Cordycepin is an adenosine derivative isolated from Cordyceps sinensis, which has been used as an herbal complementary and alternative medicine with various biological activities. The general anti-cancer mechanisms of cordycepin are regulated by the adenosine A3 receptor, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase (GSK)-3β, leading to cell cycle arrest or apoptosis. Notably, cordycepin also induces autophagy to trigger cell death, inhibits tumor metastasis, and modulates the immune system. Since the dysregulation of autophagy is associated with cancers and neuron, immune, and kidney diseases, cordycepin is considered an alternative treatment because of the involvement of cordycepin in autophagic signaling. However, the profound mechanism of autophagy induction by cordycepin has never been reviewed in detail. Therefore, in this article, we reviewed the anti-cancer and health-promoting effects of cordycepin in the neurons, kidneys, and the immune system through diverse mechanisms, including autophagy induction. We also suggest that formulation changes for cordycepin could enhance its bioactivity and bioavailability and lower its toxicity for future applications. A comprehensive understanding of the autophagy mechanism would provide novel mechanistic insight into the anti-cancer and health-promoting effects of cordycepin.

Blastocystis hominis is an intestinal protozoan that is often neglected, despite causing abdominal pain and diarrhea. Previous research has demonstrated that lipids can be synthesized by B. hominis or can accumulate in growth medium, but their function and mechanisms in the pathogenesis of Blastocystis remain unclear. Our study found that lipid-rich Blastocystis ST7-B can increase inflammation and disrupt Caco-2 cells more than the same parasite without the lipovenoes supplement. Additionally, the cysteine protease of Blastocystis, a virulence factor, is upregulated and has higher activity in lipid-rich Blastocystis. In order to better understand the effects of lipids on Blastocystis pathogenesis, we treated lipid-lowering pravastatin during Blastocystis ST7-B culturing with a lipovenoes supplement, which decreased the lipid levels of the Blastocystis and reduced the Blastocystis-induced inflammation and cell disruption of Caco-2 cells. We also analyzed the fatty acid composition and possible synthesis pathway in Blastocystis ST7-B, finding significantly higher ratios of arachidonic acid, oleic acid, and palmitic acid than in the other lipid components in lipid-rich Blastocystis ST7-B. These results suggest that lipids play a significant role in the pathogenesis of Blastocystis and provide important information on the molecular mechanisms of and potential treatments for Blastocystis infection.

This review examines the advancements in antimicrobial drug discovery with in vitro assays for Acanthamoeba, highlighting the efficacy of current topical antimicrobial agents. In recent decades, the treatment and diagnosis of Acanthamoeba keratitis (AK) have presented clinical challenges. Clinicians often rely on clinical judgment, risk factors, and patient travel history to guide initial treatment decisions. The clinical presentation of AK frequently coincides with bacterial and fungal keratitis, leading to delays in diagnostic confirmation. This review compiles a list of commonly used antimicrobial agents that may be useful in controlling and preventing Acanthamoeba and other microbial infections during the diagnostic waiting period. Due to their unique life cycle, consisting of both trophozoite and cyst stages, amoebae exhibit resistance to various clinical drugs. Current research efforts are focused on identifying alternative and effective treatment options. Despite the ongoing characterization of various cytocidal agents from natural and synthetic sources, chlorhexidine gluconate (CHG) and polyhexamethylene biguanide (PHMB) have emerged as the most effective therapies for AK. Drawing from previous studies, we catalog several commonly used antimicrobial agents that may enhance the efficacy of PHMB and CHG while also preventing other microbial infections. These alternative agents present promising options for treating AK cases. This review evaluates progress in anti-amoebic drug discovery, focusing on antibiotics and cataloging their activity at different stages of Acanthamoeba.

Acanthamoeba, a widely distributed free-living amoeba found in various environments, is an opportunistic pathogen responsible for causing Acanthamoeba keratitis, a condition that may lead to blindness. However, identifying the pathogenicity of Acanthamoeba is challenging due to its complex life cycle, ability to adapt to different environments, variable virulence factors, and intricate interactions with the host immune system. Additionally, the development of an effective model for studying Acanthamoeba pathogenicity is limited, hindering a comprehensive understanding of the mechanisms underlying its virulence and host interactions. The aim of this study was to develop an ex vivo model for Acanthamoeba infection using porcine eyeballs and to evaluate the pathogenicity of the Acanthamoeba isolates. Based on slit lamp and biopsy analysis, the developed ex vivo model is capable of successfully infecting Acanthamoeba within 3 days. Histopathological staining revealed that clinical isolates of Acanthamoeba exhibited greater corneal stroma destruction and invasion in this model than environmental isolates. Our results highlight the importance of an ex vivo porcine eye model in elucidating the pathogenesis of Acanthamoeba infection and its potential implications for understanding and managing Acanthamoeba-related ocular diseases.

Microorganisms that are involved in microbial invasion keratitis infiltrate the cornea and cause eye pain. Despite the administration of antimicrobial treatment, patients with amoebic keratitis develop bacterial coinfections. Pseudomonas aeruginosa infection accounts for 50% of the reported bacterial coinfections in these patients. However, the role of pathogenic bacteria in amoeba-induced corneal damage remains unclear. In our current study, we conducted assays to examine cytopathic effects and observed increased corneal cell damage in the group with secondary P. aeruginosa infections. Imaging revealed that the presence of A. castellanii enhanced the accumulation of P. aeruginosa in areas of cell monolayer leakage. We demonstrated that treatment of P. aeruginosa with amoeba-soluble antigen resulted in higher adhesion ability, increased biofilm formation, and more severe corneal cell damage. Overall, this research significantly contributes to our understanding of the risk of P. aeruginosa coinfection in the progression of Acanthamoeba keratitis. IMPORTANCE: At the National Cheng Kung University Hospital, numerous cases of amoebic keratitis had been identified with concurrent bacterial infections. Among these bacterial coinfections, Pseudomonas aeruginosa accounted for 50% of the reported cases. However, the impact of pathogenic bacteria on amoeba-induced corneal damage remains unclear. In our study, we successfully demonstrated that P. aeruginosa accumulated on the Acanthamoeba castellanii surface and caused more severe corneal damage. We also indicated that the exposure of P. aeruginosa to amoeba-soluble antigens enhanced its adhesion ability, promoted biofilm formation, and led to more severe corneal cell damage. These findings significantly contributed to our understanding of the risk associated with P. aeruginosa coinfection in the progression of amoeba keratitis.