STAT3 as a newly emerging target in colorectal cancer therapy: Tumorigenesis, therapy response, and pharmacological/nanoplatform strategies.

Colorectal cancer (CRC) ranks as the third most aggressive tumor globally, and it can be categorized into two forms: colitis-mediated CRC and sporadic CRC. The therapeutic approaches for CRC encompass surgical intervention, chemotherapy, and radiotherapy. However, even with the implementation of these techniques, the 5-year survival rate for metastatic CRC remains at a mere 12-14%. In the realm of CRC treatment, gene therapy has emerged as a novel therapeutic approach. Among the crucial molecular pathways that govern tumorigenesis, STAT3 plays a significant role. This pathway is subject to regulation by cytokines and growth factors. Once translocated into the nucleus, STAT3 influences the expression levels of factors associated with cell proliferation and metastasis. Literature suggests that the upregulation of STAT3 expression is observed as CRC cells progress towards metastatic stages. Consequently, elevated STAT3 levels serve as a significant determinant of poor prognosis and can be utilized as a diagnostic factor for cancer patients. The biological and malignant characteristics of CRC cells contribute to low survival rates in patients, as the upregulation of STAT3 prevents apoptosis and promotes pro-survival autophagy, thereby accelerating tumorigenesis. Furthermore, STAT3 plays a role in facilitating the proliferation of CRC cells through the stimulation of glycolysis and promoting metastasis via the induction of epithelial-mesenchymal transition (EMT). Notably, an intriguing observation is that the upregulation of STAT3 can mediate resistance to 5-fluorouracil, oxaliplatin, and other anti-cancer drugs. Moreover, the radio-sensitivity of CRC diminishes with increased STAT3 expression. Compounds such as curcumin, epigallocatechin gallate, and other anti-tumor agents exhibit the ability to suppress STAT3 and its associated pathways, thereby impeding tumorigenesis in CRC. Furthermore, it is worth noting that nanostructures have demonstrated anti-proliferative and anti-metastatic properties in CRC.

Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases.

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in the genome of this virus. S, M, H, and E proteins are structural proteins, and NSPs include accessory and replicase proteins. The structural and NSP components of SARS-CoV-2 play an important role in its infectivity, and some of them may be important in the pathogenesis of chronic diseases, including cancer, coagulation disorders, neurodegenerative disorders, and cardiovascular diseases. The SARS-CoV-2 proteins interact with targets such as angiotensin-converting enzyme 2 (ACE2) receptor. In addition, SARS-CoV-2 can stimulate pathological intracellular signaling pathways by triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, and Eph receptors, which play important roles in the progression of neurodegenerative diseases like Alzheimer's disease, epilepsy, and multiple sclerosis, and multiple cancers such as glioblastoma, lung malignancies, and leukemias. Several compounds such as polyphenols, doxazosin, baricitinib, and ruxolitinib could inhibit these interactions. It has been demonstrated that the SARS-CoV-2 spike protein has a stronger affinity for human ACE2 than the spike protein of SARS-CoV, leading the current study to hypothesize that the newly produced variant Omicron receptor-binding domain (RBD) binds to human ACE2 more strongly than the primary strain. SARS and Middle East respiratory syndrome (MERS) viruses against structural and NSPs have become resistant to previous vaccines. Therefore, the review of recent studies and the performance of current vaccines and their effects on COVID-19 and related diseases has become a vital need to deal with the current conditions. This review examines the potential role of these SARS-CoV-2 proteins in the initiation of chronic diseases, and it is anticipated that these proteins could serve as components of an effective vaccine or treatment for COVID-19 and related diseases. Video Abstract.

Engineered Biomimetic Membranes for Organ-on-a-Chip.

Organ-on-a-chip (OOC) systems are engineered nanobiosystems to mimic the physiochemical environment of a specific organ in the body. Among various components of OOC systems, biomimetic membranes have been regarded as one of the most important key components to develop controllable biomimetic bioanalysis systems. Here, we review the preparation and characterization of biomimetic membranes in comparison with the features of the extracellular matrix. After that, we review and discuss the latest applications of engineered biomimetic membranes to fabricate various organs on a chip, such as liver, kidney, intestine, lung, skin, heart, vasculature and blood vessels, brain, and multiorgans with perspectives for further biomedical applications.

Detection of Dopamine Receptors Using Nanoscale Dendrimer for Potential Application in Targeted Delivery and Whole-Body Imaging: Synthesis and In Vivo Organ Distribution.

Dopamine is one of the most important neurotransmitters released by neurons in the central nervous system, and a variety of neurological illnesses and mental disorders are associated with impairments in the secretion and functionality of dopamine. Dopamine, depending on the type of receptors, can act as a stimulant or an inhibitor. In this study, dendrimer-conjugated dopamine was utilized as a chelating agent for Technetium-99m to investigate the organ distribution of this compound in vivo using the single-photon emission computed tomography (SPECT) technique. For this purpose, dendrimers were synthesized using polyethylene glycol diacid and citric acid precursors, and dopamine was conjugated to the dendrimer using EDC/NHS cross-linker. The results showed no sign of toxicity of the dopamine-functionalized dendrimers on HEK-293 cell lines. The optimization of labeling conditions was conducted using the experimental design method (i.e., conjugate value, pH, and the amount of reducing agent), and then labeling efficiency was evaluated by thin-layer chromatography (TLC). Finally, the study of organ distribution in normal mice using SPECT imaging and comparing it with gene expression in different organs revealed that dopamine D1 receptors exhibited the highest accumulation in the liver and that the drug retained its specificity.

Folic Acid-Adorned Curcumin-Loaded Iron Oxide Nanoparticles for Cervical Cancer.

Cancer is a deadly disease that has long plagued humans and has become more prevalent in recent years. The common treatment modalities for this disease have always faced many problems and complications, and this has led to the discovery of strategies for cancer diagnosis and treatment. The use of magnetic nanoparticles in the past two decades has had a significant impact on this. One of the objectives of the present study is to introduce the special properties of these nanoparticles and how they are structured to load and transport drugs to tumors. In this study, iron oxide (Fe3O4) nanoparticles with 6 nm sizes were coated with hyperbranched polyglycerol (HPG) and folic acid (FA). The functionalized nanoparticles (10-20 nm) were less likely to aggregate compared to non-functionalized nanoparticles. HPG@Fe3O4 and FA@HPG@Fe3O4 nanoparticles were compared in drug loading procedures with curcumin. HPG@Fe3O4 and FA@HPG@Fe3O4 nanoparticles' maximal drug-loading capacities were determined to be 82 and 88%, respectively. HeLa cells and mouse L929 fibroblasts treated with nanoparticles took up more FA@HPG@Fe3O4 nanoparticles than HPG@Fe3O4 nanoparticles. The FA@HPG@Fe3O4 nanoparticles produced in the current investigation have potential as anticancer drug delivery systems. For the purpose of diagnosis, incubation of HeLa cells with nanoparticles decreased MRI signal enhancement's percentage and the largest alteration was observed after incubation with FA@HPG@Fe3O4 nanoparticles.