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1.
Article in Chinese | WPRIM | ID: wpr-1016843

ABSTRACT

ObjectiveThe differential expression of microRNAs (miRNAs) between the active stage and the remission stage of ulcerative colitis (UC) was analyzed by bioinformatics method, and the regulatory relationship was constructed by screening the differentially expressed genes (DEGs). The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database (GEO), and the most differentially expressed miRNAs were screened by GEO2R, Excel, and other tools as research objects. TargetScan, miRTarbase, miRDB, STRING, TRRUST, and Matescape databases were used to screen key DEGs, predict downstream transcription factors (TFs), gene ontology (GO), and conduct Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor (SOCS1), phosphorylated transcriptional signal transductor and activator 3 (p-STAT3), phosphorylated Janus kinase 2 (p-JAK2), and retinoic acid-associated orphan receptor-γt (ROR-γt). The expression levels of transforming growth factor-β (TGF-β), interleukin-17 (IL-17), interleukin-6 (IL-6), and interleukin-10 (IL-10) in serum were detected by enzyme linked immunosorbent assay (ELISA). ResultThe GSE48957 dataset was screened from the GEO database, and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation, as well as signaling pathways such as stem cell signaling pathway, IL-17 signaling pathway, and helper T cell 17 (Th17) cell differentiation. The Matescape database was used to screen out 10 key DEGs, among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3, p-JAK2, and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice, up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10, increase the level of anti-inflammatory factors, and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice, inhibit the phosphorylation of STAT3, inhibit the differentiation of CD4+ T cells into Th17 cells, reduce the levels of pro-inflammatory factors (IL-17 and IL-6), and increase the levels of anti-inflammatory factors (TGF-β and IL-10). As a result, the inflammation of colon mucosa in UC mice was alleviated.

2.
Article in Chinese | WPRIM | ID: wpr-1021462

ABSTRACT

BACKGROUND:Reactive oxygen species may be closely related to the occurrence and development of tendinopathy,but its exact role and related signal transduction mechanism have not been fully summarized. OBJECTIVE:To review current clinical or preclinical original studies,summarize the role of reactive oxygen species in tendinopathy and related signal transduction pathways and to explore its characteristics and whether there is a unified downstream pathway. METHODS:Relevant original studies in PubMed,Embase,Web of Science,as well as CNKI,WanFang,and VIP databases were searched by computer and the search results were screened and excluded according to the inclusion criteria.Ninety articles were finally included for review and analysis. RESULTS AND CONCLUSION:Reactive oxygen species affects the direction of tendon healing by simultaneously acting on tendon cells and the extracellular matrix,and it exhibits a bifacial effect in the treatment of tendinopathy.Concentration of reactive oxygen species may be the key to determining its direction of action.The possibility that low-dose reactive oxygen species can participate in the normal physiological healing of tendons or that tendon tissues are adaptive to stimulations may be the underlying mechanism that produces this characteristic effect.Reactive oxygen species affect the composition and structure of the extracellular matrix and normal tendon repair as well as maintain viability in response to external stimulations through matrix metalloproteinases,mitogen-activated protein kinases,mitochondrial apoptosis,the forkhead transcription factor O family,autophagy,inflammation,and antioxidant signaling pathways.Different reactive oxygen species stimulation intensities,durations,and external environments may cause different alterations in downstream molecular pathways and thus have different effects on the tendon.Due to the large gap in the number of literature included in the evaluation of the positive and negative effects of reactive oxygen species,it may cause some analytical error in the search for factors behind the characteristics of the action of reactive oxygen species in tendon.In addition,most experimental intervention conditions and results of interest are relatively homogeneous;therefore,the temporal and quantitative mechanisms of reactive oxygen species and the synergistic effects with other intervention factors have not been clarified,and the overall system of molecular actions of reactive oxygen species in tendinopathy has not been constructed.To conclude,reactive oxygen species might be involved in the treatment and prevention of tendinopathies as a beneficial factor in the future,and facilitate the exploration of oxidative stress signaling pathways and overall molecular action systems in tendinopathies thereafter,as well as lay the foundation for research on the therapeutic strategies of different antioxidants in tendinopathies to better prevent and treat tendon injury and degeneration.

