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Skeletal muscles of patients with Duchenne muscular dystrophy (DMD) show numerous alterations including inflammation, apoptosis, and necrosis of myofibers. However, the molecular mechanism that explains these changes remains largely unknown. Here, the involvement of hemichannels formed by connexins (Cx HCs) was evaluated in skeletal muscle of mdx mouse model of DMD. Fast myofibers of mdx mice were found to express three connexins (39, 43 and 45) and high sarcolemma permeability, which was absent in myofibers of mdx Cx43 fl/fl Cx45 fl/fl :Myo-Cre mice (deficient in skeletal muscle Cx43/Cx45 expression). These myofibers did not show elevated basal intracellular free Ca 2+ levels, immunoreactivity to phosphorylated p65 (active NF-κB), eNOS and annexin V/active Caspase 3 (marker of apoptosis) but presented dystrophin immunoreactivity. Moreover, muscles of mdx Cx43 fl/fl Cx45 fl/fl :Myo-Cre mice exhibited partial decrease of necrotic features (big cells and high creatine kinase levels). Accordingly, these muscles showed similar macrophage infiltration as control mdx muscles. Nonetheless, the hanging test performance of mdx Cx43 fl/fl Cx45 fl/fl :Myo-Cre mice was significantly better than that of control mdx Cx43 fl/fl Cx45 fl/fl mice. All three Cxs found in skeletal muscles of mdx mice were also detected in fast myofibers of biopsy specimens from patients with muscular dystrophy. Thus, reduction of Cx expression and/or function of Cx HCs may be potential therapeutic approaches to abrogate myofiber apoptosis in DMD.

The Paced Auditory Serial Addition Test (PASAT) is a useful cognitive test in patients with multiple sclerosis (MS), assessing sustained attention and information processing speed. However, the neural underpinnings of performance in the test are controversial. We aimed to study the neural basis of PASAT performance by using structural magnetic resonance imaging (MRI) in a series of 242 patients with MS. PASAT (3-s) was administered together with a comprehensive neuropsychological battery. Global brain volumes and total T2-weighted lesion volumes were estimated. Voxel-based morphometry and lesion symptom mapping analyses were performed. Mean PASAT score was 42.98 ± 10.44; results indicated impairment in 75 cases (31.0%). PASAT score was correlated with several clusters involving the following regions: bilateral precuneus and posterior cingulate, bilateral caudate and putamen, and bilateral cerebellum. Voxel-based lesion symptom mapping showed no significant clusters. Region of interest-based analysis restricted to white matter regions revealed a correlation with the left cingulum, corpus callosum, bilateral corticospinal tracts, and right arcuate fasciculus. Correlations between PASAT scores and global volumes were weak. PASAT score was associated with regional volumes of the posterior cingulate/precuneus and several subcortical structures, specifically the caudate, putamen, and cerebellum. This emphasises the role of both cortical and subcortical structures in cognitive functioning and information processing speed in patients with MS.

Introduction Several experimental studies have suggested the potential remyelinating effects of vitamin D (VitD) supplements regardless of the presence of VitD deficiency. This study aims to analyze neurogenesis in a model of toxic demyelination in order to evaluate the effects of VitD on demyelination and remyelination. Material and methods We used 24 male Wistar rats that had received surgical lesions to the corpus callosum and were injected with lysolecithin. Rats were divided into three groups: Group 1 included eight rats with lesions to the corpus callosum but not lysolecithin injections (sham group), group 2 included eight rats with lesions to the corpus callosum that were injected with lysolecithin (lysolecithin group), and group 3 included eight rats with lesions that were injected with lysolecithin and received VitD (VitD group). We analyzed neurogenesis both in the subventricular zone and at the lesion site. Results Administration of VitD promotes the proliferation and differentiation of neural stem cells in the subventricular zone and the migration of these cells to the lesion site in the corpus callosum; these cells subsequently differentiate into oligodendrocyte lineage cells and produce myelin basic protein. This phenomenon was not caused by microglial activation, which was less marked in rats receiving VitD. Megalin expression did not increase at the lesion site, which suggests that VitD is internalized by other mechanisms. Conclusion Our results support the hypothesis that regardless of the presence of VitD deficiency, treatment with VitD may contribute to remyelination by promoting the proliferation of oligodendrocyte precursor cells. Vitamin D promotes remyelination in rats with lysolecithin‐induced demyelination. Vitamin D promotes differentiation into oligodendrocyte lineage cells. Vitamin D promotes proliferation and differentiation of neural stem cells.

