The exploration of carbon steel corrosion inhibition in 0.5 mol L-1 H2SO4 using extracts from Hymenaea courbaril (HC) has resulted in significant findings. Extracts from the bark, leaves, fruit pulp, and fruit shell have all proven to be effective corrosion inhibitors, as demonstrated through surface studies and electrochemical methods. Infrared spectroscopy and high-performance liquid chromatography have identified the presence of phenolic compounds, which are known to have corrosion-inhibiting potential. UV-Vis spectroscopy has further revealed the adsorption of extract species on the steel surface. Electrochemical studies have confirmed the inhibition of corrosion, allowing to propose mechanisms of both chemisorption and physisorption. X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS) have provided evidence of the formation of an inhibitory layer, further supporting the inhibition of corrosion. Langmuir isotherms have indicated favorable adsorption of the extracts, while reduced surface roughness suggests improved protection of the steel surface. Activation energy calculations have demonstrated an increase in energy barriers, resulting in slower corrosion rates. These findings suggest that extracts from Hymenaea courbaril show promise as eco-friendly corrosion inhibitors, with potential industrial applications. Further research is needed to optimize the extraction process and fully understand the inhibition mechanisms. 05 0 5 0. L1 L 1 L- HSO H SO H2SO HC (HC bark leaves pulp inhibitors methods highperformance high performance compounds corrosioninhibiting inhibiting UVVis UV Vis physisorption Xray X ray XPS (XPS energydispersive dispersive SEMEDS SEM EDS (SEM-EDS layer barriers rates ecofriendly eco friendly applications

Worldwide, millions of people suffer from neurological and psychiatric conditions, such as schizophrenia, depression, and neurodegenerative diseases. These conditions are often linked to hyperactivity of monoamine oxidase B (MAO-B) in the brain, and inhibiting this enzyme can reduce oxidative stress, stabilize neurotransmitter levels, and alleviate symptoms. In this context, a pharmacophoric model was created using PharmaGist with 31 hits extracted from BindingDB to enable a pharmacophoric-based search of potential MAO-B inhibitors in ZincPharmer’s chemical space, followed by the building of 10 conformers for each molecule in the software OMEGA, screening for structural and electrostatic similarity to safinamide using ROCS (Rapid overlay of chemical structures) and EON (Electrostatic similarity for lead-hopping), respectively. In addition, the molecular docking with Gold using the score function was performed to rank the ligands with the highest probabilities of affinity to MAO-B and then discriminate those with suitable physical chemical, pharmacokinetic, and toxicological features using the tools QikProp, SwissADME, and DEREK. Four potential ligands with selective MAO-B inhibitor properties were identified, which show promise as future therapeutic agents for MAO-B-related disorders. Worldwide schizophrenia depression diseases MAOB MAO (MAO-B brain stress levels symptoms context 3 pharmacophoricbased based ZincPharmers ZincPharmer s space 1 OMEGA Rapid structures Electrostatic leadhopping, leadhopping lead hopping , lead-hopping) respectively addition pharmacokinetic QikProp SwissADME DEREK identified MAOBrelated related disorders lead-hopping

