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Pulmonary venous flow (PVF) is influenced by changes in left atrial (LA) pressure and function in various diseases. In mitral stenosis (MS), there is an alteration of LA hemodynamic due to the impaired ventricular filling caused by the stenotic valve and elevation of LA pressure. Although a variety of altered patterns of PVF have been described in MS, the potential influence of pulmonary hypertension, which is frequently associated with MS and has an adverse effect on the functional status and the prognosis of MS, on the PVF pattern is not clearly defined. The aim of this study is to determine the effects of pulmonary hypertension on PVF in patients with MS. Thirty-eight consecutive patients with pure MS and sinus rhythm (30 females, mean age 40 years old) underwent transthoracic and transesophageal echocardiography. Right heart and transseptal catheterization was also performed to measure pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), pulmonary capillary wedge pressure (PCWP), and left atrial pressure (LAP). The subjects were divided into two groups: group 1 (n = 25)included subjects with PASP < 50 mmHg, group 2(n = 13)included subjects with PASP 50 mmHg. LA size, mitral valve area (MVA), mean mitral gradient (MG), LAP, PASP, PADP, PCWP, and the peak velocity of PV systolic (PVFS), diastolic (PVFD) and atrial reversal flow (PVFAr) were also measured and compared between the two groups. There was no significant difference in age, heart rate, MVA, and LA size between the two groups. LAP, PASP, PADP, PCWP, and MG were significantly higher in group 2. However, PVFS and PVFAr were significantly lower in group2 (46.6 +/- 15.8 vs 29.9 +/- 12.8 cm/sec, P < 0.005; 22.1 +/- 6.8 vs 17.3 +/- 5.9 cm/sec, P < 0.05). There was no significant difference of PVFD between the two groups. PVFS had negative correlation to LAP, MG, PASP, PADP, and PCWP. PVFAr had negative correlation with PASP, PADP, and PCWP. There was no significant correlation between PVFAr and MVA. LA size and LAP. In conclusion, in patients with pure MS and sinus rhythm, PVF, especially PVFAr, is influenced by the presence of pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Chronic tympanic membrane (TM) perforation is a tubotympanic disease caused by either traumatic injury or inflammation. A recent study demonstrated significant progress in promoting the regeneration of chronic TM perforations through the application of nanofibers with radially aligned nanostructures and controlled release of growth factors. However, radially aligned nanostructures with stem cell-stimulating factors have never been used. In this study, insulin-like growth factor binding factor 2 (IGFBP2)-incorporated radially aligned nanofibrous patches (IRA-NFPs) were developed and applied to regenerate chronic TM perforations. The IRA-NFPs were prepared by electrospinning 8 wt% polycaprolactone in trifluoroethanol and acetic acid (9:1). Random nanofibers (RFs) and aligned nanofibers (AFs) were successfully fabricated using a flat plate and a custom-designed circular collector, respectively. The presence of IGFBP2 was confirmed via Fourier transform infrared spectroscopy and the release of IGFBP2 was sustained for up to 20 days. In vitro studies revealed enhanced cellular proliferation and migration on AFs compared to RFs, and the incorporation of IGFBP2 further promoted these effects. Quantitative real-time PCR revealed mRNA downregulation, correlating with accelerated migration and increased cell confluency. In vivo studies showed IGFBP2-loaded RF and AF patches increased regeneration success rates by 1.59-fold and 2.23-fold, respectively, while also reducing healing time by 2.5-fold compared to the control. Furthermore, IGFBP2-incorporated AFs demonstrated superior efficacy in healing larger perforations with enhanced histological similarity to native TMs. This study, combining stem cell stimulating factors and aligned nanostructures, proposes a novel approach potentially replacing conventional surgical methods for chronic TM perforation regeneration. STATEMENT OF SIGNIFICANCE: Chronic otitis media (COM) affects approximately 200 million people worldwide due to inflammation, inadequate blood supply, and lack of growth factors. Current surgical treatments have limitations like high costs and anesthetic risks. Recent research explored the use of nanofibers with radially aligned nanostructures and controlled release of growth factors to treat chronic tympanic membrane (TM) perforations. In this study, insulin-like growth factor binding protein 2 (IGFBP2)-incorporated radially aligned nanofibrous patches (IRA-NFPs) were developed and applied to regenerate chronic TM perforations. We assessed their properties and efficacy through in vitro and in vivo studies. IRA-NFPs showed promising healing capabilities with chronic TM perforation models. This innovative approach has the potential to improve COM management, reduce surgery costs, and enhance patient safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In recent decades, cultured meat has received considerable interest as a sustainable alternative to traditional meat products, showing promise for addressing the inherent problems associated with conventional meat production. However, current limitations on the scalability of production and extremely high production costs have prevented their widespread adoption. Therefore, it is important to develop novel engineering strategies to overcome the current limitations in large-scale cultured meat production. Such engineering considerations have the potential for advancements in cultured meat production by providing innovative and effective solutions to the prevailing challenges. In this review, we discuss how engineering strategies have been utilized to advance cultured meat technology by categorizing the production processes of cultured meat into three distinct steps: (1) cell preparation; (2) cultured meat fabrication; and (3) cultured meat maturation. For each step, we provide a comprehensive discussion of the recent progress and its implications. In particular, we focused on the engineering considerations involved in each step of cultured meat production, with specific emphasis on large-scale production.

Artificial Intelligence (AI) is transforming healthcare, notably in ophthalmology, where its ability to interpret images and data can significantly enhance disease diagnosis and patient care. Recent developments in oculomics, the integration of ophthalmic features to develop biomarkers for systemic diseases, have demonstrated the potential for providing rapid, non-invasive methods of screening leading to enhance in early detection and improve healthcare quality, particularly in underserved areas. However, the widespread adoption of such AI-based technologies faces challenges primarily related to the trustworthiness of the system. We demonstrate the potential and considerations needed to develop trustworthy AI in oculomics through a pilot study for HbA1c assessment using an AI-based approach. We then discuss various challenges, considerations, and solutions that have been developed for powerful AI technologies in the past in healthcare and subsequently apply these considerations to the oculomics pilot study. Building upon the observations in the study we highlight the challenges and opportunities for advancing trustworthy AI in oculomics. Ultimately, oculomics presents as a powerful and emerging technology in ophthalmology and understanding how to optimize transparency prior to clinical adoption is of utmost importance., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor's phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.

Three-dimensional bioprinting represents an innovative platform for fabricating intricate, three-dimensional (3D) tissue structures that closely resemble natural tissues. The development of hybrid bioinks is an actionable strategy for integrating desirable characteristics of components. In this study, cellulose recovered from plum seed was processed to synthesize carboxymethyl cellulose (CMC) for 3D bioprinting. The plum seeds were initially subjected to α-cellulose recovery, followed by the synthesis and characterization of plum seed-derived carboxymethyl cellulose (PCMC). Then, hybrid bioinks composed of PCMC and sodium alginate were fabricated, and their suitability for extrusion-based bioprinting was explored. The PCMC bioinks exhibit a remarkable shear-thinning property, enabling effortless extrusion through the nozzle and maintaining excellent initial shape fidelity. This bioink was then used to print muscle-mimetic 3D structures containing C2C12 cells. Subsequently, the cytotoxicity of PCMC was evaluated at different concentrations to determine the maximum acceptable concentration. As a result, cytotoxicity was not observed in hydrogels containing a suitable concentration of PCMC. Cell viability was also evaluated after printing PCMC-containing bioinks, and it was observed that the bioprinting process caused minimal damage to the cells. This suggests that PCMC/alginate hybrid bioink can be used as a very attractive material for bioprinting applications.

