during the pandemic., Methods: An ecological study with spatial analysis was conducted with all 5569 municipalities in Brazil. All reported cases of tuberculosis between January 2010 and December 2021, as well as reported cases of COVID-19 from February 2020 to December 2021, were included. The outcomes studied encompass loss to follow-up, drug-resistant tuberculosis, and death. The Getis Ord GI* technique was employed to assess spatial association, and the Kernel density estimator was used to identify areas with concentrated increases or decreases in outcomes. Bivariate Local Moran's I was used to examine the spatial association between outcomes and COVID-19 incidence. The study was approved by the Research Ethics Committee of Ribeirão Preto Nursing School, University of São Paulo., Results: There were 134,394 cases of loss to follow-up, 10,270 cases of drug resistance, and 37,863 deaths. Clusters of high and low values were identified for all three outcomes, indicating significant changes in the spatial distribution patterns. Increases in concentrations were observed for lost to follow-up cases in the Southeast, while reductions occurred in the Northeast, South, and Midwest. Drug-resistant tuberculosis experienced an increase in the Southern and Southeastern regions and a decrease in the Northeast and South. TB-related deaths showed notable concentrations in the Midwest, Northeast, South, and Southeast. There was an increase in high occurrence clusters for deaths after 2020 and 2021 in the Northeast., Conclusions: The pandemic has brought additional challenges, emphasizing the importance of enhancing efforts and disease control strategies, prioritizing early identification, treatment adherence, and follow-up. This commitment is vital for achieving the goal of tuberculosis elimination., (© 2024. The Author(s).)

The objective of this study was to develop a bioprocess for lactose hydrolysis in diverse dairy matrices, specifically skim milk and cheese whey, utilizing column reactors employing a core-shell enzymatic system featuring β-galactosidase fused to a Cellulose Binding Domain (CBD) tag (β-galactosidase-CBD). The effectiveness of reactor configurations, including ball columns and toothed columns operating in packed and fluidized-bed modes, was evaluated for catalyzing lactose hydrolysis in both skim milk and cheese whey. In a closed system, these reactors achieved lactose hydrolysis rates of approximately 50% within 5 h under all evaluated conditions. Considering the scale of the bioprocess, the developed enzymatic system was capable of continuously hydrolyzing 9.6 L of skim milk while maintaining relative hydrolysis levels of approximately 50%. The biocatalyst, created by immobilizing β-galactosidase-CBD on magnetic core-shell capsules, exhibited exceptional operational stability, and the proposed bioprocess employing these column reactors showcases the potential for scalability., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The objective of this study was to immobilize a recombinant β-galactosidase (Gal) tagged with a cellulose-binding domain (CBD) onto a magnetic core-shell (CS) cellulose system. After 30 min of reaction, 4 U/capsule were immobilized (CS@Gal), resulting in levels of yield and efficiency exceeding 80 %. The optimal temperature for β-galactosidase-CBD activity increased from 40 to 50 °C following oriented immobilization. The inhibitory effect of galactose decreased in the enzyme reactions catalyzed by CS@Gal, and Mg 2+ increased the immobilized enzyme activity by 40 % in the magnetic CS cellulose system. The relative enzyme activity of the CS@Gal was 20 % higher than that of the soluble enzyme activity after 20 min at 50 °C. The CS support and CS@Gal capsules exhibited an average size of 8 ± 1 mm, with the structure of the shell (alginate-pectin-cellulose) enveloping and isolating the magnetic core. The immobilized β-galactosidase-CBD within the magnetic CS cellulose system retained ∼80 % of its capacity to hydrolyze lactose from skim milk after 10 reuse cycles. This study unveils a novel and promising support for the oriented immobilization of recombinant β-galactosidase using a magnetic CS system and a CBD tag. This support facilitates β-galactosidase reuse and efficient separation, consequently enhancing the catalytic properties of the enzyme., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The intricate balance between the beneficial and harmful effects of selenium (Se) intake means that its quantification in food needs to be done correctly. Therefore, in this review, we systematized 105 articles to identify the most studied methodologies, analytical techniques, and food matrices. Among the analytical techniques employed, inductively coupled plasma mass spectrometry (ICP-MS) (n = 29) emerged as the most commonly used method. The most prevalent hydrolysis methodology to digest Se in food matrices involved the use of nitric acid combined with ultrasound, which improved both the yield and digestion time. Optimal recovery values were achieved when total Se quantification accounted for the sum of Se(IV) and Se(VI) (94.4-99.4%) and for SeCys (88-96.5%). These findings are relevant for advancing methodological approaches, and their results emphasize the importance of developing alternative, faster, and lower-cost protocols for Se quantification in foods and beverages., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: To evaluate the adhesion capacity and anti-inflammatory activity of lactic acid bacteria (LAB) isolated from raw cow milk and artisan cheese in Southern Brazil, investigating their effect on the release of cytokines such as TNF-α and IL-10 and their influence on the activation of the p38/MAPK pathway., Methods and Results: Lentilactobacillus parabuchneri ML4, Lacticaseibacillus paracasei ML33, Lactiplantibacillus pentosus ML82, Lactiplantibacillus plantarum CH131, and L. paracasei CH135 demonstrated high adhesion potential in an in vitro model of the intestinal epithelium, as well as anti-inflammatory activity. After a 4-hour treatment, the strains significantly increased TNF-α levels, while a 24-hour treatment led to a significant decrease in TNF-α release. Moreover, IL-10 levels significantly increased after 24-hour and 48-hour treatments with LAB. The inhibition of p38/MAPK phosphorylation was identified as one of the mechanisms by which the L. paracasei ML33 and L. plantarum CH131 strains suppressed the production and release of TNF-α., Conclusions: We identified LAB strains with potential anti-inflammatory properties that could adhere to the intestinal mucosa and alleviate the inflammatory response by reducing the production and release of TNF-α through the inhibition of the p38/MAPK pathway, while promoting the production of IL-10., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

