Brain-Wide Mapping and Synaptic Localization of C1QL3 Using a Novel Epitope-Tagged Knock-In Mouse.

Although cervical cancer ranks as the fourth leading cause of cancer-related deaths among women worldwide, it is the deadliest malignancy in 37 countries, mainly in low- and middle-income regions where screening and vaccination programs are limited. Cervical cancer remains a significant global health challenge, prompting the World Health Organization to launch a global attempt to eliminate it as a public health problem by reducing its incidence below 4 per 100,000 women-years. Surgery, chemotherapy, and radiation therapy are conventional approaches against cancer, but in many cases, they fail to destroy the malignant cells. It is because of the resistance of tumors to anticancer drugs that sometimes imposes substantial side effects on the patients. These limitations underscore the urgency of developing novel, efficient, and safe anticancer options. In this regard, researchers investigated several compounds to find new drugs. Among various bioactive agents, bacterial derivatives have emerged as alternative anticancer candidates due to their tumor-targeting capacity and low toxicity. For instance, -NT spores selectively germinate in hypoxic tumors and induce oncolysis while sparing normal tissues. Moreover, modified engineered bacterial toxins, Pseudomonas exotoxin A, fused with targeting ligands, have shown safety and efficacy in clinical trials. These examples illustrate that specific bacteria or their products can serve as a promising therapeutic option with improved selectivity and low toxicity when appropriately engineered. Nonetheless, these properties are not universal among all bacterial derivatives and depend heavily on their engineering, dosage, and tumor context. Group B streptococci (GBS) are Gram-positive cocci colonized in the vagina and rectum. This bacterium produces capsular polysaccharides (CPS), the main factor attributed to surviving in hosts. A cluster of genes located in the operon is responsible for the biosynthesis of the GBS capsular polysaccharides. This operon is composed of three main regions: the first part (cpsA–D) involved in regulating the final steps of capsule biosynthesis, the central part (cpsE–L) encoding the glycosyltransferases and a polymerase. The last part (neuA–neuD) encodes enzymes implicated in sialic acid synthesis. A key component of the GBS capsule is sialic acid, which contributes to immune evasion by mimicking host glycans and engaging inhibitory Siglec receptors on immune cells, thereby reducing phagocytosis. At the same time, although capsular components stimulate protective antibody responses, CPS surrounding the bacteria prevents complement deposition and opsonophagocytosis. Some studies provide convincing documents of the anticancer activity of GBS. Streptococcal sialic acids compete with cancer cells for binding to endothelial cells, an essential step for tumor migration. Sialic acid is a nine-carbon sugar originating from N-acetylneuraminic acid (Neu5Ac). These are similar to the sialyl-Lewis carbohydrates on the surface of mammalian cells. Carcinogenesis is closely related to the excessive deposition of sialyl-Lewis on the surface of cancer cells. These accelerate the adhesion of malignant cells to endothelial cells expressing the sialyl-Lewis receptor. The similarity of GBS capsule and surface of malignant cells is the presence of NeuNAc-Gal-GlcNAc at the end of the side chain (Fig. ). Accordingly, these polysaccharides compete with tumor cells to attach the ELAM- 1 on endothelium, hampering cancer metastasis. Besides, these polysaccharides induce an inflammatory response leading to tumor necrosis and proliferation inhibition. Hence, we selected the and genes, which are involved in the last steps of CPS biosynthesis, and designed a new recombinant fusion protein by applying bioinformatics tools, which opened up a new insight into biology. In the other step, we determine the anticancer properties of the recombinant protein by MTT, Real-Time PCR, and flow cytometry methods.