Iron homeostasis is considered a key factor in human metabolism, and abrogation in the system could create adverse effects, including cancer. Moreover, 6-gingerol is a widely used bioactive phenolic compound with anticancer activity, and studies on its exact mechanisms on non-small cell lung cancer (NSCLC) cells are still undergoing. This study aimed to find the mechanism of cell death induction by 6-gingerol in NSCLC cells. Western blotting, real-time polymerase chain reaction, and flow cytometry were used for molecular signaling studies, and invasion and tumorsphere formation assay were also used with comet assay for cellular processes. Our results show that 6-gingerol inhibited cancer cell proliferation and induced DNA damage response, cell cycle arrest, and apoptosis in NSCLC cells, and cell death induction was found to be the mitochondrial-dependent intrinsic apoptosis pathway. The role of iron homeostasis in the cell death induction of 6-gingerol was also investigated, and iron metabolism played a vital role in the anticancer ability of 6-gingerol by downregulating EGFR/JAK2/STAT5b signaling or upregulating p53 and downregulating PD-L1 expression. Also, 6-gingerol induced miR-34a and miR-200c expression, which may indicate regulation of PD-L1 expression by 6-gingerol. These results suggest that 6-gingerol could be a candidate drug against NSCLC cells and that 6-gingerol could play a vital role in cancer immunotherapy.

In this study, the high isoflavone-enriched soy leaves (IESLs) were manufactured by treating with the chemical inducer ethephon, a plant growth regulator, to confirm changes in the properties of soy leaves (SLs), which are underutilized. Ethephon treatment concentrations consisted of 0 (SL1), 150 (SL2), and 300 (SL3) μg/mL. The composition analysis and physiological activity were conducted according to the ethephon treatment concentration of SLs. There was no significant difference in the proximate composition and fatty acids, except for an increase with increasing ethephon treatment concentrations. Depending on the ethephon treatment concentration, free amino acids increased to 1413.0, 1569.8, and 2100.4 mg/100 g, and water-soluble vitamins increased to 246.7, 244.7, and 501.6 mg/100 g. In particular, the functional substance isoflavone increased significantly to 1430.11, 7806.42, and 14,968.00 μg/g. Through this study, it was confirmed that the nutritional components and isoflavones of SLs increased according to the ethephon treatment concentration, a chemical inducer treatment agent. This can be used as a high-value-added biosubstance for raw materials for functional foods, cosmetics, and for natural drugs.

Personalized medicine aims to provide tailored medical treatment that considers the clinical, genetic, and environmental characteristics of patients. iPSCs have attracted considerable attention in the field of personalized medicine; however, the inherent limitations of iPSCs prevent their widespread use in clinical applications. That is, it would be important to develop notable engineering strategies to overcome the current limitations of iPSCs. Such engineering approaches could lead to significant advances in iPSC-based personalized therapy by offering innovative solutions to existing challenges, from iPSC preparation to clinical applications. In this review, we summarize how engineering strategies have been used to advance iPSC-based personalized medicine by categorizing the development process into three distinctive steps: 1) the production of therapeutic iPSCs; 2) engineering of therapeutic iPSCs; and 3) clinical applications of engineered iPSCs. Specifically, we focus on engineering strategies and their implications for each step in the development of iPSC-based personalized medicine., (© 2023. The Author(s).)

The development of sophisticated machine learning algorithms has made it possible to detect critical health conditions like cardiac arrhythmia, directly from electrocardiogram (ECG) recordings. Large-scale machine learning models, like deep neural networks, are well known to underperform when subjected to small perturbations which would not pose a challenge to physicians. This is a hurdle that needs to be removed to facilitate wide-scale adoption. We find this to be true even for models trained using data-augmentation schemes.In this paper, we show that using memory classifiers it is possible to attain a boost in robustness using expert-informed features. Memory classifiers combine standard deep neural network training with a domain knowledge-guided similarity metric to boost the robustness of classifiers. We evaluate the performance of the models against naturally occurring physiological perturbations, specifically electrode movement, muscle artifact, and baseline wander noise. Our approach demonstrates improved robustness across all evaluated noises for an average improvement in F1 score of 3.13% compared to models using data augmentation techniques.Clinical relevance- This approach improves the robustness of deep learning methods in safety-critical medical applications.

Background: Snakebite is a neglected public health issue in Nepal. We aimed to characterize patients with snake envenoming admitted to hospital in south-western Nepal., Methods: This was a prospective cohort study of 476 snakebite patients admitted to Bheri Hospital from May to December 2017. Data were collected on patient demographics, bite circumstances, snake type, treatment-seeking behavior, clinical effects, complications and treatment., Results: There were 139/476 (29%) patients with clinical features of envenomation and 10 deaths (8%), of which six were prehospital deaths; 325/476 (68%) patients used non-recommended prehospital first aid, including 278 (58%) who applied a tourniquet and 43 (9%) consulting traditional healers. Median time to hospital arrival was 1.5 (IQR: 0.8-4) h. Also, 127 envenomated patients (91%) developed neurotoxicity and 12 (9%) hemotoxicity, while 124 patients (89%) received antivenom, with a median dose of 10 (4-30) vials. Three patients developed anaphylaxis following antivenom administration; 111 of 139 (80%) cases were admitted to the ICU and 48 (35%) were intubated. Median length of hospital stay for all cases was 0.5 (IQR: 0.5-1.2) d, but it was 2.2 (IQR: 1.5-3.8) d for envenomated cases., Conclusions: The majority of snakebite patients used non-recommended first aid or attended traditional healers. Almost one-third of patients developed systemic envenomation and required antivenom. The case fatality rate was high, but many died prior to arriving in hospital., (© The Author(s) 2023. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

The skin is the most voluminous organ of the human body and is exposed to the outer environment. Such exposed skin suffers from the effects of various intrinsic and extrinsic aging factors. Skin aging is characterized by features such as wrinkling, loss of elasticity, and skin pigmentation. Skin pigmentation occurs in skin aging and is caused by hyper-melanogenesis and oxidative stress. Protocatechuic acid (PCA) is a natural secondary metabolite from a plant-based source widely used as a cosmetic ingredient. We chemically designed and synthesized PCA derivatives conjugated with alkyl esters to develop effective chemicals that have skin-whitening and antioxidant effects and enhance the pharmacological activities of PCA. We identified that melanin biosynthesis in B16 melanoma cells treated with alpha-melanocyte-stimulating hormone (α-MSH) is decreased by PCA derivatives. We also found that PCA derivatives effectively have antioxidant effects in HS68 fibroblast cells. In this study, we suggest that our PCA derivatives are potent ingredients for developing cosmetics with skin-whitening and antioxidant effects.

