Bioengineering & Translational Medicine最新文献

The house dust mite Dermatophagoides pteronyssinus produces major allergens (Der p 1, Der p 2, and Der p 23) that require precise IgE detection for clinical diagnosis. We developed a multiplex digital ELISA using fluorescence-encoded micromagnetic beads (532 nm/638 nm dual-wavelength system) coupled with microfluidics to simultaneously quantify serum IgE against these components, with comprehensive evaluation against the clinical standard UniCAP system. The 532 nm channel measured allergen-specific signals via average brightness increase (ABMB) of enzymatically amplified fluorescence, while 638 nm enabled spectral bead differentiation. Comparative evaluation with UniCAP showed the improved digital ELISA achieved uniform 75.0% sensitivity but variable specificity (42.9%–54.5%) across allergens at the 15.8% ABMB threshold. Sample classification results (Der p 1: 9 positive/6 negative; Der p 2: 7/8; Der p 23: 7/8) demonstrated suboptimal positive predictive values (33.3%–60.0%) versus more favorable negative predictive values (60.0%–85.7%), with likelihood ratios (LR+: 1.31–1.65) and Cohen's κ (0.12–0.25) suggesting limited diagnostic reliability. The automated platform offered 60% reduced sample volume (20 μL vs. 50 μL), multiplex capability, and maintained sensitivity for low-titer samples, representing an efficient screening solution pending specificity enhancement.

The homeostasis of branched-chain amino acids (BCAAs) plays a crucial role in maintaining health, and the accumulation of BCAAs can lead to various diseases. Therefore, exogenous degradation or conversion of excessive BCAAs may help alleviate diseases caused by BCAA accumulation, such as maple syrup urine disease. This study utilized synthetic biology approaches to engineer two strains for efficient BCAA catabolism successfully—ECN-Deg and ECN-Tra—by integrating specific metabolic pathways into the chassis strain, Escherichia coli Nissle 1917 (ECN). ECN-Deg integrates a metabolic module for BCAA degradation, while ECN-Tra integrates a metabolic module for BCAA transformation. Both engineered strains demonstrate efficient BCAA catabolism in vitro and in vivo. In a high-BCAA mouse model, ECN-Deg and ECN-Tra alleviated liver and ileal damage caused by excessive BCAAs and reduced systemic inflammation levels. Furthermore, ECN-Deg and ECN-Tra were able to modulate the gut microbiota, increasing the richness of Akkermansia muciniphila and Mucispirillum schaedleri, which are associated with health benefits. Additionally, they reduced the richness of the pathogenic bacterium Streptococcus pasteurianus. Thus, this study lays the foundation for the development of probiotics for the treatment of BCAAs metabolic disorders and BCAAs-related chronic diseases.

A major concern of conventional photodynamic therapy is its non-specific toxicity due to off-site drug accumulation. Micelles tend to localize the drug to the tumor site. However, rapid drug release at high concentrations from the micelles to kill the cancer cells remains a formidable task. In this manuscript, we have introduced the 2-nitrobenzyl (2NB)-moiety as the linker between mPEG and the photosensitizer, chlorin e6 (Ce6), to prepare the conjugate, mPEG(2-nitrobenzyl)Ce6. We envision that 2NB as a linker between hydrophobic, Ce6, and hydrophilic mPEG would be more effective in releasing Ce6 by disassembling PEGylated 2-nitrobenzyl chlorin e6 (mPNCe6) Ms. Characterization through Fourier transform infrared spectroscopy and ¹H, ¹³C nuclear magnetic resonance spectra validated the successful synthesis of the conjugate. By conjugating Ce6 into the hydrophobic core of the micelles, exposure to near-infrared light significantly hastened the dissociation of the micelles, facilitating a controlled and rapid release of Ce6's hydrophobic components within the micelles. A cellular uptake study was performed, showing that Ce6 conjugation has improved the uptake of Ce6. The cell viability assay revealed that the formulation had shown concentration-dependent cytotoxicity upon laser irradiation. mPNCe6 group with laser irradiation has generated abundant reactive oxygen species (ROS) inside cells and exhibited green solid fluorescence, indicating the efficient delivery of Ce6 by mPNCe6 micelles and its excellent ROS generation ability inside cells upon laser irradiation. Further, in vivo studies on MOC2 tumor-bearing mice demonstrate reduced tumor growth, lung metastasis, and drug accumulation in the tumor region. The developed nanomedicine could be a potential treatment strategy for oral cancer, minimizing the occurrence of lung metastasis.

Ischemic stroke is a serious cerebrovascular disease with limited effective treatments. While stem cell therapy shows promise, ensuring cell survival and integration into neural networks remains a challenge. Recent research shows tissue engineering can greatly fix these flaws. Notably, we focus on the structure–activity relationship of biomaterials. How cell behavior can be most beneficially regulated by changes in the physical structure of the cell carrier itself is certainly a new perspective for cost saving and effectiveness increasing compared to the delivery of expensive biotrophic factors. However, there is a lack of research on biomaterials applied to ischemic stroke, especially in combination with stem cells. No biomaterial has even been approved for clinical trials in stroke. We provide a systematic summary of biomaterials-driven stem cell therapy for ischemic stroke in terms of pathomechanisms, applications, and clinical translational challenges; we attempt to build a bridge from laboratory research to clinical translation in stroke treatment.

