Role of Ferroptosis in Bone Homeostasis and Traditional Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Osteoporosis （OP） is a systemic metabolic bone disease characterized by bone microstructure degeneration and bone mass loss， which has a high prevalence and disability rate. Effective prevention and treatment of OP is a major difficulty in the medical community. The nature of OP is that multiple pathological factors lead to the imbalance of human bone homeostasis maintained by osteoblasts and osteoclasts. Ferroptosis is a non-apoptotic cell death pathway， and its fundamental cause is cell damage caused by iron accumulation and lipid peroxidation. Studies have shown that ferroptosis is involved in and affects the occurrence and development of OP， which leads to OP by mediating the imbalance of bone homeostasis. Ferroptosis is an adjustable form of programmed cell death. The intervention of ferroptosis can regulate the damage degree and death process of osteoblasts and osteoclasts， which is beneficial to maintain bone homeostasis， slow down the development process of OP， improve the clinical symptoms of patients， reduce the risk of disability， and improve their quality of life. However， there are few studies on ferroptosis in OP. Traditional Chinese medicine （TCM） is a medical treasure with unique characteristics and great application value in China. It has been widely used in China and has a long history. It has the multi-target and multi-pathway advantages in the treatment of OP， with high safety， few toxic and side effects， and low treatment cost， and has a significant effect in clinical application. The intervention of TCM in ferroptosis to regulate bone homeostasis may be a new direction for the prevention and treatment of OP in the future. This article summarized the regulatory mechanisms related to ferroptosis， discussed the role of ferroptosis in bone homeostasis， and reviewed the current status and progress of active ingredients in TCM compounds and monomers in the regulation of OP through ferroptosis， so as to provide a theoretical basis for the participation of TCM in the prevention and treatment of OP in the future.

Anti-aging Effect of Ginseng Radix et Rhizoma：A Review / 中国实验方剂学杂志

Ginseng Radix et Rhizoma（GRR） has the function of replenishing vital energy and can lighten the body and prolong the life when taken for a long time， which is suitable for the development of anti-aging products， so this paper intends to sort out the progress of anti-aging research on GRR. After combing， the results of modern studies have shown that a variety of components in GRR have anti-aging effect， which can prolong the lifespan of aging animal models， as well as delay the aging of various systems. The anti-aging mechanisms mainly include anti-cellular senescence， anti-oxidative stress， inhibiting telomere shortening， maintaining mitochondrial homeostasis and so on. The anti-aging ingredients of GRR involved in the researches mainly include ginsenoside Rg1 and ginsenoside Rb1， in addition， ginsenoside Rg3， ginsenoside Rd， ginsenoside Rg2， ginsenoside Re， ginsenoside Rb2， oligosaccharides of GRR， polysaccharides of GRR， water extract of GRR， total saponins of Panax ginseng stems and leaves are also included. Therefore， under current background of population aging， the in-depth development of GRR and its transformation into anti-aging products are of great significance for delaying senility and improving the health conditions of aging population.

The regulatory mechanism of physiological sleep-wake / 中国药理学通报

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

Broad-spectrum ginsentides are principal bioactives in unraveling the cure-all effects of ginseng

Stress and illness connection is complex and involves multiple physiological systems. Panax ginsengs, reputed for their broad-spectrum "cure-all" effect, are widely prescribed to treat stress and related illnesses. However, the identity of ginseng's "cure-all" medicinal compounds that relieve stress remains unresolved. Here, we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to stress. Ginsentides are disulfide-rich, cell-penetrating and proteolytic-stable microproteins. Using affinity-enrichment mass spectrometry target identification together with in vitro, ex vivo and in vivo validations, we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway, alleviate α1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta, decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet aggregation. Orally administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation, to prevent collagen and adrenaline-induced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in mice. Together, these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra- and intra-cellular proteins to reverse stress-induced damages.

Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

Solute carriers (SLCs) constitute the largest superfamily of membrane transporter proteins. These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions. They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake (e.g., SLC2A4/GLUT4), glucose reabsorption (e.g., SLC5A2/SGLT2), thermogenesis (e.g., SLC25A7/UCP-1), and ATP production (e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone (SLCO1B1/OATP1B1) and metformin (SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

Refractory Rickets

Nutritional rickets, caused by vitamin D and/or calcium deficiency is by far the most common cause of rickets. In resource-limited settings, it is therefore not uncommon to treat rickets with vitamin D and calcium. If rickets fails to heal and/or if there is a family history of rickets, then refractory rickets should be considered as a differential diagnosis. Chronic low serum phosphate is the pathological hallmark of all forms of rickets as its low concentration in extracellular space leads to the failure of apoptosis of hypertrophic chondrocytes leading to defective mineralisation of the growth plate. Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) control serum phosphate concentration by facilitating the excretion of phosphate in the urine through their action on the proximal renal tubules. An increase in PTH, as seen in nutritional rickets and genetic disorders of vitamin D-dependent rickets (VDDRs), leads to chronic low serum phosphate, causing rickets. Genetic conditions leading to an increase in FGF23 concentration cause chronic low serum phosphate concentration and rickets. Genetic conditions and syndromes associated with proximal renal tubulopathies can also lead to chronic low serum phosphate concentration by excess phosphate leak in urine, causing rickets. In this review, authors discuss an approach to the differential diagnosis and management of refractory rickets

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).

Status of Serum Magnesium in Different Stages of CKD Patients: A Tertiary Care Hospital Study in Bangladesh

Background: In chronic kidney disease (CKD), renal regulatory mechanisms may be insufficient to balance intestinal magnesium absorption hence insufficient to maintain homeostasis. But related data are relatively sparse and not readily available, especially in Bangladesh context. Aim of the study: The aim of the study was to assess the pattern of serum magnesium level in different stages of CKD patients. Material & Methods: This descriptive cross-sectional study was conducted in the Department of Medicine and the Department of Nephrology, Dhaka Medical College Hospital (DMCH) for nine months’ period. Approval for the study was taken from the ethical review committee of DMC before the commencement of the study. Diagnosed patients of chronic kidney disease (CKD) were approached for the inclusion of the study. Informed written consent was taken from each patient. All patients were subjected to detailed history taking, physical examination, and relevant investigations. For the study purpose, serum magnesium was done for all patients. Results: After compiling data from all participants, statistical analysis was performed using the statistical package for social science (SPSS) version 22 for windows, and a p < 0.05 was considered statistically significant. Mean age of the patients was 53 years with male predominance (male 64% vs female 36%). Of all, 6.7% of cases had hypomagnesemia and 55.3% had hypermagnesemia. The mean serum magnesium level was 2.68±0.81 mg/dl. Assessment of serum magnesium in a different stages of CKD showed that hypermagnesemia is associated with higher staging (p<0.05), and there is a negative correlation between lower e-GFR with serum magnesium ((r=-0.753, p<0.01). Conclusion: Nearly two-third of CKD patients were found with altered magnesium level in the form of hypomagnesemia or hypermagnesemia in this study. Serum magnesium was found increased in higher stages of CKD. That means serum magnesium level increases along with higher stage of the disease. Urinary magnesium excretion also decreases when eGFR of patient decreased.

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.

The threshold value for identifying insulin resistance (HOMA-IR) in an admixed adolescent population: A hyperglycemic clamp validated study

ABSTRACT Objectives: To validate the homeostasis model assessment (HOMA) of insulin resistance (IR) as a surrogate to the hyperglycemic clamp to measure IR in both pubertal and postpubertal adolescents, and determine the HOMA-IR cutoff values for detecting IR in both pubertal stages. Subjects and methods: The study sample comprised 80 adolescents of both sexes (aged 10-18 years; 37 pubertal), in which IR was assessed with the HOMA-IR and the hyperglycemic clamp. Results: In the multivariable linear regression analysis, adjusted for sex, age, and waist circumference, the HOMA-IR was independently and negatively associated with the clamp-derived insulin sensitivity index in both pubertal (unstandardized coefficient - B = −0.087, 95% confidence interval [CI] = −0.135 to −0.040) and postpubertal (B = −0.101, 95% CI, −0.145 to −0.058) adolescents. Bland-Altman plots showed agreement between the predicted insulin sensitivity index and measured clamp-derived insulin sensitivity index in both pubertal stages (mean = −0.00 for pubertal and postpubertal); all P > 0.05. The HOMA-IR showed a good discriminatory power for detecting IR with an area under the receiver operator characteristic curve of 0.870 (95% CI, 0.718-0.957) in pubertal and 0.861 (95% CI, 0.721-0.947) in postpubertal adolescents; all P < 0.001. The optimal cutoff values of the HOMA-IR for detecting IR were > 3.22 (sensitivity, 85.7; 95% CI, 57.2-98.2; specificity, 82.6; 95% CI, 61.2-95.0) for pubertal and > 2.91 (sensitivity, 63.6; 95% CI, 30.8-89.1, specificity, 93.7; 95%CI, 79.2-99.2) for postpubertal adolescents. Conclusion: The threshold value of the HOMA-IR for identifying insulin resistance was > 3.22 for pubertal and > 2.91 for postpubertal adolescents.

