Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration.

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.

Neural correlates of breath work, mental imagery of yoga postures, and meditation in yoga practitioners: a functional near-infrared spectroscopy study.

Objective: Previous research has shown numerous health benefits of yoga, a multicomponent physical and mental activity. The three important aspects of both traditional and modern yoga are breath work, postures, and meditation. However, the neural mechanisms associated with these three aspects of yoga remain largely unknown. The present study investigated the neural underpinnings associated with each of these three yoga components in long- and short-term yoga practitioners to clarify the neural advantages of yoga experience, aiming to provide a more comprehensive understanding of yoga's health-promoting effects. Methods: Participants were 40 Chinese women, 20 with a long-term yoga practice and 20 with a short-term yoga practice. Functional near-infrared spectroscopy was conducted while participants performed abdominal breathing, mental imagery of yoga postures, and mindfulness meditation. The oxygenated hemoglobin concentrations activated in the brain during these three tasks were used to assess the neural responses to the different aspects of yoga practice. The self-reported mastery of each yoga posture was used to assess the advantages of practicing yoga postures. Results: Blood oxygen levels in the dorsolateral prefrontal cortex during breath work were significantly higher in long-term yoga practitioners than in short-term yoga practitioners. In the mental imagery of yoga postures task, self-reported data showed that long-term yoga practitioners had better mastery than short-term practitioners. Long-term yoga practitioners demonstrated lower activation in the ventrolateral prefrontal cortex, with lower blood oxygen levels associated with performing this task, than short-term yoga practitioners. In the mindfulness meditation task, blood oxygen levels in the orbitofrontal cortex and the ventrolateral prefrontal cortex were significantly higher in long-term yoga practitioners than in short-term yoga practitioners. Conclusion: The three core yoga components, namely, yogic breathing, postures, and meditation, showed differences and similarities in the activation levels of the prefrontal cortex. Long-term practice of each component led to the neural benefits of efficient activation in the prefrontal cortex, especially in the dorsolateral prefrontal cortex, orbitofrontal cortex, and ventrolateral prefrontal cortex.

3D-printed bredigite scaffolds with ordered arrangement structures promote bone regeneration by inducing macrophage polarization in onlay grafts.

Bone tissue engineering scaffolds may provide a potential strategy for onlay bone grafts for oral implants. For determining the fate of scaffold biomaterials and osteogenesis effects, the host immune response is crucial. In the present study, bredigite (BRT) bioceramic scaffolds with an ordered arrangement structure (BRT-O) and a random morphology (BRT-R) were fabricated. The physicochemical properties of scaffolds were first characterized by scanning electron microscopy, mechanical test and micro-Fourier transform infrared spectroscopy. In addition, their osteogenic and immunomodulatory properties in an onlay grafting model were investigated. In vitro, the BRT-O scaffolds facilitated the macrophage polarization towards a pro-regenerative M2 phenotype, which subsequently facilitated the migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. In vivo, an onlay grafting model was successfully established in the cranium of rabbits. In addition, the BRT-O scaffolds grafted on rabbit cranium promoted bone regeneration and CD68 + CD206 + M2 macrophage polarization. In conclusion, the 3D-printed BRT-O scaffold presents as a promising scaffold biomaterial for onlay grafts by regulating the local immune microenvironment.

Developing and Validating an Intelligent Mouth-Opening Training Device: A New Solution for Restricted Mouth Opening.

Restricted mouth opening (trismus) is one of the most common complications following head and neck cancer treatment. Early initiation of mouth-opening exercises is crucial for preventing or minimizing trismus. Current methods for these exercises predominantly involve finger exercises and traditional mouth-opening training devices. Our research group successfully designed an intelligent mouth-opening training device (IMOTD) that addresses the limitations of traditional home training methods, including the inability to quantify mouth-opening exercises, a lack of guided training resulting in temporomandibular joint injuries, and poor training continuity leading to poor training effect. For this device, an interactive remote guidance mode is introduced to address these concerns. The device was designed with a focus on the safety and effectiveness of medical devices. The accuracy of the training data was verified through piezoelectric sensor calibration. Through mechanical analysis, the stress points of the structure were identified, and finite element analysis of the connecting rod and the occlusal plate connection structure was conducted to ensure the safety of the device. The findings support the effectiveness of the intelligent device in rehabilitation through preclinical experiments when compared with conventional mouth-opening training methods. This intelligent device facilitates the quantification and visualization of mouth-opening training indicators, ensuring both the comfort and safety of the training process. Additionally, it enables remote supervision and guidance for patient training, thereby enhancing patient compliance and ultimately ensuring the effectiveness of mouth-opening exercises.

