Tailored Physicochemical Cues Direct Human Mesenchymal Stem Cell Differentiation through Epigenetic Regulation Using Colloidal Self-Assembled Patterns.

The extracellular matrix (ECM) shapes the stem cell fate during differentiation by exerting relevant biophysical cues. However, the mechanism of stem cell fate decisions in response to ECM-backed complex biophysical cues has not been fully understood due to the lack of versatile ECMs. Here, we designed two versatile ECMs using colloidal self-assembly technology to probe the mechanisms of their effects on mechanotransduction and stem cell fate regulation. Binary colloidal crystals (BCC) with a hexagonally close-packed structure, composed of silica (5 µm) and polystyrene (0.4 µm) particles as well as a polydimethylsiloxane-embedded BCC (BCCP), were fabricated. They have defined surface chemistry, roughness, stiffness, ion release, and protein adsorption properties, which can modulate the cell adhesion, proliferation, and differentiation of human adipose-derived stem cells (hASCs). On the BCC, hASCs preferred osteogenesis at an early stage but showed a higher tendency toward adipogenesis at later stages. In contrast, the results of BCCP diverged from those of BCC, suggesting a unique regulation of ECM-dependent mechanotransduction. The BCC-mediated cell adhesion reduced the size of the focal adhesion complex, accompanying an ordered spatial organization and cytoskeletal rearrangement. This morphological restriction led to the modulation of mechanosensitive transcription factors, such as c-FOS, the enrichment of transcripts in specific signaling pathways such as PI3K/AKT, and the activation of the Hippo signaling pathway. Epigenetic analyses showed changes in histone modifications across different substrates, suggesting that chromatin remodeling participated in BCC-mediated mechanotransduction. This study demonstrates that BCCs are versatile artificial ECMs that can regulate human stem cells' fate through unique biological signaling, which is beneficial in biomaterial design and stem cell engineering.

Plasma-generated RONS in liquid transferred into cryo-microneedles patch for skin treatment of melanoma.

Malignant melanoma is the most lethal form of skin cancer. As a promising anti-cancer agent, plasma-activated water (PAW) rich in reactive oxygen and nitrogen species (RONS) has shown significant potential for melanoma treatment. However, rapid decay of RONS and inefficient delivery of PAW in conventional injection methods limit its practical applications. To address this issue, here we report a new approach for the production of plasma-activated cryo-microneedles (PA-CMNs) patches using custom-designed plasma devices and processes. Our innovation is to incorporate PAW into the PA-CMNs that are fabricated using a fast cryogenic micro-molding method. It is demonstrated that PA-CMNs can be easily inserted into skin to release RONS and slow the decay of RONS thereby prolonging their bioactivity and effectiveness. The new insights into the effective melanoma treatment suggest that the rich mixture of RONS within PA-CMNs prepared by custom-developed hybrid plasma-assisted configuration induces both ferroptosis and apoptosis to selectively kill tumor cells. A significant inhibition of subcutaneous A375 melanoma growth was observed in PA-CMNs-treated tumor-bearing nude mice without any signs of systemic toxicity. The new approach based on PA-CMNs may potentially open new avenues for a broader range of disease treatments.

LncRNA AP000842.3 Triggers the Malignant Progression of Prostate Cancer by Regulating Cuproptosis Related Gene NFAT5.