The present study reviewed and discussed the promising affinity tags for one-step purification and immobilization of recombinant proteins. The approach used to structure this systematic review was The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) methodology. The Scopus and Web of Science databases were used to perform the bibliographic survey by which 267 articles were selected. After the inclusion/exclusion criteria and the screening process, from 25 chosen documents, we identified 7 types of tags used in the last 10 years, carbohydrate-binding module tag (CBM), polyhistidine (His-tag), elastin-like polypeptides (ELPs), silaffin-3-derived pentalysine cluster (Sil3k tag), N-acetylmuramidase (AcmA tag), modified haloalkane dehalogenase (HaloTag ® ), and aldehyde from a lipase polypeptide (Aldehyde tag). The most used bacterial host for expressing the targeted protein was Escherichia coli and the most used expression vector was pET-28a. The results demonstrated two main immobilization and purification methods: the use of supports and the use of self-aggregating tags without the need of support, depending on the tag used. Besides, the chosen terminal for cloning the tag proved to be very important once it could alter enzyme activity. In conclusion, the best tag for protein one-step purification and immobilization was CBM tag, due to the eco-friendly supports that can be provided from industry wastes, the fast immobilization with high specificity, and the reduced cost of the process., Competing Interests: Conflict of interestThe authors declare they have no conflicts of interest., (© King Abdulaziz City for Science and Technology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: Lactation overnutrition is a programming agent of energy metabolism, and litter size reduction leads to the early development of obesity, which persists until adulthood. Liver metabolism is disrupted by obesity, and increased levels of circulating glucocorticoids are pointed as a possible mediator for the obesity development, since bilateral adrenalectomy (ADX) can reduce obesity in different models of obesity. Methods: This study aimed to evaluate the effects of glucocorticoids on metabolic changes and liver lipogenesis and insulin pathway induced by lactation overnutrition. For this, on the postnatal day 3 (PND), 3 pups (small litter-SL) or 10 pups (normal litter-NL) were kept with each dam. On PND 60, male Wistar rats underwent bilateral adrenalectomy (ADX) or fictitious surgery (sham), and half of ADX animals received corticosterone (CORT- 25 mg/L) diluted in the drinking fluid. On PND 74, the animals were euthanized by decapitation for trunk blood collection, and liver dissection and storage. Results and Discussion: SL rats presented increased corticosterone, free fatty acids, total and LDL-cholesterol plasma levels, without changes in triglycerides (TG) and HDL-cholesterol. The SL group also showed increased content of liver TG, and expression of fatty acid synthase (FASN), but decreased expression of PI3K p110 in the liver, compared to NL rats. In the SL group, the ADX decreased plasma levels of corticosterone, FFA, TG and HDL cholesterol, liver TG, and liver expression of FASN, and IRS2, compared to sham animals. In SL animals, CORT treatment increased plasma levels of TG and HDL cholesterol, liver TG, and expression of FASN, IRS1, and IRS2, compared with the ADX group. In summary, the ADX attenuated plasma and liver changes observed after lactation overnutrition, and CORT treatment could reverse most ADX-induced effects. Thus, increased circulating glucocorticoids are likely to play a pivotal role in liver and plasma impairments induced by lactation overnutrition in male rats., 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 de Souza, Stopa, Martins, Wunderlich, Lopes, de Fatima Silva, Komino, Zaia, Zaia, Lima and Uchoa.)

Background: In malaria-endemic areas, children presenting to hospitals with a decreased level of consciousness remain a diagnostic dilemma. The definition of cerebral malaria in a comatose child demands exclusion of other possible reasons, which requires in-depth investigations that are not easily available. The aim of this study was to investigate the frequency and clinical characteristics of PCR-confirmed malaria in a cohort of children with a decreased level of consciousness, look for potential features that would aid in differentiating children with malaria from those without, and assess the performance of traditional thick film microscopy against the cytb-qPCR-method., Methods: A total of 345 children aged 30 days-15 years old, presenting to Hospital Pediátrico David Bernardino in Luanda, Angola, with a decreased level of consciousness (Glasgow coma scale score < 15) were prospectively enrolled during 2014-2017. Malaria was defined as a positive cytb-qPCR result on any occasion in hospital. The clinical course and laboratory parameters were compared between children with malaria and those without. The performance of thick film microscopy was analysed against the PCR method., Results: 161 of 345 children (46.7%) had a positive malaria PCR test result. All cases were Plasmodium falciparum species, and 82.6% (133/161) fulfilled the WHO criteria for severe malaria. Overall, children with malaria presented to hospital with a shorter duration of symptoms and less convulsions pre-admission compared to those without malaria. The median GCS score on admission was 8, which did not differ between children with or without malaria. Clinical findings on admission were mostly similar across the whole cohort, but an infection focus outside the central nervous system was more common in malaria-negative children. Moreover, severe anaemia, thrombocytopenia, and high CRP levels occurred more frequently in children with malaria. The case fatality ratio was 28.5% (91/319) and did not differ between parasitaemic children and those without malaria, although parasitaemic children died sooner after hospital admission. When neurological sequelae were also considered, a positive malaria test was associated with a better outcome. The performance of thick film microscopy against PCR yielded a sensitivity of 96.8% and a specificity of 82.7%., Conclusions: In this cohort of children with a decreased consciousness, the frequent presence of a malarial infection could not be judged from the clinical findings on admission, but the combination of profound aneamia, thrombocytopenia, and a high CRP level increased the odds of a positive malaria test result. Mortality remained high regardless of etiology, but malaria infection associated with fewer neurological deficits at discharge. Thick film microscopy performed well compared to the cytb-qPCR method., (© 2023. The Author(s).)

Metabolic programming may be induced by reduction or enhancement of litter size, which lead to neonatal over or undernutrition, respectively. Changes in neonatal nutrition can challenge some regulatory processes in adulthood, such as the hypophagic effect of cholecystokinin (CCK). In order to investigate the effects of nutritional programming on the anorexigenic function of CCK in adulthood, pups were raised in small (SL, 3 pups per dam), normal (NL, 10 pups per dam), or large litters (LL, 16 pups per dam), and on postnatal day 60, male rats were treated with vehicle or CCK (10 µg/Kg) for the evaluation of food intake and c-Fos expression in the area postrema (AP), nucleus of solitary tract (NTS), and paraventricular (PVN), arcuate (ARC), ventromedial (VMH), and dorsomedial (DMH) nuclei of the hypothalamus. Overnourished rats showed increased body weight gain that was inversely correlated with neuronal activation of PaPo, VMH, and DMH neurons, whereas undernourished rats had lower body weight gain, inversely correlated with increased neuronal activation of PaPo only. SL rats showed no anorexigenic response and lower neuron activation in the NTS and PVN induced by CCK. LL exhibited preserved hypophagia and neuron activation in the AP, NTS, and PVN in response to CCK. CCK showed no effect in c-Fos immunoreactivity in the ARC, VMH, and DMH in any litter. These results indicate that anorexigenic actions, associated with neuron activation in the NTS and PVN, induced by CCK were impaired by neonatal overnutrition. However, these responses were not disrupted by neonatal undernutrition. Thus, data suggest that an excess or poor supply of nutrients during lactation display divergent effects on programming CCK satiation signaling in male adult rats., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Gastrointestinal tract diseases are characterized by an imbalance in physiological functions, which may involve inflammatory and metabolic pathways and trigger chronic, multifactorial, and idiopathic inflammatory disorders. The association of probiotics with prebiotics has the potential to remedy these afflictive conditions, because they attenuate or even block the adhesion of pathogenic microorganisms in the enteric environment. This article highlights the importance of using probiotics associated with fibers from Psyllium as prebiotics to maintain a healthy intestinal microbiota. We also present the technologies and encapsulating materials involved in coating to increase the survival rate of these strains when exposed to the gastrointestinal tract. The importance of products containing probiotics and fibers from Psyllium as prebiotics becomes increasingly evident when there is a health bias. Emerging health challenges and advances in research will drive selective approaches in biotechnology to discover and evaluate new probiotics and prebiotics that can potentially contribute to human health., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: Litter size reduction on the first days of life results in increased body weight and adiposity, with higher levels of circulating glucocorticoids. Obese rodents are more sensitive to the anabolic effects of glucocorticoids and less responsive to glucocorticoids feedback on hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to evaluate effects of the treatment with corticosterone on metabolic responses and HPA axis in adult male rats reared in small litters., Main Methods: From postnatal day (PND) 60 to 88, adult male rats of normal (NL- 10 pups/dam) and small (SL- 3 pups/dam) litters received oral treatment with Corticosterone (CORT-15 mg/L) in the drinking water or no treatment, composing the four experimental groups (NL-water; NL-CORT; SL-water and SL-CORT), for the evaluation of energy homeostasis and HPA axis., Key Findings: Male rats of SL-water group presented on PND88: glucose intolerance, higher adiposity, plasma triglycerides, free fatty acids, total and low-density lipoprotein (LDL) cholesterol and corticosterone. SL-water animals showed increased mRNA of corticotrophin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) and proopiomelanocortin (POMC) in the pituitary, with decreased mRNA expression of PVN mineralocorticoid receptor. NL-CORT animals presented glucose intolerance, increased body weight, food intake, total and LDL cholesterol. Glucocorticoid treatment reduced corticosterone levels and adrenal cortex thickness in NL group, associated with increased mRNA of PVN CRH and pituitary POMC, without effects on SL animals., Significance: Lactation overnutrition promotes hyperreactivity of HPA axis and reduces the responsiveness to glucocorticoids effects on energy balance and negative feedback of HPA axis in adult male rats., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib)., Methods: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe., Results: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals., Conclusion: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib., Competing Interests: Conflict of Interest All authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The initial infection by the obligate intracellular bacillus Mycobacterium leprae evolves to leprosy in a small subset of the infected individuals. Transmission is believed to occur mainly by exposure to bacilli present in aerosols expelled by infected individuals with high bacillary load. Mycobacterium leprae -specific DNA has been detected in the blood of asymptomatic household contacts of leprosy patients years before active disease onset, suggesting that, following infection, the bacterium reaches the lymphatic drainage and the blood of at least some individuals. The lower temperature and availability of protected microenvironments may provide the initial conditions for the survival of the bacillus in the airways and skin. A subset of skin-resident macrophages and the Schwann cells of peripheral nerves, two M. leprae permissive cells, may protect M. leprae from effector cells in the initial phase of the infection. The interaction of M. leprae with these cells induces metabolic changes, including the formation of lipid droplets, that are associated with macrophage M2 phenotype and the production of mediators that facilitate the differentiation of specific T cells for M. leprae -expressed antigens to a memory regulatory phenotype. Here, we discuss the possible initials steps of M. leprae infection that may lead to active disease onset, mainly focusing on events prior to the manifestation of the established clinical forms of leprosy. We hypothesize that the progressive differentiation of T cells to the Tregs phenotype inhibits effector function against the bacillus, allowing an increase in the bacillary load and evolution of the infection to active disease. Epigenetic and metabolic mechanisms described in other chronic inflammatory diseases are evaluated for potential application to the understanding of leprosy pathogenesis. A potential role for post-exposure prophylaxis of leprosy in reducing M. leprae -induced anti-inflammatory mediators and, in consequence, Treg/T effector ratios is proposed., 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 © 2022 Cabral, de Figueiredo, Gandini, de Souza, Medeiros, Lery, Lara, de Macedo, Pessolani and Pereira.)

