Multi-field-driven optomechanical entanglement.

Cavity optomechanical (COM) entanglement, playing an essential role in building quantum networks and enhancing quantum sensors, is usually weak and easily destroyed by noises. As feasible and effective ways to overcome this obstacle, optical or mechanical parametric modulations have been used to improve the quality of quantum squeezing or entanglement in various COM systems. However, the possibility of combining these powerful means to enhance COM entanglement has yet to be explored. Here, we fill this gap by studying a COM system containing an intra-cavity optical parametric amplifier (OPA), driven optically and mechanically. By tuning the relative strength and the frequency mismatch of optical and mechanical driving fields, we find that constructive interference can emerge and significantly improve the strength of COM entanglement and its robustness to thermal noises. This work sheds what we believe to be a new light on preparing and protecting quantum states with multi-field driven COM systems for diverse applications.

Dual regulation effect and mechanism of human myeloid-derived suppressor cells on anticolorectal cancer cells activity of Vγ9Vδ2 T cells.

Myeloid-derived suppressor cells (MDSC) are a group of immature inhibitory cells of bone marrow origin. Human γδ T cells (mainly Vγ9Vδ2 T cells) have emerged as dominant candidates for cancer immunotherapy because of their unique recognition pattern and broad killing activity against tumor cells. Intestinal mucosal intraepithelial lymphocytes are almost exclusively γδ T cells, so it plays an important role in inhibiting the development of colorectal cancer. In this study, we investigated the effects and molecular mechanism of human MDSC on anticolorectal cancer cells activity of Vγ9Vδ2 T cells. Our results suggested that MDSC can reduce the NKG2D expression of Vγ9Vδ2 T cells through direct cell-cell contact, which is associated with membrane-type transforming growth factor-ß. In contrast, MDSC can increase Vγ9Vδ2 T cells activation and production of IFN-γ, perforin, Granzyme B through direct cell-cell contact. This may be related to the upregulation of T-bet in Vγ9Vδ2 T cells by MDSC. However, MDSC had a dominant negative regulatory effect on the anticolorectal cancer cells activity of Vγ9Vδ2 T cells. Our study provides a theoretical basis for the immune regulatory function of human MDSC on γδ T cells. This will be conducive to the clinical development of a new antitumor therapy strategy.

Revisiting the relationship between complement and ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory bowel disorder (IBD) characterized by relapsing chronic inflammation of the colon that causes continuous mucosal inflammation. The global incidence of UC is steadily increasing. Immune mechanisms are involved in the pathogenesis of UC, of which complement is shown to play a critical role by inducing local chronic inflammatory responses that promote tissue damage. However, the function of various complement components in the development of UC is complex and even paradoxical. Some components (e.g. C1q, CD46, CD55, CD59, and C6) are shown to safeguard the intestinal barrier and reduce intestinal inflammation, while others (e.g. C3, C5, C5a) can exacerbate intestinal damage and accelerate the development of UC. The complement system was originally thought to function primarily in an extracellular mode; however, recent evidence indicates that it can also act intracellularly as the complosome. The current study provides an overview of current studies on complement and its role in the development of UC. While there are few studies that describe how intracellular complement contributes to UC, we discuss potential future directions based on related publications. We also highlight novel methods that target complement for IBD treatment.

[Progressin Tumor-Associated Macrophages in the Treatment of Pancreatic Cancer].

Pancreatic cancer is one of the digestive system tumors with a high degree of malignancy,and most of the patients are diagnosed in advanced stages.Because of limited available therapies,the mortality of this disease remains high.Tumor-associated macrophages(TAM),the main immune cells in the tumor microenvironment,are involved in the regulation of the occurrence and development of pancreatic cancer.Specifically,TAM are involved in the proliferation,invasion,immune escape,and chemoresistance of pancreatic cancer cells,demonstrating potential in the targeted therapy of pancreatic cancer.In this paper,we summarize the TAM-based therapies including consuming TAM,reprogramming TAM,dynamic imaging of TAM with nanoprobes,and regulating the phagocytic ability of TAM for pancreatic cancer,aiming to provide a theoretical basis for developing new therapies for pancreatic cancer.

