Osteoporotic Bone Regeneration via Plenished Biomimetic PLGA Scaffold with Sequential Release System.

Achieving satisfactory bone tissue regeneration in osteoporotic patients with ordinary biomaterials is challenging because of the decreased bone mineral density and aberrant bone microenvironment. In addressing this issue, a biomimetic scaffold (PMEH/SP), incorporating 4-hexylresorcinol (4HR), and substance P (SP) into the poly(lactic-go-glycolic acid) (PLGA) scaffold with magnesium hydroxide (M) and extracellular matrix (E) is introduced, enabling the consecutive release of bioactive agents. 4HR and SP induced the phosphorylation of p38 MAPK and ERK in human umbilical vein endothelial cells (HUVECs), thereby upregulating VEGF expression level. The migration and tube-forming ability of endothelial cells can be promoted by the scaffold, which accelerates the formation and maturation of the bone. Moreover, 4HR played a crucial role in the inhibition of osteoclastogenesis by interrupting the IκB/NF-κB signaling pathway and exhibiting SP, thereby enhancing the migration and angiogenesis of HUVECs. Based on such a synergistic effect, osteoporosis can be suppressed, and bone regeneration can be achieved by inhibiting the RANKL pathway in vitro and in vivo, which is a commonly known mechanism of bone physiology. Therefore, the study presents a promising approach for developing a multifunctional regenerative material for sophisticated osteoporotic bone regeneration.

Developing an Online Health Community Platform for Facilitating Empowerment in Chronic Disease Prevention and Health Promotion.

This study aimed to develop an online health community platform for facilitating the empowerment of people with chronic diseases dwelling in the community regarding disease prevention and health promotion. The user-centered design approach included four main steps: (1) identifying the health problems and needs of target users, (2) developing the content of the platform, (3) constructing the platform, and (4) pilot testing, refinement, and finalization. An online health community platform available both in a mobile application and a Web-enabled application has been launched to facilitate empowerment and self-management by people with chronic conditions. The main components of the application comprised (1) screening for chronic diseases and health problems, (2) setting personal goals for health promotion and action planning to achieve the goals themselves, (3) offering an online health community with shared group goals that help users engage with their peers to attain their goals, and (4) creating one's own online health community and inviting others to participate. The platform has the potential to encourage people with chronic conditions to proactively engage in their own health promotion. Future studies are needed to determine the impact of the application on self-management and empowerment for its users.

Human Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Neural Differentiation of Neural Progenitor Cells.

Mesenchymal stem cells (MSCs) have been adopted in various preclinical and clinical studies because of their multipotency and low immunogenicity. However, numerous obstacles relating to safety issues remain. Therefore, MSC-derived extracellular vesicles (EVs) have been recently employed. EVs are nano-sized endoplasmic reticulum particles generated and released in cells that have similar biological functions to their origin cells. EVs act as cargo for bioactive molecules such as proteins and genetic materials and facilitate tissue regeneration. EVs obtained from adipose-derived MSC (ADMSC) also have neuroprotective and neurogenesis effects. On the basis of the versatile effects of EVs, we aimed to enhance the neural differentiation ability of ADMSC-derived EVs by elucidating the neurogenic-differentiation process. ADMSC-derived EVs isolated from neurogenesis conditioned media (differentiated EVs, dEVs) increased neurogenic ability by altering innate microRNA expression and cytokine composition. Consequently, dEVs promoted neuronal differentiation of neural progenitor cells in vitro, suggesting that dEVs are a prospective candidate for EV-based neurological disorder regeneration therapy.

Enhancing Neurogenesis of Neural Stem Cells Using Homogeneous Nanohole Pattern-Modified Conductive Platform.

