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Pharmaceutics Jun 2024DOX/TPOR@CB[7] was synthesized via self-assembly, and its physicochemical properties and ability to generate reactive oxygen species (ROS) were evaluated. The impact of...
DOX/TPOR@CB[7] was synthesized via self-assembly, and its physicochemical properties and ability to generate reactive oxygen species (ROS) were evaluated. The impact of photodynamic therapy on SH-SY5Y cells was assessed using the MTT assay, while flow cytometry analysis was employed to detect cell apoptosis. Confocal laser scanning microscopy was utilized to observe the intracellular distribution of DOX/TPOR@CB[7] in SH-SY5Y cells. Additionally, fluorescence imaging of DOX/TPOR@CB[7] in nude mice bearing SH-SY5Y tumors and examination of the combined effects of photodynamic and chemical therapies were conducted. The incorporation of CB[7] significantly enhanced the optical properties of DOX/TPOR@CB[7], resulting in increased ROS production and pronounced toxicity towards SH-SY5Y cells. Moreover, both the apoptotic and mortality rates exhibited significant elevation. In vivo experiments demonstrated that tumor growth inhibition was most prominent in the DOX/TPOR@CB[7] group. π-π interactions facilitated the binding between DOX and photosensitizer TPOR, with TPOR's naphthalene hydrophilic groups encapsulated within CB[7]'s cavity through host-guest interactions with CB[7]. Therefore, CB[7] can serve as a nanocarrier to enhance the combined application of chemical therapy and photodynamic therapy, thereby significantly improving treatment efficacy against neuroblastoma tumors.
PubMed: 38931942
DOI: 10.3390/pharmaceutics16060822 -
Pharmaceutics Jun 2024Insufficient endosomal escape presents a major hurdle for successful nucleic acid therapy. Here, for the first time, a chemical electron transfer (CET) system was...
Insufficient endosomal escape presents a major hurdle for successful nucleic acid therapy. Here, for the first time, a chemical electron transfer (CET) system was integrated into small interfering RNA (siRNA) lipid nanoparticles (LNPs). The CET acceptor can be chemically excited using the generated energy between the donor and hydrogen peroxide, which triggers the generation of reactive oxygen species (ROS), promoting endosomal lipid membrane destabilization. Tetra-oleoyl tri-lysino succinoyl tetraethylene pentamine was included as an ionizable lipopeptide with a U-shaped topology for effective siRNA encapsulation and pH-induced endosomal escape. LNPs loaded with siRNA and CET components demonstrated a more efficient endosomal escape, as evidenced by a galectin-8-mRuby reporter; ROS significantly augmented galectin-8 recruitment by at least threefold compared with the control groups, with a value of 0.03. Moreover, CET-enhanced LNPs achieved a 24% improvement in apoptosis level by knocking down the tumor-protective gene nuclear factor erythroid 2-related factor 2, boosting the CET-mediated ROS cell killing.
PubMed: 38931900
DOI: 10.3390/pharmaceutics16060779 -
Pharmaceutics May 2024This review paper examines the evolution of photodynamic therapy (PDT) as a novel, minimally invasive strategy for treating atherosclerosis, a leading global health... (Review)
Review
This review paper examines the evolution of photodynamic therapy (PDT) as a novel, minimally invasive strategy for treating atherosclerosis, a leading global health concern. Atherosclerosis is characterized by the accumulation of lipids and inflammation within arterial walls, leading to significant morbidity and mortality through cardiovascular diseases such as myocardial infarction and stroke. Traditional therapeutic approaches have primarily focused on modulating risk factors such as hypertension and hyperlipidemia, with emerging evidence highlighting the pivotal role of inflammation. PDT, leveraging a photosensitizer, specific-wavelength light, and oxygen, offers targeted treatment by inducing cell death in diseased tissues while sparing healthy ones. This specificity, combined with advancements in nanoparticle technology for improved delivery, positions PDT as a promising alternative to traditional interventions. The review explores the mechanistic basis of PDT, its efficacy in preclinical studies, and the potential for enhancing plaque stability and reducing macrophage density within plaques. It also addresses the need for further research to optimize treatment parameters, mitigate adverse effects, and validate long-term outcomes. By detailing past developments, current progress, and future directions, this paper aims to highlight PDT's potential in revolutionizing atherosclerosis treatment, bridging the gap from experimental research to clinical application.
