Advanced pharmaceutical bulletin最新文献

Purpose: Sorafenib is known as one of the oral anti-cancer drugs used in liver cancer. However, its lipophilic nature can lead to side effects, variable pharmacokinetics, and poor absorption. The use of novel drug delivery systems, such as niosomes, may help address these issues and improve the effectiveness of sorafenib.

Methods: Different niosomal formulations of sorafenib were prepared. The morphology, size analysis, and physical stability were investigated. The encapsulation efficiency percent of the selected formulations was measured using the dialysis method, and the release of sorafenib was checked for four hours using the Franz diffusion cell. The cytotoxicity and in vitro effect on the HepG2 cell line was investigated using the MTT assay and flow cytometry.

Results: The mean volume diameter of Span 60/Tween 60/cholesterol (45/45/10 mole%) niosomal formulation was 6 µm with minimal size changes and good stability over six months of storage. The encapsulation efficiency percent of this formulation was 66.40±1.11, and 61.43±1.42 percent of the drug was released within 4 hours. In vitro release followed Higuchi kinetics. Cytotoxicity tests showed an IC₅₀ of 7.5 µg/mL for the niosomal formulation, compared to 15.96 µg/mL for the sorafenib solution.

Conclusion: Niosomes containing Span 60/ Tween 60/ cholesterol (45/45/10 mole%) are promising for loading and sustained release of sorafenib. The use of niosome as a carrier can enhance the effectiveness of sorafenib on the HepG2 cell line. This niosomal formulation of sorafenib shows potential for future studies.

Purpose: Parkinson's disease (PD) is the fourth most common neurodegenerative disorder, characterized by degeneration of basal ganglia and a decrease in dopamine levels in the brain. Purinergic 2X7 receptors (P2X7Rs) serve as inflammation gatekeepers. They are found in both central and peripheral nervous systems (CNS & PNS), and are activated in glial cells during inflammation. Purinergic 2X receptors (P2XRs) have been extensively studied in recent decades, particularly P2X7R, because of their important role in neuroinflammation caused by selective overexpression in glial cells. As P2X7R and its selective antagonists may provide neuroprotection by preventing the release of inflammatory mediators such as IL-1, they have become a research focus in PD. The review covers structure, signalling, molecular mechanisms, neuroprotective role, and current developments of P2X7R antagonists in PD.

Methods: A systematic analysis and review of the potential prospects of P2X7R antagonists in the treatment of PD were conducted by analyzing existing research data and reports published between 1996 and present.

Results: There is a substantial body of evidence linking P2X7R to pathology of PD. As a result, P2X7R antagonists may have therapeutic potential in treatment of PD.

Conclusion: P2X7R has been demonstrated as an efficacious target in PD. Recent advances in rational drug design have paved the way for development of therapeutically valuable P2X7R antagonists such as adamantyl cyanoguanides, small molecular weight compounds, and PET ligands for the treatment of PD. However, the exact molecular mechanism and therapeutic potential of P2X7R antagonists in treatment of PD are yet to be fully explored.

Purpose: Lichens are well-known as a source of pharmacologically active compounds. This includes anticancer compounds which have biomass constraints including using traditional techniques of lichen bioprospecting. This current study reports the use of cutting-edge metabolomics and a computational approach to discover anticancer biomarkers from Indonesian lichens.

Methods: Seven lichen crude extracts were evaluated against cervical cell lines HeLa using a MTT assay and secondary metabolites were profiled and recorded via a gas chromatography-mass spectrometry (GC-MS) protocol. A multivariate analysis orthogonal partial least-squares-discriminant analysis (OPLS-DA) was employed to determine anticancer biomarker of the lichens. A structure-based computational study against the HeLa cancer cell related protein targets (BCL-2 (4MAN), AKT-1 (4GV1), MCL-1 (5FDO), and BRAF (5VAM)) was used to determine the most potent biomarker.

