Exosomal non-coding RNA: A new frontier in diagnosing and treating pancreatic cancer: A review.

Pancreatic cancer is the most fatal malignancy worldwide. Once diagnosed, most patients are already at an advanced stage because of their highly heterogeneous, drug-resistant, and metastatic nature and the lack of effective diagnostic markers. Recently, the study of proliferation, metastasis, and drug resistance mechanisms in pancreatic cancer and the search for useful diagnostic markers have posed significant challenges to the scientific community. Exosomes carry various biomolecules (DNA, non-coding RNAs (ncRNAs), proteins, and lipids) that mediate communication between tumors and other cells. ncRNAs can be transported through exosomes to numerous relevant receptor cells and regulate local epithelial-mesenchymal transition (EMT) in tumor tissue, proliferation, drug resistance, and the establishment of pre-metastatic ecological niches in distant organs. In summary, exosomal ncRNAs promote tumor cell proliferation, invasion, and metastasis through multiple EMT, immunosuppression, angiogenesis, and extracellular matrix remodeling pathways. Moreover, we discuss the significant therapeutic significance of exosomal ncRNAs as PC biomarkers.

In situ formation of ferrous sulfide in glycyrrhizic acid hydrogels to promote healing of multi-drug resistant Staphylococcus aureus-infected diabetic wounds.

Diabetic wound treatment faces great challenges in clinic. Staphylococcus aureus (S. aureus) is one of the most frequently isolated pathogens from the diabetic infections, which can severely impede wound healing time. Herein, ferrous sulfide (FeS) nanoparticles were fabricated through an in situ reaction between Fe2+ and S2- in glycyrrhizic acid (GA) solution. As the FeS nanoparticles aged, the solution gradually transformed into a gel, exhibiting excellent mechanical strength, injectability, and biocompatibility as a wound dressing. In addition to its own pharmacological effects, GA could act as the protector for FeS from oxidation of air. It also provided a weak acidic microenvironment, facilitating the pH-dependent dissolution reaction of FeS to release H2S and Fe2+. Notably, the effective antibacterial performance of the FeS/GA hydrogels towards S. aureus and multi-drug resistant S. aureus (MRSA) was achieved via the degradedly released Fe2+ and H2S through combination of ferroptosis damage and energy metabolism disruption. Moreover, FeS/GA hydrogels effectively modulated the proportion of M1/M2 macrophages, reduced the secretion of inflammatory cytokines, and significantly enhanced the proliferation and migration of fibroblasts in vitro. Importantly, in an MRSA-infected diabetic wound model, the FeS/GA hydrogels efficiently eradicated bacteria and regulated the inflammatory microenvironment, thereby promoting the diabetic wound repair. Overall, our study establishes a novel strategy for developing multifunctional hydrogels that serve as an effective therapeutic platform for managing bacteria-infected diabetic wounds.

The huge potential of targeting copper status in the treatment of colorectal cancer

Colorectal cancer (CRC) commonly leads to cancer deaths and is often diagnosed at advanced stages. It also faces difficulties due to the poor results of conventional treatments such as surgery, chemotherapy, and radiotherapy. Copper is a mineral nutrient whose intrinsic properties have a two-way effect on the production and treatment of cancer. Copper's redox properties allow it to be used in developing anti-cancer drugs, while its potential toxicity leads to oxidative stress and even cancer. Copper status is closely related to colorectal tumors’ proliferation and metastasis. The study of the mechanisms of copper homeostasis, cuproplasia, and cuproptosis due to altered copper status plays a crucial role in developing anticancer drugs. Therefore, targeting alteration of copper status becomes a potential option for treating colorectal cancer. This review summarizes the mechanisms by which altered copper status causes CRC progression and emphasizes the potential of regulating copper status in treating CRC (AU)

The multifunction of HSP70 in cancer: Guardian or traitor to the survival of tumor cells and the next potential therapeutic target.

Heat shock protein 70 (HSP70) is a highly conserved protein composed of nucleotide-binding domains (NBD) and C-terminal substrate binding domain (SBD) that can function as a "molecular chaperone". HSP70 was discovered to directly or indirectly play a regulatory role in both internal and external apoptosis pathways. Studies have shown that HSP70 can not only promote tumor progression, enhance tumor cell resistance and inhibit anticancer effects but also induce an anticancer response by activating immune cells. In addition, chemotherapy, radiotherapy and immunotherapy for cancer may be affected by HSP70, which has shown promising potential as an anticancer drug. In this review, we summarized the molecular structure and mechanism of HSP70 and discussed the dual effects of HSP70 on tumor cells and the possibility and potential methods of using HSP70 as a target to treat cancer.

