Resposta Vascular da Triiodotironina sobre Anéis de Aortas Isoladas: Contribuição de Mecanismos Redox / Vascular Response of Triiodothyronine on Isolated Aortic Rings: Contribution of Redox Mechanisms

Resumo Fundamento A disfunção vascular constitui a etiologia de diversas doenças, incluindo infarto do miocárdio e hipertensão, diante da ruptura da homeostase oxi-redutiva ("redox"), desempenhando um papel no desequilíbrio do mecanismo de controle vasomotor. Nosso grupo demonstrou anteriormente que os hormônios tireoidianos melhoram a sinalização da angiogênese, exercendo efeitos protetores sobre o tecido aórtico de ratos infartados. Objetivos Investigar o papel da triiodotironina (T3) na resposta vascular, explorando seus efeitos em aortas isoladas e a presença de mecanismos redox vasculares. Métodos Anéis aórticos isolados (endotélio intacto e desnudado) pré-contraídos com fenilefrina foram incubados com T3 (10-8, 10-7, 10-6, 10-5 e 10-4 M) e a tensão foi registrada usando um transdutor de deslocamento de força acoplado a um sistema de coleta. Para avaliar o envolvimento do estresse oxidativo, os anéis aórticos foram pré-incubados com T3 e posteriormente submetidos a um sistema de geração de espécies reativas de oxigênio (ROS) in vitro. O nível de significância adotado na análise estatística foi de 5%. Resultados A T3 (10-4 M) promoveu o vasorrelaxamento dos anéis aórticos pré-contraídos com fenilefrina em endotélio intacto e desnudado. Os anéis aórticos pré-incubados na presença de T3 (10-4 M) também mostraram diminuição da vasoconstrição provocada pela fenilefrina (1 µM) em preparações de endotélio intacto. Além disso, o efeito vasorrelaxante da T3 (10-4 M) persistiu em anéis aórticos pré-incubados com éster metílico de NG-nitro-L-arginina (L-NAME, 10 µM), um inibidor inespecífico da NO sintase (NOS). Por fim, a T3 (10-4 M) exibiu, in vitro, um papel antioxidante ao reduzir a atividade da NADPH oxidase e aumentar a atividade da SOD nos homogenatos aórticos. Conclusão A T3 exerce efeitos dependentes e independentes de endotélio, o que pode estar relacionado ao seu papel na manutenção da homeostase redox.

Abstract Background Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling. Objective Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms. Methods Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%. Results T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates. Conclusion T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.

Perspectiva holística en salud: la contribución de la Homeopatía / Holistic Perspective in Health: The Contribution of Homeopathy

En el panorama de la salud, el cuerpo humano, en su estado natural, se revela como una intrincada unidad que opera en armonía para mantener el equilibrio dinámico. Sin embargo, esta homeostasis puede verse afectada, dando lugar a la dualidad y a trastornos que comprometen la estabilidad vital. Este artículo propone una reflexión sobre la perspectiva homeopática, destacando su enfoque único en comparación con la medicina convencional. Diferenciándose al tratar al individuo como un todo integrado, la Homeopatía reconoce la transitoriedad de la dualidad representada por las enfermedades y enfatiza la importancia de la armonía entre el cuerpo y la mente en la búsqueda de la homeostasis. Inspirada en las ideas de Hahnemann, la Homeopatía se destaca por su visión holística, rechazando el dualismo estricto y proponiendo intervenciones que van más allá de la supresión de los síntomas. Anclada en la ley de los similares, busca sustancias que reproduzcan los síntomas del paciente en un estado saludable, buscando una cura profunda y la restauración de la unidad dinámica del organismo. A pesar de los desafíos, como la resistencia y la falta de métodos de investigación universalmente aceptados, la Homeopatía persiste a nivel mundial, sugiriendo un valor único. Este artículo promueve una reflexión sobre el enfoque homeopático, enfatizando su contribución a la comprensión de la salud y su papel en el panorama terapéutico.

n the landscape of health, the human body, in its natural state, reveals itself as an intricate unity, operating harmoniously to maintain dynamic balance. However, this homeostasis can be disrupted, leading to duality and disturbances that compromise vital stability. This article reflects on the homeopathic perspective, highlighting its unique approach compared to conventional medicine. Distinguishing itself by treating the individual as an integrated whole, homeopathy recognizes the transience of duality represented by diseases and emphasizes the importance of harmony between body and mind in the pursuit of homeostasis.Inspired by Hahnemann's ideas, homeopathy stands out for its holistic view, rejecting strict dualism and proposing interventions that go beyond symptom suppression. Anchored in the Law of Similars, it seeks substances that would reproduce the patient's symptoms in a healthy state, aiming for a profound cure and the restoration of the dynamic unity of the organism. Despite challenges, such as resistance and a lack of universally accepted research methods, homeopathy persists globally, suggesting unique value. This article encourages reflection on the homeopathic approach, emphasizing

