Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders.

The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation and cognitive function. The molecular underpinnings of sleep modulation by the endocannabinoid system and its influence on glial cell activity are discussed, shedding light on the reciprocal relationships that govern these processes. Emphasis is placed on understanding the role of glial cells in mediating neuroinflammatory responses and their modulation by sleep patterns. Additionally, this review examines how the endocannabinoid system interfaces with glia-immune signaling to regulate inflammatory cascades within the central nervous system. Notably, the cognitive consequences of disrupted sleep, neuroinflammation, and glial dysfunction are addressed, encompassing implications for neurodegenerative disorders, mood disturbances, and cognitive decline. Insights into the bidirectional modulation of cognitive function by the endocannabinoid system in the context of sleep and glial activity are explored, providing a comprehensive perspective on the potential mechanisms underlying cognitive impairments associated with sleep disturbances. Furthermore, this review examines potential therapeutic avenues targeting the endocannabinoid system to mitigate neuroinflammation, restore glial homeostasis, and normalize sleep patterns. The identification of novel therapeutic targets within this intricate regulatory network holds promise for addressing conditions characterized by disrupted sleep, neuroinflammation, and cognitive dysfunction. This work aims to examine the complexities of neural regulation and identify potential avenues for therapeutic intervention.

A systematic review and meta-analysis of serum lipid concentrations in people with Down syndrome.

BACKGROUND: Down syndrome (DS) is the most prevalent chromosomal disorder, being the leading cause of intellectual disability. The increased life expectancy of individuals with DS has led to a shift in the incidence of non-communicable chronic diseases, resulting in new concerns, particularly cardiovascular disease (CVD) and Alzheimer's disease. This study aimed to analyse the blood lipid profile of a large DS cohort to establish a baseline for evaluating health risk parameters. METHODS: A comprehensive literature search was conducted on PubMed and Virtual Health Library databases to identify original articles published before July 2022. Selected studies were included in the meta-analysis. RESULTS: Fifteen studies reporting serum lipid levels in individuals with DS were incorporated into the analysis. The meta-analysis used the means and standard deviations extracted from the selected studies. The analysis encompassed 671 participants in the DS group and 898 euploid controls. The results indicated significant differences in total cholesterol [C] (mean difference [MD]: -3.34; CI: 95%: -4.94 to -1.73; P < 0.0001), HDL-C (MD: -3.39; CI: 95%: -6.72 to -0.06; P = 0.05) and triglycerides (MD: 21.48; CI: 95%: 9.32 to 33.65; P = 0.0005) levels between individuals with DS and their control counterparts. CONCLUSIONS: Individuals with DS have less favourable blood lipid concentrations than their controls, particularly HDL-C, triglycerides, and total-C, even when grouped by age. These findings underscore the importance of closer monitoring of lipid profiles in people with DS and the necessity for specific cut-offs for this population, considering the risk for ischemic heart and Alzheimer's diseases.

Interplay between the Glymphatic System and the Endocannabinoid System: Implications for Brain Health and Disease.

The intricate mechanisms governing brain health and function have long been subjects of extensive investigation. Recent research has shed light on two pivotal systems, the glymphatic system and the endocannabinoid system, and their profound role within the central nervous system. The glymphatic system is a recently discovered waste clearance system within the brain that facilitates the efficient removal of toxic waste products and metabolites from the central nervous system. It relies on the unique properties of the brain's extracellular space and is primarily driven by cerebrospinal fluid and glial cells. Conversely, the endocannabinoid system, a multifaceted signaling network, is intricately involved in diverse physiological processes and has been associated with modulating synaptic plasticity, nociception, affective states, appetite regulation, and immune responses. This scientific review delves into the intricate interconnections between these two systems, exploring their combined influence on brain health and disease. By elucidating the synergistic effects of glymphatic function and endocannabinoid signaling, this review aims to deepen our understanding of their implications for neurological disorders, immune responses, and cognitive well-being.

Scientific facts improve cannabis perception and public opinion: results from Sinaloa, México.

