Streptococcus dentisani inhibits the growth of Candida albicans and Candida glabrata: in vitro assay.

BACKGROUND: Probiotic bacteria inhibit aggregation, biofilm formation, and dimorphism of Candida spp. However, the effects of a new probiotic, Streptococcus dentisani, on the growth of Candida albicans and Candida glabrata biofilms are unknown. OBJECTIVE: To determine the effect of S. dentisani on the different phases of C. albicans and C. glabrata biofilm development. METHODS: Growth quantification and ultrastructural analyses were performed on biofilms of C. albicans ATCC 90028, C. glabrata ATCC 2001, and clinical isolates of C. albicans from oral candidiasis (CA-C1), caries (CA-CR1), and periodontal pocket (CA-P1) treated with cell suspensions of S. dentisani CECT 7746. Cell viability was determined by quantifying colony-forming units (CFU/mL). The ultrastructural analyses were done with atomic force microscopy. RESULTS: S. dentisani induced a significant reduction (p < 0.05) of CFU/mL of immature and mature biofilm in all strains of C. albicans and C. glabrata. Microscopic analysis revealed that S. dentisani reduced C. albicans density in mixed biofilm. The fungus-bacteria interaction affected cell membrane integrity in yeast. CONCLUSION: For the first time, our data elucidate the antifungal effect of S. dentisani on the development of C. albicans and C. glabrata biofilms, supporting its usefulness as a niche-specific probiotic to prevent and treat oral dysbiosis.

Effect of Live and Fragmented Saccharomyces cerevisiae in the Feed of Pigs Challenged with Mycoplasma hyopneumoniae.

Currently, the responsible use of antimicrobials in pigs has allowed the continuous development of alternatives to these antimicrobials. In this study, we describe the impact of treatments with two probiotics, one based on live Saccharomyces cerevisiae (S. cerevisiae) and another based on fragmented S. cerevisiae (beta-glucans), that were administered to piglets at birth and at prechallenge with Mycoplasma hyopneumoniae. Thirty-two pigs were divided into four groups of eight animals each. The animals had free access to water and food. The groups were as follows: Group A, untreated negative control; Group B, inoculated by nebulization with M. hyopneumoniae positive control; Group C, first treated with disintegrated S. cerevisiae (disintegrated Sc) and inoculated by nebulization with M. hyopneumoniae; and Group D, treated with live S. cerevisiae yeast (live Sc) and inoculated by nebulization with M. hyopneumoniae. In a previous study, we found that on Days 1 and 21 of blood sampling, nine proinflammatory cytokines were secreted, and an increase in their secretion occurred for only five of them: TNF-α, INF-α, INF-γ, IL-10, and IL-12 p40. The results of the clinical evolution, the degree of pneumonic lesions, and the productive parameters of treated Groups C and D suggest that S. cerevisiae has an immunomodulatory effect in chronic proliferative M. hyopneumoniae pneumonia characterized by delayed hypersensitivity, which depends on the alteration or modulation of the respiratory immune response. The data presented in this study showed that S. cerevisiae contributed to the innate resistance of infected pigs.

Familial LCAT Deficiency and Low HDL-C Levels: In silico Characterization of Two Rare LCAT Missense Mutations.

Mutations in the lecithin-cholesterol acyltransferase (LCAT) gene, which catalyzes the esterification of cholesterol, result in two types of autosomal recessive disorders: Familial LCAT deficiency (FLD) and Fish Eye Disease (FED). While both phenotypes are characterized by corneal opacities and different forms of dyslipidemia, such as low levels of high-density lipoprotein-cholesterol (HDL-C), FLD exhibits more severe clinical manifestations like splenomegaly, anemia, and renal failure. We describe the first clinically and genetically confirmed case of FLD in Colombia which corresponds to a 46-year-old woman with corneal opacity, hypothyroidism, and dyslipidemia, who does not have any manifestations of renal failure, with two pathogenic heterozygous missense variants in the LCAT gene: LCAT (NM_000229.2):c.803G>A (p.Arg268His) and LCAT (NM_000229.2):c.368G>C (p.Arg123Pro). In silico analysis of the mutations predicted the physicochemical properties of the mutated protein, causing instability and potentially decreased LCAT function. These compound mutations highlight the clinical heterogeneity of the phenotypes associated with LCAT gene mutations.

Arabinoxylans: A review on protocols for their recovery, functionalities and roles in food formulations.

