Nonpharmacological Interventions for Treating Breastfeeding Nipple Pain: Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy and safety of nonpharmacological topical interventions for treating breastfeeding nipple pain. Methods: Randomized clinical trials (RCTs) assessing lactating women suffering from breastfeeding painful nipples were included. Primary outcomes were pain, healing process, and adverse events. A comprehensive search was conducted on June 02, 2023, without date or language restrictions. Methodological quality was assessed using the Cochrane risk of bias tool and the certainty of the evidence, the GRADE approach. Results: Nineteen RCTs with unclear to high risk of bias were included. There was uncertain evidence regarding the effects of photobiomodulation versus placebo on pain reduction (mean difference [MD] -0.15; 95% confidence interval [95% CI] -1 0.49 to 1.19; 139 participants, 2 RCTs). There are uncertainties concerning the effects of lanolin versus breast milk on pain (MD -1.80; 95% CI -2.43 to -1.17; 1 RCT; 180 participants), wound healing (MD 0.10; 95% CI -0.26 to -0.46; 1 RCT; 180 participants), and any adverse events (zero events in both groups). Similar effects were observed by the other interventions assessed. Conclusion: The evidence of nonpharmacological topical interventions for painful nipples is imprecise, and future RCTs with higher methodological quality are needed to support recommendations. Considering the accessibility and low cost of these alternative treatments, the findings of this evidence synthesis could support clinical decision-making and guide future research. PROSPERO CRD42020170320.

Maternal exposure to tributyltin alters the breast milk, hormonal profile, and thyroid morphology of dams and induces sex-specific changes in neonate rat offspring.

Tributyltin (TBT) is the chemical substance commonly used worldwide to prevent biofouling of vessels. Due to its ability to bioaccumulate and biomagnify, even after being banned, significant concentrations of TBT can be detected in sediment, affecting marine and human life. Although studies have shown that direct exposure to TBT alters physiological parameters in mammals, the relationship between exposure to TBT during pregnancy and lactation, considered critical windows for metabolic programming, has not been fully elucidated. Our hypothesis is that offspring whose mothers were exposed to TBT during critical stages of development may exhibit dysfunctions in endocrine-metabolic parameters. We used pregnant Wistar rats that were divided into groups and received the following treatments from gestational day 7 until the end of lactation by intragastric gavage: vehicle (ethanol 0.01%; Control), low TBT dose (100 ng/kg of body weight (bw)/day; TBT100ng) and high TBT dose (1000 ng/kg bw/day; TBT1000ng). Dams and offspring at birth and weaning (21 days old) were studied. Maternal exposure to TBT promoted dose-dependent changes in dams. The findings for adiposity, milk composition and lipid profile were more pronounced in TBT100 ng dam; however, thyroid morphology was altered in TBT1000 ng dam. Female offspring were differentially affected by the dose of exposure. At birth, females in the TBT100ng group had low body weight, lower naso-anal length (NAL), and higher plasma T4, and at weaning, females in the TBT100ng group had lower insulin and leptin levels. Females in the TBT1000ng group had lower NAL at birth and lower leptinemia and weight of white adipose tissue at weaning. Male offspring from TBT groups showed high T3 at birth, without biometric alterations at birth or weaning. Despite these findings, both sexes exhibited dose-dependent morphological changes in the thyroid gland. Thus, maternal exposure to TBT constitutes an important route of contamination for both dams and offspring.

Association between Leukemic Evolution and Uncommon Chromosomal Alterations in Pediatric Myelodysplastic Syndrome.