Free vascularized fibula leads to hallux toe flexion deformity due to ischemic muscle contracture of flexor hallucis longus.

BACKGROUND: This study aimed to investigate the incidence of toe flexion deformity after fibular free flap transplantation and to analyze the etiology of the deformity. METHODS: Fifty patients underwent vascularized fibular free flap transplantation were retrospectively included. Statistical analysis examined correlations between deformity occurrence and resected fibula length and residual distal fibula length using the χ2 test. Doppler ultrasound and anatomical evaluations were conducted. RESULTS: Flexion deformity of the first toe was observed in all patients (100%), exacerbated by ankle dorsiflexion. χ2 test revealed no significant correlation between fibula length, distal residual fibula length, and flexion deformity. Doppler ultrasound revealed elevated echoes and blurred textures in the flexor hallucis longus post-fibular transplantation, while anatomical evaluation confirmed the peroneal artery as its primary nutrient supplier. CONCLUSION: This study reports a 100% incidence of toe flexion deformity post-transplantation. The deformity correlated strongly with ischemic contracture of the flexor hallucis longus.

Characteristics of meat flavoring prepared using hydrolyzed plant protein mix by three different heating processes.

Meat flavoring was prepared using mainly enzymatic hydrolysate of plant protein mix, VB1, cysteine, and glucose by three heating processes, including A (80 °C-140 min), B (two-stage, 80 °C-30 min/120 °C-30 min), and C (120 °C-40 min). The A-, B-, and C-heated samples exhibited the strongest fatty and weakest meaty, the strongest meaty and kokumi, and the strongest roasted and bitterness characteristics, respectively. PLS-DA for free amino acids with TAVs and that for SPME/GC-MS results with GC-O and OAVs, suggested three amino acids and eight flavor compounds contributed significantly in differentiating taste or aroma attributes of the three heated samples. Molecular weight distribution and degree of amino substitution suggested 1-5 kDa peptides contributed to kokumi taste. Overall, C- and A-heating exhibited the highest rates in Maillard reaction and lipid oxidation, respectively, while those of B heating were between these two heating processes and responsible for better flavor of meat flavoring.

Bredigite-Based Bioactive Nerve Guidance Conduit for Pro-Healing Macrophage Polarization and Peripheral Nerve Regeneration.

Structural and functional healing of peripheral nerves damaged by trauma or chronic disease remain major clinical challenges, requiring the development of an effective nerve guidance conduit (NGC). The present study investigates a NGC fabrication strategy based on bredigite (BRT, Ca7MgSi4O16) bioceramic for the treatment of peripheral nerve injury. Here, BRT bioceramic shows good biocompatibility and sustainable release of Ca2+, Mg2+, and Si4+ ions. Both BRT extracts and BRT-incorporating electrospun membranes promote the proliferation and myelination potential of RSC96 cells, as well as accelerate vascular formation by human umbilical vein endothelial cells. Notably, BRT facilitates RAW 264.7 cell polarization to the pro-healing phenotype under LPS-induced inflammatory stimulation. More importantly, the macrophages activated by BRT in turn promote RSC96 cell migration and remyelination. In a rat sciatic nerve defect model, improved electrophysiological performance and alleviated gastrocnemius muscle atrophy are observed at 12 weeks post-implantation. Further experiments verify that BRT-loaded NGC facilitates axonal regrowth and revascularization with high M2-like macrophage infiltration. These findings support the beneficial effects of BRT for creating a pro-healing immune microenvironment and orchestrating multicellular processes associated with functional nerve regeneration, indicating the potential of rationally engineered bioceramics as safe, effective, and economical materials for peripheral nerve repair.

Application of action observation therapy in stroke rehabilitation: A systematic review.