OBJECTIVES: Prostate cancer (PRAD) is a highly malignant disease with poor prognosis, and its development is regulated by a complex network of genes and signaling pathways. LncRNAs and miRNAs have significant regulatory roles in PRAD through the ceRNA network. Cuproptosis is a unique form of programmed cell death that is involved in various signaling pathways and biological processes related to tumor development. Nuclear factor of activated T cells 5 (NFAT5), a transcription factor that activates T cells, has been implicated in cuproptosis. However, the regulatory mechanism by which NFAT5 is involved in the ceRNA network in PRAD remains unclear. METHODS: Through bioinformatics analysis, we found the ceRNA axis that regulates cuproptosis. By performing ROS assay and copper ion concentration assay, we demonstrated that inhibiting NFAT5 can increase the sensitivity of PRAD to cuproptosis inducers. By using luciferase assay, we discovered that AP000842.3 acts as the ceRNA of miR-206 to regulate the expression of NFAT5. RESULTS: In this study, we found that lncRNA AP000842.3, as a ceRNA of miR-206, was involved in the regulation of levels of the transcription factor NFAT5 associated with cuproptosis in PRAD. First, knocking down NFAT5 can increase the sensitivity of PRAD to cuproptosis inducers. Meanwhile, changes in the expression of AP000842.3 and miR-206 could affect the proliferation of PRAD by regulating NFAT5. Mechanistically, AP000842.3 acts as the ceRNA of miR-206 to regulate the expression of NFAT5. In addition, the effects of lncRNA AP000842.3 on malignant progression of PRAD and NFAT5 were partially dependent on miR-206. CONCLUSION: Taken together, our study reveals a key ceRNA regulatory network in PRAD and can be regarded as a new potential target for PRAD diagnosis and treatment.

Anti-Inflammatory and α-Glucosidase Inhibitory Triterpenoid with Diverse Carbon Skeletons from the Fruits of Rosa roxburghii.

The fruits of Rosa roxburghii Tratt. are edible nutritional food with high medicinal value and have been traditionally used as Chinese folk medicine for a long time. In this study, 26 triterpenoids including four new pentacyclic triterpenoids, roxbuterpenes A-D (1, 4, 5, and 24), along with 22 known analogues (2, 3, 6-23, 25, and 26), were isolated from the fruits of R. roxburghii. Their chemical structures were determined on the basis of extensive spectroscopic analyses (including IR, HRESIMS and NMR spectroscopy). The absolute configuration of roxbuterpene A (1) was determined by an X-ray crystallographic analysis. This is the first report of the crystal structure of 5/6/6/6/6-fused system pentacyclic triterpenoid. Notably, roxbuterpenes A and B (1 and 4) possessed the A-ring contracted triterpenoid and nortriterpenoid skeletons with a rare 5/6/6/6/6-fused system, respectively. Compounds 1-7, 11, 13-15, 18-20, 24, and 25 exhibited moderate or potent inhibitory activities against α-glucosidase. Compounds 2, 4, 6, 11, and 14 showed strong activities against α-glucosidase with IC50 values of 8.4 ± 1.6, 7.3 ± 2.2, 13.6 ± 1.4, 0.9 ± 0.4, and 12.5 ± 2.4 µM, respectively (positive control acarbose, 10.1 ± 0.8 µM). Compounds 13, 14, and 16 moderately inhibited the release of NO (nitric oxide) with IC50 values ranging from 25.1 ± 2.0 to 51.4 ± 3.1 µM. Furthermore, the expressions of TNF-α (tumor necrosis factor-α) and IL-6 (interleukin-6) were detected by ELISA (enzyme-linked immunosorbent assay), and compounds 13, 14, and 16 exhibited moderate inhibitory effects on TNF-α and IL-6 release in a dose-dependent manner ranging from 12.5 to 50 µM.

MicroRNA-21 in gynecological cancers: From molecular pathogenesis to clinical significance.

Ovarian, cervical, and endometrial cancers are the three most common gynecological cancer types (GCs). They hold a significant position as the leading causes of mortality among women with cancer-related death. However, GCs are often diagnosed late, severely limiting the efficacy of current treatment options. Thus, there is an urgent, unmet need for innovative experimentation to enhance the clinical treatment of GC patients. MicroRNAs (miRNAs) are a large and varied class of short noncoding RNAs (22 nucleotides in length) that have been shown to play essential roles in various biological processes involved in development. Recent research has shown that miR-211 influences tumorigenesis and cancer formation, adding to our knowledge of the miR-21 dysregulation in GCs. Furthermore, current research that sheds light on the crucial functions of miR-21 may provide supporting evidence for its potential prognostic, diagnostic, and therapeutic applications in the context of GCs. This review will thus focus on the most recent findings concerning miR-21 expression, miR-21 target genes, and the processes behind GCs. In addition, the latest findings that support miR-21's potential use as a non-invasive biomarker and therapeutic agent for detecting and treating cancer will be elucidated in this review. The roles played by various lncRNA/circRNA-miRNA-mRNA axis in GCs are also comprehensively summarized and described in this study, along with any possible implications for how these regulatory networks may contribute to the pathogenesis of GCs. Also, it is crucial to recognize the complexity of the processes involved in tumour therapeutic resistance as a significant obstacle in treating GCs. Furthermore, this review provides an overview of the current state of knowledge regarding the functional significance miR-21 in therapeutic resistance within the context of GCs.