PubMed: 38931851
DOI: 10.3390/pharmaceutics16060729 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Efforts have been made to improve the therapeutic efficiency of tumor treatments, and metal-organic frameworks (MOFs) have shown excellent potential in tumor therapy....
Efforts have been made to improve the therapeutic efficiency of tumor treatments, and metal-organic frameworks (MOFs) have shown excellent potential in tumor therapy. Monotherapy for the treatment of tumors has limited effects due to the limitation of response conditions and inevitable multidrug resistance, which seriously affect the clinical therapeutic effect. In this study, we chose to construct a multiple cascade synergistic tumor drug delivery system MIL-101(Fe)-DOX-TCPP-MnO@PDA-Ag (MDTM@P-Ag) using MOFs as drug carriers. Under near-infrared (NIR) laser irradiation, 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) and Ag NPs loaded on MDTM@P-Ag can be activated to generate cytotoxic reactive oxygen species (ROS) and achieve photothermal conversion, thus effectively inducing the apoptosis of tumor cells and achieving a combined photodynamic/photothermal therapy. Once released at the tumor site, manganese dioxide (MnO) can catalyze the decomposition of hydrogen peroxide (HO) in the acidic microenvironment of the tumor to generate oxygen (O) and alleviate the hypoxic environment of the tumor. Fe/Mn will mediate a Fenton/Fenton-like reaction to generate cytotoxic hydroxyl radicals (·OH), while depleting the high concentration of glutathione (GSH) in the tumor, thus enhancing the chemodynamic therapeutic effect. The successful preparation of the tumor drug delivery system and its good synergistic chemodynamic/photodynamic/photothermal therapeutic effect in tumor treatment can be demonstrated by the experimental results of material characterization, performance testing and in vitro experiments.
PubMed: 38931479
DOI: 10.3390/ph17060812 -
Pharmaceuticals (Basel, Switzerland) May 2024Immunotherapy has shown promising clinical results in clear cell renal cell carcinoma (ccRCC), but low clinical target response rates due to dysfunction of the major...
Improved Immunotherapy Outcomes via Cuproptosis Upregulation of HLA-DRA Expression: Promoting the Aggregation of CD4 and CD8T Lymphocytes in Clear Cell Renal Cell Carcinoma.
Immunotherapy has shown promising clinical results in clear cell renal cell carcinoma (ccRCC), but low clinical target response rates due to dysfunction of the major histocompatibility complex (MHC) and an inhibitory tumor immune microenvironment (TIME) have largely limited the associated clinical benefits. In the present study, we explored the feasibility of enhancing tumor-specific-MHC-II-HLA-DRA expression, counteracting the TIME's suppressive effects, thereby improving the sensitivity of immune checkpoint inhibitor (ICI) therapy from the standpoint of cuproptosis. Immunohistochemical staining and in vitro experiments validated the expression of HLA-DRA in ccRCC and its positive impact on ICI therapy. Subsequently, we observed that cuproptosis upregulated HLA-DRA expression in a dose-dependent manner, further confirming the link between cuproptosis and HLA-DRA. In vivo experiments showed that cuproptosis increased the sensitivity to ICI treatment, and implementing cuproptosis alongside anti-PD-1 treatment curtailed tumor growth. Mechanistically, cuproptosis upregulates HLA-DRA expression at the transcriptional level in a dose-dependent manner by inducing the production of reactive oxygen species; high levels of HLA-DRA promote the expression of chemokines CCL5, CXCL9, and CXCL10 in the TIME, inhibiting the development of a pro-tumor microenvironment by promoting the infiltration of CD4T and CD8T cells, thereby synergizing ICI therapy and exerting anti-tumor effects. Taken together, this work highlights the role of cuproptosis in mediating TIME remodeling and synergistic immunotherapy, providing new evidence that cuproptosis can evoke effective anti-tumor immune responses.