Introduction: The coronavirus disease 2019 (COVID-19) pandemic led to the suspension or postponement of care for non-urgent conditions worldwide. Regula Mais Brasil is an initiative of the Unified Health System (SUS) in Brazil to optimize the management of referrals to specialized care by using telehealth. Objectives: To report the expansion of telehealth activities of Regula Mais Brasil in response to COVID-19 and to assess qualification of referrals in primary health care (PHC) units as well as the added value of teleconsultation in qualifying referral cases. Methods: Descriptive study of the teleconsultations carried out as an additional strategy to the remotely operated referral management system, responsible for navigating cases from PHC units to specialized care in Recife, Brazil, between May 6, 2020 and September 30, 2020. Teleconsultation was implemented as a tool for reducing delays in the access to health care due to COVID-19 and ultimately allowed for reclassification of the referral adequacy and priority. Changes in referral priority ratings and referral decisions after teleconsultation were analyzed. Results: A total of 622 referral cases were analyzed. Approved referrals represented 51.9% of cases. The main reason for approved referrals was the need for diagnostic resources. There was a reduction in priority ratings in 449 cases (72.2%) after teleconsultation. There was a statistically significant association between the change of priority ratings and the decision on referral (Pearson's χ 2 , p -value <0.0001). Results show that telemedicine had an impact on the prioritization and qualification of cases referred to specialized services. Conclusions: A need was detected to rapidly adapt tools available for telemedicine in Brazil. Our results demonstrate that teleconsultation as an additional strategy to the remotely operated referral management system has contributed toward improving equitable access to specialized services.

The physiological and behavioral responses of Pomacea canaliculata exposed to different pH values (4, 5, 6, 7, 8, 9, and 10) were evaluated. Survival, behavior (avoidance), metabolites (mantle), net ion fluxes (Na + and K + ), and ATPase activity (gills) were the parameters analyzed. The final survival rates were 100% (pH 4-9) and 90% (pH 10), and the groups did not differ significantly. Avoidance behavior was not identified in animals exposed to an extreme pH compared to pH 7. The main changes observed in the metabolites were in those exposed to an alkaline pH. Glucose (pH 9) and total protein (pH 9 and 10) levels increased, and lactate decreased (pH 9 and 10) compared to a neutral pH. There was an increase in Na + efflux at pH 4, 5, and 8 and an influx at pH 9 and 10. Extreme pH values (4 and 10) also caused an increase in K + efflux. At pH values outside the neutrality range (pH 7), there was a significant decrease in the activities of Na + /K + -ATPase (4, 5, 6, 9, and 10) and H + -ATPase (pH 4, 5, 9, and 10). Variations in environmental pH did not cause statistically significant mortality or avoidance behavior in P. canaliculata at the analyzed times. However, due to changes in energy metabolism (glucose and lactate, mainly) and ionoregulation, these can be considered sensitive biomarkers of stress in this species., (Copyright © 2022. Published by Elsevier Inc.)

This study aimed to develop single-step purification and immobilization processes on cellulosic supports of β-galactosidase from Kluyveromyces sp. combined with the Cellulose-Binding Domain (CBD) tag. After 15 min of immobilization, with an enzymatic load of 150 U/g support , expressed activity values reached 106.88 (microcrystalline cellulose), 115.03 (alkaline nanocellulose), and 108.47 IU/g (acid nanocellulose). The derivatives produced were less sensitive to the presence of galactose in comparison with the soluble purified enzyme. Among the cations assessed (Na + , K + , Mg 2+ , and Ca 2+ ), magnesium provided the highest increase in the enzymatic activity of β-galactosidases immobilized on cellulosic supports. Supports and derivatives showed no cytotoxic effect on the investigated cell cultures (HepG2 and Vero). Derivatives showed high operational stability in the hydrolysis of milk lactose and retained from 53 to 64% of their hydrolysis capacity after 40 reuse cycles. This study obtained biocatalyzers with promising characteristics for application in the food industry. Biocatalyzers were obtained through a low-cost one-step sustainable bioprocess of purification and immobilization of a β-galactosidase on cellulose via CBD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

