Among mitotic kinases, Aurora kinases are the most widely studied, since their expression is restricted to mitosis. They play a key role in chromosome segregation and cell polyploidy. Aurora kinases ...are important therapeutic targets, and several research groups have directed their efforts toward the identification of kinase inhibitors. The aim of this study is to screen and characterize Aurora kinase inhibitors from natural substances extracted from plants that are used in the Vietnamese pharmacopoeia. We have characterized in vitro Derrone, extracted from Erythrina orientalis L. MURR, as a novel Aurora kinase inhibitor. This compound exhibited an ability to inhibit the phosphorylation of histone H3 at ser10 both in kinase assay and at the cellular level. The compound was more effective against Aurora kinase B, with a lower IC50 value as compared to Aurora A. Moreover, it impaired the mitotic spindle checkpoint and led to endoreduplication in cancer cells, a phenomenon caused by an Aurora B inhibitor. Interestingly, using the xCelligence system and real-time cell analysis (RTCA) software, we set up a comparison of cell proliferation profiles between cancer cells treated with Derrone and VX680—a well-known Aurora kinase inhibitor—and we found that these profiles exhibited considerable similarity in cell morphology, growth, and death. Additionally, Derrone significantly inhibited the formation and growth of MCF7 tumor spheroids.
(1) Background: Dendritic cell (DC) vaccination has shown outstanding achievements in cancer treatment, although it still has some adverse side effects. Vaccination with DC-derived exosomes has been ...thought to overcome the side effects of the parental DCs. (2) Method: We performed the experiments to check the ability of cryopreserved umbilical cord blood mononuclear cell-derived DCs (cryo CBMDCs) and their exosomes to prime allogeneic T cell proliferation and allogeneic peripheral blood mononuclear cell (alloPBMCs) cytotoxicity against A549 lung cancer cells. (3) Results: We found that both lung tumor cell lysate-pulsed DCs and their exosomes could induce allogeneic T cell proliferation. Moreover, alloPBMCs primed with tumor cell lysate-pulsed DCs and their exosomes have a greater cytotoxic activity against A549 cells compared to unprimed cells and cells primed with unpulsed DCs and their exosomes. (4) Conclusion: Tumor cell lysate-pulsed DCs and their exosomes should be considered to develop into a novel immunotherapeutic strategy-e.g., vaccines-for patients with lung cancer. Our results also suggested that cryo umbilical cord blood mononuclear cells source, which is a readily and available source, is effective for generation of allogeneic DCs and their exosomes will be material for vaccinating against cancer.
The matrix of the stationary phase is a crucial element in affinity chromatography for protein purification. Various materials, including polymer or magnetic materials, have been employed as the ...matrix in the purification of His-tagged protein. Here, for the first time, we utilized a combination of melanin and alginate, both natural polymer materials, to synthesize Ni-melanin/alginate (Ni-M/A) beads for His-tagged protein purification. We investigated the binding of His-tagged Mpro on the Ni-M/A beads, referred to as Ni-M/A-Mpro, and assessed the elution efficiency of Mpro from the beads. Our examination involved FTIR, EDS, XRD, SDS-PAGE, and Western blotting methods. FTIR spectra revealed notable changes in the stretching patterns and intensities of hydroxyl, amine, carbonyl, imine and amide chemical groups, when Mpro protein was present in the Ni-M/A sample. XRD spectra demonstrated the occurrence of two Nickel peaks at 35–40 deg and 40–45 deg in Ni-M/A, but only one nickel peak at 35–40 deg in Ni-M/A-Mpro, indicating the binding of Mpro on the Nickel ions. EDS analysis reported a decrease in the concentration of Nickel on the surface of Ni-M/A from 16% to 7% when Mpro protein was loaded into the stationary phase. Importantly, our data indicated that the purity of the His-tagged protein Mpro after purification reached 97% after just one-step purification using the Ni-M/A stationary phase. Moreover, the binding capacity of Ni-M/A for Mpro was approximately 5.2 mg/g with recovery efficiency of 40%. Our results suggested Ni-M/A as a highly potential solid phase for affinity chromatography in the purification of His-tagged protein.
