To flourish, cancers greatly depend on their surrounding tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in TME are critical for cancer occurrence and progression because of their versatile roles in extracellular matrix remodeling, maintenance of stemness, blood vessel formation, modulation of tumor metabolism, immune response, and promotion of cancer cell proliferation, migration, invasion, and therapeutic resistance. CAFs are highly heterogeneous stromal cells and their crosstalk with cancer cells is mediated by a complex and intricate signaling network consisting of transforming growth factor-beta, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin, mitogen-activated protein kinase, Wnt, Janus kinase/signal transducers and activators of transcription, epidermal growth factor receptor, Hippo, and nuclear factor kappa-light-chain-enhancer of activated B cells, etc., signaling pathways. These signals in CAFs exhibit their own special characteristics during the cancer progression and have the potential to be targeted for anticancer therapy. Therefore, a comprehensive understanding of these signaling cascades in interactions between cancer cells and CAFs is necessary to fully realize the pivotal roles of CAFs in cancers. Herein, in this review, we will summarize the enormous amounts of findings on the signals mediating crosstalk of CAFs with cancer cells and its related targets or trials. Further, we hypothesize three potential targeting strategies, including, namely, epithelial–mesenchymal common targets, sequential target perturbation, and crosstalk-directed signaling targets, paving the way for CAF-directed or host cell-directed antitumor therapy.

Transforming growth factor-β (TGF-β) signaling has a paradoxical role in cancer progression, and it acts as a tumor suppressor in the early stages but a tumor promoter in the late stages of cancer. Once cancer cells are generated, TGF-β signaling is responsible for the orchestration of the immunosuppressive tumor microenvironment (TME) and supports cancer growth, invasion, metastasis, recurrence, and therapy resistance. These progressive behaviors are driven by an “engine” of the metabolic reprogramming in cancer. Recent studies have revealed that TGF-β signaling regulates cancer metabolic reprogramming and is a metabolic driver in the tumor metabolic microenvironment (TMME). Intriguingly, TGF-β ligands act as an “endocrine” cytokine and influence host metabolism. Therefore, having insight into the role of TGF-β signaling in the TMME is instrumental for acknowledging its wide range of effects and designing new cancer treatment strategies. Herein, we try to illustrate the concise definition of TMME based on the published literature. Then, we review the metabolic reprogramming in the TMME and elaborate on the contribution of TGF-β to metabolic rewiring at the cellular (intracellular), tissular (intercellular), and organismal (cancer-host) levels. Furthermore, we propose three potential applications of targeting TGF-β-dependent mechanism reprogramming, paving the way for TGF-β-related antitumor therapy from the perspective of metabolism.

Oral potentially malignant disorders (OPMDs) are a group of diseases involving the oral mucosa and that have a risk of carcinogenesis. The microenvironment is closely related to carcinogenesis and cancer progression by regulating the immune response, cell metabolic activities, and mechanical characteristics. Meanwhile, there are extensive interactions between the microenvironments that remodel and provide favorable conditions for cancer initiation. However, the changes, exact roles, and interactions of microenvironments during the carcinogenesis of OPMDs have not been fully elucidated. Here, we present an updated landscape of the microenvironments in OPMDs, emphasizing the changes in the immune microenvironment, metabolic microenvironment, mechanical microenvironment, and neural microenvironment during carcinogenesis and their carcinogenic mechanisms. We then propose an immuno–metabolic–mechanical–neural interaction network to describe their close relationships. Lastly, we summarize the therapeutic strategies for targeting microenvironments, and provide an outlook on future research directions and clinical applications. This review depicts a vivid microenvironment landscape and sheds light on new strategies to prevent the carcinogenesis of OPMDs.

This study is the first time to assess the synergistic efficacy and safety of plaque control on erosive non-gingival oral lichen planus (OLP). A randomized, controlled, clinical trial with blind evaluation was designed, and 48 OLP patients with erosive non-gingival OLP lesions were randomly assigned to the experimental group (n = 25, receiving intralesional triamcinolone acetonide injection, periodontal scaling, and oral hygiene instruction) and the control group (n = 23, only receiving intralesional triamcinolone acetonide injection) once a week for 2 weeks. Erosion size, pain level, plaque index, and community periodontal index were measured at every visit. Patients cured of erosion were followed up for 3 months to evaluate the recurrence rate. Adverse reactions were also recorded. At day 14 ± 2, the experimental group showed a higher completely healed percentage of erosion, a greater reduction of erosion size and pain level. However, no significant difference was observed in the recurrence rate. No participants had any severe adverse reactions. In conclusion, an improvement was observed in patients with plaque control, and future studies with larger sample sizes are needed to reinforce the external validity of this study.

An approach for analysing the coupling effects between dynamics and tooth surface wear in a helical gear transmission is proposed by integrating gear dynamics with modified Archard wear theory and the tooth time-varying meshing stiffness calculations. In this approach, the tooth time-varying meshing stiffness and dynamic backlash considering non-uniform wear are calculated and introduced into the dynamic model of a gear system to obtain the meshing force. The equivalent contact load from the meshing force using the Miner rule is brought into the wear model to predict tooth wear depths. The updated stiffness and backlash values caused by cumulative wear amount are re-submitted to the governing dynamic equation to perform a new round of calculations. Based on this analysis strategy, the coupling effects among dynamics, tooth non-uniform wear, time-varying meshing stiffness and backlash in a helical gear transmission is studied. The results indicate that the wear distributed across the tooth surface of a helical gear is non-uniform. With the increase in the cumulative amount of wear, the tooth meshing stiffness decreases and the tooth backlash converted from the accumulated wear amount is increased, which further decrease the dynamic performance of the transmission system.