Chimeric specific antigen epitope-carrying dendritic cells induce interleukin-17(+) regulatory T cells to suppress food allergy.

BACKGROUND: The on-purpose-modulated dendritic cells (DCs) have shown charming effects on restoring immune regulatory functions in subjects with immune diseases. OBJECTIVE: This study aims to construct DCs carrying chimerical antigen (Ag) peptides (CAP-DCs) to induce interleukin (IL)-17+ inducible Tregs (iTregs) to alleviate food allergy (FA) in a murine model. METHODS: In this study, we constructed CAP-DCs. The CAP is a fusion protein, consisting of a segment of recombinant scFv of anti-DEC205 antibody and an ovalbumin (OVA) epitope (IC). A murine OVA-FA model was developed to test the effects of CAP-DCs on suppressing the allergic response in the intestine. RESULTS: The CAP-DCs are characterized as that a complex of scFv-IC is presented on the surface of the cells, moderately express CD80 and CD86 as well as IL-6, IL-23, transforming growth factor (TGF)-ß and CCR9. After being passively transferred with CAP-DCs or injection of scFv-IC, Ag-specific IL-17+ Foxp3+ iTregs were induced in the intestinal lamina propria of FA mice. The iTregs showed immune suppressive effects on Ag-specific Th2 response. FA mice were adoptively transferred with the CAP-DCs or scFv-IC injection, which resulted in a significant decrease in the number of Ag-specific Th2 cells and suppression of FA response in an Ag-specific manner. CONCLUSIONS AND CLINICAL RELEVANCE: CAP-DCs can ameliorate FA response by inducing Ag-specific IL-17+ Foxp3+ iTregs and suppressing Ag-specific Th2 response. To generate CAP-DCs has the translational potential in the treatment of FA.

The angelica Polysaccharide: a review of phytochemistry, pharmacology and beneficial effects on systemic diseases.

Angelica sinensis is a perennial herb widely distributed around the world, and angelica polysaccharide (APS) is a polysaccharide extracted from Angelica sinensis. APS is one of the main active components of Angelica sinensis. A large number of studies have shown that APS has hematopoietic, promoting blood circulation, radiation resistance, lowering blood glucose, enhancing the body immunity and other pharmacological effects in a variety of diseases. However, different extraction methods and extraction sites greatly affect the efficacy of APS. In recent years, with the emerging of new technologies, there are more and more studies on the combined application and structural modification of APS. In order to promote the comprehensive development and in-depth application of APS, this narrative review systematically summarizes the effects of different drying methods and extraction sites on the biological activity of APS, and the application of APS in the treatment of diseases, hoping to provide a scientific basis for the experimental study and clinical application of APS.

Leukemia inhibitory factor promotes nestin-positive cells, and increases gp130 levels in the Parkinson disease mouse model of 6-hydroxydopamine.

OBJECTIVE: To investigate the roles of leukemia inhibitory factor (LIF) in a 6-hydroxydopamine (6-OHDA) mouse model of Parkinson disease (PD), and explore how the LIF improves PD symptoms. METHODS: This study was performed in Tianjin Medical University, Tianjin, China, between April 2008 and January 2010. Seventy-two mice were allocated into a control group (CON), sham operation group (SHA), physiological saline (NS) treatment group (PD), and LIF treatment group (LIF), n=18 for each group. The 6-OHDA was injected into the mice`s left mid-striatum to build a 6-OHDA model of PD. The LIF or NS was slowly released into the CSF through the ALZET osmotic pump catheters duct, in the LIF or NS treated groups. The whole treatment lasted 3 weeks, and the motor functions of the mice were assessed on the seventh, fourteenth, and twenty-first day during the treatment. The nestin-positive cells in the mice were counted by immunofluorescence assays, and the level of gp130 was detected with western blot analysis. RESULTS: After CSF infusion in the LIF-treated group, we observed an increased number of nestin-positive cells in the mice`s brains. The expression of a major component of the LIF receptor complex, gp130, was also increased. In the fourteenth and twenty-first day time periods; LIF treatment continuously improved the motor functions of the mouse model of PD. CONCLUSION: These results suggest the potential of LIF administration as a therapeutic method for PD.