Congenital hepatoblastoma presenting with hepatic arteriovenous fistulas: a case report.

Aim: Congenital hepatoblastoma, a rare malignant liver tumor in infancy, typically presents with abdominal distension or mass. Tumors detected antenatally or during the first three months of age are considered congenital hepatoblastoma. Hepatic arteriovenous fistulas (HAVF) are associated with high mortality in the neonatal period and can be caused by many secondary factors. This case report focuses on a patient with congenital hepatoblastoma accompanied by HAVF, highlighting the clinical and imaging characteristics and management strategies. Case presentation: A term infant presented with sudden tachypnea and heart failure on his first day of life. A cystic-solid mixed lesion in the fetus's liver was detected by an antenatal ultrasound scan. Postnatal digital subtraction angiography confirmed the presence of arteriovenous fistulas, which were treated with trans-arterial embolization. However, despite the intervention, the patient's heart failure did not improve. The patient underwent a left hepatectomy, and hepatoblastoma was discovered by histology of the resected hepatic lobe. Unfortunately, metastases were later discovered in the intracranial and ocular regions. Ultimately, the family decided to discontinue further treatment. Conclusion: Congenital hepatoblastoma presenting with hepatic arteriovenous fistulas has not been previously described. Hepatoblastoma should be considered when alpha-fetoprotein levels show a significant elevation in newborns. Prenatal diagnosis may improve pre- and postnatal management.

Defined Surface Physicochemical Cues Inhibit M1 Polarization of Human Macrophages Using Colloidal Self-Assembled Patterns.

Biophysical and biochemical cues modulate mammalian cell behavior and phenotype simultaneously. Macrophages, indispensable cells in the innate immune system, respond to external threats such as bacterial infections and implanted devices, undergoing the classical M1 polarization to become a pro-inflammatory phenotype. In the study, lipopolysaccharide (LPS)-induced M1 polarization was examined using RAW264.7, THP-1, and primary human PBMCs on a family of artificial extracellular matrix (ECM), named colloidal self-assembled patterns (cSAPs). The results showed that cSAPs were biocompatible, which cannot induce M1 or M2 polarization. Interestingly, specific cSAPs (e.g., cSAP3) suppress the level of M1 polarization (i.e., reduced nitric oxide production, down-regulated gene expression of iNOS, IL-6, TNF-α, IL-1ß, and TLR4, and reduced proportion of CD11b+CD86+ cells). Transcriptome analysis showed that cell adhesion and cell-ECM interaction participated in the M1 polarization, and the mechano-sensitive genes such as PIEZO1 were down-regulated on the cSAP3. More interestingly, these genes were also down-regulated under LPS stimulation, indicating that cells became insensitive to the LPS. The abovementioned results indicate that the defined physicochemical cues can govern macrophage polarization. This study illustrates a potential surface design at biointerface, which is critical in tissue engineering and materiobiology. The outcome is also inspiring in ECM-mediated immune responses.

Microneedle-assisted transdermal delivery of perfluorotripropylamine-based oxygenated emulsion gel loaded with 5-aminolevulinic acid for enhanced photodynamic therapy of cutaneous squamous cell carcinoma.