Arabinoxylans (AXs) are compounds with high nutritional value and applicability, including prebiotics or supplementary ingredients, in food manufacturing industries. Unfortunately, the recovery of AXs may require advanced separation and integrated strategies. Here, an analysis of the emerging techniques to extract AXs from cereals and their by-products is discussed. This review covers distinct methods implemented over the last 2-3 years, identifying that the type of method, extraction source, AX physicochemical properties and pre-treatment conditions are the main factors influencing the recovery yield. Alkaline extraction is among the most used methods nowadays, mostly due to its simplicity and high recovery yield. Concurrently, recovered AXs applied in food applications is timely reviewed, such as potential bread ingredient, prebiotic and as a wall material for probiotic encapsulation, in beer and non-alcoholic beverage manufacturing, complementary ingredient in bakery products and cookies, improvers in Chinese noodles, 3D food printing and designing of nanostructures for delivery platforms.

Accelerating sexual maturation of male Anastrepha ludens (Diptera: Tephritidae) fruit flies by adding two juvenile hormone analogues.

BACKGROUND: Improving the mating competitiveness and survival of sterile males are direct means to increase the effectiveness of the sterile insect technique (SIT). Some insecticide growth regulators, such as the juvenile hormone analogue (JHA) methoprene, have been used to improve the mating competitiveness of male tephritid flies by reducing their sexual maturation period. However, the application of methoprene reduces fly resistance to stress and decreases survival. Here, we compared the effects of methoprene and pyriproxyfen (PPF), another JHA, in Anastrepha ludens males. PPF is an insect growth regulator that exhibits higher negative effects on the larval molting process than methoprene or natural juvenile hormone. Both compounds were administered at two doses (0.05% and 0.10%) via the male diet immediately after emergence. RESULTS: Our results show that both PPF and methoprene reduced male sexual maturation. However, PPF-treated males exhibited a shorter maturation period and obtained more matings at a given age than methoprene-treated males. No significant differences were observed between the two PPF doses tested (0.05% and 0.10%). Male survival was equally reduced by the two compounds. CONCLUSION: Our results demonstrate that PPF accelerated sexual development without reducing the mating propensity of sterile male flies and can be used as a suitable alternative for methoprene. © 2023 Society of Chemical Industry.

Necrostatin-1 releasing nanoparticles: In vitro and in vivo efficacy for supporting immunoisolated islet transplantation outcomes.

Immunoisolation of pancreatic islets in alginate microcapsules allows for transplantation in the absence of immunosuppression but graft survival time is still limited. This limited graft survival is caused by a combination of tissue responses to the encapsulating biomaterial and islets. A significant loss of islet cells occurs in the immediate period after transplantation and is caused by a high susceptibility of islet cells to inflammatory stress during this period. Here we investigated whether necrostatin-1 (Nec-1), a necroptosis inhibitor, can reduce the loss of islet cells under stress in vitro and in vivo. To this end, we developed a Nec-1 controlled-release system using poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) as the application of Nec-1 in vivo is limited by low stability and possible side effects. The PLGA NPs stably released Nec-1 for 6 days in vitro and protected beta cells against hypoxia-induced cell death in vitro. Treatment with these Nec-1 NPs at days 0, 6, and 12 post-islet transplantation in streptozotocin-diabetic mice confirmed the absence of side effects as graft survival was similar in encapsulated islet grafts in the absence and presence of Nec-1. However, we found no further prolongation of graft survival of encapsulated grafts which might be explained by the high biocompatibility of the alginate encapsulation system that provoked a very mild tissue response. We expect that the Nec-1-releasing NPs could find application to immunoisolation systems that elicit stronger inflammatory responses, such as macrodevices and vasculogenic biomaterials.

PRECICE nail for the management of posttraumatic bone defects with nonunion or malunion: Experience from a Latin American center.

