Biotechnologia最新文献

Background: Type 2 diabetes (T2D) is a global health concern characterized by pancreatic β-cell dysfunction, which disrupts multiple biochemical pathways. Consequently, treatments that target various pathways are essential. This study evaluates the hepato-renal protective effects of ferulic acid (FA) in T2D, focusing on carbohydrate metabolism, oxidative stress, and inflammation using in vivo and in silico approaches.

Materials and methods: T2D was induced in male Wistar rats using fructose and streptozotocin. After 28 days of FA treatment, biochemical analyses were performed to measure glucose, glycosylated hemoglobin, insulin, liver enzymes (ALT, AST, ALP), renal markers (creatinine, uric acid, BUN), and antioxidant status (SOD, CAT, GSH, MDA) in the liver and kidney. Pro-inflammatory markers (NF-κB-p65, IL-1β, IL-6) were evaluated in the liver and kidney. Molecular docking studies were also conducted to assess FA's interaction with key T2D-related proteins.

Results: FA treatment improved pancreatic β-cell function, increased insulin levels, and reduced serum glucose and glycosylated hemoglobin. Liver function, renal markers, and hepatic glycogen content improved significantly, and diabetes-induced weight loss was reversed. FA inhibited pancreatic α-amylase, intestinal α-glucosidase, fructose-1,6-bisphosphatase, and glucose-6-phosphatase, while enhancing hexokinase activity. Notably, FA improved antioxidant status and reduced inflammatory mediators in diabetic rats. Molecular docking revealed that FA exhibits stronger binding affinity and greater inhibitory potential against key diabetes-related proteins compared to metformin.

Conclusion: FA offers hepato-renal protection in T2D by modulating carbohydrate metabolism, oxidative stress, and inflammation, highlighting its potential as a therapeutic agent against T2D.

Background: Biosurfactants derived from lactic acid bacteria (LAB) produce eco-friendly biosurfactants with antimicrobial, antiadhesive, and antibiofilm properties.

Materials and methods: LAB strains isolated from Bhatabaru were screened for biosurfactant production using multiple assays, including drop collapse, hemolytic activity, oil displacement, surface activity, and emulsifying activity. The selected strain was morphologically characterized by Gram staining and microscopy and identified through biochemical assays and 16S rRNA sequencing using Gene Tool software.

Results: The strain Bht-2 was determined to be Gram-positive, coccus-shaped, and nonendospore-forming. Biochemical and molecular analyses confirmed its identity as Enterococcus faecalis, which exhibited significant biosurfactant production.

Conclusions: Enterococcus faecalis Bht-2 exhibits strong potential as a biosurfactant-producing LAB strain. Its desirable physicochemical and biofunctional traits underscore its applicability in biotechnological, pharmaceutical, and industrial domains as a safe and eco-friendly alternative to synthetic surfactants.

Background: The increasing threat of antibiotic-resistant bacteria is a significant global health concern, with millions of people worldwide infected with these resistant strains each year. This study aims to conduct a bioinformatics analysis to investigate the biotin carboxylase (BC) B-subdomain from Lactococcus lactis subsp. lactis (Lac3) (accession number NZ_JAGRPZ010000035.1) as a potential target for the identification and development of novel antibiotics. Lac3 was isolated from one of the Indonesian traditional probiotics called dadih, and its whole-genome sequence analysis was revealed in a previous study.

Materials and methods: Whole-genome sequencing data of Lac3, generated using the Illumina MiSeq sequencer (Novogene Co., Ltd.), were used to analyze gene clusters with AntiSMASH. Molecular docking (PyRx Virtual Screening Tool; AutoDock Vina) and molecular dynamics simulations (CPPTRAJ software) were performed to elucidate the potential binding sites of the BC B-subdomain and compare them with the BC domain from a L. lactis reference strain (accession number KLK97304). The 3D structure of the BC B-subdomain was predicted using AlphaFold2. Visualization of the simulated protein-ligand complex conformations was conducted using PyMOL v2.3 software.

