Low-density lipoprotein receptor (LDLR) has been an object of research since the 1970s because of its role in various cell functions. The LDLR family members include LRP5, LRP6, and LRP8. Even though LRP5, 6, and 8 are in the same family, intriguingly, these three proteins have various roles in physiological events, as well as in regulating different mechanisms in various kinds of cancers. LRP5, LRP6, and LRP8 have been shown to play important roles in a broad panel of cancers. LRP5 is highly expressed in many tissues and is involved in the modulation of glucose-induced insulin secretion, bone development, and cholesterol metabolism, as well as cancer progression. Recently, LRP5 has also been shown to play a role in chondroblastic subtype of osteosarcoma (OS) and prostate cancer and also in noncancer case such as osteoporosis. LRP6, which has been previously discovered to share the same structures as LRP5, has also been associated with many cancer progressions such as human triple negative breast cancer (TNBC), primary chronic lymphocytic leukemia (CLL), nonsmall cell lung cancer (NSCL), lung squamous cell carcinoma (LSCC), and hepatocellular carcinoma (HCC). In addition to its role in cancer progression, LRP8 (apolipoprotein E receptor 2 [APOER2]) has also been demonstrated to regulate canonical Wnt/β-catenin signaling pathway whereby this pathway plays a role in cell migration and development. Therefore, this review aimed to elucidate the role of LRP 5, 6, and 8 in regulating the cancer progression.
Dengue viruses, mosquito-borne members of the Flaviviridae family, are the causative agents of dengue fever and its associated complications, dengue haemorrhagic fever and dengue shock syndrome. To date, more than 2.5 billion people in over 100 countries are at risk of infection, and approximately 20 million infections were reported annually. There is currently no treatment or vaccine available for dengue infection. This study employed a whole-cell organism model or in vitro methods to study the inhibitory property of the flavanoid-derived compounds against DENV2 activity. Results showed that at concentration not exceeding the maximum non-toxic dose (MNTD), these compounds completely prevented DENV2 infection in HepG2 cells as indicated by the absence of cytophatic effects. The in vitro antiviral activity assessed in HepG2 cells employing virus inhibition assay showed high inhibitory activity in a dose dependent manner. At concentration below MNTD, compounds exhibited inhibitory activity against DENV2 with a range of potency strengths of 72% to 100%. The plaque forming unit per ml (pfu/ml) was reduced prominently with a maximum reduction of 98% when the infected HepG2 cells were treated with the highest non-toxic dose of compounds. The highly potent activity of the compounds against DENV2 infection strongly suggests their potential as a lead antiviral agent for dengue.
Plant extracts of Cissus hastata, indigenously known as Semperai, have been used as an effective traditional remedy against coughs. Recently, the leaf extract was potentially shown to have anti-hemorrhoid activity, although there is a lack of scientific data due to its folklore usage. Hence, the therapeutic properties of the phytochemicals and metabolites of Semperai remain elusive. Therefore, this study aims to determine the total phenolic content and phytochemical compounds of the plant leaf extract. Total phenolic content and antioxidant activity were determined by the Folin–Ciocalteau method and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, respectively. Phytochemical compounds present in the leaf methanol extract were analyzed by a qualitative method. Results showed the extract comprised a total of 21.3 mg GAE/g of phenolic content with reference to gallic acid. The antioxidant activity was almost absence with an IC50 of 7.80 µg/mL when compared to trolox and gallic acid. Presence of the red to orange precipitate in reference to gallic acid indicate alkaloid content, while the appearance of black-blue/green color in reference to gallic acid are referred to as tannins. The steroids were represented by an upper red layer and a yellowish sulfuric acid with green fluorescence in comparison to cholesterol. Nonetheless, saponin was not detected in the extract, as indicated by the absence of the persisting foam in the test solution when compared with sodium dodecyl sulphate. In conclusion, despite not having an antioxidant property, the methanol extract of Semperai comprised a fair amount of phenolic compounds, including tannins, alkaloids, and steroids, which, potentially, are highly anti-inflammatory towards hemorrhoids.
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Objective: Despite advances in multimodal therapy, osteosarcoma (OS) still imposes big challenge due to its high rate of metastasis. The previousstudies reported that aberrant glycosylation in the cells mediates the invasion of several cancers including OS. However, its mechanism, particularlyN-glycosylation in OS progression, is still poorly understood. Thus, this study aims to investigate the effect of glycosylation inhibitions toward OS cellsinvasiveness.Materials and Methods: Both 1-deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (1-DMJ) were used to inhibit the activities ofalpha-glucosidase-I/II and alpha-1,2-mannosidase, respectively. Invasion assay and real-time polymerase chain reaction (PCR) (quantitative PCR[qPCR]) analysis of extracellular matrix-related genes were performed at post 24 h of treatment with the inhibitors, 0.5 mM 1-DNJ and 0.5 mM 1-DMJ,respectively, on the OS cell line, MG-63.Results: Results showed that the inhibition of N-glycosylation with 1-DNJ decreases the invasion rate of MG-63 cells while the inhibition ofN-glycosylation by 1-DMJ caused the invasion rate of MG-63 cells to increase. qPCR analysis showed downregulated expression of matrixmetalloproteinase (MMP2) gene in both types of treatments while the expression of its inhibitor, tissue inhibitor of metalloproteinase (TIMP2) wasupregulated in both types of treatments. In this study, MMP9 genes were not detected in both samples; however, the expression of its inhibitor, TIMP1was downregulated in MG-63 cells treated with 1-DNJ but upregulated in 1-DMJ treated cells.Conclusion: It is concluded that 1-DNJ reduced the invasion rate in MG-63 cells through downregulation of MMP2 gene which subsequently reduceddegradation of collagen type IV. However, the contrasting effect showed by 1-DMJ requires further investigation to elucidate its underlying mechanism.
Most acute gastroenteritis (AGE) outbreaks and sporadic cases in developing countries are attributable to infection by human norovirus (HuNoV), the enteric virus mainly transmitted via fecal-contaminated water. However, it has been challenging to study HuNoV due to the lack of suitable systems to cultivate and replicate the virus, hindering the development of treatments and vaccines. Researchers have been using virus-like particles (VLPs) and infectious viral clones to overcome this challenge as alternatives to fresh virus isolates in various in vitro and ex vivo models. VLPs are multiprotein structures that mimic the wild-type virus but cannot replicate in host cells due to the lack of genetic materials for replication, limiting downstream analysis of the virus life cycle and pathogenesis. The development of in vitro cloning systems has shown promise for HuNoV replication studies. This review discusses the approaches for constructing HuNoV-VLPs and infectious viral clones, the techniques involved, and the challenges faced. It also highlights the relationship between viral genes and their protein products and provides a perspective on technical considerations for producing efficient HuNoV-VLPs and infectious viral clones, which could substitute for native human noroviruses in future studies.
Osteosarcoma (OS), also known as osteogenic sarcoma, is the most common type of cancer that develops in bone. Most osteosarcoma occurs in children and young adults between the ages of 10 to 30 [1]. It accounts about 10% of childhood cancer. This cancerous (malignant) bone tumor usually develops during the period of rapid growth of an adolescence maturing into an adult. The malignant bone tumour tends to develop in the bones of the tibia (shin), femur (thigh) and humerus (upper arm).
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