Sistema glinfático: aspectos anatómicos, fisiológicos e implicaciones clínicas / Glymphatic system: Anatomo-physiological principles and their clinical implications

Introducción: El sistema glinfático comprende el conjunto de rutas perivasculares tanto arteriales como venosas que se encuentran en estrecha asociación con células astrogliales y que permiten la interacción entre el líquido cefalorraquídeo (LCR) y el líquido intersticial cerebral (LIC), para llevar a cabo procesos como la depuración de los metabolitos de desecho celular, o la distribución de nutrientes, así como contribuir al metabolismo cerebral local, la transmisión de volumen y la señalización paracrina cerebral. Contenidos: Este artículo busca profundizar en los conceptos anatómicos y fisiológicos, hasta el momento descritos, sobre este sistema macroscópico de transporte. Se realiza una búsqueda bibliográfica de revisiones y estudios experimentales sobre la anatomía, la fisiología y las implicaciones fisiopatológicas del sistema glinfático. Conclusiones: La identificación anatómica y funcional del sistema glinfático ha ampliado el conocimiento sobre la regulación del metabolismo cerebral en cuanto a distribución de nutrientes y cascadas de señalización celular. Al establecer una interacción entre el espacio subaracnoideo subyacente y el espacio intersticial cerebral, el sistema glinfático surge como uno de los mecanismos protagonistas de la homeostasis cerebral. La disfunción de esta vía hace parte de los mecanismos fisiopatológicos de múltiples trastornos neurológicos, ya sea por la acumulación de macromoléculas, como ocurre en la enfermedad de Alzheimer, o por la reducción del drenaje de sustancias químicas y citocinas proinflamatorias en patologías como la migraña o el trauma craneoencefálico.

Introduction: The glympathic system comprises the set of perivascular routes, arterials or venous, that are found in close relationship with astroglial cells and allow interaction between the cerebrospinal fluid (CSF) and the interstitial brain fluid (ISF), to carry processes like cell-wasting metabolites depuration, nutrients distribution, as well as make a contribution in the local brain metabolism, volumen transmition and brain paracrine signaling. Contents: This article seeks to deepen in the anatomical and physiological concepts, so far described, about this macroscopic transport system. A bibliographic search of reviews and experimental studies on the anatomy, physiology and pathophysiological implications of the glymphatic system is carried out. Conclusions: Anatomical and functional identification of glympathic system has broaden the knowledge about regulation of brain metabolism on the nutrients distribution and cell signaling cascades. When setting an interaction between the subarachnoid space and the brain interstitial space, the glymphatic system arise as one of the leading mechanisms of brain homeostasis. Disfunction of this pathway makes part of the patophysiological mechanisms of multiple neurological disease, either be by collection of macromolecules as in Alzheimer's disease, or by the reduction of inflammatory cytokines and chemical substances drainage as in migraine or traumatic brain injury (TBI).

Morphological Effects of Cigarette Smoking on Respiratory System and Related Functions Based on AQPs Expression

SUMMARY: A great deal of attention of air pollution on respiratory health is increasing, particularly in relation to haze days. It is that exposure to cigarette smoke augments the toxicity of common air contaminants, thereby increasing the complexity of respiratory diseases. Although there are various mechanisms involved to respiratory diseases caused or worsen by cigarette smoking, in which the role of AQPs in the lung with regard to fluid homeostasis still remains elusive. In this paper, we copied the rat models based on smoke generator, and investigated the morphological changes of mucosa and related functions depending on the balance of lining liquid of alveoli via AQPs expression. Compared with normal group, weak labelling of AQP1 and AQP5 protein abundance were clearly detected in the corresponding part of smoke exposure groups compared with normal group. Hence, it is suggested that the contribution of AQPs in the lung is diminished, thereby causing perturbed balancing between resorptive and secretory fluid homeostasis under cigarette smoking.

Cada vez se presta más atención a la contaminación del aire en la salud respiratoria, particularmente, en relación con los días de neblina. En consecuencia la exposición al humo del cigarrillo aumenta la toxicidad de los contaminantes comunes del aire, lo que además aumenta la complejidad de las enfermedades respiratorias. Aunque existen varios mecanismos involucrados en las enfermedades respiratorias causadas o empeoradas por el tabaquismo, en las que el papel de las AQP en el pulmón respecto a la homeostasis de líquidos sigue siendo difícil de alcanzar. En este artículo, copiamos los modelos de rata basados en el generador de humo e investigamos los cambios morfológicos de la mucosa y las funciones relacionadas según el equilibrio del líquido de revestimiento de los alvéolos a través de la expresión de AQP. En comparación con el grupo normal, se detectó claramente un etiquetado débil de la abundancia de proteínas AQP1 y AQP5 en la parte correspondiente de los grupos de exposición al humo en comparación con el grupo control. Por lo tanto, se sugiere que la contribución de las AQP en el pulmón está disminuida, provocando así un equilibrio perturbado entre la homeostasis del líquido secretor y de reabsorción bajo el hábito de fumar cigarrillos.

