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.

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.

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.

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.

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.

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.

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.

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.

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.

Function of vascular endothelial cells in retinal budding angiogenesis and its regulatory mechanism / 国际眼科杂志(Guoji Yanke Zazhi)

@#In the progress of retinal angiogenesis, sprouting angiogenesis plays an important role in retinal normal development and neovascular diseases. The structural and functional integrities of vascular endothelial cells are essential condition of sprouting angiogenesis. Vascular endothelial cells possess various subtypes, each of which plays a different role in sprouting angiogenesis. Many mechanisms participate in the regulation of endothelial cells under physiological and pathological conditions, such as biological signaling pathway, metabolism, immune inflammation and non-coding RNA. In this review, we provided a brief overview of the role and the related regulatory mechanisms of vascular endothelial cells in retinal sprouting angiogenesis.

Research progress of receptor protein FUNDC1 in mitophagy / 医学研究生学报

Mitochondria, which play an important role in cell metabolism, stress response and cell death, are the key organelles that regulate the energy balance of cells. Under the influence of internal and external environment, damaged or senescent mitochondria pose a serious threat to cell survival. Mitophagy refers to the selective elimination of dysfunctional mitochondria to maintain the homeostasis of the intracellular environment. FUN14 domain containing 1 (FUNDC1) is a newly discovered mitophagy receptor protein, which plays an important regulatory role in mediating mitophagy. This paper mainly reviews the recent research progress of FUNDC1 regulation mechanism and its pathophysiological significance in mitophagy.

The roles of m6A in cancer biology and its targeted therapy / 药学学报

N6-methyladenosine (m6A) modification is one of the most common modifications of eukaryotic mRNA, and has become a hotspot in the field of life sciences in recent years. m6A modification is dynamically reversible in mammalian cells and regulated by m6A methyltransferase (writers), demethylase (erasers), and "reader" proteins. m6A can regulate various biological processes of mRNA such as RNA splicing, nuclear export, protein translation and degradation. Recent studies indicated that m6A is important for the initiation and development of cancer. The present review summarized biological functions of m6A on mRNA and discussed its roles in cell proliferation, migration, invasion, cell mentalism, and angiogenesis. Further, the m6A can regulate the development of various cancers including acute myelocytic leukemia (AML), breast, liver and colorectal cancer. Nowadays, the inhibitors of m6A related enzymes including fat-mass and obesity-associated protein and AlkB homolog 5 are being developed. We further discussed the potential values of m6A and its related targets on cancer therapy and treatment.

The roles of sphingosine-1-phosphate and its receptor in Mycobacterium tuberculosis infection and novel antibiotics discovery / 药学学报

Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tuberculosis) infection remains a major public health problem of global concern, largely due to antibiotics resistance, persistence and immune evasion. Sphingolipid bioactive molecules are involved in several important pathophysiological processes. Sphingosine-1-phosphate is a key product of sphingolipid metabolism, and can play a role in two manners: autocrine and/or paracrine. Sphingosine-1-phosphate regulates T cells and a variety of antigen-presenting cells during M. tuberculosis infection, promotes antigen processing and expression in monocytes, is involved in the maturation of phagolysosome, regulates Ca2+ homeostasis, participates in the autophagy of macrophages, inhibits the survival and proliferation of M. tuberculosis within host cells, and effectively reduces the necrosis of the mouse lungs infected by M. tuberculosis. Injection of 20 nmol per mouse sphingosine-1-phosphate inhibited up to 47% of mycobacterial growth in the lung and spleen of mice infected by M. tuberculosis. In this paper, sphingosine-1-phosphate, its receptors and regulatory network were reviewed, and the specific mechanism of sphingosine-1-phosphate inhibiting the survival of M. tuberculosis-infected host cells was elaborated. This will provide novel insights into the new targets for tuberculosis prevention and treatment.