For the first time, this work reported the one-step purification and targeted immobilization process of a β-galactosidase (Gal) with the Cellulose Binding Domain (CBD) tag, by binding it to different magnetic cellulose supports. The process efficiency after β-galactosidase-CBD immobilization on magnetic cellulose-based supports showed values of approximately 90% for all evaluated enzymatic loads. Compared with free Gal, derivatives showed affinity values between β-galactosidase and the substrate 1.2 × higher in the lactose hydrolysis of milk. β-Galactosidase-CBD's oriented immobilization process on supports increased the thermal stability of the immobilized enzyme by up to 7 × . After 15 cycles of reuse, both enzyme preparations showed a relative hydrolysis percentage of 50% of lactose in milk. The oriented immobilization process developed for purifying recombinant proteins containing the CBD tag enabled the execution of both steps simultaneously and quickly and the obtention of β-galactosidases with promising catalytic characteristics for application in the food and pharmaceutical industries., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Because the process is cost-effective, microbial pectinase is used in juice clearing. The isolation, immobilization, and characterization of pectinase from Aspergillus nidulans (Eidam) G. Winter (AUMC No. 7147) were therefore the focus of the current investigation. Results: Ammonium sulphate (85%), DEAE-cellulose, and Sephadex G-200 were used to purify the enzyme. With a yield of 30.4%, the final specific activity was 400 units mg−1 protein and 125-fold purification. Using SDS-PAGE to validate the purification of the pectinase, a single band showing the homogeneity of the purified pectinase with a molecular weight of 50 kD was found. Chitosan and calcium alginate both effectively immobilized pectinase, with immobilization efficiencies of 85.7 and 69.4%, respectively. At 50, 55, 60, and 65 °C, the thermostability of both free and chitosan-immobilized pectinase was examined. The free and chitosan-immobilized enzymes had half-lives (t1/2) of 23.83 and 28.64 min at 65 °C, and their Kd values were 0.0291 and 0.0242 min−1, respectively. In addition, the Z values were 44.6 and 31.54 °C, while the D values were 79.2 and 95.1 min. Compared to the untreated one, the orange, mango, and pineapple juices treated with immobilized pure pectinase showed greater clarity. Following treatment with pure pectinase, the fruit juice's 1, 1-diphenyl-2-picrylhydrazyl and 2, 2′-azino-bis 3-ethylbenzothiazoline-6-sulfonate scavenging activities increased. Following treatment with pure pectinase, the amounts of total phenolics and total flavonoids increased. Conclusion: The procedure is deemed cost-effective in the food industry because the strong affinity of fungal pectinase for pectin. The investigated pectinase supported its usage in the food industry by being able to clear orange, mango, and pineapple juices. [ABSTRACT FROM AUTHOR]

A new method was developed to quickly produce carboxymethyl hemicellulose (CM-Hemi) and fluorescent nitrogen-doped carbon dots (N–CDs) from sugarcane bagasse (SB). These materials were then combined with calcium chloride (CaCl₂) to create hydrogel sensors with antibacterial and antifungal properties. The CM-Hemi@Ca-N–CDs hydrogel was effective against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria compared to CM-Hemi@Ca which give no antibacterial activity. Both hydrogels also exhibited antifungal properties against Candida albicans. Molecular docking studies revealed that the CM-Hemi@Ca-N–CDs hydrogel had strong binding interactions with the protein from Staphylococcus aureus and Candida albicans (1.92 A°) compard to Escherichia coli (2.01 A°), which was aligned with the inhibition zone measurements from the antibacterial test. The fluorescence microscope revealed differences in the emitted light color when the hydrogel interacted with different types of microorganisms, likely due to variations in their cell walls. Density functional theory (DFT) calculations indicate that the incorporation of N–CDs into the CM-Hemi@Ca hydrogel enhances its stability and rigidity. This is evidenced by the lower energy gap (Eg), higher electron affinity (μ), and lower softness (S) of the CM-Hemi@Ca-N–CDs compared to the CM-Hemi@Ca hydrogel. Additionally, the formation of amide bonds between the N–CDs and CM-Hemi contributes to the increased rigidity of the hydrogel.These findings supporting th effectiveness of CM-Hemi@Ca-N–CDs as an antibacterial/antifungal sensor. [ABSTRACT FROM AUTHOR]

Introduction: The CD16A protein encoding gene FcγRIIIa (FCGR3A) and its potential ligand Fibrinogen-like protein 2 (FGL2) are involved in various cell physiological activities on the extracellular surface. Aberrant expression of these genes has been linked to tumorigenesis. Methods: To assess the prognostic significance of FCGR3A and FGL2 transcription expression in glioma and explore their roles in glioma initiation and progression, we utilized multiple online databases, including TCGA, GEPIA, CGGA, cBioPortal, TISCH, LinkedOmics, Ivy Glioblastoma Atlas Project, and Human Protein Atlas. Results: Our analysis revealed that FCGR3A and FGL2 expression was significantly correlated with clinical variables such as age, tumor type, WHO grade, histology, IDH-1 mutation, and 1p19q status. A strong correlation was also observed between the transcriptional expression levels of FCGR3A and FGL2. High expression of both genes predicted poor prognosis in primary and recurrent glioma patients, particularly those with lower grade gliomas. Cox regression analysis further confirmed that elevated expression of FCGR3A and FGL2 were independent prognostic factors for shorter overall survival in glioma patients. Gene co-expression network analysis suggested that FCGR3A , FGL2 , and their co-expressed genes were involved in inflammatory activities and tumor-related signaling pathways. Additionally, tissue microarrays from glioma patients at Tiantan Hospital showed significantly higher FCGR3A protein expression in high-grade gliomas compared to low-grade gliomas. Discussion: In conclusion, our findings suggest that FCGR3A and FGL2 could serve as promising prognostic biomarkers and potential therapeutic targets for glioma patients. [ABSTRACT FROM AUTHOR]

Glioma is one of the most common malignant tumors and shows a high metastasis rate and poor prognosis. KLHDC8A has been implicated in several cancers, but its role in glioma and its potential as a biomarker remain unclear. We conducted a pan-cancer analysis of KLHDC8A using multiple databases and assessed its expression levels, survival associations, and diagnostic utility. Kaplan–Meier survival analysis and Receiver Operating Characteristic (ROC) curves were utilized to evaluate KLHDC8A's prognostic and diagnostic potential. Additionally, we investigated KLHDC8A's role in glioma cell proliferation and its involvement in the Wnt/β-catenin signaling pathway. Our pan-cancer analysis revealed significant dysregulation of KLHDC8A across various tumors. Elevated KLHDC8A expression was associated with poor overall survival (OS) in cancers including ACC, KIRP, LGG, and STAD. Disease-specific survival (DSS) analysis indicated worse outcomes in ACC, KIRP, and LGG with high KLHDC8A levels. ROC curve analysis demonstrated KLHDC8A's strong diagnostic potential for glioblastoma multiforme (GBM) and lower-grade gliomas (LGG), with AUC values of 0.920 and 0.748, respectively. In glioma patients, high KLHDC8A expression correlated with shorter OS and DSS in LGG, while no significant correlation was observed in GBM. Multivariate Cox regression confirmed KLHDC8A as an independent prognostic factor for OS and DSS in LGG. Knockdown experiments in glioma cell lines U251 and U87 showed that KLHDC8A silencing led to reduced cell proliferation and colony formation, which was associated with downregulation of key proteins in the Wnt/β-catenin pathway. Overall, KLHDC8A is a promising biomarker for the diagnosis and prognosis of LGG, and its high expression is linked to poor survival outcomes. The gene's involvement in the Wnt/β-catenin signaling pathway underscores its role in glioma progression, highlighting KLHDC8A's potential as a therapeutic target and diagnostic marker, particularly for LGG. [ABSTRACT FROM AUTHOR]

In the realm of cancer research, the tumor microenvironment (TME) plays a crucial role in tumor initiation and progression, shaped by complex interactions between cancer cells and surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted by various cellular constituents within the TME, including immune cells, cancer-associated fibroblasts, and cancer cells themselves. These cytokines facilitate intricate communication networks that significantly influence tumor initiation, progression, metastasis, and immune suppression. Pyroptosis contributes to TME remodeling by promoting the release of pro-inflammatory cytokines and sustaining chronic inflammation, impacting processes such as immune escape and angiogenesis. However, challenges remain due to the complex interplay among cytokines, pyroptosis, and the TME, along with the dual effects of pyroptosis on cancer progression and therapy-related complications like cytokine release syndrome. Unraveling these complexities could facilitate strategies that balance inflammatory responses while minimizing tissue damage during therapy. This review delves into the complex crosstalk between cytokines, pyroptosis, and the TME, elucidating their contribution to tumor progression and metastasis. By synthesizing emerging therapeutic targets and innovative technologies concerning TME, this review aims to provide novel insights that could enhance treatment outcomes for cancer patients. [ABSTRACT FROM AUTHOR]