Developing a scaffold for efficient and functional bone regeneration remains challenging. To accomplish this goal, a "scaffold-on-a-chip" device was developed as a platform to aid with the evaluation process. The device mimics a microenvironment experienced by a transplanted bone scaffold. The device contains a circular space at the center for scaffold insert and microfluidic channel that encloses the space. Such a design allows for monitoring of cell behavior at the blood-scaffold interphase. MC3T3-E1 cells were cultured with three different types of scaffold inserts to test its capability as an evaluation platform. Cellular behaviors, including migration, morphology, and osteogenesis with each scaffold, were analyzed through fluorescence images of live/dead assay and immunocytochemistry. Cellular behaviors, such as migration, morphology, and osteogenesis, were evaluated. The results revealed that our platform could effectively evaluate the osteoconductivity and osteoinductivity of scaffolds with various properties. In conclusion, our proposed platform is expected to replace current in vivo animal models as a highly relevant in vitro platform and can contribute to the fundamental study of bone regeneration.

Background: Conventional preclinical models often miss drug toxicities, meaning the harm these drugs pose to humans is only realized in clinical trials or when they make it to market. This has caused the pharmaceutical industry to waste considerable time and resources developing drugs destined to fail. Organ-on-a-Chip technology has the potential improve success in drug development pipelines, as it can recapitulate organ-level pathophysiology and clinical responses; however, systematic and quantitative evaluations of Organ-Chips' predictive value have not yet been reported., Methods: 870 Liver-Chips were analyzed to determine their ability to predict drug-induced liver injury caused by small molecules identified as benchmarks by the Innovation and Quality consortium, who has published guidelines defining criteria for qualifying preclinical models. An economic analysis was also performed to measure the value Liver-Chips could offer if they were broadly adopted in supporting toxicity-related decisions as part of preclinical development workflows., Results: Here, we show that the Liver-Chip met the qualification guidelines across a blinded set of 27 known hepatotoxic and non-toxic drugs with a sensitivity of 87% and a specificity of 100%. We also show that this level of performance could generate over $3 billion annually for the pharmaceutical industry through increased small-molecule R&D productivity., Conclusions: The results of this study show how incorporating predictive Organ-Chips into drug development workflows could substantially improve drug discovery and development, allowing manufacturers to bring safer, more effective medicines to market in less time and at lower costs., (© 2022. The Author(s).)

Aims: In biology and medicine, hypoxia refers to reduced oxygen tension or oxygen starvation resulting from various environmental or pathological conditions. Prolonged hypoxia may lead to an imbalance in protein production and a loss of muscle mass in animals. The physiological response to hypoxia includes oxidative stress-induced activation of complex cell-signaling networks such as hypoxia-inducible factor (HIF), phosphoinositide 3-kinase (PI3K), and Janus kinase/signal transducer and activator of transcription (JAK-STAT). Methylsulfonylmethane (MSM) is a natural sulfur compound that regulates HIF-1α expression and provides cytoprotection from oxidative stress. In this study, we explored the anti-hypoxic activity and cytoprotective effect of MSM in cobalt chloride (CoCl 2 )-induced hypoxic C2C12 mouse myoblast culture., Materials and Methods: We used western blotting, real time PCR, flow cytometry for molecular signaling studies and we also used MTT assay and ChIP assay along with comet assay for cellular processes., Key Findings: MSM prevented the CoCl 2 induced cytotoxicity. Molecular markers of hypoxia, induced by CoCl 2 , were normalized or reduced by MSM, which also inhibited the effect of CoCl 2 -induced JAK2/STAT5b/Cyclin D1 and PI3K/AKT signaling. CoCl 2 -induced oxidative stress results in activation of the NRF2/HO-1-mediated cell survival pathway and inhibition of DNA repair, both of which were prevented by MSM., Significance: We suggest MSM can be considered as a candidate drug for reducing the effects of hypoxia in both animals and humans., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Taraxacum officinale (dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain unclear. The present study aimed to explore the effects of luteolin, the main biologically active compound of T. officinale , on gene expression profiles in MDA-MB-231 and MCF-7 breast cancer cells. The results revealed that luteolin effectively inhibited the proliferation and motility of the MDA-MB-231 and MCF-7 cells. The mRNA expression profiles were determined using gene expression array analysis and analyzed using a bioinformatics approach. A total of 41 differentially expressed genes (DEGs) were found in the luteolin-treated MDA-MB-231 and MCF-7 cells. A Gene Ontology analysis revealed that the DEGs, including AP2B1, APP, GPNMB and DLST, mainly functioned as oncogenes. The human protein atlas database also found that AP2B1, APP, GPNMB and DLST were highly expressed in breast cancer and that AP2B1 (cut-off value, 75%) was significantly associated with survival rate ( p = 0.044). In addition, a Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were involved in T-cell leukemia virus 1 infection and differentiation. On the whole, the findings of the present study provide a scientific basis that may be used to evaluate the potential benefits of luteolin in human breast cancer. Further studies are required, however, to fully elucidate the role of the related molecular pathways.

Natural calcium phosphate cements (CPCs) derived from sintered animal bone have been investigated to treat bone defects, but their low mechanical strength remains a critical limitation. Graphene improves the mechanical properties of scaffolds and promotes higher osteoinduction. To this end, reduced graphene oxide-incorporated natural calcium phosphate cements (RGO-CPCs) are fabricated for reinforcement of CPCs' characteristics. Pulsed electromagnetic fields (PEMFs) were additionally applied to RGO-CPCs to promote osteogenic differentiation ability. The fabricated RGO-CPCs show distinct surface properties and chemical properties according to the RGO concentration. The RGO-CPCs' mechanical properties are significantly increased compared to CPCs owing to chemical bonding between RGO and CPCs. In in vitro studies using a mouse osteoblast cell line and rat-derived adipose stem cells, RGO-CPCs are not severely toxic to either cell type. Cell migration study, western blotting, immunocytochemistry, and alizarin red staining assay reveal that osteoinductivity as well as osteoconductivity of RGO-CPCs was highly increased. In in vivo study, RGO-CPCs not only promoted bone ingrowth but also enhanced osteogenic differentiation of stem cells. Application of PEMFs enhanced the osteogenic differentiation of stem cells. RGO-CPCs with PEMFs can overcome the flaws of previously developed natural CPCs and are anticipated to open the gate to clinical application for bone repair and regeneration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Embryonic cancer cells (CSCs) could cause different types of cancer, a skill that makes them even more dangerous than other cancer cells. Identifying CSCs using natural products is a good option as it inhibits the recurrence of cancer with moderate various effects. Ursolic acid (UA) is a pentacyclic triterpenoid extracted from fruit and herbal remedies and has known anticancer functions against various cancer cells. However, its potential against CSCs remains uncertain. This study was planned to examine the induction of cell apoptosis by the UA. For cell signaling studies, we performed experiments, which are real-time qPCR and immunoblotting. Also, various cellular processes were analyzed using flow cytometry. The results raised a barrier to cell proliferation by the UA in NTERA-2 and NCCIT cells. Morphological studies also confirmed the UA's ability to cause cell death in embryonic CSCs. Examination of cell death importation showed that the UA formed the expression of the iNOS and thus the cell generation and mitochondrial reactive oxygen generation, which created a reaction to cellular DNA damage by raising the protein levels of phospho-histone ATR and ATM. In addition, the UA created the binding of the G0/G1 cell cycle to NTERA-2 and NCCIT cells, improved the expression levels of p21 and p27, and reduced the expression levels of CDK4, cyclin D1, and cyclin E, confirming the UA's ability to initiate cell cycle arrest. Finally, the UA created an internal mechanism of apoptosis in the embryonic CSC using BAX and cytochrome c regulation as well as the regulation of BCL-xL and BCL-2 proteins. Therefore, UA could be the best candidate for targeting CSCs and thus suppressing the emergence of cancer., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Dong Young Kang et al.)