The in silico study aimed to suggest phytochemicals from Commiphora leptophloeos leaves essential oil as therapies against coronavirus disease (COVID-19) (or severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). For that, we used molecular docking (MD), absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and pharmacokinetic analysis. MD showed the presence of hydrophobic and hydrogen bonds for nine compounds. β-Selinene and bicyclogermacrene showed the best interaction values with the protein Mpro (ID: 6Y2F) (-5.9) and chimeric receptor complexed with its receptor human ACE2 (ID: 6VW1) (-6.1 and -5.5) proteins, as well as low gastrointestinal and high epithelial absorptions, medium permeability for Caco-2 cells and high epithelial permeability, low oral excretion, and were inhibitors of CYP2C19 and CYP2C9 enzymes. On the other hand, both were not permeable to the blood-brain barrier and inhibitors or substrates for glycoprotein-D, and showed carcinogenic potential, but only β-selinene was considered mutagenic. Although little bioavailable, both presented aspects structurally adequate, being compounds with moderate synthesis difficulty. Therefore, more analyses are necessary to evaluate the mechanism of action and unsatisfactory parameters foreseen in bioinformatic assays. COVID19 COVID 19 (COVID-19 2 SARSCoV2. SARSCoV2 SARSCoV SARS CoV . SARS-CoV-2) that MD, , (MD) absorption distribution metabolism excretion ADMET (ADMET analysis βSelinene β Selinene ID (ID 6Y2F YF Y F 5.9 59 5 9 (-5.9 ACE 6VW1 VW 6.1 61 6 1 (-6. 5.5 55 -5.5 proteins absorptions Caco2 Caco Caco- CYPC CYP C CYP2C1 CYP2C enzymes hand bloodbrain blood brain glycoproteinD, glycoproteinD glycoprotein D, D glycoprotein-D potential βselinene selinene mutagenic bioavailable adequate difficulty Therefore assays COVID1 (COVID-1 SARS-CoV-2 (MD 5. (-5. 6VW 6. (-6 -5. (COVID- SARS-CoV- (-5 (- -5 (COVID SARS-CoV ( -

Alzheimer’s disease (AD) is a most common form of dementia and results in memory loss, disorientation, impaired thinking and changes in personality as well as mood. The dementia cases mostly turn into the Alzheimer’s disease (AD). Another disease, the Parkinson’s disease (PD), mainly affects dopaminergic neurons in substantia nigra. A series of previously synthesized quinolone-triazole hybrids were investigated and evaluated for their anti-acetyl cholinesterase and against monoamine oxidase reactive properties through in silico characterization. The ground state electronic properties were determined by electron density of the compounds through DFTs (density functional theory) calculation. The geometries of all compounds were optimized using Becke-3-parameter-Lee-Yang-Parr (B3LYP) method and 6-311g basis set. Docking studies were conducted using the AutoDock and Molecular Operating Environment (MOE) software and the results of the potent derivatives found to be encouraging. The data confirmed that all the compounds have drug-like properties and was further confirmed by ADMET (absorption, distribution, metabolism, excretion and toxicity) properties. Alzheimers Alzheimer s AD (AD loss disorientation mood AD. . Parkinsons Parkinson PD, PD , (PD) nigra quinolonetriazole quinolone triazole antiacetyl anti acetyl characterization theory calculation Becke3parameterLeeYangParr BeckeparameterLeeYangParr Becke 3 parameter Lee Yang Parr B3LYP BLYP B LYP (B3LYP 6311g g 6 311g set MOE (MOE encouraging druglike drug like absorption, absorption (absorption distribution metabolism toxicity (PD parameterLeeYangParr

The inhibition of the fatty acid amide hydrolase (FAAH), an endocannabinoid system component, emerged as a potentially new therapeutic target for a range of clinical disorders such as acute and chronic pain. Some α-ketoheterocycle derivatives demonstrated interesting analgesic and anti-inflammatory activities in vitro. Ligand-Based Drug Design techniques such as knowledge graph convolutional networks (kGCN) and hologram quantitative structure-activity relationship (HQSAR) using α-ketoheterocycle derivatives from five different datasets were generated to discover the relation between the chemical structures and the inhibition activity. Meanwhile, structure-based drug design simulations as interaction fields (MIF), molecular docking, and ligand sites studies (LSI) from FAAH were performed using Autogrid software and FTmap/FTsite servers. The results of both studies were merged to propose predictive models. The resulting kGCN model demonstrated adequate accuracy area under the curve by receiver operating characteristic (AUC-ROC 0.7922). From contribution maps of the Ligand-Based Drug Design (LBDD) models and the generated probes using MIF and LSI, it was observed that the oxazole ring, the ketone group, and the apolar chain present in the structures of the inhibitors are important, besides the evidence of the Cys269 and Val270 residues importance for the potential interaction, confirmed by carried docking studies. These fragments and structural information can be used to carry out new FAAH potential inhibitors studies and report kGCN as an accurate classification technique. FAAH, , (FAAH) component pain αketoheterocycle α ketoheterocycle antiinflammatory anti inflammatory vitro LigandBased Ligand Based (kGCN structureactivity structure activity HQSAR (HQSAR Meanwhile structurebased based MIF, (MIF) LSI (LSI FTmapFTsite FTmap FTsite servers AUCROC AUC ROC 0.7922. 07922 0.7922 . 0 7922 0.7922) LBDD (LBDD ring group important Cys Cys26 Val Val27 technique (FAAH (MIF 0792 0.792 792 Cys2 Val2 079 0.79 79 07 0.7 7 0.