PubMed: 38931345
DOI: 10.3390/ph17060678 -
Pharmaceuticals (Basel, Switzerland) May 2024Photodynamic therapy (PDT) is a minimally invasive treatment for several diseases. It combines light energy with a photosensitizer (PS) to destroy the targeted cells or... (Review)
Review
UNLABELLED
Photodynamic therapy (PDT) is a minimally invasive treatment for several diseases. It combines light energy with a photosensitizer (PS) to destroy the targeted cells or tissues. A PS itself is a non-toxic substance, but it becomes toxic to the target cells through the activation of light at a specific wavelength. There are some limitations of PDT, although it has been used in clinical studies for a long time. Two-photon excitation (TPE) and upconversion (UC) for PDT have been recently developed. A TPE nanoparticle-based PS combines the advantages of TPE and nanotechnology that has emerged as an attractive therapeutic agent for near-infrared red (NIR) light-excited PDT, whilst UC is also used for the NIR light-triggered drug release, activation of 'caged' imaging, or therapeutic molecules during PDT process for the diagnosis, imaging, and treatment of cancers.
METHODS
Nine electronic databases were searched, including WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and China National Knowledge Infrastructure (CNKI), without any language constraints. TPE and UCNP were evaluated to determine if they had different effects from PDT on cancers. All eligible studies were analyzed and summarized in this review.
RESULTS
TPE-PDT and UCNP-PDT have a high cell or tissue penetration ability through the excitation of NIR light to activate PS molecules. This is much better than the conventional PDT induced by visible or ultraviolet (UV) light. These studies showed a greater PDT efficacy, which was determined by enhanced generation of reactive oxygen species (ROS) and reduced cell viability, as well as inhibited abnormal cell growth for the treatment of cancers.
CONCLUSIONS
Conventional PDT involves Type I and Type II reactions for the generation of ROS in the treatment of cancer cells, but there are some limitations. Recently, TPE-PDT and UCNP-PDT have been developed to overcome these problems with the help of nanotechnology in in vitro and in vivo studies.
PubMed: 38931331
DOI: 10.3390/ph17060663 -
Nutrients Jun 2024Free radicals and reactive oxygen species initiate when the oxidative stress arises. (1) Background: The effect of natural molecules on oxidative stress in...
Free radicals and reactive oxygen species initiate when the oxidative stress arises. (1) Background: The effect of natural molecules on oxidative stress in hyperlipidemic rats, taking statins, was observed. (2) Methods: One hundred and twelve white Wistar rats, males and females, were divided into seven: Group I received 20 mg of atorvastatin while groups II and III received a combination of 20 mg of atorvastatin and 100 mg of Sea buckthorn and grape extract. Groups IV and V received 100 mg of Sea buckthorn and grape extract, while groups VI and VII received only high-fat diet (HFD) and normal rodents' fodder. After two and six months, rats were euthanized, and blood was gathered to measure the main paraclinical values and total antioxidant capacity (TAC). Also, the liver and kidney were stored for the organs' cytoarchitecture. For statistics, two-way analysis of variance (ANOVA), was performed. (3) Results: HFD produced hyperlipidemia, accompanied by augmented serum and hepatic oxidative stress markers, in addition to a reduction in antioxidant enzyme activities and glutathione levels. Polyphenolic substances proven efficient against HFD caused oxidative stress. (4) Conclusions: Atorvastatin heightened the histological injuries caused by the fatty diet, but these were diminished by taking atorvastatin in combination with 100 mg/kg of plant extracts.
