CircSSBP2 acts as a MiR-2400 sponge to promote intramuscular preadipocyte proliferation by regulating NDRG1.

Intramuscular fat (IMF) is a critical factor in beef quality. IMF is mainly distributed between muscle fibres and its accumulation can affect the marbling and meat quality of beef. IMF formation and deposition is a complex process and in recent years a group of non-coding RNAs (ncRNAs), known as circRNAs, have been discovered to play an important role in regulating intramuscular fat deposition. CircRNAs form a covalent loop structure after reverse splicing of precursor mRNAs. They can act by adsorbing miRNAs, thereby reducing their repressive effects on downstream target genes. Based on high-throughput sequencing of circRNAs in intramuscular fat of Qinchuan and Japanese black cattle, we identified a novel circSSBP2 that is differentially expressed between the two species and associated with adipogenesis. We show that circSSBP2 knockdown promotes bovine intramuscular preadipocyte proliferation, whereas overexpression inhibits bovine intramuscular preadipocyte proliferation. We also show that circSSBP2 can act as a molecular sponge for miR-2400 and that miR-2400 overexpression promotes bovine intramuscular preadipocyte proliferation. Furthermore, N-myc downstream-regulated gene 1 (NDRG1) was identified as a direct target gene of miR-2400, and NDRG1 interference promoted the proliferation of bovine intramuscular preadipocytes. In conclusion, our results suggest that circSSBP2 inhibits the proliferation of bovine intramuscular preadipocytes by regulating the miR-2400/NDRG1 axis.

Exploring Epigenetic and Genetic Modulation in Animal Responses to Thermal Stress.

There is increasing evidence indicating that global temperatures are rising significantly, a phenomenon commonly referred to as 'global warming', which in turn is believed to be causing drastic changes to the global climate. Global warming (GW) directly impacts animal health, reproduction, production, and welfare, presenting several challenges to livestock enterprises. Thermal stress (TS) is one of the key consequences of GW, and all animal species, including livestock, have diverse physiological, epigenetic and genetic mechanisms to respond to TS. As a result, TS can significantly affect an animals' health, immune responsiveness, metabolic pathways etc. which can also influence the productivity, performance, and welfare of animals. Moreover, prolonged exposure to TS can lead to transgenerational and intergenerational changes that are mediated by epigenetic changes. For example, in several animal species, the effects of TS are encoded epigenetically during the animals' growth or productive stage, and these epigenetic changes can be transmitted intergenerationally. Such epigenetic changes can affect animal productivity by changing the phenotype so that it aligns with its ancestors' environment, irrespective of its immediate environment. Furthermore, epigenetic and genetic changes can also help protect cells from the adverse effects of TS by modulating the transcriptional status of heat-responsive genes in animals. This review focuses on the genetic and epigenetic modulation and regulation that occurs in TS conditions via HSPs, histone alterations and DNA methylation.

Biogenic synthesis of levofloxacin-loaded copper oxide nanoparticles using Cymbopogon citratus: A green approach for effective antibacterial applications.

Despite the success of antibiotics in medicine, the treatment of bacterial infection is still challenging due to emerging resistance and suitable drug delivery system, therefore, innovative approaches focused on nanoparticles based antimicrobial drug delivery systems are highly desired. This research aimed to synthesize Cymbopogon citratus (C. citratus) aqueous extract-mediated copper oxide (CuO-Nps) conjugated with levofloxacin (LFX). The synthesized CuO NPs-LFX nano conjugate was confirmed by analysis using scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and infrared and ultraviolet/visible spectroscopy. Antibacterial activities were assessed in vitro through the agar well diffusion method against six bacterial strains of clinical relevance. CuO NPs confirmed by UV-Vis analysis absorption peak observed at 380 nm. TGA analysis showed 8.98% weight loss between the 400-800 °C temperature range. The functional group's presence was confirmed by FTIR analysis. Spherical shape nanoparticles with an average particle size of 55 nm were recorded by FESEM. Results from agar well diffusion assay showed that CuO NPs-LFX prohibited the development of both gram-positive and gram-negative bacteria at all established concentrations, and the antibacterial propensity was more pronounced as compared to bare CuO NPs, Levofloxacin and C. citratus aqueous extract alone. The results showed that gram-negative bacteria are more susceptible to CuO NPs-LFX nano conjugate and at 10 µgmL-1 concentration, form a 10.1 mm zone of inhibition (ZOI), whereas gram-positive bacteria on the same concentration form 9.5 mm ZOI. LFX-loaded CuO NPs antibacterial activity was observed higher than plant extract, bare CuO NPs, and standard drug (Levofloxacin). This study provides a novel approach for the fabrication of biogenic CuO NPs with antibacterial drug levofloxacin and their usage as nano antibiotic carriers against pathogenic bacteria, especially antibiotic-resistant microbes.