Results: The MTT assessment indicated the seven lichens possessed strong, medium and weak cytotoxicity. Multivariate analysis showed an OPLS-DA score plot with distinct separation among the strong, medium and weak cytotoxic groups. The biplot OPLS-DA and GC-MS analysis proposed 13 compounds of Parmelia caroliniana and 12 compounds of Physcia cf. millegrana as anticancer biomarker candidates. Docking experiments revealed 6-amino-3,4,7-triphenylpyrido[2',3':4,5]thieno[2,3-c]pyridazine 4 from P. caroliniana to possess the highest binding affinity against BCL-2 (4MAN), AKT-1 (4GV1), MCL-1 (5FDO), and BRAF (5VAM) proteins with affinity energy values of -10.0, -11.6, -10.4, -12.6, respectively.

Conclusion: The study successfully revealed compound 4 as the anticancer biomarker against HeLa cell cancer of P. caroliniana in which can be further explored through in vitro and in vivo studies. Further, the metabolomic protocol established can be adapted as a tool for biomarker discoveries from other medicinal plants.

Purpose: It tends not only to shed lights on an emerging classification framework of disease according to the shared molecular pathogenesis across various organs/tissues, but also to inspire more efficient paradigms of pharmaceutic innovation in a broader medical perspective.

Methods: Literature review and re-thinking.

Results: This article has sorted out an updated profile of the outstanding targeted medications with an extending list of clinical indications in oncology and beyond.

Conclusion: Pharmaceutic development can be processed in a less risky and more affordable manner through drug repurpose or tissue agnostic approval.

Purpose: Hijacked journals are journals managed by cybercriminals that mimic the original journal and publish manuscripts without peer review, charging a fee to the author. Although there is literature on hijacked journals, there is a gap in the content of published papers in the hijacked journals. This study aims to analyze the content of published papers in hijacked journals to assess their alignment with various Sustainable Development Goals (SDGs).

Methods: About 21 medicine journals have been investigated and about 3300 published manuscripts in them analyzed in terms of SDGs using the text-based analyzing method.

Results: The findings indicated that published manuscripts fit in the categories of SDG 01, SDG 03, SDG 11, and SDG 16 where SDG-03 is most dominant.

Conclusion: The awareness about the problem of hijacked journals is critical, especially for developing countries, to eliminate the negative effects of these journals. It is the first research that discusses the negative effect of hijacked journals by considering SDGs and sheds light on the phenomenon.

Purpose: A lectin-like protein from the mushroom Agaricus bisporus has been shown to slightly increase the proliferation of RAW 264.7 cells. Following its identification as a mannose-binding lectin, henceforth called A. bisporus mannose-binding protein (Abmb), the protein is hypothesized to stimulate the innate immune cells response. The present work was aimed to substantiate that hypothesis. Furthermore, this study complements Abmb exploration as a potential agent for anti-breast cancer, which its treatment is hampered with compromised immunity of patient receiving chemotherapy.

Methods: Abmb's effect on the phagocytic activity of the macrophage was measured with FACS. Nitric oxide (NO) production was checked using Griess test while expression of the cytokines in the RAW 264.7 cells was analysed at gene and protein level using polymerase chain reaction (PCR) and FACS, respectively. Abmb's effect on the expression of surface markers of the human immune cells in the peripheral blood mononuclear cells (PBMCs) was checked with specific antibodies for targeted cluster differentiation (CD) and analysed using FACS.

Results: Abmb increased the phagocytic activity of the macrophage and NO production. Abmb increased the expression of cytokines i.e. tumour necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10. With the PBMCs, Abmb activated dendritic and natural killer (NK) cells, but not the B- or T-cells.

Conclusion: Abmb increased the activity of the macrophage cells and activated the immune cells that are related to the innate immune system, particularly the cellular immunity.

