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.

Neurovascular coupling and central nervous system diseases / 中国药理学通报

Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovascular units. The central nervous system diseases related to neurovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia. The main mechanism of neurovascular coupling dysfunction leading to the above diseases is cerebrovascular dysfunction or loss,which leads to serious damage to neuronal ischemia and affects its function. Therefore,this paper reviews the research status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up research. The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system diseases related to neurovascular coupling through the mechanism of neurovascular coupling.

Research progress on regulatory mechanism of long non-coding RNA CYTOR in human cancer / 中国药理学通报

Cancer is difficult to cure because of its heterogeneity, drug resistance and easy recurrence and metastasis. Revealing the molecular mechanism of cancer genesis and development, identifying new diagnostic markers and molecular therapeutic targets are undoubtedly effective strategies to solve the problems of early diagnosis, treatment and improvement of prognosis of cancer patients. More and more studies have shown that long non-coding RNA (IncRNA) is specifically expressed in human cancer and is a key regulator of cancer occurrence and development. Cytoskeleton regulator RNA (CYTOR) is a carcinogenic lncRNA found in recent years. CYTOR is highly expressed in many types of cancer and regulates the development of cancer through a variety of pathways, which may be an effective biomarker for early cancer diagnosis, molecular targeted therapy and prognosis assessment. This paper reviews the molecular regulatory mechanism and related biological characteristics of CYTOR in human cancer, in order to provide new scientific reference for clinical cancer diagnosis and treatment.

Role of lymphatic vessel function in atherosclerosis and research progress of drug intervention / 中国药理学通报

Atherosclerosis (AS) is a chronic vascular disease characterized by excessive accumulation of plaques formed by fat, cholesterol and inflammatory immune cells. Lymphatic vessels, as channels for the drainage of lipids, inflammatory substances and tissue fluids, are involved in multiple pathological processes such as lipid accumulation in the intima of AS arteries, vascular inflammation and intimal hyperplasia, and have become a new target for AS research. This article mainly discusses the role of lymphatic vessels in each pathological link of AS and related Chinese and western medicine interventions, aiming to provide feasible ideas for preventing and treating AS with Chinese and western medicines from the view of lymphatic vessels.

The Effects and Regulatory Mechanism of Targeting CXC Chemokine Receptor 1/2 Combined with Ara-C on the Malignant Biological Behaviors of U937 Cells of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate and analyze the effect of CXC chemokine receptor 1/2 (CXCR1/2) targeting inhibitor Reparixin combined with cytarabine (Ara-C) on the malignant biological behaviors of acute myeloid leukemia cells and its effect on the expression of the CXCR family, while exploring the accompanying molecular mechanism, providing scientific basis and reference for new molecular markers and targeted therapy for AML.@*METHODS@#Acute myeloid leukemia U937 cells were treated with different concentrations of Reparixin, Ara-C alone or in combination, and the cell morphology was observed under an inverted microscope; Wright-Giemsa staining was used to detect cell morphological changes; CCK-8 method was used to detect cell proliferation; the ability of cell invasion was detected by Transwell chamber method; the ability of colony formation was detected by colony formation assay; cell apoptosis was detected by Hoechst 33258 fluorescent staining and Annexin V/PI double-staining flow cytometry; monodansylcadaverine(MDC) staining was used to detect cell autophagy; the expression of apoptosis, autophagy and related signaling pathway proteins was detected by Western blot and the expression changes of CXCR family were detected by real-time quantitative polymerase chain reaction (qRT-PCR).@*RESULTS@#Reparixin could inhibit the proliferation, invasion, migration and clone formation ability of U937 cells. Compared with the single drug group, when U937 cells were intervened by Reparixin combined with Ara-C, the malignant biological behaviors such as proliferation, invasion and colony formation were significantly decreased, and the levels of apoptosis and autophagy were significantly increased (P<0.01). After Reparixin combined with Ara-C intervenes in U937 cells, it can up-regulate the expression of the pro-apoptotic protein Bax and significantly down-regulate the expression of the anti-apoptotic protein Bcl-2, and also hydrolyze and activate Caspase-3, thereby inducing cell apoptosis. Reparixin combined with Ara-C could up-regulate the expressions of LC3Ⅱ and Beclin-1 proteins in U937 cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P<0.01). MDC result showed that the green granules of vesicles increased significantly, and a large number of broken cells were seen (P<0.01). Reparixin combined with Ara-C can significantly inhibit the phosphorylation level of PI3K, AKT and NF-κB signaling molecule, inhibit the malignant biological behavior of cells by inhibiting the activation of PI3K/AKT/NF-κB pathway, and induce programmed cell death. Ara-C intervention in U937 cells had no effect on the expression of CXCR family (P>0.05). The expression of CXCR1, CXCR2, and CXCR4 mRNA could be down-regulated by Reparixin single-agent intervention in U937 cells (P<0.05), and the expression of CXCR2 was more significantly down-regulated than the control group and other CXCRs (P<0.01). When Reparixin and Ara-C intervened in combination, the down-regulated levels of CXCR1 and CXCR2 were more significant than those in the single-drug group (P<0.01), while the relative expressions of CXCR4 and CXCR7 mRNA had no significant difference compared with the single-drug group (P>0.05).@*CONCLUSION@#Reparixin combined with Ara-C can synergistically inhibit the malignant biological behaviors of U937 cells such as proliferation, invasion, migration and clone formation, and induce autophagy and apoptosis. The mechanism may be related to affecting the proteins expression of Bcl-2 family and down-regulating the proteins expression of CXCR family, while inhibiting the PI3K/AKT/NF-κB signaling pathway.

Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

In vivo delivery process and regulating mechanisms of lipid-based nanomedicines / 药学学报

Lipid-based nanocarrier is a classic drug delivery system with great biocompatibility and biodegradability. It can effectively reduce the toxicity of anti-tumor and anti-infective drugs in clinical practice. However, it has not yet met the clinical demand for enhanced therapeutic efficacy, and the clinical application is still very limited. The complex in vivo delivery process of lipid-based nanomedicine and the reciprocal interactions with body lead to unexpected changes in in vivo performance of nanomedicine and seriously hinder clinical translation. Therefore, the in-depth study of the relationships among intrinsic properties of lipid-based nanomedicine, the in vivo delivery process, and the regulatory mechanisms will not only provide guidance for the rational design of nanocarriers, but also promote the clinical translation and precision medicine of new lipid-based nanomedicine. In this review, we summarize the in vivo delivery process, regulating factors and intervention strategies for the in vivo delivery of lipid-based nanomedicine.

Progress in regulatory effects of thymic stromal lymphopoietin on immune cells / 中华微生物学和免疫学杂志

Thymic stromal lymphopoietin (TSLP), as a pleiotropic cell growth factor, not only participants in the processes of human skin fibrosis, epidermal proliferation and angiogenesis, but also plays a critical role in regulating a variety of immune cells in immune-related diseases (such as respiratory diseases and allergic diseases). TSLP regulates various innate immune cells (such as dendritic cells, mast cells, macrophages, eosinophils, basophils, natural killer T cells and innate lymphocytes) and adaptive immune cells (T lymphocytes and B lymphocytes) mainly through JAK/STAT, NF-κB and other signal pathways mediated by TSLP receptor. This paper summarized the progress in the regulatory roles of TSLP in the proliferation, differentiation and function of various immune cells.

Research progress of TCM in treating radiation enteritis based on intestinal microecology / 国际中医中药杂志

Patients with radioactive enteritis generally have certain intestinal microecological imbalance. Traditional Chinese Medicine (TCM) has showed good advantage in regulating intestinal microbial flora. In clinical practice, patients are treated based on syndrome differentiation of heat toxin damaging collaterals, cold-heat mixed syndrome, spleen deficiency and dampness stagnation, spleen and kidney yang deficiency, yin deficiency and body fluid deficiency. The Baitouweng Decoction, Wumei Pill, Sijunzi Decoction are the common prescriptions. TCM can promote the balance of intestinal microecology and treat digestive diseases such as radioactive enteritis, by improving the abundance of intestinal flora, inhibiting the level of inflammatory cytokines, and playing the role of probiotics and immune regulation.

