Expanding applications of allogeneic platelets, platelet lysates, and platelet extracellular vesicles in cell therapy, regenerative medicine, and targeted drug delivery.

Platelets are small anucleated blood cells primarily known for their vital hemostatic role. Allogeneic platelet concentrates (PCs) collected from healthy donors are an essential cellular product transfused by hospitals to control or prevent bleeding in patients affected by thrombocytopenia or platelet dysfunctions. Platelets fulfill additional essential functions in innate and adaptive immunity and inflammation, as well as in wound-healing and tissue-repair mechanisms. Platelets contain mitochondria, lysosomes, dense granules, and alpha-granules, which collectively are a remarkable reservoir of multiple trophic factors, enzymes, and signaling molecules. In addition, platelets are prone to release in the blood circulation a unique set of extracellular vesicles (p-EVs), which carry a rich biomolecular cargo influential in cell-cell communications. The exceptional functional roles played by platelets and p-EVs explain the recent interest in exploring the use of allogeneic PCs as source material to develop new biotherapies that could address needs in cell therapy, regenerative medicine, and targeted drug delivery. Pooled human platelet lysates (HPLs) can be produced from allogeneic PCs that have reached their expiration date and are no longer suitable for transfusion but remain valuable source materials for other applications. These HPLs can substitute for fetal bovine serum as a clinical grade xeno-free supplement of growth media used in the in vitro expansion of human cells for transplantation purposes. The use of expired allogeneic platelet concentrates has opened the way for small-pool or large-pool allogeneic HPLs and HPL-derived p-EVs as biotherapy for ocular surface disorders, wound care and, potentially, neurodegenerative diseases, osteoarthritis, and others. Additionally, allogeneic platelets are now seen as a readily available source of cells and EVs that can be exploited for targeted drug delivery vehicles. This article aims to offer an in-depth update on emerging translational applications of allogeneic platelet biotherapies while also highlighting their advantages and limitations as a clinical modality in regenerative medicine and cell therapies.

TAK1 blockade as a therapy for retinal neovascularization.

Retinal neovascularization, or pathological angiogenesis in the retina, is a leading cause of blindness in developed countries. Transforming growth factor-ß-activated kinase 1 (TAK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK) activated by TGF-ß1 and other proinflammatory cytokines. TAK1 is also a key mediator of proinflammatory signals and plays an important role in maintaining vascular integrity upon proinflammatory cytokine stimulation such as TNFα. However, its role in pathological angiogenesis, particularly in retinal neovascularization, remains unclear. Here, we investigate the regulatory role of TAK1 in human endothelial cells responding to inflammatory stimuli and in a rat model of oxygen-induced retinopathy (OIR) featured retinal neovascularization. Using TAK1 knockout human endothelial cells that subjected to inflammatory stimuli, transcriptome analysis revealed that TAK1 is required for activation of NFκB signaling and mediates its downstream gene expression related to endothelial activation and angiogenesis. Moreover, pharmacological inhibition of TAK1 by 5Z-7-oxozeaenol attenuated angiogenic activities of endothelial cells. Transcriptome analysis also revealed enrichment of TAK1-mediated NFκB signaling pathway in the retina of OIR rats and retinal neovascular membrane from patients with proliferative diabetic retinopathy. Intravitreal injection of 5Z-7-oxozeaenol significantly reduced hypoxia-induced inflammation and microglial activation, thus attenuating aberrant retinal angiogenesis in OIR rats. Our data suggest that inhibition of TAK1 may have therapeutic potential for the treatment of retinal neovascular pathologies.

Theranostic doxorubicin encapsulated FeAu alloy@metal-organic framework nanostructures enable magnetic hyperthermia and medical imaging in oral carcinoma.

