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Antioxidants are essential for reducing oxidative stress, protecting cells from damage, and supporting overall well-being. Functionalized mesoporous silica materials have garnered interest due to their flexible uses in diverse domains, such as drug delivery systems. This review aims to thoroughly examine and evaluate the progress made in utilizing functionalized mesoporous silica materials as a possible approach to enhancing antioxidant activity. The authors performed a thorough search of reliable databases, including Scopus, PubMed, Google Scholar, and Clarivate Web of Science, using precise keywords linked to functionalized mesoporous silica nanoparticles and antioxidants. The identified journals serve as the major framework for the main discussion in this study. Functionalized mesoporous silica nanoparticles have been reported to greatly enhance antioxidant activity by allowing for an increased loading capacity, controlled release behavior, the targeting of specific drugs, improved biocompatibility and safety, and enhanced penetration. The results emphasize the significant capacity of functionalized mesoporous silica (FSM) to bring about profound changes in a wide range of applications. FSM materials can be designed as versatile nanocarriers, integrating intrinsic antioxidant capabilities and augmenting the efficacy of current drugs, offering substantial progress in antioxidant therapies and drug delivery systems, as well as enhanced substance properties in the pharmaceutical field. Functionalized mesoporous silica materials are a highly effective method for enhancing antioxidant activity. They provide new opportunities for the advancement of cutting-edge treatments and materials in the field of antioxidant research. The significant potential of FSM materials to change drug delivery methods and improve substance properties highlights their crucial role in future breakthroughs in the pharmaceutical field and antioxidant applications.

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The Kereh River in Penang, Malaysia, has faced severe pollution for over 40 years due to untreated wastewater from swine farms in Kampung Selamat, discharged via stormwater drains. Despite official claims that all 77 swine farms treat their wastewater to meet regulatory standards, local non-governmental organizations and villagers have challenged this, though their concerns lack scientific backing. This study evaluates the river's water quality by analyzing samples from upstream (US), midstream (MS), and downstream (DS), and from Parit Cina-Parit Besar, a conduit for untreated swine wastewater. Fourteen parameters were measured against Malaysia's National Water Quality Standards (NWQS). Significant differences were found in six parameters: ammonium nitrogen (AN), biochemical oxygen demand (BOD), chemical oxygen demand (COD), dissolved oxygen (DO), total suspended solids (TSS), and oil and grease (OG). While Dunn's post hoc pairwise comparison showed no significant differences among river segments, mean values indicated increased pollution downstream, particularly after the convergence with untreated swine wastewater. River classification worsened, with water quality index dropping from 69.88 ± 11.37 score (Class III) US to 38.49 ± 12.74 and 50.44 ± 3.14 scores (Class IV) MS and downstream, respectively. A significant positive correlation between E. coli and AN (r = 0.71, p < 0.01) suggests a common point source pollutant, particularly the untreated swine wastewater. The river exhibits low oxygen levels and high organic matter and nutrient concentrations, especially MS and downstream, highlighting substantial ecological and public health risks. Effective enforcement of waste treatment regulations and enhanced monitoring are crucial for mitigating pollution and restoring the river's ecosystem. Collaboration between authorities and pig farmers is essential to improve water quality and maintain the river's ecological balance. PRACTITIONER POINTS: Severe Kereh River pollution: Untreated swine wastewater from Kampung Selamat pig farms, primarily via Parit Cina-Parit Besar, has degraded the river for over 40 years. Regulatory non-compliance: Despite official claims, untreated swine wastewater continues to pollute the river, challenging regulatory standards. Significant pollution indicators: Elevated levels of AN, BOD, COD, DO, TSS, OG, and E. coli signal severe pollution midstream and downstream. Water quality index drop: WQI scores classify midstream and downstream sections as polluted, indicating worsening conditions downstream. Urgent need for action: Enforcing regulations, improving wastewater treatment, and relocating pig farms are crucial for restoring the Kereh River.

