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Abstract Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m−1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural‐tissue‐like low conductivity (0.02–0.1 S m−1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m−1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic‐transcription‐factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural‐tissue‐like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.

Background/purpose: Human dental pulp stem cells (hDPSCs) are an emerging source of mesenchymal stem cells (MSCs) for bone tissue regeneration and engineering. In bone regeneration using transplanted MSCs, the extracellular environment or co-injected drugs can affect their success or failure. In this study, we investigated the effects and signaling mechanisms of lidocaine on osteogenic differentiation of hDPSCs after inducing inflammatory conditions with lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α). Materials and methods: To investigate the effect of lidocaine on the osteogenic differentiation of LPS/TNF-α-treated hDPSCs, alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were conducted. The expression of osteogenesis-related genes was assessed using quantitative real-time polymerase chain reaction and western blotting. The expression of mitogen-activated protein kinases was analyzed to evaluate the effect of lidocaine on osteogenic differentiation of LPS/TNF-α-treated hDPSCs. Results: Various concentrations of lidocaine (0.05, 0.2, and 1 mM) further decreased ALP and ARS staining of LPS/TNF-α-treated hDPSCs. Similarly, the mRNA and protein expression of osteogenesis-related genes was suppressed via lidocaine treatment in LPS/TNF-α-treated hDPSCs. Lidocaine treatment downregulated the protein expression of p-ERK and p-JNK in LPS/TNF-α-treated hDPSCs. Conclusion: Lidocaine intensified the inhibition of osteogenic differentiation on inflammation-induced hDPSCs by inhibiting the ERK and JNK signaling pathways. This in vitro study suggested that lidocaine may have an inhibitory effect on bone regeneration.

In recent years, there has been a surge in demand for and research focus on cell therapy, driven by the tissue-regenerative and disease-treating potentials of stem cells. Among the candidates, dental pulp stem cells (DPSCs) or human exfoliated deciduous teeth (SHED) have garnered significant attention due to their easy accessibility (non-invasive), multi-lineage differentiation capability (especially neurogenesis), and low immunogenicity. Utilizing these stem cells for clinical purposes requires careful culture techniques such as excluding animal-derived supplements. Human platelet lysate (hPL) has emerged as a safer alternative to fetal bovine serum (FBS) for cell culture. In our study, we assessed the impact of hPL as a growth factor supplement for culture medium, also conducting a characterization of SHED cultured in hPL-supplemented medium (hPL-SHED). The results showed that hPL has effects in enhancing cell proliferation and migration and increasing cell survivability in oxidative stress conditions induced by H2O2. The morphology of hPL-SHED exhibited reduced size and elongation, with a differentiation capacity comparable to or even exceeding that of SHED cultured in a medium supplemented with fetal bovine serum (FBS-SHED). Moreover, no evidence of chromosome abnormalities or tumor formation was detected. In conclusion, hPL-SHED emerges as a promising candidate for cell therapy, exhibiting considerable potential for clinical investigation.

Over recent decades, machine learning, an integral subfield of artificial intelligence, has revolutionized diverse sectors, enabling data-driven decisions with minimal human intervention. In particular, the field of educational assessment emerges as a promising area for machine learning applications, where students can be classified and diagnosed using their performance data. The objectives of Diagnostic Classification Models (DCMs), which provide a suite of methods for diagnosing students' cognitive states in relation to the mastery of necessary cognitive attributes for solving problems in a test, can be effectively addressed through machine learning techniques. However, the challenge lies in the latent nature of cognitive status, which makes it difficult to obtain labels for the training dataset. Consequently, the application of machine learning methods to DCMs often assumes smaller training sets with labels derived either from theoretical considerations or human experts. In this study, the authors propose a supervised diagnostic classification model with data augmentation (SDCM-DA). This method is designed to utilize the augmented data using a data generation model constructed by leveraging the probability of correct responses for each attribute mastery pattern derived from the expert-labeled dataset. To explore the benefits of data augmentation, a simulation study is carried out, contrasting it with classification methods that rely solely on the expert-labeled dataset for training. The findings reveal that utilizing data augmentation with the estimated probabilities of correct responses substantially enhances classification accuracy. This holds true even when the augmentation originates from a small labeled sample with occasional labeling errors, and when the tests contain lower-quality items that may inaccurately measure students' true cognitive status. Moreover, the study demonstrates that leveraging augmented data for learning can enable the successful classification of students, thereby eliminating the necessity for specifying an underlying response model.