Profiling and functional analysis of circular RNAs in yaks intramuscular fat.

Circular RNAs (circRNAs) are a new class of endogenous RNA regulating gene expression. However, the regulatory mechanisms of lipid metabolism in yaks involved in circRNAs remain poorly understood. The IMF plays a crucial role in the quality of yak meat, to greatly improve the meat quality. In this study, the fatty acid profiles of yak IMF were determined and circRNAs were sequenced. The results showed that the total of polyunsaturated fatty acid (PUFA) content of adult yak muscle was significantly higher than that in yak calves (p < 0.05). A total of 29,021 circRNAs were identified in IMF tissue, notably, 99 differentially expressed (DE) circRNAs were identified, to be associated with fat deposition, the most significant of which were circ_12686, circ_6918, circ_3582, ci_106 and ci_123 (A circRNA composed of exons is labelled 'circRNA' and a circRNA composed of introns is labelled 'ciRNA'). KEGG pathway enrichment analysis showed that the differential circRNAs were enriched in four pathways associated with fat deposition (e.g., the peroxisome proliferator-activated receptor signalling, fatty acid degradation, sphingolipid metabolism and sphingolipid signalling pathways). We also constructed co-expression networks of DE circRNA-miRNA using high-throughput sequencing in IMF deposition, from which revealed that ci_106 target binding of bta-miR-130b, bta-miR-148a, bta-miR-15a, bta-miR-34a, bta-miR-130a, bta-miR-17-5p and ci_123 target binding of bta-miR-150 were involved in adipogenesis. The study revealed the role of the circRNAs in the IMF deposition in yak and its influence on meat quality the findings demonstrated the circRNA differences in the development of IMF with the increase of age, thus providing a theoretical basis for further research on the molecular mechanism of IMF deposition in yaks.

Fat deposition, fatty acid profiles, antioxidant capacity and differentially expressed genes in subcutaneous fat of Tibetan sheep fed wheat-based diets with and without xylanase supplementation.

Xylanase, an exogenous enzyme that plays an essential role in energy metabolism by hydrolysing xylan into xylose, has been shown to positively influence nutrient digestion and utilisation in ruminants. The objective of this study was to evaluate the effects of xylanase supplementation on the back-fat thickness, fatty acid profiles, antioxidant capacity, and differentially expressed genes (DEGs) in the subcutaneous fat of Tibetan sheep. Sixty three-month-old rams with an average weight of 19.35 ± 2.18 kg were randomly assigned to control (no enzyme added, WH group) and xylanase (0.2% of diet on a dry matter basis, WE group) treatments. The experiment was conducted over 97 d, including 7 d of adaption to the diets. The results showed that xylanase supplementation in the diet increased adipocyte volume of subcutaneous fat (p < 0.05), shown by hematoxylin and eosin (H&E) staining. Gas chromatography showed greater concentrations of C14:0 and C16:0 in the subcutaneous fat of controls compared with the enzyme-treated group (p < 0.05), while opposite trend was seen for the absolute contents of C18:1n9t, C20:1, C18:2n6c, C18:3, and C18:3n3 (p < 0.05). Compared with controls, supplementation with xylanase increased the activity of T-AOC significantly (p < 0.05). Transcriptomic analysis showed the presence of 1630 DEGs between the two groups, of which 1023 were up-regulated and 607 were down-regulated, with enrichment in 4833 Gene Ontology terms, and significant enrichment in 31 terms (p < 0.05). The common DEGs were enriched in 295 pathways and significantly enriched in 26 pathways. Additionally, the expression of lipid-related genes, including fatty acid synthase, superoxide dismutase, fatty acid binding protein 5, carnitine palmytoyltransferase 1 A, and peroxisome proliferator-activated receptor A were verified via quantitative reverse-transcription polymerase chain reaction. In conclusion, dietary xylanase supplementation was found to reduce subcutaneous fat deposition in Tibetan sheep, likely through modulating the expression of lipid-related genes.