Background: Pediatric myelodysplastic syndrome (pMDS) is a group of rare clonal neoplasms with a difficult diagnosis and risk of progression to acute myeloid leukemia (AML). The early stratification in risk groups is essential to choose the treatment and indication for allogeneic hematopoietic stem cell transplantation (HSCT). According to the Revised International Prognostic Scoring System, cytogenetic analysis has demonstrated an essential role in diagnosis and prognosis. In pMDS, abnormal karyotypes are present in 30-50% of the cases. Monosomy 7 is the most common chromosomal alteration associated with poor prognosis. However, the rarity of specific cytogenetic alterations makes its prognosis uncertain. Thus, this study aimed to describe uncommon cytogenetic alterations in a cohort of 200 pMDS patients and their association with evolution to AML. Methods: The cytogenetic analysis was performed in 200 pMDS patients by G-banding and fluorescence in situ hybridization between 2000 to 2022. Results: Rare chromosome alterations were observed in 7.5% (15/200) of the cases. These chromosome alterations were divided into four cytogenetic groups: hyperdiploidy, biclonal chromosomal alterations, translocations, and uncommon deletions representing 33.3%, 33.3%, 20%, and 13.3%, respectively. Most of these patients (10/15) were classified with advanced MDS (MDS-EB and MDS/AML) and the initial subtype was present in five patients (RCC). The leukemic evolution was observed in 66.66% (10/15) of the patients. Most patients had poor clinical outcomes and they were indicated for HSCT. Conclusion: The study of uncommon cytogenetic alterations in pMDS is important to improve the prognosis and guide early indication of HSCT.

T-cell immunophenotype correlations with cortical thickness and white matter microstructure in bipolar disorder.

BACKGROUND: Inflammation and immunological alterations, such as T-cell and cytokine changes, are implicated in bipolar disorder (BD), with some evidence linking them to brain structural changes (e.g., cortical thickness (CT), gray matter (GM) volume and white matter (WM) microstructure). However, the connection between specific peripheral cell types, such as T-cells, and neuroimaging in BD remains scarcely investigated. AIMS OF THE STUDY: This study aims to explore the link between T-cell immunophenotype and neuroradiological findings in BD. METHODS: Our study investigated 43 type I BD subjects (22 depressive, 21 manic) and 26 healthy controls (HC), analyzing T lymphocyte immunophenotype and employing neuroimaging to assess CT for GM and fractional anisotropy (FA) for WM. RESULTS: In lymphocyte populations, BD patients exhibited elevated CD4+ and CD4+ central memory (TCM) cells frequencies, but lower CD8+ effector memory (TEM) and terminal effector memory (TTEM) cells. Neuroimaging analysis revealed reduced CT in multiple brain regions in BD patients; and significant negative correlations between CD4 + TCM levels and CT of precuneus and fusiform gyrus. Tract-based spatial statistics (TBSS) analysis showed widespread alteration in WM microstructure in BD patients, with negative and positive correlations respectively between FA and radial diffusivity (RD) and CD4 + TCM. Additionally, positive and negative correlations were found respectively between FA and RD and the CD8 + TEM and CD8 + TTEM subsets. CONCLUSIONS: Our research revealed distinct T lymphocyte changes and brain structure alterations in BD, underscoring possible immune-brain interactions, warranting further study and therapeutic exploration.

Sensation seeking correlates with increased white matter integrity of structures associated with visuospatial processing in healthy adults.

Introduction: The ability to process sensory information is an essential adaptive function, and hyper- or hypo-sensitive maladaptive profiles of responses to environmental stimuli generate sensory processing disorders linked to cognitive, affective, and behavioral alterations. Consequently, assessing sensory processing profiles might help research the vulnerability and resilience to mental disorders. The research on neuroradiological correlates of the sensory processing profiles is mainly limited to the young-age population or neurodevelopmental disorders. So, this study aims to examine the structural MRI correlates of sensory profiles in a sample of typically developed adults. Methods: We investigated structural cortical thickness (CT) and white matter integrity, through Diffusion Tensor Imaging (DTI), correlates of Adolescent/Adult Sensory Profile (AASP) questionnaire subscales in 57 typical developing subjects (34F; mean age: 32.7 ± 9.3). Results: We found significant results only for the sensation seeking (STS) subscale. Positive and negative correlations emerged with fractional anisotropy (FA) and radial diffusivity (RD) in anterior thalamic radiation, optic radiation, superior longitudinal fasciculus, corpus callosum, and the cingulum bundle. No correlation between sensation seeking and whole brain cortical thickness was found. Discussion: Overall, our results suggest a positive correlation between sensation seeking and higher white matter structural integrity in those tracts mainly involved in visuospatial processing but no correlation with gray matter structure. The enhanced structural integrity associated with sensation seeking may reflect a neurobiological substrate linked to active research of sensory stimuli and resilience to major psychiatric disorders like schizophrenia, bipolar disorder, and depression.

