Current pharmaceutical biotechnology最新文献

Introduction: This research aimed to investigate the effects of biosynthesized gold nanoparticles (GNPs) combined with curcumin (Curcuma longa L.) on inflammatory and oxidative stress parameters induced by percutaneous collagen induction (PCI) in Wistar rats.

Methods: Sixty rats were separated into five different groups (n=12): I. Sham Group; II. PCI Group; III. PCI+GNPs Group; IV. PCI+Cur Group; V. PCI+GNPs-Cur Group. Then, PCI, Cur, and/or GNPs were applied topically to the dorsal regions. PCI and topical actives were used at three different times with 14-day intervals between them. Euthanasia was performed 14 days after the last treatment.

Results: When evaluating pro-inflammatory cytokines, all treatment groups showed a significant decrease compared to the PCI group. In the analysis of anti-inflammatory cytokines, the PCI+GNPs-Cur group showed an increase compared to the PCI group. After assessing oxidants (ROS and NO) and antioxidants (SOD and GSH), the PCI+Cur, PCI+GNPs, and PCI+GNPs-Cur groups exhibited decreased oxidant levels and increased antioxidant levels compared to the PCI group.

Discussion: When evaluating pro-inflammatory cytokines, all treatment groups showed a significant decrease compared to the PCI group. In the analysis of anti-inflammatory cytokines, the PCI+GNPs-Cur group exhibited an increase compared to the PCI group. After assessing oxidants (ROS and NO) and antioxidants (SOD and GSH), the PCI+Cur, PCI+GNPs, and PCI+GNPs-Cur groups demonstrated decreased oxidant levels and increased antioxidant levels relative to the PCI group.

Conclusion: The results of the present study demonstrate that the anti-inflammatory and antioxidant effects are enhanced by the association of GNPs with Cur, reducing the inflammatory process caused by PCI.

The oral route is thought to have the highest patient compliance among the several administration modes. The gastrointestinal tract's sensitivity to environmental changes is the primary issue associated with oral delivery. If the drug is poorly water soluble and fails to penetrate cellular membranes, its bioavailability may be further diminished. A drugphospholipid complex method, which works similarly to the gastrointestinal tract's absorption of food components, could be used to overcome this obstacle. Drug-phospholipid complexes are excellent for oral administration because they are nontoxic and biodegradable. As a result, they are used as emulsifiers, matrix-forming excipients, and solubilizers in medications with limited solubility and permeability. Phospholipids have two different characteristics: high biocompatibility and outstanding amphiphilicity. Phospholipids have a wide range of applications in drug delivery systems, and their specific properties make them ideal to be utilized as important pharmacological excipients. The purpose of this research is to offer a thorough understanding of phospholipids, drug-phospholipid complex-building processes, phospholipids themselves, the mechanism by which they boost drug bioavailability, and some of the formulations' uses in drug delivery systems. Along with highlighting the links between phospholipid properties and applications, it will also explain how different phospholipid species influence medication delivery. The growing volume of current research on the strategy's use to boost drug oral bioavailability demonstrates its importance for effective oral administration.

Introduction: Dihydromyricetin (DMY), a phytoflavonoid with diverse pharmacological activities, is limited in cosmetic applications by poor solubility, easy discoloration, and low bioavailability. This study aimed to address these drawbacks for its practical cosmetic use.

Methods: DMY nanoliposomes (DMY-NL) were prepared via ethanol injection-high-pressure homogenization, with orthogonal tests optimizing the process using particle size, PDI, and zeta potential as indices. Tests included in vitro dialysis-based sustained-release assay, erythrocyte hemolysis/human patch tests (safety), and DPPH scavenging/hemolysis/human patch antiirritation tests (soothing efficacy).

Results: DMY-NL had >90% encapsulation efficiency, 90-day stability under different storage conditions, and 48-h sustained release (superior to control). Safety was confirmed by hemolysis and patch tests; soothing efficacy was verified via DPPH scavenging and anti-irritation tests.

Discussion: DMY-NL's high encapsulation, good stability, and sustained release solve DMY's cosmetic application limitations. Confirmed safety and soothing effects support its practical use in cosmetics.

Conclusion: This study provides a theoretical and practical basis for DMY's cosmetic application, expected to expand its use in the cosmetic industry.

