ZnO nanostructures were synthesized by hydrothermal method using different molar ratios of cetyltrimethylammonium bromide (CTAB) and Sodium dodecyl sulfate (SDS) as structure directing agents. The effect of surfactants on the morphology of the ZnO crystals was investigated by field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) techniques. The results indicate that the mixture of cationic-anionic surfactants can significantly modify the shape and size of ZnO particles. Various structures such as flakes, sheets, rods, spheres, flowers and triangular-like particles sized from micro to nano were obtained. In order to examine the possible changes in other properties of ZnO, characterizations like powder X-ray diffraction (PXRD), thermogravimetric and differential thermogravimetric analysis (TGA-DTG), FTIR, surface area and porosity and UV-visible spectroscopy analysis were also studied and discussed.
MTH1 is an enzyme that hydrolyzes 8-oxo-dGTP, which is an oxidatively damaged nucleobase, into 8-oxo-dGMP in nucleotide pools to prevent its mis-incorporation into genomic DNA. Selective and potent MTH1-binding molecules have potential as biological tools and drug candidates. We recently developed 8-halogenated 7-deaza-dGTP as an 8-oxo-dGTP mimic and found that it was not hydrolyzed, but inhibited enzyme activity. To further increase MTH1 binding, we herein designed and synthesized 7,8-dihalogenated 7-deaza-dG derivatives. We successfully synthesized multiple derivatives, including substituted nucleosides and nucleotides, using 7-deaza-dG as a starting material. Evaluations of the inhibition of MTH1 activity revealed the strong inhibitory effects on enzyme activity of the 7,8-dihalogenated 7-deaza-dG derivatives, particularly 7,8-dibromo 7-daza-dGTP. Based on the results obtained on kinetic parameters and from computational docking simulating studies, these nucleotide analogs interacted with the active site of MTH1 and competitively inhibited the substrate 8-oxodGTP. Therefore, novel properties of repair enzymes in cells may be elucidated using new compounds.
Cellulose nanofibers (CNF) isolated from plant biomass have attracted considerable interests in polymer engineering. The limitations associated with CNF-based nanocomposites are often linked to the time-consuming preparation methods and lack of desired surface functionalities. Herein, we demonstrate the feasibility of preparing a multifunctional CNF-zinc oxide (CNF-ZnO) nanocomposite with dual antibacterial and reinforcing properties via a facile and efficient ultrasound route. We characterized and examined the antibacterial and mechanical reinforcement performances of our ultrasonically induced nanocomposite. Based on our electron microscopy analyses, the ZnO deposited onto the nanofibrous network had a flake-like morphology with particle sizes ranging between 21 to 34 nm. pH levels between 8-10 led to the formation of ultrafine ZnO particles with a uniform size distribution. The resultant CNF-ZnO composite showed improved thermal stability compared to pure CNF. The composite showed potent inhibitory activities against Gram-positive (methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative Salmonella typhi (S. typhi) bacteria. A CNF-ZnO-reinforced natural rubber (NR/CNF-ZnO) composite film, which was produced via latex mixing and casting methods, exhibited up to 42% improvement in tensile strength compared with the neat NR. The findings of this study suggest that ultrasonically-synthesized palm CNF-ZnO nanocomposites could find potential applications in the biomedical field and in the development of high strength rubber composites.
Several theories have been proposed to explain the mechanisms of substance use in schizophrenia. Brain neurons pose a potential to provide novel insights into the association between opioid addiction, withdrawal, and schizophrenia. Thus, we exposed zebrafish larvae at 2 days post-fertilization (dpf) to domperidone (DPM) and morphine, followed by morphine withdrawal. Drug-induced locomotion and social preference were assessed, while the level of dopamine and the number of dopaminergic neurons were quantified. In the brain tissue, the expression levels of genes associated with schizophrenia were measured. The effects of DMP and morphine were compared to vehicle control and MK-801, a positive control to mimic schizophrenia. Gene expression analysis revealed that α1C, α1Sa, α1Aa, drd2a, and th1 were up-regulated after 10 days of exposure to DMP and morphine, while th2 was down-regulated. These two drugs also increased the number of positive dopaminergic neurons and the total dopamine level but reduced the locomotion and social preference. The termination of morphine exposure led to the up-regulation of th2, drd2a, and c-fos during the withdrawal phase. Our integrated data implicate that the dopamine system plays a key role in the deficits in social behavior and locomotion that are common in the schizophrenia-like symptoms and opioid dependence.