Results: Bioinformatics analysis showed that the BC B-subdomain gene was located in the β-lactone gene cluster on contig 7.1 and consisted of 32.1% α-helix, 37.6% β-strand, and 24.8% random coil. Physicochemical analysis indicated that the BC B-subdomain protein exhibited a high degree of solubility. The BC B-subdomain shared similarities with the ATP-grasp domain of the BC domain from the reference strain, particularly in amino acid residues involved in ATP binding (His207, Gln231, Asn234, and Glu274). Molecular docking analysis demonstrated that the BC B-subdomain-ATP complex (-6.1 kcal/mol) was comparable to the BC domain-ATP complex (-8.8 kcal/mol). This was supported by molecular dynamics simulations, which indicated that the complex models remained stable throughout the simulations, based on several validation parameters, including RMSD, RMSF, Rg, and SASA. Furthermore, ionic interactions with the phosphate group's amino acid residues - critical for ATP binding and function within ATP-grasp enzymes - were observed in both the BC B-subdomain (His207 and Lys236) and the BC domain (Lys236 and Arg290).

Conclusions: These findings suggest that the BC B-subdomain could serve as a potential target for fragment-based drug discovery and may provide a reference for developing novel BC inhibitors with potent antibacterial activity by targeting ATP binding, possibly through its phosphate group binding sites. However, further analysis is needed to support the development of innovative antibacterial treatments in the future.

The global COVID-19 pandemic has highlighted the critical role of vaccines in controlling infectious diseases, with liposome-based formulations emerging as a pivotal advancement in vaccine technology. Liposomes are spherical vesicles composed of lipid bilayers that serve as drug delivery systems and versatile adjuvants, enhancing vaccine efficacy through improved antigen stability, targeted delivery, and immunogenicity. This review explores the potential of liposomes as adjuvants in both mRNA and protein subunit SARS-CoV-2 vaccines, detailing their composition and dual impact on innate and adaptive immune responses. Notably, liposome-based mRNA vaccines, such as those developed by Pfizer and Moderna, have demonstrated high efficacy by utilizing lipid nanoparticles to encapsulate mRNA and stimulate antigen-presenting cells, thereby inducing robust immune responses. Despite their advantages, challenges remain, including the optimization of lipid compositions and the mitigation of adverse immune effects. This review also examines the broad applications of liposomes in nanomedicine - from cancer therapy to antifungal treatments - and their potential for future vaccine development. By bridging the gap between engineering and immunology, the study of liposomes underscores their transformative potential in addressing current and emerging global health challenges.

Background: The prevailing public health threat posed by malaria, especially in developing countries, remains a serious concern despite the availability of preventive and control measures. While vaccination offers a powerful means of combating malaria, it has not been fully exploited due to previous unsuccessful attempts before the launch of the RTS,S vaccine. A major challenge in malaria vaccine development continues to be the identification of effective targets capable of eliciting robust immunity, given the complexity of the parasites' life cycle. Leveraging on the breakthrough of the newly approved malaria vaccine, efforts to develop more effective prophylactic solutions continue with renewed determination.

Materials and methods: In this study, a standard structural bioinformatics pipeline was employed to design a multiepitope subunit vaccine against Plasmodium, particularly P. falciparum. Thirty subunit epitopes were mined from selected variant surface antigens of P. falciparum proteins expressed at different stages of its life cycle, based on their vaccine-likeness. These epitopes were conjugated with suitable adjuvants and linkers into a vaccine construct, which was then subjected to stringent downstream analyses.

Results: Out of an initial pool of 133 epitopes, 30 vaccine-fit epitopes were selected, resulting in a final vaccine construct comprising 570 amino acid residues. This included 12 linear B-cells, 11 cytotoxic T-lymphocytes, and 7 helper T-lymphocyte epitopes, all with favorable predicted structural, antigenic, and physicochemical properties. The construct also demonstrated strong global population coverage (95.04%), robust molecular binding, and simulated immune responses.