Exploring therapeutic targets and drug candidates for obesity: a combined network pharmacology, bioinformatics approach.

The remarkably high prevalence of obesity in Saudi Arabia reflects a global epidemic demanding urgent attention due to its associated health risks. The integration of traditional medicine, a vital cultural aspect, involves the use of medicinal plants to address various diseases, including obesity. This research merges network pharmacology (NP) and bioinformatics to innovate obesity treatment by identifying effective phytochemicals from native plants in the Taif valley. Focusing on six indigenous plants-Senna alexandrina, Capsicum annuum, Zingiber officinale, Curcuma longa, Trigonella foenum-graecum, and Foeniculum vulgare-we conducted preliminary screenings for potential bioactive compounds. We systematically compiled compound data from public databases and reviewed literature, revealing active compounds like apigenin, kaempferol, moupinamide, cyclocurcumin, chrysoeriol, isorhamnetin, rheinanthrone, cyclocurcumin, and riboflavin.Constructing a compound-target genes-obesity network unveiled their significant impact on metabolic regulation and fat accumulation, interacting notably with key proteins AKT1 and PTGS2. Molecular docking and 100 ns Molecular Dynamic (MD) simulations demonstrated robust binding affinity and stability at the docking site. Employing adipocytes as a cellular model, we gauged their viability and response to obesity-related stressors post-treatment with these native plant compounds.In conclusion, Saudi Arabia's indigenous plants hold promise as natural solutions for obesity treatment. This research opens new avenues in the battle against this pervasive health crisis by incorporating the potential of native botanicals.Communicated by Ramaswamy H. Sarma.

Therapeutic effects of Crataegus monogyna inhibitors against breast cancer.

Breast cancer is a silent killer disorder among women and a serious economic burden in healthcare management. Every 19 s, a woman is diagnosed with breast cancer, and every 74 s, a woman worldwide passes away from the disease. Despite the increase in progressive research, advanced treatment approaches, and preventive measures, breast cancer rates continue to increase. This study provides a combination of data mining, network pharmacology, and docking analysis that surely could revolutionize cancer treatment by exploiting prestigious phytochemicals. Crataegus monogyna is a small, rounded deciduous tree with glossy, deeply lobed leaves and flat sprays of cream flowers, followed by dark red berries in autumn. Various studies demonstrated that C. monogyna is therapeutically effective against breast cancer. However, the particular molecular mechanism is still unknown. This study is credited for locating bioactive substances, metabolic pathways, and target genes for breast cancer treatment. According to the current investigation, which examined compound-target genes-pathway networks, it was found that the bioactive compounds of C. monogyna may operate as a viable solution against breast cancer by altering the target genes implicated in the disease pathogenesis. The expression level of target genes was analyzed using GSE36295 microarray data. Docking analysis and molecular dynamic simulation studies further strengthened the current findings by validating the effective activity of the bioactive compounds against putative target genes. In summary, we propose that six key compounds, luteolin, apigenin, quercetin, kaempferol, ursolic acid, and oleanolic acid, contributed to the development of breast cancer by affecting the MMP9 and PPARG proteins. Integration of network pharmacology and bioinformatics revealed C. monogyna's multitarget pharmacological mechanisms against breast cancer. This study provides convincing evidence that C. monogyna might partially alleviate breast cancer and ultimately lays a foundation for further experimental research on the anti-breast cancer activity of C. monogyna.