Relação entre aspectos psicossomáticos e psoríase / Relationship between psychosomatic aspects and psoriasis / Relación entre aspectos psicosomáticos y psoriasis

Psoríase é uma dermatose de caráter inflamatório ligado a diversas composições do ser, sendo estas a genética, o sistema imune, o ambiente e o estado mental do paciente, apresentando evidências de ser um quadro clínico multifacetado. A composição da medicina psicossomática empenha-se na relação mental e emocional e do corpo, sendo importante mostrar a relação desta com a psoríase. Por isso, busca-se avaliar as evidências disponíveis na literatura sobre a relação entre a psoríase e os aspectos psicossomáticos. Foi realizado uma a revisão de literatura, por meio de seleção de artigos das base de dados Medical Literature Analysis and Retrieval System Online (PubMed/Medline), biblioteca virtual em saúde Scientific Electronic Library Online (SciElo), UpToDate e Google acadêmico. A busca por artigos científicos resultou em 20 artigos selecionados. Foi possível concluir, que há estudos fundamentados correlacionando a medicina psicossomática e a psoríase, além de que diversos fatores que afetam a homeostase corporal, provocam alterações nervosas, e consequentemente afetam as células da pele. Além disso, foi encontrado evidências que a estigmatização que os pacientes sofrem influenciam no aumento da gravidade da doença, sendo necessário a realização de um tratamento psico cognitivo-comportamental juntamente com o tratamento dos sinais e sintomas gerais da doença. Desta forma, o presente trabalho pôde olhar para a patologia com um olhar ampliado relacionado ao aspecto mental e emocional o que promove melhor compreensão e as consequências disto são a maior capacidade de intervenção sobre a psoríase.

Psoriasis is an inflammatory dermatosis linked to several compositions of the being, which are genetics, the immune system, the environment and the patient's mental state, that is, it shows evidence of being a multifaceted clinical picture. Since the composition of psychosomatic medicine is committed to the relationship between the mental, emotional, and body, it is important to show its relationship with psoriasis. Therefore, we sought to evaluate the available evidence in the literature on the relationship between psoriasis and psychosomatic aspects. A literature review was conducted by selecting articles from the Medical Literature Analysis and Retrieval System Online (PubMed/Medline), Scientific Electronic Library Online (SciElo), UpToDate and Google Scholar databases. The search for scientific articles resulted in 20 selected articles. It was possible to conclude that there are well-founded studies correlating psychosomatic medicine and psoriasis, and that several factors that affect the body's homeostasis cause nervous alterations, and consequently affect the skin cells. Moreover, it was found evidence that the stigmatization that patients suffer influences the increase of the severity of the disease, being necessary the realization of a psycho cognitive-behavioral treatment along with the treatment of the general signs and symptoms of the disease. Thus, the present work could look at the pathology with a broader view related to the mental and emotional aspect, which promotes better understanding and the consequences of this are a greater ability to intervene on psoriasis.

La psoriasis es una dermatosis inflamatoria vinculada a varias composiciones del ser, que son la genética, el sistema inmunitario, el medio ambiente y el estado mental del paciente, es decir, muestra evidencias de ser un cuadro clínico multifacético. Dado que la composición de la medicina psicosomática está comprometida con la relación entre lo mental, lo emocional y el cuerpo, es importante mostrar su relación con la psoriasis. Por lo tanto, se buscó evaluar la evidencia disponible en la literatura sobre la relación entre la psoriasis y los aspectos psicosomáticos. Se realizó una revisión bibliográfica seleccionando artículos de las bases de datos Medical Literature Analysis and Retrieval System Online (PubMed/Medline), Scientific Electronic Library Online (SciElo), UpToDate y Google Scholar. La búsqueda de artículos científicos dio como resultado 20 artículos seleccionados. Se pudo concluir que existen estudios bien fundamentados que correlacionan la medicina psicosomática y la psoriasis, y que diversos factores que afectan a la homeostasis del organismo provocan alteraciones nerviosas y, en consecuencia, afectan a las células de la piel. Además, se encontraron evidencias de que la estigmatización que sufren los pacientes influye en el aumento de la gravedad de la enfermedad, siendo necesaria la realización de un tratamiento psico cognitivo- conductual junto con el tratamiento de los signos y síntomas generales de la enfermedad. Así, el presente trabajo pudo contemplar la patología con una visión más amplia relacionada con el aspecto mental y emocional, lo que favorece una mejor comprensión y las consecuencias de ello son una mayor capacidad de intervención sobre la psoriasis.

O efeito do tratamento com rapamicina em órgãos linfoides de camundongos propensos à senescência acelerada / The effect of rapamycin treatment on lymphoid organs of senescence accelerated mice prone