Metal-organic frameworks (MOFs) have emerged as attractive candidates in cancer theranostics due to their ability to envelop magnetic nanoparticles, resulting in reduced cytotoxicity and high porosity, enabling chemodrug encapsulation. Here, FeAu alloy nanoparticles (FeAu NPs) are synthesized and coated with MIL-100(Fe) MOFs to fabricate FeAu@MOF nanostructures. We encapsulated Doxorubicin within the nanostructures and evaluated the suitability of this platform for medical imaging and cancer theranostics. FeAu@MOF nanostructures (FeAu@MIL-100(Fe)) exhibited superparamagnetism, magnetic hyperthermia behavior and displayed DOX encapsulation and release efficiency of 69.95 % and 97.19 %, respectively, when stimulated with alternating magnetic field (AMF). In-vitro experiments showed that AMF-induced hyperthermia resulted in 90 % HSC-3 oral squamous carcinoma cell death, indicating application in cancer theranostics. Finally, in an in-vivo mouse model, FeAu@MOF nanostructures improved image contrast, reduced tumor volume by 30-fold and tumor weight by 10-fold, which translated to enhancement in cumulative survival, highlighting the prospect of this platform for oral cancer treatment.

A Sandwich-Type Electrochemical Immunosensor for Insulin Detection Based on Au-Adhered Cu5 Zn8 Hollow Porous Carbon Nanocubes and AuNP Deposited Nitrogen-Doped Holey Graphene.

Rapid, accurate, and sensitive insulin detection is crucial for managing and treating diabetes. A simple sandwich-type electrochemical immunosensor is engineered using gold nanoparticle (AuNP)-adhered metal-organic framework-derived copper-zinc hollow porous carbon nanocubes (Au@Cu5 Zn8 /HPCNC) and AuNP-deposited nitrogen-doped holey graphene (NHG) are used as a dual functional label and sensing platform. The results show that identical morphology and size of Au@Cu5 Zn8 /HPCNC enhance the electrocatalytic active sites, conductivity, and surface area to immobilize the detection antibodies (Ab2 ). In addition, AuNP/NHG has the requisite biocompatibility and electrical conductivity, which facilitates electron transport and increases the surface area of the capture antibody (Ab1 ). Significantly, Cu5 Zn8 /HPCNC exhibits necessary catalytic activity and sensitivity for the electrochemical reduction of H2 O2 using (i-t) amperometry and improves the electrochemical response in differential pulse voltammetry. Under optimal conditions, the immunosensor for insulin demonstrates a wide linear range with a low detection limit and viable specificity, stability, and reproducibility. The platform's practicality is evaluated by detecting insulin in human serum samples. All these characteristics indicate that the Cu5 Zn8 /HPCNC-based biosensing strategy may be used for the point-of-care assay of diverse biomarkers.

The Effects of Different Dynamic Culture Systems on Cell Proliferation and Osteogenic Differentiation in Human Mesenchymal Stem Cells.

The culture environment plays an important role for stem cells' cultivation. Static or dynamic culture preserve differential potentials to affect human mesenchymal stem cells' (hMSCs) proliferation and differentiation. In this study, hMSCs were seeded on fiber disks and cultured in a bidirectional-flow bioreactor or spinner-flask bioreactor with a supplement of osteogenic medium. The hMSCs' proliferation, osteogenic differentiation, and extracellular matrix deposition of mineralization were demonstrated. The results showed that the spinner flask improved cell viability at the first two weeks while the bidirectional-flow reactor increased the cell proliferation of hMSCs through the four-week culture period. Despite the flow reactor having a higher cell number, a lower lactose/glucose ratio was noted, revealing that the bidirectional-flow bioreactor provides better oxygen accessibility to the cultured cells/disk construct. The changes of calcium ions in the medium, the depositions of Ca2+ in the cells/disk constructs, and alkaline phosphate/osteocalcin activities showed the static culture of hMSCs caused cells to mineralize faster than the other two bioreactors but without cell proliferation. Otherwise, cells were distributed uniformly with abundant extracellular matrix productions using the flow reactor. This reveals that the static and dynamic cultivations regulated the osteogenic process differently in hMSCs. The bidirectional-flow bioreactor can be used in the mass production and cultivation of hMSCs for applications in bone regenerative medicine.

New Combination/Application of Polymer-Based Nanoparticles for Biomedical Engineering.

