Search

Due to chemotherapeutic drug resistance, tumor recurrence is common in patients with colorectal cancer (CRC) and chemo-resistant patients are often accompanied by defects in the mismatch repair system (MMR). Our previous study has shown that Candida tropicalis ( C. tropicalis ) is closely related to the occurrence and development of colorectal cancer, but whether this conditional pathogenic fungus is involved in chemotherapy needs further investigation. Here we found that C. tropicalis promoted chemotherapy resistance of colon cancer to oxaliplatin. Compared with oxaliplatin-treated group, the expression of functional MMR proteins in tumors were decreased in C.tropicalis/ oxaliplatin -treated group, while the glycolysis level of tumors was up-regulated and the production of lactate was significantly increased in C.tropicalis/ oxaliplatin -treated group. Inhibiting lactate production significantly alleviated the chemoresistance and rescued the decreased expression of MMR caused by C. tropicalis . Furthermore, we found that lactate down-regulated the expression of MLH1 through the GPR81-cAMP-PKA-CREB axis. This study clarified that C. tropicalis promoted chemoresistance of colon cancer via producing lactate and inhibiting the expression of MLH1, which may provide novel ideas for improving CRC chemotherapy effect., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The adaptor protein CARD9 is in charge of mediating signals from PRRs of myeloid cells to downstream transcription factor NF-κB. CARD9 plays an indispensable role in innate immunity. Both mice and humans with CARD9 deficiency show increased susceptibility to fungal and bacterial infections. CARD9 signaling not only activates but also shapes adaptive immune responses. The role of this molecule in tumor progression is increasingly being revealed. Our early study found that CARD9 is associated with the development of colon cancer and functions as a regulator of antitumor immunity. In this review, we focus on the upstream and downstream signaling pathways of CARD9, then we summarize the immunological recognition and responses induced by CARD9 signaling. Furthermore, we review the function of CARD9 in multiple aspects of host immunity, ranging from fungal immunity to tumorigenesis., Competing Interests: None., (AJCR Copyright © 2020.)

Hirsutella sinensis, cultured in vitro, is an attractive substitute for Cordyceps sinensis as health supplement. The aim of this study was to demonstrate whether H. sinensis mycelium (HSM) attenuates murine pulmonary fibrosis induced by bleomycin and to explore the underlying molecular mechanisms. Using lung fibrosis modle induced by intratracheal instillation of bleomycin (BLM; 4 mg/kg), we observed that the administration of HSM reduced HYP, TGF-β1 and the production of several pro-fibrosis cytokines (α-smooth muscle actin, fibronectin and vimentin) in fibrotic mice lung sections. Histopathological examination of lung tissues also demonstrated that HSM improved BLM-induced pathological damage. Concurrently, HSM supplementation markedly reduced the chemotaxis of alveolar macrophages and potently suppressed the expression of inflammatory cytokines. Also, HSM influenced Th1/Th2 and Th17/Treg imbalance and blocked the phosphorylation of mTOR pathway in vivo. Alveolar epithelial A549 cells acquired a mesenchymal phenotype and an increased expression of myofibroblast markers of differentiation (vimentin and fibronectin) after treatment with TGF-β1. HSM suppressed these markers and blocked the phosphorylation of mTOR pathway in vitro. The results provide evidence supporting the use of HSM in the intervention of pulmonary fibrosis and suggest that HSM is a potential therapeutic agent for lung fibrosis.

The purpose of the present study was to investigate the effects of testosterone on proliferative response and IgG production by splenic lymphocytes in vitro. Splenic lymphocytes from rats were cultured in the presence of the indicated doses of testosterone propionate for 72 h. The cell viability was assessed by a trypan blue exclusion test. Proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and supravital stain neutral red assay. Levels of IgG and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). The proliferative response and IgG production of splenic lymphocytes in the presence of testosterone were lower than those of control cells. Testosterone may inhibit proliferative response and IgG production of splenic lymphocytes. The results also support that androgen may play an important role in immune regulations.