Effect of Xiangsha Liu Junzitang Combined with Phlegm-removing and Detoxifying Traditional Chinese Medicine on Immune Escape in Lewis Lung Cancer Mice / 中国实验方剂学杂志

ObjectiveTo study the effect and mechanism of Xiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine on immune escape in Lewis lung cancer mice. MethodA total of 60 specific-pathogen-free （SPF）-grade C57BL/6J male mice were injected subcutaneously with 0.2 mL of Lewis cell suspension （containing 2×106 cells·mL-1） in the right mid-axillary line. After 7 days， the mice that had been successfully modeled were randomly divided into six groups： the model group， the cisplatin group， the Xiangsha Liu Junzitang low-， medium-， and high-dose groups， and the combined group， with 10 mice in each group. The Xiangsha Liu Junzitang low-， medium- and high-dose groups were gavaged with 17.88， 35.75， 71.50 g·kg-1 Xiangsha Liu Junzitang solution once a day， respectively， and the dosage of cisplatin intraperitoneally injected into the mice was converted to 5 mg·kg-1 twice a week， and the tumour volumes of each group were measured every two days. The intervention lasted for 14 consecutive days. At the end of treatment， the tumour mass of mice in each group was weighed and the tumour inhibition rate was calculated. The morphological characteristics of tumours in each group were observed by hematoxylin-eosin （HE） staining. Fluorescent quantitative real-time polymerase chain reaction （Real-time PCR） assay was used to detect messenger ribonucleic acid （mRNA） contents of the natural killer group 2 member D （NKG2D） receptor， ribonucleic acid export-1 （RAE-1）， and γ interferon （IFN-γ） in the tumour tissues of each group. NKG2D， RAE-1， and IFN-γ mRNA in tumour tissues of each group. Immunohistochemistry （IHC） and Western blot were applied to detect the expressions of RAE-1， NKG2D， and IFN-γ in tumour tissues of each group， and Western blot was used to detect the expressions of interleukin-6 （IL-6）， Janus kinase 2 （JAK2）， p-JAK2， signal transducer and activator of transcription 3 （STAT3）， and p-STAT3 in tumour tissues of each group， as well as the protein levels of NKG2D， and RAE-1 in spleen tissues of each group. ResultCompared with that in the model group， the tumour mass decreased in all dose groups of Xiangsha Liu Junzitang， with no statistically significant difference. The tumour volume was reduced （P<0.05， P <0.01）. The pathological morphology was improved. The mRNA contents of NKG2D， RAE-1 and IFN-γ were increased in the medium-dose group （P<0.05， P<0.01）， and the protein expressions of NKG2D， RAE-1， and IFN-γ in tumour tissues were elevated （P<0.05， P<0.01）， and p-JAK2 and p-STAT3 protein expressions were decreased （P<0.05， P<0.01）. In spleen tissues， the protein expressions of NKG2D and RAE-1 in all dose groups of Xiangsha Liu Junzitang were significantly elevated （P<0.01）. Compared with those in the cisplatin group， NKG2D， RAE-1 and IFN-γ mRNA contents were elevated in the middle-dose group of Xiangsha Liu Junzitang， and the difference was not statistically significant. IHC showed that the protein expressions of NKG2D and IFN-γ in the combined group were significantly elevated （P<0.01）， and Western blot results showed that the protein expressions of RAE-1， NKG2D and IFN-γ were elevated （P<0.05， P<0.01）. p-JAK2 and p-STAT3 protein expressions were decreased in the combined group （P<0.05， P<0.01）. NKG2D and RAE-1 protein expressions were significantly increased in spleen tissues of the medium-dose groups and the combined group （P<0.01）. ConclusionXiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine can inhibit the growth of tumours in Lewis lung cancer mice by up-regulating the expressions of RAE-1/NKG2D， promoting the activation of NK cells， and inhibiting immune escape， the mechanism of which may be related to down-regulation of the JAK2/STAT3 pathway.

pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Food capture and escape behavior of Leposternon microcephalum Wagler, 1824 (Squamata: Amphisbaenia)

Abstract Amphisbaenians are fossorial reptiles that have a cylindrical and elongated body covered with scales arranged in rings, and are all apodal, except for the three species of the genus Bipes. The amphisbaenian diet consists of a variety of invertebrates and small vertebrates. As these animals live underground, many aspects of their natural history are difficult to study. Most feeding studies of amphisbaenians have focused on the composition of the diet and feeding ecology, and the data available on feeding behavior are based on precursory observations. The present study describes the food capture behavior of Leposternon microcephalum Wagler, 1824 in captivity. In this experiment we used non-live bait (moist cat food), which was placed near a burrow opening, on the surface of the substrate. Three animals were monitored visually and filmed using cellphone cameras deployed at fixed points, to capture images from the dorsal and lateral perspectives of the study subjects. Two principal types of behavior were observed: the capture of food and defense mechanisms. The strategies used to capture the food were similar to those observed in other fossorial species. Although the backward movement has already been observed and described, we were able to record this movement being used as an escape strategy. These findings enrich our knowledge on different aspects of the natural history of the amphisbaenians.

Resumo Anfisbênas são répteis fossoriais caracterizadas por apresentarem corpo cilíndrico e alongado coberto por escamas dispostas exclusivamente em anéis e todas são ápodas, com exceção das três espécies do gênero Bipes. Sua dieta consiste em uma variedade de invertebrados e pequenos vertebrados. Por viverem no subsolo, muitos aspectos de sua história natural são difíceis de observar. A maioria dos estudos sobre alimentação em anfisbenas concentra-se na dieta e na ecologia alimentar, enquanto as informações sobre o comportamento alimentar se baseiam em observações preliminares. O objetivo deste artigo foi descrever o comportamento de captura de alimentos exibido por Leposternon microcephalum Wagler, 1824, fora da galeria, em cativeiro. Para o experimento foi utilizada uma isca não viva, ração úmida de gato, que foi oferecida e posicionada próxima a uma das aberturas da galeria, na superfície do solo. Um total de três animais foi analisadopor meio de observações visuais e registros de câmeras de telefones celulares posicionadas em um ponto fixo, captando imagens de suas vistas dorsal e lateral. Foram detectados dois tipos principais de comportamento: captura de recursos alimentares e mecanismo de defesa. As estratégias utilizadas para capturar o recurso alimentar foram semelhantes às observadas em outras espécies fossoriais. Embora o movimento de marcha-à-ré tenha sido observado e descrito, o registramos sendo usado como uma estratégia de fuga. Esses resultados contribuem para enriquecer o conhecimento sobre diferentes aspectos da história natural dos Amphisbaenia.

Programmed cell death induced by Klebsiella pneumoniae infection / 中华微生物学和免疫学杂志

Klebsiella pneumoniae can cause a variety of infectious diseases, especially in immunocompromised population. The emergence of multidrug-resistant hypervirulent Klebsiella pneumoniae has greatly limited the choice of treatment for Klebsiella pneumoniae infection, and the exploration of new treatment strategies is imminent. In the process of infection, there is a complex interaction between the programmed cell death of host cells and the invasion of Klebsiella pneumoniae. This paper mainly reviewed the research progress in several mechanisms of programmed cell death such as pyroptosis, apoptosis, necroptosis and autophagy caused by Klebsiella pneumoniae.

Research progress in site mutations of SARS-CoV-2 Omicron variants / 中华微生物学和免疫学杂志

SARS-CoV-2 Omicron variant (B.1.1.529) was first discovered in South Africa in November 2021 and has since become a mainstream strain worldwide. Omicron variant was defined as the fifth "variant of concern (VOC)" by World Health Organization on November 26, 2021. This paper illustrates the mutation trends of Omicron variants in terms of SARS-CoV-2 genome and protein structure as well as nucleic acid site mutations and amino acid site mutations, describes the features of Omicron mutation sites in terms of lineage comparison among the VOCs and Omicron sublineages, and further highlights the influences of Omicron site mutations from the aspects of immune escape, virulence and transmission ability. Moreover, this paper also reviews the development of direct antiviral agents, antibodies and vaccines, aiming to provide reference for further investigation.