Polymer-based nanoparticles (PNPs) are attractive in part due to their ultra-small size, versatility and target specificity. Therefore, PNPs have been increasingly used in a variety of biomedical applications including diagnoses and therapeutic treatment. In this chapter, we focus on the recent studies (within 5 years) with some new ideas/agent's application in biomedical field and roughly divide applications of PNPs into four categories: (1) Delivery, (2) In vivo imaging, (3) Therapies, and (4) Other applications. First, we introduce how PNPs can enhance the treatment and delivery efficiency of therapeutic agent. Second, how PNPs can be used to help in vivo imaging system for disease tracking and monitor. Then, we reveal some novel PNPs which is able to function as an agent in photodynamic, photothermal, sonodynamic and neuron capture therapy. Furthermore, we also mention some interesting applications of PNPs for biomedical field in individual form or cluster employment, such as immunoswitch particles, surface fabrication. Finally, the challenges and future development of PNPs are also discussed. In delivery section, we focus on how polymer "can be used" as vehicles in delivery application. But, in the section of imaging and therapies, we carried on how polymer as an "adjuvant" for functional enhancement. The biodegradable property of PNPs is the feature that they can be controllable for itself degradation and drug release as a chief actor. Besides, in imaging and therapies application, PNPs can be the support role for helping contrast agent or photo/sonosensitizer to enlarge their imaging or therapeutic effect.

Ocular Drug Delivery: Role of Degradable Polymeric Nanocarriers for Ophthalmic Application.

Ocular drug delivery has been a major challenge for clinical pharmacologists and biomaterial scientists due to intricate and unique anatomical and physiological barriers in the eye. The critical requirement varies from anterior and posterior ocular segments from a drug delivery perspective. Recently, many new drugs with special formulations have been introduced for targeted delivery with modified methods and routes of drug administration to improve drug delivery efficacy. Current developments in nanoformulations of drug carrier systems have become a promising attribute to enhance drug retention/permeation and prolong drug release in ocular tissue. Biodegradable polymers have been explored as the base polymers to prepare nanocarriers for encasing existing drugs to enhance the therapeutic effect with better tissue adherence, prolonged drug action, improved bioavailability, decreased toxicity, and targeted delivery in eye. In this review, we summarized recent studies on sustained ocular drug/gene delivery and emphasized on the nanocarriers made by biodegradable polymers such as liposome, poly lactic-co-glycolic acid (PLGA), chitosan, and gelatin. Moreover, we discussed the bio-distribution of these nanocarriers in the ocular tissue and their therapeutic applications in various ocular diseases.

A Gelatin Hydrogel-Containing Nano-Organic PEI⁻Ppy with a Photothermal Responsive Effect for Tissue Engineering Applications.

The introduction and designing of functional thermoresponsive hydrogels have been recommended as recent potential therapeutic approaches for biomedical applications. The development of bioactive materials such as thermosensitive gelatin-incorporated nano-organic materials with a porous structure and photothermally triggerable and cell adhesion properties may potentially achieve this goal. This novel class of photothermal hydrogels can provide an advantage of hyperthermia together with a reversibly transformable hydrogel for tissue engineering. Polypyrrole (Ppy) is a bioorganic conducting polymeric substance and has long been used in biomedical applications owing to its brilliant stability, electrically conductive features, and excellent absorbance around the near-infrared (NIR) region. In this study, a cationic photothermal triggerable/guidable gelatin hydrogel containing a polyethylenimine (PEI)⁻Ppy nanocomplex with a porous microstructure was established, and its physicochemical characteristics were studied through dynamic light scattering, scanning electronic microscopy, transmission electron microscopy, an FTIR; and cellular interaction behaviors towards fibroblasts incubated with a test sample were examined via MTT assay and fluorescence microscopy. Photothermal performance was evaluated. Furthermore, the in vivo study was performed on male Wistar rat full thickness excisions model for checking the safety and efficacy of the designed gelatin⁻PEI⁻Ppy nanohydrogel system in wound healing and for other biomedical uses in future. This photothermally sensitive hydrogel system has an NIR-triggerable property that provides local hyperthermic temperature by PEI⁻Ppy nanoparticles for tissue engineering applications. Features of the designed hydrogel may fill other niches, such as being an antibacterial agent, generation of free radicals to further improve wound healing, and remodeling of the promising photothermal therapy for future tissue engineering applications.

Herbal Supplement in a Buffer for Dry Eye Syndrome Treatment.