"Surrounded, detached": the relationship between defensive peripersonal space and personality.

Introduction: Personality shapes the cognitive, affective, and behavioral interactions between individuals and the environment. Defensive peripersonal space (DPPS) is the projected interface between the body and the world with a protective function for the body. Previous studies suggest that DPPS displays inter-individual variability that is associated with psychiatric symptoms, such as anxiety. However, DPPS may share a link with personality traits. Methods: Fifty-five healthy participants were assessed with the Personality Inventory for DSM-5 (PID-5)-Adult to evaluate personality dimensions. Subjects underwent the Hand Blink Reflex (HBR) task that estimates the DPPS limits by assessing the modulation of blink intensity in response to the median nerve stimulation. Data of the HBR was analyzed with Bayesian multilevel models, while the relationship between DPPS and personality traits was explored using network analysis. Results: HBR was best modeled using a piecewise linear regression model, with two distinct slope parameters for electromyographic data. Network analyzes showed a positive correlation between the proximal slope and detachment personality trait, suggesting that individuals with higher scores in the detachment trait had an increased modulation of HBR, resulting in a larger extension of the DPPS. Discussion: Features of the detachment personality trait include avoidance of interpersonal experiences, restricted affectivity, and suspiciousness, which affect interpersonal functioning. We suggest that DPPS may represent a characteristic feature of maladaptive personality traits, thus constitute a biomarker or a target for rehabilitative interventions.

Potential of pharmaceutical formulation based on Morinda citrifolia extract for the treatment of schistosomiasis.

Schistosomiasis is a parasitic disease that can be asymptomatic, but it can progress and cause serious damage, such as hospitalization and death. This work aimed to characterize and carry out the in vivo pharmacological test of the dry extract of Morinda citrifolia and obtain a pharmaceutical dosage form based on this extract for the treatment of schistosomiasis. The aqueous extract was characterized based on the evaluation of pH, dry residue and density. The aqueous extract was dried through the freeze-drying process. The obtained dry extract was characterized through phytochemical screening, rheological analysis, acute toxicity and in vivo pharmacology. Additionally, the pre-formulation development of a pharmaceutical dosage form was pursued with the dry extract. Through the HPLC chromatogram, characteristic rutin peaks were identified. The rheological behavior of the dry extract did not show good characteristics. Acute toxicity, at a dose of 2000 mg/kg, showed excitatory activity in the central and autonomous nervous system. The in vivo pharmacological test of the dry extract showed that, at a dose of 400 mg/kg, it was possible to reduce 67.5% of the total adult worms, 66% of female worms and 60% of the number of eggs. The pharmaceutical dosage form obtained was an oral solution that was clear, transparent, without the presence of lumps and precipitates, having a density of 1.1276 g mL-1 and pH of 5.92. The results obtained will provide parameters for the production of suitable pharmaceutical formulations, as well as for the quality control of products based on M. citrifolia, with promising schistosomicidal activity.

Simultaneous determination of nine high-intensity sweeteners in liquid and powder tabletop sweeteners.

Government regulatory actions and public policies have been recently implemented in Brazil due to the excessive consumption of sugar. Therefore, it becomes relevant to determine the levels of high-intensity sweeteners in tabletop sweeteners consumed by the Brazilian population. Thus, an analytical method was developed and validated for the simultaneous determination of nine sweeteners (acesulfame potassium, aspartame, advantame, sodium cyclamate, neotame, saccharin, sucralose, stevioside, and rebaudioside A) by using ultra-high performance liquid chromatography coupled to mass spectrometry in tandem. The sample preparation encompassed only dilution steps. The method was validated taking into account the parameters of linearity, precision, accuracy, and matrix effects. The analytes were determined in two different batches of 21 commercial liquid and powder tabletop sweeteners available on the local market, totaling 42 samples. A minimum of one and a maximum of four sweeteners were found in the analyzed products and sweeteners that were not described on the label were not detected. It is expected that the established method can be used in monitoring programs and that the presented results can contribute to exposure assessments performed nationally.

In vitro evaluation of antioxidant, cytotoxic, trypanocidal and antimicrobial activities of lignin obtained from Caesalpinia ferrea leaves and its use as an excipient in the release of oxacillin and fluconazole.

