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Frontiers in Pharmacology 2024Currently 1.3 billion individuals globally engage in smoking, leading to significant morbidity and mortality, particularly among diabetic patients. There is urgent need... (Review)
Review
Currently 1.3 billion individuals globally engage in smoking, leading to significant morbidity and mortality, particularly among diabetic patients. There is urgent need for a better understanding of how smoking influences antidiabetic treatment efficacy. The review underscores the role of cigarette smoke, particularly polycyclic aromatic hydrocarbons (PAHs), in modulating the metabolic pathways of antidiabetic drugs, primarily through the induction of cytochrome P450 (CYP450) enzymes and uridine diphosphate (UDP)-glucuronosyltransferases (UGTs), thus impacting drug pharmacokinetics and therapeutic outcomes. Furthermore, the review addresses the relatively uncharted territory of how smoking cessation influences diabetes treatment, noting that cessation can lead to significant changes in drug metabolism, necessitating dosage adjustments. Special attention is given to the interaction between smoking cessation aids and antidiabetic medications, a critical area for patient safety and effective diabetes management. This scoping review aims to provide healthcare professionals with the knowledge to better support diabetic patients who smoke or are attempting to quit, ensuring tailored and effective treatment strategies. It also identifies gaps in current research, advocating for more studies to fill these voids, thereby enhancing patient care and treatment outcomes for this at-risk population.
PubMed: 38957391
DOI: 10.3389/fphar.2024.1406860 -
Advances in Pharmacological and... 2024Ginseng has a long history of drug application in China, which can treat various diseases and achieve significant efficacy. Ginsenosides have always been deemed... (Review)
Review
Ginseng has a long history of drug application in China, which can treat various diseases and achieve significant efficacy. Ginsenosides have always been deemed important ingredients for pharmacological activities. Based on the structural characteristics of steroidal saponins, ginsenosides are mainly divided into protopanaxadiol-type saponins (PDS, mainly including Rb1, Rb2, Rd, Rc, Rh2, CK, and PPD) and protopanaxatriol-type saponins (PTS, mainly including Re, R1, Rg1, Rh1, Rf, and PPT). The structure differences between PDS and PTS result in the differences of pharmacological activities. This paper provides an overview of PDS and PTS, mainly focusing on their chemical profile, pharmacokinetics, hydrolytic metabolism, and pharmacological activities including antioxidant, antifatigue, antiaging, immunodulation, antitumor, cardiovascular protection, neuroprotection, and antidiabetes. It is intended to contribute to an in-depth study of the relationship between PDS and PTS.
PubMed: 38957183
DOI: 10.1155/2024/9096774 -
International Journal of Nanomedicine 2024Salidroside (SAL) is the most effective component of , a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of , exhibiting considerable...
BACKGROUND
Salidroside (SAL) is the most effective component of , a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of , exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized.
METHODS AND RESULTS
This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/β-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery.
CONCLUSION
Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.
Topics: Osteogenesis; Animals; Nanofibers; Gelatin; Polyesters; Glucosides; Phenols; Phenanthrenes; Humans; Neovascularization, Physiologic; Human Umbilical Vein Endothelial Cells; Mesenchymal Stem Cells; Rats, Sprague-Dawley; Rats; Male; Bone Regeneration; Membranes, Artificial; Coculture Techniques; Drug Liberation; Cell Differentiation
PubMed: 38957181
DOI: 10.2147/IJN.S461141 -
Biomedical Chromatography : BMC Jul 2024Loganic acid is an iridoid compound extracted from Gentianaceae plant Gentiana macrophylla Pall. It can effectively inhibit inflammation and tumor migration and has...
Loganic acid is an iridoid compound extracted from Gentianaceae plant Gentiana macrophylla Pall. It can effectively inhibit inflammation and tumor migration and has antioxidant activity. In this paper, we establish a simple, fast, sensitive and validated LC-MS method with the purpose of quantification of loganic acid in rat plasma with gliclazide as an internal standard (IS). Methanol was used to precipitate the protein in the plasma sample, and a C column (2.1 × 50 mm, 1.7 μm) was used for the separation of the target compound. Meanwhile, 0.1% formic acid water-methanol was employed as the mobile phase. Multiple reaction monitoring detection mode was adopted in detection with m/z 375.1 > 213.2 for loganic acid and m/z 322.1 > 169.9 for the IS, respectively, in negative ion scan mode. The linear range of calibration curve was 5.77-11,540.00 ng/ml, and the lower limit of detedtion was 2.89 ng/ml. The inter-day and intra-day precision and accuracy were <15% for lower limit of quantitation, low, middle and high quality control samples. This method was successfully used for the pharmacokinetic study of loganic acid in rat plasma at a dose range of 50-150 mg/kg for oral administration and 2 mg/kg for intravenous administration. The pharmacokinetic results showed that the oral bioavailability of loganic acid was low (2.71-5.58%).