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Pullulan, a natural polysaccharide with unique biocompatibility and biodegradability, has gained prominence in nanomedicine. Its application in nanoparticle drug delivery systems showcases its potential for precision medicine. AIM OF STUDY: This scientific review aims to comprehensively discuss and summarize recent advancements in pullulan-based polymeric nanoparticles, focusing on their formulation, characterization, evaluation, and efficacy. METHODOLOGY: A search on Scopus, PubMed, and Google Scholar, using "Pullulan and Nanoparticle" as keywords, identified relevant articles in recent years. RESULTS: The literature search highlighted a diverse range of studies on the pullulan-based polymeric nanoparticles, including the success of high-selectivity hybrid pullulan-based nanoparticles for efficient boron delivery in colon cancer as the active targeting nanoparticle, the specific and high-efficiency release profile of the development of hyalgan-coated pullulan-based nanoparticles, and the design of multifunctional microneedle patches that incorporated pullulan-collagen-based nanoparticle-loaded antimicrobials to accelerate wound healing. These studies collectively underscore the versatility and transformative potential of pullulan-based polymeric nanoparticles in addressing biomedical challenges. CONCLUSION: Pullulan-based polymeric nanoparticles are promising candidates for innovative drug delivery systems, with the potential to overcome the limitations associated with traditional delivery methods.

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α-mangostin (Amg), a compound isolated from the mangosteen rind (Garcinia mangostana, L.), has demonstrated promising anticancer activity. However, its low solubility and selectivity against cancer cells limit its efficacy. To address this issue, researchers have developed chitosan/alginate polymeric nanoparticles (NANO-AMCAL) to enhance the effectiveness of Amg. In vitro studies have demonstrated that NANO-AMCAL is highly active against breast cancer cells. Therefore, an in vivo study was conducted to evaluate the efficacy of NANO-AMCAL in treating breast cancer in Wistar rats (Rattus norvegicus) and determine the effective dose. The rats were divided into seven treatment groups, including positive control, negative control, pure Amg, and NANO-AMCAL 5 mg, 10 mg, and 20 mg. The rats were injected subcutaneously with a carcinogenic agent, 7,12-dimethylbenz(a)anthracene (DMBA) and were evaluated for weight and tumor volume every three days during treatment. Surgery was performed on day 14, and histopathological studies were carried out on breast and lung cancer tissues. The results showed that NANO-AMCAL significantly enhanced the anticancer activity of Amg in treating breast cancer in Wistar rats. NANO-AMCAL containing 0.33 mg of Amg had a healing effect three times better than 20 mg pure Amg and was comparable to tamoxifen. The effective dose of NANO-AMCAL for anti-breast cancer treatment in Wistar rats was found to be 20 mg, which exhibited a good healing response, and the tumor volume continued to decrease up to 17.43% on the 14th day. Furthermore, histopathological tests showed tissue repair and no metastases. These findings suggest that NANO-AMCAL may be a promising therapeutic option for breast cancer treatment.

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Pupose: Cisplatin (CDDP), while amongst the recognised chemotherapeutic drugs currently available, is known to have limitations; the lack of a single treatment approach and non-specific targeted therapies. Therefore, the development of an innovative strategy that could achieve localised CDDP treatment is an urgent undertaking. Recent advances in titania nanotube arrays (TNAs) technology have demonstrated promising applications for localised chemotherapeutic drug treatment. The present work investigated the efficiency of a TNA nanosystem for the localised CDDP treatment of nasopharyngeal carcinoma (NPC). Methods: Two models of the TNA nanosystem were prepared: CDDP loaded onto the TNA nanosystem surface (CDDP-TNA) and the other consisted of chitosan-coated CDDP-TNA. CDDP release from these two nanosystems was comprehensively tested on the NPC cells NPC/HK-1 and C666-1. The NPC cytotoxicity profile of the two CDDP-TNA nanosystems was evaluated after incubation for 24, 48 and 72 hours. Intracellular damage profiles were studied using fluorescence microscopy analysis with Hoechst 33342, acridine orange and propidium iodide. Results: The half-maximal inhibitory concentrations (IC50) of CDDP at 24 hours were 0.50 mM for NPC/HK-1 and 0.05 mM for C666-1. CDDP in the CDDP-TNA and chitosan-coated CDDPTNA models presented a significant degree of NPC inhibition (P<0.05) after 24, 48 and 72 hours of exposure. The outcome revealed cellular damage and shrinkage of the cell membranes after 48 hours of exposure to CDDP-TNA. Conclusion: This in vitro work demonstrated the effectiveness of TNA nanosystems for the localised CDDP treatment of NPC cells. Further in vivo studies are needed to support the findings.