Gene therapy research has advanced to clinical trials, but it is hampered by unstable nucleic acids packaged inside carriers and there is a lack of specificity towards targeted sites in the body. This study aims to address gene therapy limitations by encapsidating a plasmid synthesizing a short hairpin RNA (shRNA) that targets the anti-apoptotic Bcl-2 gene using truncated hepatitis B core antigen (tHBcAg) virus-like particle (VLP). A shRNA sequence targeting anti-apoptotic Bcl-2 was synthesized and cloned into the pSilencer 2.0-U6 vector. The recombinant plasmid, namely PshRNA, was encapsidated inside tHBcAg VLP and conjugated with folic acid (FA) to produce FA-tHBcAg-PshRNA VLP. Electron microscopy revealed that the FA-tHBcAg-PshRNA VLP has an icosahedral structure that is similar to the unmodified tHBcAg VLP. Delivery of FA-tHBcAg-PshRNA VLP into HeLa cells overexpressing the folate receptor significantly downregulated the expression of anti-apoptotic Bcl-2 at 48 and 72 h post-transfection. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay demonstrated that the cells' viability was significantly reduced from 89.46% at 24 h to 64.52% and 60.63%, respectively, at 48 and 72 h post-transfection. As a conclusion, tHBcAg VLP can be used as a carrier for a receptor-mediated targeted delivery of a therapeutic plasmid encoding shRNA for gene silencing in cancer cells.
Hepatitis B is a major global health challenge. In the absence of an effective treatment for the disease, hepatitis B vaccines provide protection against the viral infection. However, some individuals do not have positive immune responses after being vaccinated with the hepatitis B vaccines available in the market. Thus, it is important to develop a more protective vaccine. Previously, we showed that hepatitis B virus (HBV) 'a' determinant (aD) displayed on the prawn nodavirus capsid (Nc) and expressed in Spodoptera frugiperda (Sf9) cells (namely, Nc-aD-Sf9) self-assembled into virus-like particles (VLPs). Immunisation of BALB/c mice with the Nc-aD-Sf9 VLPs showed significant induction of humoral, cellular and memory B-cell immunity. In the present study, the biophysical properties of the Nc-aD-Sf9 VLPs were studied using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the antigenicity of the Nc-aD-Sf9 VLPs, and multiplex ELISA was employed to quantify the cytokine response induced by the VLPs administered intramuscularly into BALB/c mice (n = 8). CD spectroscopy of Nc-aD-Sf9 VLPs showed that the secondary structure of the VLPs predominantly consisted of beta (β)-sheets (44.8%), and they were thermally stable up to ~52 °C. ELISA revealed that the aD epitope of the VLPs was significantly antigenic to anti-HBV surface antigen (HBsAg) antibodies. In addition, multiplex ELISA of serum samples from the vaccinated mice showed a significant induction (p < 0.001) of IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-12p70. This cytokine profile is indicative of natural killer cell, macrophage, dendritic cell and cytotoxic T-lymphocyte activities, which suggests a prophylactic innate and adaptive cellular immune response mediated by Nc-aD-Sf9 VLPs. Interestingly, Nc-aD-Sf9 induced a more robust release of the aforementioned cytokines than that of Nc-aD VLPs produced in Escherichia coli and a commercially used hepatitis B vaccine. Overall, Nc-aD-Sf9 VLPs are thermally stable and significantly antigenic, demonstrating their potential as an HBV vaccine candidate.
The causative agent of white tail disease (WTD) in the giant freshwater prawn is Macrobrachium rosenbergii nodavirus (MrNV). The recombinant capsid protein (CP) of MrNV was previously expressed in Escherichia coli, and it self-assembled into icosahedral virus-like particles (VLPs) with a diameter of approximately 30 nm. Extensive studies on the MrNV CP VLPs have attracted widespread attention in their potential applications as biological nano-containers for targeted drug delivery and antigen display scaffolds for vaccine developments. Despite their advantageous features, the recombinant MrNV CP VLPs produced in E. coli are seriously affected by protease degradations, which significantly affect the yield and stability of the VLPs. Therefore, the aim of this study is to enhance the stability of MrNV CP by modulating the protease degradation activity. Edman degradation amino acid sequencing revealed that the proteolytic cleavage occurred at arginine 26 of the MrNV CP. The potential proteases responsible for the degradation were predicted in silico using the Peptidecutter, Expasy. To circumvent proteolysis, specific protease inhibitors (PMSF, AEBSF and E-64) were tested to reduce the degradation rates. Modulation of proteolytic activity demonstrated that a cysteine protease was responsible for the MrNV CP degradation. The addition of E-64, a cysteine protease inhibitor, remarkably improved the yield of MrNV CP by 2.3-fold compared to the control. This innovative approach generates an economical method to improve the scalability of MrNV CP VLPs using individual protease inhibitors, enabling the protein to retain their structural integrity and stability for prominent downstream applications including drug delivery and vaccine development.