BACKGROUND: Numerous studies have described the positive effects of action observation therapy (AOT) on motor recovery among patients with stroke. However, there is no standardized procedure for when and how to intervene with AOT. OBJECTIVES: Thus, we reviewed and analyzed previous studies to provide a guideline for the application of AOT in stroke rehabilitation. METHOD: We searched PubMed, Cochrane Library, and EMBASE from inception to October 31 2022, using title and abstract search terms of "action observation" and "stroke" or "hemiplegia." Of 4108 potential articles, 29 articles (sample size = 429 in AOT groups; sample size = 423 in control groups) that met inclusion criteria were included in final analyses. RESULTS: The results suggested starting adjuvant AOT > 23 days after stroke onset and conducting 30-40 min/session, 3-5 times/week for at least 4 weeks. CONCLUSION: Based on our results, many factors will impact the effect of AOT on stroke rehabilitation, when to apply (timing) and how to apply (frequency, single, and total duration) should be fully considered when applying AOT as adjuvant therapy in stroke rehabilitation.

Cancer cell-derived extracellular vesicles drive pre-metastatic niche formation of lymph node via IFNGR1/JAK1/STAT1-activated-PD-L1 expression on FRCs in head and neck cancer.

OBJECTIVE: The aim of this study is to evaluate the role of FRCs regulated by cancer cell-derived extracellular vesicles (CEVs) played in pre-metastatic niche (PMN) formation of lymph node (LN). MATERIALS AND METHODS: The FRCs in sixty fresh cervical LNs from 20 patients were evaluated by flow cytometric analysis. Cells in LN with or without metastasis were analyzed by single-cell RNA sequencing (scRNA-seq). CEVs were isolated from the culture supernatant of primarily cultured cancer cells and cocultured with FRCs. Mass Spectrometry was used to identify LN metastasis related protein in CEVs. The activation of IFNGR1/JAK1/STAT1-activated-PD-L1 pathway in FRCs was detected by western blotting. FRCs were co-cultured with CD8+ T lymphocytes to confirm the cytotoxicity assay of FRCs. RESULTS: The proportion of fibroblastic reticular cells (FRCs) was significantly higher in micro-metastatic LN in head and neck squamous cell carcinoma patients (HNSCC, p < 0.05) and scRNA-seq analysis further showed a high focus of extracellular vesicles-related pathway on FRCs in LN with metastasis (p < 0.05). Interferon gamma receptor 1 (IFNGR1) in CEVs can be engulfed by FRCs and promote PD-L1 expression on FRCs via JAK1-STAT1 pathway, resulting in an increased CD8+ T cell exhaustion. CONCLUSION: IFNGR1, originated from cancer cell-derived extracellular vesicles, promote PD-L1 expression on FRCs and subsequent CD8+ T cell exhaustion via JAK1-STAT1 activation, which facilitate pre-metastatic niche formation and tumor metastasis in sentinel lymph node in HNSCC.

Decellularized periosteum promotes guided bone regeneration via manipulation of macrophage polarization.

Periosteum has shown potential as an effective barrier membrane for guided bone regeneration (GBR). However, if recognized as a "foreign body," insertion of a barrier membrane in GBR treatment will inevitably alter the local immune microenvironment and subsequently influence bone regeneration. The aim of this investigation was to fabricate decellularized periosteum (DP) and investigate its immunomodulatory properties in GBR. DP was successfully fabricated from periosteum from the mini-pig cranium. In vitro experiments indicated that the DP scaffold modulated macrophage polarization toward a pro-regenerative M2 phenotype, which in turn facilitated migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. A rat GBR model with a cranial critical-size defect was established, and our in vivo experiment confirmed the beneficial effects of DP on the local immune microenvironment and bone regeneration. Collectively, the findings of this study indicate that the prepared DP possesses immunomodulatory properties and represents a promising barrier membrane for GBR procedures.

A collaborative robotic platform for sensor-aware fibula osteotomies in mandibular reconstruction surgery.

Precision and safety are crucial in performing fibula osteotomy during mandibular reconstruction with free fibula flap (FFF). However, current clinical methods, such as template-guided osteotomy, have the potential to cause damage to fibular vessels. To address the challenge, this paper introduces the development of the surgical robot for fibula osteotomies in mandibular reconstruction surgery and propose an algorithm for sensor-aware hybrid force-motion control for safe osteotomy, which includes three parts: osteotomy motion modeling from surgeons' demonstrations, Dynamic-system-based admittance control and osteotomy sawed-through detection. As a result, the average linear variation of the osteotomized segments was 1.08±0.41mm, and the average angular variation was 1.32±0.65∘. The threshold of osteotomy sawed-through detection is 0.5 at which the average offset is 0.5mm. In conclusion, with the assistance of surgical robot for mandibular reconstruction, surgeons can perform fibula osteotomy precisely and safely.