Abstract Advancing the technologies for cellular reprogramming with high efficiency has significant impact on regenerative therapy, disease modeling, and drug discovery. Biophysical cues can tune the cell fate, yet the precise role of external physical forces during reprogramming remains elusive. Here the authors show that temporal cyclic‐stretching of fibroblasts significantly enhances the efficiency of induced pluripotent stem cell (iPSC) production. Generated iPSCs are proven to express pluripotency markers and exhibit in vivo functionality. Bulk RNA‐sequencing reveales that cyclic‐stretching enhances biological characteristics required for pluripotency acquisition, including increased cell division and mesenchymal‐epithelial transition. Of note, cyclic‐stretching activates key mechanosensitive molecules (integrins, perinuclear actins, nesprin‐2, and YAP), across the cytoskeletal‐to‐nuclear space. Furthermore, stretch‐mediated cytoskeletal‐nuclear mechano‐coupling leads to altered epigenetic modifications, mainly downregulation in H3K9 methylation, and its global gene occupancy change, as revealed by genome‐wide ChIP‐sequencing and pharmacological inhibition tests. Single cell RNA‐sequencing further identifies subcluster of mechano‐responsive iPSCs and key epigenetic modifier in stretched cells. Collectively, cyclic‐stretching activates iPSC reprogramming through mechanotransduction process and epigenetic changes accompanied by altered occupancy of mechanosensitive genes. This study highlights the strong link between external physical forces with subsequent mechanotransduction process and the epigenetic changes with expression of related genes in cellular reprogramming, holding substantial implications in the field of cell biology, tissue engineering, and regenerative medicine.

Abstract Background Remimazolam is a recently approved, ultra-short-acting benzodiazepine. However, few studies have investigated remimazolam in relation to postoperative nausea and vomiting (PONV). This study aimed to compare the effects of remimazolam and propofol on PONV in patients undergoing oral and maxillofacial surgery. Methods Patients (n = 206) aged 19–65 years who were scheduled for oral and maxillofacial surgery were randomized into two groups, the remimazolam (R) and propofol group (P). In the R group (n = 94), remimazolam was used to induce anesthesia at 12 mg/kg/h and to maintain anesthesia at 1–2 mg/kg/h. In the P group (n = 95), anesthesia was induced and maintained with propofol (target effect-site concentration: 3–5 µg/ml). In both groups, remifentanil was administered at a target effect-site concentration of 2.5-4 ng/ml. The primary outcome was the overall incidence of PONV during the first 24 h after surgery. Secondary outcomes included the severity of nausea, use of rescue antiemetics, severity of postoperative pain, use of rescue analgesia, and quality of recovery. Results The incidence of PONV during the first 24 h after surgery was 11.7% and 10.5% in the R group and P group, respectively, and there was no significant difference in the severity of nausea (P > 0.05). Ten patients in the R group and ten patients in the P group required rescue antiemetics during the first 24 h after surgery (P = 0.98). No inter-group differences were observed in terms of postoperative pain score, use of rescue analgesia, and quality of recovery (P > 0.05). Conclusions In this study, remimazolam did not increase the incidence and severity of PONV compared with propofol. Trial registration KCT0006965, Clinical Research Information Service (CRIS), Republic of Korea. Registration date: 26/01/2022.

