Nipah virus (NiV), a highly pathogenic henipavirus of the family Paramyxoviridae, which causes fatal encephalitis in 40-70% of affected patients, was first reported in Malaysia over 20 years ago. Pteropid bats are the natural hosts of henipaviruses, and ticks have been proposed as a possible link between bats and mammalian hosts. To investigate this hypothesis, infection of the tick cell line IDE8 with NiV was examined. Presence of viral RNA and antigen in the NiV-infected tick cells was confirmed. Infectious virions were recovered from NiV-infected tick cells and ultrastructural features of NiV were observed by electron microscopy. These results suggest that ticks could support NiV infection, potentially playing a role in transmission.
Cancer is a complex disease characterized by dysregulated cell growth and division, posing significant challenges for effective treatment. Hispidulin, a flavonoid compound, has shown promising biological effects, particularly in the field of anticancer research. The main objective of this study is to investigate the anticancer properties of hispidulin and gain insight into its mechanistic targets in cancer cells. A comprehensive literature review was conducted to collect data on the anticancer effects of hispidulin. In vitro and in vivo studies were analyzed to identify the molecular targets and underlying mechanisms through which hispidulin exerts its anticancer activities. Hispidulin has shown significant effects on various aspects of cancer, including cell growth, proliferation, cell cycle regulation, angiogenesis, metastasis, and apoptosis. It has been observed to target both extrinsic and intrinsic apoptotic pathways, regulate cell cycle arrest, and modulate cancer progression pathways. The existing literature highlights the potential of hispidulin as a potent anticancer agent. Hispidulin exhibits promising potential as a therapeutic agent for cancer treatment. Its ability to induce apoptosis and modulate key molecular targets involved in cancer progression makes it a valuable candidate for further investigation. Additional pharmacological studies are needed to fully understand the specific targets and signaling pathways influenced by hispidulin in different types of cancer. Further research will contribute to the successful translation of hispidulin into clinical settings, allowing its utilization in conventional and advanced cancer therapies with improved therapeutic outcomes and reduced side effects.
Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.
Leukemia can be a result of genetic changes associated with protein tyrosine kinase activity such as in MPL W515L and BCR/ABL genes. However, the current conventional treatment of leukemia produces severe side effects that urge the approach to use natural products. A medicinal mushroom, Lignosus rhinocerus shows potential as an anti-cancer treatment. To investigate the efficacy and mechanism of action of the L. rhinocerus cultivar (TM02®) extract on leukemogenic tyrosine kinase cell lines, a cold-water extract (CWE) was produced by using TM02® sclerotia powder at 4°C. The carbohydrate and protein contents were found to be 77.24% and 1.75% respectively. In comparison to the normal Ba/F3 cell, the CWE TM02® shows significant effects on exhibiting proliferation of Ba/F3 expressed MPL W515L and BCR/ABL, possibly due to the presence of phenolic compounds and antioxidant properties of TM02®, which contribute to act on various signaling pathways, and the reported apoptotic activity of CWE TM02®. In contrast, CWE TM02® significantly exhibited high scavenging activity of both Ba/F3 expressed MPL W515L and BCR/ABL. At concentrations of 125 μg/mL and 500 μg/mL of CWE TM02® decreased 49.5% and 67.5% of cell migration activity of Ba/F3 expressed MPL W515L and BCR/ABL respectively. Therefore, we postulate that CWE TM02® has the capability to mediate the migration route of the leukemogenic tyrosine kinase cell lines.
Theranostic nanoparticles hold promise for simultaneous imaging and therapy in colorectal cancer. Carcinoembryonic antigen can be used as a target for these nanoparticles because it is overexpressed in most colorectal cancers. Affimer reagents are synthetic proteins capable of binding specific targets, with additional advantages over antibodies for targeting. We fabricated silica nanoparticles using a water-in-oil microemulsion technique, loaded them with the photosensitiser Foslip, and functionalised the surface with anti-CEA Affimers to facilitate fluorescence imaging and photodynamic therapy of colorectal cancer. CEA-specific fluorescence imaging and phototoxicity were quantified in colorectal cancer cell lines and a LS174T murine xenograft colorectal cancer model. Anti-CEA targeted nanoparticles exhibited CEA-specific fluorescence in the LoVo, LS174T and HCT116 cell lines when compared to control particles (p < 0.0001). No toxicity was observed in LS174T cancer mouse xenografts or other organs. Following photo-irradiation, the anti-CEA targeted particles caused significant cell death in LoVo (60%), LS174T (90%) and HCT116 (70%) compared to controls (p < 0.0001). Photodynamic therapy (PDT) at 24 h in vivo showed a 4-fold reduction in tumour volume compared to control mouse xenografts (p < 0.0001). This study demonstrates the efficacy of targeted fluorescence imaging and PDT using Foslip nanoparticles conjugated to anti-CEA Affimer nanoparticles in in vitro and in vivo colorectal cancer models.
