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Eosinophilic esophagitis (EoE) is a chronic, allergen-mediated, type-2 inflammatory disease with the potential to significantly impact an individual's quality of life. Conventional treatments often result in varied responses, prompting the need for novel therapeutic approaches. We present the case of a 19-year-old male with a medical history marked by eosinophilic esophagitis, severe atopic dermatitis (AD), asthma, and allergic rhinitis. Despite undergoing diverse topical and systemic interventions to address his AD and EoE, the patient's symptoms persisted. However, following the initiation of dupilumab therapy—a dual IL-4 and IL-13 receptor antagonist—the patient experienced a substantial reduction in his Eczema Area and Severity Index score. Notably, a marked improvement was also seen regarding his symptoms of eosinophilic esophagitis. A subsequent esophageal biopsy revealed a significant decrease in eosinophilic inflammation, consistent with established clinical and histologic remission criteria. These findings corroborate the patient's reported relief from symptoms. This case underscores the potential efficacy of dupilumab as a promising therapeutic agent in managing eosinophilic esophagitis. Dupilumab offers a dual benefit of alleviating symptoms and achieving histologic and clinical remission. This novel approach presents a noteworthy advancement in the treatment of EoE. [ABSTRACT FROM AUTHOR]

Respiratory viruses can cause life-threatening illnesses. The focus of treatment is on supportive therapies and direct antivirals. However, antivirals may cause resistance by exerting selective pressure. Modulating the host response has emerged as a viable therapeutic approach for treating respiratory infections. Additionally, considering the probable future respiratory virus outbreaks emphasizes the need for broad-spectrum therapies to be prepared for the next pandemics. One of the principal bioactive constituents found in the seed extract of Aesculus hippocastanum L. (AH) is β-escin. The clinical therapeutic role of β-escin and AH has been associated with their anti-inflammatory effects. Regarding their mechanism of action, we and others have shown that β-escin and AH affect NF-κB signaling. Furthermore, we have reported the virucidal and broad-spectrum antiviral properties of β-escin and AH against enveloped viruses such as RSV, in vitro and in vivo. In this study, we demonstrate that β-escin and AH have antiviral and virucidal activities against SARS-CoV-2 and CCoV, revealing broad-spectrum antiviral activity against coronaviruses. Likewise, they exhibited NF-κB and cytokine modulating activities in epithelial and macrophage cell lines infected with coronaviruses in vitro. Hence, β-escin and AH are promising broad-spectrum antiviral, immunomodulatory, and virucidal drugs against coronaviruses and respiratory viruses, including SARS-CoV-2. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effect of the number of uses and autoclave sterilization on the cyclic fatigue resistance of four replica-like instruments RC Blue; Only One File Blue; Recip One Blue; and Micro Blue compared to the original system Reciproc Blue (VDW, Munich, Germany). The instruments were analyzed by scanning electron microscope (SEM) before being used in root canal instrumentation (baseline). Fifty molars were instrumented by ten instruments (n=10). After sterilization in an autoclave, the instruments were analyzed by SEM. This procedure was repeated twice more using different molars, totaling 3 rounds of instrumentation, sterilization and SEM analysis. Then, ten different instruments from each brand were tested for cyclic fatigue resistance. Number of uses data were analyzed using Chi-squared analysis, and cyclic fatigue data were analyzed by one-way Anova followed by Tukey's test as the data had normal distribution. The fracture times for all systems had no significant difference, but Micro Blue had significantly lower values than the other systems (p < 0.05). The SEM analysis showed distortions in the instruments after the 3rd use. Therefore, all tested instruments except of Micro Blue have similar resistance to cyclic fatigue, and all are reliable for use in up to 2-cases. [ABSTRACT FROM AUTHOR]

Objectives: Current irritable bowel syndrome (IBS) treatments have limited efficacy and probiotics like Bacillus clausii (B. clausii) were found to be effective in the management of several gastrointestinal disorders. This phase III trial assessed the efficacy and safety of adding B. clausii (four strains: O/C, N/R, SIN, T), versus placebo, to conventional treatment of pediatric IBS in Mexico. Methods: Patients aged 6–17 years 11 months with IBS (Rome IV) for at least 2 months were randomized to receive either B. clausii (oral suspension, total dose 4 billion spores/day) or placebo once daily for 8 weeks. All patients also received conventional treatment. The primary endpoint was the difference in the proportion of patients with clinical improvements at Week 8 (Global Assessment Questions [GAQ]). Secondary endpoints included responders by Subject's Global Assessment of Relief for Children with IBS (SGARC); number/consistency of stools; abdominal distention/bloating; abdominal pain/intensity; and IBS behavior. Results: 73.6% (95% confidence interval [CI] 67.3–80.0; B. clausii n = 129) and 78.5% (95% CI 72.5–84.4; placebo n = 130) of patients had symptom improvement (p = 0.8182). For Week 8 SGARC, 19.2% (B. clausii) and 20.9% (placebo) reported complete symptom relief. Stool evaluations, bloating, abdominal pain/intensity, and IBS behavior were similar between groups. Both treatments were well tolerated. Conclusion: No significant differences in efficacy between B. clausii and placebo were demonstrated in addition to conventional treatment. The sample size calculation was based on an expected placebo/conventional treatment response of 30–40%. However, the actual treatment response observed was 80% and, thus, a study with larger population would be warranted. In addition, this study was conducted during the COVID-19 pandemic, when such controlled social conditions may have resulted in better diet, greater family stability, less psychological stress, and lower risk of infections exacerbating IBS, thereby improving symptoms in both groups. EudraCT number: 2018-004519-31. [ABSTRACT FROM AUTHOR]