The essential role of adenine nucleotide translocase 4 on male reproductive function in mice

Adenine nucleotide translocator 4 (Ant4), an ATP/ADP transporter expressed in the early phases of spermatogenesis, plays a crucial role in male fertility. While Ant4 loss causes early arrest of meiosis and increased apoptosis of spermatogenic cells in male mice, its other potential functions in male fertility remain unexplored. Here, we utilized Ant4 knockout mice to delineate the effects of Ant4-deficiency on male reproduction. Our observations demonstrated that Ant4-deficiency led to infertility and impaired testicular development, which was further investigated by evaluating testicular oxidative stress, autophagy, and inflammation. Specifically, the loss of Ant4 led to an imbalance of oxidation and antioxidants. Significant ultrastructural alterations were identified in the testicular tissues of Ant4-deficient mice, including swelling of mitochondria, loss of cristae, and accumulation of autophagosomes. Our results also showed that autophagic flux and AKT-AMPK-mTOR signaling pathway were affected in Ant4-deficient mice. Moreover, Ant4 loss increased the expression of pro-inflammatory factors. Overall, our findings underscored the importance of Ant4 in regulating oxidative stress, autophagy, and inflammation in testicular tissues. Taken together, these insights provided a nuanced understanding of the significance of Ant4 in testicular development.

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation / 药物分析学报

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Discussion on the Effects of Mitochondrial Homeostasis in Heart Failure Based on"Yin-yang Theory" / 中国中医药信息杂志

Heart failure is a group of complex clinical syndromes in the middle and late stages of cardiovascular diseases.Mitochondrial homeostasis imbalance is one of the pathological mechanisms in the occurrence and development of heart failure.This article revolved around the"yin-yang theory"in TCM and explained the pathological mechanism of heart failure through mitochondrial homeostasis.Heart failure is the syndrome of deficiency in nature and excess in superficiality fundamental.Its basic pathogenesis is"yang deficiency and yin excess".Based on the deficiency of heart yang qi and the stagnation of yin pathogens,the combination of deficiency and excess runs through the entire disease.Mitochondrial homeostasis imbalance is a manifestation of yin-yang imbalance at the cellular micro level,mainly manifested as inhibition of mitochondrial biosynthesis,mitochondrial dynamics imbalance,mitophagy disorder,etc.,which affects mitochondrial structure and function and leads to abnormal myocardial energy metabolism.Therefore,based on the"yin-yang theory",the basic treatment method is to"tonify deficiency and damage excess"to regulate mitochondrial biosynthesis,mitochondrial dynamics,and mitophagy,thereby maintaining mitochondrial homeostasis and improving myocardial energy metabolism,which is of great significance for the prevention and treatment of heart failure.

Risk factors of abnormal urinary albumin/creatinine ratio in people with obesity / 中华内分泌代谢杂志

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.

Progress in zinc homeostasis-related genes in Aspergillus fumigatus / 中华微生物学和免疫学杂志

Aspergillus fumigatus is an opportunistic pathogenic fungus transmitted through the air. It targets the the lungs of immunocompromised patients and can cause severe invasive aspergillosis. Zinc, an essential trace element for microbial growth, is required by all fungi, including Aspergillus fumigatus. Some studies have shown a direct correlation between the virulence of fungi within the host and the uptake of zinc by them. However, zinc in the human body mostly binds to zinc-binding proteins, resulting in ion concentrations in the host′s tissue microenvironment much lower than the optimal growth concentration for fungi. There are several zinc transport proteins in Aspergillus fumigatus, enabling it to efficiently absorb zinc even in the condition of zinc deficiency. These proteins also protect the cells of Aspergillus fumigatu from the damage caused by excessive zinc. This article is to provide a comprehensive overview of the roles of zinc homeostasis regulation in the growth, development and virulence of Aspergillus fumigatus as well as the related genes, summarize the current research status of genes regulating zinc levels in Aspergillus fumigatus and investigate whether interference with zinc homeostasis in Aspergillus fumigatus will be a new generation of adjunctive therapy for invasive aspergillosis or antifungal strategy.