Progress of exosome research in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a global chronic autoimmune disease that invades most organs of the body, with kidney injury being the most prominent feature. Exosomes are extracellular vesicles that carry a variety of proteins, lipids and genetic material, participate in the exchange of local and intersystem information, and play an important immunoregulatory role in a variety of autoimmune diseases. At the same time, the use of exosomes as disease biomarkers and drug delivery carriers also shows great application prospects. This article reviews current progress in the application of exosomes in the pathogenesis, diagnosis and treatment of SLE.

Antiosteoporosis effects of a marine antimicrobial peptide pardaxin via regulation of the osteogenesis pathway.

Antimicrobial peptides (AMPs) are known to play an important role in natural immunity. Moreover, the diverse biological activities of AMPs showed great potency in treating many diseases. Thus, in this study, we used an AMP, that is, pardaxin, from a marine fish (Pardachirus marmoratus), which has been reported to possess antibacterial and antitumor activities. We first investigated the mechanisms of pardaxin in promoting osteogenic differentiation in vitro and in vivo. As per our data, it was determined that pardaxin could stimulate bone morphogenetic protein-2 (BMP-2) and downstream cascade. The activation of BMP-2 could further induce the phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Additionally, the activation of p-Akt and p-ERK could prompt the elevation and translocation of runt-related transcription factor 2 (runx-2), which is associated with osteoblast differentiation. The translocation of runx-2 initiated transcription and translation of osteogenesis-related markers, including alkaline phosphatase (ALP), osterix, and osteocalcin. Pardaxin significantly facilitated preosteoblast cells in mineralization and reversed dexamethasone- (DM-) induced zebrafish bone formation deficiency by activating the osteogenesis pathway. Therefore, we suggest that pardaxin could be a possible candidate for osteoporosis treatment and a promising therapeutic agent.

Effect of Angelica polysaccharide on mouse myeloid-derived suppressor cells.

Angelica polysaccharide (APS) is a polysaccharide extracted from Angelica sinensis and it is one of the main active components of Angelica sinensis. Many studies have demonstrated that APS can promote the activation and function of a variety of immune cells and is recognized as an immune enhancer, but the regulatory effect of APS on myeloid-derived suppressor cells (MDSC) is still unclear. In this study, we investigated the effects of APS on MDSC proliferation, differentiation and function through in vivo and in vitro experiments. In vitro, our results showed that APS promoted the proliferation, differentiation and immunosuppressive function of MDSC through STAT1 and STAT3 signaling pathways, and positively correlated with the expression level of Mannose receptor (MR, also known as CD206) and in a concentration-dependent manner on APS. In vivo, APS up-regulated T cells, γδT cells, CD8+T cells, natural killer cells, monocytes/macrophages, and granulocytes in the peripheral blood and spleen of mice to varying degrees and was accompanied by the same degree of increase in the proportion of MDSC. That reminds to the clinician that when applying APS as treatment they should pay attention to its possible side effects of increasing the quantity and function of MDSC, in order to increase its efficacy.

Neuroprotective Effects of Estradiol plus Lithium Chloride via Anti-Apoptosis and Neurogenesis Pathway in In Vitro and In Vivo Parkinson's Disease Models.