Conclusions: With the evolving "Omics" technologies through reverse vaccinology, discovering and designing promising vaccine candidates becomes easier without many challenging experimental rigors. This study highlights the potential of immunoinformatics-aided approaches in accelerating effective malaria vaccine development.

Background: Argyreia acuta has traditionally been used for its analgesic, antipyretic, and anti-inflammatory properties; however, scientific validation of these effects remains limited. This study aimed to evaluate the pharmacological potential of ethanol extract from A. acuta leaves (AAEE) in murine models of pain, fever, and inflammation.

Materials and methods: The pharmacological properties of A. acuta leaf extract were assessed. Analgesic activity was evaluated using a hot plate and tail-flick assays, while antipyretic effects were tested via a yeast-induced pyrexia model. The anti-inflammatory potential was investigated through carrageenan-induced paw edema and by quantifying pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, COX-2, and PGE₂. Histopathological analysis of paw tissues was performed to confirm inflammatory changes.

Results: AAEE exhibited significant, dose-dependent analgesic effects, as indicated by prolonged latency times and increased pain inhibition (p < 0.05), with the 200 mg/kg dose showing the greatest efficacy. In the antipyretic model, AAEE at 200 mg/kg reduced rectal temperature to 36.93°C, corresponding to an inhibition rate of 82.61% (p < 0.05). The extract significantly reduced paw edema (41.39% inhibition at 200 mg/kg) and markedly lowered levels of TNF-α, IL-1β, IL-6, COX-2, and PGE₂ (p < 0.05). The histological analysis supported these findings, revealing decreased edema and inflammatory cell infiltration in treated groups.

Conclusions: These findings provide scientific support for the traditional use of A. acuta, demonstrating its significant analgesic, antipyretic, and anti-inflammatory activities. AAEE may represent a promising natural therapeutic agent for treating pain, fever, and inflammation.

Background: Recently, many countries and regions have started developing targeted bioeconomy strategies and plans. The concept of the bioeconomy has evolved since the implementation of the first European Union bioeconomy strategy in 2012. Current trends include, among others, the circular economy, biotechnology, and sustainable development.

Materials and methods: This article examines the role of the bioeconomy in the strategic documents of the Wielkopolska Voivodeship, using a case study approach along with analytical and critical methods. Additionally, it explores local government initiatives supporting bioeconomy development, identified through interviews.

Results: In Wielkopolska, there is currently no formal plan to develop a dedicated bioeconomy strategy. However, numerous documents and plans related to the bioeconomy have been developed since 2020, aligning regional policies with the objectives of European Union policy. The local government of Wielkopolska is actively engaged in food waste reduction through education, investment, and support for NGOs and entrepreneurs. There is strong institutional support for bioeconomy-related innovation, including dedicated strategies, funding, competitions, and stakeholder cooperation platforms.

Conclusions: A regional bioeconomy strategy is essential for leveraging local resources, addressing region-specific challenges, and aligning with EU policy frameworks. While Wielkopolska currently lacks a formal strategy, elements of the bioeconomy are included in existing plans. Developing regionally tailored strategies, fostering public awareness, enhancing education, and encouraging cross-sector collaboration is key to building a sustainable, innovation-driven bioeconomy.

Background: Traumatic brain injury (TBI) is a significant medical crisis with no FDA-approved therapies to improve functional outcomes. Key biomarkers, such as glial fibrillary acidic protein (GFAP), S-100 calcium-binding protein B (S-100B), and ubiquitin C-terminal hydrolase L1 (UCH-L1), are crucial for understanding TBI pathology.

Materials and methods: This study integrates proteomic and bioinformatic approaches to explore established TBI biomarkers' structural and functional complexities: GFAP, S-100B, and UCH-L1.

Results: Our comprehensive secondary structure and solvent accessibility assessment, conducted with PredictProtein, confirmed the predominance of alpha-helices in GFAP and S-100B, while UCH-L1 displayed a balanced mix of helices (65.00, 67.39, and 40.81%), beta strands (6.20, 0, and 17.94%), and coils (40.81, 17.94, and 41.26%). AlphaFold and I-TASSER were identified as the best servers for full-length tertiary structure prediction for the three target proteins, based on root-mean-square deviation (RMSD), TM-score, and C-score assessments. Protein motif database scans predicted four, eight, and one protein-binding motifs and two, three, and one post-translational modifications for GFAP, S-100B, and UCH-L1, respectively.

