Kim Wei Chan

This study evaluated two novel combination therapies using 5-Fluorouracil (5-FU), Thymoquinone (TQ), and cockle shell - derived calcium carbonate nanoparticles (CaCO₃ NPs) against HT-29 colorectal cancer (CRC) cells under hyperglycemic conditions. 5-FU and TQ were successfully encapsulated into CaCO₃ NPs through encapsulation at various drug-to-nanoparticle ratios. Physicochemical characterization was performed to confirm the morphology, and particle stability. Drug release studies assessed pH-responsive behavior, while biocompatibility was evaluated on NIH/3T3 cells. Cytotoxicity and cell cycle analyses were conducted on HT-29 cells under glycemic and hyperglycemic conditions. High encapsulation efficiency was achieved at a 1:5 drug-to-nanoparticle ratio while maintaining the aragonite structure and stable physicochemical properties. The nanoformulations exhibited pH-sensitive drug release with enhanced release at acidic pH (4.8), simulating the tumor microenvironment. Improved biocompatibility and reduced toxicity were observed in normal NIH/3T3 cells compared to free drugs. Both 5-FU:TQ-CaCO₃ NPs and 5-FU-CaCO₃ NPs:TQ combinations significantly inhibited HT-29 proliferation and induced G1 cell cycle arrest, especially under hyperglycemic conditions. Combination index analysis confirmed synergistic effects of both treatments. The findings suggest the potential therapeutic efficacy of 5-FU:TQ-CaCO₃ NPs and 5-FU-CaCO₃ NPs:TQ in treating CRC associated with hyperglycemia and demonstrate the capability of biogenic CaCO₃ NPs to effectively deliver chemotherapeutic agents of different polarity with minimal toxicity.

Colorectal cancer (CRC) poses a significant global health challenge, ranking as the third most prevalent cancer and the second leading cause of cancer-related mortality. The development of CRC is driven by genetic mutations, environmental factors, and lifestyle choices. Over recent decades, chemotherapy has played a crucial role in CRC treatment. Key chemotherapeutic agents such as 5-fluorouracil, capecitabine, irinotecan, oxaliplatin, and trifluridine/tipiracil have sig-nificantly improved patient outcomes. However, chemotherapy for CRC still faces significant challenges, including severe side effects, drug resistance, and high costs. This review discusses the current status and recent advancements in chemotherapy strategies for CRC, delves into the challenges the field faces, and proposes future research directions to foster the development of more effective chemotherapeutic drugs for CRC.

Drimenol, a phytochemical with a distinct odor is found in edible aromatic plants, such as Polygonum minus (known as kesum in Malaysia) and Drimys winteri. Recently, drimenol has received increasing attention owing to its diverse biological activities. This review offers the first extensive overview of drimenol, covering its sources, bioactivities, and derivatives. Notably, drimenol possesses a wide spectrum of biological activities, including antifungal, antibacterial, anti-insect, antiparasitic, cytotoxic, anticancer, and antioxidant effects. Moreover, some mechanisms of its activities, such as its antifungal effects against human mycoses and anticancer activities, have been investigated. However, there are still several crucial issues in the research on drimenol, such as the lack of experimental understanding of its pharmacokinetics, bioavailability, and toxicity. By synthesizing current research findings, this review aims to present a holistic understanding of drimenol, paving the way for future studies and its potential utilization in diverse fields.

Colon cancer is the third most common cancer worldwide, with high mortality. Adverse side effects and chemoresistance of the first-line chemotherapy 5-fluorouracil (5-FU) have promoted the widespread use of combination therapies. Thymoquinone (TQ) is a natural compound with potent antioxidant activity. Loading antioxidants into nano delivery systems has been a major advance in enhancing their bioavailability to improve clinical application. Hence, this study aimed to prepare the optimal TQ-loaded calcium carbonate nanoparticles (TQ-CaCO₃ NPs) and investigate their therapeutic potential and underlying molecular mechanisms of TQ-CaCO₃ NPs in combination with 5-FU against colon cancer. Firstly, we developed purely aragonite CaCO₃ NPs with a facile mechanical ball-milling method. The pH-sensitive and biocompatible TQ-CaCO₃ NPs with sustained release properties were prepared using the optimal synthesized method (a high-speed homogenizer). The in vitro study revealed that the combination of TQ-CaCO₃ NPs (15 μM) and 5-FU (7.5 μM) inhibited CT26 cell proliferation and migration, induced cell apoptosis and cell cycle arrest in the G₀/G₁ phase, and suppressed the CT26 spheroid growth, exhibiting a synergistic effect. Finally, network pharmacology and molecular docking results indicated the potential targets and crucial signaling pathways of TQ-CaCO₃ NPs in combination with 5-FU against colon cancer. Therefore, TQ-CaCO₃ NPs combined with 5-FU could enhance the anti-colon cancer effects of 5-FU with broader therapeutic targets, warranting further application for colon cancer treatment.

