There exists a significant population of key lncRNAs in both tumor and normal cellular environments; these molecules serve as either diagnostic markers or novel targets for cancer treatment. Nonetheless, lncRNA-based pharmaceuticals face limitations in clinical application when contrasted with certain small non-coding RNAs. While microRNAs and other non-coding RNAs differ significantly, long non-coding RNAs (lncRNAs) often feature a larger molecular weight and a conserved secondary structure, making their delivery methods considerably more intricate than those of smaller non-coding RNAs. Bearing in mind that lncRNAs make up a significant portion of the mammalian genome, further studies on lncRNA delivery and the subsequent functional studies are crucial for potential clinical applications. The function and mechanism of lncRNAs in diseases, particularly cancer, and diverse transfection approaches utilizing multiple biomaterials are reviewed in this study.
Energy metabolism reprogramming is a fundamental characteristic of cancer, evidenced as a crucial cancer treatment strategy. In the intricate process of energy metabolism, isocitrate dehydrogenases (IDHs), encompassing IDH1, IDH2, and IDH3, play a critical role in the oxidative decarboxylation of isocitrate, leading to the formation of -ketoglutarate (-KG). Mutations in IDH1 or IDH2 enzymes lead to the production of D-2-hydroxyglutarate (D-2HG) from -ketoglutarate (α-KG), a process that facilitates the initiation and progression of cancerous growth. To date, no IDH3 mutations have been observed or recorded. In pan-cancer research, IDH1 mutations displayed a greater mutation frequency and broader cancer association than IDH2 mutations, thus marking IDH1 as a potential promising target for the development of novel anti-cancer therapies. The regulatory mechanisms of IDH1 in cancer are presented in this review through four categories: metabolic alterations, epigenetic modifications, immune microenvironment influences, and phenotypic shifts. The aim is to offer comprehensive insights into IDH1's actions and to pave the way for the development of pioneering targeted therapies. In parallel, a survey of available IDH1 inhibitors was undertaken. The clinical trial outcomes, profoundly detailed, and the varied architectures of preclinical subjects presented here deliver profound insight into research aimed at treatments for IDH1-related cancers.
Secondary tumor development in locally advanced breast cancer is facilitated by circulating tumor clusters (CTCs) that detach from the primary tumor, rendering conventional treatments such as chemotherapy and radiotherapy ineffective at preventing the spread. A groundbreaking nanotheranostic system, detailed in this study, has been engineered to monitor and eliminate circulating tumor cells (CTCs) before they form secondary tumors in breast cancer patients. This is hypothesized to reduce metastatic progression and increase the five-year survival rate. Magnetic hyperthermia and pH-responsive nanomicelles, incorporating NIR fluorescent superparamagnetic iron oxide nanoparticles, were developed using self-assembly principles. These nanomicelles were specifically designed for dual-modal imaging and dual-toxicity, enabling targeted killing of circulating tumor cells (CTCs) in the bloodstream. To simulate the characteristics of CTCs isolated from breast cancer patients, a heterogeneous tumor clusters model was generated. To further evaluate the nanotheranostic system, its targeting ability, drug release characteristics, hyperthermia potential, and cytotoxicity were assessed against an in vitro CTC model. A micellar nanotheranostic system's biodistribution and therapeutic efficacy were evaluated using a BALB/c mouse model emulating stage III and IV human metastatic breast cancer. A reduction in circulating tumor cells (CTCs) and distant organ metastasis following treatment with the nanotheranostic system showcases its potential to capture and destroy the CTCs, thus minimizing the occurrence of secondary tumor formation at distant sites.
Gas therapy emerges as a promising and advantageous therapeutic choice for cancers. CPI-0610 price Empirical evidence highlights nitric oxide (NO) as a surprisingly minuscule, yet critically important, gaseous molecule with a substantial ability to curb cancer. CPI-0610 price However, differing viewpoints and apprehension exist regarding its employment, as its physiological effects within the tumor are oppositely associated with its quantity. Hence, the mechanism by which nitric oxide (NO) combats cancer is critical to cancer treatment, and thoughtfully engineered NO delivery methods are vital to the success of NO-based biological applications. CPI-0610 price This review comprehensively examines the body's internal production of nitric oxide (NO), its physiological effects, the use of NO in combating cancer, and nanoscale systems for transporting NO donors. Moreover, a summary of the difficulties in supplying nitric oxide (NO) from diverse nanoparticles and the complexities of its integration into combined treatment protocols is presented. Potential clinical adaptations of various nitric oxide delivery methods are discussed, encompassing both their benefits and impediments.
