Drying methodology effect on the phenolic content, antioxidant activity of Myrtus communis L. leaves ethanol extracts and soybean oil oxidative stability.

In this study, different drying methodologies (convective air, oven and microwave) of Myrtus communis L. (M. communis L.) leaves were conducted to investigate their effects on the levels of phenolic compounds, antioxidant capacity of ethanolic extracts (EEs) as well as the soybean oil oxidative stability. Drying methodology significantly influenced the extractability of phenolic compounds. Microwave drying led to an increase in the amounts of total phenols, flavonoids and proanthocyanidins followed by oven drying at 70 °C. Higher temperature of drying (100 and 120 °C) led to a significant reduction of their amounts (p < 0.05). An ultra-performance liquid chromatography method combined with high resolution mass spectroscopic detection was used to analyze the phenolic fraction of extracts. Higher amounts of the identified compounds were observed when leaves were heat treated. Furthermore, the evaluation of the antioxidant activity showed that the studied extracts possess in general high antioxidant capacities, significantly dependent on the employed drying methodology. The incorporation of the different extracts at 200 ppm in soybean oil showed that its oxidative stability was significantly improved. Extracts from leaves treated with microwave (EE_MW) and at 70 °C (EE_70) have better effect than BHT. The results of the present study suggest that microwave drying could be useful to enhance the extractability of phenolic compounds and the antioxidant capacity of M. communis L. leaf extract.

The White-Spotted Bamboo Shark Genome Reveals Chromosome Rearrangements and Fast-Evolving Immune Genes of Cartilaginous Fish.

Chondrichthyan (cartilaginous fish) occupies a key phylogenetic position and is important for investigating evolutionary processes of vertebrates. However, limited whole genomes impede our in-depth knowledge of important issues such as chromosome evolution and immunity. Here, we report the chromosome-level genome of white-spotted bamboo shark. Combing it with other shark genomes, we reconstructed 16 ancestral chromosomes of bamboo shark and illustrate a dynamic chromosome rearrangement process. We found that genes on 13 fast-evolving chromosomes can be enriched in immune-related pathways. And two chromosomes contain important genes that can be used to develop single-chain antibodies, which were shown to have high affinity to human disease markers by using enzyme-linked immunosorbent assay. We also found three bone formation-related genes were lost due to chromosome rearrangements. Our study highlights the importance of chromosome rearrangements, providing resources for understanding of cartilaginous fish diversification and potential application of single-chain antibodies.

Unraveling the role of salt-sensitivity genes in obesity with integrated network biology and co-expression analysis.

Obesity is a multifactorial disease caused by complex interactions between genes and dietary factors. Salt-rich diet is related to the development and progression of several chronic diseases including obesity. However, the molecular basis of how salt sensitivity genes (SSG) contribute to adiposity in obesity patients remains unexplored. In this study, we used the microarray expression data of visceral adipose tissue samples and constructed a complex protein-interaction network of salt sensitivity genes and their co-expressed genes to trace the molecular pathways connected to obesity. The Salt Sensitivity Protein Interaction Network (SSPIN) of 2691 differentially expressed genes and their 15474 interactions has shown that adipose tissues are enriched with the expression of 23 SSGs, 16 hubs and 84 bottlenecks (p = 2.52 x 10-16) involved in diverse molecular pathways connected to adiposity. Fifteen of these 23 SSGs along with 8 other SSGs showed a co-expression with enriched obesity-related genes (r ≥ 0.8). These SSGs and their co-expression partners are involved in diverse metabolic pathways including adipogenesis, adipocytokine signaling pathway, renin-angiotensin system, etc. This study concludes that SSGs could act as molecular signatures for tracing the basis of adipogenesis among obese patients. Integrated network centered methods may accelerate the identification of new molecular targets from the complex obesity genomics data.

Dissecting the Role of NF-κb Protein Family and Its Regulators in Rheumatoid Arthritis Using Weighted Gene Co-Expression Network.

Rheumatoid arthritis (RA) is a chronic synovial autoinflammatory disease that destructs the cartilage and bone, leading to disability. The functional regulation of major immunity-related pathways like nuclear factor kappa B (NF-κB), which is involved in the chronic inflammatory reactions underlying the development of RA, remains to be explored. Therefore, this study has adopted statistical and knowledge-based systemic investigations (like gene correlation, semantic similarity, and topological parameters based on graph theory) to study the gene expression status of NF-κB protein family (NKPF) and its regulators in synovial tissues to trace the molecular pathways through which these regulators contribute to RA. A complex protein-protein interaction map (PPIM) of 2,742 genes and 37,032 interactions was constructed from differentially expressed genes (p ≤ 0.05). PPIM was further decomposed into a Regulator Allied Protein Interaction Network (RAPIN) based on the interaction between genes (5 NKPF, 31 seeds, 131 hubs, and 652 bottlenecks). Pathway network analysis has shown the RA-specific disturbances in the functional connectivity between seed genes (RIPK1, ATG7, TLR4, TNFRSF1A, KPNA1, CFLAR, SNW1, FOSB, PARVA, CX3CL1, and TRPC6) and NKPF members (RELA, RELB, NFKB2, and REL). Interestingly, these genes are known for their involvement in inflammation and immune system (signaling by interleukins, cytokine signaling in immune system, NOD-like receptor signaling, MAPK signaling, Toll-like receptor signaling, and TNF signaling) pathways connected to RA. This study, for the first time, reports that SNW1, along with other NK regulatory genes, plays an important role in RA pathogenesis and might act as potential biomarker for RA. Additionally, these genes might play important roles in RA pathogenesis, as well as facilitate the development of effective targeted therapies. Our integrative data analysis and network-based methods could accelerate the identification of novel drug targets for RA from high-throughput genomic data.

