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For years, the biochemical processes that are triggered by harmful and non-harmful stimuli at the central nervous system level have been extensively studied by the scientific community through numerous techniques and animal models. For example, one of these techniques is the use of immediate expression genes, which is a useful, accessible, and reliable method for observing and quantifying cell activation. It has been shown that both the c-fos gene and its protein c-Fos have rapid activation after stimulus, with the length of time that they remain active depending on the type of stimulus and the activation time depending on the stimulus and the structure studied. Fos requires the participation of other genes (such as c-jun) for its expression (during hetero-dimer forming). c-Fos dimerizes with c-Jun protein to form factor AP-1, which promotes the transcription of various genes. The production and removal of c-Fos is part of cellular homeostasis, but its overexpression results in increased cell proliferation. Although Fos has been used as a marker of cellular activity since the 1990s, which molecular mechanism participates in the regulation of the expression of this protein is still unknown because the gene and the protein are not specific to neurons or glial cells. For these reasons, this work has the objective of gathering information about this protein and its use in neuroscience.

Prolactin (PRL) is a polypeptide hormone synthesized in the lactotrophs of the adenohypophysis and in extrahypophyseal glands (such as the prostate and breasts) where it promotes their development. PRL is also involved in cancer development in these glands. It has been shown to stimulate cancer cell migration, suggesting its possible involvement in metastasis, in which cell migration plays an essential role. However, the role of PRL in cell migration is still unclear. Moreover, the intracellular mechanisms activated by PRL to carry out cell migration are less well understood. PRL exerts its effects via the PRL receptor (PRLR), which leads intracellularly to phosphorylation of Janus protein kinase 2 (JAK2), which in turn phosphorylates p21-activated protein kinase (PAK1), leading to an increase in cell migration. Although several studies have described the involvement of the PRL-PAK1 pathway in breast cancer cell migration, the molecular mechanisms have not been fully elucidated and there is no integration of these into signaling pathways. This study was conducted based on literature search of review articles and original research in the PubMed database, using the following keywords: PRL, cell migration, PRL and cell migration, PAK1 and signaling pathways. The aim of this review article was to describe the major signaling pathways controlled by PRL-PAK1 and propose a comprehensive model of the signaling pathways associated with PRL-PAK1.

Considered a neurodegenerative disease, Alzheimer’s disease (AD) involves a physiopathological process characterized by the presence of the beta-amyloid peptide, hyperphosphorylated Tau protein, and neuroinflammation. Diabetes mellitus (DM) is an endocrine disease characterized by insulin resistance, where decreased production of this hormone causes a constant state of hyperglycemia. Although it is recognized that DM is a risk factor for the development of AD, the compression of the mechanisms involved is not completely understood. The present review evaluates the information acquired from primary and secondary sources, focusing on the alterations in gene expression associated with AD as well as the alterations in gene expression associated with DM, to later highlight the influence that these types of alterations developed in patients with DM can have on both the development and progression of AD. Finally, we point out those alterations that impact the phosphatidyl Inositol 3 Kinase/Akt (PI3K/Akt) pathway, which seems to intervene in the physiopathological process of both diseases, considering that the compression of these gene alterations can help us understand the intricate link between DM and AD.