Curcumin has demonstrated potential cytotoxicity across various cell lines despite its poor bioavailability and rapid metabolism. Therefore, our group have synthesized curcuminoid analogues with piperidone derivatives, FLDP-5 and FLDP-8 to overcome these limitations. In this study, the analogues were assessed on LN-18 human glioblastoma cells in comparison to curcumin. Results from cytotoxicity assessment showed that FLDP-5 and FLDP-8 curcuminoid analogues caused death in LN-18 cells in a concentration-dependent manner after 24-h treatment with much lower IC50 values of 2.5 µM and 4 µM respectively, which were more potent compared to curcumin with IC50 of 31 µM. Moreover, a significant increase (p
Tor tor is an important game and food fish of India with a distribution throughout Asia from the trans-Himalayan region to the Mekong River basin to Malaysia, Pakistan, Bangladesh and Indonesia. A new cell line named TTCF was developed from the caudal fin of T. tor for the first time. The cell line was optimally maintained at 28°C in Leibovitz-15 (L-15) medium supplemented with 20% fetal bovine serum (FBS). The propagation of TTCF cells showed a high plating efficiency of 63.00%. The cytogenetic analysis revealed a diploid count of 100 chromosomes at passage 15, 30, 45 and 60 passages. The viability of the TTCF cell line was found to be 72% after 6 months of cryopreservation in liquid nitrogen (-196°C). The origin of the cell lines was confirmed by the amplification of 578- and 655-bp sequences of 16S rRNA and cytochrome oxidase subunit I (COI) genes of mitochondrial DNA (mtDNA) respectively. TTCF cells were successfully transfected with green fluorescent protein (GFP) reporter plasmids. Further, immunocytochemistry studies confirm its fibroblastic morphology of cells. Genotoxicity assessment of H₂O₂ in TTCF cell line revealed the utility of TTCF cell line as in vitro model for aquatic toxicological studies.
Tricalcium phosphate ceramic microcarrier has been developed and introduced to a new possibility for the culture of anchorage dependent animal cells of DF1. It was observed that the number of attached cells was increased with shorter time for both spinner vessel and stirred tank (ST) bioreactor. For those bioreactors, the total viable cell number that had been obtained is about 1.2 x 10(5) cell/ml.
The increasing and widespread use of synthetic food dyes raises health concerns and earlier reports suggest that certain food dyes might be harmful for human health. In this study, we have investigated the effect of three commonly used food dyes on human liver cell line, HepG2. Our findings suggest that these experimental food dyes significantly affect cell viability and this effect can be worsen in hyperglycemic condition. Accumulation of cellular fat was significantly higher in presence of these dyes. Expression pattern of the gene involved in regulating apoptosis suggests that that the observed cell death could be attributed to the activation of apoptotic pathway. These findings suggest that these experimental dyes might exert synergistic toxicity in hyperglycemia that need to be confirmed using suitable in vivo models.
A new compound, schistochilic acid D (1) and two known compounds (2 and 3) were isolated from MeOH extract of Bornean liverwort. Schistochila acuininata collected from Mount Trus Madi, Sabah. The structure of the new metabolite was established based on spectroscopic (ID NMR, 2D NMR, and IR). and HRESIMS data. In addition, another population of S. acuminata collected from Mount Alab (Sabah) yielded four known compounds, 2, 3, 4 and 5. These compounds were tested for their biological potential against the B 16-Fl0 cell line. Compounds 4 and 5 exhibited weak cytotoxic activity.
Despite of ongoing research programs and numerous clinical trials, seasonal influenza epidemics remain a major concern globally. Vaccination remains the most effective method to prevent influenza infection. However, current flu vaccines have several limitations, including limited vaccine capacity, long production times, inconsistence efficacy in certain populations, and lack of a "universal" solution. Different next-generation approaches such as cell line-based culture, reverse genetics, and virus expression technology are currently under development to address the aforementioned challenges in conventional vaccine manufacture pipeline. Such approaches hope for safe and scalable production, induce broad-spectrum immunity, create premade libraries of vaccine strains, and target nonvariable regions of antigenic proteins for "universal" vaccination. Here, we discuss the process and challenges of the current influenza vaccine platform as well as new approaches that are being investigated. These developments indicate that an exciting future lies ahead in the influenza vaccine field.