Conclusions: GFAP's role in axonal transport and synaptic plasticity was emphasized through motifs such as Filament and DUF1664. S-100B's association with neuroinflammation and oxidative stress post-TBI was supported by the S-100/ICaBP-type calcium-binding domain. UCH-L1's dualistic impact on TBI was further clarified by the Peptidase_C12 motif. This approach deepens our comprehension of these biomarkers and paves the way for targeted diagnostics in TBI.

The maternally inherited autonomous organelles, mitochondria, are responsible for a myriad of functions within the cell. They may contain more than one copy of DNA and can themselves be present in multiple numbers within a cell. The integrity of the mitochondrial genome is affected by variations in DNA copy number or the presence of mutations. Compromising this integrity has been documented to result in disorders affecting various systems. Focusing on such trends could enhance knowledge essential for developing strategies to manage these disorders. Irregular patterns of mitochondrial DNA (mtDNA) copy number (CN) variation have been identified in various cancers. Reduced mtDNA CN has been associated with neurodegenerative disorders, cardiovascular diseases, and kidney disorders. Mutations in the mitochondrial respiratory chain complex have been linked to cardiomyopathy. High rates of mtDNA deletions have been found in aging patients and subjects with Parkinson's disease. While sperm function appears to deteriorate with increased mtDNA CN, oogenesis involves a significant increase to enable the oocyte to achieve fertilization and further development. Prospective therapies to treat mitochondrial diseases may include approaches that aim to reduce the levels of mutant mtDNA below the disease-causing threshold, such as targeted removal of defective mitochondria. Mutations in mitochondrial DNA contribute to various diseases; some single substitutions appear to disrupt the normalcy of more than one organ, underscoring the importance of mitochondrial genome integrity. The presence of mutations and copy number variations may serve as diagnostic markers and also provide insight into prognosis.

Background: 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and angiotensin converting enzyme (ACE) are implicated in the pathogenesis of hyperlipidemia and hypertension, which are oxidative-stress linked conditions of public health importance. The adverse effects associated with standard clinical drugs used to inhibit these enzymes have prompted the search for alternative sources. This study was designed to investigate the in vitro inhibitory activities of lactic acid bacteria (LAB) and yeasts isolated from fermented sorghum gruels.

Materials and methods: LAB and yeast isolates were obtained and characterized using standard methods. The HMG-CoA reductase and ACE inhibitory activities of the microbial isolates were evaluated using established protocols.

Results: Screening of LAB for HMG-CoA reductase and ACE inhibitory activities revealed that at concentrations (mg/ml) of 6, 12, 24, and 48, Lactobacillus pentosus WSL5 exhibited the highest %HMG-CoA reductase inhibition of 3.21, 6.42, 9.17, and 12.84, with corresponding ACE inhibitory activities of 6.38, 13.17, 18.13, and 23.47, respectively. At concentrations (mg/ml) of 1, 2, 4, and 8, the yeast isolates Trichomonascus ciferri RSY53 demonstrated %HMG-CoA reductase inhibition of 7.71, 11.47, 14.68, and 16.97, with corresponding ACE inhibitory activities of 11.83, 20.91, 34.73, and 48.28, respectively. Furthermore, L. pentosus WSL5 recorded the lowest HMG-CoA reductase half-maximal inhibitory concentration (IC₅₀) of 219.72 µg/ml and ACE IC₅₀ of 116.22 µg/ml, while T. ciferri RSY53 had even lower IC₅₀ values of 29.55 µg/ml for HMG-CoA reductase and 7.03 µg/ml for ACE inhibition compared to the controls.

Conclusion: L. pentosus WSL5 and T. ciferri RSY53 can be considered potential starter cultures for the fermentation of functional foods aimed at supporting cardiovascular health.