Objectives Alzheimer’s disease is complex and involves several proteins. Most affected are Tau protein and amyloid precursor protein (APP) which, when cleaved by the enzymes β-secretase (BACE1) and γ-secretase (Nicastrin), yield the amyloid peptide. Although these processes take place mainly in neurons, it is not exclusive of them, as glia cells also contribute to these processes. The objective of this study was to evaluate the effect of nimesulide, resveratrol and citalopram on C6 (glioma) cells when exposed to Lipopolysaccharide (LPS). Methods Expression levels of the proteins APP, BACE1, COX-2, Nicastrin and Tau-p were evaluated by Western-blot and ELISA in C6 cells by effect of LPS, and the drugs citalopram, nimesulide and resveratrol. Results It was found that LPS is able to hyperphosphorylate Tau in this cell model and the drugs decrease hyperphosphorylation. We also found that the drugs increase the expression of APP, decrease BACE1 and promote the expression of Nicastrin. COX-2 decreases its expression when nimesulide is used. Conclusions Our results suggest that C6 cell line is useful to analyze the effect of pro-inflammatory molecules on tau phosphorylation and APP expression in vitro. The beneficial effect on the reduction of tau hyperphosphorylation shown by citalopram, nimesulide and resveratrol should be taken with caution due to the limitations of the present study and further research on these compounds is needed to determine their therapeutic use in neurodegenerative diseases such as Alzheimer’s disease. Amaç Alzheimer hastalığı karmaşıktır ve birkaç protein içerir. En çok etkilenenler, u-sekretaz (BACE1) ve γ-sekretaz (Nicastrin) enzimleri tarafından parçalandığında amiloid peptidi veren Tau proteini ve amiloid öncü proteinidir (APP). Bu süreçler esas olarak nöronlarda gerçekleşmesine rağmen, glia hücreleri de bu süreçlere katkıda bulunduğundan, bunlardan ayrı değildir. Amaç: Bu çalışmanın amacı, LPS’ye maruz kaldığında nimesulid, resveratrol ve sitalopramın C6 (glioma) hücreleri üzerindeki etkisini değerlendirmektir. Gereç ve Yöntem APP, BACE1, COX-2, Nicastrin ve Tau-p proteinlerinin ekspresyon seviyeleri, LPS’nin etkisi ile C6 hücrelerinde Western-blot ve ELISA ve sitalopram, nimesulid ve resveratrol ilaçları ile değerlendirildi. Bulgular Bu hücre modelinde LPS’nin Tau’yu hiperfosforilat edebildiği ve ilaçların hiperfosforilasyonu azalttığı bulundu. Ayrıca ilaçların APP ekspresyonunu arttırdığını, BACE1’i azalttığını ve Nicastrin ekspresyonunu teşvik ettiğini bulduk. Nimesulid kullanıldığında COX-2 ekspresyonunu azaltır. Sonuçlar Sonuçlarımız, pro-enflamatuar moleküllerin tau fosforilasyonu ve in vitro APP ekspresyonu üzerindeki etkisini analiz etmek için C6 hücre hattının yararlı olduğunu göstermektedir. Sitalopram, nimesulid ve resveratrol tarafından gösterilen tau hiperfosforilasyonunun azaltılması üzerindeki yararlı etki, mevcut çalışmanın sınırlamaları nedeniyle dikkatle alınmalı ve bu bileşikler üzerinde, Alzheimer hastalığı gibi nörodejeneratif hastalıklarda terapötik kullanımlarının belirlenmesi için daha fazla araştırmaya ihtiyaç vardır.

Androgen-dependent LNCaP and androgen-independent DU-145 cells, were treated with different concentrations of ergosterol (15 µM and 25 µM) and its respective cell viability was measured by MTT bioassay. While ergosterol showed an antiproliferative effect on LNCaP, on DU-145 promoted cell proliferation. This differential effect suggests that the effect of ergosterol might be related to its ability to act as an Androgen Receptor ligand.

The prostate is an accessory sex gland responsible for producing and excreting prostate fluid. In the male rat, hormones such as testosterone (T) and prolactin (PRL) and the pelvic and hypogastric nerves regulate the gland, providing afferent information and adrenergic and cholinergic innervation to the prostate. Damages in the innervation or alterations in the hormonal levels of T and PRL changes the prostate’s cytoarchitecture and function that can promote the presence of cancer. However, sexual activity delays effects induced by hormonal alterations or dysfunction of the autonomic nervous system, but it does not mean that they do not appear since the cases of death from prostate cancer is still increasing. That is why this review has the fundamental purpose of showing the relationship between the hormones, autonomic nervous system, and sexual behavior in the pathophysiology of the prostate, with the ultimate aim of trying to understand the role that each one plays in diseases of the prostate. To date, results show that morphological changes in the prostate correlate with an increase in prolactin serum levels, a decrease in androgen and long prolactin receptors, and an increase in short prolactin receptors. Also, damage in the innervation induces an increase in androgen and muscarinic receptors in the major pelvic ganglia that supply the nerves that control the prostate in animal with sexual experience.

Introduction The study of behaviour is a fundamental part of comprehensive patient care, since the patient should be considered as a biopsychosocial entity. In the case of Alzheimer's disease (AD), the major limitation in the diagnosis of the patient is that it can only be made after death. Therefore, identification of behaviours consistent with behavioural dysfunction, psychosis and neuropsychiatric symptoms represents a very useful tool for establishing a presumptive diagnosis in vivo of AD. Further taking into account that diabetes mellitus (DM) is a disease with a growing worldwide incidence that is considered a risk factor for the development of AD, the presence of depressive behaviours and mild cognitive impairment stand out as important elements identified in the DM/AD link. Results This study presents the results of a review of evidence obtained from secondary sources and describes characteristic behaviours identified in AD. Conclusions We conclude that the depressive behaviour identified in both AD and MD and the analysis of depressive behaviours along with mild cognitive impairment are part of the link between DM and AD.

