Dietary Patterns and Lifestyle Factors Associated with the Risk of Colorectal Cancer: A Hospital-Based Case-Control Study among Malaysians.

Background: This study aimed to examine the association between dietary patterns, lifestyle factors, and colorectal cancer (CRC) risk among the Malaysian population. Methods: We recruited 100 patients and 100 controls from two selected government hospitals. Principal component analysis was used to identify dietary patterns using a 123-item semiquantitative food frequency questionnaire. Tobacco smoking and alcohol consumption questionnaires were modified from the WHO STEPS Survey questionnaire. Physical activity levels were assessed using the revised Global Physical Activity questionnaire. Associations between dietary patterns, lifestyle factors and CRC risk were assessed using logistic regression with SPSS version 24.0. Results: Three dietary patterns were derived from factor analysis: i) vegetables; ii) meat, seafood and processed food; and iii) grains and legumes. High vegetable diet intake was independently and significantly associated with an 81% decreased risk of CRC (odds ratio [OR]: 0.19; 95% confidence interval [CI]: 0.08, 0.46). Both recreational-related physical activity (OR: 2.04; 95% CI: 1.14, 3.64) and vigorous physical activity (OR: 2.06; 95% CI: 1.13, 3.74) are significantly associated with decreased risk of CRC. Increasing the number of cigarettes smoked (≥ 16 cigarettes) per day significantly increased the odds of developing CRC (OR: 2.58; 95% CI: 1.95, 6.75). The duration of alcohol consumption cessation was inversely associated with CRC risk (OR: 2.52; 95% CI: 2.30, 10.57). Conclusion: The protective effects of a fruit and vegetable diet, and a healthy lifestyle can be used to develop interventions that help reduce the risk of CRC in the Malaysian population.

Green synthesis of ginger-encapsulated zinc oxide nanoparticles: Unveiling their characterization and selective cytotoxicity on MDA-MB 231 breast cancer cells.

Zinc oxide nanoparticles (ZnO-NPs) were synthesized using ginger (Zingiber officinale) extracts in a green synthesis approach and evaluated their in vitro cytotoxicity effect on the MDA-MB 231 breast cancer cell line. The bottom-up approach was employed to develop the green-synthesized ginger-encapsulated ZnO-NPs (GZnO-NPs) without using hazardous substances. The most substantial Fourier-transform infrared absorption peak of the ginger root extract was seen at 1634.24 cm-1. The peak also confirmed the presence of ginger root extract-encapsulated ZnO-NPs at 1556.79, 1471.54, and 1019.83 cm-1. It indicates that the biomolecules found in plant extracts behave as capping agents, aiding in the formation of nanoparticles. The mean particle sizes (PSs) of optimized GZnO-NPs of the ratios 1:2 were found to be 104.01 ± 7.12 nm with a zeta potential of -11.5 ± 1.31 mV. The X-ray diffraction and scanning electron microscope analysis confirmed that the prepared nanoparticles were spherical and crystalline, with PS ranging from 100 to 150 nm. The GZnO-NPs were subjected to MTT assay and cellular migration potential, and it was found that the inhibitory concentration on the MDA-MB 231 (breast) cancer cell line and scratch area showed a dose-dependent efficacy. The successfully green-synthesized GZnO-NPs effectively induced cell death in the MDA-MB 231 cancer cell line. The scratch assay results confirmed that prepared GZnO-NPs inhibited the proliferation and migration of cancerous cells.

CCAT 1- A Pivotal Oncogenic Long Non-Coding RNA in Colorectal Cancer.

Colorectal cancer (CRC) is ranked as the third most common cancer and second deadliest cancer in both men and women in the world. Currently, the cure rate and 5-year survival rate of CRC patients remain relatively low. Therefore, discovering a novel molecular biomarker that can be used to improve CRC screening, diagnosis, prognosis, and treatment would be beneficial. Long non-coding RNA colon cancer-associated transcript 1 (CCAT 1) has been found overexpressed in CRC and is associated with CRC tumorigenesis and treatment outcome. CCAT 1 has a high degree of specificity and sensitivity, it is readily detected in CRC tissues and is significantly overexpressed in both premalignant and malignant CRC tissues. Besides, CCAT 1 is associated with clinical manifestation and advanced features of CRC, such as lymph node metastasis, high tumor node metastasis stage, differentiation, invasion, and distant metastasis. In addition, they can upregulate oncogenic c-MYC and negatively modulate microRNAs via different mechanisms of action. Furthermore, dysregulated CCAT 1 also enhances the chemoresistance in CRC cells while downregulation of them reverses the malignant phenotypes of cancer cells. In brief, CCAT 1 serves as a potential screening, diagnostic and prognostic biomarker in CRC, it also serves as a potential therapeutic marker to treat CRC patients.

