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Selective S1P1 receptor agonists have therapeutic potential to treat a variety of immune-mediated diseases. A series of 2-imino-thiazolidin-4-one derivatives displaying potent S1P1 receptor agonistic activity were selected to establish 3D-QSAR models using CoMFA and CoMSIA methods. Internal and external cross-validation techniques were investigated as well as some measures including region focusing, progressive scrambling, bootstraping and leave-group-out. The satisfactory CoMFA model predicted a q2 value of 0.751 and an r2 value of 0.973, indicating that electrostatic and steric properties play a significant role in potency. The best CoMSIA model, based on a combination of steric, electrostatic, hydrophobic and H-bond donor descriptors, predicted a q2 value of 0.739 and an r2 value of 0.923. The models were graphically interpreted using contour plots which gave more insight into the structural requirements for increasing the activity of a compound, providing a solid basis for future rational design of more active S1P1 receptor agonists. [ABSTRACT FROM AUTHOR]

Background: The construction of a multifunctional drug delivery system with a variety of advantageous features, including targeted delivery, controlled release and combined therapy, is highly attractive but remains a challenge. Results: In this study, we developed a MoS2-based hyaluronic acid (HA)-functionalized nanoplatform capable of achieving targeted delivery of camptothecin (CPT) and dual-stimuli-responsive drug release. HA was connected to MoS2 via a disulfide linkage, forming a sheddable HA shell on the surface of MoS2. This unique design not only effectively prevented the encapsulated CPT from randomly leaking during blood circulation but also significantly accelerated the drug release in response to tumor-associated glutathione (GSH). Moreover, the MoS2-based generated heat upon near-infrared (NIR) irradiation could further increase the drug release rate as well as induce photothermal ablation of cancer cells. The results of in vitro and in vivo experiments revealed that MoS2–SS–HA–CPT effectively suppressed cell proliferation and inhibited tumor growth in lung cancer cell-bearing mice under NIR irradiation via synergetic chemo-photothermal therapy. Conclusions: The as-prepared MoS2–SS–HA–CPT with high targeting ability, dual-stimuli-responsive drug release, and synergistic chemo-photothermal therapy may provide a new strategy for cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Molybdenum disulfide (MoS2) has been widely explored for biomedical applications due to its brilliant photothermal conversion ability. In this paper, we report a novel multifunctional MoS2-based drug delivery system (MoS2-SS-HA). By decorating MoS2 nanosheets with hyaluronic acid (HA), these functionalized MoS2 nanosheets have been developed as a tumor-targeting chemotherapeutic nanocarrier for near-infrared (NIR) photothermal-triggered drug delivery, facilitating the combination of chemotherapy and photothermal therapy into one system for cancer therapy. Results: The nanocomposites (MoS2-SS-HA) generated a uniform diameter (ca. 125 nm), exhibited great biocompatibility as well as high stability in physiological solutions, and could be loaded with the insoluble anti-cancer drug erlotinib (Er). The release of Er was greatly accelerated under near infrared laser (NIR) irradiation, showing that the composites can be used as responsive systems, with Er release controllable through NIR irradiation. MTT assays and confocal imaging results showed that the MoS2-based nanoplatform could selectively target and kill CD44-positive lung cancer cells, especially drug resistant cells (A549 and H1975). In vivo tumor ablation studies prove a better synergistic therapeutic effect of the joint treatment, compared with either chemotherapy or photothermal therapy alone. Conclusion: The functionalized MoS2 nanoplatform developed in this work could be a potent system for targeted drug delivery and synergistic chemo-photothermal cancer therapy. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluates the effectiveness of Traditional Chinese Medicine (TCM) extracts in blocking the interaction between the SARS-CoV-2 Spike protein and human ACE2 receptor, utilizing a dual-method approach to explore the antiviral potential of natural compounds., Objectives: This work aims to evaluate the capability of TCM extracts in inhibiting the SARS-CoV-2 Spike protein and ACE2 receptor interaction using advanced biochemical assays., Methods: A dual-method screening approach was utilized, beginning with a pseudovirus assay to assess the inhibition capabilities of TCM extracts in vitro, followed by a split-ubiquitin yeast two-hybrid (Y2H) system to validate interactions in live cells. Active compounds were characterized and quantified using UPLC-Q-Exactive-Orbitrap-MS., Results: Among the 91 TCM extracts tested, Rosmarinus officinalis exhibited the most potent inhibition in both pseudovirus and Y2H assays, significantly reducing viral entry and disrupting the Spike-ACE2 interaction. Comprehensive chemical profiling via UPLC-Q-Exactive-Orbitrap-MS identified 132 compounds, including phenolics, flavonoids, and terpenoids., Conclusion: This research validates the use of TCM extracts in viral inhibition strategies, demonstrating the utility of integrating traditional remedies with modern scientific approaches to discover new therapeutic agents., (© 2024 John Wiley & Sons Ltd.)

