[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.

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.

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.

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.

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.

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.

[IL-2 stimulated responses of CD3(+) CD56(+) NKT cells in pulmonary tuberculosis patients].

AIM: To observe the activation and proliferation characteristics of IL-2 stimulated CD3(+);CD56(+); NKT cells in pulmonary tuberculosis (PTB) patients. METHODS: Peripheral blood mononuclear cells (PBMCs) from PTB patients and normal subjects were stimulated with IL-2 and cultured for different time points. The CD69 expression on and amount of the CD3(+);CD56(+); NKT cells were detected by multi fluorescence staining and flow cytometry at different time of stimulation and culture. RESULTS: There was no significant difference in percentage of NKT cells between PTB patients and normal healthy controls before culture. When IL-2 was used to stimulate for 0 h, 8 h, 16 h, 40 h and 64 h, the expression of CD69 on NKT cells in normal controls and PTB patients increased significantly, but the CD69 expression level of NKT cells in PTB patients was significantly higher than that in normal persons(P<0.05). In PTB patients group, PBMCs were expanded significantly after stimulated by IL-2, the absolute number of NKT cells increased from (3.44+/-1.20)x10(4); to (323.23+/-75.98) x10(4); (P<0.01), expanded by 108.69+/-59.22 fold, In normal control group the absolute number of NKT cells increased from (5.57+/-5.16)x10(4); to (1475.05+/-868.98)x10(4); (P<0.01), expanded by 246.26+/-134.06 fold, the expanding efficiency in PTB group was significantly lower than that in normal control group (P<0.05). CONCLUSION: NKT cells in PTB patients present with high activation but low proliferation after stimulated by IL-2.

Interleukin 17-producing gamma delta T cells increased in patients with active pulmonary tuberculosis.

Although it has been known that gammadelta T cells may play an important role in the immune response to infection of Mycobacterium tuberculosis (M. tb), the mechanisms by which the gammadelta T cells participate in the innate and/or acquired immunity to tuberculosis (TB) have not been full elucidated. In the present study, 27 patients with active pulmonary TB and 16 healthy donors (HD) were performed. We found that proportion of IL-17-producing cells among lymphocyte was similar between TB patients and HD, whereas the proportions of gammadelta T cells in IL-17-producing cells (59.2%) and IL-17-producing cells in gammadelta T cells (19.4%) in peripheral blood were markedly increased in TB patients when compared to those in HD (43.9% and 7.7%, respectively). In addition, the proportions of IFN-gamma-producing gammadelta T cells in TB patients were obviously lower than that in HD. Upon re-stimulated with M. tb heat-treated antigen (M. tb-HAg) in vitro, fewer IL-17-producing gammadelta T cells were generated from HD and TB patients, whereas IFN-gamma-producing gammadelta T cells were increased in TB patients compared to that in HD. Our findings in TB patients and healthy human were consistent with other murine investigation that the IL-17-producing gammadelta T cells were main source of IL-17 in mouse model of BCG infection, suggesting that gammadelta T cells might be involved in the formation of tubercular granuloma in pulmonary TB patients, but need further identification.