Few pharmaceutical agents for slowing Parkinson's disease (PD) progression existed, especially for perimenopause females. The current general medications are mostly hormone replacement therapy and may have some side effects. Therefore, there is an urgent need for a novel treatment for PD. This study examined the possibility of estradiol plus lithium chloride (LiCl), one of the metal halides used as an alternative to salt. We showed that the combination of LiCl and estradiol could enhance neurogenesis proteins GAP-43 and N-myc in the human neuronal-like cells. We also further confirmed the neurogenesis activity in zebrafish. LiCl and LiCl plus estradiol could enhance 6-OHDA-induced upregulation of TGase-2b and Rho A mRNA expression. Besides, LiCl plus estradiol showed a synergic effect in anti-apoptotic activity. LiCl plus estradiol protected SH-SY5Y cells and zebrafish against 6-OHDA-induced damage on neurons than LiCl or estradiol alone groups via p-P38, p-Akt, Bcl-2, and caspase-3 cascade. The potential for developing this combination as a candidate treatment for PD is discussed.

Apolipoprotein A-I Mimetic Peptide L-4F Suppresses Granulocytic-Myeloid-Derived Suppressor Cells in Mouse Pancreatic Cancer.

L-4F is an apolipoprotein A-I (ApoA-I) mimetic peptide, it was engineered to imitate the anti-inflammatory and anti-oxidative activity of ApoA-I. In this paper, H7 cell was used to construct a mouse model of pancreatic cancer in situ, and the mice were treated with L-4F. Then, the development of pancreatic cancer and myeloid-derived suppressor cells (MDSCs) infiltration were investigated in vivo. After L-4F treatment, the differentiation, proliferation and apoptosis of MDSCs were detected in vitro. Moreover, we test its effects on the immunosuppressive function of MDSCs ex vivo. The results show that L-4F significantly reduced the tumorigenicity of H7 cells. L-4F suppressed granulocytic myeloid-derived suppressor cells (PMN-MDSCs) differentiation and inhibited the accumulation of PMN-MDSCs in the mouse spleen and tumor tissue. L-4F weakened the immunosuppressive function of MDSCs, resulting in decreased production of ROS and H2O2 by MDSCs, and increased T cell proliferation, interferon γ and tumor necrosis factor ß secretion, and CD3+CD4+ T and CD3+CD8+ T cell infiltration into the mouse spleen and pancreatic cancer tissue. Furthermore, L-4F significantly down regulated the STAT3 signaling pathway in PMN-MDSCs. These results indicated that L-4F exerts an effective anti-tumor and immunomodulatory effect in pancreatic cancer by inhibiting PMN-MDSCs.

BIM deletion polymorphism predicts poor response to EGFR-TKIs in nonsmall cell lung cancer: An updated meta-analysis.

BACKGROUND: A germline deletion in BIM (B cell lymphoma-2-like 11) gene has been shown to impair the apoptotic response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in vitro but its impact on response to EGFR-TKIs in patients of nonsmall cell lung cancer (NSCLC) remains controversial. METHODS: Eligible literature were searched and screened. Objective response rate (ORR) and disease control rate (DCR) were extracted and aggregated with odds ratio (OR). Hazard ratio (HR) and 95% confidence interval (CI) for progression-free survival (PFS) and overall survival (OS) were extracted and aggregated based on random-effect model. RESULTS: Fourteen studies including 2694 NSCLC patients were eligible. Individuals harboring BIM deletion polymorphism had inferior ORR (OR = 0.49, 95% CI: 0.34-0.70, P < .001), inferior DCR (OR = 0.50, 95% CI: 0.30-0.84, P = .009). Patients with BIM deletion had shorter OS despite of the heterogeneity between countries (in subgroup of South Korea and Taiwan, HR = 1.34, 95% CI: 1.18-1.53, P < .001; in subgroup of other countries, HR = 2.43, 95% CI: 2.03-2.91, P < .001). The pooled analysis of PFS showed great heterogeneity (I = 79%). All the reported characteristics did not account for the heterogeneity. However, 2 subgroups could be obtained through sensitivity analysis. In one subgroup, patients with BIM deletion polymorphism had shorter PFS (HR = 2.03, 95% CI: 1.71-2.40, P < .001), while in the other subgroup, no significant difference was observed (HR = 0.92, 95% CI: 0.79-1.06, P = .25). CONCLUSION: NSCLC patients with BIM deletion polymorphism show poor ORR, DCR, and OS after EGFR-TKIs treatment. BIM deletion polymorphism indicates poor response to EGFR-TKIs, and it could be used as a predictor to identify those who would benefit from EGFR-TKIs in NSCLC patients.