Influence of athletics on muscle composition and balance of students / Influência do atletismo na composição muscular e equilíbrio de estudantes / Influencia del atletismo en la composición muscular y en el equilibrio de estudiantes

ABSTRACT Introduction The physical quality of college students decreases annually, a problem that physical education teachers should consider. Athletics can exercise the body's musculature integrally and improve young college students' physical and psychological abilities. Objective Analyze the influence of athletics on the muscle composition and hemodynamic balance of students. Methods In a given university 70 volunteers were randomly selected and divided into experimental and control classes, with 35 students each. The experimental class chose a gymnastics course, while the control class performed athletic activities represented by running. Results Under continuously increasing exercise duration and intensity, the athletes gradually shifted from aerobic to anaerobic exercise, so that muscle oxygen saturation gradually decreased. The dynamic balance ability of the students in the experimental class was greatly improved compared to the control class, reaching a balanced state. Conclusion The athletic program proposed in this paper can promote the adjustment of athletes' blood oxygen saturation, increase muscle oxygen delivery capacity, and exercise endurance, and fully promote fitness progress in the students. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução A qualidade física dos estudantes universitários decresce anualmente, sendo um problema que deve ser ponderado pelos professores de educação física. O atletismo pode exercitar integralmente a musculatura corporal além de melhorar as habilidades físicas e psicológicas dos jovens universitários. Objetivo Analisar a influência do atletismo na composição muscular e no equilíbrio hemodinâmico dos estudantes. Métodos Em uma determinada universidade foram selecionados 70 voluntários aleatoriamente divididos em classe experimental e controle, com 35 alunos cada. A classe experimental elegeu um curso de ginástica, enquanto a classe de controle realizou atividades de atletismo representados pela corrida. Resultados Sob aumento contínuo da duração e intensidade do exercício, os atletas começaram a passar gradualmente do exercício aeróbico para o anaeróbico, de modo que a saturação de oxigênio muscular diminuiu gradualmente. A capacidade de equilíbrio dinâmico dos alunos da classe experimental foi muito aprimorada comparativamente a da classe de controle, atingindo um estado equilibrado. Conclusão O programa de atletismo proposto neste artigo pode promover o ajuste da saturação de oxigênio no sangue dos atletas, aumentar a capacidade de fornecimento de oxigênio muscular e a resistência ao exercício, promovendo integralmente o progresso da aptidão física nos alunos. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción La calidad física de los estudiantes universitarios disminuye anualmente, siendo un problema sobre el que deben reflexionar los profesores de educación física. El atletismo puede ejercitar integralmente la musculatura corporal además de mejorar las capacidades físicas y psicológicas de los jóvenes universitarios. Objetivo Analizar la influencia del atletismo en la composición muscular y el equilibrio hemodinámico de los estudiantes. Métodos En una determinada universidad se seleccionaron aleatoriamente 70 voluntarios y se dividieron en clase experimental y de control, con 35 estudiantes cada una. La clase experimental eligió un curso de gimnasia, mientras que la clase de control realizó actividades atléticas representadas por la carrera. Resultados Al aumentar continuamente la duración y la intensidad del ejercicio, los atletas empezaron a pasar gradualmente del ejercicio aeróbico al anaeróbico, de modo que la saturación de oxígeno del músculo disminuyó gradualmente. La capacidad de equilibrio dinámico de los alumnos de la clase experimental mejoró mucho en comparación con la clase de control, alcanzando un estado de equilibrio. Conclusión El programa de atletismo propuesto en este artículo puede promover el ajuste de la saturación de oxígeno en la sangre de los atletas, aumentar la capacidad de entrega de oxígeno de los músculos y la resistencia al ejercicio, promoviendo integralmente el progreso de la aptitud física en los estudiantes. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Molecular and morphological alterations in uninjured skin of streptozotocin‐induced diabetic mice