Envelhecer compreende um fenômeno complexo, natural e irreversível, que submete o organismo a inúmeras alterações nos processos biológicos, fisiológicos, ambientais, psicológicos, comportamentais e sociais. Esse processo é caracterizado por um declínio gradual dos mecanismos homeostáticos do organismo, intimamente relacionados com o estado senescente. A senescência, quando diz respeito ao sistema imunológico, é denominada de imunossenescência, que pode ser definida como uma parada estável do ciclo celular associada a mudanças, com uma resposta que limita a proliferação de células envelhecidas ou danificadas. A autofagia está diretamente relacionada com a manutenção do fenótipo senescente, em que a atividade autofágica exerce um papel essencial e ativo na influência da biossíntese de proteínas e organelas. Essa via é regulada naturalmente pela proteína mTOR e quimicamente pelo fármaco rapamicina. Assim, pretendemos investigar: (1) as alterações no perfil corporal e hematimêtrico dos animais ao longo do tratamento com rapamicina; (2) avaliar o perfil de citocinas; (3) observar as modificações histológicas em órgãos linfoides primários e secundário; (4) analisar as populações de células linfoides e mieloides; e (5) avaliar a capacidade proliferativa de linfócitos in vitro. Camundongos SAMP-8 e SAMR-1 foram tratados com rapamicina durante dois meses. A mensuração da massa corporal e análises hematológicas foram realizadas antes e durante o tratamento. Amostras de soro, medula óssea, timo e baço foram analisados em ensaios de ELISA, histologia, população e subpopulações de células. Alterações na massa corporal, parâmetros hematológicos e celularidade de células foram nítidas entre os dois modelos utilizados. Diferenças também foram percebidas na detecção de citocinas IL-1ß. IL-6 e TNF-α, com resultados significantes nas amostras de baço, timo e medula óssea. As citocinas IL-7 e IL-15 apresentaram diferenças de secreção entre os grupos, sendo a primeira maior detectada em camundongos com senescência acelerada tratados com rapamicina. Em nossa análise histológica observamos que os camundongos SAM-P8 apresentaram involução tímica. E nas subpopulações de linfócitos T do baço, células TCD4+ e TCD8+ estavam, respectivamente, em maior e menor quantidade nos camundongos SAM-P8 tratados com rapamicina. Dessa forma, o camundongo da linhagem SAM-P8 é um excelente modelo para se estudar as alterações da senescência, em que o mesmo apresenta características fisiológicas distintas dos camundongos utilizados como controle (SAM-R1). Além disso, verificamos que a dose de rapamicina empregada não desencadeou alterações que pudessem comprometer a resposta imunológica desses camundongos, bem como na possibilidade de atuar na resposta contra os efeitos complexos do envelhecimento

Aging comprises a complex, natural, and irreversible phenomenon, which subjects the organism to countless alterations in biological, physiological, environmental, psychological, behavioral, and social processes. This process is characterized by a gradual decline in the organism's homeostatic mechanisms, closely related to senescence effects. Senescence, when it concerns the immune system, is called immunosenescence, which can be defined as a stable cell cycle arrest associated with changes and is a response that limits the proliferation of aged or damaged cells. Autophagy is a genetically regulated, conserved cellular process and a metabolic pathway essential for maintaining cellular homeostasis, which plays a constitutive and active role in controlling the biosynthesis of proteins and organelles. This pathway is regulated naturally by mTOR or chemically by the drug rapamycin, having a direct relationship with cellular homeostasis and maintenance of the senescent phenotype. Thus, we intend to investigate: (1) the changes in the body and hematimetic profile of the animals throughout the rapamycin treatment; (2) evaluate the cytokine profile; (3) observe histological changes in primary and secondary lymphoid organs; (4) analyze lymphoid and myeloid cell populations; and (5) evaluate the proliferative capacity of lymphocytes in vitro. SAMP-8 and SAMR-1 mice were treated with rapamycin for two months. Body mass measurement and hematological analyses were performed before and during treatment. Serum, bone marrow, thymus and spleen samples were analyzed in ELISA assays, histology, cell population and subpopulations. Changes in body mass, hematological parameters, and cellularity were clear between the two models used. Differences were also noticed in the detection of cytokines IL-1ß. IL-6 and TNF-α, with significant results in the spleen, thymus and bone marrow samples. The cytokines IL-7 and IL-15 showed differences in secretion between groups, the former being higher detected in mice with accelerated senescence treated with rapamycin. In our histological analysis we observed that SAM-P8 mice showed thymic involution. And in the spleen T-lymphocyte subpopulations, TCD4+ and TCD8+ cells were, respectively, in higher and lower quantities in SAM-P8 mice treated with rapamycin. Thus, the SAM-P8 mouse is an excellent model to study the changes of senescence, since it presents physiological characteristics different from the control mice (SAM-R1). Furthermore, we verified that the dose of rapamycin used did not trigger changes that could compromise the immune response of these mice, as well as the possibility of acting in the modulatory response against the complex effects of aging

Copper homeostasis dysregulation promoting cell damage and the association with liver diseases / 中华医学杂志(英文版)

Copper plays an important role in many metabolic activities in the human body. Copper level in the human body is in a state of dynamic equilibrium. Recent research on copper metabolism has revealed that copper dyshomeostasis can cause cell damage and induce or aggravate some diseases by affecting oxidative stress, proteasome, cuprotosis, and angiogenesis. The liver plays a central role in copper metabolism in the human body. Research conducted in recent years has unraveled the relationship between copper homeostasis and liver diseases. In this paper, we review the available evidence of the mechanism by which copper dyshomeostasis promotes cell damage and the development of liver diseases, and identify the future research priorities.

Glycogen synthase kinase-3 (GSK-3) a magic enzyme: it's role in diabetes mellitus and glucose homeostasis, interactions with fluroquionlones. A mini-review / Glicogênio sintase quinase-3 (GSK-3), uma enzima mágica: seu papel no diabetes mellitus e na homeostase da glicose: interações com fluoroquinolonas. Uma mini-revisão

Abstract Diabetes mellitus (DM) is a non-communicable disease throughout the world in which there is persistently high blood glucose level from the normal range. The diabetes and insulin resistance are mainly responsible for the morbidities and mortalities of humans in the world. This disease is mainly regulated by various enzymes and hormones among which Glycogen synthase kinase-3 (GSK-3) is a principle enzyme and insulin is the key hormone regulating it. The GSK-3, that is the key enzyme is normally showing its actions by various mechanisms that include its phosphorylation, formation of protein complexes, and other cellular distribution and thus it control and directly affects cellular morphology, its growth, mobility and apoptosis of the cell. Disturbances in the action of GSK-3 enzyme may leads to various disease conditions that include insulin resistance leading to diabetes, neurological disease like Alzheimer's disease and cancer. Fluoroquinolones are the most common class of drugs that shows dysglycemic effects via interacting with GSK-3 enzyme. Therefore, it is the need of the day to properly understand functions and mechanisms of GSK-3, especially its role in glucose homeostasis via effects on glycogen synthase.