The essential oil extracted from Anemia tomentosa (EOAT) has shown larvicidal potential against Aedes aegypti, based on methods in vitro and in silico. Chromatographic and spectrometric techniques (gas chromatography-mass spectrometry (CG-MS), gas chromatography-flame ionization detector (GC-FID)), as well as mono and bidimensional nuclear magnetic resonance spectroscopy (NMR) were used to assess 10 essential oil components. Chemical composition of essential oil comprised 87.51% sesquiterpenes, with emphasis on presilphiperfolan-1-ol (42.13%) and silphiperfol-5-ene (19.47%). Larvicidal assay conducted in vitro with EOAT has evidenced potential cytotoxic activity up to 48 h exposure to it; mortality rate observed for A. aegypti larvae exposed to essential oil reached 100%. Study conducted in silico with chemical compounds deriving from the herein investigated plant species has evidenced its potential to inhibit acetylcholinesterase in A. aegypti. Activity of triquinane sesquiterpenes ranging from -6.8 to -8.2 kcal mol-1 stood out in comparison to that of temephos (-7.5 kcal mol-1). Chemical compounds identified in the investigated essential oil presented low human and environmental toxicity, as observed in absorption, distribution, metabolism and excretion, and toxicity (ADMETox) predictions. (EOAT chromatographymass chromatography mass CGMS, CGMS CG MS , (CG-MS) chromatographyflame flame GCFID, GCFID GC FID (GC-FID)) NMR (NMR 1 components 8751 87 51 87.51 presilphiperfolan1ol presilphiperfolanol presilphiperfolan ol 42.13% 4213 42 13 (42.13% silphiperfol5ene silphiperfolene silphiperfol 5 ene 19.47%. 1947 19.47% . 19 47 (19.47%) 4 it A 100 100% 6.8 68 6 8 -6. 8.2 82 2 -8. mol1 mol mol- 7.5 75 7 (-7. mol1. mol-1) absorption distribution excretion ADMETox (ADMETox predictions (CG-MS (GC-FID) 875 87.5 42.13 421 (42.13 194 19.47 (19.47% 6. -6 8. -8 7. (-7 (GC-FID 87. 42.1 (42.1 19.4 (19.47 - (- 42. (42. 19. (19.4 ( (42 (19. (4 (19 (1

The recycle and utilization of expired drugs is a challenge for many countries at present. The employment of expired drugs as green corrosion inhibitors is expected to address both drug recycling and corrosion prevention issues, with significant economic and environmental value. Herein, the individually and combination corrosion inhibition performance of expired amoxicillin (AMC) and penicillin V potassium tablets (PVP) for lowcarbon steel in 20% acetic acid solution containing 600 mg L-1 chloride ion are evaluated by electrochemistry and weight loss method. Both the AMC and PVP present the mixed-type corrosion inhibitors mainly affect the cathode process when used individually. The optimum inhibition efficiency is 61.22% (AMC) and 79.21% (PVP), which all appear in 5.0 × 10-3 mol L-1. The AMC and PVP are adsorbed on the steel surface by mixed physisorption and chemisorption, which are consistent with the Langmuir adsorption isotherm. The corrosion inhibition rate drops sharply when AMC and PVP are combined use with a close mole ratio. But a small amount of PVP significantly enhance the corrosion inhibition effect of AMC, the corrosion inhibition rate from 61.22 to 79.72%. The corrosion inhibition rate of AMC and PVP combination inhibitor decreased with the increase of temperature. issues value Herein (AMC (PVP 20 60 L1 L 1 L- method mixedtype type 6122 61 22 7921 79 21 79.21 PVP, , 50 5 0 5. 103 10 3 10- L1. 1. chemisorption isotherm ratio 61.2 7972 72 79.72% temperature 2 6 612 792 7 79.2 61. 797 79.72 79. 79.7