Cannabis, the most prevalent drug in Latin America, has long been associated with the state of Sinaloa, Mexico, known for its cultivation and distribution. Despite increasing global acceptance, cannabis use remains stigmatized in Mexican society, driven by perceptions of it as a highly psychoactive and addictive substance lacking medicinal or industrial value. This study investigates the impact of scientific information on societal perceptions of cannabis in Sinaloa. A large convenience sample of 3162 individuals from Sinaloa participated in this research, responding to a questionnaire on cannabis consumption and attitudes. Participants were then subjected to an intervention consisting of an informative briefing based on the documents "Using Evidence to Talk About Cannabis" and "State of the Evidence: cannabis use and regulation" by the International Centre for Science in Drug Policy. After the intervention, participants' attitudes were immediately reevaluated through the same questionnaire, allowing for a comparison of pre- and post-intervention responses. The results indicate that the intervention (providing scientific information) significantly influenced attitudes toward cannabis, with education and age playing prominent roles in its effectiveness. Notably, the intervention fostered more positive or more neutral attitudes, potentially reducing stigma and promoting a better-informed perspective on cannabis. This study highlights the pivotal role of evidence in shaping informed citizens' views, while underscoring the importance of countering misinformation for societal progress. These findings have significant implications for forthcoming cannabis policy modifications in Mexico, emphasizing the necessity of engaging knowledgeable individuals in policy decisions to address the violence and inequalities associated with the illicit drug trade, particularly in Sinaloa.

Clinical Predictors of Monkeypox Diagnosis: A Case-Control Study in a Nonendemic Region during the 2022 Outbreak.

Monkeypox (Mpox) is an emerging zoonotic disease with the potential for severe complications. Early identification and diagnosis are essential to prompt treatment, control its spread, and reduce the risk of human-to-human transmission. This study aimed to develop a clinical diagnostic tool and describe the clinical and sociodemographic features of 19 PCR-confirmed Mpox cases during an outbreak in a nonendemic region of northwestern Mexico. The median age of patients was 35 years, and most were male. Mpox-positive patients commonly reported symptoms such as fever, lumbago, and asthenia, in addition to experiencing painful ulcers and a high frequency of HIV infection among people living with HIV (PLWH). Two diagnostic models using logistic regression were devised, with the best model exhibiting a prediction accuracy of 0.92 (95% CI: 0.8-1), a sensitivity of 0.86, and a specificity of 0.93. The high predictive values and accuracy of the top-performing model highlight its potential to significantly improve early Mpox diagnosis and treatment in clinical settings, aiding in the control of future outbreaks.

In Silico Prediction of Hub Genes Involved in Diabetic Kidney and COVID-19 Related Disease by Differential Gene Expression and Interactome Analysis.

Diabetic kidney disease (DKD) is a frequently chronic kidney pathology derived from diabetes comorbidity. This condition has irreversible damage and its risk factor increases with SARS-CoV-2 infection. The prognostic outcome for diabetic patients with COVID-19 is dismal, even with intensive medical treatment. However, there is still scarce information on critical genes involved in the pathophysiological impact of COVID-19 on DKD. Herein, we characterize differential expression gene (DEG) profiles and determine hub genes undergoing transcriptional reprogramming in both disease conditions. Out of 995 DEGs, we identified 42 shared with COVID-19 pathways. Enrichment analysis elucidated that they are significantly induced with implications for immune and inflammatory responses. By performing a protein-protein interaction (PPI) network and applying topological methods, we determine the following five hub genes: STAT1, IRF7, ISG15, MX1 and OAS1. Then, by network deconvolution, we determine their co-expressed gene modules. Moreover, we validate the conservancy of their upregulation using the Coronascape database (DB). Finally, tissue-specific regulation of the five predictive hub genes indicates that OAS1 and MX1 expression levels are lower in healthy kidney tissue. Altogether, our results suggest that these genes could play an essential role in developing severe outcomes of COVID-19 in DKD patients.

Novel TINF2 gene mutation in dyskeratosis congenita with extremely short telomeres: A case report.