Right now, clinical therapies for chronic kidney disease are severely limited, and most patients are dependent upon dialysis for long-term survival. Studies of the gut-kidney connection have indicated that the composition of the gut microbiota could be a potential therapeutic target for the treatment or regulation of chronic kidney disease. By altering the composition of the gut microbiota and suppressing the production of gut-derived uremic toxins, including p-cresol, this study showed that berberine, a natural substance with low oral bioavailability, substantially improved chronic kidney disease. Furthermore, berberine primarily impacted p-cresol sulfate plasma content by decreasing the numbers of *Clostridium sensu stricto* 1 and inhibiting the tyrosine-p-cresol pathway within the gut's microbial community. In the meantime, berberine augmented both butyric acid-producing bacteria and butyric acid concentrations within the stool, while simultaneously reducing the kidney-damaging trimethylamine N-oxide. The gut-kidney axis likely plays a critical role in berberine's potential therapeutic effect on chronic kidney disease, as these findings reveal.
The poor prognosis associated with triple-negative breast cancer (TNBC) is a direct result of its extremely high malignancy. A significant correlation between ANXA3 overexpression and unfavorable patient prognosis underscores the biomarker potential of Annexin A3. The suppression of ANXA3 expression demonstrably inhibits the multiplication and metastasis of TNBC, suggesting its promise as a therapeutic target for TNBC. This report introduces a first-in-class small molecule, (R)-SL18, which targets ANXA3, demonstrating potent anti-proliferative and anti-invasive effects in TNBC cells. The (R)-SL18 molecule, after direct interaction with ANXA3, prompted heightened ubiquitination and subsequent ANXA3 degradation, with a notable level of selectivity for proteins within the family. Remarkably, the (R)-SL18 treatment displayed a safe and potent therapeutic effect within a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 can decrease the amount of -catenin, thus inhibiting the Wnt/-catenin signaling cascade in TNBC cells. (R)-SL18's potential in treating TNBC, as suggested by our data, hinges on its ability to degrade ANXA3.
In biological and therapeutic research, peptides are growing in importance, yet their vulnerability to proteolytic degradation is a major obstacle. Glucagon-like peptide 1 (GLP-1), acting as a natural agonist for the GLP-1 receptor, presents significant therapeutic potential in the treatment of type-2 diabetes mellitus; however, its limited duration of action and susceptibility to degradation within the body have hampered its widespread clinical application. We present the rationale behind the design of a series of hybrid GLP-1 analogues incorporating /sulfono,AA peptides, intended to function as GLP-1 receptor agonists. In vivo and in plasma studies illustrated a marked contrast in stability between certain GLP-1 hybrid analogs (with a half-life exceeding 14 days) and the native GLP-1 molecule (whose half-life in blood plasma was less than 1 day). For the treatment of type-2 diabetes, these novel peptide hybrids could prove to be a viable alternative to semaglutide. Our findings support the potential use of sulfono,AA residues as alternatives to conventional amino acid residues, thus potentially augmenting the pharmacological activity of peptide-based treatments.
A promising new strategy for treating cancer is immunotherapy. Nevertheless, the impact of immunotherapy is constrained in cold tumors, exhibiting a shortage of intratumoral T cells and hampered T-cell activation. Researchers fabricated an on-demand integrated nano-engager, identified as JOT-Lip, to convert cold tumors into hot ones, employing an enhanced DNA damage approach and dual immune checkpoint inhibition strategies. Liposomes, loaded with oxaliplatin (Oxa) and JQ1, had T-cell immunoglobulin mucin-3 antibodies (Tim-3 mAb) attached via a metalloproteinase-2 (MMP-2)-sensitive linker to engineer the JOT-Lip formulation. JQ1's interference with DNA repair mechanisms in Oxa cells amplified DNA damage, triggering immunogenic cell death (ICD) and subsequently promoting intratumoral T cell infiltration. In conjunction with Tim-3 mAb, JQ1 further obstructed the PD-1/PD-L1 pathway, accomplishing dual immune checkpoint inhibition, and thus boosting T-cell priming. The effects of JOT-Lip include not only increased DNA damage and the release of damage-associated molecular patterns (DAMPs), but also promotion of intratumoral T cell infiltration and T cell priming, leading to the conversion of cold tumors into hot tumors and substantial anti-tumor and anti-metastasis effects. This comprehensive study lays out a rationale for an effective combined therapy and an optimal co-delivery system to convert cold tumors to hot tumors, thus possessing significant clinical potential in cancer chemoimmunotherapy.