The causes of the broad spectrum of severity in COVID-19 are unknown. A protective effect through humoral immunity from previous infections by viruses of the SARS-CoV-2 family could explain a mild form of this disease. This study aimed to address whether the presence of antibodies against human seasonal coronaviruses (HCoVs) could prevent severe manifestations of COVID-19. A cross-sectional study was carried out in 165 participants. The presence of pre-existent antibodies against the seasonal HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63 were detected. From all of the seasonal HCoVs studied, it was only found that being seropositive to HCoV-229E presented an association (p = 0.012) with developing mild clinical symptoms of COVID-19 or being asymptomatic. Multinomial regression analysis showed that being seropositive to HCoV-229E is associated with mild or moderate clinical symptoms for COVID-19. Statistical analysis also showed that being female is associated with being asymptomatic for SARS-CoV-2 infection or developing mild COVID-19. A subgroup analysis taking only seropositive to HCoV-229E revealed that females are more likely to develop asymptomatic SARS-CoV-2 infection (OR = 27.242, 95% CI 2.092–354.706, p = 0.012). Our results suggest that previous infections by HCoV-229E could prevent more serious clinical manifestations of COVID-19, but these are not the only variables that influence this event.

La próstata es una glándula sexual accesoria encargada de producir y secretar el líquido prostático. En la rata macho este órgano está regulado por hormonas tales como testosterona (T) y prolactina (PRL), así como por el sistema nervioso autónomo (SNA), quien, a través de los nervios pélvico e hipogástrico que convergen en el ganglio pélvico mayor (GPM), provee de información sensitiva e inervación adrenérgica y colinérgica a la próstata. Daños en la inervación o alteraciones en los niveles hormonales de T y PRL causan cambios en la citoarquitectura y función de la próstata, sin embargo, un aspecto importante que se ha encontrado es que la actividad sexual contribuye a que se retrase la manifestación de las enfermedades reportadas en la glándula. Por lo anterior, esta revisión tiene el propósito fundamental de mostrar la relación que existe entre el SNA sobre el funcionamiento y la citoarquitectura de la próstata, así como el impacto que ejerce la conducta sexual sobre los cambios que se generan en la glándula prostática cuando se altera la inervación autonómica.

Entre la Enfermedad de Alzheimer (EA) y la Diabetes Mellitus (DM) ha sido evidenciado que existen múltiples mecanismos en común en ambas patologías, que van desde el deterioro cognitivo en el aspecto clínico hasta alteraciones bioquímicas de las cuales destacan; el aumento de los agentes proinflamatorios y la excitotoxicidad, aumento del estrés oxidativo y aumento de los productos finales de la glicación avanzada (AGEs), alteraciones del metabolismo de la glucosa, así como alteraciones de las vías mTORC1 /S6 y GSK-3 β; así también destaca el papel de la Resistencia a la Insulina (Ri), donde esta alteración está vinculada tanto con EA como con DM en diversos puntos de su fisiopatología, ya sea mediante la influencia en los diferentes mecanismos antes mencionados o bien de forma directa. Objetivo. Se describe como la influencia de esta hormona es tal, tanto si sus niveles son altos, efecto conocido como hiperinsulinismo o bajos efecto conocido como hipoinsulinismo, puesto que ambos extremos conducen a efectos neurodegenerativos característicos de EA, principalmente en el aumento de β amiloide (Aβ) y Tau hiperfosforilada (pTau), a través de distintos procesos. Aporte.Es con base en este fenómeno que nosotros describimos lo que llamamos “La paradoja de la insulina”, en la cual además destaca la vía insulina/PI3K/Akt como punto crucial, ya que independientemente de las condiciones de hiper o hipoinsulinismo esta vía se altera en ambos escenarios. Esta relación entre EA y DM se considera desde el aspecto de los tratamientos hipoglucemiantes dirigidos a la atención de DM, los cuales parecen interferir con EA, a través de varios de los mecanismos en común que tienen estas patologías. Conclusión. Aunque es muy prematuro considerar que estos tratamientos para DM darán los mismos resultados en los casos de EA, estos datos son valiosos precedentes en la búsqueda de alternativas terapéuticas para EA.