Background: Cutaneous Leishmaniasis (CL) is a neglected tropical disease endemic in Brazil. Morbidity and disabilities caused by CL lesions require an analysis of a Global Burden of Disease (GBD), which would help discern the impact on the Brazilian population. Herein, we assess the burden of CL and its spatial and temporal patterns in Brazil between 2001 and 2021. Methodology/Principal findings: We estimated rates per 100,000 population for years lived with disabilities (YLD), years of life lost prematurely (YLL) and disability-adjusted life years (DALY) for each year of the study, sex assigned at birth, age group, and for each municipality in Brazil. In addition, the relative changes in these metrics over time for each region and sex were determined, as well as temporal trends using segmented joinpoint regression models. Using spatiotemporal analysis tools, we created choropleth maps representing DALY, YLD and YLL for three distinct periods (P1 = 2001 to 2007; P2 = 2008 to 2014; P3 = 2015 to 2021). These maps were constructed to visualize the inferences from Bayesian spatial statistics and Moran's autocorrelation using the Poisson model. The data were obtained from the DATASUS database. Although the global burden of CL has reduced over two decades, with the continual high impact among adults aged 20 to 39 years. In turn, YLL increased over time in 40-year-old populations, while among the elderly (>60 years old) this rate almost doubled from 2010 to 2021. Regarding the region of residence, we observed an average increase of 28% in YLL in Southeast, South and Central-West. Furthermore, the global burden of CL does not have a random spatial distribution, since there was a high-risk clustering of YLD in the north of the country. Interestingly, the YLL showed a vast geographic expansion through Brazilian territory. Conclusions: This study provides a comprehensive analysis of the burden of CL in Brazil, pointing out areas of highest disease burden, where control and surveillance efforts should be undertaken. Author summary: Previous studies on the burden of Cutaneous Leishmaniasis (CL) have focused on short-term investigations and concomitant with visceral leishmaniasis (VL). This might limit a more comprehensive understanding of CL dynamics. Furthermore, in Brazilian research, there is a lack of linkage between studies and the Global Burden of Disease (GBD) along with spatial and temporal analysis techniques, especially in CL. Our data showed a reduction in DALY and YLD rates. However, there was a significant increase in YLL, predominantly among adults and the elderly, and in previously unrecorded regions. It is important to emphasize the geographical disproportion of the YLD rate, given the formation of high-risk clusters in the North and Central-West regions. These results have significant implications for public health, as well as providing valuable information for directing efforts and resources. Studying the burden of CL in Brazil is crucial because it is among the countries with the highest number of global cases. Therefore, linking this study to spatial analysis has provided new insights and territorial patterns, as well as previously unknown manifestations. Additionally, it serves as a global benchmark that can help not only Brazil but also other endemic countries understand the dynamics of this disease and determine which political and surveillance measures can be taken. [ABSTRACT FROM AUTHOR]

Oxidative stress promotes T. cruzi growth and development of chronic Chagas heart dysfunction. However, the literature contains gaps that must be fulfilled, largely due to variations in parasite DTU sources, cell types, mouse strains, and tools to manipulate redox status. We assessed the impact of oxidative environment on parasite burden in cardiomyoblasts and the effects of the Nrf2-inducer COPP on heart function in BALB/c mice infected with either DTU-II Y or DTU-I Colombian T. cruzi strains. Treatment with antioxidants CoPP, apocynin, resveratrol, and tempol reduced parasite burden in cardiomyoblasts H9C2 for both DTUI- and II-strains, while H2O2 increased it. CoPP treatment improved electrical heart function when administered during acute stage of Y-strain infection, coinciding with an overall trend towards increased survival and reduced heart parasite burden. These beneficial effects surpassed those of trypanocidal benznidazole, implying that CoPP directly affects heart physiology. CoPP treatment had beneficial impact on heart systolic function when performed during acute and evaluated during chronic stage. No impact of CoPP on heart parasite burden, electrical, or mechanical function was observed during the chronic stage of Colombian-strain infection, despite previous demonstrations of improvement with other antioxidants. Treatment with CoPP also did not improve heart function of mice chronically infected with Y-strain. Our findings indicate that amastigote growth is responsive to changes in oxidative environment within heart cells regardless of the DTU source, but CoPP influence on heart parasite burden in vivo and heart function is mostly confined to the acute phase. The nature of the antioxidant employed, T. cruzi DTU, and the stage of disease, emerge as crucial factors to consider in heart function studies. Author summary: Chagas disease, caused by Trypanosoma cruzi, can lead to serious heart complications, known as Chagas cardiomyopathy. This study investigates the role of oxidative stress on the growth of T. cruzi and the effects of antioxidants, particularly protoporphyrin cobalt (CoPP), on heart health using two distinct strains of the parasite (Y and Colombian strains). We found that CoPP and other antioxidants, including apocynin, resveratrol, and tempol, reduced parasite levels in heart cells, while oxidative stress increased it. In mice infected with the Y strain of T. cruzi, CoPP treatment during the acute phase improved heart function, reduced parasite burden, and increased survival, outperforming the standard treatment with benznidazole. However, CoPP's benefits were mostly confined to the early stages of infection. When treatment was administered during the chronic phase, it did not improve heart function or reduce parasite levels in mice infected with the Colombian strain, despite previous studies showing that other antioxidants can be beneficial in this stage. These findings suggest that the type of antioxidant and the timing of treatment are crucial in managing Chagas disease. This work underscores the potential of early antioxidant treatments like CoPP to protect heart function and prevent long-term damage, potentially offering better treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: Natural biopolymers are used for various purposes in healthcare, such as tissue engineering, drug delivery, and wound healing. Bacterial cellulose and chitosan were preferred in this study due to their non-cytotoxic, biodegradable, biocompatible, and non-inflammatory properties. The study reports the development of a magnetic bacterial cellulose-chitosan (BC-CS-Fe3O4) nanocomposite that can be used as a biocompatible scaffold for tissue engineering. Iron oxide nanoparticles were included in the composite to provide superparamagnetic properties that are useful in a variety of applications, including osteogenic differentiation, magnetic imaging, drug delivery, and thermal induction for cancer treatment. Methods: The magnetic nanocomposite was prepared by immersing Fe3O4 in a mixture of bacterial cellulose-chitosan scaffold and then freeze-drying it. The resulting nanocomposite was characterized using FE-SEM and FTIR techniques. The swelling ratio and mechanical strength of the scaffolds were evaluated experimentally. The biodegradability of the scaffolds was assessed using PBS for 8 weeks at 37°C. The cytotoxicity and osteogenic differentiation of the nanocomposite were studied using human adipose-derived mesenchymal stem cells (ADSCs) and alizarin red staining. One-way ANOVA with Tukey's multiple comparisons test was used for statistical analysis. Results: The FTIR spectra demonstrated the formation of bonds between functional groups of nanoparticles. FE-SEM images showed the integrity of the fibrillar network. The magnetic nanocomposite has the highest swelling ratio (2445% ± 23.34) and tensile strength (5.08 MPa). After 8 weeks, the biodegradation ratios of BC, BC-CS, and BC-CS-Fe3O4 scaffolds were 0.75% ± 0.35, 2.5% ± 0.1, and 9.5% ± 0.7, respectively. Magnetic nanocomposites have low toxicity (P < 0.0001) and higher osteogenic potential compared to other scaffolds. Conclusion: Based on its high tensile strength, low water absorption, suitable degradability, low cytotoxicity, and high ability to induce an increase in calcium deposits by stem cells, the magnetic BC-CS-Fe3O4 nanocomposite scaffold can be a suitable candidate as a biomaterial for osteogenic differentiation. [ABSTRACT FROM AUTHOR]