3.
Article in Chinese | WPRIM | ID: wpr-1031524

ABSTRACT

Nerve growth factor (NGF) has been widely studied because it plays an important role in the survival, growth and differentiation of nerve cells. It is distributed throughout the body and plays different pathophysiological roles according to the combined receptors. TrkA is its high affinity receptor, and many studies have shown that NGF plays different roles according to its downstream signal transduction pathways after combining with it. After combining with NGF, it also has a cross-effect on other signal transduction pathways that occur in the body. This paper reviews the signal transduction pathways combined with NGF and TrkA from different disease symptoms, so as to explore the role of NGF/TrkA signal pathways in children with overactive bladder.

4.
Journal of Clinical Hepatology ; (12): 1281-1288, 2024.
Article in Chinese | WPRIM | ID: wpr-1032283

ABSTRACT

Acute liver failure (ALF) is one of the most critical liver diseases in clinical practice and seriously affects the life and health of Chinese people. Due to its high morbidity and mortality rates, unclear pathogenesis, and limited treatment methods, ALF has become a major problem that needs to be solved urgently in the field of liver diseases. In recent years, more and more studies have shown that endoplasmic reticulum stress is a key biological process in the progression of ALF, and the IRE1α/TRAF2/JNK pathway, as a part of endoplasmic reticulum stress signaling, plays a role in amplifying inflammatory response, promoting hepatocyte apoptosis, and inhibiting liver regeneration ability during the progression of diseases. As a traditional treasure of China, traditional Chinese medicine has become a research hotspot in search for effective prevention and treatment drugs for ALF from monomers of Chinese herbs. This article elaborates on the mechanism of action of the IRE1α/TRAF2/JNK pathway in the progression of ALF and summarizes the potential value of several monomers of Chinese herbs in regulating this pathway, such as salidroside, Fructus Broussonetiae, Fructus Psoraleae+Schisandra chinensis, baicalein, genipin, kaempferol, resveratrol, sea buckthorn polysaccharide extract, and luteol, in order to provide a reference for further research and clinical practice of ALF.

5.
Article in Chinese | WPRIM | ID: wpr-1013092

ABSTRACT

@#Magnetic fields are safe and used in noninvasive physical therapies. Numerous studies have confirmed that magnetic fields have good osteogenic effects and certain value for clinical application in accelerating orthodontic tooth movement, promoting bone-implant integration, promoting fracture healing and improving the effects of distraction osteogenesis. Magnetic fields are expected to become applied as effective auxiliary methods for treating oral diseases. To support the clinical application of magnetic fields, this article reviews the applications of magnetic fields in the oral cavity, the biological effects on bone cells and the molecular mechanisms through which magnetic fields regulate bone metabolism. The biological effects of magnetic fields on bone cells include promoting osteogenesis by osteoblasts and mesenchymal stem cells and inhibiting bone resorption by osteoclasts. At the molecular level, bone cells sense and respond to magnetic stimulation, and through various mechanisms, such as displacement currents, Lorentz forces, and free radical pair effects, stimuli are transformed into biologically recognizable electrical signals that activate complex downstream signaling pathways, such as the P2 purinergic receptor signaling pathway, adenosine receptor signaling pathway, transforming growth factor-β receptor signaling pathway, mammalian target of rapamycin (mTOR) pathway, and Notch pathway. In addition, magnetic parameters, which are the factors affecting the osteogenic effects of magnetic fields, are discussed. However, the mechanisms of the osteogenic effects of magnetic fields are unclear, and further studies of these mechanisms could provide effective strategies for bone regeneration and periodontal tissue regeneration. In addition, considering the target of magnetic field therapies, combination with other drugs could lead to new strategies for the treatment of oral diseases.

6.
Journal of Clinical Hepatology ; (12): 626-632, 2024.
Article in Chinese | WPRIM | ID: wpr-1013149

ABSTRACT

Polygonum multiflorum (PM), a commonly used Chinese herbal medicine in clinical practice, has been associated with frequent reports of liver injury in recent years, and the medication safety of PM has attracted more and more attention in China and globally. This article reviews the recent research advances in the signaling pathways and mechanisms of PM in causing drug-induced liver injury (DILI) and aims to provide new ideas for the proper and rational use of PM in clinical practice. The results show that PM is involved in the regulation of various signaling pathways, and it leads to the death of hepatocytes by destroying mitochondrial function, exacerbating bile acid accumulation, and inducing immune response, oxidative stress, and endoplasmic reticulum stress, thereby inducing the development and progression of DILI through multiple targets, pathways, and levels.

