Clinical applications of ginger with an expectation of clinical benefits are receiving significant attention. This systematic review aims to provide a comprehensive discussion in terms of the clinical effects of ginger in all reported areas. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline, randomized controlled trials on the effects of ginger were investigated. Accordingly, 109 eligible papers were fully extracted in terms of study design, population characteristics, evaluation systems, adverse effects, and main outcomes. The reporting quality of the included studies was assessed based on the Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials and integrated together with studies that investigated the same subjects. The included studies that examined the improvement of nausea and vomiting in pregnancy, inflammation, metabolic syndromes, digestive function, and colorectal cancer’s markers were consistently supported, whereas other expected functions were relatively controversial. Nevertheless, only 43 clinical trials (39.4%) met the criterion of having a ‘high quality of evidence.’ In addition to the quality assessment result, small populations and unstandardized evaluation systems were the observed shortcomings in ginger clinical trials. Further studies with adequate designs are warranted to validate the reported clinical functions of ginger.

Current cancer immunotherapeutic strategies mainly focus on remodeling the tumor microenvironment (TME) to make it favorable for antitumor immunity. Increasing attention has been paid to developing innovative immunomodulatory adjuvants that can restore weakened antitumor immunity by conferring immunogenicity to inflamed tumor tissues. Here, a galactan-enriched nanocomposite (Gal-NC) is developed from native carbohydrate structures through an optimized enzymatic transformation for effective, stable, and biosafe innate immunomodulation. Gal-NC is characterized as a carbohydrate nanoadjuvant with a macrophage-targeting feature. It is composed of repeating galactan glycopatterns derived from heteropolysaccharide structures of plant origin. The galactan repeats of Gal-NC function as multivalent pattern-recognition sites for Toll-like receptor 4 (TLR4). Functionally, Gal-NC-mediated TLR activation induces the repolarization of tumor-associated macrophages (TAMs) toward immunostimulatory/tumoricidal M1-like phenotypes. Gal-NC increases the intratumoral population of cytotoxic T cells, the main effector cells of antitumor immunity, via re-educated TAMs. These TME alterations synergistically enhance the Tcell-mediated antitumor response induced by αPD-1 administration, suggesting that Gal-NC has potential value as an adjuvant for immune checkpoint blockade combination therapies. Thus, the Gal-NC model established herein suggests a glycoengineering strategy to design a carbohydrate-based nanocomposite for advanced cancer immunotherapies.

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