Background: The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019. Results: The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF. Conclusion: This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common harmful high-grade brain tumor with high mortality and low survival rate. Importantly, besides routine diagnostic and therapeutic methods, modern and useful practical techniques are urgently needed for this serious malignancy. Correspondingly, the translational medicine focusing on genetic and epigenetic profiles of glioblastoma, as well as the immune framework and brain microenvironment, based on these challenging findings, indicates that key clinical interventions include immunotherapy, such as immunoassay, oncolytic viral therapy, and chimeric antigen receptor T (CAR T) cell therapy, which are of great importance in both diagnosis and therapy. Relatively, vaccine therapy reflects the untapped confidence to enhance GBM outcomes. Ongoing advances in immunotherapy, which utilizes different methods to regenerate or modify the resistant body for cancer therapy, have revealed serious results with many different problems and difficulties for patients. Safe checkpoint inhibitors, adoptive cellular treatment, cellular and peptide antibodies, and other innovations give researchers an endless cluster of instruments to plan profoundly in personalized medicine and the potential for combination techniques. In this way, antibodies that block immune checkpoints, particularly those that target the program death 1 (PD-1)/PD-1 (PD-L1) ligand pathway, have improved prognosis in a wide range of diseases. However, its use in combination with chemotherapy, radiation therapy, or monotherapy is ineffective in treating GBM. The purpose of this review is to provide an up-to-date overview of the translational elements concentrating on the immunotherapeutic field of GBM alongside describing the molecular mechanism involved in GBM and related signaling pathways, presenting both historical perspectives and future directions underlying basic and clinical practice. [ABSTRACT FROM AUTHOR]

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The pikeperch (Sander lucioperca, Linnaeus, 1758), with its unique characteristics, has gained increasing attention in the aquaculture sector. These include its highly valued and delicious meat, soft white tissue with few intermuscular bones, commendable growth performance, and favorable market acceptance. It is farmed in North, Central, Western, and East Europe through recirculation aquaculture systems (RAS), net pens, and pond aquaculture. Nevertheless, the sensitivity of pikeperch to environmental changes and other aquaculture activities has made the need to provide optimal rearing conditions for the growth and survival of this valuable species a priority in its propagation and rearing industry, whereas the aquaculture stressors (e.g., handling, transporting, stocking density) and environmental conditions (e.g., photoperiod, temperature, oxygen status, water quality, oxidative stress) are inevitable factors in pikeperch aquaculture industries that affect the entire life cycle. Meanwhile, examining the adaptive or maladaptive responses of pikeperch to these stressors, in addition to being able to determine the tolerance limit of the fish, sheds light on the type of tissue, involved organs, and adaptive or maladaptive drivers of the fish. Certainly, identifying this tolerance limit and the organs involved is crucial to optimize the breeding conditions and provide the welfare of these valuable species. Hence, the effects of environmental stressors on pikeperch physiological changes deserve further investigation. Therefore, to help ameliorate management methods in pikeperch culture, this review discussed the pikeperch adaptive or maladaptive reactions to various environmental stressors. Accordingly, this paper identified the leading and complementary indicators (effective causes) inducing stress in pikeperch during aquaculture operations and identified management errors to conserve its safety, welfare, and survival. It will prevent destructive stress consequences that lead to disease, retardation, or lack of growth and reproduction in this species. [ABSTRACT FROM AUTHOR]

This study investigated the role of O6‐methylguanine‐DNA methyltransferase promoter (MGMTp) methylation hierarchy and heterogeneity in grade 2–3 gliomas, focusing on variations in chemotherapy benefits and resection dependency. A cohort of 668 newly diagnosed grade 2–3 gliomas, with comprehensive clinical, radiological, and molecular data, formed the basis of this analysis. The extent of resection was categorized into gross total resection (GTR ≥100%), subtotal resection (STR >90%), and partial resection (PR ≤90%). MGMTp methylation levels were examined using quantitative pyrosequencing. Our findings highlighted the critical role of GTR in improving the prognosis for astrocytomas (IDH1/2‐mutant and 1p/19q non‐codeleted), contrasting with its lesser significance for oligodendrogliomas (IDH1/2 mutation and 1p/19q codeletion). Oligodendrogliomas demonstrated the highest average MGMTp methylation levels (median: 28%), with a predominant percentage of methylated cases (average methylation levels >20%). Astrocytomas were more common in the low‐methylated group (10%–20%), while IDH wild‐type gliomas were mostly unmethylated (<10%). Spatial distribution analysis revealed a decrement in frontal lobe involvement from methylated, low‐methylated to unmethylated cases (72.8%, 59.3%, and 47.8%, respectively). In contrast, low‐methylated and unmethylated cases were more likely to invade the temporal‐insular region (19.7%, 34.3%, and 40.4%, respectively). Astrocytomas with intermediate MGMTp methylation were notably associated with temporal‐insular involvement, potentially indicating a moderate response to temozolomide and underscoring the importance of aggressive resection strategies. In conclusion, our study elucidates the complex interplay of MGMTp methylation hierarchy and heterogeneity among grade 2–3 gliomas, providing insights into why astrocytomas and IDH wild‐type lower‐grade glioma might derive less benefit from chemotherapy. [ABSTRACT FROM AUTHOR]

Summary: Background: Treatment failure (TF) in leprosy following multidrug therapy (MDT) presents a significant challenge. The current World Health Organization (WHO) fixed-duration MDT regimen, based on lesion count, might not be adequate. Leprosy lacks clear-cut objective cure criteria, and the predictive value of post-MDT histopathological findings remains uncertain. This study aims to identify predictive factors for TF among leprosy patients who have completed the WHO-recommended MDT. Methods: An analysis was conducted on 80 individuals from a national leprosy reference center, comprising 40 TF cases (with a mean relapse at 13.0 months) and 40 controls (with a mean of 113.1 months without disease signs). Various epidemiological and clinical-laboratory parameters were assessed post-MDT. Results: In skin samples, the presence of foamy granuloma (OR = 7.36; 95%CI2.20-24.60; p = 0.0012) and histological bacillary index (hBI) ≥ 1+ (OR = 1.55; 95%CI1. 22-1.99; p = 0.0004) were significantly associated with TF, with odds ratios of 7.36 and 1.55, respectively. Individuals who experienced TF had a mean hBI of 3.02+ (SD ± 2.02), while the control group exhibited a mean hBI of 1.8+ (SD ± 1.88). An hBI ≥ 3 + showed a sensitivity of 73% and a specificity of 78% for TF detection (AUC: 0.75; p = 0.0001). Other histopathological features like epithelioid granulomas, and skin changes did not show significant associations (p > 0.05). Additionally, higher anti-phenolic glycolipid-I (anti-PGL-I) ELISA index (EI) levels were linked to a 1.4-fold increased likelihood for TF (OR = 1.4; 95%CI1.13-1.74; p = 0.0019). A mean EI of 4.48 (SD ± 2.80) was observed, with an EI ≥ 3.95 showing a sensitivity of 79% and a specificity of 59% for TF detection (AUC: 0.74; p = 0.0001). Moreover, the presence of Mycobacterium leprae (M. leprae) DNA in real-time polymerase chain reaction (qPCR) was associated with a 3.43-fold higher likelihood of TF. Multivariate regression analysis indicated that concurrent presentation of neural/perineural lymphocytic infiltrate, foamy granuloma, hBI ≥ 1+, and EI ≥ 1 markedly increased the likelihood of TF by up to 95.41%. Conclusion: Persistence of nerve-selective lymphocytic infiltrate, foamy granulomas, and bacilli in skin biopsies, and elevated EI post-MDT, may serve as predictive factors for identifying individuals at higher probability of TF. [ABSTRACT FROM AUTHOR]