BACKGROUND: To evaluate the clinical outcomes using the PRECICE magnetic limb lengthening intramedullary nail for the correction of lower limb length discrepancies (LLD) in adults with posttraumatic nonunion or malunion defects in a Latin American center. METHODS: A retrospective review of 25 adult patients with LLD associated with posttraumatic nonunion or malunion defects of femur or tibia treated with the PRECICE nail between January 2018 and December 2020. The primary outcomes considered were lengthening length achieved in mm, incidence of complications and quality of life (EQ-5D-3 L questionnaire). RESULTS: Twenty-five cases (20 femoral and 5 tibial nails) were performed, with a median follow-up of 27 months (Interquartile range-IQR: 17.5 to 34.5). The average age was 36.5 ± 12.9 years; 10 cases were women. Fifteen cases had an LLD secondary to a malunion defect and 10 cases had an LLD secondary to a nonunion. PRECICE nails were inserted for the treatment of a median LLD of 40.0 mm (IQR: 30.2 to 74.2) in the femur and 30.0 mm (28.5 to 50.0) in the tibia. An accuracy of 100% was reported in 18 cases (Femur: 14 and tibia: 4) and consolidation was achieved in 22/25 cases with the PRECICE nail in situ. Complications were recorded in 9 (36%) cases (6/20 femur, 3/5 tibia), mainly related to the consolidation process (5/9). The median EQ-5D and EQ-VAS were 0.79 (IQR: 0.63 to 0.79) and 80.0 (IQR: 50.0 to 90.0), respectively. CONCLUSIONS: The results of this study demonstrated that the PRECICE nail is an effective device for the management of posttraumatic LLD during the treatment of nonunion or malunion bone defects of femur and tibia, offering a reasonable quality of life, despite its postoperative complication risk.

Diagnóstico nuclear y sonográfico de tumor de Wilms bilateral multifocal estadio II sin invasión capsular / Nuclear and Sonographic Diagnosis of a Stage II Multifocal Bilateral Wilms Tumor without Capsular Invasion

Se presenta un diagnóstico nuclear y sonográfico de tumor de Wilms bilateral multifocal estadio II sin invasión capsular. Se describen voluminosas masas hipodensas en ambos riñones, estas masas presentan extensas zonas en su interior y se realzan de forma heterogénea con el medio de...(AU)

Corrigendum: MSC therapy ameliorates experimental gouty arthritis hinting an early COX-2 induction.

[This corrects the article DOI: 10.3389/fimmu.2023.1193179.].

Novel mutation in RPGRIP1L gene causing Joubert syndrome: A case report.

INTRODUCTION: Joubert syndrome is a rare disease of genetic origin with autosomal recessive inheritance and extreme genetic heterogeneity with more than 40 causative genes. Joubert syndrome 7 is caused by mutations in the RPGRIP1L gene. PATIENT CONCERNS: Our report describes a pediatric patient with clinical features compatible with JS type 7 such as hypotonia, developmental delay and aplasia of the cerebellar vermis. DIAGNOSIS: The clinical features and the MRI of the head and neck which showed alterations at the level of the posterior fossa, with absence of the vermis and horizontal disposition of the cerebellar peduncles, were compatible with Joubert syndrome. Whole exome sequencing detected the variants RPGRIP1L (NM_015272.2) c.697A > T (p. Lys233Ter) and RPGRIP1L (NM_015272.2) c.3545 del (p.Pro1182LeufsTer25). INTERVENTIONS: Resection was performed to correct the polydactyly. At age 2 years umbilical hernia, adenoid surgery and ventilatory tubes surgery were performed. Renal biopsy confirmed interstitial fibrosis and focally accentuated mild tubular atrophy with focal tubular hypertrophy, compatible with the clinical suspicion of Joubert syndrome. Congenital hip dislocation surgery was performed. The patient underwent surgery for correction of concomitant divergent strabismus and continued with glasses for astigmatism and hyperopia. OUTCOMES: Sanger sequencing confirmed the patient´s results and the father was found to be a carrier of RPGRIP1L (NM_015272.2) c.697A > T (p. Lys233Ter) and the mother and maternal grandmother as carriers of RPGRIP1L (NM_015272.2) c.3545del (p.Pro1182LeufsTer25). RPGRIP1L:c.3545del novel variant is a deletion which changes the reading frame, altering the RPGR1_C terminal domain and giving rise to an incomplete protein whose functions will be altered. CONCLUSION: This is the first genetically confirmed case of JS in Colombia, the first carrier of biallelic RPGRIP1L gene mutations with hip dislocation and incomplete glottic closure and the first report of the novel c.3545del likely pathogenic variant causing JS.

Immunometabolic actions of trabectedin and lurbinectedin on human macrophages: relevance for their anti-tumor activity.