Diabetes affects every tissue in the body, including the skin. The main skin problem is the increased risk of infections, which can lead to foot ulcers. Most studies evaluating the effects of diabetes on the skin are carried out in wound healing areas. There are fewer studies on uninjured skin, and some particularities of this tissue are yet to be elucidated. In general, cellular and molecular outcomes of diabetes are increased oxidative stress and lipid peroxidation. For our study, we used C57BL/6 mice that were divided into diabetic and non-diabetic groups. The diabetic group received low doses of streptozotocin on 5 consecutive days. To evaluate the effects of hyperglycemia on uninjured skin, we performed morphological analysis using hematoxylin/eosin staining, cellular analysis using Picrosirius red and Nissl staining, and immunostaining, and evaluated protein expression by polymerase chain reaction. We confirmed that mice were hyperglycemic, presenting all features related to this metabolic condition. Hyperglycemia caused a decrease in interleukin 6 (Il-6) and an increase in tumor necrosis factor alpha (Tnf-α), Il-10, F4/80, tumor growth factor beta (Tgf-β), and insulin-like growth factor 1 (Igf-1). In addition, hyperglycemia led to a lower cellular density in the epidermis and dermis, a delay in the maturation of collagen fibers, and a decrease in the number of neurons. Furthermore, we showed a decrease in Bdnf expression and no changes in Ntrk2 expression in the skin of diabetic animals. In conclusion, chronic hyperglycemia in mice induced by streptozotocin caused disruption of homeostasis even before loss of skin continuity.

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.

Effect of autophagic core protein Atg101 on adipocyte senescence / 中华内分泌代谢杂志

Objective:To investigate the effect of autophagy related gene Atg101 on white adipocyte senescence.Methods:An Atg101 knockdown model of 3T3-L1 mature adipocytes was constructed to probe the effect of Atg101 on autophagy-related proteins LC3 and p62 protein. The RNA-seq database of human subcutaneous adipose tissue was constructed and analyzed, and the co-expressed gene set was predicted based on the pearson correlation coefficient( R2>0.4, P<0.05) between FPKM values of Atg101 and other gene, followed by KEGG and Reactome enrichment analysis. Young mouse(8 weeks old) and old mouse(18 months old) models were established, and the expression levels of Atg101 in inguinal white adipose tissue and epididymal white adipose tissue were detected by quantitative real-time PCR(RT-qPCR) and Western blot. Furthermore, the differences in white adipocyte senescence-associated secretory phenotype(SASP), cell cycle and mitochondrial homeostasis-related genes were detected by RNA-seq, Western blot, and RT-qPCR to analyze the effects of Atg101 silencing on adipocyte senescence. Results:The autophagy-related protein LC3-Ⅱ expression was significantly decreased and p62 protein was induced after Atg101 was knockdowned in 3T3-L1 adipocytes, suggesting impaired cell autophagy. KEGG enrichment analysis revealed that Atg101 co-expressed gene set was mainly enriched in autophagy and senescence-related pathways; Reactome enrichment analysis revealed that this gene set was associated with multiple cell cycle signaling pathways. RT-qPCR and Western blot confirmed that both mRNA and protein levels of Atg101 were down-regulated in inguinal white adipose tissue of aging mice, and protein levels in epididymal white adipose tissue were also significantly reduced. Finally, it was further confirmed that SASP-related genes were induced after Atg101 knockdown in white adipocytes, and cell cycle-specific gene expression was restricted and cytokine-dependent protein kinase inhibitors p16 and p21 expressions were significantly increased, while mitochondrial homeostasis regulatory genes were also suppressed.Conclusions:Knockdown of Atg101 may regulate white adipocyte senescence by inhibiting autophagic activity, presenting impaired mitochondrial homeostasis.