Virus-like nanoparticles (VLNPs) have been studied extensively as nanocarriers for targeted drug delivery to cancer cells. However, VLNPs have intrinsic drawbacks, in particular, potential antigenicity and immunogenicity, which hamper their clinical applications. Thus, they can be eliminated easily and rapidly by host immune systems, rendering these nanoparticles ineffective for drug delivery. The aim of this study was to reduce the antigenicity of hepatitis B core antigen (HBcAg) VLNPs by shielding them with a hydrophilic polymer, poly(2-ethyl-2-oxazoline) (PEtOx). In the present study, an amine-functionalized PEtOx (PEtOx-NH2) was synthesized using the living cationic ring-opening polymerization (CROP) technique and covalently conjugated to HBcAg VLNPs via carboxyl groups. The PEtOx-conjugated HBcAg (PEtOx-HBcAg) VLNPs were characterized with dynamic light scattering and UV-visible spectroscopy. The colloidal stability study indicated that both HBcAg and PEtOx-HBcAg VLNPs maintained their particle size in Tris-buffered saline (TBS) at human body temperature (37 °C) for at least five days. Enzyme-linked immunosorbent assays (ELISA) demonstrated that the antigenicity of PEtOx-HBcAg VLNPs reduced significantly as compared with unconjugated HBcAg VLNPs. This novel conjugation approach provides a general platform for resolving the antigenicity of VLNPs, enabling them to be developed into a variety of nanovehicles for targeted drug delivery.
Heart failure is the end-stage of all cardiovascular diseases with a ~25% 5-year survival rate, and insufficient mitochondrial energy production to meet myocardial demand is the hallmark of heart failure. Mitochondrial components involved in the regulation of ATP production remain to be fully elucidated. Recently, roles of 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) in the pathophysiological processes of heart diseases have emerged, implicated by evidence that mitochondrial CNPase proteins are associated with mitochondrial integrity under metabolic stress. In this study, a zebrafish heart failure model was established, by employing antisense morpholino oligonucleotides and the CRISPR-Cas9 gene-editing system, which recapitulates heart failure phenotypes including heart dysfunction, pericardial edema, ventricular enlargement, bradycardia, and premature death. The translational implications of CNPase in the pathophysiological process of heart failure were tested in a pressure overload-induced heart hypertrophy model, which was carried out in rats through transverse abdominal aorta constriction (TAAC). AAV9-mediated myocardial delivery of CNPase mitigated the hypertrophic response through the specific hydrolysis of 2'-3'-cyclic nucleotides, supported by the decrease of cardiac hypertrophy and fibrosis, the integrity of mitochondrial ultrastructure, and indicators of heart contractility in the AAV9-TAAC group. Finally, the biometrics of a mitochondrial respiration assay carried out on a Seahorse cellular energy analyzer demonstrated that CNPase protects mitochondrial respiration and ATP production from AngII-induced metabolic stress. In summary, this study provides mechanistic insights into CNPase-2',3'-cyclic nucleotide metabolism that protects the heart from energy starvation and suggests novel therapeutic approaches to treat heart failure by targeting CNPase activity.
Blood is conventionally thought to be sterile. However, emerging evidence on the blood microbiome has started to challenge this notion. Recent reports have revealed the presence of genetic materials of microbes or pathogens in the blood circulation, leading to the conceptualization of a blood microbiome that is vital for physical wellbeing. Dysbiosis of the blood microbial profile has been implicated in a wide range of health conditions. Our review aims to consolidate recent findings about the blood microbiome in human health and to highlight the existing controversies, prospects, and challenges around this topic. Current evidence does not seem to support the presence of a core healthy blood microbiome. Common microbial taxa have been identified in some diseases, for instance, Legionella and Devosia in kidney impairment, Bacteroides in cirrhosis, Escherichia/Shigella and Staphylococcus in inflammatory diseases, and Janthinobacterium in mood disorders. While the presence of culturable blood microbes remains debatable, their genetic materials in the blood could potentially be exploited to improve precision medicine for cancers, pregnancy-related complications, and asthma by augmenting patient stratification. Key controversies in blood microbiome research are the susceptibility of low-biomass samples to exogenous contamination and undetermined microbial viability from NGS-based microbial profiling, however, ongoing initiatives are attempting to mitigate these issues. We also envisage future blood microbiome research to adopt more robust and standardized approaches, to delve into the origins of these multibiome genetic materials and to focus on host-microbe interactions through the elaboration of causative and mechanistic relationships with the aid of more accurate and powerful analytical tools.