Li-Mg-Si bioceramics provide a dynamic immuno-modulatory and repair-supportive microenvironment for peripheral nerve regeneration.

Biomaterials can modulate the local immune and repair-supportive microenvironments to promote peripheral nerve regeneration. Inorganic bioceramics have been widely used for regulating tissue regeneration and local immune response. However, little is known on whether inorganic bioceramics can have potential for enhancing peripheral nerve regeneration and what are the mechanisms underlying their actions. Here, the inorganic lithium-magnesium-silicon (Li-Mg-Si, LMS) bioceramics containing scaffolds are fabricated and characterized. The LMS-containing scaffolds had no cytotoxicity against rat Schwann cells (SCs), but promoted their migration and differentiation towards a remyelination state by up-regulating the expression of neurotrophic factors in a ß-catenin-dependent manner. Furthermore, using single cell-sequencing, we showed that LMS-containing scaffolds promoted macrophage polarization towards the pro-regenerative M2-like cells, which subsequently facilitated the migration and differentiation of SCs. Moreover, implantation with the LMS-containing nerve guidance conduits (NGCs) increased the frequency of M2-like macrophage infiltration and enhanced nerve regeneration and motor functional recovery in a rat model of sciatic nerve injury. Collectively, these findings indicated that the inorganic LMS bioceramics offered a potential strategy for enhancing peripheral nerve regeneration by modulating the immune microenvironment and promoting SCs remyelination.

Precision compensation method for visual measurement based on nonuniform refractive index field reconstruction.

Visual measurement is widely used in industrial manufacturing and assembly fields. Due to the fact that the refractive index field of the measurement environment is inhomogeneous, the transmitted light for visual measurements will produce errors. To compensate for these errors, we introduce a binocular camera for visual measurement based on the reconstruction of a nonuniform refractive index field using the schlieren method, followed by the reduction of the inverse ray path by the Runge-Kutta method to compensate for the measurement error introduced by the nonuniform refractive index field. Finally, the effectiveness of the method is experimentally verified, with a reduction in measurement error of about 60% in the built measurement environment.

Carbon Dots from Lycium barbarum Attenuate Radiation-Induced Bone Injury by Inhibiting Senescence via METTL3/Clip3 in an m6A-Dependent Manner.

Radiation-induced bone injury management remains a challenge in clinical practice, and there is no effective medicine. Recently, biomass-derived carbon dots (CDs) have attracted attention in biomedical engineering due to the advantages of abundant heteroatoms, low toxicity, and no need to drug loading. Here, we report that CDs, synthesized from Lycium barbarum via hydrothermal strategy, can effectively alleviate radiation-induced bone injury. CCK-8, apoptosis analysis, ß-galactosidase staining, quantitative polymerase chain reaction, and western blots demonstrate that CDs can mediate radiation-induced damage and senescence of bone marrow mesenchymal stem cells (BMSCs). CDs regulate osteogenic- and adipogenic-balance after irradiation, shown by alizarin red and oil red O staining. In vivo experiments reveal that CDs prevent the occurrence of osteoradionecrosis in rats, demonstrated by micro-CT and histology examination. The osseointegration of titanium implants installed in irradiated bone is promoted by CDs. Mechanistically, CDs increase the N6-methyladenosine (m6A) level of irradiated BMSCs via the increased methyltransferase-like 3 (METTL3). High-throughput sequencing facilitates detection of increased m6A levels located in the 3'-untranslated regions (UTR) of the CAP-Gly domain containing linker protein 3 (Clip3) mRNA. The dual-luciferase reporter assay shows that 3'UTR is the direct target of METTL3. Subsequently, the increased m6A modification led to enhanced degradation of mRNA and downregulated CLIP3 expression, eventually resulting in the alleviation of radiation-induced bone injury. Interfering with the METTL3/Clip3 axis can antagonize the effect of CDs, indicating that CDs mediate radiation-induced bone injury via the METTL3/Clip3 axis. Taken together, CDs from L. barbarum alleviate radiation-induced bone injury by inhibiting senescence via regulation of m6A modification of Clip3. The present study paves a new pathway for the management of radiation-induced bone injury.

