3 Biotech最新文献

Diabetes mellitus (DM) poses a major global healthcare challenge, highlighting the need for new treatments beyond current options. Currently available drugs have side effects including weight gain, nausea, vomiting, diarrhea, insulin resistance etc. Therefore, given the benefits of indole derivatives in diabetes and the lack of computational studies on bis-indole-based triazine derivatives with aldose reductase (AR), this study employs in-silico analysis to explore their potential as type-2 diabetes treatments. Based on the Differential Expression analysis, the human aldose reductase (HAR) encoding gene AKR1B1 showed overexpression in GSE30122 diabetes patients (Log2FC = 0.62, P < 0.01). Moreover, the compounds 2-((5,6-di(1H-indol-3-yl)-1,2,4-triazin-3-yl)thio)-1-(3-hydroxy-5-methylphenyl)ethan-1-one (4) and 2-((5,6-di(1H-indol-3-yl)-1,2,4-triazin-3-yl)thio)-1-(4-nitrophenyl)ethan-1-one (8) were identified as leading candidates, showing binding energies of - 62.12, - 81.73 kcal/mol and - 57.19, - 85.97 kcal/mol, respectively. Docking, MM/GBSA screening, molecular dynamics (MD) simulations, PCA, and post-MM/GBSA analysis confirmed their stability and favorable binding compared to the apo protein and control. Further in-vitro, in-vivo, and clinical studies are required to validate their therapeutic potential.

During November-December of 2019, severe witches' broom along with little leaf and stunting symptoms was observed in Glebionis coronaria at Indian Institute of Sugarcane Research, Lucknow, Uttar Pradesh with an average disease incidence of 20%. An amplicon of ~ 1.3 kb of 16S rRNA gene was amplified in symptomatic C. coronarium plants using universal phytoplasma-specific nested primer pairs (P1/P7 followed by 3Fwd/3Rev). Additionally, in another host, Catharanthus roseus, growing in near beds and the leafhopper species Hishimonus phycitis, amplification of similar amplified products were obtained using the similar nested PCR primer pairs. Further, phytoplasma presence was confirmed by amplifying non-ribosomal genes including secA, rp and secY in the symptomatic G. coronaria, Catharanthus roseus and Hishimonus phycitis using gene-specific primers of secA, secY, and rp genes. The comparison of 16S rRNA, secA, rp, and secY gene sequences through BLASTn, phylogeny and in silico RFLP analysis of C. coronarium, C. roseus, and the leafhopper species Hishimonus phycitis identified the presence of 'Candidatus Phytoplasma trifolii'-related strain (16SrIV-D subgroup) in all the plants and leafhopper samples. These findings demonstrated the utility of multilocus genes for accurate identification of phytoplasma strains in the plant and insect samples. This is the first report of 16SrVI-D subgroup of phytoplasmas associated with witches' broom, little leaf and stunting disease in Glebionis coronaria.

Gastric cancer is one of the major cancers with high cancer mortality and shows significant heterogeneity. The development of precise prognostic models is crucial for advancing treatment strategies. Recognizing the pivotal role of DNA damage in tumor progression, we conducted a consensus clustering analysis of DNA damage-related genes to categorize gastric cancer patients from the TCGA clinical cohort into distinct subtypes. Prognostic models were then constructed utilizing machine learning algorithms following Cox regression with differentially expressed genes. Validation was performed using the GSE gastric cancer cohort. Additionally, we investigated other characteristic responses of patients through gene mapping and drug sensitivity analysis. This study 12 differentially prognostic signature genes between the 2 DNA damage subtypes identified were used to calculate risk scores for the patients. This score predicts the prognosis of patients with gastric cancer and their overall survival time. Higher risk scores mean less drug sensitivity, lower survival, and possibly a poorer response to immunotherapy. Our findings provide the basis for future studies targeting DNA damage and its immune microenvironment to improve prognosis and response to immunotherapy.