Resumo A doença renal do diabetes (DRD) permanece como a principal causa de doença renal crônica (DRC) mundialmente. A patogênese da DRD é influenciada por mecanismos funcionais, histopatológicos e imunológicos, incluindo a atividade do inflamassoma NLRP3 e estresse oxidativo. Os inibidores do cotransportador de sódio-glicose 2 (iSGLT2) demonstraram benefícios metabólicos e a capacidade de retardar a progressão da DRD em diversos estudos clínicos ao longo dos anos. Estudos recentes sugerem que a atividade antidiabética também se estende à inibição da resposta inflamatória, incluindo modulação do inflamassoma NLRP3, redução de marcadores pró-inflamatórios e redução do estresse oxidativo. Aqui, avaliamos a eficácia dos iSGLT2 no tratamento da DRC e discutimos o papel da resposta inflamatória no desenvolvimento da DRD, incluindo sua relação com o inflamassoma NLRP3 e o estresse oxidativo. (DRD (DRC mundialmente funcionais imunológicos NLRP oxidativo sódioglicose sódio glicose iSGLT (iSGLT2 anos próinflamatórios pró inflamatórios Aqui (iSGLT

Abstract Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease (CKD) worldwide. The pathogenesis of DKD is influenced by functional, histopathological, and immune mechanisms, including NLRP3 inflammasome activity and oxidative stress. The sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown metabolic benefits and the ability to slow the progression of DKD in several clinical studies over the years. Recent studies suggest that the antidiabetic activity also extends to inhibition of the inflammatory response, including modulation of the NLRP3 inflammasome, reduction of pro-inflammatory markers and reduction of oxidative stress. Here we review the efficacy of SGLT2i in the treatment of CKD and discuss the role of the inflammatory response in the development of DKD, including its relationship to the NLRP3 inflammasome and oxidative stress. (DKD (CKD worldwide functional histopathological mechanisms NLRP stress sodiumglucose sodium glucose SGLTi SGLT i (SGLT2i years proinflammatory pro

Resumen La seguridad de los psicofármacos durante el embarazo es un tema crucial en la práctica clínica. En esta revisión, se hace un breve recorrido sobre los cambios en el embarazo que impactan en la farmacodinamia de los medicamentos, además, se analizan los principales grupos farmacológicos en psiquiatría y sus efectos durante el embarazo. Se identifican tres períodos críticos durante el embarazo. El período de las primeras dos semanas se asocia con un mayor riesgo de aborto espontáneo. El período de la segunda a la décima semana es el más riesgoso, ya que pueden ocurrir alteraciones teratogénicas que afectan el desarrollo fetal. El período posterior a la décima semana se caracteriza por alteraciones en el crecimiento y desarrollo funcional del feto, pero suelen ser menos graves. Los antidepresivos, especialmente los inhibidores selectivos de la receptación de serotonina (ISRS) y los antipsicóticos de segunda generación se consideran los más seguros, pero estos últimos pueden estar asociados con síndrome metabólico, cardiopatías congénitas y trastornos del neurodesarrollo. El litio se ha asociado con efectos teratogénicos y malformaciones cardíacas, mientras que el valproato está relacionado con defectos congénitos importantes. Las benzodiacepinas pueden tener efectos tóxicos y causar síndrome de abstinencia en el recién nacido. La seguridad de los psicofármacos durante el embarazo requiere una evaluación individualizada de los beneficios y riesgos. Aunque algunos grupos de psicofármacos se consideran relativamente seguros, es necesario tener precaución y considerar las posibles complicaciones asociadas con su uso durante el embarazo.