Biocompatible platforms, wherein cells attach and grow, are important for controlling cytoskeletal dynamics and steering stem cell functions, including differentiation. Among various components, membrane integrins play a key role in focal adhesion of cells (18-20 nm in size) and are, thus, highly sensitive to the nanotopographical features of underlying substrates. Hence, it is necessary to develop a platform/technique that can provide high flexibility in controlling nanostructure sizes. We report a platform modified with homogeneous nanohole patterns, effective in guiding neurogenesis of mouse neural stem cells (mNSCs). Sizes of nanoholes were easily generated and varied using laser interference lithography (LIL), by changing the incident angles of light interference on substrates. Among three different nanohole patterns fabricated on conductive transparent electrodes, 500 nm-sized nanoholes showed the best performance for cell adhesion and spreading, based on F-actin and lamellipodia/filopodia expression. Enhanced biocompatibility and cell adhesion of these nanohole patterns ultimately resulted in the enhanced neurogenesis of mNSCs, based on the mRNAs expression level of the mNSCs marker and several neuronal markers. Therefore, platforms modified with homogeneous nanohole patterns fabricated by LIL are promising for the precise tuning of nanostructures in tissue culture platforms and useful for controlling various differentiation lineages of stem cells.

Three-Dimensional Graphene-RGD Peptide Nanoisland Composites That Enhance the Osteogenesis of Human Adipose-Derived Mesenchymal Stem Cells.

Graphene derivatives have immense potential in stem cell research. Here, we report a three-dimensional graphene/arginine-glycine-aspartic acid (RGD) peptide nanoisland composite effective in guiding the osteogenesis of human adipose-derived mesenchymal stem cells (ADSCs). Amine-modified silica nanoparticles (SiNPs) were uniformly coated onto an indium tin oxide electrode (ITO), followed by graphene oxide (GO) encapsulation and electrochemical deposition of gold nanoparticles. A RGD-MAP-C peptide, with a triple-branched repeating RGD sequence and a terminal cysteine, was self-assembled onto the gold nanoparticles, generating the final three-dimensional graphene-RGD peptide nanoisland composite. We generated substrates with various gold nanoparticle-RGD peptide cluster densities, and found that the platform with the maximal number of clusters was most suitable for ADSC adhesion and spreading. Remarkably, the same platform was also highly efficient at guiding ADSC osteogenesis compared with other substrates, based on gene expression (alkaline phosphatase (ALP), runt-related transcription factor 2), enzyme activity (ALP), and calcium deposition. ADSCs induced to differentiate into osteoblasts showed higher calcium accumulations after 14-21 days than when grown on typical GO-SiNP complexes, suggesting that the platform can accelerate ADSC osteoblastic differentiation. The results demonstrate that a three-dimensional graphene-RGD peptide nanoisland composite can efficiently derive osteoblasts from mesenchymal stem cells.

Effects of two-dimensional materials on human mesenchymal stem cell behaviors.

Graphene, a typical two-dimensional (2D) material, is known to affect a variety of stem cell behaviors including adhesion, spreading, growth, and differentiation. Here, we report for the first time the effects of four different emerging 2D materials on human adipose-derived mesenchymal stem cells (hADMSCs). Graphene oxide (GO), molybdenum sulfide (MoS2), tungsten sulfide (WS2), and boron nitride (BN) were selected as model two-dimensional materials and were coated on cell-culture substrates by a drop-casting method. Acute toxicity was not observed with any of the four different 2D materials at a low concentration range (<5 µg/ml). Interestingly, the 2D material-modified substrates exhibited a higher cell adhesion, spreading, and proliferation when compared with a non-treated (NT) substrate. Remarkably, in the case of differentiation, the MoS2-, WS2-, and BN-modified substrates exhibited a better performance in terms of guiding the adipogenesis of hADMSCs when compared with both NT and GO-modified substrates, based on the mRNA expression level (qPCR) and amount of lipid droplets (ORO staining). In contrast, the osteogenesis was found to be most efficiently induced by the GO-coated substrate (50 µg/mL) among all 2D-material coated substrates. In summary, 2D materials could act as favorable sources for controlling the stem cell growth and differentiation, which might be highly advantageous in both biomedical research and therapy.

Validation of the efficacy of a personalized information-provision and exercise-coaching app on the quality of life of menopausal women.