[Effect of acupuncture on TGF-ß1/Smads pathway in mice with airway remodeling mic].

OBJECTIVE: To investigate the effect of acupuncture on TGF-ß1/Smads signaling pathway in the lung tissue of mice with airway remodeling. METHODS: Thirty specific pathogen-free mice were randomly divided into blank group, model group and acupuncture group (n=10). Mouse models of asthma were established in the model group and the acupuncture group, and the mice in the latter group received 7 acupuncture therapies (at bilateral Fei Shu, Da Zhui and Zu Sanli, 20 min each time) every other day, starting on the 10th day after the modeling. At 24 h after the last acupuncture, the mice were subjected to inhalation of 1% OVA for 3 days, and 24 h after the last challenge, the mice were given methacholine chloride (Mch) inhalation at different concentrations for measurement of lung resistance using a noninvasive stroke volume meter. HE staining was used to observe the pathological changes in the lung tissues, and TGF-ß1 levels in the the bronchoalveolar lavage fluid (BALF) and serum were detected using ELISA; Western blotting was used to detect the differential protein expressions in the airway smooth muscles between the two groups. The airway smooth muscle cells were isolated from the mice in the acupuncture group and treated with a TGF- ß1 inhibitor (LY2157299), and the relative expressions of type-Ⅰ and Smads proteins were detected using Western blotting. RESULTS: The mice in the model showed obvious tracheal fistula with airway pathologies including lumen narrowing, bronchial mucosa thickening, dissociation of the epithelial cells, and thickening of the alveolar septum and airway smooth muscles. These pathological changes were obviously milder in the acupuncture group. The asthmatic mice exhibited significantly increased lung resistance in positive correlation with Mch concentration. Serum TGF-ß1 level was significantly elevated in asthmatic mice (P < 0.05); TGF-ß1 levels in the serum and BALF were significantly lower in the acupuncture group than in the model group (P < 0.05). In the model group, the expressions of α-SMA, TGF-ß1 and Smads in the airway smooth muscles were significantly higher than those in the other two groups (both P < 0.05). In cultured airway smooth muscle cells, the expressions of type-Ⅰ and Smads were significantly higher in cells treated with LY2157299 than in the control cells (P>0.05). CONCLUSIONS: Acupuncture can inhibit airway remodeling by inhibiting the expression of airway TGF-ß1 and down-regulating the expression of Smads and α-SMA to reduce airway inflammatory response. Airway expressions of type-Ⅰ and Smads proteins remain high after inhibiting TGF-ß1. Acupuncture may control asthma progression through the TGF-ß1/Smads pathway.

Cervical varices unrelated to placenta previa as an unusual cause of antepartum hemorrhage: A case report and literature review.

OBJECTIVE: Ruptured cervical varicose veins can cause significant vaginal bleeding during the third trimester of pregnancy. The etiology is not uncommon, yet receives little discussion in current literature. We here report such a case with complete evaluations, managements and follow ups; while analyzing similar cases published. CASE REPORT: A 34-year-old pregnant woman, gravida 1, presented with sudden onset of painless antepartum hemorrhage at 31+5 weeks of gestation. Speculum examination revealed ruptured cervical varicose veins; further evaluations with transvaginal sonography and magnetic resonance imaging were done to study the extensiveness and characteristics of the lesion. The cervical varices spontaneously regressed by postpartum day 4 and no recurrence was observed in the immediate postpartum follow-up period or in the subsequent pregnancy. CONCLUSION: The case is unique for the lack of association with placenta previa. Cervical varicose veins rupture should be considered for painless vaginal bleeding during the third trimester pregnancy.