Given the need for novel and effective therapies for colon cancer, this study aimed to investigate the effects of 5-fluorouracil-loaded calcium carbonate nanoparticles (5FU-CaCO₃np) combined with thymoquinone (TQ) against colon cancer. A shaking incubator and a high-speed homogenizer were used to prepare the optimal 5FU-CaCO₃np, with characterizations of physicochemical properties, in vitro drug release profile, and biocompatibility. In vitro experiments and molecular docking were employed to evaluate the therapeutic potential of the combination for colon cancer treatment. Study results revealed that 5FU-CaCO₃np with a size of approximately 130 nm was synthesized using the high-speed homogenizer. Its favorable biocompatibility, pH sensitivity, and sustained release properties facilitated reduced toxic side effects of 5-FU on NIH3T3 normal cells and enhanced inhibitory effects on CT26 colon cancer cells. The combination of 5FU-CaCO₃np (1.875 μM) and TQ (30 μM) showed significantly superior anti-colon cancer effects to 5FU-CaCO₃np alone in terms of cell proliferation and migration inhibition, cell apoptosis induction, and spheroid growth suppression in CT26 cells (p < 0.05), with strong interactions between the drugs and targets (E-cadherin, Bcl-2, PCNA, and MMP-2). These results provide evidence for 5FU-CaCO₃np as a novel regimen against colon cancer. Combining 5FU-CaCO₃np and TQ may offer a new perspective for colon cancer therapy.

Edible bird’s nest (EBN) is an animal product with the world’s highest market price due to its value. The nests are made exclusively from the saliva secreted by swiftlet, a species of bird native to Southeast Asia. For over a century, EBN has been consumed in many parts of the world as a nutritious food. The high economic value of EBN attracts people to invest and engage in the bird nest industry. Currently, China is the largest importer of EBN, while Southeast Asian countries, namely, Indonesia, Malaysia, and Thailand, are the three largest exporters of EBN. An analysis of EBN’s compositions from most previous studies revealed that protein, carbohydrate, moisture, fat, and ash in EBN from the three central producing countries did not have apparent differences in their origins and were comparable to each other. Before 2011, EBN trade with China was unregulated. Consequently, the industry encountered problems due to the high nitrite content in EBN. Since then, these three countries have taken great measures to deal with this food safety issue and formulated a standard operating procedure (SOP) to meet the specific criteria listed for exporting EBN to China. Hence, this review discusses the quality and safety standards of EBN from the three countries and China’s standards for EBN importation.

Allergic diseases (ADs) are a major concern when it comes to public well‐being. Moringa oleifera Lam is a tropical plant that is used in traditional medicine due to the presence of isothiocyanate. The present study investigated the antiallergic properties of 4‐(α‐L‐rhamnopyranosyloxy)‐benzyl isothiocyanate or moringin isolated from Moringa oleifera seeds in the form of alpha‐cyclodextrin‐moringin (α‐CD/MG) complex on rat basophilic leukaemia (RBL‐2H3) cell line at both the early and late stages of an allergic reaction. The α‐CD/MG complex was initially elucidated using nuclear magnetic resonance (NMR) followed by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium inner salt proliferation assay to evaluate the cytotoxicity and cell viability with respect to ketotifen fumarate (KF) and α‐CD/MG. The release of beta‐hexosaminidase (β‐hexosaminidase) and histamine was used to determine the level of inhibition in the early stage while the suppression of the release of prostaglandin (PGD2), tumour necrosis factor‐alpha (TNF‐α), and interleukin (IL‐4) was considered in the late stage. Higher concentrations of α‐CD/MG (5 μM, p < 0.001) in mast cell degranulation significantly inhibited the expression of β‐hexosaminidase, histamine, TNF‐α, PGD2, and IL‐4 in both the early and late stages. Thus, α‐CD/MG can potentially be developed as an antiallergic drug as it has the ability to inhibit allergic responses in the late and early stages.