Aim: This study was aimed at evaluating the anticancer potential of curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) based nanoparticles (NPs) in MDA-MB231 human breast cancer cells. Methods: Curcumin-loaded PLGA NPs were developed using a modified solvent evaporation technique. Physical characterization was performed on the formulated NPs. Furthermore, in vitro experiments were conducted to study the biological activity of the curcumin-loaded NPs. Results: Curcumin-loaded PLGA NPs demonstrated high encapsulation efficiency and sustained payload release. Moreover, the NPs exhibited a significant reduction in cell viability, cell migration and cell invasion in the MDA-MB231 cells. Conclusion: The study revealed that the formulated curcumin-loaded PLGA NPs possessed significant anti-metastatic properties. The findings showcased the possible potential of curcumin-loaded NPs in the management of debilitating conditions such as cancer. In addition, this study could form the basis for further research and advancements in this area.
Eupatorin is a polymethoxy flavone extracted from Orthosiphon stamineus and was reported to exhibit cytotoxic effects on several cancer cell lines. However, its effect as an anti-breast cancer agent in vivo has yet to be determined. This study aims to elucidate the potential of eupatorin as an anti-breast cancer agent in vivo using 4T1 challenged BALB/c mice model. In this article, BALB/c mice (20-22 g) challenged with 4T1 cells were treated with 5 mg/kg or 20 mg/kg eupatorin, while the untreated and healthy mice were fed with olive oil (vehicle) via oral gavage. After 28 days of experiment, the mice were sacrificed and blood was collected for serum cytokine assay, while tumors were harvested to extract RNA and protein for gene expression assay and hematoxylin-eosin staining. Organs such as spleen and lung were harvested for immune suppression and clonogenic assay, respectively. Eupatorin (20 mg/kg) was effective in delaying the tumor development and reducing metastasis to the lung compared with the untreated mice. Eupatorin (20 mg/kg) also enhanced the immunity as the population of NK1.1+ and CD8+ in the splenocytes and the serum interferon-γ were increased. Concurrently, eupatorin treatment also has downregulated the expression of pro-inflammatory and metastatic related genes (IL-1β. MMP9, TNF-α, and NF-κB). Thus, this study demonstrated that eupatorin at the highest dosage of 20 mg/kg body weight was effective in delaying the 4T1-induced breast tumor growth in the animal model.
Photothermal therapy (PTT) is a minimally invasive procedure for treating cancer. The two significant prerequisites of PTT are the photothermal therapeutic agent (PTA) and near-infrared radiation (NIR). The PTA absorbs NIR, causing hyperthermia in the malignant cells. This increased temperature at the tumor microenvironment finally results in tumor cell damage. Nanoparticles play a crucial role in PTT, aiding in the passive and active targeting of the PTA to the tumor microenvironment. Through enhanced permeation and retention effect and surface-engineering, specific targeting could be achieved. This novel delivery tool provides the advantages of changing the shape, size, and surface attributes of the carriers containing PTAs, which might facilitate tumor regression significantly. Further, inclusion of surface engineering of nanoparticles is facilitated through ligating ligands specific to overexpressed receptors on the cancer cell surface. Thus, transforming nanoparticles grants the ability to combine different treatment strategies with PTT to enhance cancer treatment. This review emphasizes properties of PTAs, conjugated biomolecules of PTAs, and the combinatorial techniques for a better therapeutic effect of PTT using the nanoparticle platform.
In this study, tumorspheres were generated from TW06 nasopharyngeal carcinoma cell line and examined their expression of putative cancer stem-like cell surface markers and drug sensitivity. The rate of tumorsphere expansion from dissociated late passage TW06 tumorspheres (≥ passage 15) was higher than that from parental cells and dissociated 10-day-old (passage 0) tumorspheres. The expression of CD24 surface marker was lost in the generation of tumorspheres and the loss was reversible after differentiating the tumorspheres in monolayer culture conditions. Drug sensitivity assay showed that late passage tumorspheres were resistant to docetaxel and oxaliplatin treatment. Our data suggest that serially passaged tumorspheres possess the characteristics of CSCs that render them a suitable preclinical in vitro model for evaluating anticancer drug efficacy and elucidating the underlying mechanisms of drug resistance.
The role of microRNA (miRNA) in ovarian cancer has been extensively studied as a regulator for its targeted genes. However, its specific role in metastatic serous ovarian cancer (SOC) is yet to be explored. This paper aims to investigate the differentially expressed miRNAs in metastatic SOC compared to normal. Locked nucleic acid PCR was performed to profile miRNA expression in 11 snap frozen metastatic SOC and 13 normal ovarian tissues. Functional analysis and regulation of their targeted genes were assessed in vitro. Forty-eight miRNAs were significantly differentially expressed in metastatic SOC as compared to normal. MiR-19a is a novel miRNA to be upregulated in metastatic SOC compared to normal. DLC1 is possibly regulated by miR-141 in SOC. MiR-141 inhibition led to significantly reduced cell viability. Cell migration and invasion were significantly increased following miRNA inhibition. This study showed the aberrantly expressed miRNAs in metastatic SOC and the roles of miRNAs in the regulation of their targeted genes and ovarian carcinogenesis.