Although it has been reported that bone marrow-derived cells (BMDCs) can transdifferentiate into neural cells, the findings are considered unlikely. It has been argued that the rapid neural transdifferentiation of BMDCs reported in culture studies is actually due to cytotoxic changes induced by the media. While transplantation studies indicated that BMDCs can form new neurons, it remains unclear whether the underlying mechanism is transdifferentiation or BMDCs-derived cell fusion with the existing neuronal cells. Cell fusion has been put forward to explain the presence of gene-marked binucleated neurons after gene-marked BMDCs transplantation. In the present study, we demostrated that human BMDCs can rapidly adopt a neural-like morphology through active neurite extension and binucleated human BMDCs can form with independence of any cell fusion events. We also showed that BMDCs neural-like differentiation involves the formation of intermediate cells which can then redifferentiate into neural-like cells, redifferentiate back to the mesenchymal fate or even repeatedly switch lineages without cell division. Furthermore, we have discovered that nuclei from intermediate cells rapidly move within the cell, adopting different morphologies and even forming binucleated cells. Therefore, our results provide a stronger basis for rejecting the idea that BMDCs neural transdifferentiation is merely an artefact. [ABSTRACT FROM AUTHOR]

The gut microbiota is intrinsically linked to human health; disturbances in microbial homeostasis are implicated in both intestinal and extraintestinal disorders. Probiotics are "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host," and many commercial preparations comprising a diverse range of species are available. While probiotics have been much researched, better understanding of the probiotic effects and applications of species such as Bacillus clausii is warranted. In this narrative literature review, we review the characteristics and mechanisms of action supporting B. clausii as a probiotic and discuss the evidence from clinical studies evaluating B. clausii probiotics for the management of a variety of gastrointestinal disorders and symptoms in children and adults. Finally, we highlight the challenges of future research and the need for more robust and diverse clinical evidence to guide physicians in the clinical application of probiotics for gastrointestinal disorders and other conditions. [ABSTRACT FROM AUTHOR]

Although it has been reported that mesenchymal stem cells isolated from adult tissues can be induced to overcome their mesenchymal fate and transdifferentiate into neural cells, the findings and their interpretation have been challenged. The main argument against this process is that the cells rapidly adopt neuron-like morphologies through retraction of the cytoplasm rather than active neurite extension. In this study, we examined the sequence of biological events during neural differentiation of human periodontal ligament-derived stem cells (hPDLSCs), human bone marrow-derived stem cells (hBMSCs) and human dental pulp-derived stem cells (hDPSCs) by time-lapse microscopy. We have demonstrated that hPDLSCs, hBMSCs and hDPSCs can directly differentiate into neuron-like cells without passing through a mitotic stage and that they shrink dramatically and change their morphology to that of neuron-like cells through active neurite extension. Furthermore, we observed micronuclei movement and transient cell nuclei lobulation concurrent to in vitro neurogenesis from hBMSCs and hDPSCs. Our results demonstrate that the differentiation of hPDLSCs, hBMSCs and hDPSCs towards a neural lineage occurs through a dedifferentiation step followed by differentiation to neural phenotypes, and therefore we definitively confirm that the rapid acquisition of the neural phenotype is via a differentiation trait. [ABSTRACT FROM AUTHOR]