Background/purpose: Various studies have used stem cells in the field of bone tissue engineering to repair bone defects. Dental pulp stem cells (DPSCs) have multipotent properties and can be acquired in a noninvasive manner; therefore, they are frequently used in experiments in regenerative medicine. The objective of this study was to investigate the odontogenic/osteogenic differentiation of human DPSCs (hDPSCs) using propofol, a widely used intravenous anesthetic agent. Materials and methods: Alkaline phosphatase (ALP) staining was used to investigate the effects of various concentrations of propofol (5, 20, 50 and 100 μM) on the osteogenic differentiation of hDPSCs. Real-time qPCR and Western blot analysis were used to detect the effect of propofol on the expression of odontogenic/osteogenic genes, such as DMP1, RUNX2, OCN, and BMP2. Odontogenic/osteogenic differentiation of hDPSCs was estimated at days 7 and 14. Results: ALP staining of hDPSCs was significantly decreased by propofol treatment. The mRNA expression of DMP1, RUNX2, OCN, and BMP2 decreased after propofol treatment for 14 days. The protein expression of DMP1 and BMP2 was decreased by propofol at days 7 and 14, and that of RUNX2 was decreased by propofol at day 14 only. Conclusion: Propofol attenuated odontogenic/osteogenic differentiation of hDPSCs in vitro. This result suggests that propofol, which is widely used for dental sedation, may inhibit the odontogenic/osteogenic differentiation of hDPSCs.

Objective Lidocaine is an amide local anaesthetic commonly used for pain control, however, few studies have investigated the effect of lidocaine on the osteogenic differentiation of human dental pulp stem cells (HDPSCs). The present study aimed to determine the effect of lidocaine on HDPSC viability and osteogenic differentiation. Methods HDPSCs were incubated with 0, 0.05, 0.2, 0.5, and 1 mM lidocaine for 24, 48 and 72 h, after which, MTT assays were performed. HDPSCs cultured with the above lidocaine concentrations and osteogenic differentiation medium for 7 and 14 days were stained for alkaline phosphatase (ALP). Protein and mRNA levels of relevant osteogenic factors (bone morphogenetic protein-2 [BMP-2] and runt-related transcription factor 2 [RUNX2]) were examined using western blotting and real-time reverse-transcription polymerase chain reaction, respectively. Results Lidocaine did not affect the viability of HDPSCs, however, lidocaine reduced ALP activity in HDPSCs. Levels of ALP, BMP-2, and RUNX2 mRNA were reduced with lidocaine, and levels of BMP-2 and RUNX2 proteins were decreased, versus controls. Conclusions Lidocaine inhibits osteogenic differentiation markers in HDPSCs in vitro , even at low concentrations, without cytotoxicity. This study suggests that lidocaine may inhibit osteogenic differentiation in HDPSC-mediated regenerative medicine, including pulp regeneration and repair.

Abstract Novel polycaprolactone‐based polyurethane (PCL‐PU) copolymers with hyperelasticity, shape‐memory, and ultra‐cell‐adhesion properties are reported as clinically applicable tissue‐regenerative biomaterials. New isosorbide derivatives (propoxylated or ethoxylated ones) were developed to improve mechanical properties by enhanced reactivity in copolymer synthesis compared to the original isosorbide. Optimized PCL‐PU with propoxylated isosorbide exhibited notable mechanical performance (50 MPa tensile strength and 1150% elongation with hyperelasticity under cyclic load). The shape‐memory effect was also revealed in different forms (film, thread, and 3D scaffold) with 40%–80% recovery in tension or compression mode after plastic deformation. The ultra‐cell‐adhesive property was proven in various cell types which were reasoned to involve the heat shock protein‐mediated integrin (α5 and αV) activation, as analyzed by RNA sequencing and inhibition tests. After the tissue regenerative potential (muscle and bone) was confirmed by the myogenic and osteogenic responses in vitro, biodegradability, compatible in vivo tissue response, and healing capacity were investigated with in vivo shape‐memorable behavior. The currently exploited PCL‐PU, with its multifunctional (hyperelastic, shape‐memorable, ultra‐cell‐adhesive, and degradable) nature and biocompatibility, is considered a potential tissue‐regenerative biomaterial, especially for minimally invasive surgery that requires small incisions to approach large defects with excellent regeneration capacity.