Introduction: Ropivacaine (RPV), a commonly used local anesthetic, is limited in its effectiveness for postoperative pain management due to its short duration of action. To address this issue, this study further explores the development of poly(lactic-co-glycolic) acid (PLGA)- PVA nanocarriers designed to extend RPV's release and efficacy.

Methods: PLGA-PVA-RPV nanocarriers were synthesized via an emulsion technique and comprehensively characterized using transmission scanning electron microscopy, Malvern ZS90, and Fourier transform infrared spectroscopy. The cytotoxicity of these nanocarriers against HaCaT cells was determined using the Cell Counting Kit-8 viability assay and calcein-acetoxymethyl/ propidium iodide staining. Flow cytometry and scratch assays were used to assess their effects on the HaCaT cell cycle, apoptosis, and migration.

Results: The PLGA-PVA-RPV nanocarriers exhibited a spherical morphology, small size (10.90 ± 2.19 nm), uniform distribution, and stable zeta potential (-7.93 ± 0.81 mV). The PLGAPVA- RPV nanoparticles demonstrate excellent biocompatibility; even at a high concentration of 1000 μg/mL, the cell viability remains above 80%, which is significantly higher than that of the free RPV group (67.3%, P < 0.05). Further mechanistic studies showed that PLGA-PVA-RPV nanoparticles induced cell cycle arrest and inhibited cell migration, collectively demonstrating their low toxicity, excellent biocompatibility, and sustained-release potential.

Discussion: The PLGA-PVA-RPV nanocarriers demonstrate enhanced efficacy and biocompatibility for prolonged ropivacaine release offering a promising strategy for postoperative pain management. Future work should focus on in vivo validation and parameter optimization to facilitate clinical translation Conclusion: PLGA-PVA-RPV nanocarriers possess optimal physicochemical properties (small size, homogeneity, stability) and superior biosafety, providing a promising strategy for extending RPV's analgesic efficacy. This technology has significant potential to improve postoperative pain management.

Introduction: Sepsis, a life-threatening systemic response to infection, frequently causes multiple organ dysfunction, with intestinal barrier injury playing a critical role. While METTL3, a key RNA methyltransferase, is involved in many biological processes, its specific function in sepsis remains unknown.

Methods: We analyzed METTL3 expression in intestinal tissues from 30 sepsis patients (2020- 2022) undergoing partial bowel resection. We then used mice with intestine-specific METTL3 deletion (METTL3IEC-/- ) and Wild-Type (WT) controls, subjecting them to Cecal Ligation and Puncture (CLP) to model sepsis. Intestinal inflammation, barrier function, and the NF-κB/MLCK pathway were assessed. We also evaluated the therapeutic effect of curcumin administered via gavage at different doses.

Results: METTL3 expression was significantly reduced in necrotic/perforated tissues from sepsis patients. METTL3IEC-/- mice exhibited worsened intestinal inflammation and barrier dysfunction after CLP compared to WT mice. This was associated with increased activity of the NFκB/MLCK pathway. Crucially, curcumin treatment effectively reduced the expression of key pathway components (p65 and MLCK). This led to significant improvements: reduced intestinal injury, decreased inflammation, and enhanced barrier function.

Discussion: METTL3 is essential for maintaining intestinal barrier integrity during sepsis. Its deficiency exacerbates damage via the NF-κB/MLCK pathway. Targeting this pathway, potentially with curcumin, represents a promising therapeutic strategy for sepsis-induced intestinal injury. These findings clarify METTL3's role and highlight curcumin's therapeutic potential.

Conclusion: METTL3 is essential for maintaining intestinal barrier integrity during sepsis. Its deficiency exacerbates damage, mediated through the NF-κB/MLCK pathway. Targeting this pathway, potentially with curcumin, represents a promising therapeutic strategy for sepsisinduced intestina.