Can adjuvant radiotherapy be omitted for oral cavity cancer patients who received neoadjuvant therapy and surgery? A retrospective cohort study.

BACKGROUND: Surgery and postoperative adjuvant therapy comprise the standard treatment for locally advanced resectable oral squamous cell carcinoma (LAROSCC), while preoperative neoadjuvant therapy is being explored without sufficient confirmation of improved survival. De-escalation regimens after neoadjuvant therapy, such as those omitting adjuvant radiotherapy, may provide comparable or better outcomes, suggesting rigorous assessment of adjuvant therapy outcomes is needed in LAROSCC patients. The authors thus performed this retrospective study in LAROSCC patients who received neoadjuvant therapy and surgery, to compare the outcomes for overall survival (OS) and locoregional recurrence-free survival (LRFS) between the adjuvant radiotherapy (radio) and nonradiotherapy (nonradio) cohorts. MATERIALS AND METHODS: Patients diagnosed with LAROSCC who received neoadjuvant therapy and surgery were enrolled and divided into radio and nonradio cohorts to determine whether adjuvant radiotherapy could be omitted after neoadjuvant therapy and surgery. RESULTS: From 2008 to 2021, 192 patients were enrolled. No significant differences were found in OS or LRFS between the radio and nonradio patient cohorts. The 10-year estimated OS rates were 58.9 versus 44.1% in radio versus nonradio cohorts, while 10-year estimated LRFS rates were 55.4 versus 48.2%, respectively. For clinical stage III patients, 10-year OS rates were 62.3 versus 62.6% (radio vs. nonradio), and estimated 10-year LRFS rates were 56.5 versus 60.7% (radio vs. nonradio). Multivariate Cox regression modeling of postoperative variables showed pathologic response of primary tumor and pathologic regional lymph nodes staging were associated with survival, while the adjuvant radiotherapy exposure was not included in the model due to nonsignificance. CONCLUSION: These findings support further prospective evaluation of adjuvant radiotherapy omission, and suggest that de-escalation trials are warranted for LAROSCC surgery patients who received neoadjuvant therapy.

Ginseng-based carbon dots inhibit the growth of squamous cancer cells by increasing ferroptosis.

Background: Recent studies indicated that Ginseng potentiate cancer treatments. Ginseng-based carbon dots (GCDs) might possess properties to kill cancer cells and inhibit malignant tumor development and invasion. This study aimed to prepare GCDs, examine their effects on cancer cell growth and invasion, and explore the mechanisms involved. Methods: GCDs were synthesized, purified, and characterized. Cells were cultured with GCDs and were tested for growth, invasiveness, and wound healing. RNA was extracted for transcriptomics analysis. Protein expression was evaluated using western blot and immunohistochemistry. Mice were injected with cancer cells and treated with PBS or GCDs. Tumor volume was evaluated. Results: GCDs were successfully synthesized and purified. The solution was yellow under sunlight and fluorescent blue under ultraviolet light. Electron microscopy showed GCDs with a uniform shape without apparent aggregation and an average diameter of about 4 nm. GCDs inhibited Cal-27, SCC-25, and SCC-7 cancer cell growth at concentrations of >250-300 µg/mL, while GCDs inhibited the non-cancerous HaCaT cells at concentrations >400 µg/mL. Immunofluorescence showed that GCDs could enter the cells. Transcriptomics revealed 552 downregulated mRNAs and 338 upregulated ones, including mRNAs involved in the oxidative phosphorylation and ferroptosis pathways. GCDs induced the ferroptosis of cancer cells, as shown by decreased GPX-4 and increased COX-2. GCDs decreased cell invasion and migration. In vivo, GCDs decreased tumor growth without apparent organ toxicity and promoted CD4+ T cell infiltration in the tumor. Conclusion: GCDs appear to possess anticancer properties by increasing ferroptosis, resulting in cancer cell growth inhibition in vitro and in vivo.

The 3D-Printed Ordered Bredigite Scaffold Promotes Pro-Healing of Critical-Sized Bone Defects by Regulating Macrophage Polarization.