Dry eye syndrome (DES) is one of the most common types of ocular diseases. There is a major need to treat DES in a simple yet efficient way. Artificial tears (AT) are the most commonly used agents for treating DES, but are not very effective. Herbal extractions of ferulic acid (FA), an anti-oxidant agent, and kaempferol (KM), an anti-inflammatory reagent, were added to buffer solution (BS) to replace ATs for DES treatment. The cytotoxicity and anti-inflammatory effects were examined in vitro by co-culture with human corneal epithelial cells (HCECs) to obtain the optimal concentration of KM and FA for treating HCECs. Physical properties of BS, such as pH value, osmolality, and refractive index were also examined. Then, rabbits with DES were used for therapeutic evaluation. Tear production, corneal damage, and ocular irritation in rabbits' eyes were examined. The non-toxic concentrations of KM and FA for HCEC cultivation over 3 days were 1 µM and 100 µM, respectively. Live/dead stain results also show non-toxicity of KM and FA for treating HCECs. Lipopolysaccharide-stimulated HCECs in inflammatory conditions treated with 100 µM FA and 1 µM KM (FA100/KM1) showed lower IL-1B, IL-6, IL-8, and TNFα expression when examined by real-time PCR. The BS with FA100/KM1 had neutral pH, and a similar osmolality and refractive index to human tears. Topical delivery of BS + FA100/KM1 showed no irritation to rabbit eyes. The corneal thickness in the BS + FA100/KM1 treated group was comparable to normal eyes. Results of DES rabbits treated with BS + FA100/KM1 showed less corneal epithelial damage and higher tear volume than the normal group. In conclusion, we showed that the combination of FA (100 µM) and KM (1 µM) towards treating inflamed HCECs had an anti-inflammatory effect, and it is effective in treating DES rabbits when BS is added in combination with these two herbal supplements and used as a topical eye drop.

Cranioplasty Using a Novel Osteoconductive Scaffold and Platelet Gel.

BACKGROUND: Commonly used materials for cranioplasty include autogenous bone grafts, methyl methacrylate, and titanium mesh. We evaluated a novel osteoconductive scaffold [N-isopropylacrylamide cross-linked with acrylic acid using γ-rays (ANa powder)] mixed with platelet gel for cranioplasty. METHODS: ANa powder mixed with platelet gel was implanted into a 15 × 15-mm, full-thickness calvarial bone defect in 5 New Zealand white rabbits. ANa powder mixed with phosphate-buffered saline was implanted in 5 rabbits. The calvarial bone defect was left unreconstructed in another 5 rabbits. Twelve weeks after surgery, computed tomography examination was used to evaluate the radiographic evidence of bone healing in vivo. Bone specimens were then retrieved for histologic study. RESULTS: The ANa scaffold mixed with platelet gel is biocompatible, biodegradable, and both osteoconductive and osteoinductive, leading to progressive growth of new bone into the calvarial bone defect. CONCLUSION: The use of this novel osteoconductive scaffold combined with osteoinductive platelet gel offers a valuable alternative for the reconstruction of calvarial bone defects.

Animal models to assess the therapeutic efficacy of human serum and serum-converted platelet lysates for dry eye syndrome: Seeing is believing.

There is much interest in the clinical use of serum-converted human blood or platelet concentrates in regenerative medicine, most specifically for wound healing and tissue repair of soft and hard tissues. The scientific rationale supporting the clinical efficacy of these preparations is based on the expectation that their physiological mixture of natural growth factors can orchestrate cell expansion and differentiation in vivo. However, a lack of standardization and regulatory oversight of these blood materials maintain a perception of uncertainty in the scientific and medical community on the value of these preparations for some clinical indications. More studies are needed to understand the mechanism of action underlying their expected efficacy and standardize their use, and benefit from their biological versatility. One application of serum is as eye drop for treating dry eye syndrome (DES), a multifactorial disease of the ocular surface, which has a prevalence of 15% of more in the population. DES can lead to chronic inflammation of the ocular surface, surface impairment in the cornea and conjunctiva, and, in patients with Sjogren syndrome, result in a disruption of the ocular surface epithelium. Objective experimental assessment of safety and efficacy of serum eye drops can help establish scientific rationale in optimal product composition and use. This can be achieved, first, through cell cultures with relevant cell models, before considering, then, animal studies using DES animal models. Several models have been evaluated and are reported in this concise review. The model we have developed encompasses the use of rabbits, where their eyes are treated with 0.1% benzalkonium chloride (BAC), a common preservative in ophthalmic agents, 3 times daily for 4 weeks. This relatively mild treatment results in moderate DES pathology, with a stable shortage of tear secretion throughout a 7-week study period, which we found suitable for assessing efficacy of serum eye drops.