Effect of electroacupuncture on calcium homeostasis in hippocampal neurons of mice with sepsis-associated encephalopathy / 中华麻醉学杂志

Objective:To investigate the effect of electroacupuncture on calcium homeostasis in hippocampal neurons of mice with sepsis-associated encephalopathy (SAE).Methods:Twenty-four healthy male C57BL/6J mice, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SAE group, SAE plus electroacupuncture group (SAE+ EA group), and SAE plus sham electroacupuncture group (SAE+ SEA group). The virus carrying calcium ion (Ca 2+ ) fluorescent probes was injected and then an optical fiber was implanted into the hippocampal CA1 area to record the fluorescence signals of Ca 2+ . SAE was induced by cecal ligation and puncture in anesthetized mice at 3 weeks after administration. Starting from 3 days before surgery, Baihui and bilateral Quchi and bilateral Zusanli acupoints were stimulated for 30 min per day for 7 consecutive days in SAE+ EA group. In SAE+ SEA group, electroacupuncture was performed at the points 0.2 mm lateral to the corresponding acupoints without electrical stimulation. Open field tests were conducted at 5 days after surgery to record the number of rearing and changes in related Ca 2+ signals in hippocampal CA1 neurons. Novel object recognition tests were conducted at 6-7 days after surgery to record the recognition time and changes in related Ca 2+ signals in hippocampal CA1 neurons. Mice were sacrificed after the end of behavioral testing on 7 days after surgery, and brain tissues ipsilateral to the optical fiber implant were obtained and the fluorescence intensity of Ca 2+ in the hippocampal CA1 neurons was acquired using a fluorescent microscope. Results:Compared with Sham group, the number of rearing and amplitudes of related Ca 2+ signals in hippocampal CA1 neurons while rearing were significantly decreased in SAE group and SAE+ SEA group ( P<0.05), and no statistically significant changes were found in the parameters mentioned above in SAE+ EA group ( P>0.05), and the recognition index and amplitudes of related Ca 2+ signals while recognizing were significantly deceased, and the fluorescence intensity of Ca 2+ in hippocampal CA1 neurons was increased in SAE, SAE+ EA and SAE+ SEA groups ( P<0.05). Compared with SAE group and SAE+ SEA group, the number of rearing and amplitudes of related Ca 2+ signals in hippocampal CA1 neurons while rearing were significantly increased, the recognition index and amplitudes of related Ca 2+ signals in hippocampal CA1 neurons while recognizing were increased, and the fluorescence intensity of Ca 2+ in hippocampal CA1 neurons was decreased in SAE+ EA group ( P<0.05). There were no statistically significant differences in the parameters mentioned above between SAE group and SAE+ SEA group ( P>0.05). Conclusions:The mechanism by which electroacupuncture alleviates SAE may be related to regulation of Ca 2+ homeostasis in hippocampal neurons of mice.

Effect of repeated episodes of ventricular fibrillation and defibrillation on arterial acid-base and electrolytes changes in a swine model / 中华急诊医学杂志

Objective:To investigate changes in arterial acid-base and electrolytes after repeated episodes of ventricular fibrillation (VF) and defibrillation in a swine model.Methods:Sixteen Peking white swine, weighting (32±2.5) kg, were placed with temporary pacemaker electrodes via the left femoral vein into the right ventricle after anesthesia. Then VF was electrically induced by using a programmed electrical stimulation instrument. An arterial cannula was inserted into the left femoral artery to measure mean arterial blood pressure and cardiac output using a PiCCO monitor, with blood samples collected. The pigs were randomly divided into two group: the manual defibrillation group (MD, n=8) and the automated external defibrillation group (AED, n=8). The first defibrillation was attempted with the manufacturer’s dose (150 J) for 15 s after the successful induction of VF in the MD group. If spontaneous circulation was not recovered, 2-min chest compression and subsequent defibrillation (200 J) were attempted. For the AED group, the defibrillation was delivered following voice prompts of the AED. After the return of spontaneous circulation, the pig was allowed to stabilize for 30 min, followed by the induction of the next episode of VF. The above process was repeated five times. Arterial blood gas, cardiac biomarkers, and hemodynamic variables were measured at 30 min after the return of spontaneous circulation. Results:All pigs were successfully induced VF five times and defibrillated successfully. There were no significant changes in heart rate and mean arterial blood pressure between the two groups after repeated episodes of VF and defibrillation. Compared with baseline measurements, cardiac output tended to decrease after repeated episodes of VF and defibrillation but was not statistically significant (all P>0.05). There were no significant differences in arterial pH, HCO 3-, sodium, and lactic acid in the two groups between each measurement time point and baseline values after repeated VF (all P>0.05), but potassium levels in the two groups decreased with time, and the difference was statistically significant compared with the baseline measurement (all P<0.05). There were no significant differences in myoglobin, creatine kinase isoenzyme-MB, and cardiac troponin I for the two groups compared with baseline values after repeated episodes of VF and defibrillation or various episodes of VF between the two groups (all P > 0.05). Conclusions:Repeated episodes of VF and defibrillation have no significant effect on pH balance, but significantly decrease blood potassium. Clinical approaches (MD vs. AED) do not affect defibrillation effect, with no significant differences in hemodynamic variables and myocardial injuries.