Topical photodynamic therapy (TPDT) is a clinical treatment for cutaneous squamous cell carcinoma (CSCC). However, the therapeutic efficacy of TPDT for CSCC is significantly weakened by hypoxia, which is caused by the oxygen-poor environment of the skin and CSCC and by the high oxygen consumption of TPDT itself. To overcome these problems, we developed a topically applied perfluorotripropylamine-based oxygenated emulsion gel loaded with the photosensitizer 5-ALA (5-ALA-PBOEG) by a simple ultrasound-assisted emulsion method. With the aid of the microneedle roller, 5-ALA-PBOEG dramatically increased the accumulation of 5-ALA in the epidermis and the dermis, as well as throughout the dermis; a total of 67.6% ± 9.97% of the applied dose penetrated into and through the dermis, which is 19.1±3.2-fold that of the 5-ALA-PBOEG without microneedle treatment group, and 16.9±0.3-fold that of the aminolevulinic acid hydrochloride topical powder treatment group (p<0.001). Meanwhile, PBOEG enhanced the singlet oxygen yield of 5-ALA-induced protoporphyrin IX. The results of in vivo antitumor activity in human epidermoid carcinoma (A431) bearing mice showed that by increasing the oxygen content in tumor tissues, the developed 5-ALA-PBOEG plus microneedle treatment and laser irradiation showed better tumor growth inhibition than the respective control formulations. In addition, the results of safety studies, including the multiple-dose skin irritation study, allergy tests, and skin H&E staining, demonstrated the safety of 5-ALA-PBOEG plus microneedle treatment. In conclusion, the 5-ALA-PBOEG plus microneedle treatment shows great potential in the fight against CSCC and other skin cancers.

The Complex, Unique, and Powerful Imaging Instrument for Dynamics (CUPI2D) at the Spallation Neutron Source (invited).

The Oak Ridge National Laboratory is planning to build the Second Target Station (STS) at the Spallation Neutron Source (SNS). STS will host a suite of novel instruments that complement the First Target Station's beamline capabilities by offering an increased flux for cold neutrons and a broader wavelength bandwidth. A novel neutron imaging beamline, named the Complex, Unique, and Powerful Imaging Instrument for Dynamics (CUPI2D), is among the first eight instruments that will be commissioned at STS as part of the construction project. CUPI2D is designed for a broad range of neutron imaging scientific applications, such as energy storage and conversion (batteries and fuel cells), materials science and engineering (additive manufacturing, superalloys, and archaeometry), nuclear materials (novel cladding materials, nuclear fuel, and moderators), cementitious materials, biology/medical/dental applications (regenerative medicine and cancer), and life sciences (plant-soil interactions and nutrient dynamics). The innovation of this instrument lies in the utilization of a high flux of wavelength-separated cold neutrons to perform real time in situ neutron grating interferometry and Bragg edge imaging-with a wavelength resolution of δλ/λ ≈ 0.3%-simultaneously when required, across a broad range of length and time scales. This manuscript briefly describes the science enabled at CUPI2D based on its unique capabilities. The preliminary beamline performance, a design concept, and future development requirements are also presented.

A new chamigrane sesquiterpene from the rice fermentation of Antrodiella albocinnamomea.

A new chamigrane sesquiterpene, albocimea A (1), and one known compound, 6-hydroxy-8-methoxy-3S,5-dimethylisochroman (2), were isolated from the rice fermentation of the fungus Antrodiella albocinnamomea. The structure of new compound was elucidated by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. Both compounds were evaluated for their cytotoxicity against five human cancer cell lines, but no significant cytotoxicity was found (IC50 values > 40 µM).

A new chamigrane sesquiterpene from the basidiomycete Antrodiella albocinnamomea.

One new chamigrane sesquiterpene, antroalbol A (1), was isolated from the cultures of the higher fungus Antrodiella albocinnamomea. Its structure was established by means of spectroscopic methods, and the absolute configuration of 1 was confirmed by single crystal x-ray diffraction analysis. The compound was evaluated for its cytotoxicity against five human cancer cell lines, but no significant cytotoxicity was found.

Mutual spin-phonon driving effects and phonon eigenvector renormalization in nickel (II) oxide.

The physics of mutual interaction of phonon quasiparticles with electronic spin degrees of freedom, leading to unusual transport phenomena of spin and heat, has been a subject of continuing interests for decades. Despite its pivotal role in transport processes, the effect of spin-phonon coupling on the phonon system, especially acoustic phonon properties, has so far been elusive. By means of inelastic neutron scattering and first-principles calculations, anomalous scattering spectral intensity from acoustic phonons was identified in the exemplary collinear antiferromagnetic nickel (II) oxide, unveiling strong spin-lattice correlations that renormalize the polarization of acoustic phonon. In particular, a clear magnetic scattering signature of the measured neutron scattering intensity from acoustic phonons is demonstrated by its momentum transfer and temperature dependences. The anomalous scattering intensity is successfully modeled with a modified magneto-vibrational scattering cross-section, suggesting the presence of spin precession driven by phonon. The renormalization of phonon eigenvector is indicated by the observed "geometry-forbidden" neutron scattering intensity from transverse acoustic phonon. Importantly, the eigenvector renormalization cannot be explained by magnetostriction but instead, it could result from the coupling between phonon and local magnetization of ions.