Introduction Vitamin D (VD) deficiency has been associated with multiple sclerosis (MS) and other autoimmune diseases (AIDs). However, the effect of the genetics of VD on the risk of MS is subject to debate. This study focuses on genes linked to the VD signaling pathway in families with MS. The evaluation of gene variants in all the members of families could contribute to an additional knowledge on the information obtained from case‐control studies that use nonrelated healthy people. Material and Methods We studied 94 individuals from 15 families including at least two patients with MS. We performed whole‐exome next generation sequencing on all individuals and analyzed variants of the DHCR7, CYP2R1, CYP3A4, CYP27A1, GC, CYP27B1, LRP2, CUBN, DAB2, FCGR, RXR, VDR, CYP24A1, and PDIA3 genes. We also studied PTH, FGF23, METTL1, METTL21B, and the role of the linkage disequilibrium block on the long arm of chromosome 12, through analysis of the CDK4, TSFM, AGAP2, and AVIL genes. We compared patients with MS, other AIDs and unaffected members from different family types. Results The study described the variants in the VD signaling pathway that appear in families with at least two patients with MS. Some infrequent variants were detected in these families, but no significant difference was observed between patients with MS and/or other AIDs and unaffected family members in the frequency of these variants. Variants previously associated with MS in the literature were not observed in these families or were distributed similarly in patients and unaffected family members. Conclusion The study of genes involved in the VD signaling pathway in families that include more than one patient with MS did not identify any variants that could explain the presence of the disease, suggesting that VD metabolism could probably play a role in MS more as an environmental factor rather than as a genetic factor. Our study also supports the analysis of cases and unaffected individuals within families in order to determine the influence of genetic factors. The study described variants in VD signaling pathway that appear in families with at least two MS patients. Our study supports that VD metabolism could probably play a role in MS more as an environmental factor rather than as a genetic factor. In addition, our study shows the importance of the analysis of cases and unaffected individuals within families to determine the influence of genetic factors.

Introduction Numerous genetic variants have been associated with susceptibility to multiple sclerosis (MS). Variants located in genes involved in specific pathways, such as those affecting TNF‐α, can contribute to the risk of MS. The purpose of this study was to determine whether variants of these genes are associated with greater risk of MS. Methods We used whole‐exome sequencing to study genes coding for TNF‐α receptors and ligands, and proteins promoting TNF‐α expression in 116 individuals from 19 families including at least two MS patients. We compared patients with MS, patients with other autoimmune diseases, and healthy individuals. Results Greater polymorphism was observed in several genes in families with familial MS compared to the general population; this may reflect greater susceptibility to autoimmune diseases. Pedigree analysis also revealed that LT‐α variants rs1041981 and rs2229094 and LT‐β variant rs4647197 were associated with MS and that LT‐β variant rs4647183 was associated with other autoimmune diseases. The association between autoimmune disease and TNFAIP2 variant rs1132339 is particularly noteworthy, as is the fact that TNFAIP6 variant rs1046668 appears to follow a recessive inheritance pattern. Conclusions Our findings support the idea that the risk of familial MS is associated with variants of signaling pathways, including those involving TNF‐α. Pathways affecting TNF‐α are involved in immune signaling. Whole‐exome sequencing in 116 members of 19 families including at least two patients with multiple sclerosis was performed. Several nonsynonymous variants in TNF‐α pathways were found. The findings support the idea that the risk of familial MS is associated with variants of TNF‐α signaling pathways.

Post-COVID condition (PCC) and multiple sclerosis (MS) share some clinical and demographic features, including cognitive symptoms and fatigue. Some pathophysiological mechanisms well-known in MS, such as autoimmunity, neuroinflammation and myelin damage, have also been implicated in PCC. In this study, we aimed to compare the cognitive phenotypes of two large cohorts of patients with PCC and MS, and to evaluate the relationship between fatigue and cognitive performance. Cross-sectional study including 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol and were categorized according to the International Classification of Cognitive Disorders system. Fatigue and depression were also assessed. Cognitive profiles of PCC and MS largely overlapped, with a greater impairment in episodic memory in MS, but with small effect sizes. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC. Still, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. There were no differences in the severity of depression among groups. Our study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS. Further comparative studies addressing the mechanisms related to cognitive dysfunction and fatigue may be of interest to advance the knowledge of these disorders and develop new therapies.