7.
Article in Chinese | WPRIM | ID: wpr-1013337

ABSTRACT

ObjectiveTo investigate the effect of Xuanfei Zhisou prescription on the interleukin-17 (IL-17) signaling pathway in model rats with chronic obstructive pulmonary disease (COPD). MethodA total of 60 Wistar rats were randomly divided into a blank group (10 rats) and a model group (50 rats), and COPD model rats were established by tracheal infusion of lipopolysaccharide combined with passive fumigation. After modeling, the rats were divided into the model group, dexamethasone group, and high, medium, and low-dose Xuanfei Zhisou prescription groups (3.6, 1.8, 0.9 g·kg-1·d-1) according to the random number table. Rats in the blank group and model group were given normal saline of 10 mL·kg-1·d-1 by gavage administration, and the intervention groups of Xuanfei Zhisou prescription were given corresponding drugs. Rats in the dexamethasone group were given dexamethasone of 2.57×10-4 g·kg-1·d-1 for 28 days. The level of pulmonary function indexes in rats was measured by a pulmonary function detector. The contents of interleukin-6 (IL-6), interleukin-8 (IL-8), IL-17, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The positive expressions of IL-17A, IL-17RA, nuclear factor-κB activator 1 (Act1), tumor necrosis factor-associated factor 6 (TRAF6), p-p38 mitogen-activated protein kinase (p-p38 MAPK), nuclear factor-κB p65 (NF-κB p65), and phosphorylation were detected by immunohistochemistry (IHC). The protein expression levels of IL-17A, IL-17RA, Act1, and TRAF6 in the lung tissue were detected by Western blot. The mRNA expressions of IL-17A, IL-17RA, Act1, and TRAF6 in the lung tissue were detected by Real-time polymerase chain reaction (Real-time PCR). ResultCompared with the blank group, the serum contents of IL-6, IL-8, IL-17, IL-1β, and TNF-α in the model group were significantly increased (P<0.05), and the flow rate and volume indexes of pulmonary function in the model group were significantly decreased (P<0.05), while the time indexes and other indexes were significantly increased (P<0.05). The mRNA and protein expression levels of IL-17A, IL-17RA, Act1, and TRAF6 in pulmonary tissue and the positive expressions of downstream NF-κB p65, p-NF-κB p65, and p-p38 MAPK were increased (P<0.05). Compared with the model group, the levels of IL-6, IL-8, IL-17, IL-1β, and TNF-α in the serum of all treatment groups were decreased to varying degrees (P<0.05), and the indexes of pulmonary function were improved to different degrees (P<0.05). The mRNA and protein levels of IL-17A, IL-17RA, Act1, and TRAF6 and the positive expression of downstream NF-κB p65, p-NF-κB p65, and p-p38 MAPK in high and medium-dose Xuanfei Zhisou prescription groups were significantly decreased (P<0.05). ConclusionXuanfei Zhisou prescription can effectively resist inflammation of COPD rats. The mechanism may be related to down-regulating the protein expression of IL-17A, IL-17RA, Act1, and TRAF6, inhibiting downstream NF-κB and p38 MAPK signaling pathways, and reducing the release of IL-6, IL-8, TNF-α, IL-17, and IL-1β, thus reducing the airway inflammation response.