BACKGROUND: Dyskeratosis congenita is a rare disease characterized by bone marrow failure and a clinical triad of oral leukoplakia, nail dystrophy, and abnormal skin pigmentation. The genetics of dyskeratosis congenita include mutations in genes involved in telomere maintenance, including TINF2. CASE SUMMARY: Here, we report a female patient who presented thrombocytopenia, anemia, reticulate hyperpigmentation, dystrophy in fingernails and toenails, and leukoplakia on the tongue. A histopathological study of the skin showed dyskeratocytes; however, a bone marrow biopsy revealed normal cell morphology. The patient was diagnosed with dyskeratosis congenita, but her family history did not reveal significant antecedents. Whole-exome sequencing showed a novel heterozygous punctual mutation in exon 6 from the TINF2 gene, namely, NM_001099274.1:c.854delp.(Val285Alafs*32). An analysis of telomere length showed short telomeres relative to the patient's age. CONCLUSION: The disease in this patient was caused by a germline novel mutation of TINF2 in one of her parents.

Incidence, Mortality, and Trends of Prostate Cancer in Mexico from 2000 to 2019: Results from the Global Burden of Disease Study 2019.

In 2019, the Global Burden of Disease (GBD) estimated that prostate cancer (PC) was the 16th most common cause of death globally in males. In Mexico, PC epidemiology has been studied by a number of metrics and over various periods, although without including the most up-to-date estimates. Herein, we describe and compare the burdens and trends of PC in Mexico and its 32 states from 2000 to 2019. For this study, we extracted online available data from the GBD 2019 to estimate the crude and age-standardized rates (ASR per 100,000 people) of the incidence and mortality of PC. In Mexico, PC caused 27.1 thousand (95% uncertainty intervals, 20.6-36.0 thousand) incident cases and 9.2 thousand (7.7-12.7 thousand) deaths in males of all ages in 2019. Among the states, Sinaloa had the greatest ASR of incidence, and Guerrero had the highest mortality. The burden of PC showed an increasing trend, although the magnitude of change differed between metrics and locations. We found both an increasing national trend and subnational variation in the burden of PC. Our results confirm the need for updated and timely estimates to design effective diagnostic and treatment campaigns in locations where the burden of PC is the highest.

Profiling of circulating chromosome 21-encoded microRNAs, miR-155, and let-7c, in down syndrome.

BACKGROUND: Down syndrome (DS) is the most common chromosomal survival aneuploidy. The increase in DS life expectancy further heightens the risk of dementia, principally early-onset Alzheimer's disease (AD). AD risk in DS is higher, considering that this population may also develop metabolic diseases such as obesity, dyslipidemias, and diabetes mellitus. The extra genetic material that characterizes DS causes an imbalance in the genetic dosage, including over-expression of AD's key pathophysiological molecules and the gene expression regulators, the microRNAs (miRNAs). Two miRNAs, chromosome 21-encoded, miR-155, and let-7c, are associated with cognitive impairment and dementia in adults; but, expression dynamics and relationship with clinical variables during the DS's lifespan had remained hitherto unexplored. METHODS: The anthropometric, clinical, biochemical, and profile expression of circulating miR-155 and let-7c were analyzed in a population of 52 control and 50 DS subjects divided into the young group (Aged ≤20 years) and the adult group (Aged ≥21 years). RESULTS: The expression changes for miR-155 were not significant; nevertheless, a negative correlation with HDL-Cholesterol concentrations was observed. Notably, let-7c was over-expressed in DS from young and old ages. CONCLUSION: Overall, our results suggest that let-7c plays a role from the early stages of DS's cognitive impairment while overexpression of miR-155 may be related to lipid metabolism changes. Further studies of both miRNAs will shed light on their potential as therapeutic targets to prevent or delay DS's cognitive impairment.

Glioblastoma multiforme: a multi-omics analysis of driver genes and tumour heterogeneity.