Resumo O diabetes mellitus (DM) é uma doença não transmissível em todo o mundo, na qual existe nível glicêmico persistentemente alto em relação à normalidade. O diabetes e a resistência à insulina são os principais responsáveis ​​pelas morbidades e mortalidades de humanos no mundo. Essa doença é regulada principalmente por várias enzimas e hormônios, entre os quais a glicogênio sintase quinase-3 (GSK-3) é uma enzima principal e a insulina é o principal hormônio que a regula. A GSK-3, que é a enzima-chave, normalmente mostra suas ações por vários mecanismos que incluem sua fosforilação, formação de complexos de proteínas e outras distribuições celulares e, portanto, controla e afeta diretamente a morfologia celular, seu crescimento, mobilidade e apoptose do célula. Perturbações na ação da enzima GSK-3 podem levar a várias condições de doença que incluem resistência à insulina que leva ao diabetes, doenças neurológicas como a doença de Alzheimer e câncer. As fluoroquinolonas são a classe mais comum de drogas que apresentam efeitos disglicêmicos por meio da interação com a enzima GSK-3. Portanto, é necessário hoje em dia compreender adequadamente as funções e mecanismos da GSK-3, principalmente seu papel na homeostase da glicose via efeitos na glicogênio sintase.

Novel Microglia-based Therapeutic Approaches to Neurodegenerative Disorders / 神经科学通报·英文版

As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In the diseased brain, microglia are crucial mediators of neuroinflammation that regulates a broad spectrum of cellular responses. In this review, we summarize current knowledge on the multifunctional contributions of microglia to homeostasis and their involvement in neurodegeneration. We further provide a comprehensive overview of therapeutic interventions targeting microglia in neurodegenerative diseases. Notably, we propose microglial depletion and subsequent repopulation as promising replacement therapy. Although microglial replacement therapy is still in its infancy, it will likely be a trend in the development of treatments for neurodegenerative diseases due to its versatility and selectivity.

Exosome-mediated regulatory mechanisms in skeletal muscle: a narrative review / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Skeletal muscle plays a paramount role in physical activity, metabolism, and energy balance, while its homeostasis is being challenged by multiple unfavorable factors such as injury, aging, or obesity. Exosomes, a subset of extracellular vesicles, are now recognized as essential mediators of intercellular communication, holding great clinical potential in the treatment of skeletal muscle diseases. Herein, we outline the recent research progress in exosomal isolation, characterization, and mechanism of action, and emphatically discuss current advances in exosomes derived from multiple organs and tissues, and engineered exosomes regarding the regulation of physiological and pathological development of skeletal muscle. These remarkable advances expand our understanding of myogenesis and muscle diseases. Meanwhile, the engineered exosome, as an endogenous nanocarrier combined with advanced design methodologies of biomolecules, will help to open up innovative therapeutic perspectives for the treatment of muscle diseases.

Homeostatic medicine: new strategy and concept of health maintenance as well as diagnosis and treatment of diseases / 中华口腔医学杂志

Homeostasis is a dynamic balance process of self-regulating. Biological systems remain stable through adapting to changing external conditions to maintain normal life activities. Homeostatic medicine is the science of studying homeostasis of human molecules, cells, organs and the whole body. It is a comprehensive discipline based on maintaining homeostasis to keep human health and assist for diseases prevention and diagnoses. Homeostatic medicine focuses on the whole body and on the role of homeostasis in health and disease, which is expected to provide new ideas and strategies for maintaining health as well as diagnosing and treating diseases. Nitric oxide (NO) plays an important role in the control of multisystem homeostasis. Nitrate is an important substance in regulating NO homeostasis through the nitrate-nitrite-NO pathway. Sialin, nitrate transporter which is located in the cell membrane and cytoplasm, mediates multiple cellular biological functions. The nitrate-nitrite-NO pathway and sialin-mediated biological functions play an important role in the regulation of body homeostasis.

Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling / 中国中药杂志

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Zuogui Jiangtang Qinggan Prescription promotes recovery of intestinal mucosal barrier in mice with type 2 diabetes mellitus and nonalcoholic fatty liver disease by improving intestinal flora homeostasis / 中国中药杂志