Construction of Meridian and Collateral Homeostasis Model from Phenomics / 中医杂志

By applying "homeostasis" to the study of the meridian and collateral system， the concept of meridian and collateral homeostasis has been proposed which refers to a balanced and stable state of meridian and collateral system， and plays an important role in maintaining body health and can provide a reference for the diagnosis and treatment of diseases. Phenomics realizes the cross-scale correlation from micro-phenotypic data， such as genome， proteome， and metabolome， to macro-phenotypic data， such as physiological state， behavioral activities， and external manifestations. From the perspective of phenomics， this paper proposes a meridian and collateral homeostasis dynamic mapping model of "macroscopic signs and microscopic expression". This model combines macro signs such as the four examinations of traditional Chinese medicine （TCM）， biophysical indicators of acupoints， and micro expression information such as genes， proteins， and metabolism， and systematically investigates the relationship between meridian and collateral homeostasis and health and disease， thereby providing ideas and references for the identification of pre-disease states as well as precise diagnosis and treatment in TCM.

Exploration of Myopia Prevention and Control Strategies of Myopia in Children and Adolescents from the Perspective of "Rhythmic Equilibrium" / 中医杂志

The theory of “rhythmic equilibrium” is developed based on the idea of sharing the same laws between nature and human， and by integrating with the medical concept of homeostasis of calm yin and sound yang. "Rhythmic instability" runs through the entire process of the occurrence and development of myopia， covering four aspects including imbalance of rhythm （high-risk period of myopia）， imbalance of qi and blood （premyopia）， imbalance of sinew-membranes （low myopia）， and imbalance of essence and blood （high myopia）. The treatment should focus on adjusting the rhythm and harmonizing situation， which can help balance yin and yang， and nourish the eye system. For high-risk period of myopia， adjusting sleeping time and increasing outdoor activities are stressed to adjust the rhythm in a timely manner. In the stage of premyopia， appropriate techniques of traditional Chinese medicine （TCM） such as pressing needles can be added to harmonize qi and blood. In the period of low myopia， appropriate TCM techniques such as pressing needles and ear acupuncture are mainly used， supplemented by modified Danggui Buxue Decoction （当归补血汤） to soften tendons and unblock collaterals. During the period of high myopia， it is recommended to control the development of existing disease and put focus on nourishing essence and blood， usually with Zhujing Pill （驻景丸） or modified Siwu Wuzi Decoction （四物五子汤） to restore the stability of the eyes and the whole body.

Research progress in ceruloplasmin regulation of lipid metabolism homeostasis / 上海交通大学学报（医学版）

Ceruloplasmin(Cp)is a crucial protein secreted by the liver and plays a vital role in regulating the distribution and transport of copper throughout the body,thereby maintaining copper homeostasis.Additionally,Cp functions as a significant enzyme known as ferroxidase,which is involved in iron metabolism within the body.Numerous studies have suggested a close relationship between Cp and metabolic disorders,such as diabetes and cardiovascular diseases.Recent research has also shed light on the involvement of Cp in the regulation of lipid metabolism.The various activities associated with lipid metabolism,including lipid synthesis,adipose hydrolysis,fatty acid oxidation,lipid transport,and absorption,collectively contribute to maintaining lipid homeostasis.Dysregulation of lipid metabolism can lead to metabolic disorders and cardiovascular complications.Cp regulates lipid metabolism through two main mechanisms.Firstly,Cp participates in the regulation of oxidative stress by modulating iron metabolism through its ferroxidase activity and involvement in redox reaction.Secondly,copper along with copper-dependent enzymes directly participates in the processes such as cholesterol metabolism,lipoprotein metabolism,and fatty acid synthesis.As a result,the role of Cp in maintaining the homeostasis of copper and iron allows it to regulate lipid metabolism by influencing copper or iron-dependent enzymes and related pathways.Although the correlation between Cp and lipid metabolism has been identified,an in-depth exploration of the precise mechanisms by which Cp governs lipid metabolism is warranted.This article provides an overview of the role of Cp in lipid metabolism and highlights the progress in related research,with the aim of providing new insights for the development and treatment of disorders related to lipid metabolism.