Glioblastoma (GBM) is the most aggressive and common brain cancer in adults with the lowest life expectancy. The current neuro-oncology practice has incorporated genes involved in key molecular events that drive GBM tumorigenesis as biomarkers to guide diagnosis and design treatment. This study summarizes findings describing the significant heterogeneity of GBM at the transcriptional and genomic levels, emphasizing 18 driver genes with clinical relevance. A pattern was identified fitting the stem cell model for GBM ontogenesis, with an upregulation profile for MGMT and downregulation for ATRX, H3F3A, TP53 and EGFR in the mesenchymal subtype. We also detected overexpression of EGFR, NES, VIM and TP53 in the classical subtype and of MKi67 and OLIG2 genes in the proneural subtype. Furthermore, we found a combination of the four biomarkers EGFR, NES, OLIG2 and VIM with a remarkable differential expression pattern which confers them a strong potential to determine the GBM molecular subtype. A unique distribution of somatic mutations was found for the young and adult population, particularly for genes related to DNA repair and chromatin remodelling, highlighting ATRX, MGMT and IDH1. Our results also revealed that highly lesioned genes undergo differential regulation with particular biological pathways for young patients. This multi-omic analysis will help delineate future strategies related to the use of these molecular markers for clinical decision-making in the medical routine.

Association of Total and High Molecular Weight Adiponectin with Components of Metabolic Syndrome in Mexican Children

Objective: Childhood obesity linked to metabolic alterations, tend to appear simultaneously with altered adipocytokines, suggesting a role in pathogenetic development. Low circulating level of total and high molecular weight (HMW) adiponectin have been associated with components of the metabolic syndrome (MetS) and could represent an independent risk factor with potential use as a biomarker. To examine the prevalence of MetS in Mexican school children and to investigate the association of total and HMW adiponectin levels with biochemical parameters related to MetS. Methods: The study included a population of boys and girls, from 8 to 11 years old. Anthropometric and biochemical parameters were evaluated according to weight and MetS status. A correlation analysis was fitted to establish an association between adiponectin concentrations and metabolic indicators. Results: One-hundred and fifty five children participated (59.4% females) from 8-11 years of age. The prevalence of MetS was of 10.3%. Impaired biochemical parameters, including total and HMW adiponectin, were associated with obesity. The adiponectin level was significantly lower in MetS than in non-MetS subjects (4.5 vs. 5.4 µg/mL). Total- but not HMW adiponectin concentration was negatively correlated with blood pressure, fasting insulin, fasting blood sugar and Homeostatic Model Assessment for Insulin Resistance. Conclusion: In young children, the total adiponectin level is associated with impaired biochemical parameters of carbohydrate metabolism and could be an excellent early predictor of metabolic complications.

Involvement of the Notch pathway in terminal astrocytic differentiation: role of PKA.

The Notch pathway is a highly conserved signaling system essential for modulating neurogenesis and promoting astrogenesis. Similarly, the cAMP signaling cascade can promote astrocytic commitment in several cell culture models, such as the C6 glioma cell line. These cells have the capacity to differentiate into oligodendrocytes or astrocytes, characteristics that allow their use as a glial progenitor model. In this context, we explore here the plausible involvement of cAMP in Notch-dependent signal transactions. The exposure of C6 cells to a non-hydrolysable cAMP analogue resulted in a sustained augmentation of Notch activity, as detected by nuclear translocation of its intracellular domain portion (NICD) and transcriptional activity. The cAMP effect is mediated through the activation of the γ-secretase complex, responsible for Notch cleavage and is sensitive to inhibitors of the cAMP-dependent protein kinase, PKA. As expected, Notch cleavage and nuclear translocation resulted in the up-regulation of the mRNA levels of one of its target genes, the transcription factor Hair and enhancer of split 5. Moreover, the glutamate uptake activity, as well as the expression of astrocytic markers such as glial fibrillary acidic protein, S100ß protein and GLAST was also enhanced in cAMP-exposed cells. Our results clearly suggest that during the process of C6 astrocytic differentiation, cAMP activates the PKA/γ-secretase/NICD/RBPJ(κ) pathway and Notch1 expression, leading to transcriptional activation of the genes responsible for glial progenitor cell fate decision.