Four New Sesquiterpenoids from the Rice Fermentation of Antrodiella albocinnamomea.

Albocimea B-E (1-4), four new sesquiterpenoids, and four known compounds, steperoxide A (5), dankasterone (6), 1H-indole-3-carboxylic acid (7), and (+)-formylanserinone B (8), were isolated from the rice fermentation of the fungus Antrodiella albocinnamomea. The structures of new compounds were elucidated by comprehensive spectroscopic techniques, the planar structures of new compounds were determined by comprehensive spectroscopic techniques, and their absolute configurations were confirmed via gauge-independent atomic orbital calculations (GIAO), calculation of the electronic circular dichroism (ECD), and optical rotation (OR). These were determined by spectroscopic data analysis.

Colloidal Self-Assembled Patterns Maintain the Pluripotency and Promote the Hemopoietic Potential of Human Embryonic Stem Cells.

The generation of blood cells in a significant amount for clinical uses is still challenging. Human pluripotent stem cells-derived hemopoietic cells (hPSC-HCs) are a promising cell source to generate blood cells. Previously, it has been shown that the attached substrates are crucial in the maintenance or differentiation of hPSCs. In this study, a new family of artificial extracellular matrix (ECM) called colloidal self-assembled patterns (cSAPs: #1-#5) was used for the expansion of mouse and human PSCs. The optimized cSAP (i.e., #4 and #5) was selected for subsequent hemopoietic differentiation of human embryonic stem cells (hESCs). Results showed that the hematopoietic potential of hESCs was enhanced approx 3-4 folds on cSAP #5 compared to the flat control. The cell population of hematopoietic progenitors (i.e., CD34+CD43+ cells) and erythroid progenitors (i.e., CD71+GPA+ cells) were enhanced 4 folds at day 8 and 3 folds at day 14. RNA sequencing analysis of cSAP-derived hESCs showed that there were 300 genes up-regulated and 627 genes down-regulated compared to the flat control. The enriched signaling pathways, including up-regulation (i.e., Toll-like receptor, HIF-1a, and Notch) or down-regulation (i.e., FAs, MAPK, JAK/STAT, and TGF-ß) were classic in the maintenance of hESC phenotype Real time PCR confirmed that the expression of focal adhesion (PTK2, VCL, and CXCL14) and MAPK signaling (CAV1) related genes was down-regulated 2-3 folds compared to the flat control. Altogether, cSAP enhances the pluripotency and the hematopoietic potential of hESCs that subsequently generates more blood-like cells. This study reveals the potential of cSAPs on the expansion and early-stage blood cell lineage differentiation of hPSCs.

High Matrix Metalloproteinase 28 Expression is Associated with Poor Prognosis in Pancreatic Adenocarcinoma.