Tricyclohexylphosphanegold(I) n-mercaptobenzoate (n = 2, 3, 4) labelled as 1-3 were previously reported to significantly suppress thioredoxin reductase (TrxR) activities towards ovarian cancer cells, A2780, in vitro. Herein, we explored the role of 1-3 for their apoptosis inducing ability against A2780 cells. 1-3 exhibited IC50 values at 1.19 ± 0.03 µM, 2.28 ± 0.04 μM and 0.78 ± 0.01 μM, respectively, compared to cisplatin at 26.8 ± 0.15 µM. The compounds induced A2780 apoptosis via a caspase-dependent mitochondrion pathway as evidenced by ROS production, cytochrome c release, caspases-3/7, -8, -9 and -10 activation, APAF1 and BAX upregulation as well as BCL2A1 and BCL2 genes' downregulation. In addition, the death mode of 1-3 was also mediated via death receptor extrinsic pathway manifested by FAS, FASL, FADD, and TNFR1 genes' upregulation via Human Rt PCR analysis. In addition, 1-3 significantly caused A2780 arrest at S phase, which was associated with the upregulation of TP53, E2F1, RB1 and CDKN1A upregulation and downregulation of CDK1, CDK4, CDC25A and CDC25C genes. Based on these promising results, these phosphanegold(I) thiolate derivatives could act as feasible candidates for further advanced in vivo ovarian cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.
Non-small cell lung cancer (NSCLC) is reported to have a high incidence rate and is one of the most prevalent types of cancer contributing towards 85% of all incidences of lung cancer. Berberine is an isoquinoline alkaloid which offers a broad range of therapeutical and pharmacological actions against cancer. However, extremely low water solubility and poor oral bioavailability have largely restricted its therapeutic applications. To overcome these limitations, we formulated berberine-loaded liquid crystalline nanoparticles (LCNs) and investigated their in vitro antiproliferative and antimigratory activity in human lung epithelial cancer cell line (A549). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), trypan blue staining, and colony forming assays were used to evaluate the anti-proliferative activity, while scratch wound healing assay and a modified Boyden chamber assay were carried out to determine the anti-migratory activity. We also investigated major proteins associated with lung cancer progression. The developed nanoparticles were found to have an average particle size of 181.3 nm with spherical shape, high entrapment efficiency (75.35%) and have shown sustained release behaviour. The most remarkable findings reported with berberine-loaded LCNs were significant suppression of proliferation, inhibition of colony formation, inhibition of invasion or migration via epithelial mesenchymal transition, and proliferation related proteins associated with cancer progression. Our findings suggest that anti-cancer compounds with the problem of poor solubility and bioavailability can be overcome by formulating them into nanotechnology-based delivery systems for better efficacy. Further in-depth investigations into anti-cancer mechanistic research will expand and strengthen the current findings of berberine-LCNs as a potential NSCLC treatment option.
Here, we collected 154 plant species in China ancient forests looking for novel efficient bioactive compounds for cancer treatments. We found 600 bioactive phyto-chemicals that induce apoptosis of liver cancer cell in vitro. First, we screen the plant extract's in vitro cytotoxicity inhibition of cancer cell growth using in vitro HepG2 cell lines and MTT cytotoxicity. The results from these initial MTT in vitro cytotoxicity tests show that the most efficient plants towards hepatoma cytoxicity is Cephalotaxus sinensis, mint bush (Elsholtzia stauntonii) and winged spindle tree (Euonymus alatus). We then used in cell-counting kit-8 (CCK-8) to further understand in vivo tumor growth using nude mice and GC-MS and LC-QTOF-MS to analyze the composition of compounds in the extracts. Extracted chemically active molecules analyzed by network pharmacology showed inhibition on the growth of liver cancer cells by acting on multiple gene targets, which is different from the currently used traditional drugs acting on only one target of liver cancer cells. Extracts from Cephalotaxus sinensis, mint bush (Elsholtzia stauntonii) and winged spindle tree (Euonymus alatus) induce apoptosis in hepatoma cancer cell line HepG2 with a killing rate of more than 83% and a tumor size decrease by 62-67% and a killing rate of only 6% of normal hepatocyte LO2. This study highlight efficient candidate species for cancer treatment providing a basis for future development of novel plant-based drugs to help meeting several of the UN SDGs and planetary health.