Expression of TPX2 in kidney renal clear cell carcinoma and its clinical significance / 国际肿瘤学杂志

Objective:To analyze the expression of targeting protein for Xklp2 (TPX2) in kidney renal clear cell carcinoma (KIRC) and its clinical significance.Methods:The postoperative tissue samples of 54 patients with KIRC admitted to the Department of Urology, the First Affiliated Hospital of Bengbu Medical College from July 2017 to June 2019 were collected. Immunohistochemistry was used to detect the protein expression of TPX2 in renal carcinoma and paracancerous tissues. The difference of TPX2 mRNA expression between KIRC tissues and normal tissues was analyzed by using the TIMER database, which verified the immunohistochemical results. The UALCAN database and the Kaplan-Meier plotter database were used to analyze the relationship between TPX2 mRNA expression and clinical stage, molecular subtypes, lymph node metastasis, and prognosis of patients with KIRC. The protein interaction network was constructed by STRING database to obtain TPX2-related proteins, and the genes corresponding to the related proteins were enriched for the KEGG pathway. The relationship between TPX2 expression and immune cell infiltration and the immune checkpoint was studied by using the TIMER database.Results:Immunohistochemical results showed that the positive expression rate of TPX2 protein was 48.15% (26/54) in cancer tissues, which was higher than that in paracancerous tissues (20.37%, 11/54) ( χ2=9.25, P=0.002). The results of bioinformatics analysis showed that TPX2 mRNA expression was significantly up-regulated in KIRC [cancer tissue: 1.89 (1.49, 2.42), normal tissue: 0.35 (0.24, 0.57), U=2 297.00, P<0.001]. The expression of TPX2 mRNA was related to the clinical stage ( χ2=34.36, P<0.001), molecular subtypes ( χ2=30.15, P<0.001), and lymph node metastasis status ( χ2=27.21, P<0.001) of KIRC patients. The 5-year survival rate (53.80%) in patients with high TPX2 expression was lower than that in patients with low TPX2 expression (74.40%, χ2=18.87, P<0.001). STRING database protein interaction network construction obtained 20 TPX2-related proteins, and the genes corresponding to the related proteins were enriched in the cell cycle. The expression of TPX2 was positively correlated with B cells ( r=0.30, P<0.001), CD8 + T cells ( r=0.23, P<0.001), CD4 + T cells ( r=0.18, P<0.001), macrophages ( r=0.20, P<0.001), neutrophils ( r=0.31, P<0.001), dendritic cells ( r=0.39, P<0.001) infiltration and most of its biomarkers (all P<0.05). It was positively correlated with immune checkpoint PD-1 ( r=0.31, P<0.001) and CTLA-4 ( r=0.27, P<0.001), but not correlated with PD-L1 ( r=0.07, P=0.146) . Conclusion:TPX2 is highly expressed in KIRC and is closely associated with poor prognosis. It is expected to be a new therapeutic target for KIRC.

Recent Insights into Mechanisms Governing Breast Cancer Dormancy / 肿瘤防治研究

Tumor dormancy refers to the status of disseminated cancer cells that remain in a viable yet not proliferating state for a prolonged period. Dormant cells will eventually "re-awake" resume their proliferation, and produce overt metastasis. The dormancy mechanism of cancer has attracted attention because of the close relationship between late recurrence and tumor dormancy. In this review, we illustrate the latest discoveries on the biological underpinnings of breast cancer dormancy and offer clinicians an overview of dormancy in breast cancer to guide them in the basic understanding of the complexity that underlies this process.