Background: The radiogenomic analysis has provided valuable imaging biomarkers with biological insights for gliomas. The radiogenomic markers for molecular profile such as DNA methylation remain to be uncovered to assist the molecular diagnosis and tumor treatment. Methods: We apply the machine learning approaches to identify the magnetic resonance imaging (MRI) features that are associated with molecular profiles in 146 patients with gliomas, and the fitting models for each molecular feature (MoRad) are developed and validated. To provide radiological annotations for the molecular profiles, we devise two novel approaches called radiomic oncology (RO) and radiomic set enrichment analysis (RSEA). Results: The generated MoRad models perform well for profiling each molecular feature with radiomic features, including mutational, methylation, transcriptional, and protein profiles. Among them, the MoRad models have a remarkable performance in quantitatively mapping global DNA methylation. With RO and RSEA approaches, we find that global DNA methylation could be reflected by the heterogeneity in volumetric and textural features of enhanced regions in T2-weighted MRI. Finally, we demonstrate the associations of global DNA methylation with clinicopathological, molecular, and immunological features, including histological grade, mutations of IDH and ATRX, MGMT methylation, multiple methylation-high subtypes, tumor-infiltrating lymphocytes, and long-term survival outcomes. Conclusions: Global DNA methylation is highly associated with radiological profiles in glioma. Radiogenomic global methylation is an imaging-based quantitative molecular biomarker that is associated with specific consensus molecular subtypes and immune features. [ABSTRACT FROM AUTHOR]

Dermatology is an important specialty in veterinary medicine, focusing on the skin and its appendages. Therefore, the present study highlighted the percentage of skin disorders, as well as their associated risk factors, from cases received at the Parasitology-Dermatology clinic of the Hassan II Institute of Agronomy and Veterinary Medicine (IAV Hassan II), Rabat, Morocco for two years. A total of 1561 dogs (1450 dogs were in 28 different pure breeds and 111 dogs were mongrels, 805 males, and 756 females, with an average age of 6.5 years old) were presented at the University Veterinary Teaching Hospital (UVTH) of the IAV Hassan II from the end of October 2020 to the end of May 2022 (including vaccinations) and 125 dogs were assessed and 161 skin diseases were found (a few dogs had more than one skin disease). Dermatological examinations represented an average of 8.00% (125/1561) of all canine cases received at the University Veterinary Teaching Hospital. The most common clinical signs were pruritus, alopecia, erythema, onychogryphosis, and visible ectoparasites. Parasitic dermatoses were the most frequent, representing 44.10% of all dermatological cases, followed by allergic dermatoses (25.47%) and fungal skin infections (19.25%). Bacterial skin infections and dermatological manifestations of endocrine disorders were infrequent, representing 8.70% and 2.48%, respectively of all observed cases. Risk factors contributing to the occurrence of canine skin disorders included age and lifestyle for sarcoptic mange. An apparent predilection for the living environment was observed in the case of canine leishmaniosis, and an apparent predilection for sex regarding otodectic mange was also demonstrated. Similar results were found for the living environment and lifestyle concerning canine atopic dermatitis. Data reported herein fill gaps in knowledge of skin disorders and their associated risk factors in dogs in Morocco, demonstrating the dominance of skin diseases of zoonotic interest, including flea bite allergy dermatitis (FBAD), dermatophytosis, and canine leishmaniosis. [ABSTRACT FROM AUTHOR]

Background and Aim: The most prevalent form of leishmaniasis is cutaneous leishmaniasis (CL), which manifests as a single ulcerative or nodular lesion that usually heals on its own. The aims of this study were to investigate the histopathologic and clinical features of CL patients. Methods: This cross-sectional study was accomplished on 70 CL patients that referred to Razi dermatology hospital in Iran, over a five-year period from 2016 to 2020. Included patients were those who were diagnosed clinically suspected patients whom their disease was confirmed through histopathology examination. Results: The age of patients ranged from 2 to 76 years with a mean of 42.26 ± 20.86 years. The majority of patients were men (54.3%). The plaque form lesions were the most frequent type (64.3%). Respecting lesion site, face, and upper limbs were more frequent with the abundances of 47.1% and 34.3%, respectively. All of the patients had evidence of cellulitis on ultrasound. The most prevalent change of epidermis was hyperkeratosis (42.8%). Regarding dermal histopathologic changes, infiltration of lymphocytes (61.4%), plasma cells (58.6%), and histiocytes (48.6%), as well as granuloma formation (54.3%) and leishman body presence (54.3%) were the dominant changes. Some patients had atypical forms of CL as six of them had lupoid cutaneous leishmaniasis (LCL) and five had sporotrichoid cutaneous leishmaniasis (SCL). Conclusion: In this study, men and those who were in middle age were more susceptible to be infected, so it suggests considering them particularly in the preventive programs. Moreover, histopathological findings of CL, including LCL and SCL, are presented. These findings may be beneficial for dermatologists and dermatopathologists to differentiate them from other cutaneous diseases. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GC) and parathyroid hormone (PTH) are widely used therapeutic endocrine hormones where their effects on bone and joint arise from actions on multiple skeletal cell types. In osteocytes, GC and PTH exert opposing effects on perilacunar canalicular remodeling (PLR). Suppressed PLR can impair bone quality and joint homeostasis, including in GC-induced osteonecrosis. However, combined effects of GC and PTH on PLR are unknown. Given the untapped potential to target osteocytes to improve skeletal health, this study sought to test the feasibility of therapeutically mitigating PLR suppression. Focusing on subchondral bone and joint homeostasis, we hypothesize that PTH(1-34), a PLR agonist, could rescue GC-suppressed PLR. The skeletal effects of GC and PTH(1-34), alone or combined, were examined in male and female mice by microcomputed tomography, mechanical testing, histology, and gene expression analysis. For each outcome, females were more responsive to GC and PTH(1-34) than males. GC and PTH(1-34) exerted regional differences, with GC increasing trabecular bone volume but reducing cortical bone thickness, stiffness, and ultimate force. Despite PTH(1-34)'s anabolic effects on trabecular bone, it did not rescue GC's catabolic effects on cortical bone. Likewise, cartilage integrity and subchondral bone apoptosis, tartrate-resistant acid phosphatase (TRAP) activity, and osteocyte lacunocanalicular networks showed no evidence that PTH(1-34) could offset GCdependent effects. Rather, GC and PTH(1-34) each increased cortical bone gene expression implicated in bone resorption by osteoclasts and osteocytes, including Acp5, Mmp13, Atp6v0d2, Ctsk, differences maintained when GC and PTH(1-34) were combined. Since PTH(1-34) is insufficient to rescue GC's effects on young female mouse bone, future studies are needed to determine if osteocyte PLR suppression, due to GC, aging, or other factors, can be offset by a PLR agonist. [ABSTRACT FROM AUTHOR]