•Novel Ni-melanin/alginate (Ni-M/A) beads were created for His-tagged protein purification.•The purity of the His-tagged protein Mpro after purification reached to 97% using the Ni-M/A beads as stationary phase.•The binding capacity of Ni-M/A beads for His-tagged protein Mpro was around 5.2 mg/g with recovery efficiency of 40%.•Ni-M/A beads acted as a very potential solid phase of affinity chromatography for His-tagged protein purification.
Ribavirin and remdesivir have been preclinically reported as potential drugs for the treatment of SARS-CoV-2 infection, while light silver tetrylene complexes (NHE
Ph
-AgCl and (NHE
Ph
-AgCl)
2
with ...E = C, Si, and Ge) have gained significant interest due to their promising applicability on the cytological scale. Firstly, the structures and bonding states of silver-tetrylene complexes (
NHE-Ag
) and bis-silver-tetrylene complexes (
NHE-Ag-bis
) were investigated using density functional theory (DFT) at the BP86 level with the def2-SVP and def2-TZVPP basis sets. Secondly, the inhibitory capabilities of the carbene complexes (
NHC-Ag
and
NHC-Ag-bis
) and the two potential drugs (ribavirin and remdesivir) on human-protein ACE2 and SARS-CoV-2 protease PDB6LU7 were evaluated using molecular docking simulation. The carbene ligand
NHC
bonds in a head-on configuration with AgCl and (AgCl)
2
, whereas, the other
NHE
(E = Si and Ge) tetrylene ligands bond in a side-on mode to the metal fragments. The bond dissociation energy (BDE) of the NHE-Ag bond in the complex families follows the order of
NHC-Ag
>
NHSi-Ag
>
NHGe-Ag
and
NHSi-Ag-bis
>
NHGe-Ag-bis
>
NHC-Ag-bis
. The natural bond orbital analysis implies that the NHE
Ph
→AgCl and (NHE
Ph
)
2
→(AgCl)
2
donations are derived mainly from the σ- and π-contributions of the ligands. The docking results indicate that both the ACE2 and PDB6LU7 proteins are strongly inhibited by silver-carbene
NHC-Ag
, bis-silver-carbene
NHC-Ag-bis
, ribavirin, and remdesivir with the docking score energy values varying from −17.5 to −16.5 kcal mol
−1
and −16.9 to −16.6 kcal mol
−1
, respectively. The root-mean-square deviation values were recorded to be less than 2 Å in all the calculated systems. Thus, the present study suggests that silver-carbene
NHC-Ag
and bis-silver-carbene
NHC-Ag-bis
complexes are potential candidates to inhibit ACE2 and PDB6LU7, and thus potentially conducive to prevent infection caused by the SARS-CoV-2 virus.
Simultaneous inhibition of silver-carbene complexes to ACE2 and PDB6LU7 is conducive for the prevention of SARS-CoV-2 infection: a virtual prediction.
(1) Colorectal cancer (CRC) is an increasingly prevalent disease with a high mortality rate in recent years. Immune cell-based therapies have received massive attention among scientists, as they have ...been proven effective as low-toxicity treatments. This study evaluated the safety and effectiveness of autologous immune enhancement therapy (AIET) for CRC. (2) An open-label, single-group study, including twelve patients diagnosed with stages III and IV CRC, was conducted from January 2016 to December 2021. Twelve CRC patients received one to seven infusions of natural killer (NK)-cell and cytotoxic T-lymphocyte (CTL). Multivariate modelling was used to identify factors associated with health-related quality-of-life (HRQoL) scores. (3) After 20−21 days of culture, the NK cells increased 3535-fold, accounting for 85% of the cultured cell population. Likewise, CTLs accounted for 62.4% of the cultured cell population, which was a 1220-fold increase. Furthermore, the QoL improved with increased EORTC QLQ-C30 scores, decreased symptom severity, and reduced impairment in daily living caused by these symptoms (MDASI-GI report). Finally, a 14.3 ± 14.1-month increase in mean survival time was observed at study completion. (4) AIET demonstrated safety and improved survival time and HRQoL for CRC patients in Vietnam.