Matrix metalloproteinase-12 (MMP12), or macrophage metalloelastase, plays important roles in extracellular matrix (ECM) component degradation. Recent reports show MMP12 has been implicated in the pathogenesis of periodontal diseases. To date, this review represents the latest comprehensive overview of MMP12 in various oral diseases, such as periodontitis, temporomandibular joint dysfunction (TMD), orthodontic tooth movement (OTM), and oral squamous cell carcinoma (OSCC). Furthermore, the current knowledge regarding the distribution of MMP12 in different tissues is also illustrated in this review. Studies have implicated the association of MMP12 expression with the pathogenesis of several representative oral diseases, including periodontitis, TMD, OSCC, OTM, and bone remodelling. Although there may be a potential role of MMP12 in oral diseases, the exact pathophysiological role of MMP12 remains to be elucidated. Understanding the cellular and molecular biology of MMP12 is essential, as MMP12 could be a potential target for developing therapeutic strategies targeting inflammatory and immunologically related oral diseases.
Cardiac c-kit cells show promise in regenerating an injured heart. While heart disease commonly affects elderly patients, it is unclear if autologous cardiac c-kit cells are functionally competent and applicable to these patients. This study characterised cardiac c-kit cells (CCs) from aged mice and studied the effects of human Wharton's Jelly-derived mesenchymal stem cells (MSCs) on the growth kinetics and cardiac differentiation of aged CCs in vitro. CCs were isolated from 4-week- and 18-month-old C57/BL6N mice and were directly co-cultured with MSCs or separated by transwell insert. Clonogenically expanded aged CCs showed comparable telomere length to young CCs. However, these cells showed lower Gata4, Nkx2.5, and Sox2 gene expressions, with changes of 2.4, 3767.0, and 4.9 folds, respectively. Direct co-culture of both cells increased aged CC migration, which repopulated 54.6 ± 4.4% of the gap area as compared to aged CCs with MSCs in transwell (42.9 ± 2.6%) and CCs without MSCs (44.7 ± 2.5%). Both direct and transwell co-culture improved proliferation in aged CCs by 15.0% and 16.4%, respectively, as traced using carboxyfluorescein succinimidyl ester (CFSE) for three days. These data suggest that MSCs can improve the growth kinetics of aged CCs. CCs retaining intact telomere are present in old hearts and could be obtained based on their self-renewing capability. Although these aged CCs with reduced growth kinetics are improved by MSCs via cell-cell contact, the effect is minimal.
The objective of this study was to investigate the salivary proteins that are associated with periodontitis in patients with Type 2 diabetes mellitus (T2DM). Volunteers for the study were patients from the Diabetic Unit, University of Malaya Medical Centre, whose periodontal status was determined. The diabetic volunteers were divided into two groups, i.e., patients with periodontitis and those who were periodontally healthy. Saliva samples were collected and treated with 10% TCA/acetone/20 mM DTT to precipitate the proteins, which were then separated using two-dimensional polyacrylamide gel electrophoresis. Gel images were scanned using the GS-800(TM) Calibrated Densitometer. The protein spots were analyzed and expressed in percentage volumes. The percentage volume of each protein spot was subjected to Mann-Whitney statistical analysis using SPSS software and false discovery rate correction. When the expression of the salivary proteins was compared between the T2DM patients with periodontitis with those who were periodontally healthy, seven proteins, including polymeric immunoglobulin receptor, plastin-2, actin related protein 3, leukocyte elastase inhibitor, carbonic anhydrases 6, immunoglobulin J and interleukin-1 receptor antagonist, were found to be differentially expressed (p < 0.01304). This implies that the proteins may have the potential to be used as biomarkers for the prediction of T2DM patients who may be prone to periodontitis.