Role of HBV DNA polymerase in mediating the immune escape of tumor cells in HBV-related hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo determine whether HBV DNA polymerase is associated with T-cell failure and thus mediates the immune escape of HBV-related hepatocellular carcinoma （HCC） tumor cells， and to investigate the specific molecular mechanisms. MethodsLiver cancer cell lines Huh7 and HepG2 stably transfected with HBV DNA polymerase expression plasmid with Flag （Flag-HBV-P） and intercellular adhesion molecule-1 （ICAM1） were co-cultured with Jurkat cells， and MTT assay， qRT-PCR， and ELISA were used to measure Jurkat cell proliferation， activation （CD69 expression）， and secretion of the cytokine IFN-γ. RNA-seq was used to screen for differentially expressed immune-associated molecules between stably transfected cell lines and control cells， and mRNA half-life and protein half-life assays were used to determine the specific levels of the immune-associated molecules that were affected by HBV DNA polymerase. Related websites were used to predict the transcription factors that may bind to the promoter region of this immune-associated molecule， Western blot was used to verify the effect of transcription factors on the immune-associated molecule， and rescue experiment was used to determine whether HBV DNA polymerase affects the expression level of the immune-associated molecule through this transcription factor. The independent-samples t test was used for comparison between two groups. ResultsThe experimental group had significant reductions in Jurkat cell proliferation， activation， and cytokine secretion compared with the control group （all P<0.01）. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had significant reductions in the mRNA and protein expression levels of ICAM1 （all P<0.01）. Website prediction identified the ICAM1 promoter and preliminarily highlighted NFKB1， RELA， and STAT3. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had a significant reduction in the protein expression level of p65 （all P<0.01）. After p65 overexpression， there was a significant increase in the protein expression level of ICAM1， and after the expression of p65 was reduced， there was a significant reduction in the protein expression level of ICAM1 （all P<0.01）. In the rescue experiment， there was no significant difference in the protein expression level of ICAM1 between the control group and the experimental group after p65 overexpression （all P>0.05）. After the overexpression of ICAM1， there were no significant differences in the proliferation， activation， and cytokine secretion of Jurkat cells between the control group and the experimental group （Huh7 and HepG2 cell lines） （all P>0.05）. ConclusionHBV DNA polymerase downregulates the level of ICAM1 to mediate HCC immune escape by inhibiting the expression of p65 in NF-κB.

Helicobacter pylori infection influences the efficacy of immunotherapies for gastric cancer / 中国临床药理学与治疗学

Gastric cancer is a common malignant tumor of digestive tract, and its incidence rate and mortality are very high in China. In recent years, immunotherapy represented by immunocheckpoint inhibitors has brought new therapeutic hope for patients with inoperable advanced gastric cancer. Helicobacter pylori infection is closely related to the occurrence and development of gastric cancer. In this review, we summarized the current status of immunotherapy for gastric cancer, the latest research progress on the impact of Helicobacter pylori infection on gastric mucosal immunity and tumor immunotherapy, and summarized the current challenges and future research directions, with a view to providing new ideas for clinical therapy and scientific research.

Lipid carriers for mRNA delivery

Messenger RNA (mRNA) is the template for protein biosynthesis and is emerging as an essential active molecule to combat various diseases, including viral infection and cancer. Especially, mRNA-based vaccines, as a new type of vaccine, have played a leading role in fighting against the current global pandemic of COVID-19. However, the inherent drawbacks, including large size, negative charge, and instability, hinder its use as a therapeutic agent. Lipid carriers are distinguishable and promising vehicles for mRNA delivery, owning the capacity to encapsulate and deliver negatively charged drugs to the targeted tissues and release cargoes at the desired time. Here, we first summarized the structure and properties of different lipid carriers, such as liposomes, liposome-like nanoparticles, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanoemulsions, exosomes and lipoprotein particles, and their applications in delivering mRNA. Then, the development of lipid-based formulations as vaccine delivery systems was discussed and highlighted. Recent advancements in the mRNA vaccine of COVID-19 were emphasized. Finally, we described our future vision and perspectives in this field.