8.
Journal of Clinical Hepatology ; (12): 327-334, 2024.
Article in Chinese | WPRIM | ID: wpr-1007248

ABSTRACT

ObjectiveTo investigate the effect of kinesin family member 15 (KIF15) on the proliferation of hepatocellular carcinoma (HCC) cells and its mechanism of action. MethodsTCGA and GEPIA datasets were analyzed to determine the expression of KIF15 in HCC and its effect on tumor stage and survival. Quantitative real-time PCR and Western blot were used to measure the expression level of KIF15 in human-derived HCC cell lines (HepG2, Hep3B, MHCC-97H, and LM3) and human normal liver cell line L02 cultured in vitro, and Hep3B and HepG2 were selected for subsequent studies. CCK-8 assay, plate colony formation assay, and EdU staining were performed for Hep3B cells transfected with shRNA-NC or shRNA-KIF15 and HepG2 cells transfected with LV-vector or LV-KIF15 to evaluate the viability and proliferative capacity of these cells. GSEA was used to analyze the potential signaling pathways associated with KIF15 in HCC, and Western blot was used for detection. The independent-samples t test was used for comparison of continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsThe analysis of TCGA and GEPIA datasets showed that in HCC patients, the expression of KIF15 in HCC tissue was significantly higher than that in normal tissue, and the HCC patients with high KIF15 expression tended to have a poorer prognosis. Compared with sh-NC-Hep3B, sh3-Hep3B showed significant reductions in the mRNA and protein levels of KIF15 (P<0.05), cell viability, clone formation number, and EdU positive rate (all P<0.05). Compared with vector-HepG2, LV-KIF15-HepG2 showed significant increases in the mRNA and protein levels of KIF15 (P<0.05), cell viability, clone formation number, and EdU positive rate (all P<0.05). Subcutaneous tumor assay showed that compared with sh-NC-Hep3B, sh3-Hep3B showed reductions in tumor volume and tumor weight, as well as a significant reduction in the immunohistochemical score of Ki67 and a significant increase in the immunohistochemical score of TUNEL (P<0.05). GSEA analysis showed that the PI3K/AKT/mTOR pathway was positively correlated with KIF15 in HCC (NES=1.59, P<0.001). Western blot showed that LY294002 could inhibit the PI3K/AKT/mTOR pathway upregulated in LV-KIF15-HepG2, and compared with LV-KIF15-HepG2, LY294002+LV-KIF15-HepG2 showed significant reductions in cell viability, clone formation number, and EdU positive rate (all P<0.05). ConclusionKIF15 enhances the viability and proliferative capacity of HCC cells by upregulating the PI3K/AKT/mTOR signaling pathway.

9.
Article in Chinese | WPRIM | ID: wpr-1025128

ABSTRACT

AMP-activated protein kinase(AMPK)is a conserved cellular energy receptor that plays an important role in regulating cell growth,proliferation,differentiation,autophagy,phosphorylation,crosstalk,and glucose and lipid metabolism.AMPK is activated during low-energy or other extreme conditions,and it is suppressed by an excess of nutrients to maintain the energy balance.Additionally,the regulatory mechanism of the AMPK signaling pathway mediating ferroptosis reflects its unique role.AMPK plays a specialized regulatory function in various organelles,which provides a new direction for disease therapy.It is also a therapeutic target to prevent diseases such as reproductive system diseases,aging,cancer,inflammation and cardiac dysfunction.This article reviews cellular energy imbalance.AMPK stimulates its potential therapeutic potential in diseases and drugs through diverse signal regulatory mechanisms.It provides a new treatment for different system diseases.This review summarizes the diverse regulatory mechanisms of the AMPK signaling pathway and provides a theoretical reference for cancer therapy and other disease therapies targeting AMPK.

10.
Arq. neuropsiquiatr ; Arq. neuropsiquiatr;82(3): s00441779296, 2024. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1557126

ABSTRACT

Abstract Extracellular vesicles (EVs) are small vesicles released by cells that facilitate cell signaling. They are categorized based on their biogenesis and size. In the context of the central nervous system (CNS), EVs have been extensively studied for their role in both normal physiological functions and diseases like Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by cognitive decline and neuronal death. EVs have emerged as potential biomarkers for AD due to their involvement in disease progression. Specifically, EVs derived from neurons, astrocytes, and neuron precursor cells exhibit changes in quantity and composition in AD. Neuron-derived EVs have been found to contain key proteins associated with AD pathology, such as amyloid beta (Aß) and tau. Increased levels of Aß in neuron-derived EVs isolated from the plasma have been observed in individuals with AD and mild cognitive impairment, suggesting their potential as early biomarkers. However, the analysis of tau in neuron-derived EVs is still inconclusive. In addition to Aß and tau, neuron-derived EVs also carry other proteins linked to AD, including synaptic proteins. These findings indicate that EVs could serve as biomarkers for AD, particularly for early diagnosis and disease monitoring. However, further research is required to validate their use and explore potential therapeutic applications. To summarize, EVs are small vesicles involved in cell signaling within the CNS. They hold promise as biomarkers for AD, potentially enabling early diagnosis and monitoring of disease progression. Ongoing research aims to refine their use as biomarkers and uncover additional therapeutic applications.