Background: Repairing critical-sized bone defects secondary to traumatic or tumorous damage is a complex conundrum in clinical practice; in this case, artificial scaffolds exhibited preferable outcomes. Bredigite (BRT, Ca7MgSi4O16) bioceramic possesses excellent physicochemical properties and biological activity as a promising candidate for bone tissue engineering. Methods: Structurally ordered BRT (BRT-O) scaffolds were fabricated by a three-dimensional (3D) printing technique, and the random BRT (BRT-R) scaffolds and clinically available ß-tricalcium phosphate (ß-TCP) scaffolds were compared as control groups. Their physicochemical properties were characterized, and RAW 264.7 cells, bone marrow mesenchymal stem cells (BMSCs), and rat cranial critical-sized bone defect models were utilized for evaluating macrophage polarization and bone regeneration. Results: The BRT-O scaffolds exhibited regular morphology and homogeneous porosity. In addition, the BRT-O scaffolds released higher concentrations of ionic products based on coordinated biodegradability than the ß-TCP scaffolds. In vitro, the BRT-O scaffolds facilitated RWA264.7 cells polarization to pro-healing M2 macrophage phenotype, whereas the BRT-R and ß-TCP scaffolds stimulated more pro-inflammatory M1-type macrophages. A conditioned medium derived from macrophages seeding on the BRT-O scaffolds notably promoted the osteogenic lineage differentiation of BMSCs in vitro. The cell migration ability of BMSCs was significantly enhanced under the BRT-O-induced immune microenvironment. Moreover, in rat cranial critical-sized bone defect models, the BRT-O scaffolds group promoted new bone formation with a higher proportion of M2-type macrophage infiltration and expression of osteogenesis-related markers. Therefore, in vivo, BRT-O scaffolds play immunomodulatory roles in promoting critical-sized bone defects by enhancing the polarization of M2 macrophages. Conclusion: 3D-printed BRT-O scaffolds can be a promising option for bone tissue engineering, at least partly through macrophage polarization and osteoimmunomodulation.

Association of salivary miRNAs with onset and progression of oral potentially malignant disorders: Searching for noninvasive biomarkers.

Background/purpose: There is an urgent need for noninvasive biomarkers to diagnose oral potentially malignant disorders (OPMD). A wide range of over 20 miRNAs in saliva of OPMD patients have been investigated in different studies. Yet, which of the ones provide a better power of discrimination for the diagnosis of OPMD onset and progression are uncertain. Materials and methods: A total of 17 eligible studies including 426 cases of OPMD and 486 control subjects (352 normal mucosa and 134 oral squamous cell carcinoma) were summarized. Results: The bubble chart analysis showed that the most power salivary miRNA associated with OPMD onset was miR-21, followed by miR-31 and miR-142; the better power miRNAs associated with recurrence and malignant progression of OPMD were miR-31, miR-21, and miR-184. Conclusion: Salivary miRNAs, especially miR-21 and miR-31, were associated with onset and progression of OPMD, and could then serve as noninvasive biomarkers for screening OPMD and detecting malignant changes.

Curcumin nanoemulsions inhibit oral squamous cell carcinoma cell proliferation by PI3K/Akt/mTOR suppression and miR-199a upregulation: A preliminary study.

BACKGROUND: Accumulating evidence indicates that curcumin (CUR) has anticancer properties in various cancers including oral squamous cell carcinoma (OSCC), but CUR is greatly restricted in clinical studies and applications due to its low bioavailability. Interestingly, the bioavailability of CUR was found to be significantly improved using loaded lipid nanoemulsions (NEs). OBJECTIVES: To investigate the effect of CUR-NEs on cell proliferation of OSCC HSC-3 cells in vitro, and explore the potential mechanism of this effect in a preliminary study. RESULTS: CUR-NEs exhibited significantly cytotoxic effects on OSCC cells in a dose-dependent manner, compared with the control. The percentage of cells in proliferative phases (S + G2/M) was gradually decreased in a dose- or time-dependent manner caused by CUR-NEs. Moreover, CUR-NEs downregulated the protein expression of PI3K/Akt/mTOR and upregulated the expression of miR-199a that targeted PI3K in a dose- or time-dependent manner in OSCC cells. Importantly, CUR-NEs cloud effectively counteract the influence on cell proliferation of OSCC cells and the proliferative phases of cell cycle caused by miR-199a inhibitor a time-dependent manner. CONCLUSIONS: This in vitro preliminary study indicated that CUR-NEs may be an effective therapeutic agent for OSCC. Such effects could be related to inhibition of OSCC cell proliferation by PI3K/Akt/mTOR suppression and miR-199a upregulation.