Stem cell therapy has emerged as a promising approach for regenerative medicine, offering potential treatments for a wide range of diseases and injuries. Although stem cell therapy has great promise, several obstacles have prevented its broad clinical adoption. The effectiveness of therapy has been inhibited by problems such as ineffective stem cell differentiation, low post-transplantation survival rates, and restricted control over stem cell behavior. Furthermore, the implementation of stem cell therapies is further complicated by the possibility of immunological rejection and cancer. Innovative strategies that provide precise control over stem cell characteristics and maximize their therapeutic potential are desperately needed to overcome these obstacles. Recent studies have shown that the effectiveness of stem cell treatments can be greatly increased by nanoscale advances. By establishing an ideal microenvironment and precisely offering growth factors, nanomaterials such as nanoparticles, nanocomposites, and quantum dots have been demonstrated to improve stem cell differentiation and proliferation. This article provides an overview of the recent trends and applications of nanoscale innovations in the context of stem cell therapy. The recent development of precision medicine has been facilitated by the incorporation of nanotechnology into stem cell therapy. The ability to manipulate stem cells at the nanoscale offers unprecedented control over their behavior and function, opening up exciting possibilities for personalized and highly effective therapeutic interventions. This review paper highlights the recent trends and applications of nanotechnology in advancing stem cell therapy, showcasing its potential to revolutionize regenerative medicine.

The fixed dose combination of valsartan (VAL) and hydrochlorothiazide (HCTZ) is the most commonly prescribed medicine for the effective treatment of hypertension. In this study, a simple sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantitation of VAL and HCTZ in human plasma by using irbesartan (IRB) and hydroflumethiazide (HFMZ) as their specific internal standards (ISs). HLB cartridge-based solid-phase extraction was used for the extraction of analytes and ISs. The chromatographic separation was achieved on Lichrocart RP Select (125 × 4 mm), 5 nm with the mobile phase composition of acetonitrile: 10 mM ammonium acetate buffer: 95:05, v/v, at flow rate of 0.5 mL/min. The turbo ion electrospray ionization in negative mode was used as ion source for the sample ionization. The precursor to product ion transitions were 434.10 > 179.10 (VAL), 295.70 > 204.90 (HCTZ), 427.10 > 192.90 (IRB), and 329.90 > 302.40 (HFMZ) for detection and quantification of analytes and their ISs. The retention times of VAL and HCTZ were 1.90 min and 2.30 min, respectively. The range for the calibration curves of VAL and HCTZ were 50.2–6018.6 ng/mL and 1.25–507.63 ng/mL, respectively, with good linearity having correlation coefficient values of ≥0.995 for both VAL and HCTZ. All validation parameter results (selectivity, precision and accuracy, matrix effects and stabilities) were within the acceptable range as per USFDA guideline for bioanalytical method validation. The intra-day and inter-day accuracy data for VAL were within the range of 105.68–114.22% and 98.41–108.16%, respectively, whereas for HCTZ they were 87.01–101.18% and 95.16–99.37%, respectively. The ion suppression effects produced for VAL and ion enhancement effects produced for HCTZ were insignificant according to the proposed sample cleanup procedure. The developed LC-MS/MS method was successfully applied to bioequivalence study on healthy volunteers.

The vacuolar H⁺-ATPase (V-ATPase) is an ATP-dependent proton pump that governs the pH of various intracellular compartments and also functions at the plasma membrane in certain cell types, including cancer cells. Membrane targeting of the V-ATPase is controlled by isoforms of subunit a, and we have previously shown that isoforms a3 and a4 are important for the migration and invasion of several breast cancer cell lines in vitro. Using CRISPR-mediated genome editing to selectively disrupt each of the four a subunit isoforms, we also recently showed that a4 is critical to plasma membrane V-ATPase localization, as well as in vitro migration and invasion of 4T1-12B murine breast cancer cells. We now report that a4 is important for the growth of 4T1-12B tumors in vivo. We found that BALB/c mice bearing a4^−/− 4T1-12B allografts had significantly smaller tumors than mice in the control group. In addition, we determined that a4^−/− allografts showed dramatically reduced metastases to the lung and reduced luminescence intensity of metastases to bone relative to the control group. Taken together, these results suggest that the a4 isoform of the V-ATPase represents a novel potential therapeutic target to limit breast cancer growth and metastasis.

New quinazoline derivatives were designed and synthesized to target VEGFR-2, aiming to identify potential anticancer agents. The synthesized compounds underwent in vitro screening to evaluate their cytotoxic effects across 60 cancer cells following the NCI protocol. The most promising derivatives, 3i and 3j, underwent further evaluation via a five-dose test to assess broad-spectrum anticancer activity. Their VEGFR-2 inhibitory potential was compared to sorafenib. Cell cycle analyses, annexin V-FITC, and apoptotic markers were used to examine HT-29 colon cancer cells after treatment with 3j for cell cycle arrest and apoptosis induction. Molecular docking and MD simulations explored binding interactions, while ADMET studies assessed pharmacokinetics. Compounds 3i and 3j exhibited potent to moderate cytotoxic activity, with compound 3j showing the highest activity against colon cancer cell lines (GI₅₀ = 3.29 μM). Both compounds demonstrated promising VEGFR-2 inhibitory activity (IC₅₀ = 0.120 and 0.197 µM, respectively), comparable to sorafenib (IC₅₀ = 0.088 µM). Cell cycle analysis displayed G1 phase arrest and pro-apoptotic effects. Docking studies confirmed favorable VEGFR-2 binding affinity (-7.57 and -7.83 kcal/mol). ADMET profiling indicated promising drug-like properties. Compounds 3i and 3j exhibit promising VEGFR-2 inhibitory properties and significant anticancer activity, warranting further investigation.

Background: There is an urgent need to identify new biomarkers for early diagnosis and development of therapeutic strategies for diabetes mellitus (DM) patients who have invasive breast cancer (BC). We previously reported the increased activated form of 70 kDa ribosomal protein S6 kinase 1 (phospho-p70S6K1) in a triple-negative BC (TNBC) cell line MDA-MB-231 exposed to glycated albumin (GA) and in invasive ductal carcinoma tissues from T2DM patients, compared to untreated cells and their non-diabetic counterparts, respectively. Objective: We aimed to explore the function of p70S6K1 in GA-promoted TNBC progression. Methods: By employing small interference (si)RNA technology or blocking its kinase activity using its specific pharmacological inhibitor, we monitored cell invasion using Transwell^® inserts and the expression levels of activated signaling proteins and cancer-related proteins using Western blot. Results: In silico analysis revealed that high mRNA levels of p70S6K1 were associated with an unfavorable prognosis and progression to advanced stages of TNBC in DM patients. The downregulation/blockade of p70S6K1 inhibited GA-promoted MDA-MB-231 cell invasion and the phosphorylation of protein S6 and ERK1/2, the p70S6K1 downstream effector, and the key oncogenic signaling protein, respectively. The suppression of the expression of GA-upregulated cancer proteins, including enolase-2, capping protein CapG, galectin-3, and cathepsin D, was observed after p70S6K1 downregulation/blockade. Further in silico validation analyses revealed increased gene expression of galectin-3 in DM TNBC patients, resulting in poor overall survival and disease-free survival. Conclusions: Targeting p70S6K1 may present a valuable therapeutic strategy, while galectin-3 could serve as a potential prognostic biomarker for invasive BC progression in DM patients.