Resumo As vesículas extracelulares (VEs) são pequenas estruturas liberadas pelas células que agem na sinalização celular. No sistema nervoso central (SNC), as VEs são estudadas em relação à doença de Alzheimer (DA), um distúrbio neurodegenerativo que cursa com declínio cognitivo e morte neuronal. As VEs podem ser biomarcadores potenciais para a DA devido ao seu papel na progressão da doença. As VEs derivadas de neurônios, astrócitos e células precursoras apresentam alterações na DA, contendo proteínas associadas à patologia da DA, como beta-amiloide (Aß) e tau. Níveis elevados de Aß foram observados nas VEs de neurônios de indivíduos com DA, sugerindo seu potencial como biomarcadores precoces. A análise de tau nas VEs de neurônios ainda é inconclusiva. Além disso, as VEs neurais carregam outras proteínas relacionadas à DA, incluindo proteínas sinápticas. As VEs podem ser promissoras como biomarcadores para o diagnóstico precoce e monitoramento da DA, porém mais pesquisas são necessárias para validar seu uso e explorar aplicações terapêuticas. Em resumo, as VEs são vesículas envolvidas na sinalização celular no SNC, com potencial como biomarcadores para a DA.

11.
Einstein (São Paulo, Online) ; 22: eRW0552, 2024. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1534332

ABSTRACT

ABSTRACT Introduction Triple-negative breast cancer is an aggressive subtype of breast cancer characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. This phenotype renders triple-negative breast cancer cells refractory to conventional therapies, resulting in poor clinical outcomes and an urgent need for novel therapeutic approaches. Recent studies have implicated dysregulation of the Notch receptor signaling pathway in the development and progression of triple-negative breast cancer. Objective This study aimed to conduct a comprehensive literature review to identify potential therapeutic targets of the Notch pathway. Our analysis focused on the upstream and downstream components of this pathway to identify potential therapeutic targets. Results Modulating the Notch signaling pathway may represent a promising therapeutic strategy to treat triple-negative breast cancer. Several potential therapeutic targets within this pathway are in the early stages of development, including upstream (such as Notch ligands) and downstream (including specific molecules involved in triple-negative breast cancer growth). These targets represent potential avenues for therapeutic intervention in triple-negative breast cancer. Comments Additional research specifically addressing issues related to toxicity and improving drug delivery methods is critical for the successful translation of these potential therapeutic targets into effective treatments for patients with triple-negative breast cancer.

12.
Acta Pharmaceutica Sinica B ; (6): 998-1013, 2023.
Article in English | WPRIM | ID: wpr-971741

ABSTRACT

The skeletal system, which contains bones, joints, tendons, ligaments and other elements, plays a wide variety of roles in body shaping, support and movement, protection of internal organs, production of blood cells and regulation of calcium and phosphate metabolism. The prevalence of skeletal diseases and disorders, such as osteoporosis and bone fracture, osteoarthritis, rheumatoid arthritis, and intervertebral disc degeneration, increases with age, causing pain and loss of mobility and creating a huge social and economic burden globally. Focal adhesions (FAs) are macromolecular assemblies that are composed of the extracellular matrix (ECM), integrins, intracellular cytoskeleton and other proteins, including kindlin, talin, vinculin, paxillin, pinch, Src, focal adhesion kinase (FAK) and integrin-linked protein kinase (ILK) and other proteins. FA acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell-environment communications and modulates important processes, such as cell attachment, spreading, migration, differentiation and mechanotransduction, in different cells in skeletal system by impacting distinct outside-in and inside-out signaling pathways. This review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases.

13.
Journal of Clinical Hepatology ; (12): 663-670, 2023.
Article in Chinese | WPRIM | ID: wpr-971910

ABSTRACT

As a chronic liver inflammation disease caused by the lack of immune tolerance, autoimmune hepatitis is regulated by various signaling pathways, such as the NF-κB/NLRP3 pathway, the SIRT1/Nrf2/HO-1 pathway, the Hippo-YAP/TAZ pathway, the JAK/STAT pathway, the PI3K/Akt pathway, and the TRAF6/JNK pathway. These pathways can play a role against autoimmune hepatitis by participating in the processes including the proliferation and apoptosis of cytokines, immune response, and oxidative stress. In view of the problems of suboptimal response, obvious adverse reactions, and high recurrence rate in the clinical application of hormones and immune preparations for the treatment of autoimmune hepatitis, this article summarizes the research articles on autoimmune hepatitis-related signaling pathways and the mechanism of effective constituents (glycosides, terpenoids, flavonoids, quinones, and phenols) in traditional Chinese medicine intervening against the disease process of autoimmune hepatitis through the above signaling pathways, in order to provide a theoretical basis for scientific and effective utilization of effective constituents in traditional Chinese medicine to develop anti-autoimmune hepatitis drugs.