In this context, the objective of this work was to isolate an alkaline lignin from the leaves of C. ferrea, in addition to investigating different biological activities and its use in the production of releasing tablets in vitro. Initially, the analysis of the composition of the leaves was performed, the contents were: cellulose (33.09 ± 0.3 %), hemicellulose (25.13 ± 0.1 %), lignin (18.29 ± 0.1 %), extractives (17.28 ± 1.0 %) and ash (6.20 ± 0.1 %). The leaves were fractionated to obtain alkaline lignin. The yield of obtaining lignin was 80.12 ± 0.1 %. The obtained lignin was characterized by the techniques: elemental analysis, FTIR, UV/Vis, 2D-NMR, GPC, TGA/DTG, DSC and PY-GC/MS. The results showed that the lignin obtained is of the GSH type, of low molecular weight and thermally stable. The in vitro antioxidant activity was evaluated by different assays promoting results only for DPPH (559.9 ± 0.8 µg/mL) and ABTS (484.1 ± 0.1 µg/mL) being able to promote low antioxidant activity. In addition, it showed low cytotoxicity in normal mammalian cells and promising antitumor and trypanocidal activity. Regarding antimicrobial activity, it was able to inhibit the growth of a strain of Staphylococcus aureus resistant to methicillin, presenting MIC values equal to the standard antibiotic oxacillin. It was also able to inhibit a strain of Candida albicans HAM13 sensitive to fluconazole. In addition, lignin promoted a synergistic effect by promoting a decrease in MIC against these two strains evaluated. Finally, lignin proved to be an excipient with potential for controlled release of antimicrobials.

Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula.

Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A2A receptors (A2AR)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A2AR are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A2AR antagonists, prompting their clinical translation.

Resazurin Reduction-Based Assays Revisited: Guidelines for Accurate Reporting of Relative Differences on Metabolic Status.

Cell viability and metabolic activity are ubiquitous parameters used in biochemistry, molecular biology, and biotechnological studies. Virtually all toxicology and pharmacological projects include at some point the evaluation of cell viability and/or metabolic activity. Among the methods used to address cell metabolic activity, resazurin reduction is probably the most common. At variance with resazurin, resorufin is intrinsically fluorescent, which simplifies its detection. Resazurin conversion to resorufin in the presence of cells is used as a reporter of metabolic activity of cells and can be detected by a simple fluorometric assay. UV-Vis absorbance is an alternative technique but is not as sensitive. In contrast to its wide empirical "black box" use, the chemical and cell biology fundamentals of the resazurin assay are underexplored. Resorufin is further converted to other species, which jeopardizes the linearity of the assays, and the interference of extracellular processes has to be accounted for when quantitative bioassays are aimed at. In this work, we revisit the fundamentals of metabolic activity assays based on the reduction of resazurin. Deviation to linearity both in calibration and kinetics, as well as the existence of competing reactions for resazurin and resorufin and their impact on the outcome of the assay, are addressed. In brief, fluorometric ratio assays using low resazurin concentrations obtained from data collected at short time intervals are proposed to ensure reliable conclusions.

Low-dimensionality carbon-based biosensors: the new era of emerging technologies in bioanalytical chemistry.

Since the last decade, carbon nanomaterials have had a notable impact on different fields such as bioimaging, drug delivery, artificial tissue engineering, and biosensors. This is due to their good compatibility toward a wide range of chemical to biological molecules, low toxicity, and tunable properties. Especially for biosensor technology, the characteristic features of each dimensionality of carbon-based materials may influence the performance and viability of their use. Surface area, porous network, hybridization, functionalization, synthesis route, the combination of dimensionalities, purity levels, and the mechanisms underlying carbon nanomaterial interactions influence their applications in bioanalytical chemistry. Efforts are being made to fully understand how nanomaterials can influence biological interactions, to develop commercially viable biosensors, and to gain knowledge on the biomolecular processes associated with carbon. Here, we present a comprehensive review highlighting the characteristic features of the dimensionality of carbon-based materials in biosensing.

Diagnosing acute kidney injury ahead of time in critically ill septic patients using kinetic estimated glomerular filtration rate.

