Targeting autophagy may serve as a promising strategy for cancer therapy. Ganoderma lucidum polysaccharide (GLP) has been shown to exert promising anti-cancer effects. However, the underlying mechanisms remain elusive. Whether GLP regulates autophagy in cancer has never been reported. In this study, GLP induced the initiation of autophagy in colorectal cancer (CRC) HT-29 and HCT116 cells, as evidenced by enhanced level of LC3-II protein, GFP-LC3 puncta, and increased formation of double membrane vacuoles. However, GLP treatment caused marked increase of p62 expression. Addition of late stage autophagy inhibitor, chloroquine (CQ), further enhanced LC3-II and p62 level, as well as increased autophagosome accumulation, suggesting a blockage of autophagic flux by GLP in CRC cells. We then found GLP blocked autophagosome and lysosome fusion as determined by mRFP-GFP-LC3 colocalization analysis. Mechanistic study revealed that GLP-induced disruption of autophagosome-lysosome fusion is due to reduced lysosome acidification and lysosomal cathepsin activities. Cell viability and flow cytometry assays revealed that GLPinduced autophagosome accumulation is responsible for GLP-induced apoptosis in CRC cells. In line with this, inhibition of autophagy initiation by 3-methyladenine (3-MA), an early stage autophagy inhibitor, attenuated GLPinduced apoptosis. In contrast, suppression of autophagy at late stage by CQ enhanced the anti-cancer effect of GLP. Furthermore, we demonstrated that GLP-induced autophagosome accumulation and apoptosis is mediated via MAPK/ERK activation. Finally, GLP inhibited tumor growth and also inhibited autophagic flux in vivo. These results unveil new molecular mechanism underlying anti-cancer effects of GLP, suggesting that GLP is a potent autophagy inhibitor and might be useful in anticancer therapy.

T helper 17 cells (Th17) constitute a distinct subset of helper T cells with a unique transcriptional profile (STAT3, RORγ, and RORα), cytokine production pattern (IL17 family), and requirement of specific cytokines for their differentiation (TGF-β, IL6, IL21, and IL23). Recent studies involving experimental animals and humans have shown that Th17/IL17 plays a crucial role in host defense against a variety of pathogens, including bacteria and viruses. The underlying mechanisms by which Th17 performs include dendritic cell (DC) regulation, neutrophil recruitment, Th1 modulation, and T regulatory cell (Treg) balance. In recent years, researchers have generated an accumulating wealth of evidence on the role of Th17/IL17 in protective immunity to intracellular bacterial pathogens, such as Mycobacterium tuberculosis and Chlamydia trachomatis, which are one of the most important pathogens that inflict significant socioeconomic burden across the globe. In this article, we reviewed the current literature on the functions and mechanisms by which Th17/IL17 responds to intracellular bacterial infections. A better understanding of Th17/IL17 immunity to pathogens would be crucial for developing effective prophylactics and therapeutics.

High glucose represents a good environment for bacterial growth on the skin, on the ocular surface (OS) and in the tears of type 2 diabetes mellitus (T2DM) patients, affecting the conjunctival bacterial community. This study aimed to investigate the OS bacterial flora of T2DM patients and healthy subjects using 16S rRNA sequencing-based bacterial identification. Among 23 healthy subjects (CON) and 31 T2DM patients, 54 eyes were examined to investigate the OS bacterial community. Factors potentially affecting the microbial growth were controlled. Results showed the OS microbiota presented higher diversity in the T2DM group than in the CON group. Bioinformatic analysis showed a lower abundance of Proteobacteria and a higher abundance of Bacteroidetes at the phyla level as well as a significantly increased abundance of Acinetobacter and Pseudomonas at the genus level in the T2DM group. The difference in OS microbiota at taxonomic level was associated with Ocular Surface Disease Index and course of T2DM. These findings indicate the OS flora in T2DM patients is significantly different from that in healthy subjects, which may be closely associated with OS discomfort and course of T2DM.

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