Saudi Journal of Biological Sciences最新文献

TWIST1, a basic helix-loop-helix transcription factor with versatile roles in cancer, is frequently deregulated in cancers, through established pathway perturbations. However. the significance of TWIST1 methylation in the deregulation of TWIST1 in gastrointestinal cancers is not fully clear. This study hypothesized that TWIST1 promoter methylation deregulates TWIST1 expression independent of established deregulators such as the WNT, TGFB, NOTCH and miRNA pathways. To prove this hypothesis, colon, gastric and rectal cancer genomic data comprising gene expression, DNA methylation, and miRNA data were retrieved from the Cancer Genome Atlas cohorts which are publicly available in cancer genomic databases, the Genome Data Commons and the cBioportal.org. About 217 variables comprising expression levels of genes of the WNT, TGFB, NOTCH and miRNA signalling pathways, as well as the beta values of 17 TWIST1 methylation loci were subjected to Principal Component Regression Analysis, and then standard Linear Regression Analysis. The results showed that TWIST1 methylation is a predictor of TWIST1 expression in the gastrointestinal cancers, independent of WNT, TGFB, and NOTCH signalling and miRNA deregulation. The results also showed that different TWIST1 methylation loci may deregulate TWIST1 expression in different cancer types. The inference that can be drawn from this study is that TWIST1 DNA methylation is an important TWIST1 deregulation mechanism in colon, rectal and gastric cancers.

Background

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder influenced by genetic and environmental factors. This study examined the specific gene variants, dopamine transporter 1 (DAT1) rs6350, dopamine receptor D3 (DRD3) rs6280, dopamine receptor D2 (DRD2) rs6277, and catechol-O-methyltransferase (COMT) rs4633, in relation to ADHD among Pakistani children by exploring the potential gene-gene and gene-environment interactions.

Methods

A total of 100 cases of ADHD and 100 healthy children were recruited. The tetra-primer amplification refractory mutation system (ARMS) assays were designed for genotyping the selected variants in both groups, and their association with ADHD was determined in different genetic models. Gene-gene and gene-environmental interactions were determined by the multifactor dimensionality reduction (MDR) method.

Results

The DAT1 rs6350 SNV AA genotype showed a significantly increased risk for ADHD in the codominant and recessive models. Conversely, the AG genotype demonstrated a protective factor for ADHD in the codominant and overdominant models. The DRD3 rs6280 T allele exhibited a decreased risk for ADHD, and the TT genotype showed a reduced risk in the recessive and log-additive models. No association between the DRD2 rs6277 and COMT rs4633 SNVs with ADHD was found in our population. The MDR analysis of the best three-fold interaction model showed redundancy between DAT1 rs6350 and DRD3 rs6280; however, the risk was increased with the gender variable, which showed a weak synergistic interaction with these SNVs.

Conclusion

Genes associated with dopaminergic neurotransmission may contribute to the occurrence of ADHD. Furthermore, gene-gene and gene-environmental interactions may increase ADHD susceptibility.

The dried leaves of Melastoma malabathricum L., locally named Karamunting or Senduduk, is traditionally consumed in many regions in Indonesia as herbal tea to cure different illnesses, including diabetes. To date, information on the compounds responsible for their antidiabetic activity is still very rare. The study aimed to identify bioactive compounds of M. malabathricum L. leaves using LC-MS based metabolomics and molecular docking approaches. The leaves brewed with different methods were subjected to LC−MS measurements and several bioactivity tests (in vivo and in vitro antihyperglycemic, and in vitro antioxidant). LC−MS data were linked to the activity data using multivariate data analysis. Molecular docking using alpha-glucosidase, alpha-amylase, and insulin receptor as protein targets was used to verify the results and study the interaction between the identified compound and protein targets. As results, isoquercetin and myricitrin were identified as compounds strongly associated with alpha-amylase inhibitors, while rutin and epicatechin were identified as alpha-glucosidase inhibitors. Quercitrin, citric acid, quercetin, epicatechin, isoquercitrin, and 7-hydroxycoumarine were strongly correlated with both antihyperglycemic and antioxidant activities. The results of metabolomics were confirmed with molecular docking studies, which showed that some of these compounds acted as competitive inhibitors, while others acted as non-competitive ones. Possible synergism between epicatechin and citric acid in their interaction with IR was detected. Metabolomics combined with molecular docking efficiently identified and confirmed several antihyperglycemic and antioxidant compounds from M. malabathricum L., leaf. This study provides scientific evidence for the traditional use of M. malabathricum L. as an antidiabetic herbal.