Exosomes are nano-scale and closed membrane vesicles which are promising for therapeutic applications due to exosome-enclosed therapeutic molecules such as DNA, small RNAs, proteins and lipids. ...Recently, it has been demonstrated that mesenchymal stem cell (MSC)-derived exosomes have capacity to regulate many biological events associated with wound healing process, such as cell proliferation, cell migration and blood vessel formation. This study investigated the regenerative potentials for cutaneous tissue, in regard to growth factors associated with wound healing and skin cell proliferation and migration, by exosomes released from primary MSCs originated from bone marrow (BM), adipose tissue (AD), and umbilical cord (UC) under serum- and xeno-free condition. We found crucial wound healing-mediated growth factors, such as vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), hepatocyte growth factor (HGF), and platelet-derived growth factor BB (PDGF-BB) in exosomes derived from all three MSC sources. However, expression levels of these growth factors in exosomes were influenced by MSC origins, especially transforming growth factor beta (TGF-β) was only detected in UCMSC-derived exosomes. All exosomes released by three MSCs sources induced keratinocyte and fibroblast proliferation and migration; and, the induction of cell migration is a dependent manner with the higher dose of exosomes was used (20 μg), the faster migration rate was observed. Additionally, the influences of exosomes on cell proliferation and migration was associated with exosome origins and also target cells of exosomes that the greatest induction of primary dermal fibroblasts belongs to BMMSC-derived exosomes and keratinocytes belongs to UCMSC-derived exosomes. Data from this study indicated that BMMSCs and UCMSCs under clinical condition secreted exosomes are promising to develop into therapeutic products for wound healing treatment.
Novel active coating from gelatin/agarose (GA) functionalized with Ocimum gratissimum L. essential oil (OGO) had been developed as a medium to evaluate their properties before being applied for ...avocado preservation. The resultant coating films showed enhanced mechanical, water-barrier, bactericidal, antioxidant, and UV-shielding properties by adding OGO. The best tensile strength (2.91 MPa) and flexibility (45.82 %) was found in the GA film containing 5 % w/w OGO (GA-OGO-5). Furthermore, this coating formulation presented moderate antibacterial activities against Listeria, Pseudomonas, Salmonella, and Escherichia. The GA-OGO-5 coating film also divulged the highest hydrophobicity and adequate antioxidant function (30.75 μg/mL) and thus, was chosen to coat on ‘Booth 7’ avocados by dipping method. The GA-OGO-5 coating layers were to be efficient to decline the respiration rate of avocado during 6-day storage at 25 °C and 64 %RH. Peel color, weight loss (5.22 %), total soluble solids (8.14 %), and solution pH (6.79) at the end of storage also indicated that the GA-OGO-5 coating presented the best effectiveness for enhancing the storability of avocado as compared to uncoated and GA-treated fruit. Therefore, the GA-OGO coating has been considered as an alternative post-harvest technique to enhance the avocado storability and could be further commercialized for industry application.
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•Gelatin/agarose (GA) coating was enriched with Ocimum gratissimum L. essential oil (OGO).•Enhanced mechanical, antioxidant, antimicrobial, and UV shielding properties of GA film by adding OGO•GA included 5 % OGO enhanced storability of postharvest avocado up to 8 d at 20 °C and 64 % RH.
The aim of this study was to determine factors including biochemical markers, dietary habits, and social-anthropometric associated with uncontrolled hypertension among elderly hypertension in rural ...regions of Vietnam.