INTRODUCTION: Accurate and actionable diagnosis of Acute Kidney Injury (AKI) ahead of time is important to prevent or mitigate renal insufficiency. The purpose of this study was to evaluate the performance of Kinetic estimated Glomerular Filtration Rate (KeGFR) in timely predicting AKI in critically ill septic patients. METHODS: We conducted a retrospective analysis on septic ICU patients who developed AKI in AmsterdamUMCdb, the first freely available European ICU database. The reference standard for AKI was the Kidney Disease: Improving Global Outcomes (KDIGO) classification based on serum creatinine and urine output (UO). Prediction of AKI was based on stages defined by KeGFR and UO. Classifications were compared by length of ICU stay (LOS), need for renal replacement therapy and 28-day mortality. Predictive performance and time between prediction and diagnosis were calculated. RESULTS: Of 2492 patients in the cohort, 1560 (62.0%) were diagnosed with AKI by KDIGO and 1706 (68.5%) by KeGFR criteria. Disease stages had agreement of kappa = 0.77, with KeGFR sensitivity 93.2%, specificity 73.0% and accuracy 85.7%. Median time to recognition of AKI Stage 1 was 13.2 h faster for KeGFR, and 7.5 h and 5.0 h for Stages 2 and 3. Outcomes revealed a slight difference in LOS and 28-day mortality for Stage 1. CONCLUSIONS: Predictive performance of KeGFR combined with UO criteria for diagnosing AKI is excellent. Compared to KDIGO, deterioration of renal function was identified earlier, most prominently for lower stages of AKI. This may shift the actionable window for preventing and mitigating renal insufficiency.

The structure and matrix dynamics of bacterial biofilms as revealed by antimicrobial peptides' diffusion.

From the biological point of view, bacterial biofilms are communities of bacteria embedded in a self-produced gel matrix composed of polysaccharides, DNA, and proteins. Considering the biophysical point of view, the biofilm matrix is a highly dense, crowded medium that imposes constraints to solute diffusion, depending on the size, conformational dynamics, and net charge. From the pharmacological point of view, biofilms are additional difficulties to drug development as heterogeneity in oxygen and nutrient distribution, and consequently, heterogeneity in bacterial metabolic status leads to recalcitrance. For peptide scientists, biofilms are both a challenge and an opportunity. Biofilms can be intruded by peptides, revealing important biological, biophysical, and pharmacological insights. Peptides can be engineered for different sizes, flexibilities, and net charges, unravelling the determinants of diffusion; they kill bacteria by lysis, overcoming the hurdles of metabolic status heterogeneity, and they are able to kill bacteria in the biofilm core, leaving the matrix intact, that is, without causing bacterial biofilm dispersion as side effect. This concise review addresses the knowledge reached while interrogating bacterial biofilms with peptides and other reporter molecules, and the advances therefrom in biology, biophysics, and drug development.

Futile cycle of ß-oxidation and de novo lipogenesis are associated with essential fatty acids depletion in lipoatrophy.

Total absence of adipose tissue (lipoatrophy) is associated with the development of severe metabolic disorders including hepatomegaly and fatty liver. Here, we sought to investigate the impact of severe lipoatrophy induced by deletion of peroxisome proliferator-activated receptor gamma (PPARγ) exclusively in adipocytes on lipid metabolism in mice. Untargeted lipidomics of plasma, gastrocnemius and liver uncovered a systemic depletion of the essential linoleic (LA) and α-linolenic (ALA) fatty acids from several lipid classes (storage lipids, glycerophospholipids, free fatty acids) in lipoatrophic mice. Our data revealed that such essential fatty acid depletion was linked to increased: 1) capacity for liver mitochondrial fatty acid ß-oxidation (FAO), 2) citrate synthase activity and coenzyme Q content in the liver, 3) whole-body oxygen consumption and reduced respiratory exchange rate in the dark period, and 4) de novo lipogenesis and carbon flux in the TCA cycle. The key role of de novo lipogenesis in hepatic steatosis was evidenced by an accumulation of stearic, oleic, sapienic and mead acids in liver. Our results thus indicate that the simultaneous activation of the antagonic processes FAO and de novo lipogenesis in liver may create a futile metabolic cycle leading to a preferential depletion of LA and ALA. Noteworthy, this previously unrecognized cycle may also explain the increased energy expenditure displayed by lipoatrophic mice, adding a new piece to the metabolic regulation puzzle in lipoatrophies.