Ginsenoside Rg_3 based liposomes target delivery of dihydroartemisinin and paclitaxel for treatment of triple-negative breast cancer / 中国中药杂志

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.

Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

A rationally designed cancer vaccine based on NIR-II fluorescence image-guided light-triggered remote control of antigen cross-presentation and autophagy

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.

The impact of lipids on the cancer-immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy

Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.

Neural Circuit Mechanisms Involved in Animals' Detection of and Response to Visual Threats / 神经科学通报·英文版

Evading or escaping from predators is one of the most crucial issues for survival across the animal kingdom. The timely detection of predators and the initiation of appropriate fight-or-flight responses are innate capabilities of the nervous system. Here we review recent progress in our understanding of innate visually-triggered defensive behaviors and the underlying neural circuit mechanisms, and a comparison among vinegar flies, zebrafish, and mice is included. This overview covers the anatomical and functional aspects of the neural circuits involved in this process, including visual threat processing and identification, the selection of appropriate behavioral responses, and the initiation of these innate defensive behaviors. The emphasis of this review is on the early stages of this pathway, namely, threat identification from complex visual inputs and how behavioral choices are influenced by differences in visual threats. We also briefly cover how the innate defensive response is processed centrally. Based on these summaries, we discuss coding strategies for visual threats and propose a common prototypical pathway for rapid innate defensive responses.

Research progress of cell membrane-coated biomimetic nanoparticle delivery systems for the treatment of lung diseases / 药学学报

Lung is susceptible to external disturbance, resulting in a variety of acute and chronic lung diseases. Functionalized nanoparticles as carriers can carry drugs through multiple biological barriers of lung into lung lesions, but there are some problems such as poor targeting and low therapeutic efficiency. As a drug carrier, membrane-coated biomimetic nanoparticles have the characteristics of immune system escape, active targeting, inflammatory chemotaxis and crossing physiological barriers due to the retention of the characteristics of the source cells. Therefore, it has been widely used in the treatment of lung diseases in recent years. In this review, the application of membrane-coated biomimetic nanoparticles in the treatment of lung diseases in the recent years was summarized and classified. Cell membrane sources include erythrocyte membrane, platelet membrane, macrophage membrane, neutrophil membrane, lung epithelial membrane, lung surfactant, endothelial membrane, cancer cell membrane, bacterial membrane, hybrid membrane and so on. The purpose of this review is to provide a new idea for treating lung diseases with membrane-coated biomimetic nanoparticles.

Immune escape of hepatic echinococcosis based on the PD-1/PD-L1 signaling pathway / 临床肝胆病杂志

PD-1 and PD-L1 together constitute the stimulus signaling pathway of adaptive immune response, which has been widely used in the research on the mechanism of tumor immune escape and tumor therapy. At the same time, its signaling pathway has been proved to be closely associated with the immune escape of hepatic echinococcosis. This article reviews the chemical structures of PD-1 and PD-L1, the mechanism of the PD-1/PD-L1 signaling pathway, and the role of the PD-1/PD-L1 signaling pathway in immune escape of hepatic echinococcosis, i.e., the PD-1/PD-L1 signaling pathway is involved in immune escape of hepatic echinococcosis under three theories, so as to explore the immune escape of hepatic echinococcosis from a new perspective and provide a basis and ideas for the diagnosis and treatment of hepatic echinococcosis.

Effect of Lactate on Immune Cells in Tumor Microenvironment and Progress of Related Target Therapy / 肿瘤防治研究

The relationship between tumor metabolism and immunity is complex and diverse. To date, the role of tumor-specific metabolic reprogramming in shaping the specific tumor microenvironment in tumor immunotherapy remains unclear. Lactic acid is the main product of glycolysis, and the aerobic glycolysis of tumor cells causes lactic acid to accumulate in the microenvironment. Recent studies have shown that the accumulation of lactic acid in the tumor microenvironment hinders anti-tumor immunity, especially affects the function, differentiation, and metabolism of immune cells, and participates in tumor immune escape, thus promoting tumor. This article reviews the effects of lactate accumulation in the tumor microenvironment on dendritic cells, T cells, NK cells, tumor-associated macrophages, and myeloid-derived suppressor cells. Targeted intervention of lactate production and efflux by tumor cells is expected to become a new strategy for tumor immunotherapy.