6-Phosphogluconate dehydrogenases (6PGDHs) are widely existing as reduced cofactor (NADH/NADPH) regeneration biocatalysts. Herein, a thermostable 6PGDH from Hydrogenobacter thermophilus (Ht6PGDH) was overexpressed in Escherichia coli and enzymologically characterized. Ht6PGDH exhibited exceptional stability and catalytic activity under high-temperature conditions, with an optimum temperature of 85 °C and the ability to maintain high activity for prolonged periods at 70 °C, which could be purified through a one-step heat treatment. Moreover, Ht6PGDH exhibited a preference for NAD⁺ with a K _m value of 0.4 mM and a k _cat value of 28.6 s⁻¹, demonstrating a significant preference over NADP⁺. These properties render Ht6PGDH a potentially valuable enzyme for high-temperature bioconversion and in vitro synthetic biosystems. Additional research showed that Ht6PGDH excelled in the regeneration of NADH, achieving efficient lactate production when integrated into an in vitro synthetic biosystem containing lactate dehydrogenase (LDH). Furthermore, the cascade reaction of Ht6PGDH with glucose-6-phosphate dehydrogenase (G6PDH) was explored for NADH regeneration using starch as the substrate, further validating its potential application in complex biosynthetic systems.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04165-6.

Adenine is frequently utilized as a model medication for chronic renal disease. Adenine can affect organs other than the kidneys, including the heart and the intestine. The liver is a vital organ involved in the in vivo metabolism of adenine. Adenine may negatively impact liver function. Research indicated that adenine caused dysbiosis of the gut microbiota in mice. Investigations into the gut-liver axis have demonstrated a substantial association between drug-induced hepatic dysfunction and gut microbiota. Consequently, we delivered distinct dosages of adenine via gavage to mice to examine the correlation between adenine-induced liver impairment and gut microbiota dysbiosis. Mice were treated with low-dose adenine suspension (NLA), medium-dose adenine suspension (NMA), high-dose adenine suspension (NHA), and sterile water (NC) as a control. The results indicated that mice in the NLA, NMA, and NHA groups had decreased body weight and a reduction in liver index. Subsequent to adenine administration, the concentrations of AST, ALT, and LDH increased, whereas SDH levels decreased. As doses increased, liver function impairment and hepatic energy metabolism abnormalities aggravated. Adenine also damaged the colonic architecture in mice. Moreover, adenine modified the makeup and structure of the gut mucosal microbiota, enhancing specific bacterial genera and influencing the microbiota's energy metabolism-related functions. The results of our research established a correlation among certain bacteria, liver function injury, and hepatic energy metabolism. The gut mucosal microbiota was involved in adenine-induced liver injury and hepatic energy metabolism. These results can offer novel insights into the role of gut microbiota in drug-induced liver injury and provide specific guidelines for the modeling and therapeutic application of adenine.

Hexokinases (HXK) not only facilitate carbohydrate metabolism but also play important roles in sugar sensing in higher plants. HXK gene families have been extensively discussed in many plant species; however, comprehensive information regarding HXKs in sorghum remains unclear. To address this gap, we identified 7 putative sorghum HXKs (SbHXK1 to SbHXK7), and the features of their conserved domains, gene structure, evolutionary tree, and cis-acting elements were systematically characterized to reveal the evolutionary conservation between different plant species. Based on expression profiling, we found that different expression patterns of SbHXKs were associated with different physiological processes, including abiotic stresses. Further qRT-PCR verification under salt and sucrose treatment confirmed that SbHXK2, SbHXK4, and SbHXK5 may play very important roles under high osmotic pressure. Notably, SbHXKs are predominantly localized in the cytoplasm, in contrast to some rice and Arabidopsis HXKs, which are localized in chloroplasts or mitochondria, suggesting divergent roles for SbHXKs. In summary, our study provides a theoretical foundation for understanding the HXK gene family and offers fundamental insights of SbHXKs in sorghum.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04190-5.

This study investigated the anticancer phytocompounds in leaf extracts of Oxalis latifolia Kunth. Quantitative analysis of the phytochemical composition showed high levels of primary metabolites: carbohydrates (45.11 ± 2.15 GLE mg/100 mg), proteins (28.13 ± 0.94 BSA mg/100 mg), and amino acids (13.25 ± 1.16 LE mg/100 mg). Ethyl acetate extracts had the highest concentrations of secondary metabolites, including phenolic content (122.52 ± 4.27 GAE mg/100 mg), total flavonoids (91.86 ± 2.65 QE mg/100 mg), and alkaloids (82.18 ± 0.72 COLE mg/100 mg). In addition, strong antioxidant activities were observed in the DPPH^• scavenging assay (IC₅₀ 11.51 ± 2.28 µg/mL), ABTS^·+ radical cation scavenging activity (97.42 ± 7.19 µM TE/g), and FRAP assay (14.34 ± 1.24 mM Fe(II)/mg). Based on preliminary analysis, the ethyl acetate extract was fractionated using thin-layer chromatography (TLC), yielding two distinct fractions with Rf values of 0.31 and 0.76. GC-MS analysis of these fractions identified 33 bioactive compounds. These fractions exhibited anticancer activity against the A549 lung cancer cell line, with IC₅₀ values of 47.25 µg/mL and 48.31 µg/mL, as determined by the MTT assay. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies on 25 selected compounds indicated favorable pharmacokinetic properties and drug-likeness. In silico molecular docking showed strong binding affinities of these bioactive compounds to the p21 protein, comparable to the synthetic drug Cisplatin-quercetin. The results highlight the potential of O. latifolia in anticancer therapy, particularly through modulation of the p21 pathway, supported by in vitro cytotoxicity assessments, molecular docking, and ADMET analysis.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04167-4.

