A substantial number of crucial lncRNAs are present in both tumor and normal cells, functioning either as biological markers or as potential targets for anti-cancer therapies. Compared to some small non-coding RNA therapeutics, lncRNA-based drug applications in clinical settings encounter limitations. Distinguishing them from microRNAs and other non-coding RNAs, long non-coding RNAs (lncRNAs) tend to have a higher molecular weight and a conserved secondary structure, leading to a more intricate delivery process compared to 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 review below comprehensively examines the function, mechanisms, and diverse approaches for lncRNA transfection employing multiple biomaterials, particularly within the context of cancer and other diseases.

One of cancer's key characteristics is the reprogramming of energy metabolism, an established and vital approach to cancer treatment. Isocitrate dehydrogenases (IDHs), including IDH1, IDH2, and IDH3, are a group of key proteins involved in the metabolic process of isocitrate, transforming it via oxidative decarboxylation into -ketoglutarate (-KG). When IDH1 or IDH2 genes are mutated, the consequence is the formation of D-2-hydroxyglutarate (D-2HG) from -ketoglutarate (α-KG), a process that fuels the development and progression of cancer. No instances of IDH3 mutations have been identified in the available data. 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. By systematically examining IDH1's regulatory mechanisms in cancer from four interconnected angles – metabolic reprogramming, epigenetic modifications, immune microenvironment dynamics, and phenotypic shifts – this review intends to provide a framework for understanding IDH1's contributions and the development of innovative targeted treatment approaches. In conjunction with other analyses, a review of the IDH1 inhibitor options was also performed. This comprehensive exploration of clinical trial findings and the intricate designs of preclinical models reveals a deep understanding of the research dedicated to IDH1-related cancers.

Circulating tumor clusters (CTCs), arising from the primary tumor in locally advanced breast cancer, are the driving force behind the formation of secondary tumors, a challenge that conventional treatments such as chemotherapy and radiotherapy often fail to overcome. A smart nanotheranostic system developed in this study aims to detect and eradicate circulating tumor cells (CTCs) before they can establish secondary tumors, thereby preventing metastatic progression and potentially increasing the five-year survival rate for breast cancer patients. Dual-modal imaging and dual-toxicity mechanisms, based on self-assembly of targeted multiresponsive nanomicelles, were implemented to eliminate circulating tumor cells (CTCs) in the bloodstream. These nanomicelles incorporate NIR fluorescent superparamagnetic iron oxide nanoparticles, exhibiting magnetic hyperthermia and pH responsiveness. To mimic the CTCs isolated from breast cancer patients, a heterogenous tumor clusters model was constructed. In vitro, the nanotheranostic system's targeting capability, drug release kinetics, hyperthermic effect, and cytotoxic effect on a developed CTC model were further examined. An in vivo model of stage III and IV human metastatic breast cancer, replicated in BALB/c mice, was established to evaluate the biodistribution and therapeutic effectiveness of a micellar nanotheranostic system. Post-treatment with the nanotheranostic system, the observed decrease in circulating tumor cells (CTCs) and distant organ metastasis underscores its potential for capturing and eliminating CTCs, thereby mitigating the formation of secondary tumors at distant sites.

Gas therapy stands as a promising and advantageous treatment option for various cancers. Selleck Disufenton Studies have consistently demonstrated that nitric oxide (NO), a significantly small gas molecule with a notable structure, possesses the potential to combat cancer. Selleck Disufenton Yet, debate and apprehension persist regarding its employment, since it produces the opposite physiological outcomes depending on its concentration in the tumor. Thus, the anti-cancer mechanism of nitric oxide (NO) is paramount for cancer treatment, and the development of targeted NO delivery systems is essential to maximizing the efficacy of NO-based medical applications. Selleck Disufenton The review investigates nitric oxide's natural production, its physiological effects, its application in cancer treatment, and the use of nanoscale delivery systems to administer NO donors. In addition, it summarizes the obstacles faced in the conveyance of nitric oxide (NO) from disparate nanoparticles, and the complications arising from its use in combined therapeutic regimens. A review of the benefits and obstacles presented by diverse NO delivery platforms is presented, aiming to pave the way for potential clinical implementation.