Objective: Evaluate, in vivo, the biocompatibility via subcutaneous inflammatory tissue response and mineralization ability of the new MTA Flow compared to MTA Angelus and ProRoot MTA.Materials and methods: Forty male Wistar rats were assigned and received subcutaneous polyethylene tube implants containing the test materials and a control group with empty tube (n = 10 animals/group). After days 7, 15, 30, and 60, the animals were euthanized and the polyethylene tubes were removed with the surrounding tissues. Inflammatory infiltrate and thickness of the fibrous capsule were histologically evaluated. Mineralization was analyzed by Von Kossa staining and under polarized light. Data were analyzed via Kruskal-Wallis and Dunn's test with a significance level of 5%.Results: MTA Angelus induced the mildest reaction after 7 (P > .05) and 15 days (P < .05) followed by MTA Flow, both cements achieving mild inflammatory reaction after 15 days. ProRoot MTA induced a severe inflammation on day 7 and was reducing after day 15 (P > .05). No difference was observed after days 30 or 60 (P > .05). Von Kossa staining and birefringent structures were positive to all materials.Conclusions: At the end of the experiment, the novel MTA Flow showed biocompatibility and induced biomineralization in all time periods.Clinical relevance: The final consistence obtained in MTA Flow may facilitate several procedures, indicating that the MTA Flow has a promising application in endodontics. [ABSTRACT FROM AUTHOR]

Objective: Evaluate, in vitro, the antimicrobial activity of Psidium cattleianum leaf extracts combined with calcium hydroxide against Enterococcus faecalis and Candida albicans biofilm.Materials and methods: Dentin specimens obtained from extracted bovine incisors were infected during 14 days with E. faecalis ATCC 29212 and C. albicans ATCC 10231. The specimens were filled with calcium hydroxide pastes prepared with the following vehicles: Psidium cattleianum ethanolic, Psidium cattleianum propylene glycolic, distilled water, and saline as control. After 24 h, 3, 7, and 14 days, the canals were irrigated with sterile saline and dried. Dentin samples were collected from the canals with burs of increasing diameters. To determine the number of colony-forming units (CFU), samples were inoculated onto BHI agar supplemented with yeast extract (0.5%), at 37 °C, for 48 h, in CO2 enriched atmosphere. Comparisons among the groups for the variation factors were performed by ANOVA and Tukey’s test.Results: Ethanolic and propylene glycolic extracts showed significantly higher antimicrobial activity against E. faecalis (p < 0.01) when compared with distilled water. The ethanolic extract exhibited in 24 h the same antibacterial activity that propylene glycolic extract and distilled water after 7 and 14 days. For C. albicans, all were effective in reducing the number of CFU at all periods.Conclusion: The P. cattleianum ethanolic extract presented the fastest and highest antimicrobial activity against E. faecalis, significantly reducing the microbial load in 24 h. All medications were effective against C. albicans.Clinical relevance: The antibacterial potential of P. cattleianum and its biological compatibility associated with calcium hydroxide indicate promising applications in the field of dentistry. [ABSTRACT FROM AUTHOR]

An approach to evaluate the structural reliability taking into account the degradation of the structural capacity due to corrosion of reinforced concrete buildings at the end of a time interval is proposed. The structural reliability is expressed in terms of the confidence factor, within a Demand and Capacity Factor Design format (DCFD). A new closed-form mathematical expression that considers the non-linear structural capacity degradation due to corrosion by means of a second degree polynomial function is developed. The confidence factors are obtained under the assumption that the structural capacity degradation due to corrosion follows a linear and non-linear function over a time interval. The structural reliability is obtained for a three-story reinforced concrete building subjected to two sets of real seismic ground motions recorded in Acapulco Bay Mexico. Both, aleatory and epistemic uncertainties are taken into account into the analysis. A maximum difference of 3.5% between both functions after 83 years from the construction of the building was found. [ABSTRACT FROM AUTHOR]

The diencephalon is a complex brain area that derives from the caudal region of the prosencephalon. This structure is divided into four longitudinal neuroepithelial zones: roof, alar, basal and floor plates, which constitute its dorso-ventral (DV) columnar domains. Morphogenetic differences between alar and basal plates in the prosencephalon and mesencephalon contribute to the characteristic expansion of alar plate derivatives in the brain and the formation of the cephalic flexure. Although differential histogenesis among DV regions seems to be relevant in understanding structural and functional complexity of the brain, most of our knowledge about DV regionalization comes from the spinal cord development. Therefore, it seems of interest to study the molecular mechanisms that govern DV patterning in the diencephalon, the brain region where strong differences in size and complexity between alar and basal derivatives are evident in all vertebrates. Different morphogenetic signals, which induce specific progenitors fate to the neighboring epithelium, are involved in the spinal cord DV patterning. To study if Wnt1, one of these signaling molecules, has a role for the establishment of the diencephalic longitudinal domains, we carried out gain- and loss-of-function experiments, using mice and chick embryos. Our results demonstrated functional differences in the molecular mechanisms downstream of Wnt1 function in the diencephalon, in relation to the spinal cord. We further demonstrated that Bmp4 signal induces Wnt1 expression in the diencephalon, unraveling a new molecular regulatory code downstream of primary dorsalizing signals to control ventral regionalization in the diencephalon. [ABSTRACT FROM AUTHOR]