The cryopreservation of spermatogonia stem cells (SSCs) has been widely used as an alternative treatment for infertility. However, cryopreservation itself induces cryoinjury due to oxidative and osmotic stress, leading to reduction in the survival rate and functionality of SSCs. Glial-derived neurotrophic factor family receptor alpha 1 (GFRα1) and promyelocytic leukemia zinc finger (PLZF) are expressed during the self-renewal and differentiation of SSCs, making them key tools for identifying the functionality of SSCs. To the best of our knowledge, the involvement of GFRα1 and PLZF in determining the functionality of SSCs after cryopreservation with therapeutic intervention is limited. Therefore, the purpose of this review is to determine the role of GFRα1 and PLZF as biomarkers for evaluating the functionality of SSCs in cryopreservation with therapeutic intervention. Therapeutic intervention, such as the use of antioxidants, and enhancement in cryopreservation protocols, such as cell encapsulation, cryoprotectant agents (CPA), and equilibrium of time and temperature increase the expression of GFRα1 and PLZF, resulting in maintaining the functionality of SSCs. In conclusion, GFRα1 and PLZF have the potential as biomarkers in cryopreservation with therapeutic intervention of SSCs to ensure the functionality of the stem cells.
Previous research reported that prolonged benzene exposure during in utero fetal development causes greater fetal abnormalities than in adult-stage exposure. This phenomenon increases the risk for disease development at the fetal stage, particularly carcinogenesis, which is mainly associated with hematological malignancies. Benzene has been reported to potentially act via multiple modes of action that target the hematopoietic stem cell (HSCs) niche, a complex microenvironment in which HSCs and multilineage hematopoietic stem and progenitor cells (HSPCs) reside. Oxidative stress, chromosomal aberration and epigenetic modification are among the known mechanisms mediating benzene-induced genetic and epigenetic modification in fetal stem cells leading to in utero carcinogenesis. Hence, it is crucial to monitor exposure to carcinogenic benzene via environmental, occupational or lifestyle factors among pregnant women. Benzene is a well-known cause of adult leukemia. However, proof of benzene involvement with childhood leukemia remains scarce despite previously reported research linking incidences of hematological disorders and maternal benzene exposure. Furthermore, accumulating evidence has shown that maternal benzene exposure is able to alter the developmental and functional properties of HSPCs, leading to hematological disorders in fetus and children. Since HSPCs are parental blood cells that regulate hematopoiesis during the fetal and adult stages, benzene exposure that targets HSPCs may induce damage to the population and trigger the development of hematological diseases. Therefore, the mechanism of in utero carcinogenicity by benzene in targeting fetal HSPCs is the primary focus of this review.
Our preliminary screening has shown that curcumin derivative BDMC33 [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] exerted promising nitric oxide inhibitory activity in activated macrophages. However, the molecular basis and mechanism for its pharmacological action is yet to be elucidated. The aim of this study was to investigate the anti-inflammatory properties of BDMC33 and elucidate its underlying mechanism action in macrophage cells. Our current study demonstrated that BDMC33 inhibits the secretion of major pro-inflammatory mediators in stimulated macrophages, and includes NO, TNF-α and IL-1β through interference in both nuclear factor kappaB (NF-κB) and mitogen activator protein kinase (MAPK) signaling cascade in IFN-γ/LPS-stimulated macrophages. Moreover, BDMC33 also interrupted LPS signaling through inhibiting the surface expression of CD-14 accessory molecules. In addition, the inhibitory action of BDMC33 not only restricted the macrophages cell (RAW264.7), but also inhibited the secretion of NO and TNF-α in IFN-γ/LPS-challenged microglial cells (BV-2). The experimental data suggests the inflammatory action of BDMC33 on activated macrophage-like cellular systems, which could be used as a future therapeutic agent in the management of chronic inflammatory diseases.
Clear cell renal cell carcinoma (ccRCC) is a hypervascular tumor that is characterized by bi-allelic inactivation of the VHL tumor suppressor gene and mTOR signalling pathway hyperactivation. The pro-angiogenic factor PDGFB, a transcriptional target of super enhancer-driven KLF6, can activate the mTORC1 signalling pathway in ccRCC. However, the detailed mechanisms of PDGFB-mediated mTORC1 activation in ccRCC have remained elusive. Here, we investigated whether ccRCC cells are able to secrete PDGFB into the extracellular milieu and stimulate mTORC1 signalling activity. We found that ccRCC cells secreted PDGFB extracellularly, and by utilizing KLF6- and PDGFB-engineered ccRCC cells, we showed that the level of PDGFB secretion was positively correlated with the expression of intracellular KLF6 and PDGFB. Moreover, the reintroduction of either KLF6 or PDGFB was able to sustain mTORC1 signalling activity in KLF6-targeted ccRCC cells. We further demonstrated that conditioned media of PDGFB-overexpressing ccRCC cells was able to re-activate mTORC1 activity in KLF6-targeted cells. In conclusion, cancer cell-derived PDGFB can mediate mTORC1 signalling pathway activation in ccRCC, further consolidating the link between the KLF6-PDGFB axis and the mTORC1 signalling pathway activity in ccRCC.
