3 Biotech最新文献

The study aims to investigate the clinicopathological significance of MRPL24 in human cancers, with a particular focus on breast cancer (BC). Comprehensive bioinformatics analyses were conducted using data from The Cancer Genome Atlas (TCGA) and various advanced database, including cBioPortal, UALCAN, TIMER, Prognoscan, TISIDB, KM Plotter, and The Human Protein Atlas, to provide a detailed evaluation of MRPL55's role in cancer. The findings were further validated through experimental studies. Pan-cancer analysis of TCGA/ICGC data revealed significant amplification of MRPL24 across multiple cancer types, with the highest amplification rate of 60% observed in metastatic breast cancer. MRPL24 was found to be overexpressed in primary breast tumors, metastatic, and various molecular subtypes of breast cancer. High MRPL24 expression was associated with poor prognosis and lower survival rates in breast cancer patients. RT-PCR and western blot confirmed MRPL24 depletion in breast cancer cells. Knockdown of MRPL24 was shown to suppress proliferation, and clonogenic potential in breast cancer cells and inhibit cell migration. Additionally, MRPL24 depletion sensitized breast cancer cells to PD0325901 and 5-FU treatment. Mechanistic studies revealed that MRPL24 knock-down downregulates mRNA levels of oncogenic genes, including c-MYC, BRD4, WNT3, and STAT3. Positive correlations were observed between MRPL24 and key genes involved in ferroptosis regulation, such as ERBB2, ERBB3, GRB2, PIK3CA, AKT1, MAPK3, and MAPK1. Finally, through virtual screening and molecular dynamics simulations, we have identified three FDA-approved drugs with strong binding affinities and interactions with MRPL24. These findings underscore MRPL24's oncogenic role in breast cancer and suggest potential therapeutic strategies targeting this protein.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04196-z.

Insulin resistance is major factor in the development of metabolic syndrome and type 2 diabetes (T2D). We extracted 430 genes from literature associated with both insulin resistance and inflammation. The highly significant pathways were Toll-like receptor signaling, PI3K-Akt signaling, cytokine-cytokine receptor interaction, pathways in cancer, TNF signaling, and NF-kappa B signaling. Among the 297 common genes in all datasets of various T2D patients' tissues including blood, muscle, liver, pancreas, and adipose tissues, 71% and 60% of these genes were differentially expressed in pancreas (GSE25724) and liver (GSE15653), respectively. A total of 169 genes contain highly conserved motifs for various transcription factors involved in immune response, thereby suggesting coordinated expression. Through co-expression analysis, we obtained three modules. The respective modules had 78, 158, and 55 genes, and TRAF2, HMGA1, and RGS5 as hub genes. Further, we used the BioNSi pathways simulation tool and identified the following five KEGG pathways perturbed in four or more tissues, namely Toll-like receptor signaling pathway, RIG-1-like receptor signaling pathway, pathways in cancer, NF-kappa B signaling pathway, and insulin resistance pathway. The genes NFKBIA and IKBKB are common to all these five pathways. In addition, using the NF-κB computational activation model, we identified that the reversal of NF-κB constitutive activation through overexpression of NFKB1 (P50 homodimer), PPARG, PIAS3 could reduce insulin resistance by almost half of its original value. To conclude, co-expression studies, gene expression network simulation, and NF-κB computational modeling substantiate the causal role of NF-κB pathway in insulin resistance. These results taken together with other published evidence suggests that the TNF-TRAF2-IKBKB-NF-κB axis could be explored as a potential target in combination with available metabolic targets in the management of insulin resistance.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04202-4.