14.
Article in Chinese | WPRIM | ID: wpr-1017939

ABSTRACT

Ferroptosis is a cell death mode characterized by iron-dependent and excessive accumulation of lipid hydroperoxides, which has been discovered in recent years. Its regulatory mechanisms mainly involve iron metabolism, lipid peroxidation and amino acid metabolism. Ferroptosis is closely associated with the pathogenesis of ischemic stroke and is a promising therapeutic target for ischemic stroke. This article elaborates on the role of the main regulatory pathways of ferroptosis in ischemic stroke, providing new therapeutic ideas and targets for targeting the ferroptosis pathway to improve the outcome of ischemic stroke.

15.
Article in Chinese | WPRIM | ID: wpr-1017949

ABSTRACT

Brain arteriovenous malformations (bAVMs) are a complex congenital cerebrovascular disease. The lack of common capillaries results in blood flowing directly from the arteries to the veins, forming abnormal vascular malformations between the arteries and veins. BAVMs are usually found due to "epilepsy, intracranial hemorrhage, and focal neurological dysfunction", with a low incidence rate but a high mortality and disability rate. However, the specific pathogenesis of bAVMs is not fully understood. This article reviews the signaling pathways, pathophysiological mechanisms, and non-coding RNAs related to the pathogenesis of bAVMs, with the aim of providing new diagnostic and therapeutic strategies for bAVMs.

16.
Chinese Journal of Geriatrics ; (12): 1001-1007, 2023.
Article in Chinese | WPRIM | ID: wpr-1028159

ABSTRACT

Diabetes is a prevalent disease among the elderly population.Among the antidiabetic drugs, Metformin is the most commonly used, and has been found to have unique anti-aging effects through nutritional sensing regulation, maintenance of protein homeostasis, protection of mitochondrial function, alteration of intercellular communication, and telomere protection, among other mechanisms.The results of studies have shown that Metformin has significant anti-aging potential, thereby necessitating a thorough analysis and summary of its molecular mechanism and research progress in this regard.

17.
Journal of Clinical Hepatology ; (12): 1134-1143, 2023.
Article in Chinese | WPRIM | ID: wpr-973204

ABSTRACT

Objective To investigate the expression and role of the Sonic Hedgehog (Shh) signaling pathway in intestinal mucosal barrier injury in rats with severe acute pancreatitis (SAP). Methods A total of 48 Sprague-Dawley rats were divided into sham-operation group (Sham group), SAP model group (SAP group), SAP+Shh signaling pathway-specific agonist purmorphamine group (PUR+SAP group), and SAP+Shh signaling pathway-specific antagonist cyclopamine group (CYC+SAP group) using a random number table, with 12 rats in each group, and each group was further divided into 12-hour and 24-hour subgroups, with 6 rats in each subgroup. Rats were given retrograde injection of 5% sodium taurocholate into the pancreatic and bile ducts to establish a model of SAP, and rats in the intervention groups were given intraperitoneal injection of 0.69 mg/kg purmorphamine and 0.69 mg/kg cyclopamine before modeling. Related samples were collected at 12 and 24 hours after modeling. HE staining was used to observe the pathological changes of the pancreas and the ileum; ELISA was used to measure the serum levels of amylase, lipase, diamine oxidase (DAO), and endotoxin-core antibody (EndoCAb); the TUNEL method was used to observe the apoptosis of intestinal epithelial cells; Western blot was used to measure the expression levels of Shh, Ptch1, and Gli1 in ileal tissue. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. Results Compared with the Sham group, the SAP group had significant increases in the pathological scores of pancreatic and ileum tissue, the serum levels of lipase, amylase, DAO, and EndoCAb, the apoptosis of intestinal epithelial cells, and the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Compared with the SAP group, the PUR+SAP group had significantly alleviated pathological injury and dysfunction of the pancreas and intestine, a significant reduction in the apoptosis of intestinal epithelial cells, and significant increases in the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Compared with the SAP group, the CYC+SAP group had significant aggravation of the pathological injury and dysfunction of the pancreas and intestine, a significant increase in the apoptosis of intestinal epithelial cells, and significant reductions in the protein expression levels of Shh, Ptch1, and Gli1 in ileal tissue (all P < 0.05). Conclusion The Shh signaling pathway may be involved in intestinal mucosal barrier injury in SAP and exerts a protective effect.