The present study describes a real-time PCR approach with high resolution melting-curve (HRM) assay developed for the detection and differentiation of Schistosoma mansoni and S. haematobium in fecal and urine samples collected from rural Yemen. The samples were screened by microscopy and PCR for the Schistosoma species infection. A pair of degenerate primers were designed targeting partial regions in the cytochrome oxidase subunit I (cox1) gene of S. mansoni and S. haematobium using real-time PCR-HRM assay. The overall prevalence of schistosomiasis was 31.8%; 23.8% of the participants were infected with S. haematobium and 9.3% were infected with S. mansoni. With regards to the intensity of infections, 22.1% and 77.9% of S. haematobium infections were of heavy and light intensities, respectively. Likewise, 8.1%, 40.5% and 51.4% of S. mansoni infections were of heavy, moderate and light intensities, respectively. The melting points were distinctive for S. mansoni and S. haematobium, categorized by peaks of 76.49 ± 0.25 °C and 75.43 ± 0.26 °C, respectively. HRM analysis showed high detection capability through the amplification of Schistosoma DNA with as low as 0.0001 ng/µL. Significant negative correlations were reported between the real-time PCR-HRM cycle threshold (Ct) values and microscopic egg counts for both S. mansoni in stool and S. haematobium in urine (p < 0.01). In conclusion, this closed-tube HRM protocol provides a potentially powerful screening molecular tool for the detection of S. mansoni and S. haematobium. It is a simple, rapid, accurate, and cost-effective method. Hence, this method is a good alternative approach to probe-based PCR assays.
The transient response of magnetorheological (MR) materials, in general, is very important for design consideration in MR-based devices. Better response to magnetic fields is beneficial for a better response rate to the electrical current applied in the electromagnetic coil. As a result, MR-based devices would have a high response to external stimuli. In this work, the principal characteristics of magnetorheological greases (MRGs) which have two different particle shapes are experimentally investigated. One type of particle distributed in the grease medium is conventional spherical-shaped carbonyl iron (CI) particles, while the other is plate-like CI particles made using a high-energy rotary ball mill from spherical CI particles. A set of bidisperse MRG samples are firstly prepared by adjusting the weight percentage of the plate-like CI particles and mixing with the spherical CI particles. Subsequently, three important properties of MRGs in terms of their practical application are measured and compared between the two different particle shapes. The field-dependent apparent viscoelastic properties of the prepared MRG samples are measured, followed by the field-dependent storage and loss moduli using an oscillatory shear rheometer. In addition, the transient response time, which indicates the speed in the actuating period of MRGs, is measured by changing the strain amplitude. Then, a comparative assessment on the three properties are undertaken between two different particle shapes by presenting the corresponding results in the same plot. It is shown that the bidisperse MRG with plate-like CI particles exhibits an increase in the initial apparent viscosity as well as stiffness property compared to the MRG with spherical particles only.
Hematologic malignancies constitute about 9% of all new cases of cancers as reported via the GLOBOCAN series by International Agency for Research on Cancer (IARC) in 2008. So far, the conventional therapeutic and surgical approaches to cancer therapy have not been able to curtail the rising incidence of cancers, including hematological malignancies, worldwide. The last decade has witnessed great research interest in biological activities of phenolic compounds that include anticancer, anti-oxidation and anti-inflammation, among other things. A large number of anticancer agents combat cancer through cell cycle arrest, induction of apoptosis and differentiation, as well as through inhibition of cell growth and proliferation, or a combination of two or more of these mechanisms. Various phenolic compounds from different sources have been reported to be promising anticancer agents by acting through one of these mechanisms. Honey, which has a long history of human consumption both for medicinal and nutritional uses, contains a variety of phenolic compounds such as flavonoids, phenolic acids, coumarins and tannins. This paper presents a review on the molecular mechanisms of the anti-leukemic activity of various phenolic compounds on cell cycle, cell growth and proliferation and apoptosis, and it advocates that more studies should be conducted to determine the potential role of honey in both chemoprevention and chemotherapy in leukemia.