Abstract: The safety of psychoactive drugs during pregnancy is a crucial issue in clinical practice. In this review, a brief overview of the changes in pregnancy that impact the pharmacodynamics of drugs is made; in addition, the main pharmacological groups in psychiatry and their effects during pregnancy are analyzed. Three critical periods during pregnancy are identified. The period of the first two weeks is associated with an increased risk of miscarriage. The period from the second to the tenth week is the most at risk , since teratogenic effects that affect fetal development can take place. The period after the tenth week is characterized by alterations in fetal growth and functional development , however ,less severe defects. Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), and second-generation antipsychotics are considered the safest, but the latter may be associated with metabolic syndrome, congenital heart disease, and neurodevelopmental disorders. Lithium has been associated with teratogenic effects and cardiac malformations, while valproate is associated with major birth defects. Benzodiazepines can have toxic effects and cause Neonatal Withdrawal Syndrome . The safety of psychotropic drugs during pregnancy requires an individualized assesment of the benefits and risks. Although some groups of psychiatric drugs are considered relatively safe, caution is needed when considering the potential complications associated with their use during pregnancy.

Resumen (Objetivo) Plasmodium vivax infecta ampliamente a muchas personas en algunas regiones. La singularidad de formar una etapa latente hace que la malaria vivax pueda ser inducida por una recaída por una infección adicional. En el presente estudio, utilizamos un enfoque de simulación dinámica y acoplamiento molecular ara predecir la posibilidad de que compuestos bioactivos de la familia de plantas Zingiberaceae sean candidatos a fármaco contra la malaria dirigiéndose a la proteína de unión a Duffy de Plasmodium vivax (PvDBP). Se requiere la interacción molecular PvDBP-DARC para mediar el proceso de invasión de merozoitos en los glóbulos rojos. La inhibición de este proceso posiblemente pueda controlar el crecimiento y desarrollo del parásito. (Metodología) El análisis de acoplamiento molecular dio como resultado los dos compuestos principales con el valor de energía de unión más bajo, incluida la 5,7-dihidroxiflavanona (-9,3 kcal/mol) y la pinostrobina (-9,2 kcal/mol). (Resultados) Estos compuestos previstos tienen una interacción más fuerte que la cloroquina como control. Además, los compue potenciales también interactúan con los residuos del sitio de unión de DARC y lo mantienen durante el proceso de simulación de dinámica molecular. De lo contrario, la cloroquina como control no puede retener el 75% de los residuos de unión hacia PvDBP. El estudio de dinámica molecular reveló que los tres complejos tienen una estabilidad relativamente similar. (Conclusiones) Predijimos que los dos compuestos bioactivos tienen potencial como inhibidores de la invasión de merozoitos.

Resumo (Objetivo) O Plasmodium vivax infecta amplamente muitas pessoas em algumas regiões. A singularidade de formar um estágio latente significa que a malária vivax pode ser induzida por recaída devido à infecção adicional. No presente estudo, utilizamos uma abordagem de simulação dinâmica e de acoplamento molecular para prever a possibilidade de compostos bioativos da família de plantas Zingiberaceae como candidatos a medicamentos antimaláricos, visand o aproteína de ligação Duffy do Plasmodium vivax (PvDBP). A interação molecular PvDBP-DARC é necessária para mediar o processo de invasão de merozoítos nos glóbulos vermelhos. A inibição deste processo pode possivelmente controlar o crescimento e desenvolvimento do parasita. (Metodologia) A análise de acoplamento molecular resultou nos dois principais compostos com o menor valor de energia de ligação, incluindo ,7-dihidroxiflavanona (-9,3 kcal/mol) e pinostrobina (-9,2 kcal/mol). (Resultados) Esses compostos previstos têm uma interação mais forte do que a cloroquina como controle. Além disso, os compostos potenciais também interagem e mantêm resíduos do sítio de ligação do DARC durante o processo de simulação de dinâmica molecular. Caso contrário, a cloroquina como controle não pode reter 75% dos resíduos de ligação ao três complexos apresentam estabilidade relativa compostos bioativos têm potencial como inibidor Palavras chave: Medicamentos antimalária; ePvmeesdmsilDBP. ntesa invício;O estudo de dinâmica molecular revelou que os emelhante. (Conclusões) Previmos que os dois asão de merozoítos. Plasmodium vivax; PvDBP; Zingiberáceas.