H19: An Oncogenic Long Non-coding RNA in Colorectal Cancer.

Colorectal cancer (CRC) has been recorded amongst the most common cancers in the world, with high morbidity and mortality rates, and relatively low survival rates. With risk factors such as chronic illness, age, and lifestyle associated with the development of CRC, the incidence of CRC is increasing each year. Thus, the discovery of novel biomarkers to improve the diagnosis and prognosis of CRC has become beneficial. Long non-coding RNAs (lncRNAs) have been emerging as potential players in several tumor types, one among them is the lncRNA H19. The paternally imprinted oncofetal gene is expressed in the embryo, downregulated at birth, and reappears in tumors. H19 aids in CRC cell growth, proliferation, invasion, and metastasis via various mechanisms of action, significantly through the lncRNA-microRNA (miRNA)-messenger RNA (mRNA)-competitive endogenous RNA (ceRNA) network, where H19 behaves as a miRNA sponge. The RNA transcript of H19 obtained from the first exon of the H19 gene, miRNA-675 also promotes CRC carcinogenesis. Overexpression of H19 in malignant tissues compared to adjacent non-malignant tissues marks H19 as an independent prognostic marker in CRC. Besides its prognostic value, H19 serves as a promising target for therapy in CRC treatment.

CRNDE: A Pivotal Oncogenic Long Non-Coding RNA in Cancers.

Colorectal Neoplasia Differentially Expressed (CRNDE), a long non-coding RNA that was initially identified as aberrantly expressed in colorectal cancer (CRC) has also been observed to exhibit elevated expression in various other human malignancies. Recent research has accumulated substantial evidence implicating CRNDE as an oncogenic player, exerting influence over critical cellular processes linked to cancer progression. Particularly, its regulatory interactions with microRNAs and proteins have been shown to modulate pathways that contribute to carcinogenesis and tumorigenesis. This review will comprehensively outline the roles of CRNDE in colorectal, liver, glioma, lung, cervical, gastric and prostate cancer, elucidating the mechanisms involved in modulating proliferation, apoptosis, migration, invasion, angiogenesis, and radio/chemoresistance. Furthermore, the review highlights CRNDE's potential as a multifaceted biomarker, owing to its presence in diverse biological samples and stable properties, thereby underscoring its diagnostic, therapeutic, and prognostic applications. This review aims to provide comprehensive insights of CRNDE-mediated oncogenesis and identify CRNDE as a promising target for future clinical interventions.

Implications of Porphyromonas gingivalis peptidyl arginine deiminase and gingipain R in human health and diseases.

Porphyromonas gingivalis is a major pathogenic bacterium involved in the pathogenesis of periodontitis. Citrullination has been reported as the underlying mechanism of the pathogenesis, which relies on the interplay between two virulence factors of the bacterium, namely gingipain R and the bacterial peptidyl arginine deiminase. Gingipain R cleaves host proteins to expose the C-terminal arginines for peptidyl arginine deiminase to citrullinate and generate citrullinated proteins. Apart from carrying out citrullination in the periodontium, the bacterium is found capable of citrullinating proteins present in the host synovial tissues, atherosclerotic plaques and neurons. Studies have suggested that both virulence factors are the key factors that trigger distal effects mediated by citrullination, leading to the development of some non-communicable diseases, such as rheumatoid arthritis, atherosclerosis, and Alzheimer's disease. Thus, inhibition of these virulence factors not only can mitigate periodontitis, but also can provide new therapeutic solutions for systematic diseases involving bacterial citrullination. Herein, we described both these proteins in terms of their unique structural conformations and biological relevance to different human diseases. Moreover, investigations of inhibitory actions on the enzymes are also enumerated. New approaches for identifying inhibitors for peptidyl arginine deiminase through drug repurposing and virtual screening are also discussed.