PubMed: 38956830
DOI: 10.1002/bmc.5951 -
Biomedical Chromatography : BMC Jul 2024α-Bisabolol (α-BIS) is a sesquiterpene alcohol present in chamomile essential oil [Chamomilla recutita (L.) Rauschert]. Despite its numerous pharmacological effects,...
α-Bisabolol (α-BIS) is a sesquiterpene alcohol present in chamomile essential oil [Chamomilla recutita (L.) Rauschert]. Despite its numerous pharmacological effects, its pharmacokinetics remain understudied. An analytical method capable of quantifying α-BIS in plasma is crucial to enable pharmacokinetic analysis. Presently, only one study has quantified it using mass spectrometry. Administering α-BIS requires a nanoemulsion for intravenous injection. This study aimed to develop and validate a bioanalytical method using high-performance liquid chromatography with an ultraviolet detector to quantify α-BIS in rat plasma. The method employed acetonitrile and ultrapure water (80:20, v/v) as the mobile phase, with a flow rate of 1 ml/min and concentrations ranging from 465 to 29.625 μg/ml. All US Food and Drug Administration-designated assays were successful, indicating the method's precision, accuracy, sensitivity and linearity in determining α-BIS in rat plasma. The developed nanoemulsion, assessed through dynamic light scattering analysis, the ensemble collection of particles and polydispersity index evaluation, proved safe and effective for intravenous administration. The pharmacokinetic parameters such as volume of distribution, clearance and half-life indicated that α-BIS tends to persist in the body. This study provides a foundation for further research to explore α-BIS's potential pharmaceutical applications in the future.
PubMed: 38956820
DOI: 10.1002/bmc.5949 -
Pediatric Blood & Cancer Jul 2024The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We studied vincristine exposure in...
The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We studied vincristine exposure in Kenyan children and dose-escalated in case of low vincristine exposure (NCT05844670). Average vincristine exposure was high. Individual vincristine exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia, or malnutrition. None of the 15 participants developed VIPN. Low vincristine exposure was seen in one participant: a dose increase was implemented without side effects. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.
PubMed: 38956809
DOI: 10.1002/pbc.31160 -
Stem Cell Research & Therapy Jul 2024Mesenchymal stem cells (MSCs) demonstrate a wide range of therapeutic capabilities in the treatment of inflammatory bowel disease (IBD). The intraperitoneal injection of...
BACKGROUND
Mesenchymal stem cells (MSCs) demonstrate a wide range of therapeutic capabilities in the treatment of inflammatory bowel disease (IBD). The intraperitoneal injection of MSCs has exhibited superior therapeutic efficacy on IBD than intravenous injection. Nevertheless, the precise in vivo distribution of MSCs and their biological consequences following intraperitoneal injection remain inadequately understood. Additional studies are required to explore the correlation between MSCs distribution and their biological effects.
METHODS
First, the distribution of human umbilical cord MSCs (hUC-MSCs) and the numbers of Treg and Th17 cells in mesenteric lymph nodes (MLNs) were analyzed after intraperitoneal injection of hUC-MSCs. Subsequently, the investigation focused on the levels of transforming growth factor beta1 (TGF-β1), a key cytokine to the biology of both Treg and Th17 cells, in tissues of mice with colitis, particularly in MLNs. The study also delved into the impact of hUC-MSCs therapy on Treg cell counts in MLNs, as well as the consequence of TGFB1 knockdown hUC-MSCs on the differentiation of Treg cells and the treatment of IBD.
RESULTS
The therapeutic effectiveness of intraperitoneally administered hUC-MSCs in the treatment of colitis was found to be significant, which was closely related to their quick migration to MLNs and secretion of TGF-β1. The abundance of hUC-MSCs in MLNs of colitis mice is much higher than that in other organs even the inflamed sites of colon. Intraperitoneal injection of hUC-MSCs led to a significant increase in the number of Treg cells and a decrease in Th17 cells especially in MLNs. Furthermore, the concentration of TGF-β1, the key cytokine for Treg differentiation, were also found to be significantly elevated in MLNs after hUC-MSCs treatment. Knockdown of TGFB1 in hUC-MSCs resulted in a noticeable reduction of Treg cells in MLNs and the eventually failure of hUC-MSCs therapy in colitis.
CONCLUSIONS
MLNs may be a critical site for the regulatory effect of hUC-MSCs on Treg/Th17 cells and the therapeutic effect on colitis. TGF-β1 derived from hUC-MSCs promotes local Treg differentiation in MLNs. This study will provide new ideas for the development of MSC-based therapeutic strategies in IBD patients.