Endophytes are symbiotic microbial communities residing within plants and represent a significant source of bioactive secondary metabolites. As integral components of plant microecosystems, endophytes establish stable and mutually beneficial interactions with their hosts, which not only contribute to plant growth and stress resistance but also drive the diversity of their secondary metabolic products through long-term coevolution. These metabolites exhibit diverse biological activities, including anti-inflammatory, antimicrobial, cytotoxic, antiviral, and antioxidant effects, and these bioactive properties make them promising candidates for the development of new agents in multiple fields, including pharmaceuticals, agrochemicals, and functional materials, due to their natural origins and relatively low environmental impact. This review comprehensively summarizes recent advances in understanding the bioactivities of endophyte- derived secondary metabolites, highlighting novel compounds and their pharmacological potential. Alongside traditional approaches, recent technological advancements in separation, purification, and structural identification have further facilitated the discovery and characterization of these metabolites, expanding the pool of potential bioactive molecules for research and application. We also detail common methodologies for investigating endophyte metabolites, such as fermentation optimization and biotransformation, and briefly touch on how these strategies have been widely adopted to enhance metabolite production and explore structural modifications. With the deepening of interdisciplinary research involving microbiology, chemistry, pharmacology, and biotechnology, the exploration of endophyte secondary metabolites has entered a more systematic and in-depth stage. Finally, we discuss current challenges in translating these findings into practical applications, including issues related to resource accessibility, production scalability, and comprehensive efficacy evaluation, and outline promising future research directions for drug discovery in the field of medicine, encompassing the excavation of untapped endophytic resources, the optimization of production processes, and the in-depth evaluation of safety and efficacy, so as to better harness their potential for human health and sustainable development.

Objective: Recent genomic analyses identified a distinct pilVWXY operon in hypervirulent Aeromonas hydrophila ATCC 7966, encoding PilV and two previously uncharacterized orthologs, AHA_0694 (Pil94) and AHA_0695 (Pil96), hypothesized to mediate host-pathogen interactions.

Methods: Complete A. hydrophila genomes (n = 53) were retrieved from NCBI, and the distribution of pilV, pil94, and pil96 was assessed using STRING v11.5. Physicochemical and structural features were analyzed via ExPASy-ProtParam, homology modeling, and validation using RAMPAGE, ProQ, and ProSA. Representative models were docked with eight human β- integrins using the HADDOCK server and evaluated by HADDOCK score, cluster size, van der Waals energy, RMSD (root-mean-square deviation), buried surface area, and Z-score.

Results: Twenty-eight strains of A. hydrophila (predominantly hypervirulent) encoded all three proteins, whereas 11 non-virulent strains lacked them. Structural modelling revealed a conserved lollipop-like conformation with an extended N-terminal α-helix characteristic of Type IV pilins. Docking simulations indicated selective, high-affinity binding patterns (PilV with Integrin β3/β4/β7; Pil94 with integrin β1/β2/β3/β5; Pil96 with integrin β1/β3/β5/β7/β8), suggesting roles in multi-tissue adhesion and systemic dissemination.

Conclusion: The restricted occurrence of pilV, pil94, and pil96 in virulent strains and their predicted affinity for human β-integrins underscore their importance in host colonization and pathogenesis, identifying them as promising molecular targets for diagnostic or therapeutic development.

Introduction: This study aimed to evaluate the protective effects of glibenclamide and magnesium sulfate in fructose-induced type 2 diabetes mellitus (T2DM).

Materials and methods: An experimental T2DM model was established in female Sprague Dawley rats using a 20% fructose solution for 12 weeks. The effects of glibenclamide and magnesium sulfate were assessed on glycemic control, oxidative stress, lipid profile, and tissue macro- and trace-element levels. Biochemical parameters were determined spectrophotometrically, and data were analyzed using one-way ANOVA in SPSS (version 22).

Results: Treatment with glibenclamide and magnesium sulfate significantly (p<0.05) reduced serum insulin, insulin resistance, amylase, triglycerides, total and free cholesterol, LDL-C, VLDL-C, hepatic malondialdehyde (MDA), and iron levels. Conversely, both agents markedly increased body weight, serum HDL-C, hepatic catalase and superoxide dismutase (SOD) activities, and hepatic zinc and magnesium concentrations compared with the diabetic control group.

Discussion: The findings indicate that glibenclamide and magnesium sulfate effectively attenuated hyperglycemia, dyslipidemia, oxidative stress, and trace element disturbances induced by fructose feeding. Glibenclamide enhanced β-cell activity and insulin secretion, while magnesium sulfate improved insulin sensitivity, antioxidant defenses, and glucose homeostasis through modulation of the Nrf2 and PI3K/Akt pathways.