In recent years, the central role of cell bioenergetics in regulating immune cell function and fate has been recognized, giving rise to the interest in immunometabolism, an area of research focused on the interaction between metabolic regulation and immune function. Thus, early metabolic changes associated with the polarization of macrophages into pro-inflammatory or pro-resolving cells under different stimuli have been characterized. Tumor-associated macrophages are among the most abundant cells in the tumor microenvironment; however, it exists an unmet need to study the effect of chemotherapeutics on macrophage immunometabolism. Here, we use a systems biology approach that integrates transcriptomics and metabolomics to unveil the immunometabolic effects of trabectedin (TRB) and lurbinectedin (LUR), two DNA-binding agents with proven antitumor activity. Our results show that TRB and LUR activate human macrophages toward a pro-inflammatory phenotype by inducing a specific metabolic rewiring program that includes ROS production, changes in the mitochondrial inner membrane potential, increased pentose phosphate pathway, lactate release, tricarboxylic acids (TCA) cycle, serine and methylglyoxal pathways in human macrophages. Glutamine, aspartate, histidine, and proline intracellular levels are also decreased, whereas oxygen consumption is reduced. The observed immunometabolic changes explain additional antitumor activities of these compounds and open new avenues to design therapeutic interventions that specifically target the immunometabolic landscape in the treatment of cancer.

Effects of Tofacitinib on Muscle Remodeling in Experimental Rheumatoid Sarcopenia.

Sarcopenia is a frequent comorbidity of rheumatoid arthritis (RA). Clinical trials have shown that JAK inhibitors (JAKi) produce an asymptomatic increase in serum creatine kinase (CK) in RA, suggesting an impact on muscle. We evaluated the effect of JAKi in muscle remodeling in an experimental RA model. Antigen-induced arthritis (experimental RA, e-RA) was performed in 14 rabbits. Seven rabbits received tofacitinib (TOFA, orally 10 mg/kg/day). Animals were euthanized one day after the last ovalbumin injection, and muscles were prepared for histology, RT-PCR, and WB. C-reactive protein (CRP) and Myostatin (MSTN) serum concentration were determined by ELISA. Creatine and creatine kinase (CK) were analyzed. An increase in body weight as well as tibialis anterior cross-sectional area and diameter was observed in e-RA+TOFA vs. e-RA. e-RA decreased type II fibers and increased the myonuclei number, with all reverted by TOFA. TOFA did not modify CRP levels, neither did MSTN. TOFA significantly reduced IL-6, atrogin-1, and MuRF-1 compared with e-RA. e-RA+TOFA showed higher CK and lower creatine levels compared with e-RA. No differences in PAX-7 were found, while TOFA prevented the increase in MyoD1 in e-RA. Our model reflects the features of rheumatoid sarcopenia in RA. JAKi increased muscle mass through attenuating IL-6/JAK/STAT activation, decreasing atrogenes, and restoring muscle differentiation markers. These data together with an increase in CK support the role of CK as a valuable marker of muscle gain following JAKi treatment.

Thermoluminescent glow curve of Gd1-xRExAlO3 (RE=Dy or Pr) beta irradiated phosphors.

Phosphors composed of Gd1-xRExAlO3 (0≤x ≤ 5 RE = Dy or Pr) stoichiometries were synthesized using the reverse coprecipitation pathway. The thermoluminescent responses of all phosphors were studied under beta radiation exposure. Doping the gadolinium aluminate host improved the thermoluminescent response of the phosphors, with the phosphors composed of Gd0.99Dy0.01AlO3 and Gd0.95Pr0.05AlO3 being the most sensitive. The Dy3+ ions produced a higher improvement of the thermoluminescent signal than the Pr3+ ions. Additionally, a proportional relationship between the similarity of the atomic numbers of the dopant and replaced ions and the sensitivity to thermoluminescence was confirmed. Besides, a slight shift of the thermoluminescent peaks toward lower temperatures was detected for doped phosphors. In the repeatability tests applied to the phosphor composed of Gd0.99Dy0.01AlO3, an anomalous increase in sensitization was observed. The observed sensitization was associated with the formation of electron trap clusters resulting from the continuous exposure to beta radiation. Furthermore, another sensitization phenomenon was detected in the phosphor with Gd0.95Pr0.05AlO3 stoichiometry when it was heated at low temperatures. The aforementioned striking behavior was related to quasi-continuous distributions of electron traps and the tunneling effect. In regard to linearity, the phosphor composed of Gd0.99Dy0.01AlO3 exhibited a linear response with the dose across the entire range of beta doses. However, the response of the Gd0.95Pr0.05AlO3 phosphor lost linearity beyond 26.4 Gy of beta dose. The results obtained through the use of the Tmax-Tstop method and deconvolutions suggested an enhancement in the efficiency of the thermoluminescent mechanisms due to the incorporation of activators.

Organ xenotransplantation acceptance in veterinary students: A multicentric opinion study in Spain.