(1) Apical periodontitis (AP) is the inflammatory response of the periapical tissue to bacterial antigens and toxins arriving from inside the root canal after pulp necrosis. To control AP, it is necessary to interrupt the passage of antigens from the root canal to the periapex, which is achieved via a root canal treatment (RCT), which is the indicated endodontic therapy in cases of AP. The prevalence of root-filled teeth (RFT) is an indicator of the frequency of endodontic infections and the degree of dental care. Diabetes is associated with AP and has been identified as the main prognostic factor in RCT. The aim of this study was to carry out a systematic review with meta-analysis answering the following question: What is the prevalence of RFT among diabetic patients? (2) This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines 2020. A literature search was undertaken without limits on time or language until 12 January 2023 in PubMed-MEDLINE, Embase and Scielo. All studies reporting the prevalence of RFT among diabetic patients via radiographic examination; both panoramic and periapical radiographs were included. Meta-analyses were calculated with Open Meta Analyst software. The main outcome variable was the prevalence of RFT, calculated as the total number of RFT divided by the total number of teeth, which is expressed as a percentage. As a secondary outcome variable, the prevalence of diabetic patients with at least one RFT, expressed as a percentage, was also calculated. The quality of evidence of the included studies was analyzed according to the guidelines provided by the Centre for Evidence-Based Medicine in Oxford. The risk of bias was assessed using the Newcastle-Ottawa Scale, which was adapted for cross-sectional studies. To estimate the variance and heterogeneity amongst the trials, the Higgings I2 test was employed. (3) Eight studies fulfilled the inclusion criteria. Four studies were classified as having a high risk of bias, and four were classified as having a moderate risk of bias. The prevalence of RFT was estimated for 37,922 teeth and 1532 diabetic patients. The overall calculated prevalence of RFT among diabetic patients was 5.5% (95% CI = 4.1-6.9%; p < 0.001). The percentage of diabetics who had at least one RFT was 42.7% (95% CI = 23.9-61.4%; p < 0.001). (4) This systematic review and meta-analysis concluded that the prevalence of RFT among diabetic patients is 5.5%. More than 40% of diabetics have at least one RFT. In daily clinics, dentists should suspect that patients are undiagnosed diabetics when multiple RCT failures are observed in the same patient.

Neurological disorders are a leading cause of morbidity worldwide, giving rise to a growing need to develop treatments to revert their symptoms. This review highlights the great potential of recent advances in cell therapy for the treatment of neurological disorders. Through the administration of pluripotent or stem cells, this novel therapy may promote neuroprotection, neuroplasticity, and neuroregeneration in lesion areas. The review also addresses the administration of these therapeutic molecules by the intranasal route, a promising, non-conventional route that allows for direct access to the central nervous system without crossing the blood–brain barrier, avoiding potential adverse reactions and enabling the administration of large quantities of therapeutic molecules to the brain. Finally, we focus on the need to use biomaterials, which play an important role as nutrient carriers, scaffolds, and immune modulators in the administration of non-autologous cells. Little research has been conducted into the integration of biomaterials alongside intranasally administered cell therapy, a highly promising approach for the treatment of neurological disorders.

The implantation of oligodendrocyte precursor cells may be a useful therapeutic strategy for targeting remyelination. However, it is yet to be established how these cells behave after implantation and whether they retain the capacity to proliferate or differentiate into myelin-forming oligodendrocytes. One essential issue is the creation of administration protocols and determining which factors need to be well established. There is controversy around whether these cells may be implanted simultaneously with corticosteroid treatment, which is widely used in many clinical situations. This study assesses the influence of corticosteroids on the capacity for proliferation and differentiation and the survival of human oligodendroglioma cells. Our findings show that corticosteroids reduce the capacity of these cells to proliferate and to differentiate into oligodendrocytes and decrease cell survival. Thus, their effect does not favour remyelination; this is consistent with the results of studies with rodent cells. In conclusion, protocols for the administration of oligodendrocyte lineage cells with the aim of repopulating oligodendroglial niches or repairing demyelinated axons should not include corticosteroids, given the evidence that the effects of these drugs may undermine the objectives of cell transplantation.

Background. Post-treatment apical periodontitis (PAP) is a frequent consequence of root canal treatment (RCT) failure, often caused by untreated missed canals in root-filled teeth (RFT). While cone-beam computed tomography (CBCT) has been used to find these missed canals, the results are controversial. This systematic review and meta-analysis investigates the association between PAP in RFT and missed canals detected via CBCT. Methods. Two independent reviewers searched PubMed, Scopus, Dialnet, and SciELO for relevant articles published up until 17 February 2025. The main outcome was the prevalence of PAP in RFT with and without missed canals detected via CBCT. The overall odds ratio (OR) was calculated using a binary random effects model meta-analysis (OpenMeta Analyst). Risk of bias was assessed using the Newcastle–Ottawa Scale, and certainty was evaluated using GRADE. Results. Eight cross-sectional studies (9983 RFT) were included in the review. The pooled prevalence of PAP was significantly higher in RFT with missed canals (85.1%) than those without (56.3%). The meta-analysis showed a strong association between missed canals and PAP (OR = 7.17, 95% CI = 4.55–11.29), indicating a sevenfold increased likelihood. Maxillary molars, especially first molars, most commonly had missed canals. Heterogeneity was high (I2 = 86%), and evidence certainty was low, due to methodological limitations. Conclusions. Untreated missed canals significantly increase the likelihood of PAP in RFT, highlighting the need for thorough canal detection and treatment. Clinicians should prioritize anatomical knowledge and advanced imaging to minimize treatment failure.