Small extracellular vesicle-mediated metabolic reprogramming: from tumors to pre-metastatic niche formation.

Metastasis, the spread of a tumor or cancer from the primary site of the body to a secondary site, is a multi-step process in cancer progression, accounting for various obstacles in cancer treatment and most cancer-related deaths. Metabolic reprogramming refers to adaptive metabolic changes that occur in cancer cells in the tumor microenvironment (TME) to enhance their survival ability and metastatic potential. Stromal cell metabolism also changes to stimulate tumor proliferation and metastasis. Metabolic adaptations of tumor and non-tumor cells exist not only in the TME but also in the pre-metastatic niche (PMN), a remote TME conducive for tumor metastasis. As a novel mediator in cell-to-cell communication, small extracellular vesicles (sEVs), which have a diameter of 30-150 nm, reprogram metabolism in stromal and cancer cells within the TME by transferring bioactive substances including proteins, mRNAs and miRNAs (microRNAs). sEVs can be delivered from the primary TME to PMN, affecting PMN formation in stroma rewriting, angiogenesis, immunological suppression and matrix cell metabolism by mediating metabolic reprogramming. Herein, we review the functions of sEVs in cancer cells and the TME, how sEVs facilitate PMN establishment to trigger metastasis via metabolic reprogramming, and the prospective applications of sEVs in tumor diagnosis and treatment. Video Abstract.

The huge potential of targeting copper status in the treatment of colorectal cancer.

Colorectal cancer (CRC) commonly leads to cancer deaths and is often diagnosed at advanced stages. It also faces difficulties due to the poor results of conventional treatments such as surgery, chemotherapy, and radiotherapy. Copper is a mineral nutrient whose intrinsic properties have a two-way effect on the production and treatment of cancer. Copper's redox properties allow it to be used in developing anti-cancer drugs, while its potential toxicity leads to oxidative stress and even cancer. Copper status is closely related to colorectal tumors' proliferation and metastasis. The study of the mechanisms of copper homeostasis, cuproplasia, and cuproptosis due to altered copper status plays a crucial role in developing anticancer drugs. Therefore, targeting alteration of copper status becomes a potential option for treating colorectal cancer. This review summarizes the mechanisms by which altered copper status causes CRC progression and emphasizes the potential of regulating copper status in treating CRC.

Intratumoral microbiota: A new force in diagnosing and treating pancreatic cancer.

Pancreatic cancer is an increasingly growing source of cancer-related deaths and is often diagnosed at advanced stages. Its treatment is difficult because of the poor results of conventional treatments, such as surgery, chemotherapy, and radiotherapy. Microbiota and their products can regulate the microenvironment of pancreatic tumors, the biological behavior of pancreatic cancer cells, and the functionality of the immune system. Promising results have been achieved in treating pancreatic cancer by regulating microbiota. However, intratumoral microbiota is still in its infancy as a new field of discovery for pancreatic cancer. This review summarizes the mechanisms by which intratumoral microbiota causes pancreatic cancer tumorigenesis, progression, and metastasis and demonstrates their significant potential in diagnosing and treating pancreatic cancer. Additionally, we present an outlook on the future of intratumoral microbiota in treating pancreatic cancer.

Galectins Are Central Mediators of Immune Escape in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is highly immune tolerant. Although there is immune cell infiltration in PDAC tissues, most of the immune cells do not function properly and, therefore, the prognosis of PDAC is very poor. Galectins are carbohydrate-binding proteins that are intimately involved in the proliferation and metastasis of tumor cells and, in particular, play a crucial role in the immune evasion of tumor cells. Galectins induce abnormal functions and reduce numbers of tumor-associated macrophages (TAM), natural killer cells (NK), T cells and B cells. It further promotes fibrosis of tissues surrounding PDAC, enhances local cellular metabolism, and ultimately constructs tumor immune privileged areas to induce immune evasion behavior of tumor cells. Here, we summarize the respective mechanisms of action played by different Galectins in the process of immune escape from PDAC, focusing on the mechanism of action of Galectin-1. Galectins cause imbalance between tumor immunity and anti-tumor immunity by coordinating the function and number of immune cells, which leads to the development and progression of PDAC.