Topics: Animals; Atorvastatin; Oxidative Stress; Rats, Wistar; Hyperlipidemias; Male; Hippophae; Vitis; Plant Extracts; Female; Antioxidants; Diet, High-Fat; Liver; Rats; Biomarkers; Kidney
PubMed: 38931308
DOI: 10.3390/nu16121954 -
Nutrients Jun 2024Endothelial dysfunction decreases exercise limb blood flow (BF) and muscle oxygenation. Acute L-Citrulline supplementation (CIT) improves muscle tissue oxygen saturation... (Randomized Controlled Trial)
Randomized Controlled Trial
Endothelial dysfunction decreases exercise limb blood flow (BF) and muscle oxygenation. Acute L-Citrulline supplementation (CIT) improves muscle tissue oxygen saturation index (TSI) and deoxygenated hemoglobin (HHb) during exercise. Although CIT improves endothelial function (flow-mediated dilation [FMD]) in hypertensive women, the impact of CIT on exercise BF and muscle oxygenation (TSI) and extraction (HHb) are unknown. We examined the effects of CIT (10 g/day) and a placebo for 4 weeks on blood pressure (BP), arterial vasodilation (FMD, BF, and vascular conductance [VC]), and forearm muscle oxygenation (TSI and HHb) at rest and during exercise in 22 hypertensive postmenopausal women. Compared to the placebo, CIT significantly ( < 0.05) increased FMD (Δ-0.7 ± 0.6% vs. Δ1.6 ± 0.7%) and reduced aortic systolic BP (Δ3 ± 5 vs. Δ-4 ± 6 mmHg) at rest and improved exercise BF (Δ17 ± 12 vs. Δ48 ± 16 mL/min), VC (Δ-21 ± 9 vs. Δ41 ± 14 mL/mmHg/min), TSI (Δ-0.84 ± 0.58% vs. Δ1.61 ± 0.46%), and HHb (Δ1.03 ± 0.69 vs. Δ-2.76 ± 0.77 μM). Exercise BF and VC were positively correlated with improved FMD and TSI during exercise (all < 0.05). CIT improved exercise artery vasodilation and muscle oxygenation via increased endothelial function in hypertensive postmenopausal women.
Topics: Humans; Female; Postmenopause; Citrulline; Middle Aged; Hypertension; Muscle, Skeletal; Hand Strength; Dietary Supplements; Vasodilation; Regional Blood Flow; Aged; Exercise; Blood Pressure; Oxygen; Oxygen Consumption; Double-Blind Method; Endothelium, Vascular
PubMed: 38931289
DOI: 10.3390/nu16121935 -
Nutrients Jun 2024Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind... (Randomized Controlled Trial)
Randomized Controlled Trial
Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, subsp. LY-66, PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion ( < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage ( < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in following supplementation with PL-02 and LY-66 ( < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants.
Topics: Humans; Probiotics; Double-Blind Method; Lactobacillus plantarum; Male; Lactococcus lactis; Gastrointestinal Microbiome; Muscle Strength; Physical Endurance; Female; Adult; Young Adult; Oxygen Consumption; Muscle, Skeletal; Exercise
PubMed: 38931275
DOI: 10.3390/nu16121921 -
Nutrients Jun 2024Advanced glycation end products (AGEs) accumulate in the plasma of pregnant women with hyperglycemia, potentially inducing oxidative stress and fetal developmental...
Advanced glycation end products (AGEs) accumulate in the plasma of pregnant women with hyperglycemia, potentially inducing oxidative stress and fetal developmental abnormalities. Although intrauterine hyperglycemia has been implicated in excessive fetal growth, the effects of maternal AGEs on fetal development remain unclear. We evaluated the differentiation regulators and cellular signaling in the skeletal muscles of infants born to control mothers (ICM), diabetic mothers (IDM), and diabetic mothers supplemented with either cis-palmitoleic acid (CPA) or trans-palmitoleic acid (TPA). Cell viability, reactive oxygen species levels, and myotube formation were assessed in AGE-exposed C2C12 cells to explore potential mitigation by CPA and TPA. Elevated receptors for AGE expression and decreased Akt and AMPK phosphorylation were evident in rat skeletal muscles in IDM. Maternal palmitoleic acid supplementation alleviated insulin resistance by downregulating RAGE expression and enhancing Akt phosphorylation. The exposure of the C2C12 cells to AGEs reduced cell viability and myotube formation and elevated reactive oxygen species levels, which were attenuated by CPA or TPA supplementation. This suggests that maternal hyperglycemia and plasma AGEs may contribute to skeletal muscle disorders in offspring, which are mitigated by palmitoleic acid supplementation. Hence, the maternal intake of palmitoleic acid during pregnancy may have implications for fetal health.
Topics: Fatty Acids, Monounsaturated; Glycation End Products, Advanced; Female; Animals; Pregnancy; Receptor for Advanced Glycation End Products; Rats; Muscle, Skeletal; Reactive Oxygen Species; Cell Line; Cell Survival; Mice; Dietary Supplements; Proto-Oncogene Proteins c-akt; Oxidative Stress; Insulin Resistance; Humans; Phosphorylation; Rats, Sprague-Dawley; Pregnancy in Diabetics; Male; Fetal Development
PubMed: 38931253
DOI: 10.3390/nu16121898