The natural population of Bambusa polymorpha have not been genetically enumerated due to a lack of genome sequence information or robust species-specific molecular marker. The present study was conducted to develop and validate genome-wide de novo simple sequence repeat (SSRs) markers in B. polymorpha through shallow-pass genome sequencing. The genome sequence data of about 13 Gb was generated using Illumina technology, and high-quality sequence reads were de novo assembled into 1,390,995 contigs with GC content 42.34%, contig N 50 value 1047 bp. The Benchmark Universal Single-Copy Ortholog (BUSCO) analysis indicated 75.29% of complete and single-copy genome assembly. By scanning of genome assembly, a total of 73,468 simple sequence repeats (SSRs) were identified, and 44,383 primer pairs were designed. Repeat analysis revealed that the dinucleotide and trinucleotide repeats were most abundantly distributed in the genome with 52.95 and 41.17%, respectively. A subset of 33 SSRs was randomly selected for their PCR amplification and polymorphism in 16 random individuals. Of these, 29 SSRs were successfully amplified with the expected product size and 20 showed polymorphic banding patterns. Polymorphic SSRs were characterized by high expected heterozygosity (H _e = 0.72) and polymorphism information content (PIC = 0.68). The clustering pattern obtained using the neighbor joining (NJ) dendrogram revealed the genotypes were clustered in accordance with their geographical locations. The genomic and marker information generated in this study are novel and useful for future studies for genetic improvement and conservation of B. polymorpha.

This study investigates drug-loaded liposomes targeting macrophages as a promising strategy to enhance Tuberculosis (TB) treatment. The focus is on optimizing liposomal formulations for encapsulating OX-23, a previously identified anti-mycobacterial agent with a minimum inhibitory concentration (MIC) of 1.56 µg/ml, and assessing their efficacy in macrophage infection models. Liposomal formulations were characterized for particle size, polydispersity index (PDI), and zeta potential using dynamic light scattering (DLS), with morphology analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Macrophage infection assays, including those with the THP-1 macrophage cell line, were performed to evaluate the targeting efficiency and therapeutic potential of the formulations. Results showed that OX-23 could be successfully encapsulated in liposomes with various charges, achieving high encapsulation efficiency, optimal particle size, and acceptable PDI values. In-vitro studies with the THP-1 cell line demonstrated sustained release of the drug from the liposomes, with morphological analysis confirming that the liposomes were spherical and non-aggregated. The formulations exhibited significant penetration into infected macrophages and effectively inhibited the growth of intracellular Mycobacterium tuberculosis at the tested concentrations. These findings support the potential of liposomal OX-23 in targeting both extracellular and intracellular M. tuberculosis, offering a promising approach to TB treatment.

Developing an efficient and reproducible regeneration protocol holds paramount significance for advancing genetic transformation technologies in rice, facilitating their utilisation in crop improvement. Nagina 22 (N22), a climate-resilient Aus-type rice genotype known for its tolerance against multiple stresses, lacks a standardised transformation protocol, limiting its utilisation as a background for genetic transformation. This study reports, for the first time, a highly efficient transformation and regeneration protocol for N22 using a CRISPR/Cas9 vector. Mature seeds were used to induce embryogenic calli on CHU(N6)-based callus induction media (CIM) with varying concentrations of 2,4-dichlorophenoxyacetic acid (2,4-D). The highest callus induction efficiency (~ 94%) was achieved using 3 mgL^-1 2,4-D. For regeneration, calli were transferred to different regeneration media-I (RM-Ia to RM-Ie), where a combination of 5 mgL^-1 6-benzylaminopurine (BAP) and 0.02 mgL^-1 naphthalene acetic acid (NAA) resulted in ~ 44% regeneration frequency. Subsequent optimisation of regeneration media-II (RM-II) with low NAA concentration enhanced shoot elongation and root development. Furthermore, reducing basal salt concentration in the resuspension media significantly enhanced transformation efficiency to 44%, achieved, by only using sterile distilled water (SDW) with 150 mM acetosyringone for calli infection. The optimised protocol was successfully validated using CRISPR/Cas9 vector, facilitating targeted gene knockouts for functional genomic studies. This approach addresses a critical gap in N22 genetic transformation, providing a reliable protocol for advancing rice improvement through gene editing. It offers valuable insights for future research and practical applications in genetic transformation of this elite rice genotype for various agronomic and scientific purposes.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04210-y.