Abstract (Objective) Plasmodium vivax predominantly infects many people in numerous tropical areas, including Southeast Asia, the Western Pacific, the Americas, and the Eastern Mediterranean. The uniqueness of forming dormant stages can lead to relapse in vivax malaria upon further infection. This study used molecular docking and dynamic simulation to predict potential bioactive compounds from the Zingiberaceae plant family as inhibitors by targeting Plasmodium vivax Duffy Binding Protein (PvDBP). PvDBP-DARC molecular interaction is required to mediate the merozoite invasion process into red blood cells. Inhibiting this process can possibly control parasite growth and development. (Methodology) Molecular docking screening was conducted by using 138 natural compounds from the Zingiberaceae plant family targeting Plasmodium vivax Duffy binding protein (PvDBP). The top two compounds with the lowest binding energy were selected to be analyzed by pharmacokinetics prediction and molecular dynamic (MD) simulation. (Results) Molecular docking screening resulted in the top two compounds with the lowest binding energy value, including 5,7-dihydroxyflavanone (-9.3 kcal/mol) and pinostrobin (-9.2 kcal/mol). These compounds are predicted to have stronger interaction than chloroquine as a control. Furthermore, the potential compounds also interact with DARC binding site residues and maintain them during the molecular dynamic simulation process. Otherwise, chloroquine as a control cannot retain 75% binding residues towards PvDBP. A molecular dynamic study revealed that all three complexes have relatively similar stability. (Conclusions) We predicted that the two bioactive compounds (5,7-dihydroxyflavanone and pinostrobin) have the potential as merozoite invasion inhibitors.

Abstract GLP1 receptor agonists (GLP1-RAs) are drugs that mimic the effects of the incretin hormone GLP1 and were initially introduced in medicine for the treatment of diabetes in 2005 and for obesity in 2014. Over time, data from secondary and exploratory objectives of large randomized controlled-trials suggested that GLP1-RAs could also exert renal action by slowing the progression of kidney disease in patients with and without diabetes. Based on this rationale, the Flow study (1 mg semaglutide vs placebo) was designed and recruitment began in 2019 until May 2021. The recently published results confirmed the effect of semaglutide in reducing the composite renal outcome. However, similar to SGLT2 inhibitors, the potential mechanisms behind the renal effects of GLP1-RAs still need to be elucidated. The aim of this review is to address the different physiological mechanisms of GLP1-RAs at the renal level, using evidence from experimental studies and current scientific literature. GLP GLP1RAs GLPRAs RAs (GLP1-RAs 200 2014 time controlledtrials controlled trials rationale 1 ( placebo 201 2021 outcome However SGLT inhibitors elucidated level literature 20 202 2

