3 Biotech最新文献

The present study examined the anti-inflammatory and functional improvement of the uterus and ovary, respectively, in bisphenol-A (BPA)-fed adult Wistar rats following the ingestion of methanolic extract of wheatgrass (WG-ME). Four groups of rats were conditioned as vehicle-treated control, BPA-treated (100 mg/kg b.w.), BPA + WG-ME (100 mg BPA/kg b.w. + 200 mg WG-ME/kg b.w.), and WG-ME (200 mg/kg b.w.) groups. The LC-MS study confirmed the presence of numerous bioactive components in WG-ME. ELISA, PAGE, real-time PCR, and immunohistostaining were executed to test the efficacy of WG-ME against BPA. WG-ME was shown to induce significant weight gain of the uterus and ovaries as well as improve the estrous cycle and antioxidant status. WG-ME effectively suppressed the mRNA expression of TNF-α (tumor necrosis factor-alpha) and NF-κB (nuclear factor kappa-B). This extract also increased the expression of the antiapoptotic factor BCL2 (B-cell lymphoma 2) in the uterine tissue of rats administered BPA while impeding the abnormal expression of the tumor proteins p53, cylcin-D1, and BAX (BCL2-associated protein X). An enhanced steroidogenic event was supported by improved gonadotropins and reproductive hormone levels, feeble signaling of androgen receptors, and improved ovarian follicular growth with a distinct appearance of granulosa layer as well as better uterine histomorphology. The abundance of apigenin and catechin compounds in WG-ME may potentiate the above effects. The molecular interaction study predicted that apigenin inhibits TNF-α by interacting with its major site. Hence, WG-ME may exert its preventive efficacy in managing the functional imbalance of reproductive organs caused by BPA.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04117-0.

The goal of the research was to develop a hydrophobic octanoate salt of chitosan (CS-OA) and use the salt as a nanoparticle platform for the delivery of curcumin (CUR) into prostate cancer cells. The nanoprecipitation technique was used to prepare the nanoparticles, which were measured for particle size and encapsulation efficacy relative to CUR-CS nanoparticles. The cytotoxicity of CUR-OA-CS nanoparticles was evaluated in prostate cancerous cells (PC3 and DU145) in comparison with the corresponding blank nanoparticles and hydroalcoholic CUR solution. PXRD, SEM, and TEM were also used to examine the CUR-CS-OA nanoparticles. The average diameters of the CUR-CS-OA and CUR-CS nanoparticles were 268.90 ± 3.77 nm and 221.90 ± 2.79 nm, respectively, with encapsulation efficiencies of 61.37 ± 1.70% and 60.20 ± 3.17%. PXRD and SEM suggested CUR amorphization in the CS-OA nanoparticles. The void nanoparticles exhibited concentration-dependent antiproliferative action, which was attributed to the cellular uptake of CS. CUR loading into these nanoparticles increased their cytotoxicity even more. The potential of CS-OA nanoparticles as a special delivery system for additional cytotoxic drugs into different malignant cells can be further explored.

Malaria is a significant global public health issue, particularly prevalent in Africa, Asia, and Latin America, necessitating urgent research into novel and efficient therapies. In the current research, we have designed pyridine substituted pyrazole 1,3,5-triazine derivatives as antimalarials. A library including 300 compounds, designated as 7S (1-300), has been generated using a variety of aliphatic and aromatic amines. Ten compounds have been selected via in silico screening such as molecular properties, toxicity study, docking study and conventional synthesis for antimalarial evaluation against P. falciparum strains 3D7 (chloroquine-sensitive) and Dd2 (chloroquine-resistant). The docking results of compounds 7s258 and 7s5 revealed higher binding interaction with amino acids Leu46, Phe58, Phe116, Ala16 (-341.33 kcal/mol), Ser111, Ile112, Val45 Pro113, Leu119 (-335.16 kcal/mol) and Phe58, Ser111, Ile112, Phe116 (-354.47 kcal/mol), Phe58, Met55, Leu46, Leu164, Pro113 (-346.34 kcal/mol) against wild (1J3I) and quadruple mutant (1J3K) type of Pf-DHFR inhibitors. Further these compounds were synthesized by simple nucleophilic substitution reaction and characterized by different spectroscopic methods. The in vitro antimalarial assay results suggested that these compounds exhibit considerable antimalarial activity with IC₅₀ values of 32.74-46.80 μM and 28.05-54.95 μM against both the chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains of P. falciparum, respectively. Among the ten derivatives, compound 7s258 and 7s5 show substantial potential as antimalarial agents. They are highly suitable for further refinement in the field of drug development to effectively decrease the global malarial burden.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04129-w.