Genetic variants of TORC1 gene promoter and their association with carcass quality and body measurement traits in Qinchuan beef cattle.

In the present study, sequencing of TORC1 prompter region explored three SNPs at loci g.80G>T, g.93A>T, and g.1253G>A. The SNP1 produced GG, GT and TT, SNP2 AA, AT and TT, and SNP3 produced GG, GA and AA genotypes. Allelic and genotypic frequencies analysis exhibited that SNP1 is within Hardy-Weinberg equilibrium (HWE). All three SNPs were found highly polymorphic as PIC value (0.25 < PIC < 0.50). At loci g.80G>T the cattle with genotype GG showed significantly (P <0.01) larger body length (BL), Wither height (WH), Hip height (HH), Rump length (RL), Hip width (HW), Chest depth (CD), and Chest circumference (CC). The genotype AA at g.93A>T showed significantly (P< 0.01 and 0.05) Larger body length (BL), Wither height (WH), Hip height, Rump length (RL), Hip width (HW), Chest depth (CD), and Chest circumference (CC). Interestingly, the carcass quality parameters such as Ultrasound loin area (ULA) and Intramuscular fat percentage (IF%) was highest in genotype GG at loci g.1253G>A. These findings conclude that genotype GG at loci g.80 G>T and AA at loci g.93A>T could be used as genetic markers for body measurement and genotype GG at loci g.1253G>A for carcass quality traits of TORC1 gene in Qinchuan beef cattle.

Selection signatures of Qinchuan cattle based on whole-genome sequences.

Qinchuan cattle has gradually improved in body shape and growth rate in the long-term breeding process from the draft cattle to beef cattle. As the head of the five local yellow cattle in China, the Qinchuan cattle has been designated as a specialized beef cattle breed. We investigated the selection signatures using whole genome sequencing data in Qinchuan cattle. Based on Fst, we detected hundreds of candidate genes under selection across Qinchuan, Red Angus, and Japanese Black cattle. Through protein-protein interaction analysis and functional annotation of candidate genes, the results revealed that KMT2E, LTBP1 and NIPBL were related to brain size, body characteristics, and limb development, respectively, suggesting that these potential genes may affect the growth and development traits in Qinchuan cattle. ARIH2, DACT1 and DNM2, et al. are related to meat quality. Meanwhile, TBXA2R can be used as a gene associated with reproductive function, and USH2A affect coat color. This provided a glimpse into the formation of breeds and molecular genetic breeding. Our findings will promote genome-assisted breeding to improve animal production and health.

Metabolomics approach reveals high energy diet improves the quality and enhances the flavor of black Tibetan sheep meat by altering the composition of rumen microbiota.

This study aims to determine the impact of dietary energy levels on rumen microbial composition and its relationship to the quality of Black Tibetan sheep meat by applying metabolomics and Pearson's correlation analyses. For this purpose, UHPLC-QTOF-MS was used to identify the metabolome, whereas 16S rDNA sequencing was used to detect the rumen microbiota. Eventually, we observed that the high energy diet group (HS) improved the carcass quality of Black Tibetan sheep and fat deposition in the longissimus lumborum (LL) compared to the medium energy diet group (MS). However, HS considerably increased the texture, water holding capacity (WHC), and volatile flavor of the LL when compared to that of MS and the low energy diet group (LS). Metabolomics and correlation analyses revealed that dietary energy levels mainly affected the metabolism of carbohydrates and lipids of the LL, which consequently influenced the content of volatile flavor compounds (VOCs) and fats. Furthermore, HS increased the abundance of Quinella, Ruminococcus 2, (Eubacterium) coprostanoligenes, and Succinivibrionaceae UCG-001, all of which participate in the carbohydrate metabolism in rumen and thus influence the metabolite levels (stachyose, isomaltose, etc.) in the LL. Overall, a high-energy diet is desirable for the production of Black Tibetan sheep mutton because it improves the mouthfeel and flavor of meat by altering the composition of rumen microbiota, which influences the metabolism in the LL.