Zwitterionic modified and freeze-thaw reinforced foldable hydrogel as intraocular lens for posterior capsule opacification prevention.

Posterior capsule opacification (PCO) is a predominant postoperative complication, often leading to visual impairment due to the aberrant proliferation and adhesion of lens epithelial cells (LECs) and protein precipitates subsequent to intraocular lens (IOL) implantation. To address this clinical issue, a foldable and antifouling sharp-edged IOL implant based on naturally-derived cellulose hydrogel is synthesized. The mechanical strength and transparency of the hydrogel is enhanced via repeated freeze-thaw (FT) cycles. The incorporated zwitterionic modifications can remarkably prevent the incidence of PCO by exhibiting proteins repulsion and cell anti-adhesion properties. The graft of dopamine onto both the haptic and the periphery of the posterior surface ensures the adhesion of the hydrogel to the posterior capsule and impedes the migration of LECs without compromising transparency. In in vivo study, the zwitterionic modified foldable hydrogel exhibits uveal and capsular biocompatibility synchronously with no signs of inflammatory response and prevent PCO formation, better than that of commercialized and PEG-modified IOL. With foldability, endurability, antifouling effect, and adhesive to posterior capsule, the reported hydrogel featuring heterogeneous surface design displays great potential to eradicate PCO and attain post-operative efficacy after cataract surgery.

Enhancing wound healing and adhesion through dopamine-assisted gelatin-silica hybrid dressings.

Gelatin, widely employed in hydrogel dressings, faces limitations when used in high fluid environments, hindering effective material adhesion to wound sites and subsequently reducing treatment efficacy. The rapid degradation of conventional hydrogels often results in breakdown before complete wound healing. Thus, there is a pressing need for the development of durable adhesive wound dressings. In this study, 3-glycidoxypropyltrimethoxysilane (GPTMS) was utilized as a coupling agent to create gelatin-silica hybrid (G-H) dressings through the sol-gel method. The coupling reaction established covalent bonds between gelatin and silica networks, enhancing structural stability. Dopamine (DP) was introduced to this hybrid (G-H-D) dressing to further boost adhesiveness. The efficacy of the dressings for wound management was assessed through in-vitro and in-vivo tests, along with ex-vivo bioadhesion testing on pig skin. Tensile bioadhesion tests demonstrated that the G-H-D material exhibited approximately 2.5 times greater adhesion to soft tissue in wet conditions compared to pure gelatin. Moreover, in-vitro and in-vivo wound healing experiments revealed a significant increase in wound healing rates. Consequently, this material shows promise as a viable option for use as a moist wound dressing.

Assessment of cardiac adverse events following COVID-19 vaccination by speckle tracking echocardiography.

Cardiac discomfort has been reported periodically in COVID-19-vaccinated individuals. Thus, this study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Totally, 121 subjects who received at least one dose of vaccine within 6 weeks underwent laboratory tests, electrocardiogram (ECG), and echocardiogram. Two-dimensional speckle tracking echocardiography (2D-STE) was implemented to analyze changes in the left ventricular myocardium. After vaccination, 66 individuals (55.4 ± 17.4 years) developed cardiac discomforts, such as chest tightness, palpitations, dyspnea, and chest pain. The ECG readings exhibited both premature ventricular contractions and premature atrial contractions (n = 24, 36.4%), while none of the individuals in the control group manifested signs of cardiac arrhythmia. All had normal serum levels of creatine phosphokinase, creatine kinase myocardial band, troponin, N-terminal pro b-type natriuretic peptide, platelets, and D-dimer. Left ventricular ejection fraction in the symptomatic group (71.41% ± 7.12%) and the control group (72.18% ± 5.11%) (p = 0.492) were normal. Use of 2D-STE presented global longitudinal strain (GLS) and global circumferential strain (GCS) was reduced in the symptomatic group (17.86% ± 3.22% and 18.37% ± 5.22%) compared to the control group (19.54% ± 2.18% and 20.73% ± 4.09%) (p = 0.001 and p = 0.028). COVID-19 vaccine-related cardiac adverse effects can be assessed early by 2D-STE. The prognostic implications of GLS and GCS enable the evaluation of subtle changes in myocardial function after vaccination.