This study aimed to investigate the recovery effect of Zuogui Jiangtang Qinggan Prescription on intestinal flora homeostasis control and intestinal mucosal barrier in type 2 diabetes mellitus(T2DM) with nonalcoholic fatty liver disease(NAFLD) induced by a high-fat diet. NAFLD was established in MKR transgenic mice(T2DM mice) by a high-fat diet(HFD), and subsequently treated for 8 weeks with Zuogui Jiangtang Qinggan Prescription(7.5, 15 g·kg~(-1)) and metformin(0.067 g·kg~(-1)). Triglyceride and liver function were assessed using serum. The hematoxylin-eosin(HE) staining and Masson staining were used to stain the liver tissue, while HE staining and AB-PAS staining were used to stain the intestine tissue. 16S rRNA sequencing was utilized to track the changes in the intestinal flora of the mice in each group. Polymerase chain reaction(PCR) and immunofluorescence were used to determine the protein and mRNA expression levels of ZO-1, Occludin, and Claudin-1. The results demonstrated that Zuogui Jiangtang Qinggan Prescription increased the body mass of T2DM mice with NAFLD and decreased the hepatic index. It down-regulated the serum biomarkers of liver function and dyslipidemia such as alanine aminotransferase(ALT), aspartate transaminase(AST), and triglycerides(TG), increased insulin sensitivity, and improved glucose tolerance. According to the results of 16S rRNA sequencing, the Zuogui Jiangtang Qinggan Prescription altered the composition and abundance of the intestinal flora, increasing the relative abundances of Muribaculaceae, Lactobacillaceae, Lactobacillus, Akkermansia, and Bacteroidota and decreasing the relative abundances of Lachnospiraceae, Firmicutes, Deslfobacteria, Proteobacteria, and Desulfovibrionaceae. According to the pathological examination of the intestinal mucosa, Zuogui Jiangtang Qinggan Prescritpion increased the expression levels of the tight junction proteins ZO-1, Occludin, and Claudin-1, promoted intestinal mucosa repair, protected intestinal villi, and increased the height of intestinal mucosa villi and the number of goblet cells. By enhancing intestinal mucosal barrier repair and controlling intestinal microbiota homeostasis, Zuogui Jiangtang Qinggan Prescription reduces intestinal mucosal damage induced by T2DM and NAFLD.

Effect of moxibustion on immune function homeostasis in rats with diarrhea irritable bowel syndrome based on SCF/c-kit signaling pathway / 中国针灸

OBJECTIVE@#To observe the effects of moxibustion on the stem cell factor (SCF)/tyrosine kinase receptor (c-kit) signaling pathway and immune function in rats with diarrhea irritable bowel syndrome (IBS-D), and to explore the mechanism of moxibustion for IBS-D.@*METHODS@#Among 52 young rats born from 6 healthy pregnant SPF rats, 12 rats were randomly selected into the normal group, and the remaining 40 rats were treated with the three-factor combination method of maternal separation, acetic acid enema and chronic restraint stress to establish the IBS-D rat model. Thirty-six rats with successful IBS-D model were randomly divided into a model group, a moxibustion group, and a medication group, 12 rats in each group. The rats in the moxibustion group were treated with suspension moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37); the rats in the medication group were treated with intragastric administration of rifaximin suspension (150 mg/kg). All the treatments were given once a day for 7 consecutive days. The body mass, loose stool rate (LSR), the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were measured before acetic acid enema (35 days old), after modeling (45 days old), and after intervention (53 days old). After intervention (53 days old), HE staining was used to observe the morphology of colon tissue, and spleen and thymus coefficients were measured; ELISA method was used to detect serum inflammatory factors (tumor necrosis factor a [TNF-a], interleukin [IL]-10, IL-8), T-lymphocyte subsets (CD+4, CD+8, CD+45), value of CD+4/CD+8 and immune globulin (IgA, IgG, IgM); real-time PCR method and Western blot method was used to detect the expression of SCF, c-kit mRNA and protein in colon tissue; immunofluorescence staining method were used to detect positive expression of SCF and c-kit.@*RESULTS@#After intervention, compared with the normal group, in the model group, the body mass and the minimum volume threshold when AWR scored 3 were decreased (P<0.01), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD+4, CD+45, CD+4/CD+8, IgA, IgG, IgM were increased (P<0.01), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were decreased (P<0.01), and the positive expression of SCF and c-kit was decreased (P<0.01). Compared with the model group, in the moxibustion group and the medication group, the body mass and the minimum volume threshold when AWR scored 3 were increased (P<0.01, P<0.05), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD+4, CD+8, CD+45, CD+4/CD+8, IgA, IgG, IgM were decreased (P<0.01, P<0.05), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were increased (P<0.01), and the positive expression of SCF and c-kit was increased (P<0.01). Compared with the medication group, in the moxibustion group, the level of serum CD+4 was decreased (P<0.05), the value of CD+4/CD+8 was increased (P<0.01), and there was no significant difference in other indexes (P>0.05). The expression of SCF and c-kit mRNA was positively correlated with the minimum volume threshold when AWR scored 3 and IL-10 (P<0.01), and negatively correlated with remaining indexes (P<0.01, P<0.05).@*CONCLUSION@#Moxibustion could reduce visceral hypersensitivity, improve symptoms of abdominal pain and diarrhea in IBS-D rats, and its mechanism may be related to up-regulation of the expression of SCF/c-kit signaling pathway and improvement of IBS-D immune function.

4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.

Research progress on the effect of mitochondrial network remodeling on macrophages / 细胞与分子免疫学杂志

Remodeling of the mitochondrial network is an important process in the maintenance of cellular homeostasis and is closely related to mitochondrial function. Interactions between the biogenesis of new mitochondria and the clearance of damaged mitochondria (mitophagy) is an important manifestation of mitochondrial network remodeling. Mitochondrial fission and fusion act as a bridge between biogenesis and mitophagy. In recent years, the importance of these processes has been described in a variety of tissues and cell types and under a variety of conditions. For example, robust remodeling of the mitochondrial network has been reported during the polarization and effector function of macrophages. Previous studies have also revealed the important role of mitochondrial morphological structure and metabolic changes in regulating the function of macrophages. Therefore, the processes that regulate remodeling of the mitochondrial network also play a crucial role in the immune response of macrophages. In this paper, we focus on the molecular mechanisms of mitochondrial regeneration, fission, fusion, and mitophagy in the process of mitochondrial network remodeling, and integrate these mechanisms to investigate their biological roles in macrophage polarization, inflammasome activation, and efferocytosis.