Inhibition of Porphyromonas gingivalis peptidyl arginine deiminase, a virulence factor, by antioxidant-rich Cratoxylum cochinchinense: In vitro and in silico evaluation.

Porphyromonas gingivalis, the cause of periodontitis, is also linked to many systemic disorders due to its citrullination capability from a unique peptidyl arginine deiminase (PPAD). Protein citrullination is able to trigger an autoimmune response, increasing the severity of rheumatoid arthritis. The main objective of this study is to evaluate the inhibitory activity of Cratoxylym cochinchinense leaves extract towards the PPAD in vitro and in silico. Methanolic extract of Cratoxylum cochinchinense (CCM) was tested for total phenolic and flavonoid contents along with antioxidative assays. Inhibition of PPAD activities was conducted thereafter using recombinant PPAD in cell lysate. Phytocompounds postulated present in the CCM such as mangiferin, vismiaquinone A, δ-tocotrienol and α-tocotrienol and canophyllol were used as ligands in a simulated docking study against PPAD. Results obtained indicated high antioxidant potential in CCM while recording abundant phenolic (129.0 ± 2.5495 mg GA/g crude extract) and flavonoid (159.0 ± 2.1529 mg QE/g crude extract) contents. A dose-dependent inhibition of PPAD was observed when CCM was evaluated at various concentrations. CCM at 1 mg/mL exhibited citrulline concentration of 24.37 ± 3.25 mM which was 5 times lower than the negative control (114.23 ± 3.31 mM). Molecular docking simulation revealed that mangiferin and vismiaquinone A engaged in H-bonding and pi-pi interactions with important active site residues (Asp130, Arg152, Arg154 and Trp127) of PPAD and could be the potential phytochemicals that accounted for the inhibitory activities observed in the methanolic leaves extract. As such, CCM could be further explored for its therapeutic properties not only for periodontitis, but also for other systemic diseases like rheumatoid arthritis.

Structure-based discovery and bio-evaluation of a cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-one as a phosphodiesterase 10A inhibitor.

Phosphodiesterase10A (PDE10A) is a potential therapeutic target for the treatment of several neurodegenerative disorders. Thus, extensive efforts of medicinal chemists have been directed toward developing potent PDE10A inhibitors with minimal side effects. However, PDE10A inhibitors are not approved as a treatment for neurodegenerative disorders, possibly due to the lack of research in this area. Therefore, the discovery of novel and diverse scaffolds targeting PDE10A is required. In this study, we described the identification of a new PDE10A inhibitor by structure-based virtual screening combining pharmacophore modelling, molecular docking, molecular dynamics simulations, and biological evaluation. Zinc42657360 with a cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-one scaffold from the zinc database exhibited a significant inhibitory activity of 1.60 µM against PDE10A. The modelling studies demonstrated that Zinc42657360 is involved in three hydrogen bonds with ASN226, THR187 and ASP228, and two aromatic interactions with TYR78 and PHE283, besides the common interactions with the P-clamp residues PHE283 and ILE246. The novel scaffold of Zinc42657360 can be used for the rational design of PDE10A inhibitors with improved affinity.

Hypoglycemic Effects of Plant Flavonoids: A Review.

Diabetes mellitus is a metabolic disorder with chronic high blood glucose levels, and it is associated with defects in insulin secretion, insulin resistance, or both. It is also a major public issue, affecting the world's population. This disease contributes to long-term health complications such as dysfunction and failure of multiple organs, including nerves, heart, blood vessels, kidneys, and eyes. Flavonoids are phenolic compounds found in nature and usually present as secondary metabolites in plants, vegetables, and fungi. Flavonoids possess many health benefits such as anti-inflammatory and antioxidant activities, and naturally occurring flavonoids contribute to antidiabetic effects.Many studies conducted in vivo and in vitro have proven the hypoglycemic effect of plant flavonoids. A large number of studies showed that flavonoids hold positive results in controlling the blood glucose level in streptozotocin (STZ)-induced diabetic rats and further prevent the complications of diabetes. The future development of flavonoid-based drugs is believed to provide significant effects on diabetes mellitus and diabetes complication diseases. This review aims at summarizing the various types of flavonoids that function as hyperglycemia regulators such as inhibitors of α-glucosidase and glucose cotransporters in the body. This review article discusses the hypoglycemic effects of selected plant flavonoids namely quercetin, kaempferol, rutin, naringenin, fisetin, and morin. Four search engines, PubMed, Google Scholar, Scopus, and SciFinder, are used to collect the data.