Background We conducted an observational study of 15 patients from a Southeastern area of Mexico with symptoms compatible with SARS-Cov-2, which were treated with the antiviral amantadine. Methodology In this study, data were collected from 15 individuals with clinical symptoms of COVID-19 infection, which were treated on an ambulatory basis with 100 mg of amantadine for a period of 14 days. Results This drug demonstrated its effectiveness, as patients recovered successfully with this treatment without the necessity of attending a hospital to use mechanical ventilation. All patients developed IgG antibodies to SARS-Cov-2. Conclusion Amantadine can be used as a viable and cost-effective alternative for treating people with severe acute respiratory syndrome (SARS-Cov-2) on an ambulatory basis, while the vaccine is not available.

The SARS-CoV-2 virus has spread around the world. At this time, there is no vaccine that can help people prevent the spread of coronavirus. We are proposing amantadine as a drug that can be used to mitigate the effects of the virus. It is demonstrated by docking models how amantadine can exert its action on Coronavirus viroporin E.

El trastorno del espectro autista (TEA) abarca un grupo complejo de trastornos del desarrollo neural que se caracterizan por presentar deficiencias en la interacción social, la comunicación y motricidad del individuo. El TEA tiene un impacto en la salud pública, por lo que sería de gran utilidad contar con biomarcadores que permitan la identificación temprana del trastorno. En este sentido, los microRNAs (miRNAs), que son reguladores de una gran variedad de funciones celulares y cuyas alteraciones en su expresión han sido observadas en individuos con TEA, se comienzan a considerar como blancos potenciales para el desarrollo de estrategias de diagnóstico y terapéuticas para estos trastornos. Esta revisión se enfoca en algunos estudios sobre la participación de miRNAs en el TEA, en modelos animales y humanos, y hace una aproximación a su posible uso como biomarcadores.

Prostate function is regulated by androgens and a neural control via the pelvic and hypogastric nerves. As such, this sexual gland contains receptors for acetylcholine and noradrenaline, although it is unknown whether the expression of these receptors is affected by sexual behavior and even less by denervation of the gland. Thus, the purpose of this work was to evaluate the effect of repeated sexual behavior on the expression of noradrenaline, acetylcholine, and androgen receptors at the prostate, and how they are affected by denervation. To achieve this, we used sexually experienced males denervated at the pelvic or hypogastric nerves, or both. The messenger (mRNA) and protein for androgen, noradrenergic, and cholinergic receptors were evaluated. The weight of the gland and the levels of serum testosterone were also measured. We found that: (1) sexual behavior was not affected by denervation; (2) blood testosterone levels increased due to sexual behavior but such increase is prevented by denervation; (3) the weight of the ventral prostate increased with sexual behavior but was not affected by denervation; (4) AR messenger levels increased with sexual behavior but were not altered by denervation; (5) the messenger for noradrenergic and cholinergic receptors decreased after denervation, and those for muscarinic receptors increased, and (6) only AR protein decreased after denervation of both nerves, while those for other receptors remained unchanged. In summary, we show that the three receptors have different regulatory mechanisms, and that only androgen receptors are regulated by both autonomic systems.

Cell migration is the process by which cells move through tissues, and it is crucial to carry out a wide variety of physiological and pathological processes. The study methods to evaluate cell migration are very useful tools for biomedical research. Among these methods, the wound and healing assay is one of the simplest, most economical and is widely used in research. However, one of its disadvantages is that the width and shape of the wound can vary among experimental samples since the scraping is carried out manually, representing a difficult variable to control. In the present article a variant of the razor scrape assay is addressed, which eliminates this variation in the width of the wound, thus facilitating the measurement and comparison using the total area of cell migration.•A method that can be carried out under standard culture conditions.•Avoids the disadvantage of variation in width and shape of the wound.•It constitutes a simple, cheap option and multiple advantages over the traditional method., Graphical abstract Image, graphical abstract

El trastorno por consumo de alcohol (TCA) es una enfermedad derivada de la ingesta excesiva y prolongada de esta sustancia, con efectos negativos a nivel cognitivo. Durante muchos años se ha estudiado la etiología de la dependencia al alcohol y se ha encontrado que la impulsividad es uno de sus rasgos más distintivos, una característica cognitiva que no solo predispone al consumo de sustancias, sino que puede crear un efecto inverso. La presente revisión tiene como objetivo dar a conocer la forma como se interrelacionan estos dos factores (dependencia e impulsividad) y trata de explicar cuáles son las estructuras del cerebro implicadas en dicho proceso. Asimismo, se abordan aspectos moleculares, genéticos o epigéneticos que generan cambios en un circuito cerebral extremadamente complejo, dando lugar a la aparición de conductas negativas, tales como la impulsividad hacia la ingesta de alcohol.