Progress in ERAS-based anesthetic management for patients undergoing deep inferior epigastric perforator flap breast reconstruction / 复旦学报（医学版）

At present,the development of enhanced recovery after surgery(ERAS)pathways in deep inferior epigastric perforator(DIEP)flap breast reconstruction is still in the initial stage worldwide,lacking established guidelines.In the multidisciplinary ERAS pathways,the department of anesthesiology is responsible for some core elements such as optimizing anestheticprotocols,perioperative fluid management and homeostasis regulation,prevention of hypothermia,improvement of perioperative analgesia,and postoperative nausea and vomiting prophylaxis.We summarized the anesthetic management in the ERAS pathways for patients undergoing DIEP flap breast reconstruction in Fudan University Shanghai Cancer Center,along with the recent progress,aiming to establish and improve the perioperative strategy based on ERAS pathways in DIEP flap breast reconstruction.

Electrophysiological Mechanisms of Sleep Homeostasis / 生物化学与生物物理进展

The brain’s neural circuits consist of a large number of highly unstable networks. Despite the existence of many internal and external factors that continuously disturb the balance, our brains employ an array of homeostatic mechanisms that allow neurons or neural circuits to sense how active they are, and when they deviate from a target value, whereby a force must be generated to move neuronal activity back toward this target. Sleep is one of the well-known physiological states in the regulation of homeostasis. Sleep pressure increases during wakefulness and decreases during sleep. When sleep is lost (e.g., sleep deprivation), this loss is compensated by extending or strengthening subsequent sleep. These phenomena are known as sleep homeostasis. The dysregulation of sleep homeostasis accompanies brain-related diseases such as schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder. More importantly, it can significantly undermine the basis of traditional sleep hygiene practices for these diseases. Therefore, clarifying the mechanisms of sleep homeostasis is important for therapy, but it remains an unsolved mystery. In addition to pharmacological treatment, non-invasive brain stimulation has become one of the most promising tools for clinical treatment in recent years due to its low cost, portability and low incidence of side effects. In order to promote relevant technologies, this review will focus on the electrophysiological mechanisms of sleep homeostasis. We first discuss the electrophysiological marker of sleep homeostasis, slow-wave activity, then move to the neuronal firing rates, finally discuss more aspects of sleep homeostasis, including differences in brain area, sleep stages, learning and individual differences.

Extracellular vesicles in sarcopenic obesity:roles and mechanisms / 中国组织工程研究

BACKGROUND:Extracellular vesicles can regulate insulin resistance and control inflammatory response by participating in intercellular communication,while repairing skeletal muscles and promoting skeletal muscle regeneration,which is expected to be a novel treatment modality for sarcopenic obesity. OBJECTIVE:To review the biogenesis of extracellular vesicles,their biological functions,their relationship with sarcopenic obesity,and recent advances in the pathogenesis,diagnosis,and treatment of sarcopenic obesity. METHODS:The first author performed a computer search of PubMed,Embase,CNKI and other databases for relevant studies involving extracellular vesicle in sarcopenic obesity.The search keywords were"extracellular vesicle,exosome,sarcopenic obesity,obese sarcopenia,skeletal muscle regeneration,skeletal muscle mass regulation"in English and Chinese,respectively.The search period was from June 2022 to November 2022.After screening,87 articles were included for further review. RESULTS AND CONCLUSION:Extracellular vesicles are important vectors of bidirectional cell communication and participate in the regulation of normal physiological and pathological processes through autocrine,paracrine and endocrine ways.Sarcopenic obesity is a complex multi-factor disease.Extracellular vesicles are involved in the occurrence and development of sarcopenic obesity mainly by regulating the inflammatory response of skeletal muscle and the homeostasis of muscle cells.Cytokines secreted by adipose tissue and skeletal muscle are released into the extracellular circulation through extracellular vesicle encapsulation and interact with each other to promote skeletal muscle insulin resistance and lipogenesis,which is the main pathophysiology of skeletal muscle atrophy in sarcopenic obesity.Extracellular vesicles not only promote the development of sarcopenic obesity by providing specific pathogenic markers,but also are a valuable diagnostic indicator of sarcopenic obesity.Release of extracellular vesicles from skeletal muscle during exercise enhances metabolic response and promotes skeletal muscle regeneration.Extracellular vesicles can not only be used as therapeutic targets for sarcopenic obesity but also be used to treat sarcopenic obesity by loading drugs to effectively improve drug bioavailability.