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Natural compounds provide precursors with various pharmacological activities and play an important role in discovering new chemical entities, including radiopharmaceuticals. In the development of new radiopharmaceuticals, iodine radioisotopes are widely used and interact with complex compounds including natural products. However, the development of radiopharmaceuticals from natural compounds with iodine radioisotopes has not been widely explored. This review summarizes the development of radiopharmaceuticals from natural compounds using iodine radioisotopes in the last 10 years, as well as discusses the challenges and strategies to improve future discovery of radiopharmaceuticals from natural resources. Literature research was conducted via PubMed, from which 32 research articles related to the development of natural compounds labeled with iodine radioisotopes were reported. From the literature, the challenges in developing radiopharmaceuticals from natural compounds were the purity and biodistribution. Despite the challenges, the development of radiopharmaceuticals from natural compounds is a golden opportunity for nuclear medicine advancement.

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Fluorescent organic nanoparticles (FONs) are a large family of nanostructures constituted by organic components that emit light in different spectral regions upon excitation, due to the presence of organic fluorophores. FONs are of great interest for numerous biological and medical applications, due to their high tunability in terms of composition, morphology, surface functionalization, and optical properties. Multifunctional FONs combine several functionalities in a single nanostructure (emission of light, carriers for drug-delivery, functionalization with targeting ligands, etc.), opening the possibility of using the same nanoparticle for diagnosis and therapy. The preparation, characterization, and application of these multifunctional FONs require a multidisciplinary approach. In this review, we present FONs following a tutorial approach, with the aim of providing a general overview of the different aspects of the design, preparation, and characterization of FONs. The review encompasses the most common FONs developed to date, the description of the most important features of fluorophores that determine the optical properties of FONs, an overview of the preparation methods and of the optical characterization techniques, and the description of the theoretical approaches that are currently adopted for modeling FONs. The last part of the review is devoted to a non-exhaustive selection of some recent biomedical applications of FONs.

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The halal status of meat products is an important factor being considered by many parties, especially Muslims. Analytical methods that have good specificity for the authentication of halal meat products are important as quality assurance to consumers. Metabolomic and lipidomic are two useful strategies in distinguishing halal and non-halal meat. Metabolomic and lipidomic analysis produce a large amount of data, thus chemometrics are needed to interpret and simplify the analytical data to ease understanding. This review explored the published literature indexed in PubMed, Scopus, and Google Scholar on the application of chemometrics as a tool in handling the large amount of data generated from metabolomic and lipidomic studies specifically in the halal authentication of meat products. The type of chemometric methods used is described and the efficiency of time in distinguishing the halal and non-halal meat products using chemometrics methods such as PCA, HCA, PLS-DA, and OPLS-DA is discussed.

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Protein is one of the essential macronutrients required by all living things. The breakdown of protein produces monomers known as amino acids. The concept of conjugating natural compounds with amino acids for therapeutic applications emerged from the fact that amino acids are important building blocks of life and are abundantly available; thus, a greater shift can result in structural modification, since amino acids contain a variety of sidechains. This review discusses the data available on amino acid-natural compound conjugates that were reported with respect to their backgrounds, the synthetic approach and their bioactivity. Several amino acid-natural compound conjugates have shown enhanced pharmacokinetic characteristics, including absorption and distribution properties, reduced toxicity and increased physiological effects. This approach could offer a potentially effective system of drug discovery that can enable the development of pharmacologically active and pharmacokinetically acceptable molecules.

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Because of the extraordinary advancements in biomedical nanotechnology over the last few decades, traditional drug delivery systems have been transformed into smart drug delivery systems that respond to stimuli. These well-defined nanoplatforms can boost therapeutic targeting efficacy while reducing the side effects/toxicities of payloads, which are crucial variables for enhancing patient compliance by responding to specific internal or external triggers. Cubosomes are lipid-based nano systems that are analogous to well-known vesicular systems, such as lipo- and niosomes. They could be used as part of a unique drug delivery system that includes hydro-, lipo-, and amphiphilic drug molecules. In this review, we critically analyze the relevant literature on cubosomesregarding theories of cubosomeself-assembly, composition, and manufacturing methods, with an emphasis on tumor-targeted drug delivery applications. Due to the bioadhesive and -compatible nature of cubosome dispersion, this review also focuses on a variety of drug delivery applications, including oral, ophthalmic and transdermal.