Protective effects of antioxidin-RL from Odorrana livida against ultraviolet B-irradiated skin photoaging.

The unavoidable daily exposure of the skin to ultraviolet (UV) B radiation is proven to have deleterious effects. The action mechanism of antioxidin-RL, an antioxidant peptide purified from skin secretions of frog Odorrana livida with amino acid sequence of AMRLTYNRPCIYAT, is well characterized by NMR titration and mutation based on ABTS+ scavenging activities. In order to explore the protective effects of antioxidin-RL against UVB-irradiated skin photoaging, cell uptake assay was used to detect the location of antioxidin-RL molecules serving various biological functions in the cells. The protective effects of antioxidin-RL on UVB-induced response were examined in vitro and in vivo. Results showed that antioxidin-RL successfully penetrated the cell membrane and exerted a positive effect on cell migration. It also effectively inhibited the UVB-induced excessive production of ROS and prevented oxidative damage to DNAs and proteins. Moreover, the mRNA expressions of MMP-1, VEGF, COX-2, and pro-inflammatory cytokines, such as IL-6 and TNF-α in antioxidin-RL-treated HaCaT and HSF cells were significantly down-regulated whereas those of FGF, procollagen type I and TGF-ß1 up-regulated. Antioxidin-RL effectively prevented UVB-induced erythema on mouse skin, thereby inhibiting UVB-induced skin thickening and inflammation and increasing collagen deposition as demonstrated by in vivo experiments. Hence, the novel antioxidant peptide antioxidin-RL can effectively reduce UVB-induced skin reactions in vivo and in vitro, providing potential molecules against UVB-induced inflammation and photoaging.

Carboxymethyl chitosan nanoparticles loaded with bioactive peptide OH-CATH30 benefit nonscar wound healing.

BACKGROUND: Nonscar wound healing is a desirable treatment for cutaneous wounds worldwide. Peptide OH-CATH30 (OH30) from king cobra can selectively regulate the innate immunity and create an anti-inflammatory micro-environment which might benefit nonscar wound healing. PURPOSE: To overcome the enzymatic digestion and control release of OH30, OH30 encapsulated in carboxymethyl chitosan nanoparticles (CMCS-OH30 NP) were prepared and their effects on wound healing were evaluated. METHODS: CMCS-OH30 NP were prepared by mild ionic gelation method and properties of the prepared CMCS-OH30 NP were determined by dynamic light scattering. Encapsulation efficiency, stability and release profile of OH30 from prepared CMCS-OH30 NP were determined by HPLC. Cytotoxicity, cell migration and cellular uptake of CMCS-OH30 NP were determined by conventional methods. The effects of prepared CMCS-OH30 NP on the wound healing was investigated by full-thickness excision animal models. RESULTS: The release of encapsulated OH30 from prepared CMCS-OH30 NP was maintained for at least 24 h in a controlled manner. CMCSOH30 NP enhanced the cell migration but had no effects on the metabolism and proliferation of keratinocytes. In the full-thickness excision animal models, the CMCS-OH30 NP treatment significantly accelerated the wound healing compared with CMCS or OH30 administration alone. Histopathological examination suggested that CMCS-OH30 NP promoted wound healing by enhancing the granulation tissue formation through the re-epithelialized and neovascularized composition. CMCS-OH30 NP induced a steady anti-inflammatory cytokine IL10 expression but downregulated the expressions of several pro-inflammatory cytokines. CONCLUSION: The prepared biodegradable drug delivery system accelerates the healing and shows better prognosis because of the combined effects of OH30 released from the nanoparticles.

Management of pregnancy in pancreas alone transplant recipient complicated with stage-4 chronic renal insufficiency and superimposed pre-eclampsia: Case report and literature review.