Research progress in mitochondrial dynamic changes regulated by exercise / 中国组织工程研究

BACKGROUND:Mitochondrial quality control is a complex process,which involves three aspects:mitochondrial biogenesis,mitochondrial dynamics change and mitochondrial autophagy,among which mitochondrial dynamics change is the intermediate link between mitochondrial biogenesis and mitochondrial autophagy.Mitochondria can improve their own quality control through dynamics change and then maintain their stable state. OBJECTIVE:To explore the molecular mechanism underlying the influence of exercise on mitochondrial dynamics,so as to provide theoretical basis for improving mitochondrial network homeostasis and promoting functional health. METHODS:Using the method of literature review,CNKI,Bailianyun Library,PubMed,Web of Science,EBCSO were searched for relevant literature with the keywords of"Exercise,Mitochondrial Steady State,Mitochondrial Quality Control,Mitochondrial Dynamics,Mitochondrial Fusion and Mitochondrial Division"in Chinese and English.The finally obtained literature was screened,read,and summarized. RESULTS AND CONCLUSION:Dynamin-related proteins 1/2 are responsible for mitochondrial fission,while mitofusins 1/2 and optic atrophy type 1 mediate the fusion of outer membrane and inner mitochondrial membranes respectively.Exercise training can improve the function of mitochondria by up-regulating the protein expression of mitofusins 1/2 and optic atrophy type 1 and down-regulating the protein expression level of dynamin-related protein 1,promoting mitochondrial fusion and inhibiting mitochondrial fission.The findings that a single acute exercise affects changes in mitochondrial dynamics are controversial.Furthermore,there is tissue variability in exercise-mediated changes in mitochondrial dynamics.

Mechanical stress affects occurrence and development of osteoarthritis by regulating Hippo pathway / 中国组织工程研究

BACKGROUND:Osteoarthritis is a common chronic inflammation of joints caused by degenerative changes of articular cartilage.More and more studies have shown that mechanical stress is closely related to the development of osteoarthritis.The Hippo pathway is not only involved in the development of tissue cells,but also an effecting factor of mechanical stress,which is involved in the regulation of bone metabolism and cartilage metabolism. OBJECTIVE:Regulation of the Hippo pathway may become one of the new targets for intervention in osteoarthritis.Therefore,this paper reviewed the research on the effect of mechanical stress regulation of the Hippo pathway on osteoarthritis to provide ideas for the pathogenesis of osteoarthritis and provide a new theoretical basis for the treatment of osteoarthritis. METHODS:PubMed,Web of Science,Embase,CNKI,VIP,and WanFang databases were used for a literature search for articles published from inception to 2023 concerning the influence of mechanical stress on osteoarthritis and mechanical stress,Hippo pathway,and osteoarthritis.A total of 75 articles were finally reviewed. RESULTS AND CONCLUSION:(1)Different mechanical stresses may play different roles in cell proliferation,apoptosis and differentiation,osteoarthritis inflammation,and vascular homeostasis in osteoarthritis.(2)Hard extracellular matrix,low cell density,medium shear force,medium tensile force,and compression force can achieve cell proliferation,osteogenic differentiation,and vascular homeostasis,and inhibit inflammatory response by activating YAP/TAZ.(3)Soft extracellular matrix,high cell density,excessive shear force,excessive tensile force,and compressive force inhibit cell proliferation,enhance cartilage differentiation,disrupt vascular homeostasis,and promote inflammation through inactivation of YAP/TAZ,thus promoting the process of osteoarthritis.

Regulation of chondrocyte autophagy by acupotomy to promote chondrocyte homeostasis in osteoarthritis / 中国组织工程研究