Topics: T-Lymphocytes, Regulatory; Transforming Growth Factor beta1; Animals; Mesenchymal Stem Cells; Humans; Colitis; Mesenchymal Stem Cell Transplantation; Mice; Lymph Nodes; Th17 Cells; Cell Differentiation; Umbilical Cord; Mesentery; Mice, Inbred C57BL; Mice, Inbred BALB C; Male; Inflammatory Bowel Diseases
PubMed: 38956621
DOI: 10.1186/s13287-024-03809-x -
BMC Urology Jul 2024Prostate cancer (PCa) is a complex and biologically diverse disease with no curative treatment options at present. This study aims to utilize computational methods to...
Prostate cancer (PCa) is a complex and biologically diverse disease with no curative treatment options at present. This study aims to utilize computational methods to explore potential anti-PCa compounds based on differentially expressed genes (DEGs), with the goal of identifying novel therapeutic indications or repurposing existing drugs. The methods employed in this study include DEGs-to-drug prediction, pharmacokinetics prediction, target prediction, network analysis, and molecular docking. The findings revealed a total of 79 upregulated DEGs and 110 downregulated DEGs in PCa, which were used to identify drug compounds capable of reversing the dysregulated conditions (dexverapamil, emetine, parthenolide, dobutamine, terfenadine, pimozide, mefloquine, ellipticine, and trifluoperazine) at a threshold probability of 20% on several molecular targets, such as serotonin receptors 2a/2b/2c, HERG protein, adrenergic receptors alpha-1a/2a, dopamine D3 receptor, inducible nitric oxide synthase (iNOS), epidermal growth factor receptor erbB1 (EGFR), tyrosine-protein kinases, and C-C chemokine receptor type 5 (CCR5). Molecular docking analysis revealed that terfenadine binding to inducible nitric oxide synthase (-7.833 kcal.mol) and pimozide binding to HERG (-7.636 kcal.mol). Overall, binding energy ΔG (Total) at 0 ns was lower than that of 100 ns for both the Terfenadine-iNOS complex (-101.707 to -103.302 kcal.mol) and Ellipticine-TOPIIα complex (-42.229 to -58.780 kcal.mol). In conclusion, this study provides insight on molecular targets that could possibly contribute to the molecular mechanisms underlying PCa. Further preclinical and clinical studies are required to validate the therapeutic effectiveness of these identified drugs in PCa disease.
Topics: Prostatic Neoplasms; Humans; Male; Molecular Docking Simulation; Computer Simulation; Antineoplastic Agents; Gene Expression Regulation, Neoplastic; Gene Expression Profiling
PubMed: 38956591
DOI: 10.1186/s12894-024-01521-9 -
Scientific Reports Jul 2024Exposure of firefighting instructors to polycyclic aromatic hydrocarbons (PAHs) such as naphthalene is unavoidable during live fire training. The study aimed to...
Exposure of firefighting instructors to polycyclic aromatic hydrocarbons (PAHs) such as naphthalene is unavoidable during live fire training. The study aimed to investigate naphthalene uptake by measuring the urinary excretion of the naphthalene metabolite 1,2-dihydroxynaphthalene (DHN), to describe the DHN elimination kinetics and to evaluate the results by comparison to further biomarkers of PAH exposure. N = 6 male non-smoking firefighting instructors completed five training sessions each in a residential fire simulation unit under respiratory protection. All participants provided two urine samples before and another seven samples within an 18-h-interval after each session. DHN was detected by gas chromatography/tandem mass spectrometry (GC-MS/MS) in all samples (n = 237) with median concentrations ranging from 3.3 µg/g crea. (range 0.9-10.2) before exposure to 134.2 µg/g crea. (43.4-380.4) post exposure. Maximum elimination found 3.3 h (median) after onset of exposure decreased with a mean half-life of 6.6 h to 27.1 µg/g crea. (15.7-139.5) 18 h after training. DHN sensitively indicated a presumed dermal naphthalene intake during training, showing similar elimination kinetics like other naphthalene metabolites. Internal exposure of the participants transiently exceeded exposures determined for non-smokers in the general population, but was lower than at other workplaces with PAH exposure. Despite limited uptake, accumulation is possible with daily exposure.
Topics: Humans; Male; Firefighters; Occupational Exposure; Adult; Polycyclic Aromatic Hydrocarbons; Naphthols; Naphthalenes; Renal Elimination; Gas Chromatography-Mass Spectrometry; Biomarkers; Middle Aged; Fires
PubMed: 38956405
DOI: 10.1038/s41598-024-62388-2 -
Scientific Reports Jul 2024Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable...
Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/βcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC.
Topics: Male; Elastin; Humans; Cell Line, Tumor; Nanogels; Prostatic Neoplasms, Castration-Resistant; Drug Delivery Systems; Cell Survival; Drug Liberation; Antineoplastic Agents; Benzopyrans; Butyrates
PubMed: 38956125
DOI: 10.1038/s41598-024-65999-x