Bone organ is comprised of an organic and inorganic environment, in which the collagen element and the mineral part are structured into spongy constructions. Hydroxyapatite (HAp) is the chief inorganic constituent of human bone. HAp is extensively utilized in bone tissue regeneration for its biocompatibility and a rising number of investigators are discovering ways to recover the physical belongings and biological roles of HAp. However, this biomimetic material indicates poor mechanical strength, for example, low tensile and compressive strength, which offer it inappropriate for bone tissue engineering. For this point, HAp is frequently utilized in a mixture with diverse polymers to increase their mechanical strengths and the general function of the implantable biomaterials advanced for orthopedic usage. In this review, we attempt to contribute a brief and inclusive outline of HAp-based natural and synthetic polymer materials to strengthen structures and their applications in bone tissue regeneration.

Purpose: The activities and functions of natural killer (NK) cells are regulated by a limited repertoire of activating and inhibitory receptors. Thus, we provided a study of inhibition of the NKG2A using monoclonal antibodies (mAbs), and as a primary endpoint, we evaluated whether it can be translated to enhance adoptive NK cell immunotherapy, as the secondary endpoint, we investigated safety and feasibility.

Methods: In this study, we investigated the safety of anti-NKG2A-pretreated NK cells in improving ADCC function to manage hepatocellular carcinoma (HCC). After a conditioning regimen, we initiated a pilot study of expanded donor haploidentical NK cell infusion. Patients received a fludarabine/cyclophosphamide conditioning followed by adoptive immunotherapy with IL2-activated haploidentical NK cells. Anti-NKG2A pretreated NK cells were infused on days 0,+5, and+10 post-conditioning regimens at a dose of 7×10⁸ cells (n=3). The median follow-up was 4 months for all patients.

Results: Although all patients were alive at the last follow-up, two of them showed progressive disease and an increase in tumor size. In addition, all patients showed a relative decrease in alpha-fetoprotein (AFP) expression levels after one month.

Conclusion: This study demonstrated the safety and feasibility of infusing high doses of ex vivo expanded NK cells after conditioning with transient side effects.

Purpose: T cell-based immunotherapy, especially chimeric antigen receptor (CAR)-T cells, has emerged as an appropriate approach for treating hematologic malignancies and is currently under investigation in clinical trials for solid tumors. Despite significant improvements in CAR-T cell production processes, the isolation and expansion of CAR-engineered T cells continue to pose significant challenges. The aim of this research is to provide a simple and cost-effective method for the isolation and expansion of human CAR-T cells. This novel concept applies coated fetal bovine serum (FBS) culture plates and focuses on enhancing viability and functionality to improve the adherence of suspended T cells.

Methods: This study evaluated a two-dimensional (2D) culture technique for isolating the CAR-T cells that target prostate-specific membrane antigen (PSMA) utilizing matrices pre-coated with 0.2% glutaraldehyde and FBS. Jurkat cells were transduced with a lentiviral vector encoding the anti-PSMA CAR construct. FBS-coated and commercialized Matrigel-coated matrices were used for single-cell isolation and clonal expansion. Functional tests were conducted to assess the activation and proliferation of CAR-T cells and the IFN-γ release assay subsequent to cloning and expansion.

Results: Transfection efficiency markedly improved, with 88.4% of Lenti-X 293T cells demonstrating green fluorescent protein (GFP) expression. Among the Jurkat cells, 57.1% showed GFP expression post-transduction, of which 34.1% showed surface expression of anti-PSMA CAR. Clonal expansion on the FBS-coated matrix proved effective, yielding 92.1% GFP-positive isolated cells. Functional assays demonstrated that CAR-T cells co-cultured with LNCaP cells exhibited significantly enhanced proliferation, activation (as indicated by CD69 and CD25 expression), and cytokine release assay (IFN-γ) compared with those co-cultured with DU 145 and mock cells.

Conclusion: This new approach is efficient, economical, and scalable for isolating specific homogenous T cells and promoting their clonal proliferation and expansion. Furthermore, this method improves T cell adherence, proliferation, and functional effectiveness, offering a potential foundation for advancing CAR-T cell therapies aimed at solid tumors. Future research should concentrate on optimizing culture conditions and testing this method in preclinical animal models to ensure its clinical applicability and efficacy.