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Cyclic peptides have been widely reported to have therapeutic abilities in the treatment of cancer. This has been proven through in vitro and in vivo studies against breast, lung, liver, colon, and prostate cancers, among others. The multitude of data available in the literature supports the potential of cyclic peptides as anticancer agents. This review summarizes the findings from previously reported studies and discusses the different cyclic peptide compounds, the sources, and their modes of action as anticancer agents. The prospects and future of cyclic peptides will also be described to give an overview on the direction of cyclic peptide development for clinical applications.

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Neuraminidase (NA) is an enzyme that prevents virions from aggregating within the host cell and promotes cell-to-cell spread by cleaving glycosidic linkages to sialic acid. The best-known neuraminidase is the viral neuraminidase, which present in the influenza virus. Thus, the development of anti-influenza drugs that inhibit NA has emerged as an important and intriguing approach in the treatment of influenza. Garcinia atroviridis L. (GA) dried fruits (GAF) are used commercially as seasoning and in beverages. The main objective of this study was to identify a new potential neuraminidase inhibitor from GA. A bioassay-guided fractionation method was applied to obtain the bioactive compounds leading to the identification of garcinia acid and naringenin. In an enzyme inhibition study, garcinia acid demonstrated the highest activity when compared to naringenin. Garcinia acid had the highest activity, with an IC50 of 17.34-17.53 µg/mL or 91.22-92.21 µM against Clostridium perfringens-NA, and 56.71-57.85 µg/mL or 298.32-304.31 µM against H1N1-NA. Based on molecular docking results, garcinia acid interacted with the triad arginine residues (Arg118, Arg292, and Arg371) of the viral neuraminidase, implying that this compound has the potential to act as a NA enzyme inhibitor.

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Antibiotic resistance is a major health concern globally and has been estimated to cause 10 million deaths worldwide by year 2050 if the current trend of inappropriate and excessive use of antibiotics continues. Although, the discovery of antibiotics has saved countless of lives for the past 80 years, increasing levels of bacterial resistance to antibiotics would jeopardize the progress in clinical and agricultural sectors and may cause life-threatening situations even for previously treatable bacterial infections. Antibiotic resistance would increase the levels of poverty of low-middle income countries mostly due to extended hospital stays, higher cost of treatment and untimely deaths that directly affect the total productivity rate. Recent incidences of antibiotic resistance have been gradually increasing globally and this may potentiate horizontal transmission of the resistant gene and have been linked with cross-resistance to other antibiotic families as well. This review summarizes the global burden of antibiotic resistance from the economic viewpoint, highlights the recent incidences of antibiotic resistance mainly related to Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella spp. and Staphylococcus aureus, describes the common mechanistic actions of antibiotic resistance and potential strategies to overcome antibiotic resistance.

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Drug targeting is a progressive area of research with folate receptor alpha (FRα) receiving significant attention as a biological marker in cancer drug delivery. The binding affinity of folic acid (FA) to the FRα active site provides a basis for recognition of FRα. In this study, FA was conjugated to beta-cyclodextrin (ßCD) and subjected to in silico analysis (molecular docking and molecular dynamics (MD) simulation (100 ns)) to investigate the affinity and stability for the conjugated system compared to unconjugated and apo systems (ligand free). Docking studies revealed that the conjugated FA bound into the active site of FRα with a docking score (free binding energy < -15 kcal/mol), with a similar binding pose to that of unconjugated FA. Subsequent analyses from molecular dynamics (MD) simulations, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) demonstrated that FA and FA-ßCDs created more dynamically stable systems with FRα than the apo-FRα system. All systems reached equilibrium with stable RMSD values ranging from 1.9-2.4 Å and the average residual fluctuation values of the FRα backbone atoms for all residues (except for terminal residues ARG8, THR9, THR214, and LEU215) were less than 2.1 Å with a consistent Rg value of around 16.8 Å throughout the MD simulation time (0-100 ns). The conjugation with ßCD improved the stability and decreased the mobility of all the residues (except residues 149-151) compared to FA-FRα and apo-FRα systems. Further analysis of H-bonds, binding free energy (MM-PBSA), and per residue decomposition energy revealed that besides APS81, residues HIS20, TRP102, HIS135, TRP138, TRP140, and TRP171 were shown to have more favourable energy contributions in the holo systems than in the apo-FRα system, and these residues might have a direct role in increasing the stability of holo systems.