Breast cancer is the most common cancer diagnosed in women, and in 2020, there were 684, 996 deaths due to this disease. Epidermal growth factor receptors (EGFRs) and their respective ligands have been blamed for the pathogenesis and resistance to treatment in specific breast cancer cases. With EGFR having four homologues: EGFR1, EGFR2, EGFR3, and EGFR4, in-depth understanding of EGFR biology led to the discovery of small-molecule inhibitors and antibodies against this receptor. Gefitinib (GEF), a tyrosine kinase inhibitor of EGFR1, possesses a vast potential for treatment against breast cancer and is supported by a multiplicity of experiments. Unfortunately, in clinical trials, GEF did not show the outcomes expected with complete response and disease progress. This is due to incomplete understanding of the molecular mechanisms involved in EGFR signaling and endocrine sensitivity. Hence, additional in-depth experiments are needed regarding various molecular pathways and crosstalk pathways to comprehend GEF’s action mechanism thoroughly in breast cancer patients. In this review, the role of EGFR in the development and pathogenesis of breast cancer and the pharmacokinetics and pharmacotherapy of GEF for the treatment of breast cancer have been elaborated. Nanomedicines synthesized with GEF have shown positive experimental response, paving a promising path for GEF against breast cancer.

Atherosclerosis is the underlying cause of the majority of cardiovascular diseases (CVDs) due to high-cholesterol deposition in the aorta, resulting in hardening and narrowing of blood vessels and subsequently leading to an obstructed blood flow. There are few previous publications showing the preventive effects of edible birds nest (EBN) on CVD, but the study on cholesterol homeostasis related to atherosclerosis is limited. In this study, we have determined the mechanisms by which EBN modulates cholesterol metabolism by identifying genes and biomarkers. Male New Zealand white rabbits were fed either a high-fat high-cholesterol (HFC) diet or a HFC diet supplemented with EBN (500mg/kg b.w/day) for 12weeks. For comparison purposes, a group of rabbits receiving a HFC diet was supplemented with simvastatin (10mg/kg b.w/day) as a standard drug treatment for hypercholesterolemia. EBN supplementation significantly improved lipid and coagulation profiles, reduced hepatosteatosis, and stabilized atherosclerotic plaque formation in hypercholesterolemic rabbits. Cholesterol accumulation in liver and aorta tissues, as well as hepatic HMGCR levels, was reduced in the hypercholesterolemic rabbits supplemented with EBN. Gene expression analysis showed that EBN induced many genes related to cholesterol uptake (LDLR, LOX-1, and CD36), cholesterol efflux (ABCA1, LCAT, and CYP7A1), and cholesterol-sensing signaling (LXRα and PPARγ). In conclusion, our studies suggest that EBN supplementation could be an effective food product for the treatment or prevention of atherosclerosis by regulating cholesterol metabolism.

Diabetes is associated with an imbalance between oxidants and antioxidants, leading to oxidative stress. This imbalance contributes to the development and progression of diabetic complications. Similarly, renal and liver diseases are characterised by oxidative stress, where an excess of oxidants overwhelms the antioxidant defense mechanisms, causing tissue damage and dysfunction. Restoring the oxidant–antioxidant balance is essential for mitigating oxidative stress-related damage under these conditions. In this current study, the efficacy of stingless bee honey (SBH) and its phenolic-rich extract (PRE) in controlling the oxidant–antioxidant balance in high-fat diet- and streptozotocin/nicotinamide-induced diabetic rats was investigated. The administration of SBH and PRE improved systemic antioxidant defense and oxidative stress-related measures without compromising liver and renal functioning. Analyses of the liver, skeletal muscle and adipose tissues revealed differences in their capacities to scavenge free radicals and halt lipid peroxidation. Transcriptional alterations hypothesised tissue-specific control of KEAP1-NRF2 signalling by upregulation of Nrf2, Ho1 and Sod1 in a tissue-specific manner. In addition, hepatic translational studies demonstrated the stimulation of downstream antioxidant-related protein with upregulated expression of SOD-1 and HOD-1 protein. Overall, the results indicated that PRE and SBH can be exploited to restore the oxidant–antioxidant imbalance generated by diabetes via regulating the KEAP1-NRF2 signalling pathway.