In this study, we have analysed the effects of a silane coupling agent on the volume fraction of zirconia for digital light processing (DLP)-based additive manufacturing processes. Zirconia suspension was prepared by the incorporation of silane-modified zirconia particles (experimental group) or untreated zirconia particles (control group). Furthermore, the control and experimental group were subdivided into three groups based on the volume fraction (52, 54, and 56 vol%) of zirconia particles. The disk-shaped zirconia samples were 3D (three-dimensional) printed using the DLP technique and their physical and mechanical properties were evaluated. The addition of a silane coupling agent to the zirconia samples was found to have influence of about 6% on the hardness and biaxial flexural strength. Moreover, the decrease in minute air gaps inside the zirconia layers significantly increased the material density (visualized from the microstructure analysis). Thus, from this study, it was established that the silane-modified zirconia particles had a positive effect on the physical properties of the zirconia parts.

Globally, the incidence rate for breast cancer ranks first. Treatment for early-stage breast cancer is highly cost effective. Five-year survival rate for stage 0-2 breast cancer exceeds 90%. Screening mammography has been acknowledged as the most reliable way to diagnose breast cancer at an early stage. Taiwan government has been urging women without any symptoms, aged between 45 and 69, to have a screening mammogram bi-yearly. This brings about a large workload for radiologists. In light of this, this paper presents a deep neural network (DNN)-based model as an efficient and reliable tool to assist radiologists with mammographic interpretation. For the first time in the literature, mammograms are completely classified into BI-RADS categories 0, 1, 2, 3, 4A, 4B, 4C and 5. The proposed model was trained using block-based images segmented from a mammogram dataset of our own. A block-based image was applied to the model as an input, and a BI-RADS category was predicted as an output. At the end of this paper, the outperformance of this work is demonstrated by an overall accuracy of 94.22%, an average sensitivity of 95.31%, an average specificity of 99.15% and an area under curve (AUC) of 0.9723. When applied to breast cancer screening for Asian women who are more likely to have dense breasts, this model is expected to give a higher accuracy than others in the literature, since it was trained using mammograms taken from Taiwanese women.

The near-perivascular accumulation in solid tumors and short-lived span in circulation, derails even the most competent nanoparticles (NPs) from achieving their maximum therapeutic potential. Moreover, delivering them across the blood brain/tumor barrier (BBB/BTB) is further challenging to sought anticancer effect. To address these key challenges, we designed a linearly aligned nucleic acid-complexed polydixylitol-based polymeric nanochains (X-NCs), with inherent hyperosmotic properties enabling transmigration of the BBB/BTB and navigation through deeper regions of the brain tumor. The high aspect ratio adds shape-dependent functional aspects to parent particles by providing effective payload increment and nuclear factor of activated T cells-5 (NFAT5)-mediated cellular uptake. Therefore, serine hydroxymethyltransferase 1 (SHMT1) siRNA-loaded nanochains not only demonstrated to transmigrate the BTB, but also resulted in remarkably reducing the tumor size to 97% in the glioblastoma xenograft brain tumor mouse models. Our study illustrates how the hyperosmotic nanochains with high aspect ratio and aligned structure can accelerate a therapeutic effect in aggressive brain tumors post-transmigration of the BBB/BTB by utilizing an NFAT5 mode of uptake mechanism., (Copyright © 2021. Published by Elsevier Ltd.)

During a survey of fungal diversity associated with insects, mud, soil, and freshwater niches in different areas in Korea, nine interesting fungal strains were isolated. Based on their morphological characteristics and molecular phylogeny analyses, using a combined data set of β-tubulin ( BenA ), calmodulin ( CaM ), and second largest subunit of RNA polymerase ( RPB2 ) sequences, the strains CNUFC AM-44, CNUFC JCW3-4, CNUFC S708, CNUFC WT202, CNUFC AS1-29, CNUFC JCW3-5, CNUFC JDP37, and CNUFC JDP62 were identified as Aspergillus alabamensis , A. floridensis , A. subversicolor , Penicillium flavigenum , P . laevigatum , P. lenticrescens , Talaromyces adpressus , and T . beijingensis , respectively. The strain CNUFC JT1301 belongs to series Westlingiorum in section Citrina and is phylogenetically related to P . manginii . However, slow growth when cultivated on CYA, MEA, CREA is observed and the property can be used to easily distinguish the new species from these species. Additionally, P. manginii is known to produce sclerotia, while CNUFC JT1301 strain does not. Herein, the new fungal species is proposed as P . aquadulcis sp. nov. Eight species, A . alabamensis , A. floridensis , A. subversicolor , P . flavigenum , P . laevigatum , P. lenticrescens , T . adpressus , and T . beijingensis , have not been previously reported in Korea. The present study expands the known distribution of fungal species belonging to the families Aspergillaceae and Trichocomaceae in Korea., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

Abstract: Sarcopenia, characterized by a decline of skeletal muscle mass, has emerged as an important prognostic factor for cancer patients. Trunk computed tomography (CT) is a commonly used modality for assessment of cancer disease extent and treatment outcome. CT images can also be used to analyze the skeletal muscle mass filtered by the appropriate range of Hounsfield scale. However, a manual depiction of skeletal muscle in CT scan images for assessing skeletal muscle mass is labor-intensive and unrealistic in clinical practice. In this paper, we propose a novel U-Net based segmentation system for CT scan of paravertebral muscles in the third and fourth lumbar spines. Since the number of training samples is limited (i.e., 1024 CT images only), it is well-known that the performance of the deep learning approach is restricted due to overfitting. A data augmentation strategy to enlarge the diversity of the training set to boost the performance further is employed. On the other hand, we also discuss how the number of features in our U-Net affects the performance of the semantic segmentation. The efficacies of the proposed methodology based on w/ and w/o data augmentation and different feature maps are compared in the experiments. We show that the Jaccard score is approximately 95.0% based on the proposed data augmentation method with only 16 feature maps used in U-Net. The stability and efficiency of the proposed U-Net are verified in the experiments in a cross-validation manner., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Embryonic cancer stem cells (CSCs) can differentiate into any cancer type. Targeting CSCs with natural compounds is a promising approach as it suppresses cancer recurrence with fewer adverse effects. 6-Gingerol is an active component of ginger, which exhibits well-known anti-cancer activities. This study determined the mechanistic aspects of cell death induction by 6-gingerol. To analyze cellular processes, we used Western blot and real-time qPCR for molecular signaling studies and conducted flow cytometry. Our results suggested an inhibition of CSC marker expression and Wnt/β-catenin signaling by 6-gingerol in NCCIT and NTERA-2 cells. 6-Gingerol induced reactive oxygen species generation, the DNA damage response, cell cycle arrest, and the intrinsic pathway of apoptosis in embryonic CSCs. Furthermore, 6-gingerol inhibited iron metabolism and induced PTEN, which both played vital roles in the induction of cell death. The activation of PTEN resulted in the inhibition of PD-L1 expression through PI3K/AKT/p53 signaling. The induction of PTEN also mediated the downregulation of microRNAs miR-20b, miR-21, and miR-130b to result in PD-L1 suppression by 6-gingerol. Hence, 6-gingerol may be a promising candidate to target CSCs by regulating PTEN-mediated PD-L1 expression., Competing Interests: Author J-ML was employed by company SK Bioscience. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sp, Kang, Jo, Lee, Bae and Jang.)

Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selectively target such cells are urgently required. Reactive oxygen species (ROS)-producing enzymes are the reason for an elevated tumor oxidant status. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor, which upon detecting cellular oxidative stress, binds to the promoter region of antioxidant genes. By triggering a cytoprotective response, Nrf2 maintains cellular redox status. Cripto-1 participates in the self-renewal of CSCs. Herein, luteolin, a flavonoid found in Taraxacum &nbsp; officinale extract, was determined to inhibit the expressions of stemness-related transcriptional factors, the ATP-binding cassette transporter G2 (ABCG2), CD44, aldehyde dehydrogenase 1 activity as well as the sphere formation properties of breast CSCs. Furthermore, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features. The combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells. These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments.

Embryonic cancer stem cells (CSCs) can differentiate into any cancer type. Targeting CSC using natural compounds is a good approach as it suppresses cancer recurrence with fewer adverse effects, and methylsulfonylmethane (MSM) is a sulfur-containing compound with well-known anticancer activities. This study determined the mechanistic aspects of the anticancer activity of MSM. We used Western blotting and real-time qPCR for molecular signaling studies and conducted flow cytometry for analyzing the processes in cells. Our results suggested an inhibition in the expression of CSC markers and Wnt/β-catenin signaling. MSM induced TRAIL-mediated extrinsic apoptosis in NCCIT and NTERA-2 cells rather than an intrinsic pathway. Inhibition of iron metabolism-dependent reactive oxygen species (ROS) generation takes part in TRAIL-mediated apoptosis induction by MSM. Suppressing iron metabolism by MSM also regulated p38/p53/ERK signaling and microRNA expressions, such as upregulating miR-130a and downregulating miR-221 and miR-222, which resulted in TRAIL induction and thereby extrinsic pathway of apoptosis. Hence, MSM could be a good candidate for neoadjuvant therapy by targeting CSCs by inhibiting iron metabolism.

Iron metabolism and heme biosynthesis are essential processes in cells during the energy cycle. Alteration in these processes could create an inflammatory condition, which results in tumorigenesis. Studies are conducted on the exact role of iron/heme metabolism in induced inflammatory conditions. This study used lipopolysaccharide (LPS)- or high-glucose-induced inflammation conditions in THP-1 cells to study how iron/heme metabolism participates in inflammatory responses. Here, we used iron and heme assays for measuring total iron and heme. We also used flow cytometry and Western blotting to analyze molecular responses. Our results demonstrated that adding LPS or high-glucose induced iron formation and heme synthesis and elevated the expression levels of proteins responsible for iron metabolism and heme synthesis. We then found that further addition of heme or 5-aminolevulinic acid (ALA) increased heme biosynthesis and promoted inflammatory responses by upregulating TLR4/NF-κB and inflammatory cytokine expressions. We also demonstrated the inhibition of heme synthesis using succinylacetone (SA). Moreover, N-MMP inhibited LPS- or high-glucose-induced inflammatory responses by inhibiting TLR4/NF-κB signaling. Hence, iron/heme metabolism checkpoints could be considered a target for treating inflammatory conditions.

Tumor immune escape is a common process in the tumorigenesis of non-small cell lung cancer (NSCLC) cells where programmed death ligand-1 (PD-L1) expression, playing a vital role in immunosuppression activity. Additionally, epidermal growth factor receptor (EGFR) phosphorylation activates Janus kinase-2 (JAK2) and signal transduction, thus activating transcription 3 (STAT3) to results in the regulation of PD-L1 expression. Chemotherapy with commercially available drugs against NSCLC has struggled in the prospect of adverse effects. Nobiletin is a natural flavonoid isolated from the citrus peel that exhibits anti-cancer activity. Here, we demonstrated the role of nobiletin in evasion of immunosuppression in NSCLC cells by Western blotting and real-time polymerase chain reaction methods for molecular signaling analysis supported by gene silencing and specific inhibitors. From the results, we found that nobiletin inhibited PD-L1 expression through EGFR/JAK2/STAT3 signaling. We also demonstrated that nobiletin exhibited p53-independent PD-L1 suppression, and that miR-197 regulates the expression of STAT3 and PD-L1, thereby enhancing anti-tumor immunity. Further, we evaluated the combination ability of nobiletin with an anti-PD-1 monoclonal antibody in NSCLC co-culture with peripheral blood mononuclear cells. Similarly, we found that nobiletin assisted the induction of PD-1/PD-L1 blockade, which is a key factor for the immune escape mechanism. Altogether, we propose nobiletin as a modulator of tumor microenvironment for cancer immunotherapy.

The use of bone graft materials is required for the treatment of bone defects damaged beyond the critical defect; therefore, injectable calcium phosphate cement (CPC) is actively used after surgery. The application of various polymers to improve injectability, mechanical strength, and biological function of injection-type CPC is encouraged. We previously developed a chitosan-PEG conjugate (CS/PEG) by a sulfur (VI) fluoride exchange reaction, and the resulting chitosan derivative showed high solubility at a neutral pH. We have demonstrated the CPC incorporated with a poly (ethylene glycol) (PEG)-grafted chitosan (CS/PEG) and developed CS/PEG CPC. The characterization of CS/PEG CPC was conducted using Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The initial properties of CS/PEG CPCs, such as the pH, porosity, mechanical strength, zeta potential, and in vitro biocompatibility using the WST-1 assay, were also investigated. Moreover, osteocompatibility of CS/PEG CPCs was carried out via Alizarin Red S staining, immunocytochemistry, and Western blot analysis. CS/PEG CPC has enhanced mechanical strength compared to CPC, and the cohesion test also demonstrated in vivo stability. Furthermore, we determined whether CS/PEG CPC is a suitable candidate for promoting the osteogenic ability of Dental Pulp Stem Cells (DPSC). The elution of CS/PEG CPC entraps more calcium ion than CPC, as confirmed through the zeta potential test. Accordingly, the ion trapping effect of CS/PEG is considered to have played a role in promoting osteogenic differentiation of DPSCs. The results strongly suggested that CS/PEG could be used as suitable additives for improving osteogenic induction of bone substitute materials.