The Mechanistic Action of Biosynthesised Silver Nanoparticles and Its Application in Aquaculture and Livestock Industries.

Nanotechnology is a rapidly developing field due to the emergence of various resistant pathogens and the failure of commercial methods of treatment. AgNPs have emerged as one of the best nanotechnology metal nanoparticles due to their large surface-to-volume ratio and success and efficiency in combating various pathogens over the years, with the biological method of synthesis being the most effective and environmentally friendly method. The primary mode of action of AgNPs against pathogens are via their cytotoxicity, which is influenced by the size and shape of the nanoparticles. The cytotoxicity of the AgNPs gives rise to various theorized mechanisms of action of AgNPs against pathogens such as activation of reactive oxygen species, attachment to cellular membranes, intracellular damage and inducing the viable but non-culturable state (VBNC) of pathogens. This review will be centred on the various theorized mechanisms of actions and its application in the aquaculture, livestock and poultry industries. The application of AgNPs in aquaculture is focused around water treatment, disease control and aquatic nutrition, and in the livestock application it is focused on livestock and poultry.

The Potential Benefits of Nanotechnology in Treating Alzheimer's Disease.

Alzheimer's disease is a neurodegenerative disorder that is caused by the accumulation of beta-amyloid plaques in the brain. Currently, there is no definitive cure available to treat Alzheimer's disease. The available medication in the market has the ability to only slow down its progression. However, nanotechnology has shown its superiority that can be applied for medical usage and it has a great potential in the therapy of Alzheimer's disease, specifically in the disease diagnosis and providing an alternative approach to treat Alzheimer's disease. This is done by increasing the efficiency of drug delivery by penetrating and overcoming the blood-brain barrier. Having said that, there are limitations that need to be further investigated and researched in order to minimize the adverse effects and potential toxicity and to improve drug bioavailability. The recent advances in the treatment of Alzheimer's disease using nanotechnology include the regeneration of stem cells, nanomedicine, and neuroprotection. In this review, we will discuss the advancement of nanotechnology which helps in the diagnosis and treatment of neurodegenerative disorders such as Alzheimer's disease as well as its challenges.

Biodecolourisation of Reactive Red 120 as a Sole Carbon Source by a Bacterial Consortium-Toxicity Assessment and Statistical Optimisation.

The application of microorganisms in azo dye remediation has gained significant attention, leading to various published studies reporting different methods for obtaining the best dye decolouriser. This paper investigates and compares the role of methods and media used in obtaining a bacterial consortium capable of decolourising azo dye as the sole carbon source, which is extremely rare to find. It was demonstrated that a prolonged acclimation under low substrate availability successfully isolated a novel consortium capable of utilising Reactive Red 120 dye as a sole carbon source in aerobic conditions. This consortium, known as JR3, consists of Pseudomonas aeruginosa strain MM01, Enterobacter sp. strain MM05 and Serratia marcescens strain MM06. Decolourised metabolites of consortium JR3 showed an improvement in mung bean's seed germination and shoot and root length. One-factor-at-time optimisation characterisation showed maximal of 82.9% decolourisation at 0.7 g/L ammonium sulphate, pH 8, 35 °C, and RR120 concentrations of 200 ppm. Decolourisation modelling utilising response surface methodology (RSM) successfully improved decolourisation even more. RSM resulted in maximal decolourisation of 92.79% using 0.645 g/L ammonium sulphate, pH 8.29, 34.5 °C and 200 ppm RR120.

Improvement of Ficin-Based Inhibitive Enzyme Assay for Toxic Metals Using Response Surface Methodology and Its Application for Near Real-Time Monitoring of Mercury in Marine Waters.