Research Progress of Squalene Monooxygenase and Cancer / 肿瘤防治研究

Squalene monooxygenase (SQLE) is the rate-limiting enzyme of cholesterol biosynthesis. It plays a crucial role in regulating cholesterol homeostasis. Increasing evidence shows that SQLE is closely related to the occurrence, development, metastasis, and poor prognosis of various cancers. SQLE can not only promote the proliferation of cancer cells and epithelial-mesenchymal transformation but also play an important role in maintaining the stemness of cancer stem cells and regulating cholesterol homeostasis. SQLE may be a potential molecular target for cancer therapy. In this review, the role of SQLE in regulating cholesterol homeostasis in vivo; its function in the occurrence, development, and metastasis of various cancers; and its molecular mechanism were summarized. Screening new SQLE inhibitors may provide new ideas for targeted cancer therapy.

Mechano-Chemical Coupling in Living Organisms and Possible Road Map of Mechanomedicine / 医用生物力学

In view of fundamental challenges to the current life and medical researches, this paper analyzes the mechano-chemical coupling behaviors of living organisms at molecular, sub-cellular, cellular and tissue levels, attempting to explain the quantitative relationships in those mechano-chemical coupling behaviors at different scales. These quantitative relationships show that the structures of living organisms at various scales are closely related to their tensional homeostasis, i. e. , the structural changes will inevitably lead to the changes of tensional homeostasis; Conversely, the changes of the tensional homeostasis will inevitably lead to structural changes. The tensional homeostasis in living organisms stems from contractile force in actin cytoskeleton generated by the action of myosin II at molecular level, and the tensional homeostasis at higher structural levels is realized with the help of hierarchical structures of the living organisms. Therefore, the mechano-chemical coupling mechanisms and their corresponding quantitative relationships inspire scientists to develop a new way of understanding and dealing with diseases, called as mechanomedicine. Finally, the paper discusses possible ways / road maps of mechanomedicine to understand and treat diseases, in order to provide diagnostic and therapeutic ideas for this new medical paradigm.

Protective mechanism of Yinchenzhufu decoction against cholestatic liver injury induced by lithic acid based on network pharmacology / 药学学报

Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.

Molecular mechanism of high altitude hypoxia induced intestinal homeostasis imbalance and research progress of traditional Chinese medicine / 中国临床药理学与治疗学

Hypoxia is one of the factors restricting the survival of people at high altitudes, which can cause various symptoms such as vomiting, diarrhea, palpitations, shortness of breath and acute coma. About 80% of patients with acute mountain sickness have at least one symptom of a gastrointestinal distress (e. g., anorexia, nausea, diarrhea, vomiting, etc.). The pathological characteristics, pathogenesis and drug treatment of intestinal injury caused by high-altitude hypoxia were studied, which is conducive to the diagnosis and treatment of plateau gastrointestinal diseases. Therefore, by summarized relevant literature and systematically expounds the related researches on intestinal damage caused by high altitude hypoxia. We summarized the changes of intestinal morphology, intestinal cells, intestinal flora and other intestinal homeostasis caused by high altitude hypoxia, the mechanism of intestinal inflammation and oxidative damage, and the treatment of traditional Chinese medicine, which provide reference and information for reference for scientific research workers and clinicians.