Recently, there has been a growing interest in the application of beneficial microorganisms to enhance crop performance. Magnetospirillum gryphiswaldense (MSR-1) are spiral-shaped, gram-negative bacteria that exhibit magnetotaxis with the help of magnetosomes (iron oxide or iron sulphide). They have exhibited biomedical and environmental applications; however, the agricultural utilization of these strains is yet to be explored. This study investigates the nitrogen fixation, iron supplementation, and plant growth promotion (PGP) activity of MSR-1 on Vigna radiata (Green gram). Firstly, agriculturally important genes including nif (360 bp), fur (480 bp), and feoB (675 bp) were identified in MSR-1. Further, the strain was used to produce the Magnetospirillum Liquid Biofertilizer (MLB) and analyzed using GC-MS and LC-HRMS to identify beneficial compounds for agriculture. The findings indicated the presence of biostimulant compounds including proline, indole-3-acetic acid, koninginin, and glutamate. Furthermore, different dilutions (20%, 40%, 60%, 80%, and 100%) of MLB were supplemented to V.radiata to explore its nitrogen-fixing capacity, iron enhancement effects, plant growth and yield. Plants treated with 20% MLB exhibited a significant increase in plant length (85.6%), seed weight (74.5%), total chlorophyll content (58.3%), protein (95.91%), leaf nitrogen content (71.72%) compared to the control group treated with distilled water. Under iron deficiency conditions, 60% MLB improved the plant length (70.38%), seed weight (66.6%), total chlorophyll (84.16%), protein (66.19%), iron content of leaves (80.79%) compared to the control group. The findings indicate that MSR-1 enhances plant productivity and it can be used as a source of iron fertilizer for addressing iron deficiency in plants.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04206-8.

Sclerotium rolfsii is the causal agent of stem rot of many crops, a highly destructive disease of groundnut (Arachis hypogaea L.). Based on evidence that many groundnut genotypes have an inherent ability to tolerate the pathogenicity of Sclerotium species, twenty-two genotypes of groundnut were screened against Sclerotium rolfsii infection in sick plot field experiment; four genotypes, namely CS19, GG16, GG20 and TG37A, were selected as being the most tolerant, moderately tolerant, susceptible and highly susceptible to stem rot, respectively. Stem tissues (1cm from the collar region) from infected and healthy plants of four selected genotypes differing in Sclerotium rolfsii susceptibility were examined using a scanning electron microscope (SEM). Differential formation and deposition of tyloses, calcium-oxalate, and fibrillar networks were observed in xylem tissue elements in tolerant and susceptible genotypes in infected plants. To elucidate the mechanisms underlying the defense responses and tolerance to stem rot in groundnut plants, the patterns of pathogenesis-related proteins (PR) and polygalacturonase inhibiting protein (PGIP) gene expression in the selected genotypes were studied using qRT-PCR. Genes encoding PR-proteins are the most important inducible defense-related antifungal proteins and the genes encoding PGIP that inhibit the pectin-depolymerizing were highly expressed in the tolerant genotype as compared to the susceptible genotype, suggesting that PR and PGIP are important components for Sclerotium rolfsii tolerance in groundnut. Results of cis-regulatory elements analysis of PGIP promoter regions showed enrichment of ERF, MYB and bHLH transcription factors binding sites that are known to be preferentially and co-ordinately expressed during various stresses.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04211-x.