The last few decades have seen an increased interest in 'Mental Health Literacy (MHL)' which addresses knowledge and beliefs relating to mental health problems and is likely to hinder treatment-seeking behaviors. Although MHL research to date has explored various mental disorders, far too little attention has been paid to Internet Gaming Disorder (IGD) and Problematic Smartphone use (PSU). The objective of this study is to develop an MHL questionnaire for IGD and PSU by adopting the MHL approach in the previous literature and examine MHL of IGD and PSU in Korean teenagers by focusing on their ability to recognize addictions, and perceptions and help-seeking attitudes towards a person with addictions. The current study also aimed to compare Korean teenagers' MHL depending on low- and high-risk of IGD and PSU. A total of 169 teenagers aged 10 and 16 years were recruited from schools and children's centers in Seoul and completed the newly developed MHL questionnaire and screening questionnaires for IGD and PSU. The MHL questionnaire for IGD and PSU was designed as a vignette-based questionnaire that depicted behavioral characteristics of a severe problem with Internet and smartphone usage. Korean teenagers had a poor ability to recognize IGD and PSU and were more prone to seek parental help than professional help. The current study also showed that teenagers had better recognition of IGD than PSU and perceived that a person with IGD has a more difficult life than a person with PSU. Furthermore, a low-risk or high-risk group of IGD or PSU showed minimal differences in MHL. The current study provided empirical evidence to support a need to develop educational programs to improve Korean teenagers' MHL for both IGD and PSU.

Regenerative endodontic treatment based on tissue engineering has recently gained interest in contemporary restorative dentistry. However, low survival rates and poor potential differentiation of stem cells could undermine the success rate of pulp regenerative therapy. Human gingival fibroblast-conditioned medium (hGF-CM) has been considered a potential therapy for tissue regeneration due to its stability in maintaining multiple factors essential for tissue regeneration compared to live cell transplantation. This study aimed to investigate the potency of hGF-CM on stem cells from human dental pulp (DPSC) in pulp regeneration. A series of experiments confirmed that hGF-CM contributes to a significant increase in proliferation, migration capability, and cell viability of DPSC after H2O2 exposure. Moreover, it has been proved to facilitate the odontogenic differentiation of DPSC via qRT-PCR, ALP (alkaline phosphatase), and ARS (Alizarin Red S) staining. It has been discovered that such highly upregulated odontogenesis is related to certain types of ECM proteins (collagen and laminin) from hGF-CM via proteomics. In addition, it is found that the ERK pathway is a key mechanism via inhibition assay based on RNA-seq result. These findings demonstrate that hGF-CM could be beneficial biomolecules for pulp regeneration.

Extracellular vesicles (EVs), including exosomes, carry the genetic packages of RNA, DNA, and proteins and are heavily involved in cell-cell communications and intracellular signalings. Therefore, EVs are spotlighted as therapeutic mediators for the treatment of injured and dysfunctional tissues as well as biomarkers for the detection of disease status and progress. Several key issues in EVs, including payload content and bioactivity, targeting and bio-imaging ability, and mass-production, need to be improved to enable effective therapeutics and clinical translation. For this, significant efforts have been made recently, including genetic modification, biomolecular and chemical treatment, application of physical/mechanical cues, and 3D cultures. Here we communicate those recent technological advances made mainly in the biogenesis process of EVs or at post-collection stages, which ultimately aimed to improve the therapeutic efficacy in tissue healing and disease curing and the possibility of clinical translation. This communication will help tissue engineers and biomaterial scientists design and produce EVs optimally for tissue regenerative therapeutics.

Pulp regeneration has recently attracted interest in modern dentistry. However, the success ratio of pulp regeneration is low due to the compromising potential of stem cells, such as their survival, migration, and odontoblastic differentiation. Stem cells from human exfoliated deciduous teeth (SHED) have been considered a promising tool for regenerative therapy due to their ability to secrete multiple factors that are essential for tissue regeneration, which is achieved by minimally invasive procedures with fewer ethical or legal concerns than those of other procedures. The aim of this study is to investigate the potency of SHED-derived conditioned media (SHED CM) on dental pulp stem cells (DPSCs), a major type of mesenchymal stem cells for dental pulp regeneration. Our results show the promotive efficiency of SHED CM on the proliferation, survival rate, and migration of DPSCs in a dose-dependent manner. Upregulation of odontoblast/osteogenic-related marker genes, such as ALP, DSPP, DMP1, OCN, and RUNX2, and enhanced mineral deposition of impaired DPSCs are also observed in the presence of SHED CM. The analysis of SHED CM found that a variety of cytokines and growth factors have positive effects on cell proliferation, migration, anti-apoptosis, and odontoblast/osteogenic differentiation. These findings suggest that SHED CM could provide some benefits to DPSCs in pulp regeneration.