Weighted Gene Co-expression Network Analysis Revealed That CircMARK3 Is a Potential CircRNA Affects Fat Deposition in Buffalo.

Background: Buffalo meat is increasingly widely accepted for consumption as it shares several quality attributes with cattle meat (beef). Hence, there is a huge opportunity for growth in the buffalo meat industry. However, buffalo meat has relatively low intramuscular fat (IMF) content, affecting its flavor, tenderness and juiciness. As there is a dearth of information on factors that control fat deposition, this study was undertaken to provide new candidate factor associated with buffalo fat deposition. Circular RNA (circRNA) is a novel class of non-coding RNA with a closed-loop structure, and play an important role in fat deposition. Methods: In this study, weighted gene co-expression network analysis (WGCNA) was used to construct a circRNA co-expression network and revealed a candidate circRNA that may affect the IMF deposition of buffalo as determined by RT-qPCR, semiquantitative PCR and gain-of-function experiments. Results: Herein, WGCNA determined that one module (turquoise module) is significantly associated with the growth and development stages of buffalo. Further analysis revealed a total of 191 overlapping circRNAs among differentially expressed (DE) circRNAs and the co-expression module. A candidate circRNA was found, 21:6969877|69753491 (circRNA_ID), with a reported involvement in lipid metabolism. This circRNA is stably expressed and originates from the MARK3 gene, hence the name circMARK3. circMARK3 is highly expressed in adipose tissue and mature adipocytes and is located in the cytoplasm. Gain-of-function experiments demonstrated that circMARK3 promoted adipogenic differentiation of buffalo adipocytes and 3T3-L1 cells by up-regulating the expression levels of adipogenic marker genes PPARG, C/EBPα and FABP4. Conclusion: These results indicate that circMARK3 is a potential factor that promotes fat deposition by regulating adipocyte differentiation and adipogenesis in buffalo.

Bioinformatics role of the WGCNA analysis and co-expression network identifies of prognostic marker in lung cancer.

Lung cancer is the most talked about cancer in the world. It is also one of the cancers that currently has a high mortality rate. The aim of our research is to find more effective therapeutic targets and prognostic markers for human lung cancer. First, we download gene expression data from the GEO database. We performed weighted co-expression network analysis on the selected genes, we then constructed scale-free networks and topological overlap matrices, and performed correlation modular analysis with the cancer group. We screened the 200 genes with the highest correlation in the cyan module for functional enrichment analysis and protein interaction network construction, found that most of them focused on cell division, tumor necrosis factor-mediated signaling pathways, cellular redox homeostasis, reactive oxygen species biosynthesis, and other processes, and were related to the cell cycle, apoptosis, HIF-1 signaling pathway, p53 signaling pathway, NF-κB signaling pathway, and several cancer disease pathways are involved. Finally, we used the GEPIA website data to perform survival analysis on some of the genes with GS > 0.6 in the cyan module. CBX3, AHCY, MRPL12, TPGB, TUBG1, KIF11, LRRC59, MRPL17, TMEM106B, ZWINT, TRIP13, and HMMR was identified as an important prognostic factor for lung cancer patients. In summary, we identified 12 mRNAs associated with lung cancer prognosis. Our study contributes to a deeper understanding of the molecular mechanisms of lung cancer and provides new insights into drug use and prognosis.

Tissue Expression Analysis, Cloning, and Characterization of the 5'-Regulatory Region of the Bovine LATS1 Gene.

As a member of the large tumor suppressor (LATS) gene family, LATS1 plays an important role in regulating muscle growth and development. In this study, we determined the distinct exhibit patterns of tissue expression of bovine LATS1. Further, we determined the functional proximal minimal promoter of bovine LATS1 and identified the key transcription factors in the core promoter region to elucidate its molecular regulation mechanism. The results showed that bovine LATS1 was highly expressed in the longissimus thoracis and upregulation in infancy muscle. An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay in combination with site-directed mutation and small interfering RNA (siRNA) interference demonstrated that myogenic differentiation 1 (Myod1) and myocyte enhancer factor 2A (MEF2A) binding in the core promoter region (-298/-123 bp) play important roles in the transcriptional regulation of the bovine LATS1 promoter. Taken together, these interactions provide insight into the regulatory mechanisms of LATS1 transcription in mediating skeletal muscle growth in cattle.