Male sex hormones such as testosterone and dihydrotestosterone play important roles in several physiological and pathological processes. The biological activities of the aforementioned metabolites are mediated by the multidomain androgen receptor (AR), which is therefore a well-studied drug target. Ganoderma mushroom lanostanoid extracts have previously been shown to exert antiandrogenic activity; therefore, this work aims to identify which lanostane derivatives might act as selective ligands for AR. Because protein flexibility is of paramount importance for ligand binding, different conformations of AR were sampled to account for binding modes within a ligand binding site, then subjected to virtual screening against a metabolite library. Fifteen Ganoderma lanostanoids were selected as AR ligands, according to their calculated binding affinity to this nuclear receptor. The results show the relevance of certain structural and chemical aspects of our ligands, such as the presence of a ketonic group on C-3, which influences the process through which they bind to AR.

The abnormal elevation of serum PRL, referred to as hyperprolactinemia (HyperPRL), produces alterations in several reproductive parameters of male rats such as penile erection or decreased tendency to reach ejaculation. Additionally, this situation produces a significant modification of prostate histology, as observed in the epithelial structure and alveolar area, which could reach a level of hyperplasia in the long-term. In this tissue, HyperPRL produces an increase in expression of PRL receptors and activation of the Stat3 signaling pathway that is correlated with the evolution of prostate pathologies. However, the impact of HyperPRL in long-term sexually active male rats is unknown. In this work, using constantly copulating Wistar male rats with induced HyperPRL, we analyzed the level of serum PRL, the effect on prostate PRL receptors, and activation of pStat3, pStat5 and Mapk signaling pathways. Two procedures to induce HyperPRL were employed, comprising daily IP administration or adenohypophysis transplant, and although neither affected the execution of sexual behavior, the serum PRL profile following successive ejaculations was affected. Messenger RNA expression of the short and long isoforms of the PRL receptor at the ventral prostate was affected in different ways depending on the procedure to induce HyperPRL. The ventral prostate did not show any modification in terms of activation of the pStat5 signaling pathway in subjects with daily administration of PRL, although this was significantly increased in ADH transplanted subjects in the second and fourth consecutive ejaculation. A similar profile was found for the pStat3 pathway which additionally showed a significant increase in the third and fourth ejaculation of daily-injected subjects. The Mapk signaling pathway did not show any modifications in subjects with daily administration of PRL, but showed a significant increase in the second and third ejaculations of subjects with ADH transplants. Thus, although sexual behavior was not modified, HyperPRL modified the expression of PRL receptors and the activation of signal pathways in the prostate tissue. Hence, it is probable that prostatic alterations precede the sexual behavioral deficits observed in subjects with HyperPRL.

Prolactin (PRL) is a key hormone for prostate function, with a basal level in serum and associated with two characteristic circadian peaks. In the male rat, the execution of one bout of sexual behavior with consecutive ejaculations produces a significant transient increase in PRL. However, the impact of a constant sexual life on both PRL levels and prostate function is unknown. Thus, by using constantly copulating males we analyzed the levels of serum PRL, the effect on prostate PRL receptors, and activation of pStat3, pStat5 and Mapk signaling pathways. Sexually experienced Wistar male rats were used, which underwent periodic sessions of sexual behavior tests. Males were subjected to a session of sexual behavior to achieve at least one and up to four ejaculations. Of these, a blood sample was collected from randomly selected males and the ventral prostate was removed for analysis. Serum PRL was quantified, the mRNA for PRL receptors was determined, and signaling pathways were analyzed. Data show that a constant sexual life produced a constant elevation of PRL in serum during four consecutive ejaculations. The ventral prostate showed a different mRNA expression profile for the long and short isoform of the PRL receptor, and both mRNA levels increased. Although the gland did not show modification of the activation of the pStat5 signaling pathway, the levels of pStat3 increased, and the Mapk pathway showed one significant elevation after the third ejaculation. Thus, we showed that an active and constant sexual life produces a sustained increase in serum PRL, its receptors, and the pStat3 signaling pathway. These responses seem to underlie the required physiological need to produce the quantity and quality of prostatic semen to ensure the appropriate environment for sperm to reach and fertilize the ovum.