Faith leaders (FL) have a key role in suicide prevention. One of their roles is to address suicide stigma in faith communities. Are they ready to do so? The Clergy Suicide Prevention Skills Developmental Rubric (CSPCDR) was developed to understand and assess clergy suicide prevention skills. The psychometric properties of the CSPCDR are reported in order to assess FL’ readiness to address suicide stigma. Sample 1, 186 Protestant seminary students completed the CSPCDR twice, resulting in Pearson’s r = 0.77. Sample 2, 187 Protestant clergy and lay ministers completed the CSPCDR before and after one of eight trainings to test construct validity; the CSPCDR performed as expected. Results suggest how to expand FL’ readiness to address suicide stigma in faith communities.

Nanomaterials can enhance interactions with stem cells for tissue regeneration. This study aimed to investigate the biological effects of tricalcium silicate nanoparticle-containing cement (Biodentine™) during or after setting on stem cells from human exfoliated deciduous teeth (SHED) to mimic clinically relevant situations in which materials are adapted. Specimens were divided into four groups depending on the start of extraction time (during (3, 6 and 12 min) or after setting (24 h)) and extracted in culture medium for 24 h for further physicochemical and biological analysis. After cell viability in serially diluted extracts was evaluated, odontogenic differentiation on SHED was evaluated by ARS staining using nontoxic conditions. A physicochemical analysis of extracts or specimens indicated different Ca ion content, pH, and surface chemistry among groups, supporting the possibility of different biological functionalities depending on the extraction starting conditions. Compared to the ‘after setting’ group, all ‘during setting’ groups showed cytotoxicity on SHED. The during setting groups induced more odontogenic differentiation at the nontoxic concentrations compared to the control. Thus, under clinically simulated extract conditions at nontoxic concentrations, Biodentine™ seemed to be a promising odontoblast differentiating biomaterial that is helpful for dental tissue regeneration. In addition, to simulate clinical situations when nanoparticle-containing cement is adjusted, biological effects during setting need to be considered.

Biodegradable polyfumarateurethane (PFU) for use as a bupivacaine delivery vehicle, synthesized using di-(2-hydroxypropyl fumarate) (DHPF), polyethylene glycol (PEG) and 1,6-hexamethylene diisocyanate (HMDI), was designed to be degradable through the hydrolysis and enzymatic degradation of the ester bonds in its polymer backbone. Using a water-in-oil-in-water double emulsion techniques, nanoparticles encapsulating water or fluorescein isothiocyanate (FITC) were fabricated to avoid the immune system owing to the presence of PEG on their surface. The morphologies of these nanoparticles were characterized by DLS, TEM, FE-SEM, and fluorescent microscopies. The present study explored the encapsulation, loading efficiency and in vitro drug release of bupivacaine encapsulated with biodegradable PFU nanoparticles for the treatment of local anesthesia. Various concentrations of bupivacaine were encapsulated into nanoparticles and their encapsulation efficiencies and drug loading were investigated. Encapsulation efficiency was highest when 2.5% bupivacaine was encapsulated. Drug release behavior from the bupivacaine-loaded PFU nanoparticles followed a sustained release profile.