The pathogenesis of many viral infections lies on the damage caused by the immune response against the virus. Current antiviral drugs do not act on the inflammatory component of the disease. Thus, new compounds that inhibit both viral multiplication and the immunopathology elicited by the virus are an approach that should be considered. In the present study, we identified two jatropholones (2A and 5B) and one carnosic acid derivative (9C) that significantly inhibited multiplication of TK+ and TK− strains of HSV-1 in Vero cells. Compounds 2A, 5B and 9C also prevented HSV-1- and TLRs-induced inflammatory response in cultivated murine macrophages. In macrophages infected with HSV-1, the inhibitory effect of compounds 2A, 5B and 9C on TNF-α and IL-6 production could be associated with the block of ERK pathway, whereas NF-κB pathway was not hampered by any of the compounds. Besides, 2A, 5B and 9C also inhibited ERK pathway and reduced TNF-α production in macrophages stimulated with TLR2, TLR4 or TLR9 agonists and were able to hinder IL-6 secretion after activation with TLR2 or TLR4, but not with TLR9. The immunomodulatory effect of 2A, 5B and 9C in macrophages infected with HSV-1 may be a consequence of the inhibition of ERK pathway activated by TLRs. The availability of compounds with both antiviral and immunomodulatory properties which affect TLR signaling pathways might be a useful strategy to control the progress of virus-induced disease. [ABSTRACT FROM AUTHOR]

The combination of cell therapy with growth factors could be a useful approach to treat progressive muscular dystrophies. Here, we demonstrate, for the first time, that IGF-1 considerably enhances the myogenesis of human umbilical cord (UC) mesenchymal stromal cells (MSCs) in vitro and that IGF-1 enhances interaction and restoration of dystrophin expression in co-cultures of MSCs and muscle cells from Duchenne patients. In vivo studies showed that human MSCs were able to reach the skeletal muscle of LAMA2 dystrophic mice, through systemic delivery, without immunosuppression. Moreover, we showed, for the first time, that IGF-1 injected systemically together with MSCs markedly reduced muscle inflammation and fibrosis, and significantly improved muscle strength in dystrophic mice. Our results suggest that a combined treatment with IGF-1 and MSCs enhances efficiency of muscle repair and, therefore, should be further considered as a potential therapeutic approach in muscular dystrophies. [ABSTRACT FROM AUTHOR]

Element concentrations in biological tissues of Dmd/J and C57BL/6 J mice strains were determined using the neutron activation analysis technique. Samples of whole blood, bones and organs (heart and muscle) of these strains were irradiated in the IEA-R1 nuclear reactor at IPEN-CNEN/SP (Brazil). To perform this investigation biological samples of two-month-old adult females ( n = 10) and males ( n = 9) for Dmd/J (dystrophic mice), and males ( n = 12) for C57BL/6 J (control group), originally obtained from the Jackson Laboratory (Maine, USA) and further inbred at IPEN-CNEN/SP (São Paulo, Brazil), were used. A significant change was observed in the analysis of the heart of dystrophic mice suggesting that this dysfunction affects severely the heart muscle. These data may, in the future, contribute to the healthcare area, in veterinary medicine and in the pharmaceutical industry allowing the evaluation of the best procedures in diagnosis, treatment and investigations of neuromuscular diseases (muscular dystrophy) of patients through the use of animal models. [ABSTRACT FROM AUTHOR]

Understanding the sequence of events from undifferentiated stem cells to neuron is not only important for the basic knowledge of stem cell biology, but also for therapeutic applications. In this study we examined the sequence of biological events during neural differentiation of human periodontal ligament stem cells (hPDLSCs). Here, we show that hPDLSCs-derived neural-like cells display a sequence of morphologic development highly similar to those reported before in primary neuronal cultures derived from rodent brains. We observed that cell proliferation is not present through neurogenesis from hPDLSCs. Futhermore, we may have discovered micronuclei movement and transient cell nuclei lobulation coincident to in vitro neurogenesis. Morphological analysis also reveals that neurogenic niches in the adult mouse brain contain cells with nuclear shapes highly similar to those observed during in vitro neurogenesis from hPDLSCs. Our results provide additional evidence that it is possible to differentiate hPDLSCs to neuron-like cells and suggest the possibility that the sequence of events from stem cell to neuron does not necessarily requires cell division from stem cell. [ABSTRACT FROM AUTHOR]

Presents a comment on the purification of progenitor cells from heterogeneous cultures published in an article in the March 2000 issue of 'Nature Medicine.' Ability of progenitors to differentiate into mature neurons; Belief of a definite interference of enhanced green fluorescent protein with the normal biological properties of human neural stem cells.