Progress in surfactant protein D-involved immune inflammatory responses / 中华微生物学和免疫学杂志

Surfactant protein D ( SP-D) is an important component of the surfactant family and ex-pressed in lung as well as many other organs. SP-D is a natural immune protein, which plays an important role in immune defense in lung tissues and in the regulation of inflammatory responses. Moreover, it also participates in immune inflammatory responses in other organs. This paper reviewed the function of SP-D in the regulation of immune inflammatory responses and its regulatory mechanisms in common diseases, and summarized the prospect of SP-D in disease treatment.

Non aromatic hydrocarbon receptor dependent regulatory mechanism of cytochrome P4501A1 and its role in infection and inflammation / 中华危重病急救医学

Infectious and inflammatory diseases are important diseases threatening human health. Without timely control, a series of complications will occur in patients, such as sepsis, inflammatory factor storm, and even lead to death. It has been found that cytochrome P4501A1 (CYP1A1) plays a key role in the development of infectious and inflammatory diseases through aromatic hydrocarbon receptor (AhR) dependent and non-dependent pathways in different cells and organs induced by different substances. The non AhR dependent regulatory mechanism of CYP1A1 and the different roles of CYP1A1 in infection and inflammation is reviewed in order to provide reference for further research on the relationship between CYP1A1 and infection and inflammation.

Mechanism of immune regulatory dysfunction in surgical sepsis / 医学研究生学报

Surgical sepsis induced by major trauma, burns and hemorrhage remains a main cause of death of the patients in intensive care units, and may result in both the widespread activation and dysfunction of the innate and adaptive responses in the host immune system. A large amount of information concerning the subsets of innate and adaptive immune cells in sepsis has implicated that these cells, including neutrophils, macrophages, dendritic cells, T lymphocytes, regulatory T cells, and natural killer cells, have significant effects on immunoreactivity during acute insults or sepsis through modulating multiple receptor expressions or cytokine release, in turn contributing to the development and outcome of sepsis. Therefore, a deeper insight into the mechanism of immune regulatory dysfunction in surgical sepsis is of great significance in helping assess the prognosis of sepsis and guide the treatment of its complications.

Research Progress of the Role of EMT in EGFR-TKIs Resistance of Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer is the one of the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC) makes up about 80%. Nowadays, molecular targeted therapy has been the first-line treatment for NSCLC. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are increasingly used in the clinical treatment, but the EGFR-TKIs acquired resistance becomes the bottleneck of continuation of EGFR-TKIs therapy. Epithelial-mesenchymal transition (EMT) is a biological phenomenon in which epithelial cells are transformed into mesenchymal cells. EMT promoted metastasis, invasion of lung cancer and conferred characteristic of stem cell on cancer cells. Meanwhile, EMT is one of an important cause of EGFR-TKIs resistance in NSCLC. The recent studies have found that resistant cells restored the sensitivity to EGFR-TKIs by reversing EMT which suggested that the target of EMT may contribute to inhibit or even reverse the resistance of EGFR-TKIs. Here we make a review about research progress of EMT in EGFR-TKIs resistance in NSCLC.
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Long non-coding RNAs in prostate cancer: An update / 中华男科学杂志

In the human genome, there is a group of RNAs, called long non-coding RNA (lncRNA) with do not have the function of encoding proteins and whose transcript length is greater than 200 nucleotides. The disorders of lncRNAs are often involved in the occurrence and progression of malignant tumors. A large number of studies have indicated the aberrant expression of lncRNAs in prostate cancer (PCa) can regulate gene expressions at epigenetic, transcriptional and post-transcriptional levels and cause changes in the biological behaviors of PCa cells. Some lncRNAs have been shown to be closely related to the castration resistance of PCa. In recent years, a variety of lncRNAs have been detected in the PCa tissue, prostatic fluid, serum, and urine, and somehow influenced radiotherapy and chemotherapy of tumors. The expressions of some lncRNAs are also associated with disease prognosis. Thus, lncRNAs are expected to become new diagnostic markers and a therapeutic target for PCa. This review focuses on the roles and action modes and mechanisms of some lncRNAs as well as their potential value of clinical application in the diagnosis, treatment and prognosis of PCa.