PURPOSE: Pancreatic adenocarcinoma (PAAD) is a devastating disease with high mortality and morbidity. Matrix metalloproteinase 28 (MMP28) has been associated with carcinogenesis of many human cancers. However, little is known about the potential prognostic value and underlying regulatory mechanisms of MMP28 in PAAD. METHODS: The relationship between MMP28 expression level and various clinicopathological parameters was analyzed in TCGA-PAAD cohorts. MMP28-correlated genes in the TCGA-PAAD cohort were identified and enrichment analysis according to the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes was conducted using LinkedOmics. Protein-protein interaction and transcription factors-miRNA co-regulatory networks were constructed with the use of NetworkAnalyst. Then, the distribution of immune cells related to MMP28 expression in blood was analyzed using the Human Protein Atlas, and the tumor microenvironment of PAAD was analyzed by the TIMER 2.0 database. To investigate the biological function of MMP28 in PAAD, siRNA was constructed to knock down the MMP28 gene in vitro. RESULTS: High MMP28 expression is associated with poor overall survival and disease-free survival in PAAD patients. The expression of MMP28 in PAAD is most significantly correlated with KRT19, IL1RN, and ANXA2 genes. Network analysis revealed that MIR-181 family, TAFs, and CDC6 are potential regulators of MMP28. Furthermore, naive CD4+ T cell, naive CD8+ T cell, and mucosal-associated invariant T cell enrichment in blood were correlated with MMP28 expression. Furthermore, high MMP28 expression was correlated with a decrease in B cell, naive CD4+ T cell, naive CD8+ T cell, and endothelial cell presence in the tumor microenvironment in PAAD. Finally, genetic knockdown of MMP28 could restrain the proliferation, migration, and invasion of PAAD cells. CONCLUSION: Our findings indicate that high MMP28 expression in PAAD is associated with cancer progression, invasion, and metastasis. Hence, MMP28 might serve as an independent prognostic biomarker and a prospective therapeutic target for PAAD.

Efficacy and safety of Huaiqihuang granule as adjuvant treatment for primary nephrotic syndrome in children: a meta-analysis and systematic review.

BACKGROUND: Huaiqihuang (HQH) granule is a traditional Chinese herbal complex that has been used as an adjuvant treatment in clinics for the primary nephrotic syndrome (PNS) for many years. However, the effectiveness and safety of HQH have not been systematically discussed. This review aimed to evaluate the effectiveness and safety of HQH in paediatric patients with PNS. METHODS: The following databases were searched from inception to Mar 2019: MEDLINE, Cochrane Library, EMBASE, CNKI, Wanfang Database, the Chinese Scientific Journal Database and the Chinese biomedical literature service system. All the randomized controlled trials (RCTs) eligible for inclusion were included. The primary outcomes were relapse, infection, remission and adverse events. The secondary outcomes included serum immunoglobulin levels (IgA, IgG or IgM), T-lymphocyte subtype (CD3+ , CD4+ , CD8+ , CD4+ /CD8+), IL-10, TNF-α, TNF-γ, total cholesterol and time of proteinuria turning negative. RESULTS: Fourteen RCTs (885 patients) were identified. Treatment with HQH reduced the chance of relapse [relative risk (RR): 0.47; 95% CI: 0.34, 0.66; P < 0.001] and infections (RR: 0.47; 95% CI: 0.35, 0.62; P < 0.001). No significant difference was found in adverse events. HQH also increased the serum levels of IgA [weighted mean difference (WMD): 0.40; 95% CI: 0.20, 0.60; P < 0.001] and IgG (WMD: 1.58; 95% CI: 1.38-1.78; P < 0.001), as well as CD4+ [standard mean difference (SMD): 0.90; 95% CI: 0.12-1.68; P = 0.02], CD3+ (WMD: 4.04; 95% CI: 3.27-4.82; P < 0.001), and the CD4+/CD8+ratio (WMD: 0.31; 95% CI: 0.21-0.41; P < 0.001), but decreased the level of CD8+ cells (WMD: -3.39; 95% CI: -5.73-1.05; P = 0.004). No statistically significant difference was found in IgM (WMD: 0.05; 95% CI: -0.13, 0.24; P = 0.57). CONCLUSIONS: HQH could reduce the rate of relapse and the frequency of infection in children with PNS. No apparent adverse effects were found. Moreover, the beneficial influence of HQH may act through immunomodulation. Additional multi-center, large-sample, high-quality studies are needed to confirm the effectiveness and safety of HQH.

Application of photodynamic therapy in immune-related diseases.

Photodynamic therapy (PDT) is a therapeutic modality that utilizes photodamage caused by photosensitizers and oxygen after exposure to a specific wavelength of light. Owing to its low toxicity, high selectivity, and minimally invasive properties, PDT has been widely applied to treat various malignant tumors, premalignant lesions, and infectious diseases. Moreover, there is growing evidence of its immunomodulatory effects and potential for the treatment of immune-related diseases. This review mainly focuses on the effect of PDT on immunity and its application in immune-related diseases.