The Escherichia coli phage UFJF_EcSW4 was isolated from polluted stream water and showed clear lysis plaques on the host, measuring 0.67 ± 0.43 mm, with a titer of 9.57 ± 0.23 log PFU/ml. It demonstrated a very narrow host range, infecting only its host. Additionally, it has a short latent period of 9 min, a burst size of 49 PFU/infected cell, and stability over a wide range of pH, temperature, and free residual chlorine. The phage has a double-stranded DNA genome spanning 40,299 bp, with a GC content of 49.87% and short-direct terminal repeats (DTR) sequences of 286 bp. The UFJF_EcSW4 genome contains 55 genes, organized into functional modules with a unidirectional arrangement, regulated by 22 promoters (three from the phage and 19 from the host) and three Rho-independent terminators. Comparative analysis revealed that the UFJF_EcSW4 genome shares an average genomic similarity of 77.82% with the genome sequences of phages from the Kayfunavirus genus but does not surpass the 95% threshold necessary for species classification. Therefore, the UFJF_EcSW4 is a novel Kayfunavirus UFJF_EcSW4 species belonging to the Studiervirinae subfamily.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04172-7.

This study aims to assess the neuroprotective effects of the methanolic extract of Sargassum wightii against oxidative stress and cell death induced by neurotoxins MPP ⁺ in SH-SY5Y cells. Briefly, the methanolic extract of S.wightii decreased the cytotoxicity of MPP ⁺ in SH-SY5Y cells. Treatment with S.wightii extract at a concentration of 400 µg/ml resulted in a notable decrease in cell death, particularly in MPP ⁺ -induced cells. Flow cytometry analysis with annexin V/PI staining reveals apoptosis and necrosis in SH-SY5Y cell lines upon exposure to 1 mM of MPP ⁺ . However, 100-400 µg/ml concentrations of S.wightii extract effectively decrease apoptosis in SH-SY5Y cells. Furthermore, S.wightii inhibits caspase-3 activity, effectively shielding neuronal cells against MPP ⁺ -induced cell death. Mitochondrial membrane potential (MMP) assay using a JC-1 fluorescent probe indicates that the methanolic extract of S.wightii exhibits protective effects against MPP ⁺ -induced cell death and maintains mitochondrial membrane potential. Our results conclude that exposing SH-SY5Y cells to a methanolic extract of S.wightii could potentially increase the likelihood of inhibiting the cascade mechanism, stopping MPP⁺-induced apoptosis, and preventing the rupture of the mitochondrial membrane. However, the lack of low solubility and poor bioavailability reduce the therapeutic efficacy of S.wightii. Liposome-based drug delivery systems can improve the bioavailability and stability of bioactive compounds, enhancing their therapeutic potential. Hence, S.wightii may hold promise as an innovative treatment for neurological ailments.

Skin aging is characterized by progressive loss of functionality and regenerative potential of the skin, resulting in the appearance of wrinkles, irregular pigmentation, a decrease of elasticity, dryness, and rough texture. Damage to the skin caused by oxidative stress could substantially be slowed down by the use of phytochemicals that function as natural antioxidants. Although phytochemicals have immense potential as anti-aging medicines, their effectiveness as therapeutic agents is restricted by their poor solubility, biodistribution, stability, and hydrophilicity. Given their improved stability, solubility, efficacy, and occlusive properties, nanoformulations have emerged as promising drug delivery platforms for phytochemicals to achieve anti-aging effects. The efficacy of these nanoformulated phytochemicals in suppressing enzymes that accelerate skin aging, such as collagenase, tyrosinase and hyaluronidase, as well as enhancing superoxide dismutase, catalase, and collagen levels to improve skin appearance during aging has been demonstrated.