Objective: To assess the expression of vascular normalization genes in different molecular subtypes of breast cancer and to determine whether molecular subtypes with a higher vascular normalization gene expression can be identified using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI)., Materials and Methods: This prospective study evaluated 306 female (mean age ± standard deviation, 50 ± 10 years), recruited between January 2014 and August 2017, who had de novo breast cancer larger than 1 cm in diameter (308 tumors). DCE MRI followed by IVIM DWI studies using 11 different b-values (0 to 1200 s/mm²) were performed on a 1.5T MRI system. The Tofts model and segmented biexponential IVIM analysis were used. For each tumor, the molecular subtype (according to six [I-VI] subtypes and PAM50 subtypes), expression profile of genes for vascular normalization, pericytes, and normal vascular signatures were determined using freshly frozen tissue. Statistical associations between imaging parameters and molecular subtypes were examined using logistic regression or linear regression with a significance level of p = 0.05., Results: Breast cancer subtypes III and VI and PAM50 subtypes luminal A and normal-like exhibited a higher expression of genes for vascular normalization, pericyte markers, and normal vessel function signature ( p < 0.001 for all) compared to other subtypes. Subtypes III and VI and PAM50 subtypes luminal A and normal-like, versus the remaining subtypes, showed significant associations with K trans , k ep , v p , and IAUGC BN 90 on DEC MRI, with relatively smaller values in the former. The subtype grouping was significantly associated with D, with relatively less restricted diffusion in subtypes III and VI and PAM50 subtypes luminal A and normal-like., Conclusion: DCE MRI and IVIM parameters may identify molecular subtypes of breast cancers with a different vascular normalization gene expression., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Janus kinase 2 (JAK2) and STAT3 signaling is considered a major pathway in lipopolysaccharide (LPS)‑induced inflammation. Toll‑like receptor 4 (TLR‑4) is an inflammatory response receptor that activates JAK2 during inflammation. STAT3 is a transcription factor for the pro‑inflammatory cytokine IL‑6 in inflammation. Sulfur is an essential element in the amino acids and is required for growth and development. Non‑toxic sulfur (NTS) can be used in livestock feeds as it lacks toxicity. The present study aimed to inhibit LPS‑induced inflammation in C2C12 myoblasts using NTS by regulating TLR‑4 and JAK2/STAT3 signaling via the modulation of IL‑6. The 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay was conducted to analyze cell viability and reverse transcription polymerase chain reaction and western blotting performed to measure mRNA and protein expression levels. Chromatin immunoprecipitation and enzyme‑linked immunosorbent assays were used to determine the binding activity of proteins. The results indicated that NTS demonstrated a protective effect against LPS‑induced cell death and inhibited LPS‑induced expression of TLR‑4, JAK2, STAT3 and IL‑6. In addition, NTS inhibited the expression of nuclear phosphorylated‑STAT3 and its binding to the IL‑6 promoter. Therefore, NTS may be a potential candidate drug for the treatment of inflammation.

Recently, natural compounds have been used globally for cancer treatment studies. Silibinin is a natural compound extracted from Silybum marianum (milk thistle), which has been suggested as an anticancer drug through various studies. Studies on its activity in various cancers are undergoing. This study demonstrated the molecular signaling behind the anticancer activity of silibinin in non-small cell lung cancer (NSCLC). Quantitative real-time polymerase chain reaction and Western blotting analysis were performed for molecular signaling analysis. Wound healing assay, invasion assay, and in vitro angiogenesis were performed for the anticancer activity of silibinin. The results indicated that silibinin inhibited A549, H292, and H460 cell proliferation in a concentration-dependent manner, as confirmed by the induction of G0/G1 cell cycle arrest and apoptosis and the inhibition of tumor angiogenesis, migration, and invasion. This study also assessed the role of silibinin in suppressing tumorsphere formation using the tumorsphere formation assay. By binding to the epidermal growth factor receptor (EGFR), silibinin downregulated phosphorylated EGFR expression, which then inhibited its downstream targets, the JAK2/STAT5 and PI3K/AKT pathways, and thereby reduced matrix metalloproteinase, PD-L1, and vascular endothelial growth factor expression. Binding analysis demonstrated that STAT5 binds to the PD-L1 promoter region in the nucleus and silibinin inhibited the STAT5/PD-L1 complex. Altogether, silibinin could be considered as a candidate for tumor immunotherapy and cancer stem cell-targeted therapy.

Endoscopic submucosal dissection (ESD) is a surgical procedure to remove early neoplastic lesions in the gastrointestinal tract with the critical issue of perforation. A submucosal fluid cushion, such as normal saline, is used as a cushioning agent to prevent perforation; however, its cushioning maintenance is insufficient for surgery. In this study, we introduce an injectable thermosensitive chitosan solution (CS) with β -glycerophosphate ( β -GP) as a submucosal injection agent for ESD. The CS/ β -GP system with optimal β -GP concentration showed drastic viscosity change near body temperature while other commercial products did not. Additionally, the injectability of the solution was similar to or greater than other commercial products. The solution with low β -GP concentration showed low cytotoxicity similar to other products. An in vivo preclinical study illustrated maintenance of the high cushioning of the thermosensitive solutions. These results indicate that a CS/ β -GP system with optimal β -GP concentration might be used as a submucosal injection agent in ESD, and further studies are needed to validate the effectiveness of the solutions in vivo.

Lipopolysaccharide (LPS)-induced inflammatory response leads to serious damage, up to and including tumorigenesis. Natural mineral sulfur, non-toxic sulfur (NTS), and methylsulfonylmethane (MSM) have anti-inflammatory activity that may inhibit LPS-induced inflammation. We hypothesized that sulfur compounds could inhibit LPS-induced inflammatory responses in CCD-986Sk skin fibroblasts. We used Western blotting and real-time PCR to analyze molecular signaling in treated and untreated cultures. We also used flow cytometry for cell surface receptor analysis, comet assays to evaluate DNA damage, and ELISA-based cytokine detection. LPS induced TLR4 activation and NF-κB signaling via canonical and protein kinase C (PKC)-dependent pathways, while NTS and MSM downregulated that response. NTS and MSM also inhibited LPS-induced nuclear accumulation and binding of NF-κB to proinflammatory cytokines COX-2, IL-1β, and IL-6. Finally, the sulfur compounds suppressed LPS-induced ROS accumulation and DNA damage in CCD-986Sk cells. These results suggest that natural sulfur compounds could be used to treat inflammation and may be useful in the development of cosmetics.