Role and research progress of CYP46A1 in neurodegenerative diseases / 中国临床药理学与治疗学

Cytochrome P450 (CYP46A1) is a central neuro-specific metabolic enzyme that converts cholesterol into 24-hydroxycholesterol. This metabolic process is the main mechanism of cholesterol elimination in brain and is closely related to the occurrence and development of neurodegenerative diseases. This review focuses on the relationship between CYP46A1 and neurodegenerative diseases, from the aspects of regulatory mechanism of CYP46A1 enzyme, the relationship between CYP46A1 and cognitive dysfunction, epileptic encephalopathy, and CYP46A1 enzyme activity modifiers (inhibitors and agonists) to illustrate the pivotal role of CYP46A1 in the development and prevention of neurodegenerative diseases in hope of providing new target and direction for the research and development of new drugs.

Regulatory Mechanism of PD-L1 Expression in Primary Liver Cancer / 肿瘤防治研究

The application of immunotherapy has become a hot spot in tumor research currently. In particular, immune checkpoint inhibitors have played an important role in the treatment of advanced unresectable primary liver cancer. However, the efficacy of immune checkpoint inhibitors varies greatly in the treatment of different patients, which has aroused people's attention to the regulatory mechanism of PD-L1 in the immune escape of liver tumors. PD-L1 is regulated by multiple levels and multiple signaling pathways in liver cancer, including gene mutation, epigenetic mechanisms, transcriptional regulation, post-transcriptional regulation and post-translational modification. Studies have also found that the high expression of PD-L1 may be the main factor affecting the immunotherapy of primary liver cancer. Therefore, it can provide more evidence for immunotherapy and immune combination therapy strategies of primary liver cancer by clarifying the regulatory mechanism of PD-L1.

Pathogenesis, diagnosis, and management for sepsis: update progress and scientific problems / 中华危重病急救医学

Sepsis is caused by various pathogens and toxic factors, which can lead to multiple organ dysfunction. The underlying mechanism of sepsis appears to be complex, involving epigenetic reprogramming, metabolic failure, immune dysfunction, neuroendocrine system disorders, coagulation abnormalities, tissue or organ failure, and many other scientific issues. With our deep understanding of the host reaction and development of sepsis, it is of great significance to explore predicative markers and therapeutic targets according to the atypical characteristics of sepsis, thereby contributing to the reduction of morbidity and mortality of sepsis.

Mechanism of UGT2A3 differentially expression in the occurrence and early diagnosis of colorectal cancer / 国际生物医学工程杂志

Objective:To investigate the role and regulatory mechanism of UGT2A3 differential expression in colorectal carcinogenesis.Methods:Nine CRC datasets were downloaded from GEO database and TCGA. R language was used to analyze the differential expression of UGT2A3 in cancer and normal tissues. According to the expression level of UGT2A3 in TCGA, the top 20 samples with the highest expression and the lowest expression were selected from normal tissues and CRC tissues, respectively. The abundance of immune cells and immune enrichment score were compared, the differentially expressed genes and differentially expressed miRNAs were screened, and the pathway enrichment analysis of differentially expressed genes was performed.Results:UGT2A3 was down regulated in all 9 CRC datasets. In all sample types, compared with the UGT2A3 high expression group, the UGT2A3 low expression group had significantly higher ImmuneScore, EstimateScoreandStromalScore, and had higher abundance of immune cells (except memory B cells). In normal tissues, the differential expression of UGT2A3 mainly affects cancer-related pathways, while in tumor tissues, it mainly affects metabolic pathways. miR-194-2, miR-224 and miR-551b were differentially expressed in all groups, which were considered as potential UGT2A3 upstream regulatory genes in CRC.Conclusions:UGT2A3, miR-194-2, miR-224 and miR-551b can be used as potential biomarkers for the diagnosis of CRC.

Mechanistic Studies of Post-translational Modifications on the Proteasome / 中国生物化学与分子生物学报

The proteasome is the main complex for specific protein degradation in eukaryotic cells, which plays a key role in protein quality control and cell homeostasis maintenance. It is found that abnormal content or function of the proteasome can lead to many human serious diseases such as cancer and neurodegenerative disorders, and several targeted drugs have been developed for the regulation of proteasome activity. Therefore, it is of great academic value and clinical significance to strengthen the research on the precise regulation mechanism of proteasome activity. The content, assembly and activity of the proteasome are regulated rigorously by multiple levels. In this paper, we summarize the composition subunits, structural features, transcriptional regulation and assembly mechanism of proteasome, and focus on the mechanistic regulation and biological significance of post-translational modifications such as phosphorylation, ubiquitination and acetylation on proteasome, which might be helpful to reveal the regulation mechanism of proteasome in the near future.