Resumo Os agonistas do receptor de GLP1 (GLP1-RAs) são medicamentos que imitam os efeitos do hormônio incretínico GLP1. Eles foram inicialmente introduzidos na medicina para o tratamento do diabetes em 2005 e para a obesidade em 2014. Com o passar do tempo, dados provenientes de objetivos secundários e exploratórios de amplos ensaios clínicos randomizados sugeriram que os GLP1-RAs também poderiam exercer ação renal ao retardar a progressão da doença renal em pacientes com e sem diabetes. Com base nesse raciocínio, o estudo Flow (semaglutida 1 mg vs. placebo) foi desenhado e o recrutamento começou em 2019, estendendo-se até maio de 2021. Os resultados publicados recentemente confirmaram o efeito da semaglutida na redução do desfecho renal composto. No entanto, assim como os inibidores do SGLT2, os mecanismos potenciais por trás dos efeitos renais dos GLP1-RAs ainda precisam ser elucidados. O objetivo desta revisão é abordar os diferentes mecanismos fisiológicos dos GLP1-RAs em nível renal, utilizando evidências de estudos experimentais e da literatura científica atual. GLP GLP1RAs GLPRAs RAs (GLP1-RAs 200 2014 tempo raciocínio vs placebo 2019 estendendose estendendo se 2021 composto entanto SGLT2 SGLT elucidados atual 20 201 202 2

Abstract Hailey-Hailey disease is a rare genodermatosis described in 1939, with an autosomal dominant inheritance pattern, characterized by compromised adhesion between epidermal keratinocytes. It has an estimated prevalence of 1/50,000, with no gender or race predilection. It results from a heterozygous mutation in the ATP2C1 gene, which encodes the transmembrane protein hSPA1C, present in all tissues, with preferential expression in keratinocytes. Mutations in the ATP2C1 gene cause changes in the synthesis of junctional proteins, leading to acantholysis. It usually begins in adulthood, with isolated cases at the extremes of life. It manifests as vesico-bullous lesions mainly in the flexural areas, which develop into erosions and crusts. Chronic lesions may form vegetative or verrucous plaques. Pruritus, a burning feeling and pain are common. It evolves with periods of remission and exacerbation, generally triggered by humidity, friction, heat, trauma and secondary infections. The diagnosis is based on clinical and histopathological criteria: marked suprabasal acantholysis, loosely joined keratinocytes, giving the appearance of a “dilapidated brick wall”, with a few dyskeratotic cells. The acantholysis affects the epidermis and spares the adnexal epithelia, which helps in the differential diagnosis with pemphigus vulgaris. Direct immunofluorescence is negative. The main differential diagnoses are Darier disease, pemphigus vegetans, intertrigo, contact dermatitis, and inverse psoriasis. There is no cure and the treatment is challenging, including measures to control heat, sweat and friction, topical medications (corticosteroids, calcineurin inhibitors, antibiotics), systemic medications (antibiotics, corticosteroids, immunosuppressants, retinoids and immunobiologicals) and procedures such as botulinum toxin, laser and surgery. There is a lack of controlled clinical trials to support the choice of the best treatment. HaileyHailey Hailey 1939 pattern keratinocytes 150000 1 50 000 1/50,000 predilection ATPC ATP C ATP2C hSPA1C hSPAC hSPA tissues proteins adulthood life vesicobullous vesico bullous areas crusts plaques Pruritus common exacerbation humidity friction heat infections criteria dilapidated wall, wall , wall” cells epithelia vulgaris negative vegetans intertrigo dermatitis psoriasis challenging corticosteroids (corticosteroids inhibitors antibiotics, antibiotics antibiotics) (antibiotics immunosuppressants immunobiologicals toxin surgery 193 15000 5 00 1/50,00 19 1500 0 1/50,0 150 1/50, 15 1/50 1/5 1/