Development and functional evaluation of a hyaluronic acid coated nano-formulation with kaempferol as a novel intra-articular agent for Knee Osteoarthritis treatment.

Knee osteoarthritis (OA) involves articular cartilage degradation driven mainly by inflammation. Kaempferol (KM), known for its anti-inflammatory property, holds potential for OA treatment. This study investigated the potential of hyaluronic acid (HA)-coated gelatin nanoparticles loaded with KM (HA-KM GNP) for treating knee OA. KM was encapsulated into gelatin nanoparticles (KM GNP) and then coated with HA to form HA-KM GNPs. Physical properties were characterized, and biocompatibility and cellular uptake were assessed in rat chondrocytes. Anti-inflammatory and chondrogenic properties were evaluated using IL-1ß-stimulated rat chondrocytes, compared with HA-coated nanoparticles without KM (HA GNP) and KM alone. Preclinical efficacy was tested in an anterior cruciate ligament transection (ACLT)-induced knee OA rat model treated with intra-articular injection of HA-KM GNP. Results show spherical HA-KM GNPs (88.62 ± 3.90 nm) with positive surface charge. Encapsulation efficiency was 98.34 % with a sustained release rate of 18 % over 48 h. Non-toxic KM concentration was 2.5 µg/mL. In IL-1ß-stimulated OA rat chondrocytes, HA-KM GNP significantly down-regulated RNA expression of IL-1ß, TNF-α, COX-2, MMP-9, and MMP-13, while up-regulating SOX9 compared to HA GNP, and KM. In vivo imaging demonstrated significantly higher fluorescence intensity within rat knee joints for 3 hours post HA-KM GNP injection compared with KM GNP (185.2% ± 34.1% vs. 45.0% ± 16.7%). HA-KM GNP demonstrated significant effectiveness in reducing subchondral sclerosis, attenuating inflammation, inhibiting matrix degradation, restoring cartilage thickness, and reducing the severity of OA in the ACLT rat model. In conclusion, HA-KM GNP holds promise for knee OA therapy.

Injectable cross-linked hyaluronic acid hydrogels with epigallocatechin gallate loading as vitreous substitutes.

Hyaluronic acid (HA) serves as a vitreous substitute owing to its ability to mimic the physical functions of native vitreous humor. However, pure HA hydrogels alone do not provide sufficient protection against potential inflammatory risks following vitrectomy. In this study, HA was crosslinked with 1,4-butanediol diglycidyl ether (BDDE) to form HA hydrogels (HB). Subsequently, the anti-inflammatory agent epigallocatechin gallate (EGCG) was added to the hydrogel (HBE) for ophthalmic applications as a vitreous substitute. The characterization results indicated the successful preparation of HB with transparency, refractive index, and osmolality similar to those of native vitreous humor, and with good injectability. The anti-inflammatory ability of HBE was also confirmed by the reduced expression of inflammatory genes in retinal pigment epithelial cells treated with HBE compared with those treated with HB. In a New Zealand white rabbit model undergoing vitreous substitution treatment, HBE 50 (EGCG 50 µM addition) exhibited positive results at 28 days post-surgery. These outcomes included restored intraocular pressure, improved electroretinogram responses, minimal increase in corneal thickness, and no inflammation during histological examination. This study demonstrated the potential of an injectable HA-BDDE cross-linked hydrogel containing EGCG as a vitreous substitute for vitrectomy applications, offering prolonged degradation time and anti-inflammatory effects postoperatively.

NIR-Responsive Methotrexate-Modified Iron Selenide Nanorods for Synergistic Magnetic Hyperthermic, Photothermal, and Chemodynamic Therapy.

Breast cancer is a malignant tumor with a high mortality rate among women. Therefore, it is necessary to develop novel therapies to effectively treat this disease. In this study, iron selenide nanorods (FeSe2 NRs) were designed for use in magnetic hyperthermic, photothermal, and chemodynamic therapy (MHT/PTT/CDT) for breast cancer. To illustrate their efficacy, FeSe2 NRs were modified with the chemotherapeutic agent methotrexate (MTX). MTX-modified FeSe2 (FeSe2-MTX) exhibited excellent controlled drug release properties. Fe2+ released from FeSe2 NRs induced the release of •OH from H2O2 via a Fenton/Fenton-like reaction, enhancing the efficacy of CDT. Under alternating magnetic field (AMF) stimulation and 808 nm laser irradiation, FeSe2-MTX exerted potent hyperthermic and photothermal effects by suppressing tumor growth in a breast cancer nude mouse model. In addition, FeSe2 NRs can be used for magnetic resonance imaging in vivo by incorporating their superparamagnetic characteristics into a single nanomaterial. Overall, we presented a novel technique for the precise delivery of functional nanosystems to tumors that can enhance the efficacy of breast cancer treatment.