Chili, renowned globally and deeply ingrained in various cultures. Regrettably, the onset of diseases instigated by pests and pathogens has inflicted substantial losses on chili crops, with some farms experiencing complete production decimation. Challenges confronting chili cultivation include threats from pathogenic microbes like Xanthomonas, Fusarium, Phytophthora, Verticillium, Rhizoctonia, Colletotrichium and Viruses, alongside pests such as whiteflies, mites, thrips, aphids, and fruit flies. While conventional farming practices often resort to chemical pesticides to combat these challenges, their utilization poses substantial risks to both human health and the environment. In response to this pressing issue, this review aims to evaluate the potential of microbe-based biological control as eco-friendly alternatives to chemical pesticides for chili cultivation. Biocontrol agents such as Bacillus spp., Trichoderma spp., and entomopathogenic fungi present safer and more environmentally sustainable alternatives to chemical pesticides. However, despite the recognised potential of biocontrol agents, research on their efficacy in controlling the array of pests and pathogens affecting chili farming remains limited. This review addresses this gap by evaluating the efficiency of biocontrol agents, drawing insights from existing studies conducted in other crop systems, regarding pest and pathogen management. Notably, an analysis of Scopus publications revealed fewer than 30 publications in 2023 focused on these three microbial agents. Intriguingly, India, as the world’s largest chili producer, leads in the number of publications concerning Bacillus spp., Trichoderma spp., and entomopathogenic fungi in chili cultivation. Further research on microbial agents is imperative to mitigate infections and reduce reliance on chemical pesticides for sustainable chili production.

This paper outlines a methodical approach for isolating 6-gingerol (1a) from Zingiber officinale Roscoe rhizomes on a gram-scale, resulting in a product of high purity and significant yield. Further, 6-gingerol (1a) [SSG1] derivatives, including 1-(4-hydroxy-3-methoxyphenyl)decane-3,5-dione (1ab), were synthesized via a semi-synthetic pathway involving DMP-mediated fast oxidation and replication. Subsequently, a new series of 1,4-benzodiazepines (3a-c) was synthesized quantitatively using a basic technique. This synthesis necessitated the interaction of 1ab with various o-phenylenediamine (2a-c) compounds. Spectroscopic methods were employed to characterize the synthesized 1,4-benzodiazepines (3a-c)[SSG2, SSG3 & SSG4]. Despite extensive investments by pharmaceutical companies in traditional drug research and development for diseases like type 2 diabetes (T2D), successful treatments remain elusive. Medication repurposing has gained traction as a strategy to address not only diabetes but also other disorders. Leveraging existing molecular pharmacology data accelerates the development of new medications. This paper underscores the importance of repurposing traditional medicines to combat a range of communicable and non-communicable diseases, offering a promising avenue for therapeutic advancement. Additionally, molecular docking studies suggested that one derivative (SSG2) exhibited stronger binding affinity compared to the reference standards. Overall, the findings of this study highlight the potential of semi-synthetic gingerol derivatives for the development of novel therapeutic agents.

Interleukin-8 (IL-8) is a chemokine, a type of signaling molecule that has a role in immunological responses and inflammation. In recent years, IL-8 is additionally related to cancer growth and recurrence. Breast cancer growth, progression, and metastatic development are all linked to IL-8. Breast cancer cells are known to develop faster when IL-8 stimulates their proliferation and survival. It can also cause angiogenesis, or the creation of new blood vessels, which is necessary for tumor nutrition and growth. IL-8 and curcumin have been subjects of interest in drug design, particularly in the context of inflammation-related disorders and cancer. This study aims to give an overview of the role of IL-8. Inhibitor-based treatment approaches were being used to target IL-8 with curcumin. Molecular docking method was employed to find a potential interaction to supress competitive inhibition of IL-8 with curcumin. PASS analysis and ADMET characteristics were also being carried out. In the end, IL-8 complexed with curcumin is chosen for MD simulations. Overall, our results showed that during the simulation, the complex stayed comparatively stable. It is also possible to investigate curcumin further as a possible treatment option. The combined results imply that IL-8 and their genetic alterations can be studied in precision cancer therapeutic treatments, utilizing target-driven therapy and early diagnosis.