Conclusion: Both glibenclamide and magnesium sulfate demonstrated significant protective and therapeutic effects against fructose-induced T2DM. Their combined ability to restore metabolic balance, enhance antioxidant capacity, and correct trace element deficiencies suggests potential clinical relevance of magnesium supplementation as an adjunct therapy in the management of type 2 diabetes mellitus.

Introduction: Neurodegenerative diseases are a group of life-threatening conditions characterized by gradual and severe neuronal degeneration, posing a significant global health challenge. Many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, share identical and recognizable etiologies, such as neuronal degeneration, apoptosis, oxidative stress, lipid peroxidation, Ca2+ overload, neuroinflammation, protein aggregation, endoplasmic reticulum stress, and mitochondrial dysfunction. Among these etiologies, oxidative stress and mitochondrial dysfunction are the primary contributing factors, involving several enzymes and signaling molecules in the underlying mechanism of disease progression. Globally available treatments provide only temporary symptomatic relief with side effects, and yet there is no medication to eradicate the disease-related cause.

Materials and methods: Extensive research has explored novel herbal medications offered as neuroprotective against these debilitating conditions, aiming to reverse or halt the disease progression with minimal adverse effects. Pinostrobin is a major bioactive flavonoid primarily isolated from Boesenbergia rotunda (Fingerroot). Established research has reported that pinostrobin exhibits a wide array of pharmacological activities, including anti-inflammatory, antileukemia, antioxidant, antimicrobial properties, as well as protective effects against mitochondrial dysfunction and neurodegeneration.

Results and discussion: Based on preclinical studies, we have summarised the current knowledge of pinostrobin's neuroprotective actions, highlighting its effectiveness in mitigating neuronal damage, preserving synaptic function, reducing oxidative stress, neuroinflammation, protein aggregation, mitochondrial apoptosis, and calcium overload. These mechanisms collectively support its therapeutic potential in modulating the molecular pathways underlying Alzheimer's and Parkinson's disease.

Conclusion: This review offers a comprehensive analysis of pinostrobin and its molecular pathways in combating neurodegenerative diseases, highlighting its promising effectiveness as a natural neuroprotective agent in Alzheimer's and Parkinson's disease by modulating mitochondrial and oxidative stress-mediated pathways.

Introduction: Psoriasis is a chronic autoimmune disorder characterized by immune dysregulation and excessive keratinocyte proliferation. The mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in driving inflammation in psoriatic skin.

Methods: This study investigated the expression of MAPK-related messenger RNAs (mRNAs) and their regulatory microRNAs (miRNAs) in lipopolysaccharide (LPS)-stimulated human adult low-calcium high-temperature keratinocytes (HaCaT cells). Differential gene and miRNA expression at 2, 8, and 24 hours post-LPS exposure was analyzed using oligonucleotide microarrays. Selected genes were validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and protein levels were assessed using enzyme-linked immunosorbent assay (ELISA).

Results: Of 248 MAPK-associated mRNAs, 28 showed significant differential expression. Notably, dual specificity phosphatase 1 (DUSP1), mitogen-activated protein kinase kinase 2 (MAP2K2), MAP2K7, MAP3K2, and MAPK9 were downregulated, while transforming growth factor beta 1 (TGFB1) and interleukin-1 beta (IL1B) were upregulated. Protein-level changes confirmed mRNA findings. Four miRNAs, namely miR-34a, miR-4692a, miR-200-5p, and miR- 1275, exhibited inverse expression trends relative to their predicted targets.

Discussion: These results suggest that LPS-induced inflammation causes coordinated dysregulation of MAPK signaling components and their regulatory miRNAs in keratinocytes. The identified miRNAs may serve as potential biomarkers or therapeutic targets for chronic skin inflammation.

Conclusion: LPS stimulation alters MAPK-related mRNA and protein expression in HaCaT cells and is accompanied by changes in specific regulatory miRNAs. This integrative transcriptomic- proteomic analysis highlights candidate miRNA-mRNA axes relevant to psoriasis pathophysiology and supports further validation in disease-relevant models.