Six new phenylpropanoid glycosides ( 1 - 6 ), two new phenylethanol glycosides ( 7 and 8 ), one new phenylmethanol glycoside ( 9 ), three new phenylpropanoid dimers ( 10 - 12 ), two new phenylpropanoid-flavan-3-ol heterodimers ( 13 and 14 ), and six known relevant compounds ( 15 - 20 ) were isolated and identified from the well-liked edible and medicinal substance (the bark of Cinnamomum cassia (L.) J.Presl). The structures of these isolates were determined by using spectroscopic analyses, chemical methods, and quantum chemical calculations. Notably, compounds 4 - 9 were rare apiuronyl-containing glycosides, and compounds 13 and 14 were heterodimers of phenylpropanoids and flavan-3-ols linked through C-9″-C-8 bonds. The antioxidant and α-glucosidase inhibitory activities of all isolates were evaluated. Compounds 10 and 12 exhibited DPPH radical scavenging capacities with IC 50 values of 20.1 and 13.0 μM, respectively (vitamin C IC 50 value of 14.3 μM). In the ORAC experiment, all these compounds exhibited different levels of capacity for scavenging free radicals, and compound 10 displayed extraordinary free radical scavenging capacity with the ORAC value of 6.42 ± 0.01 μM TE/μM (EGCG ORAC value of 1.54 ± 0.02 μM TE/μM). Compound 12 also showed significant α-glucosidase inhibitory activity with an IC 50 of 56.3 μM (acarbose IC 50 of 519.4 μM).

Objective: To investigate the effect of flunarizine combined with ginkgo leaf extract and dipyridamole injection (GDI) on hemorheology of elderly patients with vertigo., Methods: Clinical data of 105 elderly patients with vertigo who were treated in The First People's Hospital of Lin'an District from June 2019 to December 2022 were retrospectively selected. Of them, 54 patients received flunarizine combined with GDI (Study group) while 51 patients received flunarizine treatment alone (Control group). The treatment effect and adverse reactions of the two groups, functional rehabilitation before and after treatment, including the Simplified Vertigo Symptom Score Scale (VSS-SF), Berg Balance Scale (BBS), and Dizziness Handicap Inventory (DHI) were measured. Hemodynamics including blood flow velocity (Vm) of basilar artery (BA), left vertebral artery (LVA), and right vertebral artery (RVA) before and after treatment were also assessed., Results: The total efficacy of the treatment in the study group was higher than that in the control group (94.4 % vs . 75.9%; P<0.05). After the treatment, the Vm of the BA, LVA, and RVA was increased in both groups compared to before treatment, and the increase was greater in the study group than in the control group (P<0.05). In addition, the BBS scores of the two groups after the treatment were higher than before the treatment, while the DHI and VSS-SF scores were lower than before the treatment. BBS scores of the study group were higher than those of the control group, while the DHI and VSS-SF scores were lower than those of the control group (P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the study group (5.6%) and the control group (2.0%; P>0.05)., Conclusions: The combination of flunarizine and GDI in elderly patients with vertigo can effectively regulate hemodynamics of the patient, reduce the degree of vertigo, improve balance, and have a significant overall therapeutic effect without increasing the risk of adverse reactions., (Copyright: © Pakistan Journal of Medical Sciences.)