BACKGROUND: The shortage of available transplant organs has made it necessary to search for alternatives, one of which is xenotransplantation. However, the use of animal organs could face rejection from society and the personnel involved in its implementation. OBJECTIVES: (a) to analyze the attitudes of Veterinary Degree students in six Spanish Universities towards xenotransplantation; and (b) to determine the factors that affect its acceptance. METHODS: Of the 2815 students surveyed in the degree program, 2683 valid surveys were obtained. Attitudes towards organ xenotransplantation were evaluated using a validated questionnaire of organ donation. RESULTS: If xenotransplantation was confirmed as a clinical reality, 93% (n = 2493) of those surveyed would accept a xenotransplanted organ, whilst 7% would not. If the results of xenotransplantation were worse than those obtained with human donors and it entailed more risk, 12% (n = 318) would be in favor. 56% (n = 1497) of the students would accept a xenotransplantation provisionally pending the arrival of a human organ. Attitudes towards xenotransplantation were affected by the academic year in which a student was studying, with more favorable attitudes among students in the last year (88% in first year vs. 95% in fifth year; p < .001). More favorable attitudes are also observed depending on the attitude they have towards organ transplantation, with those students being more in favor of donating their organs when they die (94% vs. 88%; p < .001). CONCLUSION: Veterinary students would have a very favorable attitude toward xenotransplantation if these animal organs functioned as well as human organs. Therefore, these students could play an important role in the future promotion of this technique.

MSC therapy ameliorates experimental gouty arthritis hinting an early COX-2 induction.

Objective: The specific effect of Adipose-Derived Mesenchymal Stem Cells (Ad-MSC) on acute joint inflammation, where the response mostly depends on innate immunity activation, remains elusive. The pathogenesis of gouty arthritis, characterized by the deposition of monosodium urate (MSU) crystals in the joints, associated to acute flares, has been associated to NLRP3 inflammasome activation and subsequent amplification of the inflammatory response. Our aim was to study the effect of human Ad-MSC administration in the clinical inflammatory response of rabbits after MSU injection, and the molecular mechanisms involved. Methods: Ad-MSC were administered by intraarterial route shortly after intraarticular MSU crystal injections. Joint and systemic inflammation was sequentially studied, and the mechanisms involved in NLRP3 inflammasome activation, and the synthesis of inflammatory mediators were assessed in the synovial membranes 72h after insult. Ad-MSC and THP-1-derived macrophages stimulated with MSU were co-cultured in transwell system. Results: A single systemic dose of Ad-MSC accelerated the resolution of local and systemic inflammatory response. In the synovial membrane, Ad-MSC promoted alternatively M2 macrophage presence, inhibiting NLRP3 inflammasome and inducing the production of anti-inflammatory cytokines, such as IL-10 or TGF-ß, and decreasing nuclear factor-κB activity. Ad-MSC induced a net anti-inflammatory balance in MSU-stimulated THP-1 cells, with a higher increase in IL-10 and IDO expression than that observed for IL-1ß and TNF. Conclusion: Our in vivo and in vitro results showed that a single systemic dose of Ad-MSC decrease the intensity and duration of the inflammatory response by an early local COX-2 upregulation and PGE2 release. Ad-MSCs suppressed NF-kB activity, NLRP3 inflammasome, and promoted the presence of M2 alternative macrophages in the synovium. Therefore, this therapeutic approach could be considered as a pharmacological alternative in patients with comorbidities that preclude conventional treatment.

Delayed graft rejection in autoimmune islet transplantation via biomaterial immunotherapy.

The induction of operational immune tolerance is a major goal in beta-cell replacement strategies for the treatment of type 1 diabetes. Our group previously reported long-term efficacy via biomaterial-mediated programmed death ligand 1 (PD-L1) immunotherapy in islet allografts in nonautoimmune models. In this study, we evaluated autoimmune recurrence and allograft rejection during islet transplantation in spontaneous nonobese diabetic (NOD) mice. Graft survival and metabolic function were significantly prolonged over 60 days in recipients of syngeneic islets receiving the biomaterial-delivered immunotherapy, but not in control animals. The biomaterial-mediated PD-L1 immunotherapy resulted in delayed allograft rejection in diabetic NOD mice compared with controls. Discrimination between responders and nonresponders was attributed to the enriched presence of CD206+ program death 1+ macrophages and exhausted signatures in the cytotoxic T cell compartment in the local graft microenvironment. Notably, draining lymph nodes had similar remodeling in innate and adaptive immune cell populations. This work establishes that our biomaterial platform for PD-L1 delivery can modulate immune responses to transplanted islets in diabetic NOD mice and, thus, can provide a platform for the development of immunologic strategies to curb the allo- and autoimmune processes in beta-cell transplant recipients.