Effects of lncRNA-UCA1 targeting miR-204-5p on the proliferation, migration, apoptosis and immune escape of endometrial carcinoma cells / 中华肿瘤杂志

Objective: To investigate the effect of long non-coding RNA urothelial carcinoma-associated 1 (UCA1) gene on the proliferation, migration, apoptosis and immune escape of endometrial cancer cells and its molecular mechanism. Methods: Endometrial cancer tissues and adjacent normal tissues of patients with endometrioid adenocarcinoma who underwent total or partial hysterectomy in Henan Provincial People's Hospital from 2017 to 2019 were collected. The expressions of UCA1 and miR-204-5p were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the cell proliferation, migration and apoptosis were detected by cell counting kit 8 (CCK8) method, Transwell method, flow cytometry, and dual-luciferase reporter assay was used to explore the target relationship between UCA1 and miR-204-5p. HEC-1A-sh-NC or HEC-1A-sh-UCA1 cells were co-cultured with peripheral blood mononuclear cells (PBMC) or cytokine-induced killer cells in vitro to explore the role of UCA1 in immune escape. Results: The expression level of UCA1 in endometrial cancer tissue (17.08±0.84) was higher than that in adjacent normal endometrial tissue (3.00±0.37), and the expression level of miR-204-5p (0.98±0.16) was lower than that in adjacent normal endometrial tissue (2.00±0.20, P<0.05). Pearson correlation analysis showed that the expression of miR-204-5p was negatively correlated with the expression of UCA1 (r=-0.330, P=0.030). The expressions of UCA1 and miR-204-5p were associated with the International Federation of Gynecology and Obstetrics stage of endometrial cancer, lymph node metastasis and vascular invasion (P<0.05). The relative ratio of absorbance (0.58±0.11) and the number of cell migration [(199.68±18.44)] in the sh-UCA1 group were lower than those in the sh-NC group (1.24±0.17 and 374.76±24.83), respectively. The apoptosis rate of sh-UCA1 group [(28.64±7.80)%] was higher than that of sh-NC group [(14.27±4.38)%, P<0.05]. After different ratios of effector cells and target cells were cultured, the cell survival rate of HEC-1A-sh-UCA1 group was lower than that of HEC-1A-sh-NC group, and the difference was statistically significant (P<0.05). UCA1 had a binding site for miR-204-5p. The relative ratio of absorbance (1.74±0.08) and the number of cell migration (426.00±18.00) cells in the UCA1+ anti-miR-204-5p group were higher than those in the control group [1.00±0.03 and (284.00±8.00) cells, respectively]. The apoptosis rate of UCA1+ anti-miR-204-5p group [(5.42±0.93)%] was lower than that of control group [(14.82±1.48)%, P<0.05]. HEC-1A-sh-UCA1 cells could induce higher interferon gamma (IFN-γ) expression when co-cultured with PBMC, and the levels of IFN-γ expression in PHA group and PHA+ pre-miR-204-5p group cells were 2.42±0.49 and 1.88±0.26, which were higher than that in the PHA+ pre-NC group (0.85±0.10, P<0.05). When co-cultured with cytokine-induced killer cells (different ratios) in vitro, the HEC-1A-sh-UCA1 group and the HEC-1A-pre-miR-204-5p group had lower survival rates than that in the HEC-1A-pre-miR-204-5p group. In the HEC-1A-pre-NC group, the differences were statistically significant (P<0.05). Conclusion: UCA1/miR-204-5p may play an important role in human endometrial cancer.