Nanotechnology in the regulation of stem cell behavior.

Stem cells are known for their potential to repair damaged tissues. The adhesion, growth and differentiation of stem cells are likely controlled by the surrounding microenvironment which contains both chemical and physical cues. Physical cues in the microenvironment, for example, nanotopography, were shown to play important roles in stem cell fate decisions. Thus, controlling stem cell behavior by nanoscale topography has become an important issue in stem cell biology. Nanotechnology has emerged as a new exciting field and research from this field has greatly advanced. Nanotechnology allows the manipulation of sophisticated surfaces/scaffolds which can mimic the cellular environment for regulating cellular behaviors. Thus, we summarize recent studies on nanotechnology with applications to stem cell biology, including the regulation of stem cell adhesion, growth, differentiation, tracking and imaging. Understanding the interactions of nanomaterials with stem cells may provide the knowledge to apply to cell-scaffold combinations in tissue engineering and regenerative medicine.

Inhibition of microRNA-328 Increases Ocular Mucin Expression and Conjunctival Goblet Cells.

We previously reported anti-miR-328 therapy for dry eye disease (DED). Since decreased mucin secretion is a risk factor for DED, we aimed to explore whether anti-miR-328 affects mucin expression and goblet cells. MiR-328 was increased in goblet cells when they were under desiccating stress or treated with benzalkonium chloride (BAC), both of which are risk factors for DED. Based on bioinformatics tool results, miR-328 was predicted to directly target the transcription factor CREB1 that has been known to promote the expression of mucin5AC. The inhibitory effect of miR-328 on CREB1 was confirmed by the transfection assay. A miR-328 binding site on the CREB1 gene was confirmed by the luciferase assay. Furthermore, anti-miR-328 increased CREB1 and mucin5AC in cultured goblet cells according to qPCR, Western blot, and IF staining experiments. Anti-miR-328 increased mucin5AC secretion from the cultured goblet cells based on an ELISA assay for the cultured medium. Finally, impression cytology data revealed anti-miR-328 increased conjunctival goblet cells in the DED rabbits induced by BAC. In conclusion, anti-miR-328 increases CREB1 expression leading to an increase in mucin5AC production and secretion. Furthermore, anti-miR-328 also increases conjunctival goblet cells. These results warrant the further development of anti-miR-328 therapy for DED.

Synthesis of Methotrexate-Loaded Dumbbell-Shaped Titanium Dioxide/Gold Nanorods Coated with Mesoporous Silica and Decorated with Upconversion Nanoparticles for Near-Infrared-Driven Trimodal Cancer Treatment.

This study prepared dumbbell-shaped titanium dioxide (TiO2)/gold nanorods (AuNRs) coated with mesoporous silica shells (mS) (AuNRs-TiO2@mS). Methotrexate (MTX) was further loaded into the AuNRs-TiO2@mS, and then upconversion nanoparticles (UCNPs) were decorated to form AuNRs-TiO2@mS-MTX: UCNP nanocomposites. TiO2 is used as an intense photosensitizer (PS) to produce cytotoxic reactive oxygen species (ROS), leading to photodynamic therapy (PDT). Concurrently, AuNRs exhibited intense photothermal therapy (PTT) effects and photothermal conversion efficiency. In vitro results suggested that these nanocomposites can kill oral cancer cells (HSC-3) without toxicity through irradiation of NIR laser, owing to the synergistic effect. The in vivo studies indicated that these nanocomposites exhibited excellent antitumor effects through synergistic PDT/PTT/chemotherapy under a near-infrared (NIR) 808 nm laser irradiation. Thus, these AuNRs-TiO2@mS: UCNP nanocomposites have great potential to undergo deep tissue penetration with enhanced synergistic effects through NIR-triggered light for cancer treatment.