Antiviral Efficacy of Selected Natural Phytochemicals against SARS-CoV-2 Spike Glycoprotein Using Structure-Based Drug Designing.

SARS-CoV-2 is a highly virulent coronavirus that first surfaced in late 2019 and has since created a pandemic of the acute respiratory sickness known as "coronavirus disease 2019" (COVID-19), posing a threat to human health and public safety. S-RBD is a coronaviral protein that is essential for a coronavirus (CoV) to bind and penetrate into host cells. As a result, it has become a popular pharmacological target. The goal of this study was to find potential candidates for anti-coronavirus disease 2019 (COVID-19) drugs by targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-RBD with novel bioactive compounds and molecular interaction studies of 15,000 phytochemicals belonging to different flavonoid subgroups. A spike protein crystal structure attached to the ACE2 structure was obtained from the PDB database. A library of 15,000 phytochemicals was made by collecting compounds from different databases, such as the Zinc-database, PubChem-database, and MPD3-database. This library was docked against a receptor binding domain of a spike glycoprotein through the Molecular Operating Environment (MOE). The top drug candidates Phylloflavan, Milk thistle, Ilexin B and Isosilybin B, after virtual screening, were selected on the basis of the least binding score. Phylloflavan ranked as the top compound because of its least binding affinity score of -14.09 kcal/mol. In silico studies showed that all those compounds showed good activity and could be used as an immunological response with no bioavailability issues. Absorption, distribution, metabolism, excretion and a toxicological analysis were conducted through SwissADME. Stability and effectiveness of the docked complexes were elucidated by performing the 100 ns molecular dynamic simulation through the Desmond package.

Genetic variants in the serum amyloid A2 (SAA2) gene as a potential marker for milk production traits in Chinese Holstein cows.

BACKGROUND: This study was conducted to detect potential polymorphisms of the serum amyloid A2 (SAA2) gene and explore their relationships with milk production traits in Chinese Holstein cows. OBJECTIVES: THIS STUDY USED: sequencing technology conducted in 532 Chinese Holstein cows. METHODS: Three single nucleotide polymorphisms (SNPs) were identified within intron 1, named g.14061A>G, g.14072G>C and g.14819C>T. Eight estimated haplotypes were identified, of which three major haplotypes had a frequency of Hap3 (-ACC-), Hap5 (-GCC-) and Hap2 (-AGT-), with 17.9%, 12.30% and 8.10%, respectively. RESULTS: The association analysis of single markers (g.14061A>G and g.14819C>T) and combined genotypes (Hap1/5) revealed prominent effects on milk production traits in Chinese Holstein cows (p < 0.05). CONCLUSIONS: Our results suggest that the SAA2 gene is associated with economic traits in Chinese Holstein cows and may be used as candidate gene for marker-assisted selection and management in breeding programs.

Molecular dynamics simulation analysis of the beta amyloid peptide with docked inhibitors.

Beta amyloid peptide is widely studied due to its association with Alzheimer disease (AD). Various study reported that the accumulation of beta amyloid in brain cells leads to Alzheimer disease. Hence, Beta amyloid peptide could be a potential target of anti-AD therapy. Hence, it is of interest to develop potent inhibitors for Beta amyloid peptide in the context of Alzheimer disease (AD). We report the binding features of Ascorbic acid, Cysteine, Dithioerythriol, Dithiothreitol, Malic acid and α-Tocopherol with beta amyloid having binding energy values of -6.7, -6.5, -6.0, -6.5, -6.7 and - 7.0 kcal/mol respectively. The molecular docking of top-scoring compounds with beta amyloid suggests that amino acids such as ASP23, GLU22, Phe19, are crucial in binding. Molecular dynamics simulation study showed steady-state interaction of compounds with beta amyloid for further consideration.