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Cancer is associated with single or multiple gene defects. Recently, much research has focused on incorporating genetic materials as one of the means to treat various types of carcinomas. RNA interference (RNAi) conveys an alternative genetic approach for cancer patients, especially when conventional medications fail. RNAi involves the inhibition of expression of specific messenger RNA that signals for uncontrollable cell growth and proliferation, most notably with carcinoma cells. This molecular technology is promising as genetic materials allow us to overcome issues associated with chemotherapeutic agents including organ damage associated with severe drug toxicities. Nonetheless, vast challenges impede successful gene therapy application, including low tumor localization, low stability and rapid clearance from the blood circulation. Owing to the limited treatment opportunities for the management of cancer, the development of effective siRNA carrier systems involving nanotherapeutics has been extensively explored. Over the past years, several siRNA nanotherapeutics have undergone a period of clinical investigation, with some demonstrating promising antitumor activities and safety profiles. Extensive observation of siRNA-nanoparticles is necessary to ensure commercial success. Therefore, this review mainly focuses on the progress of siRNAs-loaded nanoparticles that have undergone clinical trials for cancer treatment. The status of the siRNA nanotherapeutics is discussed, allowing comprehensive understanding of their gene-mediated therapeutics.

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Coffee has been studied for its health benefits, including prevention of several chronic diseases, such as type 2 diabetes mellitus, cancer, Parkinson's, and liver diseases. Chlorogenic acid (CGA), an important component in coffee beans, was shown to possess antiviral activity against viruses. However, the presence of caffeine in coffee beans may also cause insomnia and stomach irritation, and increase heart rate and respiration rate. These unwanted effects may be reduced by decaffeination of green bean Arabica coffee (GBAC) by treatment with dichloromethane, followed by solid-phase extraction using methanol. In this study, the caffeine and chlorogenic acid (CGA) level in the coffee bean from three different areas in West Java, before and after decaffeination, was determined and validated using HPLC. The results showed that the levels of caffeine were reduced significantly, with an order as follows: Tasikmalaya (2.28% to 0.097% (97 ppm), Pangalengan (1.57% to 0.049% (495 ppm), and Garut (1.45% to 0.00002% (0.2 ppm). The CGA levels in the GBAC were also reduced as follows: Tasikmalaya (0.54% to 0.001% (118 ppm), Pangalengan (0.97% to 0.0047% (388 ppm)), and Garut (0.81% to 0.029% (282 ppm). The decaffeinated samples were then subjected to the H5N1 neuraminidase (NA) binding assay to determine its bioactivity as an anti-influenza agent. The results show that samples from Tasikmalaya, Pangalengan, and Garut possess NA inhibitory activity with IC50 of 69.70, 75.23, and 55.74 µg/mL, respectively. The low level of caffeine with a higher level of CGA correlates with their higher levels of NA inhibitory, as shown in the Garut samples. Therefore, the level of caffeine and CGA influenced the level of NA inhibitory activity. This is supported by the validation of CGA-NA binding interaction via molecular docking and pharmacophore modeling; hence, CGA could potentially serve as a bioactive compound for neuraminidase activity in GBAC.

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Lung cancers, the number one cancer killer, can be broadly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with NSCLC being the most commonly diagnosed type. Anticancer agents for NSCLC suffer from various limitations that can be partly overcome by the application of nanomedicines. Nanoparticles is a branch within nanomedicine that can improve the delivery of anticancer drugs, whilst ensuring the stability and sufficient bioavailability following administration. There are many publications available in the literature exploring different types of nanoparticles from different materials. The effectiveness of a treatment option needs to be validated in suitable in vitro and/or in vivo models. This includes the developed nanoparticles, to prove their safety and efficacy. Many researchers have turned towards in vitro models that use normal cells or specific cells from diseased tissues. However, in cellular works, the physiological dynamics that is available in the body could not be mimicked entirely, and hence, there is still possible development of false positive or false negative results from the in vitro models. This article provides an overview of NSCLC, the different nanoparticles available to date, and in vitro evaluation of the nanoparticles. Different types of cells suitable for in vitro study and the important precautions to limit the development of false results are also extensively discussed.

