Cancer is among the leading cause of deaths worldwide. Although conventional therapies have been applied in the fight against the cancer, the poor oxygen, low extracellular pH, and high interstitial fluid pressure of the tumor microenvironment mean that these treatments fail to completely eradicate cancer cells. Recently, bacteria have increasingly been considered to be a promising platform for cancer therapy thanks to their many unique properties, such as specific tumor-targeting ability, high motility, immunogenicity, and their use as gene or drug carriers. Several types of bacteria have already been used for solid and metastatic tumor therapies, with promising results. With the development of synthetic biology, engineered bacteria have been endowed with the controllable expression of therapeutic proteins. Meanwhile, nanomaterials have been widely used to modify bacteria for targeted drug delivery, photothermal therapy, magnetothermal therapy, and photodynamic therapy, while promoting the antitumor efficiency of synergistic cancer therapies. This review will provide a brief introduction to the foundation of bacterial biotherapy. We begin by summarizing the recent advances in the use of many different types of bacteria in multiple targeted tumor therapies. We will then discuss the future prospects of bacteria-mediated cancer therapies.

Background: FAT4 (FAT Atypical Cadherin 4) is a member of the cadherin-associated protein family, which has been shown to function as a tumor suppressor by inhibiting proliferation and metastasis. The Wnt/β-catenin pathway activation is highly associated with PD-L1-associated tumor immune escape. Here, we report the mechanism by which FAT4 overexpression regulates anti-tumor immunity in cervical cancer by inhibiting PD-L1 N-glycosylation and cell membrane localization in a β-catenin-dependent manner. Methods: FAT4 expression was first detected in cervical cancer tissues and cell lines. Cell proliferation, clone formation, and immunofluorescence were used to determine the tumor suppressive impact of FAT4 overexpression in vitro, and the findings were confirmed in immunodeficient and immunocomplete mice xenografts. Through functional and mechanistic experiments in vivo and in vitro, we investigated how FAT4 overexpression affects the antitumor immunity via the β-catenin/STT3/PD-L1 axis. Results: FAT4 is downregulated in cervical cancer tissues and cell lines. We determined that FAT4 binds to β-catenin and antagonizes its nuclear localization, promotes phosphorylation and degradation of β-catenin by the degradation complexes (AXIN1, APC, GSK3β, CK1). FAT4 overexpression decreases programmed death-ligand 1 (PD-L1) mRNA expression at the transcriptional level, and causes aberrant glycosylation of PD-L1 via STT3A at the post-translational modifications (PTMs) level, leading to its endoplasmic reticulum (ER) accumulation and polyubiquitination-dependent degradation. We found that FAT4 overexpression promotes aberrant PD-L1 glycosylation and degradation in a β-catenin-dependent manner, thereby increasing cytotoxic T lymphocyte (CTL) activity in immunoreactive mouse models. Conclusions: These findings address the basis of Wnt/β-catenin pathway activation in cervical cancer and provide combination immunotherapy options for targeting the FAT4/β-catenin/STT3/PD-L1 axis. Graphical Schematic cartoons showing the antitumor immunity mechanism of FAT4. (left) when Wnts bind to their receptors, which are made up of Frizzled proteins and LRP5/6, the cytoplasmic protein DVL is activated, inducing the aggregation of degradation complexes (AXIN, GSK3β, CK1, APC) to the receptor. Subsequently, stable β-catenin translocates into the nucleus and binds to TCF/LEF and TCF7L2 transcription factors, leading to target genes transcription. The catalytically active subunit of oligosaccharyltransferase, STT3A, enhances PD-L1 glycosylation, and N-glycosylated PD-L1 translocates to the cell membrane via the ER-to-Golgi pathway, resulting in immune evasion. (Right) FAT4 exerts antitumor immunity mainly through following mechanisms: (i) FAT4 binds to β-catenin and antagonizes its nuclear localization, promotes phosphorylation and degradation of β-catenin by the degradation complexes (AXIN1, APC, GSK3β, CK1); (ii) FAT4 inhibits PD-L1 and STT3A transcription in a β-catenin-dependent manner and induces aberrant PD-L1 glycosylation and ubiquitination-dependent degradation; (iii) Promotes activation of cytotoxic T lymphocytes (CTL) and infiltration into the tumor microenvironment.

MiR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b. Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases. It is involved in regulating the pathological process of myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, atrial fibrillation, diabetic cardiomyopathy, atherosclerosis, pulmonary hypertension, cerebral ischemia/reperfusion injury, Parkinson's disease, and Alzheimer's disease. Obviously, miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases. However, the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed. Therefore, in this review, we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases. Drugs targeting miR-135b for the treatment of diseases and related patents, highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases, have been discussed.

Cerebellar degeneration-related protein 1 antisense RNA (CDR1as), also known as ciRS-7, is a circular natural antisense transcript of CDR1. It is a widely studied and powerful representative of circular RNAs. Based on its widely reported role in cancer, CDR1as is considered one of the most promising biomarkers for diagnosing and treating tumours. However, some recent studies have extensively focused on its regulatory role in cardio-cerebrovascular diseases instead of in tumours. Studies have shown that CDR1as plays a unique role in the occurrence of cardio-cerebrovascular diseases; thus, it may be a potential target for preventing and treating cardio-cerebrovascular diseases. Furthermore, CDR1as has also been found to be related to signal transduction pathways related to inflammatory response, oxidative stress, etc., which may reveal its potential mechanism in cardio-cerebrovascular diseases. However, there is no literature to summarize the role and possible mechanism of CDR1as in cardio-cerebrovascular diseases. Therefore, in the present review, we have comprehensively summarised the latest progress in the biological characteristics, development processes, regulatory mechanisms, and roles of CDR1as in cardio-cerebrovascular diseases, aiming to provide a reference and guidance for future studies.

The incidence and mortality of cervical cancer in female malignancies are second only to breast cancer, which brings a heavy health and economic toll worldwide. Paclitaxel (PTX)-based regimens are the first-class choice; however, severe side effects, poor therapeutic effects, and difficulty in effectively preventing tumor recurrence or metastasis are unavoidable. Therefore, it is necessary to explore effective therapeutic interventions for cervical cancer. Our previous studies have shown that PMGS, a marine sulfated polysaccharide, exhibits promising anti-human papillomavirus (anti-HPV) effects through multiple molecular mechanisms. In this article, a continuous study identified that PMGS, as a novel sensitizer, combined with PTX exerted synergistic anti-tumor effects on cervical cancer associated with HPV in vitro. Both PMGS and PTX inhibited the proliferation of cervical cancer cells, and the combination of PMGS with PTX displayed significant synergistic effects on Hela cells. Mechanistically, PMGS synergizes with PTX by enhancing cytotoxicity, inducing cell apoptosis and inhibiting cell migration in Hela cells. Collectively, the combination of PTX and PMGS potentially provides a novel therapeutic strategy for cervical cancer.