The Regulatory Mechanism and Role of CircRNA in Tumors / 中国生物化学与分子生物学报

Circular RNAs (circRNAs) are a class of non-coding RNAs that form closed rings in structure. They contain a high content in eukaryotic transcripts, and are characterized by richness, stability, high conservatism and tissue specificity. In recent years, it has been gradually revealed that circRNA can bind to some miRNAs or proteins and participate in the regulatory mechanisms of biogenesis and molecular functions, including the regulation of miRNAs molecular sponge, protein translation, gene transcription and RNA splicing. With the application of high-throughput sequencing and bioinformatics, circRNA has gradually become a new research hotspot in the field of non-coding RNA due to its special properties. The latest research evidence shows that circRNA plays a key role in the occurrence and development of tumors, and is inextricably linked with cell proliferation, apoptosis, angiogenesis, and metastasis, indicating that targeting circRNA will be attractive treatment strategies and potential biomarkers. In this paper, the characteristics and mechanism of circRNA were briefly described, the mechanism of action and regulation of circRNAs in human tumors were summarized, and the strategies and development prospects of circRNA in tumor research were further discussed. In sum, circRNA plays an important role in early diagnosis, precise treatment and prognosis prediction of tumors.

Advances in the biosynthesis of natamycin and its regulatory mechanisms / 生物工程学报

Natamycin is a polyene macrolide antibiotics with strong and broad spectrum antifungal activity. It not only effectively inhibits the growth and reproduction of fungi, but also prevents the formation of some mycotoxins. Consequently, it has been approved for use as an antifungal food preservative in most countries, and is also widely used in agriculture and healthcare. Streptomyces natalensis and Streptomyces chatanoogensis are the main producers of natamycin. This review summarizes the biosynthesis and regulatory mechanism of natamycin, as well as the strategies for improving natamycin production. Moreover, the future perspectives on natamycin research are discussed.

Natural medicinal ingredients induce tumor ferroptosis and related mechanisms / 浙江大学学报·医学版

Ferroptosis is an iron-dependent programmed cell death characterized by reactive oxygen species-induced lipid peroxide accumulation, which is different from cell apoptosis, pyroptosis, necrosis or autophagy. Ferroptosis plays an important role in the regulation of tumorigenesis and tumor development. Recent studies have shown that natural medicinal ingredients can induce ferroptosis in tumor cells through glutathione (GSH)/glutathione peroxidase 4 (GPx4) pathway, iron metabolism, lipid metabolism or other mechanisms. It has been reported that more than 30 natural medicinal ingredients can induce ferroptosis in tumor cells with multiple pathways and multiple targets. This article reviews the current research progress on the antitumor effects of natural medicinal ingredients through inducing cell ferroptosis.

Research Advance on the Factors Influencing / 中国医学科学院学报

The biofilm formation is a dynamic process of bacterial growth,and the extracellular components can encase these microorganisms,making them more resistant to antibiotics and host immune attack.The formation of antibiotic-resistant bacterial biofilms will be a major challenge for the treatment and control of clinical infections.

Advances in Research on Regulatory Mechanism of Abnormal MiRNA Expression in Digestive System Diseases / 胃肠病学

MicroRNA (miRNA) is a non-coding single strand endogenous RNA, with a length of 20-25 bp. It regulates the transcription and translation of target mRNA by binding to its 3' untranslated regions (UTR). Abnormal expression of miRNA plays an important role in the occurrence and development of digestive system diseases. Clarifying the regulatory mechanism of miRNA will be of great help for early diagnosis and treatment of diseases. This article reviewed the advances in research on regulatory mechanism of abnormal miRNA expression in digestive system diseases.

Regulation of plant MYB transcription factors in anther development / 生物工程学报

MYB transcription factor is one of the largest transcription families and involved in plant growth and development, stress response, product metabolism and other processes. It regulates the development of plant flowers, especially anther development, a key role in the reproduction of plant progeny. Here, we discuss the regulatory effects of MYB transcription factors on the development of anther, including tapetum development, anther dehiscence, pollen development, carbohydrates and hormone pathways. We provide a reference for the further study of the regulation mechanism and network of plant anther development.