The innate immune system is the first line of the host defense program against pathogens and harmful substances. Antiviral innate immune responses can be triggered by multiple cellular receptors sensing viral components. The activated innate immune system produces interferons (IFNs) and cytokines that perform antiviral functions to eliminate invading viruses. Coronaviruses are single-stranded, positive-sense RNA viruses that have a broad range of animal hosts. Coronaviruses have evolved multiple means to evade host antiviral immune responses. Successful immune evasion by coronaviruses may enable the viruses to adapt to multiple species of host organisms. Coronavirus transmission from zoonotic hosts to humans has caused serious illnesses, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease-2019 (COVID-19), resulting in global health and economic crises. In this review, we summarize the current knowledge of the mechanisms underlying host sensing of and innate immune responses against coronavirus invasion, as well as host immune evasion strategies of coronaviruses.

Hormone-specific anticancer drugs for breast cancer treatment can cause serious side effects. Thus, treatment with natural compounds has been considered a better approach as this minimizes side effects and has multiple targets. 6-Gingerol is an active polyphenol in ginger with various modalities, including anticancer activity, although its mechanism of action remains unknown. Increases in the level of reactive oxygen species (ROS) can lead to DNA damage and the induction of DNA damage response (DDR) mechanism, leading to cell cycle arrest apoptosis and tumorsphere suppression. Epidermal growth factor receptor (EGFR) promotes tumor growth by stimulating signaling of downstream targets that in turn activates tumor protein 53 (p53) to promote apoptosis. Here we assessed the effect of 6-gingerol treatment on MDA-MB-231 and MCF-7 breast cancer cell lines. 6-Gingerol induced cellular and mitochondrial ROS that elevated DDR through ataxia-telangiectasia mutated and p53 activation. 6-Gingerol also induced G0/G1 cell cycle arrest and mitochondrial apoptosis by mediating the BAX/BCL-2 ratio and release of cytochrome c. It also exhibited a suppression ability of tumorsphere formation in breast cancer cells. EGFR/Src/STAT3 signaling was also determined to be responsible for p53 activation and that 6-gingerol induced p53-dependent intrinsic apoptosis in breast cancer cells. Therefore, 6-gingerol may be used as a candidate drug against hormone-dependent breast cancer cells.

Targeted therapy based on natural compounds is one of the best approaches against non-small cell lung cancer. Ursolic acid (UA), a pentacyclic triterpenoid derived from medicinal herbs, has anticancer activity. Studies on the molecular mechanism underlying UA's anticancer activity are ongoing. Here, we demonstrated UA's anticancer activity and the underlying signaling mechanisms. We used Western blotting and real-time quantitative polymerase chain reaction for molecular signaling analysis. We also used in vitro angiogenesis, wound healing, and invasion assays to study UA's anticancer activity. In addition, we used tumorsphere formation and chromatin immunoprecipitation assays for binding studies. The results showed that UA inhibited the proliferation of A549 and H460 cells in a concentration-dependent manner. UA exerted anticancer effects by inducing G0/G1 cell cycle arrest and apoptosis. It also inhibited tumor angiogenesis, migration, invasion, and tumorsphere formation. The molecular mechanism underlying UA activity involves UA's binding to epidermal growth factor receptor (EGFR), reducing the level of phospho-EGFR, and thus inhibiting the downstream JAK2/STAT3 pathway. Furthermore, UA reduced the expressions of vascular endothelial growth factor (VEGF), metalloproteinases (MMPs) and programmed death ligand-1 (PD-L1), as well as the formation of STAT3/MMP2 and STAT3/PD-L1 complexes. Altogether, UA exhibits anticancer activities by inhibiting MMP2 and PD-L1 expression through EGFR/JAK2/STAT3 signaling.

Periodontal diseases occur through bacterial infection in the oral cavity, which can cause alveolar bone loss. Several efforts have been made to reconstruct alveolar bone, such as grafting bone substitutes and 3D-printed scaffolds. Poly(ε-caprolactone) (PCL) is biocompatible and biodegradable, thus demonstrating its potential as a biomaterial substitute; however, it is difficult for cells to adhere to PCL because of its strong hydrophobicity. Therefore, its use as a biomaterial has limitations. In this study, we used graphene oxide (GO) as a coating material to promote the osteogenic differentiation ability of PCL scaffolds. First, 3D-printed PCL scaffolds were fabricated, and the oxygen plasma treatment and coating conditions were established according to the concentration of GO. The physical and chemical properties of the prepared scaffolds were evaluated through water contact angle analysis, Raman spectroscopy, and image analysis. In addition, the adhesion and proliferation of periodontal ligament stem cells (PDLSCs) on the GO scaffolds were assessed via the water-soluble tetrazolium salt-1 (WST-1) assay, and the osteogenic differentiation ability was evaluated through alizarin red S staining. The results confirmed that the cell proliferation and osteogenic differentiation of the PDLSCs were enhanced in the scaffolds coated with oxygen plasma and GO. In conclusion, the plasma-treated GO-coating method that we developed can be used to promote the cell proliferation and osteogenic differentiation of the scaffolds.

Calcium phosphate cements (CPCs) are regarded as promising graft substitutes for bone tissue engineering. However, their wide use is limited by the high cost associated with the complex synthetic processes involved in their fabrication. Cheaper xenogeneic calcium phosphate (CaP) materials derived from waste animal bone may solve this problem. Moreover, the surface topography, mechanical strength, and cellular function of CPCs are influenced by the ratio of micro- to nano-sized CaP (M/NCaP) particles. In this study, we developed waste equine bone (EB)-derived CPCs with various M/NCaP particle ratios to examine the potential capacity of EB-CPCs for bone grafting materials. Our study showed that increasing the number of NCaP particles resulted in reductions in roughness and porosity while promoting smoother surfaces of EB-CPCs. Changes in the chemical properties of EB-CPCs by NCaP particles were observed using X-ray diffractometry. The mechanical properties and cohesiveness of the EB-CPCs improved as the NCaP particle content increased. In an in vitro study, EB-CPCs with a greater proportion of MCaP particles showed higher cell adhesion. Alkaline phosphatase activity indicated that osteogenic differentiation by EB-CPCs was promoted with increased NCaP particle content. These results could provide a design criterion for bone substitutes for orthopedic disease, including periodontal bone defects.

Hydroxyapatite (HA) is a representative substance that induces bone regeneration. Our research team extracted nanohydroxyapatite (EH) from natural resources, especially equine bones, and developed it as a molecular biological tool. Polyethylenimine (PEI) was used to coat the EH to develop a gene carrier. To verify that PEI is well coated in the EH, we first observed the morphology and dispersity of PEI-coated EH (pEH) by electron microscopy. The pEH particles were well distributed, while only the EH particles were not distributed and aggregated. Then, the existence of nitrogen elements of PEI on the surface of the pEH was confirmed by EDS, calcium concentration measurement and fourier transform infrared spectroscopy (FT-IR). Additionally, the pEH was confirmed to have a more positive charge than the 25 kD PEI by comparing the zeta potentials. As a result of pGL3 transfection, pEH was better able to transport genes to cells than 25 kD PEI. After verification as a gene carrier for pEH, we induced osteogenic differentiation of DPSCs by loading the BMP-2 gene in pEH (BMP-2/pEH) and delivering it to the cells. As a result, it was confirmed that osteogenic differentiation was promoted by showing that the expression of osteopontin (OPN), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2) was significantly increased in the group treated with BMP-2/pEH. In conclusion, we have not only developed a novel nonviral gene carrier that is better performing and less toxic than 25 kD PEI by modifying natural HA (the agricultural byproduct) but also proved that bone differentiation can be effectively promoted by delivering BMP-2 with pEH to stem cells., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 [The Author/The Authors].)