The genetic association study of TP53 polymorphisms in Saudi obese patients.

Obesity is a multifactorial metabolic disorder characterized by low grade chronic inflammation. Rare and novel mutations in genes which are vital in several key pathways have been reported to alter the energy expenditure which regulates body weight. The TP53 or p53 gene plays a prominent role in regulating various metabolic activities such as glycolysis, lipolysis, and glycogen synthesis. Recent genome-wide association studies reported that tumor suppressor gene p53 variants play a critical role in the predisposition of type 2 diabetes and obesity. Till date, no reports are available from the Arabian population; hence the present study was intended to assess the association between p53 variants with risk of obesity development in the Saudi population. We have selected three p53 polymorphisms, rs1642785 (C > G), and rs9894946 (A > G), and rs1042522 (Pro72Arg; C > G) and assessed their association with obesity risk in the Saudi population. Phenotypic and biochemical parameters were also evaluated to check their association with p53 genotypes and obesity. Genotyping was carried out on 136 obese and 122 normal samples. We observed that there is significantly increased prevalence p52 Pro72Arg (rs1042522) polymorphism in obese persons when compared to controls at GG genotype in overall comparison (OR: 2.169, 95% CI: 1.086-4.334, p = 0.02716). Male obese subjects showed three-fold higher risk at GG genotype (OR: 3.275, 95% CI: 1.230-8.716, p = 0.01560) and two-fold risk at G allele (OR: 1.827, 95% CI: 1.128-2.958, p = 0.01388) of p53 variant Pro72Arg respectively. This variant has also shown significant influence on cholesterol, LDL level, and random insulin levels in obese subjects (p ≤ 0.05). In conclusion, p53 Pro72Arg variant is highly prevalent among obese individuals and may act as a genetic modifier for obesity development among Saudis.

Identification of key regulatory genes connected to NF-κB family of proteins in visceral adipose tissues using gene expression and weighted protein interaction network.

Obesity is connected to the activation of chronic inflammatory pathways in both adipocytes and macrophages located in adipose tissues. The nuclear factor (NF)-κB is a central molecule involved in inflammatory pathways linked to the pathology of different complex metabolic disorders. Investigating the gene expression data in the adipose tissue would potentially unravel disease relevant gene interactions. The present study is aimed at creating a signature molecular network and at prioritizing the potential biomarkers interacting with NF-κB family of proteins in obesity using system biology approaches. The dataset GSE88837 associated with obesity was downloaded from Gene Expression Omnibus (GEO) database. Statistical analysis represented the differential expression of a total of 2650 genes in adipose tissues (p = <0.05). Using concepts like correlation, semantic similarity, and theoretical graph parameters we narrowed down genes to a network of 23 genes strongly connected with NF-κB family with higher significance. Functional enrichment analysis revealed 21 of 23 target genes of NF-κB were found to have a critical role in the pathophysiology of obesity. Interestingly, GEM and PPP1R13L were predicted as novel genes which may act as potential target or biomarkers of obesity as they occur with other 21 target genes with known obesity relationship. Our study concludes that NF-κB and prioritized target genes regulate the inflammation in adipose tissues through several molecular signaling pathways like NF-κB, PI3K-Akt, glucocorticoid receptor regulatory network, angiogenesis and cytokine pathways. This integrated system biology approaches can be applied for elucidating functional protein interaction networks of NF-κB protein family in different complex diseases. Our integrative and network-based approach for finding therapeutic targets in genomic data could accelerate the identification of novel drug targets for obesity.

The first chromosome-level genome for a marine mammal as a resource to study ecology and evolution.

Marine mammals are important models for studying convergent evolution and aquatic adaption, and thus reference genomes of marine mammals can provide evolutionary insights. Here, we present the first chromosome-level marine mammal genome assembly based on the data generated by the BGISEQ-500 platform, for a stranded female sperm whale (Physeter macrocephalus). Using this reference genome, we performed chromosome evolution analysis of the sperm whale, including constructing ancestral chromosomes, identifying chromosome rearrangement events and comparing with cattle chromosomes, which provides a resource for exploring marine mammal adaptation and speciation. We detected a high proportion of long interspersed nuclear elements and expanded gene families, and contraction of major histocompatibility complex region genes which were specific to sperm whale. Using comparisons with sheep and cattle, we analysed positively selected genes to identify gene pathways that may be related to adaptation to the marine environment. Further, we identified possible convergent evolution in aquatic mammals by testing for positively selected genes across three orders of marine mammals. In addition, we used publicly available resequencing data to confirm a rapid decline in global population size in the Pliocene to Pleistocene transition. This study sheds light on the chromosome evolution and genetic mechanisms underpinning sperm whale adaptations, providing valuable resources for future comparative genomics.