Harnessing Colloidal Self-Assembled Patterns (cSAPs) to Regulate Bacterial and Human Stem Cell Response at Biointerfaces In Vitro and In Vivo.

The generation of complex physicochemical signals on the surface of biomedical materials is still challenging despite the fact that a broad range of surface modification methods have been developed over the last few decades. Colloidal self-assembled patterns (cSAPs) are combinations of unique colloids differing in size and surface chemistry acting as building blocks that can be programmed to generate surface patterns with exquisite control of complexity. This study reports on producing a variety of pre-modified colloids for the fabrication of cSAPs as well as post-assembly modifications to yield complex surfaces. The surface of cSAPs presents hierarchical micro- and nanostructures, localized hydrophilic/hydrophobic characteristics, and tunable surface functionality imparted by the individual colloids. The selected cSAPs can control bacterial adhesion (S. aureus, P. aeruginosa, and E. coli) and affect the cell cycle of human bone marrow stem cells (hBMSCs). Moreover, in a mouse subcutaneous model, cSAPs with selective [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium (SBMA) modification can reduce the inflammatory response after being challenged with bacteria. This study reveals that functionalized cSAPs are versatile tools for controlling cellular responses at biointerfaces, which is instructive for biomaterials or biodevices.

Human Platelet Lysate Supports Mouse Skeletal Myoblast Growth but Suppresses Cell Fusion on Nanogrooves.

The fusion of skeletal myoblasts is a critical step in myotube formation and muscle maturation. Previously, we demonstrated that nanogrooves improved myoblast fusion via end-to-end fusion, which in turn generated parallel myotubes. However, the effect of serum components on the end-to-end fusion mechanism is unclear. In the current study, the synergistic effect of nanogrooves and human platelet lysate (hPL) on the growth and fusion of skeletal myoblasts was studied. Four types of nanogrooves (400 and 800 nm width; 100 and 400 nm depth) were used. Cell spreading, growth, and differentiation were screened on these nanogrooves in media formulated with hPL or fetal bovine serum (FBS), along with the flat substrate as a control group. The results showed that the deeper nanogrooves induced better alignment of myoblasts. hPL-adapted skeletal myoblasts (i.e., myoblasts@hPL) showed a smaller cell size with a more elongated morphology than myoblasts@FBS. During cell growth, the expression of myogenic genes (Myf5, MyoD, and MyoG) in myoblasts@hPL was lower than in myoblasts@FBS. During cell differentiation, myoblasts@hPL also expressed a lower level of myogenic and myosin heavy chain (MHC) genes. MHC-positive myoblasts@hPL without myotubes were found on all surfaces. Myomaker, an essential myoblast fusion gene, was upregulated during growth but downregulated during differentiation in myoblasts@hPL. Fibronectin-coated surfaces facilitate cell spreading and growth but still cannot support myoblast@hPL fusion. The results implied that hPL either lacks promotor factors or contains inhibitors on mouse skeletal myoblast fusion. This study reveals the effect of biophysical and biochemical cues on myoblast fusion and their potential for muscle tissue engineering.

A simple in vitro tumor chemosensitivity assay based on cell penetrating peptide tagged luciferase.

The analysis of intracellular ATP can reveal the response of cells to different treatments and is important for individualized medicine. In the present study, we developed a cell penetrating peptides (CPPs) tagged luciferase (TAT-LUC) for tumor chemosensitivity assay. The activity of recombinant TAT-LUC was evaluated using ATP standard solution and tumor cells. This recombinant TAT-LUC was then used for the analysis of sensitivity index (SI) of four strains of tumor cells. The results showed that TAT-LUC could detect less than 10 nM extracellular ATP with a strong correlation between the luminescence intensity and the ATP content (R2 = 0.994). Without cell lysis, the detection limit for intracellular ATP analysis was 40 tumor cells. Furthermore, chemosensitivity of four strains of tumor cells (Skov-3/DDP, A549/DDP, MDA-MB-231, Huh-7) was determined by this assay successfully. The cell penetration ability of TAT-LUC enables the assay not only to reflect drug resistance of tumor cells real-timely but also to minimize the test time, which can be a valuable aid for personalized cancer chemotherapy.