Single-Cell Microgels for Diagnostics and Therapeutics

Cell encapsulation within hydrogel droplets is transforming what is feasible in multiple fields of biomedical science such as tissue engineering and regenerative medicine, in vitro modeling, and cell-based therapies. Recent advances have allowed researchers to miniaturize material encapsulation complexes down to single-cell scales, where each complex, termed a single-cell microgel, contains only one cell surrounded by a hydrogel matrix while remaining <100 μm in size. With this achievement, studies requiring single-cell resolution are now possible, similar to those done using liquid droplet encapsulation. Of particular note, applications involving long-term in vitro cultures, modular bioinks, high-throughput screenings, and formation of 3D cellular microenvironments can be tuned independently to suit the needs of individual cells and experimental goals. In this progress report, an overview of established materials and techniques used to fabricate single-cell microgels, as well as insight into potential alternatives is provided. This focused review is concluded by discussing applications that have already benefited from single-cell microgel technologies, as well as prospective applications on the cusp of achieving important new capabilities.     

Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives

Resistance to chemotherapy still remains a major challenge in the clinic, impairing the quality of life and survival rate of patients. The identification of unconventional chemosensitizing agents is therefore an interesting aspect of cancer research. Resveratrol has emerged in the last decades as a fascinating molecule, able to modulate several cancer-related molecular mechanisms, suggesting a possible application as an adjuvant in cancer management. This review goes deep into the existing literature concerning the possible chemosensitizing effect of resveratrol associated with the most conventional chemotherapeutic drugs. Despite the promising effects observed in different cancer types in in vitro studies, the clinical translation still presents strong limitations due to the low bioavailability of resveratrol. Recently, efforts have been moved in the field of drug delivery to identifying possible strategies/formulations useful for a more effective administration. Despite the necessity of a huge implementation in this research area, resveratrol appears as a promising molecule able to sensitize resistant tumors to drugs, suggesting its potential use in therapy-refractory cancer patients.     

Antibacterial and photocatalytic behaviour of green synthesis of Zn0.95Ag0.05O nanoparticles using herbal medicine extract

The present work aimed to synthesize Zn_0.95Ag_0.05O (ZnAgO) nanoparticles using rosemary leaf extracts as a green chemistry method. The characterization of Ag-doped ZnO nanoparticles was performed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and ultraviolet–visible spectrophotometry (UV–visible). The XRD, FTIR, and UV–visible spectra confirmed the formation of the presence of hexagonal ZnAgO nanoparticles. FESEM micrograph shows that the nanoparticles have been distributed homogeneously and uniformly. The morphology of ZnAgO nanoparticles is quasi-spherical configuration. Also, the mean particle size is in the range of 22–40 nm. The photocatalytic degradation of methylene blue in the presence of Ag-doped ZnO nanoparticles is nearly 98.5% after exposing 100 min. The ultraviolet lamp was used as the light source for photocatalyst degradation. The disc diffusion method was chosen to study the antibacterial activity of as-synthesized ZnAgO nanoparticles. Antibacterial activity of Zn_0.95Ag_0.05O nanoparticles against Staphylococcus aureus and Escherichia coli revealed that the as-synthesized ZnAgO nanoparticles were efficient in inhibition of bacterial growth.     

Characterization of Dog Glutathione Transferase P1-1, an Enzyme Relevant to Veterinary Medicine

Glutathione transferases (GSTs) form a family of detoxication enzymes instrumental in the inactivation and elimination of electrophilic mutagenic and carcinogenic compounds. The Pi class GST P1-1 is present in most tissues and is commonly overexpressed in neoplastic cells. GST P1-1 in the dog, Canis lupus familiaris, has merits as a marker for tumors and as a target for enzyme-activated prodrugs. We produced the canine enzyme CluGST P1-1 by heterologous bacterial expression and verified its cross-reactivity with antihuman-GST P1-1 antibodies. The catalytic activity with alternative substrates of biological significance was determined, and the most active substrate found was benzyl isothiocyanate. Among established GST inhibitors, Cibacron Blue showed positive cooperativity with an IC₅₀ value of 43 nM. Dog GST P1-1 catalyzes activation of the prodrug Telcyta, but the activity is significantly lower than that of the human homolog.     

Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications

Stem cells for regenerative medicine purposes offer therapeutic benefits, but disadvantages are still ill defined. The benefit of stem cells may be attributed to their secretion of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs), including exosomes. We present a novel cell-free stem cell-derived extract (CCM), formulated from human progenitor endothelial stem cells (hPESCs), characterized for biologically active factors using ELISA, nanoparticle tracking analysis and single particle interferometric reflectance imaging sensing. The effect on fibroblast proliferation and ability to induce stem cell migration was analyzed using Alamar Blue proliferation and Transwell migration assays, respectively. GFs including IGFBP 1, 2, 3, and 6, insulin, growth hormone, PDGF-AA, TGF-α, TGF-β1, VEGF, and the anti-inflammatory cytokine, IL-1RA were detected. Membrane enclosed particles within exosome size range and expressing exosome tetraspanins CD81 and CD9 were identified. CCM significantly increased cell proliferation and induced stem cell migration. Analysis of CCM revealed presence of GFs, CKs, and EVs, including exosomes. The presence of multiple factors including exosomes within one formulation, the ability to promote cell proliferation and induce stem cell migration may reduce inflammation and pain, and augment tissue repair.     

临床血流动力学30年

从肺动脉漂浮导管第一次介绍到中国开始,临床血流动力学在我国已经发生了天翻地覆的变化。从监测指标的临床应用,到对血流动力学理论的系统认识;从仅限于循环系统内,到指标遍布整个机体;从对血流动力学无处不在的临床认识,到对重症治疗每一个细节的把控;从对临床治疗与再损伤的认识,到通过血流动力学指标对临床行为的定量管理;终于使血流动力学监测走向治疗。继而,在此基础上,新指标的出现不仅拓宽了视野,并导致对已有体系的重新认识。血流动力学连续与动态特征和目标与目的的实施策略可以付诸实践,才使得"临床血流动力学治疗"的概念,以完整的理论体系、规范的临床应用,终于破茧而出。在深入地植根于临床实践后,今天的临床血流动力学治疗正在从微循环走向器官功能,从个体化走向器官化。     

远志种植管理技术

远志是山西省的道地药材,山西省襄汾县已形成规模种植,成为当地农民增收致富的主导产业,文章总结了襄汾县远志种植管理技术,为农户提供参考。     

生物标志物在生物药临床研究中的应用及生物分析策略

中国生物药研发进入快车道，新药研发费用不断攀升，但并没有提高药物上市的成功率，因此亟需对药物研发模式进行转变。为了提高药物研发成功率，以生物标志物为核心的转化医学新药研发模式被普遍接受。本文综述了以生物标志物为核心的转化医学新药研发思路，生物标志物在生物药临床研究中的应用，生物标志物生物分析策略，生物标志物在生物药临床研究中的机遇与挑战。通过对标国际，寻找中国优势，从生物标志物为立足点的转化医学研发模式寻找机遇，中国可以尽早做成具有全球影响力的创新药。