Clinical interventions for chronic kidney disease, at this stage, are remarkably constrained, and the great majority of patients are forced to rely on dialysis to support their lives for a prolonged time. While other avenues of treatment exist, investigations into the gut-kidney axis demonstrate the gut's microbiome as a promising avenue for managing or reversing chronic kidney disease. The present study indicated that berberine, a natural drug with low oral bioavailability, notably improved chronic kidney disease by modulating the gut microbiome and inhibiting the generation of gut-derived uremic toxins, specifically including p-cresol. Berberine, in effect, significantly reduced p-cresol sulfate levels in the blood, mainly through a decrease in the bacterial count of *Clostridium sensu stricto* 1 and inhibition of the tyrosine-p-cresol pathway within the gut's microbiome. While berberine simultaneously increased the number of butyric acid-producing bacteria and the butyric acid content in fecal matter, it conversely reduced the levels of the renal-toxic trimethylamine N-oxide. These findings propose berberine as a potentially therapeutic agent for chronic kidney disease, with the gut-kidney axis as a possible mediating factor.

The poor prognosis associated with triple-negative breast cancer (TNBC) is a direct result of its extremely high malignancy. Patients with elevated levels of Annexin A3 (ANXA3) demonstrate a poor prognosis, suggesting its potential as a prognostic biomarker. The inactivation of ANXA3 expression decisively inhibits TNBC's multiplication and dispersion, indicating the viability of ANXA3 as a promising therapeutic target for TNBC. A new small molecule, (R)-SL18, specifically targeting ANXA3, displays noteworthy anti-proliferative and anti-invasive activity against TNBC cells, as reported. (R)-SL18's direct binding to ANXA3 initiated a cascade leading to elevated ubiquitination and subsequent degradation of ANXA3, showing moderate selectivity across the family. Significantly, (R)-SL18 exhibited a therapeutic efficacy that was both safe and effective in a TNBC patient-derived xenograft model with high ANXA3 expression. In conclusion, (R)-SL18 contributes to decreased -catenin levels, thereby inhibiting the Wnt/-catenin signaling network in TNBC cells. Our data collectively indicated that (R)-SL18-mediated ANXA3 degradation may prove beneficial in TNBC treatment.

Peptides are becoming ever more critical in biological and therapeutic advancements, but their susceptibility to proteolytic degradation remains a major hurdle. Glucagon-like peptide 1 (GLP-1), a natural GLP-1R agonist, holds considerable clinical promise for treating type-2 diabetes mellitus, although its inherent in vivo instability and short half-life have hindered its practical application. A rational design approach is employed to create a set of /sulfono,AA peptide hybrid GLP-1 analogues, acting as GLP-1 receptor agonists. In contrast to the very brief blood plasma half-life (less than 24 hours) of native GLP-1, certain hybrid GLP-1 analogs exhibited remarkable stability, with half-lives exceeding 14 days in both in vivo and in vitro plasma environments. In the realm of type-2 diabetes treatment, these newly developed peptide hybrids could 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.

Immunotherapy stands as a promising strategy in the fight against cancer. Nevertheless, the impact of immunotherapy is constrained in cold tumors, exhibiting a shortage of intratumoral T cells and hampered T-cell activation. Through the creation of an on-demand integrated nano-engager (JOT-Lip), cold tumors were targeted for conversion to hot tumors by mechanisms involving increased DNA damage and dual immune checkpoint inhibition. By coupling T-cell immunoglobulin mucin-3 antibodies (Tim-3 mAb) to liposomes containing oxaliplatin (Oxa) and JQ1, using a metalloproteinase-2 (MMP-2)-sensitive linker, JOT-Lip was synthesized. The DNA repair mechanisms of Oxa cells were undermined by JQ1, thus leading to amplified DNA damage, immunogenic cell death (ICD), and ultimately, facilitated intratumoral T-cell infiltration. JQ1, in conjunction with Tim-3 mAb, disrupted the PD-1/PD-L1 pathway, thus leading to a dual immune checkpoint blockade, enhancing T-cell priming. JOT-Lip's demonstrated effect includes not only augmenting DNA damage and facilitating the release of damage-associated molecular patterns (DAMPs), but also bolstering intratumoral T cell infiltration and promoting T cell priming, thereby successfully transforming cold tumors into hot ones, exhibiting substantial anti-tumor and anti-metastasis capabilities. This study presents a rational approach for a powerful combination regimen and a superior co-delivery method for transforming cold tumors into hot ones, which is highly promising for clinical cancer chemoimmunotherapy applications.