18.
Journal of Clinical Hepatology ; (12): 1351-1357, 2023.
Article in Chinese | WPRIM | ID: wpr-978790

ABSTRACT

Objective To investigate the role and mechanism of action of Scabiosa atropurea in inhibiting the proliferation of hepatic stellate cells using cell experiment. Methods A total of 20 Wistar rats were randomly divided into control group and administration group, with 10 rats in each group. The rats in the control group were given normal saline by gavage, and those in the administration group were given Scabiosa atropurea by gavage to prepare drug-containing serum. HSC-T6 cells were incubated with the serum from the control group (10%) or the low-, middle-, and high-dose serum containing Scabiosa atropurea (10%, 15%, and 20%, respectively). MTT assay was used to observe the effect of different drug concentrations on cells in different periods of time; flow cytometry was used to measure cell apoptosis; qRT-PCR and Western blot were used to measure the mRNA and protein expression levels of fibrosis markers (α-SMA, collagen Ⅰ) and PI3K/Akt signaling pathway-related factors in hepatic stellate cells (HSCs). A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t - test was used for further comparison between two groups. Results Compared with the control group, the low-, middle-, and high-dose serum containing Scabiosa atropurea groups had a significant reduction in the OD value of cells (all P < 0.05) and a significant increase in the overall apoptosis rate of cells (all P < 0.05). The results of qRT-PCR showed that compared with the control group, the low-, middle-, and high-dose serum containing Scabiosa atropurea groups had significant reductions in the mRNA expression levels of α-SMA, collagen Ⅰ, PI3K, and Akt and a significant increase in the mRNA expression level of PTEN (all P < 0.05); Western blot showed that compared with the control group, the low-, middle-, and high-dose serum containing Scabiosa atropurea groups had significant reductions in the protein expression levels of α-SMA, collagen Ⅰ, PI3K, Akt, and p-Akt and a significant increase in the protein expression level of PTEN (all P < 0.05). Conclusion The Mongolian medicine Scabiosa atropurea can inhibit the proliferation of HSC-T6 cells and promote their apoptosis, possibly by regulating fibrosis markers and the PI3K/Akt signaling pathway to exert an anti-liver fibrosis effect.

19.
Journal of Clinical Hepatology ; (12): 1708-1713, 2023.
Article in Chinese | WPRIM | ID: wpr-978844

ABSTRACT

The incidence rate of alcoholic liver disease (ALD) is increasing year by year China, and there is a gradual increase in disease burden among Chinese people. Oxidative stress response in hepatocytes is an important pathogenic mechanism of ALD. The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is an important endogenous anti-oxidative stress pathway in the body, and Nrf2 is activated in response to oxidative stress and exerts its transcriptional activity to induce high HO-1 expression. HO-1 is an important oxidative stress response protein and plays a role in anti-inflammation, anti- oxidation, and cell apoptosis regulation together with heme hydrolysis products (bilirubin, carbon monoxide, and iron). This article reviews the research advances in the role of the Nrf2/HO-1 signaling pathway in ALD in recent years, so as to find a theoretical basis for the development and progression of ALD and an entry point for treatment.