Orphan genes (OGs), also known as lineage-specific genes, are species-specific genes that play a crucial role in species-specific adaptations to various stresses. Although OGs have been identified in several plant species, there is no information on OGs in banana genomes. This study aimed to systematically identify OGs in twelve banana (sub)species using comparative genomics. The results showed that OG content varied widely among these (sub)species, from 0.4% in Musa itinerans to 7.3% in Ensete glaucum. Genetic structure analysis showed that banana OGs have significantly shorter protein lengths, smaller molecular weight, fewer exons, and shorter exon lengths than non-orphan genes (NOGs). Subcellular localization predictions showed that banana OGs are mainly found in the chloroplast, nucleus, and cytosol, and are evenly distributed across chromosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses suggested that OGs may be involved in cellular processes, metabolic processes, and molecular transport. The transcriptome analysis of 9 AAA cultivars against 4 M. acuminata subspecies genomes showed the OGs content. Analysis of gene expression in M. acuminata subsp. malaccensis showed 75 differentially expressed (DE) OGs in response to abiotic stresses and 46 DE OGs related to biotic stresses, indicating that these OGs might play important roles in response to abiotic and biotic stresses. This study provides a foundation for further in-depth research into the functions of OGs in bananas.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04213-9.

The persistent challenge posed by antibiotic-resistant bacteria and tuberculosis necessitates innovative approaches to antimicrobial treatment. This study explores the synthesis and characterization of NiZrO₃ nanoparticles integrated with graphene nanoplatelets (GNP) and multi-walled carbon nanotubes (MWCNT), using a microwave-assisted green synthesis route, employing fenugreek (Trigonella foenum-graecum) seed extract as a gelling agent. The synthesised nanocomposites were systematically analyzed using XRD, FT-IR, Raman spectroscopy, HR-SEM and HR TEM analysis to assess structural, optical, and morphological properties. The antimicrobial and antibiofilm efficacy was evaluated against drug-resistant strains, including Escherichia coli and Klebsiella pneumoniae, by well diffusion method and crystal violet-Microtitre plate (CV-MtP) method. Notably, the NiZrO₃@MWCNT composite exhibited a maximum antibacterial inhibition zone of 13 mm and showed superior biofilm inhibition of 92.8% against K. pneumoniae at 500 ppm. In contrast, NiZrO₃@GNP demonstrated a biofilm inhibition of 97% at 500 ppm. Furthermore, the microplate Alamar Blue assay (MABA) was employed to determine the minimum inhibitory concentration (MIC) against Mycobacterium smegmatis (MTS) with NiZrO₃@MWCNT achieving 96% inhibition and at 500 ppm. These results confirm the enhanced antimicrobial efficacy of the carbon-integrated nanocomposites over pure NiZrO₃, which showed limited activity. This research underscores the promise of NiZrO₃-based nanocomposites as advanced antimicrobial agents, offering a novel strategy to combat the global health threat of antibiotic resistance.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04201-5.

Coumarin derivatives are one of the naturally occurring bioactive molecule. Dihydropyrano coumarins are one of the medicinally important derivatives of coumarin which have been reported to exhibit various bioactivity. However, there are no reports on their antihyperglycemic activities. Herein, we report their antihyperglycemic potential through α-Amylase inhibition. In this study, a series of 24 derivatives of dihydropyrano coumarins was synthesized and studied for alpha-Amylase inhibitory activity. All the derivatives of dihydropyrano coumarins (4a-x) were screened via molecular docking studies against human pancreatic alpha-Amylase (PDB id: 2QV4) followed by DNS assay to check their α-Amylase inhibitory potential. Six derivatives with o-chloro(4b), o-nitro(4c), p-nitro(4o), p-cyano(4q), p-allyloxy(4t) and m, p-dimethoxy(4v) displayed best binding with the α-Amylase enzyme via H-bond and Pi-alkyl interactions. Also, their physicochemical parameters revealed their drug likeliness. Further through DNS assay, minimal inhibitory concentration, i.e., IC₅₀ values of these six derivatives were calculated. All the six derivatives possess IC₅₀ values in the range 5.67 ± 0.02 to 8.92 ± 0.64 µM comparable to standard acarbose (0.85 ± 0.01 µM). Further DFT analysis gave a comparative study of band gap energy of most potent compound 4o with that of standard acarbose.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04194-1.