Abstract Prurigo is a reactive, hyperplastic skin condition characterized by pruritic papules, plaques, and/or nodules. The temporal classification includes acute/subacute and chronic disease (≥ 6 weeks), with different clinical variants, synonymies, and underlying etiological factors. The immunology of chronic prurigo shows similarities with atopic dermatitis due to the involvement of IL-4 and IL-13, IL-22, and IL-31. Treatment includes antihistamines, topical steroids, dupilumab, and JAK inhibitors. Several conditions manifest clinically as prurigo-like lesions, and the correct clinical diagnosis must precede correct treatment. Furthermore, chronic prurigos represent a recalcitrant and distressing dermatosis, and at least 50% of these patients have atopic diathesis, the treatment of which may induce adverse effects, especially in the elderly. The quality of life is significantly compromised, and topical treatments are often unable to control symptoms and skin lesions. Systemic immunosuppressants, immunobiologicals, and JAK inhibitors, despite the cost and potential adverse effects, may be necessary to achieve clinical improvement and quality of life. This manuscript reviews the main types of prurigo, associated diseases, their immunological bases, diagnosis, and treatment. reactive papules plaques andor or nodules acutesubacute acute subacute ≥ ( weeks, weeks , weeks) variants synonymies factors IL4 IL 4 IL- IL13, IL13 13, 13 IL-13 IL22, IL22 22, 22 IL-22 IL31. IL31 31. 31 IL-31 antihistamines steroids dupilumab inhibitors prurigolike like lesions Furthermore dermatosis 50 diathesis effects elderly compromised immunosuppressants immunobiologicals diseases bases IL1 1 IL-1 IL2 2 IL-2 IL3 3 IL-3 5

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also “gliflozin” our patients with kidney stone disease? worldwide lithiasis iSGLT question gliflozin “gliflozin disease

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também “gliflozinar” os litiásicos? mundo iSGLT pergunta gliflozinar “gliflozinar litiásicos

Resumo O complexo da esclerose tuberosa (CET) é uma doença autossômica dominante caracterizada pelo desenvolvimento de hamartomas no sistema nervoso central, coração, pele, pulmões e rins e outras manifestações, incluindo convulsões, tubérculos corticais, linhas de migração radial, autismo e deficiência cognitiva. A doença está associada a variantes patogênicas nos genes TSC1 ou TSC2, resultando na hiperativação da via mTOR, um importante regulador do crescimento e metabolismo celular. Consequentemente, a hiperativação da via mTOR leva à proliferação anormal do tecido e ao desenvolvimento de tumores sólidos. O envolvimento renal no CET é caracterizado pelo desenvolvimento de lesões císticas, carcinoma de células renais e angiomiolipomas renais, que podem progredir e causar dor, sangramento e perda da função renal. Nos últimos anos, houve uma mudança notável na abordagem terapêutica do CET, especialmente no tratamento das manifestações renais. Os inibidores de mTOR surgiram como a principal opção terapêutica, enquanto intervenções cirúrgicas como nefrectomia e embolização são reservadas principalmente para complicações que não respondem ao tratamento clínico, como hemorragia renal grave. Esta revisão se concentra nas principais características clínicas do CET, nos mecanismos subjacentes ao envolvimento renal, nos recentes avanços na terapia para lesões renais e nas perspectivas futuras. (CET central coração pele convulsões corticais radial cognitiva TSC TSC2 celular Consequentemente sólidos císticas dor anos clínico grave futuras

Abstract Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas in the central nervous system, heart, skin, lungs, and kidneys and other manifestations including seizures, cortical tubers, radial migration lines, autism and cognitive disability. The disease is associated with pathogenic variants in the TSC1 or TSC2 genes, resulting in the hyperactivation of the mTOR pathway, a key regulator of cell growth and metabolism. Consequently, the hyperactivation of the mTOR pathway leads to abnormal tissue proliferation and the development of solid tumors. Kidney involvement in TSC is characterized by the development of cystic lesions, renal cell carcinoma and renal angiomyolipomas, which may progress and cause pain, bleeding, and loss of kidney function. Over the past years, there has been a notable shift in the therapeutic approach to TSC, particularly in addressing renal manifestations. mTOR inhibitors have emerged as the primary therapeutic option, whereas surgical interventions like nephrectomy and embolization being reserved primarily for complications unresponsive to clinical treatment, such as severe renal hemorrhage. This review focuses on the main clinical characteristics of TSC, the mechanisms underlying kidney involvement, the recent advances in therapy for kidney lesions, and the future perspectives. (TSC system heart skin lungs seizures tubers lines disability genes metabolism Consequently tumors lesions angiomyolipomas pain bleeding function years option treatment hemorrhage perspectives