Ecklonia cava (E. cava; CA) is an edible brown alga with beneficial effects in diabetes via regulation of various metabolic processes such as lipogenesis, lipolysis, inflammation, and the antioxidant defense system in liver and adipose tissue. We investigated the effect of the polyphenol-rich fraction of E. cava produced from Gijang (G-CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-fed mice. C57BL6 mice were fed a HFD for six weeks and then the HFD group was administered 300 mg/kg of G-CA extracts by oral intubation for 10 weeks. Body weight, fat mass, and serum biochemical parameters were reduced by G-CA extract treatment. MRI/MRS analysis showed that liver fat and liver volume in HFD-induced obese mice were reduced by G-CA extract treatment. Further, we analyzed hepatic gene expression related to inflammation and lipid metabolism. The mRNA expression levels of inflammatory cytokines and hepatic lipogenesis-related genes were decreased in G-CA-treated HFD mice. The mRNA expression levels of cholesterol 7 alpha-hydroxylase 1 (CYP7A1), the key enzyme in bile acid synthesis, were dramatically increased by G-CA treatment in HFD mice. We suggest that G-CA treatment ameliorated hepatic steatosis by inhibiting inflammation and improving lipid metabolism.

In this study, a soft structure with its stiffness tunable by an external field is proposed. The proposed soft beam structure consists of a skin structure with channels filled with a magnetorheological fluid (MRF). Two specimens of the soft structure are fabricated by three-dimensional printing and fused deposition modeling. In the fabrication, a nozzle is used to obtain channels in the skin of the thermoplastic polyurethane, while another nozzle is used to fill MRF in the channels. The specimens are tested by using a universal tensile machine to evaluate the relationships between the load and deflection under two different conditions, without and with permanent magnets. It is empirically shown that the stiffness of the proposed soft structure can be altered by activating the magnetic field.

Congenital tracheal stenosis (CTS), though rare, is important because the mortality and morbidity rates are high in infants. Especially, associated congenital heart disease (CHD) in these infants may compound the effects of airway pathology. A 3-week-old patient with long-segmental tracheal stenosis below an anomalous right-upper lobe (RUL) bronchus had undergone a total correction of double outlet right ventricle. On third postoperative day, hypercarbia developed, and severe airway obstruction and atelectasis were detected. An emergency slide tracheoplasty was performed under cardiopulmonary bypass (CPB). The patient recovered well after the surgery. Thus, special attention needs to be paid during the postoperative intensive care of patients with congenital tracheal anomalies. Early detection and prompt diagnosis of airway obstruction can help reduce the morbidity and mortality rates. Further, it is important to select the suitable treatment of CTS associated with CHD.

BackgroundEtomidate frequently induces myoclonus, so it may affect electromyographics (EMG). And EMG commonly has an effect on the bispectral index scale (BIS) and spectral entropy. This study was performed to compare the effect of etomidate on BIS, response entropy (RE) and state entropy (SE) during induction of anesthesia.MethodsFifty patients (ASA I or II) scheduled for elective surgery were included in this study. Anesthesia was induced with etomidate (0.3 mg/kg) and rocuronium (0.6 mg/kg). Patients also inhaled 4 vol% sevoflurane and 100% oxygen and, then intubated. BIS, RE, SE and Modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) were measured 4 times (before injection of etomidate [T0], at loss of eyelash reflex [T1], 90 seconds after rocuronium injection [T2], and after intubation [T3]). We also checked whether myoclonus occurred.ResultsBaseline values (T0) were 93.1 ± 4.7 for BIS, 95.8 ± 3.7 for RE and, 87.3 ± 3.5 for SE. In comparison with T0, there were significantly differences in BIS (50.2 ± 16.3), RE (76.8 ± 18.5) and SE (66.3 ± 17.4) at T1 (all P < 0.05). There were no significant differences at T2 and T3. Thirty one patients had myoclonus. At the occurrence of myoclonus, RE and SE values significantly increased but not BIS (P < 0.05).ConclusionsIn patients with myoclonus, at the loss of consciousness, spectral entropy did not decrease where as BIS did, suggesting that BIS may evaluate hypnotic levels better than spectral entropy during induction of anesthesia with etomidate.