Research progress on the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis / 中国修复重建外科杂志

OBJECTIVE@#To summarize the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis (OA) and analyze its application prospects.@*METHODS@#The recent literature at home and abroad was reviewed to summarize the mechanism of mitochondrial homeostasis imbalance, the relationship between mitochondrial homeostasis imbalance and the pathogenesis of OA, and the application prospect in the treatment of OA.@*RESULTS@#Recent studies have shown that mitochondrial homeostasis imbalance, which is caused by abnormal mitochondrial biogenesis, the imbalance of mitochondrial redox, the imbalance of mitochondrial dynamics, and damaged mitochondrial autophagy of chondrocytes, plays an important role in the pathogenesis of OA. Abnormal mitochondrial biogenesis can accelerate the catabolic reaction of OA chondrocytes and aggravate cartilage damage. The imbalance of mitochondrial redox can lead to the accumulation of reactive oxygen species (ROS), inhibit the synthesis of extracellular matrix, induce ferroptosis and eventually leads to cartilage degradation. The imbalance of mitochondrial dynamics can lead to mitochondrial DNA mutation, decreased adenosine triphosphate production, ROS accumulation, and accelerated apoptosis of chondrocytes. When mitochondrial autophagy is damaged, dysfunctional mitochondria cannot be cleared in time, leading to ROS accumulation, which leads to chondrocyte apoptosis. It has been found that substances such as puerarin, safflower yellow, and astaxanthin can inhibit the development of OA by regulating mitochondrial homeostasis, which proves the potential to be used in the treatment of OA.@*CONCLUSION@#The mitochondrial homeostasis imbalance in chondrocytes is one of the most important pathogeneses of OA, and further exploration of the mechanisms of mitochondrial homeostasis imbalance is of great significance for the prevention and treatment of OA.

A disciplina psicologia do esporte nos cursos de psicologia e educação física / Sports psychology in psychology and physical education courses / La materia psicología del deporte en los cursos de psicología y educación física

Este discute a representatividade da disciplina Psicologia do Esporte nos cursos de Psicologia e Educação Física em instituições de ensino superior reconhecidas pelo MEC e situadas na região Sul do país. Foi realizado um estudo documental, com base nos currículos das Instituições. Os resultados revelaram que no Sul do Brasil 21,02% dos cursos de Psicologia, 41,96% dos cursos de bacharelado em Educação Física e apenas 14,83% dos cursos de licenciatura em Educação Física apresentam a disciplina Psicologia do Esporte em sua grade curricular. Observou-se que a disciplina é ofertada mais frequentemente em regime obrigatório nos cursos de bacharelado em Educação Física. Nos cursos de Psicologia, quando ofertada, costuma ser optativa. Os resultados evidenciam uma maior oferta da disciplina para os estudantes de Educação Física, em relação aos de Psicologia, o que pode estar relacionado ao próprio contexto de surgimento da disciplina e sua popularização no meio acadêmico. Para que esse panorama possa mudar e se possa oferecer uma formação adequada no curso de Psicologia para fomentar essa opção de carreira, há necessidade de se repensar o currículo e o próprio perfil do egresso, de forma a dar mais oportunidade aos estudantes para que conheçam as bases teóricas e os campos de aplicação da Psicologia do Esporte. Tal lacuna pode acarretar a fragilização da disseminação desse conhecimento aos estudantes de graduação e a consequente ocupação do mercado de trabalho.(AU)

This study discusses the representativeness of Sports Psychology in Psychology and Physical Education courses at higher education institutions from Southern Brazil. A documentary study was conducted based on the institutions' curricula. Results show that 21.02% of the Psychology major, 41.96% of the bachelor's in Physical Education, and only 14.83% of the license in Physical Education offer Sports Psychology in their curricula. Sports Psychology is most often offered as a compulsory subject in the bachelor's program in Physical Education, whereas Psychology courses offer it mainly as an elective. Physical Education students have greater contact with the discipline when compared with Psychology students, which may be explained by its context of development and popularization in the academic environment. To change this scenario and offer adequate education in the Psychology programs to foster this career option, institutions must rethink their curriculum and the graduate profile itself. This would give students better opportunity to get to know its theoretical bases and fields of application. Such a gap can hinder the dissemination of this knowledge to undergraduate students and the consequent labor market occupation.(AU)

El objetivo de este estudio es discutir la representatividad de la materia Psicología del Deporte en los cursos de Psicología y Educación Física en instituciones de educación superior de la región Sur de Brasil, reconocidas por el Ministerio de Educación (MEC). Se realizó un estudio documental, basado en los planes de estudio de las instituciones. Los resultados revelaron que, en el Sur de Brasil, el 21,02% de los cursos de Psicología, el 41,96% de los cursos de licenciatura en Educación Física y sólo el 14,83% de los cursos de profesorado en Educación tienen la materia Psicología del Deporte en sus planes de estudio. Se observó que la materia Psicología del Deporte se ofrece con mayor frecuencia como asignatura obligatoria en los cursos de licenciatura en Educación Física. Cuando se ofrece en los cursos de Psicología, es una materia optativa. Los resultados muestran una mayor oferta para los estudiantes de Educación Física en comparación con Psicología, lo que puede estar relacionado con el contexto del surgimiento de la Psicología del Deporte como materia y su popularización en el ámbito académico. Para que este escenario cambie y sea posible ofrecer una formación adecuada en el curso de Psicología con el fin de fomentar esta opción de carrera, es necesario repensar el plan de estudios y el perfil del egresado, así los estudiantes tendrán más oportunidades de conocer sus bases teóricas y sus campos de actuación. Tal brecha puede debilitar la difusión de este conocimiento a los estudiantes de grado y la consecuente ocupación en el mercado laboral.(AU)