Potentially toxic metals pollution in the Straits of Malacca warrants the development of rapid, simple and sensitive assays. Enzyme-based assays are excellent preliminary screening tools with near real-time potential. The heavy-metal assay based on the protease ficin was optimized for mercury detection using response surface methodology. The inhibitive assay is based on ficin action on the substrate casein and residual casein is determined using the Coomassie dye-binding assay. Toxic metals strongly inhibit this hydrolysis. A central composite design (CCD) was utilized to optimize the detection of toxic metals. The results show a marked improvement for the concentration causing 50% inhibition (IC50) for mercury, silver and copper. Compared to one-factor-at-a-time (OFAT) optimization, RSM gave an improvement of IC50 (mg/L) from 0.060 (95% CI, 0.030-0.080) to 0.017 (95% CI, 0.016-0.019), from 0.098 (95% CI, 0.077-0.127) to 0.028 (95% CI, 0.022-0.037) and from 0.040 (95% CI, 0.035-0.045) to 0.023 (95% CI, 0.020-0.027), for mercury, silver and copper, respectively. A near-real time monitoring of mercury concentration in the Straits of Malacca at one location in Port Klang was carried out over a 4 h interval for a total of 24 h and validated by instrumental analysis, with the result revealing an absence of mercury pollution in the sampling site.

Draft Genome Sequence of Lactarius deliciosus Strain CBS 582.63 from the CBS-KNAW Culture Collection.

A type strain of Lactarius deliciosus was obtained from the CBS-KNAW culture collection. The mycelium was cultured using potato dextrose agar, and the extracted genomic DNA was subjected to PacBio genome sequencing. Upon assembly and annotation, the genome size was estimated to be 54 Mbp, with 12,753 genes.

HMG-CoA Reductase as Target for Drug Development.

The main strategy for lowering blood cholesterol levels is through the inhibition of the NADPH-dependent HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase). The enzyme catalyses the reduction of HMG-CoA to mevalonate and this process is inhibited by statins that form the bulk of the therapeutic agents to treat high cholesterol since the 1970s. Newer drugs that are safer than statins are constantly being developed. The inhibition of candidate drugs to HMG-CoA reductase remains the mainstay of drug development research. The determination of the enzyme activity is important for the correct assessment of potency of the enzyme as well as determining the inhibition of potential therapeutic agents from the plant and microbial extracts. Also, this chapter covers the use of the popular four-parameter logistics model that can yield accurate estimation of the IC50 values of therapeutic agents and their 95% confidence intervals.

Anti-HMG-CoA Reductase, Antioxidant, and Anti-Inflammatory Activities of Amaranthus viridis Leaf Extract as a Potential Treatment for Hypercholesterolemia.

Inflammation and oxidative stress are believed to contribute to the pathology of several chronic diseases including hypercholesterolemia (elevated levels of cholesterol in blood) and atherosclerosis. HMG-CoA reductase inhibitors of plant origin are needed as synthetic drugs, such as statins, which are known to cause adverse effects on the liver and muscles. Amaranthus viridis (A. viridis) has been used from ancient times for its supposedly medically beneficial properties. In the current study, different parts of A. viridis (leaf, stem, and seed) were evaluated for potential anti-HMG-CoA reductase, antioxidant, and anti-inflammatory activities. The putative HMG-CoA reductase inhibitory activity of A. viridis extracts at different concentrations was determined spectrophotometrically by NADPH oxidation, using HMG-CoA as substrate. A. viridis leaf extract revealed the highest HMG-CoA reductase inhibitory effect at about 71%, with noncompetitive inhibition in Lineweaver-Burk plot analysis. The leaf extract showed good inhibition of hydroperoxides, 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), and ferric ion radicals in various concentrations. A. viridis leaf extract was proven to be an effective inhibitor of hyaluronidase, lipoxygenase, and xanthine oxidase enzymes. The experimental data suggest that A. viridis leaf extract is a source of potent antioxidant and anti-inflammatory agent and may modulate cholesterol metabolism by inhibition of HMG-CoA reductase.

Antiartherosclerotic effects of plant flavonoids.

Atherosclerosis is the process of hardening and narrowing the arteries. Atherosclerosis is generally associated with cardiovascular diseases such as strokes, heart attacks, and peripheral vascular diseases. Since the usage of the synthetic drug, statins, leads to various side effects, the plants flavonoids with antiartherosclerotic activity gained much attention and were proven to reduce the risk of atherosclerosis in vitro and in vivo based on different animal models. The flavonoids compounds also exhibit lipid lowering effects and anti-inflammatory and antiatherogenic properties. The future development of flavonoids-based drugs is believed to provide significant effects on atherosclerosis and its related diseases. This paper discusses the antiatherosclerotic effects of selected plant flavonoids such as quercetin, kaempferol, myricetin, rutin, naringenin, catechin, fisetin, and gossypetin.