Supramolecular hydrogels are considered promising drug carriers in the tissue engineering field due to their versatile nature. Chitosan hydrogels without chemical cross-linkers have low cytotoxicity and good delivery capacity; however, they have lower mechanical properties for injectable hydrogel usage. In this study, we developed novel chitosan derivatives via click chemistry for fabricating supramolecular hydrogels with higher mechanical strength under mild conditions. The chitosan derivative was successfully synthesized by a sulfur fluoride exchange reaction, and the synthesized chitosan-mPEG/Pluronic-F127 (CS-mPEG/F127) interacted with α-cyclodextrin (α-CD) to form a supramolecular hydrogel via a host-guest reaction. The gelation dynamics, hydrogel properties, and bovine serum albumin (BSA) release could be modulated by the concentration ratio of chitosan-mPEG and F127. This supramolecular hydrogel is a promising protein releasing carrier candidate for long term regeneration therapy.

The 3D-printed bioactive ceramic incorporated Poly(ε-caprolactone) (PCL) scaffolds show great promise as synthetic bone graft substitutes. However, 3D-printed scaffolds still lack adequate surface properties for cells to be attached to them. In this study, we modified the surface characteristics of 3D-printed poly(ε-caprolactone)/hydroxyapatite scaffolds using O2 plasma and sodium hydroxide. The surface property of the alkaline hydrolyzed and O2 plasma-treated PCL/HA scaffolds were evaluated using field-emission scanning microscopy (FE-SEM), Alizarin Red S (ARS) staining, and water contact angle analysis, respectively. The in vitro behavior of the scaffolds was investigated using human dental pulp-derived stem cells (hDPSCs). Cell proliferation of hDPSCs on the scaffolds was evaluated via immunocytochemistry (ICC) and water-soluble tetrazolium salt (WST-1) assay. Osteogenic differentiation of hDPSCs on the scaffolds was further investigated using ARS staining and Western blot analysis. The result of this study shows that alkaline treatment is beneficial for exposing hydroxyapatite particles embedded in the scaffolds compared to O2 plasma treatment, which promotes cell proliferation and differentiation of hDPSCs.

Background: γ-Poly-Glutamic Acid (γ-PGA) is a naturally occurring homo-polyamide produced by various strains of Bacillus. It is made from repeating units of L-glutamic acid, D-glutamic acid, or both connected through amide linkages between α-amino and γ-carboxylic acid groups. As a biopolymer substance, the attractive properties of γ-PGA are that it is water-soluble, biodegradable, biocompatible, non-toxic, non-immunogenic, and edible. Therefore, it can be used as a green and environmentally friendly biological material., Methods: The review concentrates on the reports revealing the functions and potential use of γ-PGA and its derivatives in medicine., Results & Discussion: γ-PGA is described to possess several properties that may be exploited in medicine. The biopolymer reportedly has been successfully applied not only as a metal chelator, drug carrier/ deliverer, and gene vector, but also used safely as a vaccine adjuvant, tissue engineering material, and contrast agent., Conclusion: γ-PGA could be potentially considered as a potential biomedical material in the field of medicine., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To understand the athletic characteristics of Thoroughbreds, high-throughput analysis has been conducted using horse muscle tissue. However, an in vitro system has been lacking for studying and validating genes from in silico data. The aim of this study is to validate genes from differentially expressed genes (DEGs) of our previous RNA-sequencing data in vitro. Also, we investigated the effects of exercise-induced stress including heat, oxidative, hypoxic and cortisol stress on horse skeletal muscle derived cells with the top six upregulated genes of DEGs., Methods: Enriched pathway analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool with upregulated genes in horse skeletal muscle tissue after exercise. Among the candidates, the top six genes were analysed through geneMANIA to investigate gene networks. Muscle cells derived from neonatal horse skeletal tissue were maintained and subjected to exercise-related stressors. Transcriptional changes in the top six genes followed by stressors were investigated using qRT-PCR., Results: The inflammation response pathway was the most commonly upregulated pathway after horse exercise. Under non-cytotoxic conditions of exercise-related stressors, the transcriptional response of the top six genes was different among types of stress. Oxidative stress yielded the most similar expression pattern to DEGs., Conclusion: Our results indicate that transcriptional change after horse exercise in skeletal muscle tissue strongly relates to stress response. qRT-PCR results showed that stressors contribute differently to the transcriptional regulation. These results would be valuable information to understand horse exercise in the stress aspect.

Post-surgery failure of dental implants due to alveolar bone loss is currently critical, disturbing the quality of life of senior dental patients. To overcome this problem, bioceramic or bone graft material is loaded into the defect. However, connective tissue invasion instead of osteogenic tissue limits bone tissue regeneration. The guided bone regeneration concept was adapted to solve this problem and still has room for improvements, such as biochemical similarity or oriented structure. In this article, an aligned electrospun-guided bone regeneration barrier with xenograft equine bone-derived nano hydroxyapatite (EBNH-RB) was fabricated by electrospinning EBNH/PCL solution on high-speed rotating drum collector and fiber characterization, viability and differentiation enhancing properties of mesenchymal dental pulp stem cell on the barrier was determined. EBNH-RB showed biochemical and structural similarity to natural bone tissue electron microscopy image analysis and x-ray diffractometer analysis, and had a significantly better effect in promoting osteogenesis based on the increased bioceramic content by promoting cell viability, calcium deposition and osteogenic marker expression, suggesting that they can be successfully applied to regenerate alveolar bone as a guided bone regeneration barrier.

Helicobacter pylori infection is an important pathogenic risk factor for gastric cancer, but it is still unclear what tumor markers for gastric cancer induced by H. pylori can be consistently detected. Using an miRNA microarray, we found that miR-18a-3p (6.02-fold) and miR-4286 (5.73-fold) were significantly increased in H. pylori- associated gastric cancer. In a cohort of gastric cancer patients (N = 104), serum expression of miR-18a-3p and miR-4286 was positively and significantly correlated with H. pylori; furthermore, miR-18a-3p was positively correlated with invasion (P = 0.029), and miR-4286 was positively correlated with tumor stage (P = 0.033), tumor size (P = 0.041), and lymph node metastasis (P = 0.009). Overexpression of miR-18a-3p and miR-4286 also increased cancer cell proliferation and motility and both inhibited expression of BZRAP1, resulting in tumor progression in vitro. In addition, lipopolysaccharide co-mediated the expression of miR-18a-3p and miR-4286 by activating the NF-κB transcription factor, but TAK-242 (TLR4 inhibitor) blocked this effect. These results demonstrate that serum miR-18a-3p and miR-4286 levels in H. pylori-associated gastric cancer may be useful prognostic biomarkers and suggest a novel signaling pathway of targeting BZRAP1 in gastric cancer., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)