Introduction: Deep learning (DL) for screening diabetic retinopathy (DR) has the potential to address limited healthcare resources by enabling expanded access to healthcare. However, there is still limited health economic evaluation, particularly in low- and middle-income countries, on this subject to aid decision-making for DL adoption., Methods: In the context of a middle-income country (MIC), using Thailand as a model, we constructed a decision tree-Markov hybrid model to estimate lifetime costs and outcomes of Thailand's national DR screening program via DL and trained human graders (HG). We calculated the incremental cost-effectiveness ratio (ICER) between the two strategies. Sensitivity analyses were performed to probe the influence of modeling parameters., Results: From a societal perspective, screening with DL was associated with a reduction in costs of ~ US$ 2.70, similar quality-adjusted life-years (QALY) of + 0.0043, and an incremental net monetary benefit of ~ US$ 24.10 in the base case. In sensitivity analysis, DL remained cost-effective even with a price increase from US$ 1.00 to US$ 4.00 per patient at a Thai willingness-to-pay threshold of ~ US$ 4.997 per QALY gained. When further incorporating recent findings suggesting improved compliance to treatment referral with DL, our analysis models effectiveness benefits of ~ US$ 20 to US$ 50 depending on compliance., Conclusion: DR screening using DL in an MIC using Thailand as a model may result in societal cost-savings and similar health outcomes compared with HG. This study may provide an economic rationale to expand DL-based DR screening in MICs as an alternative solution for limited availability of skilled human resources for primary screening, particularly in MICs with similar prevalence of diabetes and low compliance to referrals for treatment., (© 2023. The Author(s).)

Glioma is the most common malignant tumor in the central nervous system, and its unique pathogenesis often leads to poor treatment outcomes and prognosis. In 2021, the World Health Organization (WHO) divided gliomas into five categories based on their histological characteristics and molecular changes. Non-coding RNA is a type of RNA that does not encode proteins but can exert biological functions at the RNA level, and long non-coding RNA (lncRNA) is a type of non-coding RNA with a length exceeding 200 nt. It is controlled by various transcription factors and plays an indispensable role in the regulatory processes in various cells. Numerous studies have confirmed that the dysregulation of lncRNA is critical in the pathogenesis, progression, and malignancy of gliomas. Therefore, this article reviews the proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, glycolysis, stemness, and drug resistance changes caused by the dysregulation of lncRNA in gliomas, and summarizes their potential clinical significance in gliomas. [ABSTRACT FROM AUTHOR]

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The esterification of starches with octenyl succinic anhydride (OSA) under alkaline conditions is a modification process that takes a long time. Ultrasound-assisted esterification was investigated as an alternative for obtaining esterified starches with higher degree of substitution (DS) and reaction efficiency (RE), which could have more possibilities of application. Andean native potato starches were subjected to a conventional esterification process (OSA) and esterification with ultrasound-assisted treatment (US-OSA). The morphological and size distribution of granules, molecular features (infrared spectroscopy and X-ray diffraction), thermal, and rheological characteristics were assessed. The DS and RE for US-OSA starches were higher than those for OSA ones. Modified starches showed some peeled granules with a few pores in their surfaces, and also, span values of US-OSA starches were lower than OSA ones. Molecular studies showed that both starches, OSA and US-OSA, did not exhibit notable differences. Enthalpy of gelatinization for US-OSA starches was lower than of OSA ones. Hence, the results suggest that the esterification process of starches can be facilitated with a green technology such as ultrasound-assisted treatment, which is fast-paced and does not change the esterified starch characteristics. [ABSTRACT FROM AUTHOR]

The parasite Leishmania (Viannia) braziliensis is widely distributed in Brazil and is one of the main species associated with human cases of different forms of tegumentary leishmaniasis (TL) such as cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML). The mechanisms underlying the pathogenesis of TL are still not fully understood, but it is known that factors related to the host and the parasite act in a synergistic and relevant way to direct the response to the infection. In the host, macrophages have a central connection with the parasite and play a fundamental role in the defense of the organism due to their ability to destroy intracellular parasites and present antigens. In the parasite, some intrinsic factors related to the species or even the strain analyzed are fundamental for the outcome of the disease. One of them is the presence of Leishmania RNA Virus 1 (LRV1), an endosymbiont virus that parasitizes some species of Leishmania that triggers a cascade of signals leading to a more severe TL phenotype, such as ML. One of the strategies for understanding factors associated with the immune response generated after Leishmania/host interaction is through the analysis of molecular patterns after infection. Thus, the gene expression profile in human monocyte-derived macrophages obtained from healthy donors infected in vitro with L. braziliensis positive (LbLRV1+) and negative (LbLRV1-) for LRV1 was evaluated. For this, the microarray assay was used and 162 differentially expressed genes were identified in the comparison LbLRV1+ vs. LbLRV1-, 126 upregulated genes for the type I and II interferons (IFN) signaling pathway, oligoadenylate synthase OAS/RNAse L, non-genomic actions of vitamin D3 and RIG-I type receptors, and 36 down-regulated. The top 10 downregulated genes along with the top 10 upregulated genes were considered for analysis. Type I interferon (IFNI)- and OAS-related pathways results were validated by RT-qPCR and Th1/Th2/Th17 cytokines were analyzed by Cytometric Bead Array (CBA) and enzyme-linked immunosorbent assay (ELISA). The microarray results validated by RT-qPCR showed differential expression of genes related to IFNI-mediated pathways with overexpression of different genes in cells infected with LbLRV1+ compared to LbLRV1- and to the control. No significant differences were found in cytokine levels between LbLRV1+ vs. LbLRV1- and control. The data suggest the activation of gene signaling pathways associated with the presence of LRV1 has not yet been reported so far. This study demonstrates, for the first time, the activation of the OAS/RNase L signaling pathway and the non-genomic actions of vitamin D3 when comparing infections with LbLRV1+ versus LbLRV1- and the control. This finding emphasizes the role of LRV1 in directing the host's immune response after infection, underlining the importance of identifying LRV1 in patients with TL to assess disease progression. Author summary: Leishmania (Viannia) braziliensis is a parasite prevalent in Brazil and associated with tegumentary leishmaniasis (TL), including cutaneous (CL) and mucosal (ML) forms. The mechanisms of pathogenesis of TL are not fully understood, including some factors related to the host and parasite interaction in response to infection, and especially about Leishmania RNA Virus 1 (LRV1), an endosymbiont virus parasitizing Leishmania species, particularly triggers ML. Molecular approaches are usually applied to compare situations and to understand these interactions. Here, microarray analysis identified 162 differentially expressed genes in LbLRV1+ vs. LbLRV1- infection, with 126 upregulated genes related to IFN signaling, OAS/RNAse L, vitamin D3, and RIG-I type receptors. Additionally, 36 down-regulated genes were observed. Then, two validation assays were performed to confirm these results (RT-qPCR and Cytometric Bead Array). The main results comprise the differential gene expression in cells infected with LbLRV1+ compared to LbLRV1- and control, with overexpression of various genes in LbLRV1+ cells. Cytokine levels showed no significant differences between LbLRV1+ and LbLRV1-. This study highlighted the activation of the OAS/RNase L signaling pathway and the non-genomic actions of vitamin D3 in LbLRV1+ infection compared to LbLRV1- and control. This research contributes to our understanding of the immune response and molecular pathways involved in Leishmania infections, particularly in the presence of LRV1. [ABSTRACT FROM AUTHOR]