BACKGROUND:Acupotomy is an effective method for the clinical treatment of osteoarthritis,with affirmed clinical outcomes,but the specific mechanisms remain unclear OBJECTIVE:To investigate the role of acupotomy in modulating chondrocyte autophagy to promote chondrocyte homeostasis in osteoarthritis. METHODS:Twenty-eight New Zealand rabbits were randomly divided into control group,osteoarthritis group,acupotomy group,and hyaluronic acid group,with seven rabbits in each group.The knee osteoarthritis rabbit model was prepared using the Videman method in the latter three groups.After modeling,the control group and osteoarthritis group received no interventions.The acupotomy group received acupotomy treatment 15 minutes per time,once a week,while the hyaluronic acid group received intra-articular injection of hyaluronic acid once a week,with a continuous treatment duration of 5 weeks.The day after the final intervention,knee joint macrostructure was observed using DR imaging,chondrocyte ultrastructure was examined through transmission electron microscopy,apoptosis of chondrocytes was assessed using Tunel staining,and western blot analysis was used to detect the expression of proteins related to the PI3K/Akt/mTOR pathway. RESULTS AND CONCLUSION:The DR imaging results revealed that the osteoarthritis group exhibited narrowed knee joint spaces and the formation of periarticular osteophytes,while the hyaluronic acid group and acupotomy group showed widened knee joint spaces with a reduction in periarticular osteophytes.Transmission electron microscopy results demonstrated a decreased number of autophagosomes in chondrocytes in the osteoarthritis group,along with nuclear shrinkage,nuclear membrane rupture,incomplete organelle morphology,and a clear tendency towards cell death.In contrast,both the hyaluronic acid group and acupotomy group exhibited a significant increase in autophagosomes,intact nuclear membranes,and a well-preserved cellular state.Tunel staining results indicated a considerable decrease in the number of apoptotic cells in the hyaluronic acid group and acupotomy group compared with the osteoarthritis group.Western blot results revealed that,compared with the control group,the expression levels of Beclin1,Cath D,and LC3II/LC3I were significantly decreased in the osteoarthritis group(P<0.05),while the expression levels of p-Akt/Akt and p-mTOR/mTOR were significantly increased(P<0.05);compared with the osteoarthritis group,the expression levels of Beclin1,Cath D,and LC3II/LC3I were significantly increased in both the hyaluronic acid group and acupotomy group(P<0.05),while the expression levels of p-Akt/Akt and p-mTOR/mTOR were significantly decreased(P<0.05).To conclude,acupotomy intervention can modulate the PI3K/Akt/mTOR signaling pathway to enhance the autophagic level in chondrocytes,thereby maintaining chondrocyte homeostasis.This ultimately leads to a slowdown in cartilage degeneration.

Factor analysis of pelvic tilt outcome after primary unilateral total hip arthroplasty / 中国组织工程研究

BACKGROUND:Pelvic tilt,which is often seen in hip diseases,is also a common functional problem after total hip arthroplasty. OBJECTIVE:To investigate the mechanism of occurrence and recovery of pelvic tilt after unilateral total hip arthroplasty in patients with femoral head necrosis. METHODS:The clinical data of 100 patients with femoral head necrosis who underwent unilateral total hip arthroplasty in the Department of Femoral Head Necrosis,Bone Injury Center of First Affiliated Hospital of Guangzhou University of Chinese Medicine were collected retrospectively from June 2021 to February 2023.The patients were divided into three groups,namely,groups A(<2°,n=48),B(2°-3°,n=34),and C(>3°,n=18),according to the severity of pelvic tilt on postoperative 3 day.Statistical data were collected and compared between the pre-and postoperative periods of patients of these three groups in terms of the angle of the coronal plane of the pelvis tilt,the length of the gluteus medius muscles of the bilateral sides,the heights of the rotational centers of the femoral heads,the difference in the lengths of the gluteus medius muscles of the bilateral sides and the heights of the rotational centers of the femoral heads,and the ratio of changes in the angle of the pelvic tilt.Pearson correlation coefficient was used to examine the correlation between pelvic tilt angle and other indexes. RESULTS AND CONCLUSION:(1)Pelvic tilt aggravation occurred in the short term after surgery.(2)The ratio of change in pelvic tilt angle from postoperative 3 days to postoperative 1 month time period differed between the groups,with group C>group B>group A.There was a difference between group C and the other groups in the time period from postoperative 1 to postoperative 3 months,with the ratio of change being the smallest in group C.There was no difference in the ratio of change between the groups in the time period from postoperative 3 days to postoperative 3 months.(3)The difference in bilateral gluteus medius muscles decreased gradually after surgery,and there was no difference in the comparison of bilateral gluteus medius muscles in the time period from postoperative 3 months.(4)The difference between bilateral centers of rotation increased after surgery,and the difference between bilateral heights at 3 months after surgery was smaller than that before surgery.(5)The pelvic tilt angle at 3 days after surgery,the duration of the disease and the pelvic tilt angle at 3 months after surgery were significantly correlated(all P=0.000),and the difference between bilateral gluteus medius muscles before surgery and the pelvic tilt angle at 3 days after surgery was significantly correlated(P=0.006)(6)The functional pelvic tilt occurred in the patients with femoral head necrosis after total hip arthroplasty.Correction of the pelvic tilt after surgery was based on the adaptive restoration of the functional pelvic tilt angle after surgery.Functional pelvic tilt arises as a compensatory adaptation of the organism based on the short-term postoperative reconstruction of bony structures and the survival of cumulative soft tissue damage.

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.

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.

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.