The proliferation, differentiation, and migration of keratinocytes are essential in the early stages of wound healing. Hypoxia-Reoxygenation (H/R) injury to keratinocytes can occur in various stressful environments such as surgery, trauma, and various forms of ulcers. The effects of remifentanil on human keratinocytes under hypoxia-reoxygenation have not been fully studied. Therefore, we investigated the effects of remifentanil on the proliferation, apoptosis, and autophagic activation of human keratinocytes during hypoxic-reoxygenation. Human keratinocytes were cultured under 1% oxygen tension for 24 h. The cells were then treated with various concentrations of remifentanil (0.01, 0.1, 0.5, and 1 ng/mL) for 2 h. Thereafter, the cells were reoxygenated for 12 h at 37°C. We measured cell viability via MTT assay. Using quantitative real-time PCR and western blot analysis, we measured the expression levels of proteins associated with apoptosis and autophagy. Quantification of apoptotic cells was performed using flow cytometer analysis and autophagic vacuoles were observed under a fluorescence microscope. Remifentanil treatment brought about an increase in the proliferation of human keratinocytes damaged by hypoxia-reoxygenation and decreased the apoptotic cell death, enhancing autophagic activity. However, the autophagy pathway inhibitor 3-MA inhibited the protective effect of remifentanil in hypoxia-reoxygenation injury. In conclusion, the current study demonstrated that remifentanil treatment stimulated autophagy and reduced apoptotic cell death in a hypoxia-reoxygenation model of human keratinocytes. Our results provide additional insights into the relationship between apoptosis and autophagy.

Phloroglucinol is a phenolic compound that is one of the major compounds in Ecklonia cava (brown alga). It has many pharmacological activities, but its anti-diabetic effect is not yet fully explored. In this study, we investigated the effect of phloroglucinol on the control of blood glucose levels and the regulation of hepatic glucose production. Phloroglucinol significantly improved glucose tolerance in male C57BL/6J mice fed a high fat diet (HFD) and inhibited glucose production in mouse primary hepatocytes. The expression of phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase mRNA and protein (G6Pase), enzymes involved in gluconeogenesis, were inhibited in liver tissue from phloroglucinol-treated mice and in phloroglucinol-treated HepG2 cells. In addition, phloroglucinol treatment increased phosphorylated AMP-activated protein kinase (AMPK)α in HepG2 cells. Treatment with compound C, an AMPKα inhibitor, inhibited the increase of phosphorylated AMPKα and the decrease of PEPCK and G6Pase expression caused by phloroglucinol treatment. We conclude that phloroglucinol may inhibit hepatic gluconeogenesis via modulating the AMPKα signaling pathway, and thus lower blood glucose levels.

Purpose: This study compared the functional and cosmetic treatment outcomes of intramedullary nailing (IM nail) and minimally invasive plate osteosynthesis (MIPO) for distal tibia shaft fractures. Materials and Methods: Forty-eight patients with distal tibia shaft fractures (distal 1/3 of the diaphysis, AO/OTA [AO Foundation/ Orthopaedic Trauma Association]) 43 managed by an IM nail (n=30) or MIPO (n=18) who had minimum one-year follow-up were enrolled in this study. The radiological, functional, and cosmetic outcomes in the two groups were compared retrospectively. Results: All patients achieved bone union. The mean bone union time of the IM nail and MIPO groups was 18.5 and 22.6 weeks, respectively (p=0.078). One patient in the MIPO group showed posterior angulation and valgus deformity of more than five degrees. The mean American Orthopaedic Foot and Ankle Society (AOFAS) functional scores were similar: 83.3 in the IM nail group and 84.6 in the MIPO group (p=0.289). The most salient difference was the cosmetic result of the surgical scar. The length of the scars around the ankle in the IM nail group was significantly smaller than the MIPO group (2.6 cm vs. 10.6 cm; p=0.035). The patient satisfaction survey of surgical scars revealed a significantly higher satisfaction rate in the IM nail group than in the MIPO group (93% vs. 44%; p<0.001). Conclusion: This study showed that both treatment methods for distal tibia shaft fractures have similar therapeutic efficacy regarding the radiological and functional outcomes. On the other hand, the IM nail technique showed superior cosmetic outcomes than the MIPO technique. IM nails may be more recommended in patients with high demand for cosmetic results. [ABSTRACT FROM AUTHOR]