Alzheimer's disease (AD) is a major neurodegenerative condition that affects a significant number of people around the world, making understanding the underlying molecular mechanisms fundamental for identifying predictive biomarkers and therapeutic targets for treating AD. Analysis of the gene expression profile GSE5281, consisting of 161 samples (87 AD and 74 control samples) revealed differentially expressed genes (DEGs) used for KEGG screening to connect dysregulated genes to metabolic pathways or other neurological diseases including Parkinson's, prion, and Huntington's and construction of a protein interaction network. Protein-protein interaction (PPI) network and module analysis uncovered the hub genes ACTB, ACTG1, ATP5A1, CCT2, CDC42, EGFR, FN1, GAPDH, GFAP, GRIA1, HSP90AB1, MAPK1, PSMA3, PSMD14, SNAP25, SNCA, SOD1, SOX2, TPI1, and YWHAZ. The analysis revealed a link between dysregulated genes and processes in AD pathology, including the promotion of osteoporosis, an altered nucleotide metabolism, microtubule stability, and the dysfunctionality of the blood-brain barrier (BBB). These targets might be used as predictive biomarkers or to develop curative and preventive therapeutic approaches for treating AD.

In the present study, CeO₂ nanoparticles were synthesized using one-pot green route with high yield using microalgae Chlorella sorokiniana. The synthesized CeO₂ nanoparticles (CeO₂-np) exhibited rapid photocatalytic degradation 98.2% of doxycycline (DC) (20 mg/L) in only 30 min under visible light at pH7 in water. It was encouraging that CeO₂-np did not demonstrate a loss of photocatalytic activity up to five repeated cycles, confirming its stability during the degradation process. Moreover, cytotoxicity evaluation of CeO₂-nps on the green alga Chlorella sorokiniana advocated its non-toxic nature by supporting algal growth (0.52 g/L biomass) with 13% total lipids after 12 days in DC treated water. Ultimately, the produced algal biomass could be further utilized as a feedstock of biofuel production.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04134-z.

Ergosterol is widely used in skin care products and drug preparation. Lanosterol 14α-demethylase (Erg11p, 14DM, CYP51) is the rate-limiting enzyme for the biosynthesis of various steroid compounds in Saccharomyces cerevisiae. Herein, Erg11p was engineered to extend the in vivo catalytic half-life and increase the turnover rate. Single mutations resulting in lower folding energy were selected, and mutant P201H had an ergosterol yield of 576.9 mg·L^-1. Through consensus design, single mutations resulting in higher sequence identity to homologs were tested and mutant K352L had an ergosterol yield of 677.9 mg·L^-1. The key residues for substrate binding were confirmed via alanine scanning mutagenesis and mutant F384A had an ergosterol yield of 657.8 mg·L^-1. Molecular dynamics (MD) simulation was conducted to investigate the contributions of pocket residues and eight residues were found to engage in weak interactions with lanosterol. Saturation mutagenesis was applied to these residues to enhance binding to lanosterol, and mutant F384E had an ergosterol yield of 733.8 mg·L^-1. Meanwhile, MD simulations were conducted to assess the impact of mutant F384E on enzyme activity. The results consistently showed that single point mutation F384E had the greatest effect, outperforming the combination mutations. Batch fermentation increased the ergosterol yield of mutant F384E to 3067.5 mg·L^-1, the highest reported to date. The successful engineering of Erg11p may pave the way for industrial-scale production of ergosterol and other steroids.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04136-x.

The aim of this study was to explore the molecular mechanisms underlying carbamazepine (CBZ)-induced testicular toxicity and testosterone reduction in rats. For this purpose, Sprague-Dawley (SD) rats were intervened with 200 mg/kg CBZ for 12 weeks, and R2C cells were exposed to CBZ at concentrations of 0.5, 1 and 1.5 mM for 24 h. HE, Tunel, ELISA, immunofluorescence staining, RT-qPCR, and western blot were used to reveal the effects of CBZ on spermatozoa quality, testicular tissue structure, testosterone level and testosterone synthesis-related enzymes in rats. The results showed that CBZ significantly damaged the testicular tissue structure of rats, induced cell apoptosis, down-regulated the gene and protein expression levels of testosterone synthesis-related enzymes (STAR, TSPO, 17β-HSD and 3β-HSD), inhibited the expression of related proteins in the cAMP/PKA/CREB signalling pathway, and suppressed testosterone levels. In addition, the use of Db-cAMP (a PKA activator) significantly upregulated the protein expressions of PKA and p-CREB, evidently alleviated the CBZ-induced decrease in testosterone levels. In conclusion, CBZ induced testosterone resynthesis by inhibiting the cAMP/PKA/CREB pathway, affecting the expression of steroid synthesis-related enzymes and reducing testosterone levels.