This study included 272 hypertension patients aged over 60 years. Demographic data, anthropometric measurements, and risk factors associated with hypertension were from the cross-sectional study of 272 customers at the Medical Examination Department, Samson General Hospital, Thanh Hoa Province, Vietnam. Biochemical markers including total cholesterol, triglycerides, and fasting blood glucose were measured. Dietary habits were by using a frequency questionnaire. Uncontrolled hypertension was defined as systolic blood pressure of ≥140 mmHg and/or diastolic blood pressure of ≥90 mmHg in a patient taking anti-hypertensive medication.
Generalized multiple linear regression was used to assess the impact of related factors on blood pressure, which were used as the dependent variables. Logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of related factors for hypertension status.
The study found that men had more uncontrolled hypertension than women among the elderly population. The prevalences of hyperglycemia, hypertriglyceridemia, and hypercholesterolemia were high in both controlled and uncontrolled groups. There was an inverse association between fruits (p=0.021) and vegetable consumption (p=0.038) and a positive correlation between salty habits (p=0.040) and processed food (p<0.001) with blood pressure in the uncontrolled hypertension group. Notably, in multivariable models, a high level of drinking habits was positively associated with uncontrolled hypertension (OR: 8.0; 95% CI: 1.0–63.2) and lack of vegetables (OR: 2.4; 95% CI: 1.1–5.0) in compared to those with controlled hypertension.
This study suggests that unhealthy dietary habits including lack of vegetable consumption and high drinking habits are important factors associated with uncontrolled hypertension in elderly patients in rural Vietnam.
Dendritic cells (DC) are professional antigen-presenting cells that activate T cells to kill cancer cells. The extracellular products of DCs have also been reported to perform the same function. In ...this study, we examined the in vitro differentiation of umbilical cord blood monocytes into DCs in the presence of GM-CSF, and interferon (IFN)-α. The resulting DC population (called IFN-DCs) were then matured in the presence of TNF-α, and pulsed with total protein extracted from A549 cancer cell line. The pulsed DCs and their conditioned medium were then used to stimulate allogeneic lymphocytes (alloLym). The proliferation and cytotoxicity of alloLym were then determined. The results showed that after 5 days of differentiation, the stimulated monocytes had the typical morphology and characteristic surface markers of DCs. Both unpulsed and pulsed IFN-DCs can induce the proliferation of alloLym, especially Vγ9γδ T cells. The conditioned medium from pulsed and unpulsed IFN-DCs culture also prompted the growth of Vγ9γδ T cells. Moreover, alloLym stimulated with pulsed DCs and their conditioned medium had a greater cytotoxic effect on A549 cells than the ones that were not stimulated. Our results indicated that IFN-DCs and their conditioned medium could induce the anti-tumor immunity in vitro, providing evidence for application of cord blood monocytes-derived, interferon-α- stimulated dendritic cells and their extracellular products in anti-cancer therapy.
Although curcumin in the form of nanoparticles has been demonstrated as a potential anti-tumor compound, the impact of curcumin and nanocurcumin in vitro on normal cells and in vivo in animal models ...is largely unknown. This study evaluated the toxicity of curcumin-loaded micelles in vitro and in vivo on several tumor cell lines, primary stromal cells, and zebrafish embryos. Breast tumor cell line (MCF7) and stromal cells (human umbilical cord vein endothelial cells, human fibroblasts, and human umbilical cord-derived mesenchymal stem cells) were used in this study. A zebrafish embryotoxicity (FET) assay was conducted following the Organisation for Economic Co-operation and Development (OECD) Test 236. Compared to free curcumin, curcumin PM showed higher cytotoxicity to MCF7 cells in both monolayer culture and multicellular tumor spheroids. The curcumin-loaded micelles efficiently penetrated the MCF7 spheroids and induced apoptosis. The nanocurcumin reduced the viability and disturbed the function of stromal cells by suppressing cell migration and tube formation. The micelles demonstrated toxicity to the development of zebrafish embryos. Curcumin-loaded micelles demonstrated toxicity to both tumor and normal primary stromal cells and zebrafish embryos, indicating that the use of nanocurcumin in cancer treatment should be carefully investigated and controlled.
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