OBJECTIVE: With the prolonged life expectancy in solid organ transplant recipients, their quality of life and fertility desire become of particular concern. Pregnancy in pancreas-alone transplantation, although rare and complicated to manage, is not impossible anymore. We here report such a case with literature review to address this issue. CASE REPORT: A 29-year-old, primigravida patient with underlying stage 4 chronic renal insufficiency and type 1 diabetes mellitus post pancreas-alone transplantation 5 years prior to her initial visit consulted our service. Antepartum care with intensive monitoring of blood pressure, renal function, and tacrolimus serum concentration were given. Successful maternal and fetal outcomes are presented here. CONCLUSION: Child-bearing in solid organ transplantation recipients has become more promising nowadays, even for a difficult case of pancreas-alone transplant recipient complicated with chronic renal insufficiency and superimposed pre-eclampsia. Thorough antepartum counseling and cautious monitoring of maternal, fetal and graft conditions by multidisciplinary specialties are key to favorable pregnancy outcomes.

Apolipoprotein A-I mimetic peptide 4F suppresses tumor-associated macrophages and pancreatic cancer progression.

Pancreatic cancer is an aggressive malignancy that is unresponsive to conventional radiation and chemotherapy. Therefore, development of novel immune therapeutic strategies is urgently needed. L-4F, an Apolipoprotein A-I (ApoA-I) mimetic peptide, is engineered to mimic the anti-inflammatory and anti-oxidative functionalities of ApoA-I. In this work, H7 cells were orthotopically implanted in C57BL/6 mice and treated with L-4F. Then, pancreatic cancer progression and the inflammatory microenvironment were investigated in vivo. The cytotoxicity of L-4F toward H7 cells was assessed in vitro. Furthermore, we investigated the effects of L-4F on macrophage polarization by analyzing the polarization and genes of mouse bone marrow-derived macrophages in vitro. The results show that L-4F substantially reduced the tumorigenicity of H7 cells. L-4F inhibited inflammation by reducing the accumulation of inflammatory cells, such as IL-17A-, IL-4-, GM-CSF-, IL-1ß-, and IL-6-producing cells and Th1 and Th17. Notably, L-4F also decreased the percentage of macrophages in tumor tissues, especially M2 macrophages (CD11b+F4/80+CD206+), which was also confirmed in vitro. Additionally, the expression of the M2 marker genes Arg1, MRC1, and CCL22 and the inflammatory genes IL-6, iNOS, and IL-12 was decreased by L-4F, indicating that L-4F prevents M2 type macrophage polarization. However, L-4F could not directly attenuate H7 cell invasion or proliferation and did not induce apoptosis. In addition, L-4F potently down-regulated STAT3, JNK and ERK signaling pathways but not affects the phosphorylation of p38 in RAW 264.7 cells. These results suggest that L-4F exhibits an effective therapeutic effect on pancreatic cancer progression by inhibiting tumor-associated macrophages and inflammation.

CAR-T cell therapy in gastrointestinal tumors and hepatic carcinoma: From bench to bedside.

The chimeric antigen receptor (CAR) is a genetically engineered receptor that combines a scFv domain, which specifically recognizes the tumor-specific antigen, with T cell activation domains. CAR-T cell therapies have demonstrated tremendous efficacy against hematologic malignancies in many clinical trials. Recent studies have extended these efforts to the treatment of solid tumors. However, the outcomes of CAR-T cell therapy for solid tumors are not as remarkable as the outcomes have been for hematologic malignancies. A series of hurdles has arisen with respect to CAR-T cell-based immunotherapy, which needs to be overcome to target solid tumors. The major challenge for CAR-T cell therapy in solid tumors is the selection of the appropriate specific antigen to demarcate the tumor from normal tissue. In this review, we discuss the application of CAR-T cells to gastrointestinal and hepatic carcinomas in preclinical and clinical research. Furthermore, we analyze the usefulness of several specific markers in the study of gastrointestinal tumors and hepatic carcinoma.