Symphorema polyandrum belongs to the Lamiaceae family and is locally known as Badichang or mahasindhu. In this study, we performed Soxhlet extraction to prepare methanolic and hydromethanolic extracts, followed by quantification of their total phenolic content and total flavonoid content. Qualitative analysis of both the extracts was conducted to determine the presence of different phytochemicals. In addition, we aimed to identify the important phytochemical constituents in the methanolic extracts of S. polyandrum (SPM) using ultra-performance liquid chromatography hyphenated with high-resolution mass spectrometry (UPLC-ESI-QTOF-MS^E). Furthermore, this study investigated the antioxidant, anticancer and anti-inflammatory properties of SPM and its safety profile in the normal fibroblast cell line L929. A colony proliferation assay and a Griess assay were performed to evaluate the effects of SPM on colony formation and nitric oxide (NO) production. A total of 13 important phytochemicals were identified and reported. The methanolic extract of SPM demonstrated significant antioxidant activity. SPM also showed substantial antiproliferative activity on MDA-MB-231 triple-negative breast cancer cells, with an IC₅₀ value of 45.53 ± 1.63 µg/ml, and also reduced the survival of these cancer cells by promoting nuclear fragmentation and condensation without causing harm to normal cells. SPM inhibits the colony formation and reduces the nitric oxide (NO) production. The anti-inflammatory potential of SPM was assessed utilizing the murine alveolar macrophages (J774.A.1) as an in vitro model, and SPM effectively lowered the levels of proinflammatory cytokines such as TNF-α and IL-6. These findings emphasized the antiproliferative potential of SPM to cancer cells, along with its anti-inflammatory, and antioxidant capabilities, indicating the therapeutic efficacy of this medicinal plant.

Previous research leads have affirmed the crucial role of plant growth-promoting rhizobacteria (PGPR) strains Bacillus safensis (NBRI 12 M), Bacillus subtilis (NBRI 28B, NBRI 33N), and Jeotgalicoccus huakuii (NBRI 13E) in salt stress amelioration and plant growth promotion. In the present study, whole-genome analysis unveiled the underlying molecular mechanisms accounting for phyto-beneficial and stress-mitigating traits of the selected PGPR strains. The genomic characterization has revealed that NBRI 12 M, NBRI 28B, NBRI 33N, and NBRI 13E possessed a single circular chromosome of 3.73 Mb, 4.07 Mb, 4.10 Mb, and 2.17 Mb size, respectively. The genome analysis of these strains demonstrated varied genes such as mrp and yfiY for plant growth promotion, nutrient metabolism, and other secondary metabolites biosynthesis. High salinity tolerance genes (yicL, ydhP_1, spoIIQ, and spoIIID), encoding for membrane transporter, dormancy, and sporulation, were also identified. In addition, several chemotaxis (cheA, cheY, and cheW) and motility gene clusters (motB_1, motB_2) were found in the PGPR strains for successful rhizosphere colonization. Further, NBRI 12 M has significantly increased the shoot and root length and dry weight by 14.13%, 20.63%, and 9.63%, respectively, under salt stress. In addition, NBRI 12 M inoculation reduced defense enzymes by 79.77%, 84.75%, 74.11%, 70.77%, and 57.75% for SOD, APX, GPX, CAT, and PPO, respectively. Overall findings from this study offered a detailed comparative genomic analysis of salt stress ameliorating PGPR of Bacillus genera towards enhancing the deep insights for host-PGPR association.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04164-7.

Jumonji and AT Rich Interacting Domain2 (JARID2), a pivotal accessory component of Polycomb Repressive Complex 2 (PRC2) is a critical factor in cancer development. The objective of the study was to determine the role of JARID2 in Oral Squamous Cell Carcinoma (OSCC). RT-PCR, qRT-PCR, immunofluorescence, immunohistochemistry, and western blot were used to analyze the gene and protein expression in OSCC clinical samples and OSCC cell lines. The experiments have collectively demonstrated the downregulation of JARID2 mRNA and protein expression during OSCC metastasis. The cytoplasmic localization of JARID2 in OSCC tissues and cell lines were also observed. In addition, JARID2 was knocked down in HSC-3 cells by performing siRNA-mediated transfection which revealed an increase in the expression of mesenchymal markers, N-cadherin and vimentin, and a downregulation of epithelial marker E-cadherin. Moreover, silencing JARID2 significantly increased the metastatic features such as migration, invasion, and colony-formation ability in HSC-3 cells. Also, the knockdown significantly reduced the number of apoptotic cells, suggesting that JARID2 knockdown has critically promoted HSC-3 cell metastasis by enhancing the mesenchymal markers. Taken together, the study has confirmed that JARID2 acts as a tumor suppressor, the downregulation of which promotes OSCC progression by regulating Epithelial-to-Mesenchymal Transition (EMT).

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04163-8.