20.
Chinese Journal of Rheumatology ; (12): 28-33,C1-4, 2023.
Article in Chinese | WPRIM | ID: wpr-992914

ABSTRACT

Objective:To investigate the expression and clinical significance of decoy receptor 3 (DcR3) and its signal pathway-related molecules in PBMCs of patients with ankylosing spondylitis (AS).Methods:Peripheral blood samples, clinical data and laboratory test results were collected from 100 patients with ankylosing spondylitis [50 patients with AS activity (ASA), 50 patients with AS stability (ASS)], 30 patients with osteoarthritis and 30 patients with gouty arthritis (as disease control group), and 60 healthy controls (HC). The mRNA expression levels of DcR3 and its signal pathway related genes (DR3, TL1A, Fas, FasL, LIGHT, LIGHTR, LTβR) were measured by real-time fluorescence quantitative polymerase chain reaction. Measurement data among the three groups in normal distribution were analyzed by t test or one-way analysis of variance, pairwise comparisons using LSD- t test, non-normal distribution data were analyzed by Mann-Whitney test or Kruskal-Wallis H test, χ2 test was used for correlation analysis of categorical variables. Correlation analysis between variables were analyzed using Spearman correlation analysis. Results:① By comparing the AS group, disease control group and HC group, the expression levels of DcR3 mRNA and DR3 mRNA in the AS group were lower than those in disease control group and HC group, and DcR3 mRNA and DR3 mRNA in disease control group were lower than those in the HC group {DcR3mRNA: [6.21 (3.89, 10.70)]×10 -4vs [9.51 (5.89, 16.65)]×10 -4vs [17.81 (11.27, 24.20)]×10 -4, H=55.28, P<0.001; DR3 mRNA: [41.05 (24.09, 66.95)]×10 -4vs [58.28 (28.41, 94.38)]×10 -4vs [94.79 (54.07, 144.51)]×10 -4, H=37.10, P<0.001}. The expression level of TL1A mRNA in the AS group was higher than that in disease control group {[14.71(4.91, 42.22)]×10 -4vs [4.00(1.07, 16.60)]×10 -4vs [7.70 (3.52, 27.83)]×10 -4, H=17.71, P<0.001}; The expression level of Fas mRNA in AS group and disease control group was lower than that in HC group {[20.99(4.63, 62.89)]×10 -4vs [23.97(15.82, 38.99)]×10 -4vs [78.45 (27.32, 146.46)]×10 -4, H=31.17, P<0.001}. The expression level of FasL mRNA in AS group was higher than that in disease control group and HC group {[42.87(6.57, 91.21)]×10 -4vs [5.45(2.83, 10.32)]×10 -4vs [6.88 (4.57, 23.79)]×10 -4, H=46.42, P<0.001}. The expression level of LIGHTR mRNA in AS group was lower than that in disease control group {[52.66 (7.20, 143.21)]×10 -4vs [98.80 (53.11, 166.24)]×10 -4vs [63.47(40.85, 138.07)]×10 -4, H=11.96, P<0.001}. There were no significant differences in LIGHT mRNA and LTβR mRNA among all groups ( H=0.86, P>0.05; H=3.18, P>0.05). ②The expression levels of DcR3 mRNA, DR3 mRNA and Fas mRNA in ASA group and ASS group were lower than those in HC group. DcR3 mRNA in ASA group was higher than that in ASS group, and DR3 mRNA in ASA group was lower than that in ASS group {DcR3 mRNA: [7.28 (4.92, 16.56)]×10 -4vs [4.59 (2.49, 7.03)]×10 -4vs [17.81 (11.27, 24.20)]×10 -4, H=62.63, P<0.001; DR3 mRNA: [30.93(16.18, 66.66)]×10 -4vs [47.17(29.91, 67.40)]×10 -4vs [94.79(54.07, 144.51)]×10 -4, H=41.48, P<0.001; Fas mRNA: [20.04(3.29, 62.30)]×10 -4vs [22.49(5.63, 64.79)]×10 -4vs [78.45(27.32, 146.46)]×10 -4, H=23.54, P<0.001}. The expression levels of TL1A mRNA and LTβR mRNA in the ASA group were higher than those in the ASS group and the HC group {TL1A mRNA: [32.36(10.09, 97.84)]×10 -4vs [9.98(1.29, 21.63)]×10 -4vs [7.70(3.52,27.83)]×10 -4, H=21.14, P<0.001; LTβR mRNA: [6.13(2.16,20.06)×10 -4vs [2.13(0.53,8.04)]×10 -4vs [2.72 (1.24,5.73)]×10 -4, H=12.86, P<0.001}. The expression level of FasL mRNA in the ASA group and the ASS group was higher than that in the HC group {[60.70 (8.16, 106.16)]×10 -4vs [30.14 (5.37, 78.40)]×10 -4vs [6.88 (4.57, 23.79)]×10 -4, H=18.99, P<0.001}. The expression level of LIGHTR mRNA in ASS group was lower than that in HC group {[49.79(10.75, 168.48)]×10 -4vs [15.92(3.27, 105.91)]×10 -4vs [63.47(40.85, 138.07)]×10 -4, H=11.80, P<0.001]. There was no significant difference in LIGHT mRNA among all groups ( H=4.15, P>0.05). ③Spearman correlation analysis showed that DcR3 level was positively correlated with BASDAI score and hsCRP in AS patients ( r=0.52, P<0.001; r=0.35, P<0.01), and DR3 level was negatively correlated with BASDAI score, ESR and hsCRP level ( r=-0.28, P<0.001; r=-0.25, P<0.001; r=-0.31, P<0.001). TL1A was positively correlated with BASDAI score, ESR and hsCRP level ( r=0.23, P=0.046; r=0.26, P=0.015; r=0.25, P=0.017). Conclusion:DcR3 and its signal pathway-related molecules are differentially expressed in PBMCs of patients with AS, suggesting that they may participate in the occurrence and development of AS.

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