Reflexo e sombra: o duplo e o narcisismo em hoffmann e chamisso / Reflection and shadow: the double and the narcissism in hoffmann and chamisso / Reflejo y penumbra: el doble y el narcisismo en hoffman y chamisso

Esta é uma pesquisa qualitativa, em formato de ensaio, que realiza o estudo comparado de duas obras literárias, de A. Von Chamisso e E. T. A. Hoffmann, e de uma anotação do diário deste último para problematizar a repercussão de algumas formas de desestabilizações do Eu na dinâmica psíquica da neurose. O foco dos textos referidos está no fenômeno do duplo na sua forma negativizada, isto é, como o desaparecimento da imagem exterior que dá suporte ao Eu. As ausências da sombra e do reflexo são entendidas como representações metafóricas de uma alteração do Eu que engendra repercussões importantes na homeostase psíquica, sobretudo nas relações sociais de troca. Explora-se daí a menção no diário de Hoffmann de instrumentos ópticos para interrogar o uso desses aparelhos como modelos metapsicológicos na psicanálise. Salienta-se, ainda, a participação de processos de natureza estética na dinâmica psíquica do infamiliar, tomando como referência a ligação entre o conto de Hoffmann e o relato de Stendhal sobre a sua estadia em Florença.(AU)

This is a qualitative research, in essay format, which performs the comparative study of two literary works, by A. Von Chamisso and E. T. A. Hoffmann, and an annotation in the latter's diary to problematize the repercussion of some forms of destabilization of the Ego's in the psychic dynamics of neurosis. The focus of the referred texts is on the phenomenon of the double in its negative form, that is, as the disappearance of the outer image that supports the Ego. The absences of the shadow and the reflection are understood as metaphorical representations of an alteration of the Ego that generates important repercussions on psychic homeostasis, above all in social relationships of exchange. Thus, we analyze the mention of optical instruments in Hoffmann's diary to question the use of these devices as metapsychological models in psychoanalysis. Note, also, the participation of processes of aesthetic nature in the psychic dynamics of the uncanny, taking as reference the connection between Hoffmann's short story and Stendhal's account of his stay in Florence.(AU)

Este ensayo cualitativo realiza un estudio comparativo de dos obras literarias de A. Von Chamisso y de E. T. A. Hoffmann, junto con una anotación en el diario de este último para problematizar la repercusión de algunas formas de desestabilizaciones de la función del Yo en la dinámica psíquica de la neurosis. Los textos se centran en el fenómeno del doble en su forma negativa, como la desaparición de la imagen exterior que sostiene el Yo. Se entienden las ausencias de la penumbra y el reflejo como una representación metafórica de una alteración de la función del Yo que genera importantes repercusiones en la regulación psíquica, sobre todo en las relaciones de intercambio social. Se analiza la presencia en el diario de Hoffmann de instrumentos ópticos para discutir el uso de estos dispositivos como modelos metapsicológicos en psicoanálisis. Se destaca la reverberación de procesos de naturaleza estética en la dinámica psíquica de lo ominoso, tomando como referencia la conexión entre el cuento de Hoffmann y el relato de Stendhal sobre su estancia en Florencia.(AU)

Orientação a pais por chamadas de áudio durante a pandemia de covid-19 / Support for parents via audio calls during the covid-19 pandemic / Orientación de los padres mediante llamadas de audio durante la pandemia de covid-19

O distanciamento social ocasionado pela pandemia de Covid-19 levou a profundas mudanças na rotina das famílias com crianças pequenas, aumentando o estresse no ambiente doméstico. Este estudo analisou a experiência de planejamento e implementação de um projeto de extensão universitária que ofereceu orientação a pais com filhos de 0 a 11 anos por meio de chamadas de áudio durante a pandemia. O protocolo de atendimento foi desenvolvido para atender às necessidades de famílias de baixa renda e listava problemas específicos relacionados ao confinamento em casa e ao fechamento das escolas seguidos por uma variedade de estratégias de enfrentamento. A análise de 223 queixas relatadas pelos usuários em 130 ligações revelou que 94% dos problemas referidos pelos pais foram contemplados pelo protocolo de atendimento e estavam relacionados aos problemas externalizantes (39%) ou internalizantes (26%) das crianças ou ao declínio do bem-estar subjetivo dos pais (29%). Serviços de apoio devem orientar os pais quanto ao uso de práticas responsivas e assertivas que promovam o bem-estar emocional da criança e estabeleçam expectativas comportamentais em contextos estressantes. A diminuição dos conflitos entre pais e filhos resultante do uso dessas estratégias tende a reduzir o sofrimento dos pais, aumentando sua sensação de bem-estar subjetivo. Recomenda-se ampla divulgação dessas iniciativas e seguimento dos casos.(AU)