A Purine Derivative Containing an Organoselenium Group Protects Against Memory Impairment, Sensitivity to Nociception, Oxidative Damage, and Neuroinflammation in a Mouse Model of Alzheimer's Disease.

In the present study, the effect of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) was tested against memory impairment and sensitivity to nociception induced by intracerebroventricular injection of amyloid-beta peptide (Aß) (25-35 fragment), 3 nmol/3 µl/per site in mice. Memory impairment was determined by the object recognition task (ORT) and nociception by the Von-Frey test (VFT). Aß caused neuroinflammation with upregulation of glial fibrillary acidic protein (GFAP) (in hippocampus), nuclear factor-κB (NF-κB), and the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in cerebral cortex and hippocampus. Additionally, Aß increased oxidant levels and lipid peroxidation in cerebral cortex and hippocampus, but decreased heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prdx1) expression in the hippocampus. Anti-neuroinflammatory effects of FSP were demonstrated by a decrease in the expression of GFAP and NF-κB in the hippocampus, as well as a decrease in proinflammatory cytokines in both the hippocampus and cerebral cortex FSP protected against oxidative stress by decreasing oxidant levels and lipid peroxidation and by increasing HO-1 and Prdx1 expressions in the hippocampus of mice. Moreover, FSP prevented the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the hippocampus of mice induced by Aß. In conclusion, treatment with FSP attenuated memory impairment, nociception sensitivity by decreasing oxidative stress, and neuroinflammation in a mouse model of Alzheimer's disease.

Expression of type 1 cannabinoid receptor gene in bipolar disorder.

BACKGROUND: The Endocannabinoid System (ECBs) may have a crucial role in bipolar disorder (BD). Previous reports have not detected abnormalities in the expression of the cannabinoid receptor gene CNR1, encoding for CB1. However, we hypothesized that differentiating between mania and depression may uncover differences in CNR1 expression levels. METHODS: We recruited 44 subjects with BD type I (BD-I), in mania (n = 22) and depression (n = 22) and 25 Healthy Controls (HC). CNR1 gene expression was analyzed using a quantitative real-time polymerase chain reaction from peripheral blood mononuclear cells. Data were analyzed using frequentist non-parametric and Bayesian approaches (generalized location-scale model based on lognormal and gamma distributions). RESULTS: Using the frequentist non-parametric approach, the depression group had lower CNR1 expression compared to the mania group (p = 0.004). In addition, there was a negative correlation between CNR1 expression and Hamilton Depression Scale score (rho = -0.37; p = 0.007). Bayesian analyses further revealed that CNR1 expression in the mania group was higher and less variable than among HC (>95% probability), while CNR1 expression in the depression group was lower and more variable than among HC (100% probability). LIMITATIONS: Lack of participants with bipolar disorder in the euthymic phase, lack of toxicology screening and evaluation of CNR1 variants. CONCLUSION: CNR1 expression is higher and less variable in mania than in depression. It is highly probable that these differences also distinguish individuals in different illness phases from healthy controls. Future studies are needed to clarify the role of the endocannabinoid system in bipolar disorder.

Oral Lichen Planus and Oral Squamous Cell Carcinoma share key oncogenic signatures.

To investigate similarities in the gene profile of Oral Lichen Planus and Oral Squamous Cell Carcinoma that may justify a carcinogenic potential, we analyzed the gene expression signatures of Oral Lichen Planus and Oral Squamous Cell Carcinoma in early and advanced stages. Based on gene expression data from public databases, we used a bioinformatics approach to compare expression profiles, estimate immune infiltrate composition, identify differentially and co-expressed genes, and propose putative therapeutic targets and associated drugs. Our results revealed gene expression patterns related to processes of keratinization, keratinocyte differentiation, cell proliferation and immune response in common between Oral Lichen Planus and early and advanced Oral Squamous Cell Carcinoma, with the cornified envelope formation and antigen processing cross-presentation pathways in common between Oral Lichen Planus and early Oral Squamous Cell Carcinoma. Together, these results reveal that key tumor suppressors and oncogenes such as PI3, SPRR1B and KRT17, as well as genes associated with different immune processes such as CXCL13, HIF1A and IL1B are dysregulated in OLP.