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Folate receptor alpha (FRα) is known as a biological marker for many cancers due to its overexpression in cancerous epithelial tissue. The folic acid (FA) binding affinity to the FRα active site provides a basis for designing more specific targets for FRα. Heterocyclic rings have been shown to interact with many receptors and are important to the metabolism and biological processes within the body. Nineteen FA analogs with substitution with various heterocyclic rings were designed to have higher affinity toward FRα. Molecular docking was used to study the binding affinity of designed analogs compared to FA, methotrexate (MTX), and pemetrexed (PTX). Out of 19 FA analogs, analogs with a tetrazole ring (FOL03) and benzothiophene ring (FOL08) showed the most negative binding energy and were able to interact with ASP81 and SER174 through hydrogen bonds and hydrophobic interactions with amino acids of the active site. Hence, 100 ns molecular dynamics (MD) simulations were carried out for FOL03, FOL08 compared to FA, MTX, and PTX. The root mean square deviation (RMSD) and root mean square fluctuation (RMSF) of FOL03 and FOL08 showed an apparent convergence similar to that of FA, and both of them entered the binding pocket (active site) from the pteridine part, while the glutamic part was stuck at the FRα pocket entrance during the MD simulations. Molecular mechanics Poisson-Boltzmann surface accessible (MM-PBSA) and H-bond analysis revealed that FOL03 and FOL08 created more negative free binding and electrostatic energy compared to FA and PTX, and both formed stronger H-bond interactions with ASP81 than FA with excellent H-bond profiles that led them to become bound tightly in the pocket. In addition, pocket volume calculations showed that the volumes of active site for FOL03 and FOL08 inside the FRα pocket were smaller than the FA-FRα system, indicating strong interactions between the protein active site residues with these new FA analogs compared to FA during the MD simulations.

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Seventeen methanol extracts from different plant parts of five different Cassia species, including C. timorensis, C. grandis, C. fistula, C. spectabilis, and C. alata were screened against acetylcholinesterase (AChE). C. timorensis extracts were found to exhibit the highest inhibition towards AChE whereby the leaf, stem, and flower methanol extracts showed 94-97% inhibition. As far as we are aware, C. timorensis is one of the least explored Cassia spp. for bioactivity. Further fractionation led to the identification of six compounds, isolated for the first time from C. timorensis: 3-methoxyquercetin (1), benzenepropanoic acid (2), 9,12,15-octadecatrienoic acid (3), ß-sitosterol (4), stigmasterol (5), and 1-octadecanol (6). Compound 1 showed moderate inhibition towards AChE (IC50: 83.71 µM), while the other compounds exhibited poor to slightly moderate AChE inhibitory activity. Molecular docking revealed that the methoxy substitution of 1 formed a hydrogen bond with TYR121 at the peripheral anionic site (PAS) and the hydroxyl group at C5 formed a covalent hydrogen bond with ASP72. Additionally, the OH group at the C3' position formed an interaction with the protein at the acyl pocket (PHE288). This possibly explains the activity of 1 in blocking the entry of acetylcholine (ACh, the neurotransmitter), thus impeding the hydrolysis of ACh.

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Nanoparticles (NPs) have been shown to have good ability to improve the targeting and delivery of therapeutics. In the field of photodynamic therapy (PDT), this targeting advantage of NPs could help ensure drug delivery at specific sites. Among the commonly reported NPs for PDT applications, NPs from zinc oxide, titanium dioxide, and fullerene are commonly reported. In addition, graphene has also been reported to be used as NPs albeit being relatively new to this field. In this context, the present review is organized by these different NPs and contains numerous research works related to PDT applications. The effectiveness of these NPs for PDT is discussed in detail by collecting all essential information described in the literature. The information thus assembled could be useful in designing new NPs specific for PDT and/or PTT applications in the future.