The social distancing the COVID-19 pandemic entailed has led to profound changes in the routine of families with young children, increasing stress in the home environment. This study analyzed the experience of planning and implementing a university extension program that offered support to parents with children from 0 to 11 years old via audio calls during the COVID-19 pandemic. The service protocol was developed to meet the needs of low-income families and listed specific problems related to home confinement and school closure followed by a variety of coping strategies. The analysis of 223 complaints reported by users in 130 calls revealed that 94% of the problems reported by parents were addressed by the protocol and were related to children's externalizing (39%) or internalizing (26%) problems or to the decline in parents' subjective well-being (29%). Support services should guide parents on the use of responsive and assertive practices that promote the child's emotional well-being and set behavioral expectations in stressful contexts. The reduction in conflicts between parents and children resulting from the use of these strategies tends to reduce parents' suffering, increasing their sense of subjective well-being. Wide dissemination of these initiatives and case follow-up are recommended.(AU)

La distancia social causada por la pandemia de COVID-19 condujo a cambios profundos en la rutina de las familias con niños pequeños, aumentando el estrés en el entorno del hogar. Este estudio analizó la experiencia de planificar e implementar un proyecto de extensión universitaria que ofreció orientación a los padres con niños de cero a 11 años a través de llamadas de audio durante la pandemia COVID-19. El protocolo de atención se desarrolló para satisfacer las necesidades de las familias de bajos ingresos y enumeró problemas específicos relacionados con el confinamiento en el hogar y el cierre de la escuela, seguido de una variedad de estrategias de afrontamiento. El análisis de 223 quejas informadas por los usuarios en 130 llamadas reveló que el 94% de los problemas informados por los padres fueron abordados por el protocolo de atención y estaban relacionados con los problemas de externalización (39%) o internalización (26%) de los niños o la disminución del bienestar subjetivo de los padres (29%). Los servicios de apoyo deberían aconsejar a los padres sobre el uso de prácticas receptivas y asertivas que promuevan el bienestar emocional del niño y establezcan expectativas de comportamiento en contextos estresantes. La reducción de los conflictos entre padres e hijos como resultado del uso de estas estrategias tiende a reducir el sufrimiento de los padres, aumentando su sensación de bienestar subjetivo. Se recomienda una amplia difusión de estas iniciativas y seguimiento de casos.(AU)

Activación de sensores del estrés del retículo endoplásmico por dietas asociadas a enfermedades metabólicas y COVID-19 / Activation of endoplasmic reticulum stress sensors by metabolic disease-associated diets and COVID-19

El retículo endoplásmico es un organelo abundante, dinámico y sensor de energía. Sus abundantes membranas, rugosa y lisa, se encuentran distribuidas en diferentes proporciones dependiendo del linaje y requerimiento celular. Su función es llevar a cabo la síntesis de proteínas y lípidos, y es el almacén principal de Ca2+ intracelular. La sobrecarga calórica y la glucolipotoxicidad generada por dietas hipercalóricas provoca la alteración del retículo endoplásmico, activando la respuesta a proteínas mal plegadas (UPR, Unfolded Protein Response, por sus siglas en inglés) como reacción al estrés celular relacionado con el retículo endoplásmico y cuyo objetivo es restablecer la homeostasis del organelo al disminuir el estrés oxidante, la síntesis de proteínas y la fuga de Ca2+. Sin embargo, durante un estrés crónico, la UPR induce formación de especies reactivas de oxígeno, inflamación y apoptosis, exacerbando el estado del retículo endoplásmico y propagando un efecto nocivo para los demás organelos. Es por ello que el estrés del retículo endoplásmico se ha considerado un inductor del inicio y desarrollo de enfermedades metabólicas, incluido el agravamiento de COVID-19. Hasta el momento, existen pocas estrategias para reestablecer la homeostasis del retículo endoplásmico, las cuales son dirigidas a los sensores que desencadenan la UPR. Por tanto, se justifica con urgencia la identificación de nuevos mecanismos y terapias novedosas relacionadas con mitigar el impacto del estrés del retículo endoplásmico y las complicaciones asociadas.

The endoplasmic reticulum is an abundant, dynamic and energy-sensing organelle. Its abundant membranes, rough and smooth, are distributed in different proportions depending on the cell lineage and requirement. Its function is to carry out protein and lipid synthesis, and it is the main intracellular Ca2+ store. Caloric overload and glycolipotoxicity generated by hypercaloric diets cause alteration of the endoplasmic reticulum, activating the Unfolded Protein Response (UPR) as a reaction to cellular stress related to the endoplasmic reticulum and whose objective is to restore the homeostasis of the organelle by decreasing oxidative stress, protein synthesis and Ca2+ leakage. However, during chronic stress, the UPR induces reactive oxygen species formation, inflammation and apoptosis, exacerbating the state of the endoplasmic reticulum and propagating a deleterious effect on the other organelles. This is why endoplasmic reticulum stress has been considered an inducer of the onset and development of metabolic diseases, including the aggravation of COVID-19. So far, few strategies exist to reestablish endoplasmic reticulum homeostasis, which are targeted to sensors that trigger UPR. Therefore, the identif ication of new mechanisms and novel therapies related to mitigating the impact of endoplasmic reticulum stress and associated complications is urgently warranted.

Boletín epidemiológico 10 - 2022. Semana epidemiológica del 06 al 12 de marzo del 2022 / Epidemiological bulletin 10 - 2022. Epidemiological week from March 06 to 12, 2022

El riñón es un órgano clave para mantener el balance "homeostasis" del medio interno (agua, electrolitos, equilibrio ácido básico y el equilibrio osmótico), depura la sangre de productos de desechos metabólicos endógenos y exógenos, regula el volumen circulante efectivo y la presión arterial, y sintetiza la eritropoyetina y la vitamina D. Todas estas funciones se ejecutan en el nefrón que constituye la unidad funcional renal