Pain is a key symptom associated with rheumatoid arthritis (RA) and can persist even in the context of overall disease control by standard-of-care disease modifying anti-rheumatic drugs (DMARDs). Analgesic agents and corticosteroids are often used to supplement DMARDs for pain relief but lack disease modifying properties, and their sustained use carries adverse risks. In this work, we characterized the progression of pain sensitivity in the SKG mouse model of RA and evaluated the potential therapeutic interventions. Male and female SKG mice, after systemic mannan injection, developed a mechanical pain phenotype and joint swelling, with a strong inverse correlation between clinical arthritis scores and pain thresholds. To test potential interventions for pain alleviation, we evaluated all-trans retinoic acid (ATRA)-loaded poly(lactic-co-glycolic acid) microparticles (ATRA-PLGA MP) administered via intra-articular injection, which we have previously demonstrated to be disease-modifying. The pain and inflammation patterns assessed by the von Frey test and clinical scoring showed ATRA-PLGA MP monotherapy reduced inflammation and alleviated mechanical allodynia in arthritic SKG mice, an effect that was amplified by combination treatments with standard-of-care agents. In early-stage arthritis, co-administration with cytotoxic T-lymphocyte-associated protein (CTLA)-4-Ig, clinically known as abatacept, delayed disease progression and sustained the reduction of mechanical allodynia. In established arthritis, sequential treatment with the corticosteroid dexamethasone (Dex) reduced cumulative disease burden and reduced mechanical allodynia. These findings highlight the potential of combining ATRA-PLGA MP with standard-of-care treatments as a potential strategy to enhance the efficacy and durability of disease modification and pain alleviation for arthritis management.

Ureteral carcinoma remains a major clinical challenge and requires effective localized treatment. Here, we report a novel ¹²⁵I seed brachytherapy (ISB) and doxorubicin (DOX) chemotherapy integrated ureteral stent (IUS), which enables simultaneous urinary drainage and chemoradiotherapy. This study was divided into three parts. First, ISB and DOX significantly reduced T24 cell viability and inhibited migration and invasion in an in vivo study (p < 0.01). Second, a T24 xenograft mouse model demonstrated that the (DOX + ISB) group exhibited greater tumor suppression than the DOX (p = 0.08) and ISB (p = 0.02) groups, with decreased Ki-67 and Bcl-2 expression and increased apoptosis (all p < 0.01) in an in vitro study. Third, the IUS was successfully implanted in normal beagle dogs (n = 30) without surgical complications. The ureteral diameter increased with increasing cumulative brachytherapy and sustained DOX release (p < 0.05). Histological analysis revealed progressive tissue damage and fibrosis, with increased expression of α-SMA, Caspase-3, and Collagen-1 in the 0.8 mCi + 20 mg DOX group (p < 0.05), whereas PCNA expression was highest in the Control group (0 mCi + 0 mg DOX). In conclusion, the newly designed IUS is safe and technically feasible in animals; clinical studies will be required to evaluate its use in humans.

Treatment of High-grade serous ovarian cancer (HGSOC) is often ineffective due to frequent late-stage diagnosis and development of resistance to therapy. Timely selection of the most effective (combination of) drug(s) for each patient would improve outcomes, however the tools currently available to clinicians are poorly suited to the task. We here present a computational simulator capable of recapitulating cell response to treatment in ovarian cancer. The technical development of the in silico framework is described, together with its validation on both cell lines and patient- derived laboratory models. A calibration procedure to identify the parameters that best recapitulate each patient's response is also presented. Our results support the use of this tool in preclinical research, to provide relevant insights into HGSOC behavior and progression. They also provide a proof of concept for its use as a personalized medicine tool and support disease monitoring and treatment selection.

This comprehensive review explores the therapeutic potential of carbon nanomaterials, including carbon nanotubes, graphene, carbon dots, and other related materials, in wound healing applications. These materials offer a cutting-edge approach by modulating critical cellular processes, addressing current challenges in wound care, and advancing tissue regeneration techniques. The article thoroughly examines recent developments in carbon nanomaterials, highlighting their integration into wound care strategies and the ongoing efforts to overcome limitations such as biocompatibility, toxicity, and long-term safety. Unlike previous reviews, this work not only acknowledges recent advancements but also provides a critical analysis of the still existing barriers and novel strategies for effectively translating these materials from research to clinical applications. By emphasizing both the potential and the challenges, the review aims to present a unique perspective on the future of carbon nanomaterials in wound healing, paving the way for more efficient and personalized treatment options.

Elevated levels of low-density lipoprotein cholesterol (LDL-C) play a critical role in the onset and progression of cardiovascular disease (CVD). Inhibitors or monoclonal antibody drugs targeting pro-protein convertase subtilisin/kexin type 9 (PCSK9) are novel cholesterol-lowering medications that can effectively reduce serum LDL-C levels. However, these drugs are usually expensive and require injections, which can reduce patient compliance and increase the financial burden. In this study, we constructed an engineered probiotic strain containing a prokaryotic expression element and a high-affinity fragment of the human PCSK9 nanobody (PCSK9nb). The engineered bacterium was evaluated in vitro and in vivo for its ability to express and release PCSK9nb, as well as for its biocompatibility and stability. The therapeutic potential of the engineered probiotics was confirmed using mouse models of hyperlipidemia and atherosclerosis. We analyzed differences in mouse gut microbiota using high-throughput sequencing and compared the therapeutic efficacy of the engineered bacteria with that of atorvastatin in a mouse model of hyperlipidemia. The engineered bacteria were found to express and release PCSK9nb in vivo after oral administration, achieving the effect of lowering serum cholesterol levels, alleviating atherosclerosis, and reducing body weight. In vivo, PCSK9nb was found to increase hepatic LDL receptor (LDLR) expression levels, decrease serum LDL-C content, regulate the diversity and community structure of gut microbiota, reduce lipid accumulation in the liver, and decrease systemic inflammation. By comparing their efficacy with that of statins, the engineered probiotics demonstrated similar therapeutic effects. The research results provide a new strategy for the development of orally delivered PCSK9 antibody drugs, reducing healthcare costs and minimizing statin drug tolerance.