OBJECTIVES: Menopausal symptoms severely impact women's quality of life (QoL). Digital health interventions provide an accessible, personalized alternative for managing menopausal symptoms. In this study, we validated the Menopause Assistant Manager (MAMA®; Hudit, Seoul, S. Korea) app developed to provide personalized information, exercise coaching, and management of appointments and medications to menopausal women, and evaluated its efficacy on their QoL. STUDY DESIGN: This nonrandomized interventional trial enrolled 48 peri- and postmenopausal women into experimental (MAMA) and control (Waitlist) groups (n = 24 each). Participants in the MAMA group used the app for 8 weeks, whereas the Waitlist group received no intervention. Both groups continued their usual treatments. MAIN OUTCOME MEASURES: Clinical assessments at baseline and study completion included the World Health Organization Quality of Life Brief Version (WHOQOL-BREF), Menopause Rating Scale, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-15 (PHQ-15), Menopause Emotional Symptom Questionnaire, and Subjective Memory Complaints Questionnaire. RESULTS: Compared with the Waitlist group, the MAMA group showed postintervention improvements in WHOQOL-BREF physical health (F = 4.84, P = .03) and environmental (F = 5.01, P = .03) domains and GAD-7 (F = 5.53, P = .02) and PHQ-15 (F = 4.14, P = .048) scores. Changes in WHOQOL-BREF physical health scores negatively correlated with PHQ-15 scores (ρ = -0.53, P = .004). CONCLUSION: By increasing treatment accessibility, the app improved physical and environmental QoL and reduced anxiety and somatic symptoms. App-based exercise coaching alleviated somatic symptoms, and the in-app psychological content reduced anxiety by normalizing menopausal symptoms, providing accurate information, decreasing uncertainty, and improving symptom perception. TRIAL REGISTRATION: Clinical Research Information Service KCT 0008603; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=25078&status=5&seq_group=25078&search_page=M.

Efficacy of cognitive behavioral therapy for menopausal symptoms and quality of life in Korean perimenopausal women: A pilot randomized controlled trial.

OBJECTIVES: Therapeutic interventions are crucial for perimenopausal women, given the challenging physical and psychological symptoms they face. This study focused on the development and verification of the efficacy of a cognitive behavioral therapy (CBT) protocol designed specifically for Korean perimenopausal women. STUDY DESIGN: A CBT protocol for perimenopausal women was newly developed based on theory and evidence. Forty menopausal women were randomly assigned to either the CBT group (n = 19) or treatment-as-usual (TAU) group (n = 21). Participants in the CBT group underwent 60-min weekly sessions for eight weeks. The TAU group received standard care from gynecologists. MAIN OUTCOME MEASURES: At baseline and follow-up, participants completed the Menopausal Rating Scale (MRS), World Health Organization Quality of Life Brief Version (WHOQOL-BREF), Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-15 (PHQ-15), Menopause Emotional Symptom Questionnaire (MESQ), and Subjective Memory Complaints Questionnaire. RESULTS: The CBT group showed significant changes in their MRS (F = 4.18, p = .048), WHOQOL-BREF (7.60, 0.009), GAD-7 (4.61, 0.038), PHQ-15 (5.49, 0.025), and MESQ scores (7.19, 0.011) compared to the TAU group. In the CBT group, changes in GAD-7 scores were correlated with PHQ-15 (ρ = 0.57, p < .05), MESQ (0.57, < 0.05), and WHOQOL-BREF scores (-0.53, < 0.05). CONCLUSION: CBT prevents the worsening of menopausal and emotional symptoms, anxiety, and quality of life. CBT may have had a therapeutic effect through the following mechanisms: managing anxiety by changing perceptions of menopause through education and training for coping with various menopausal symptoms and improving self-efficacy in symptom management. CLINICAL TRIAL REGISTRATION NUMBER: KCT0007517.

Diagnostic Accuracy of Plasma Renin Concentration and Renin Activity in Predicting Mortality and Kidney Outcomes in Patients With Septic Shock and Hypoperfusion or Hypotension: A Multicenter, Prospective, Observational Study.

Background: Lactate is a commonly used biomarker for sepsis, although it has limitations in certain cases, suggesting the need for novel biomarkers. We evaluated the diagnostic accuracy of plasma renin concentration and renin activity for mortality and kidney outcomes in patients with sepsis with hypoperfusion or hypotension. Methods: This was a multicenter, prospective, observational study of 117 patients with septic shock treated at three tertiary emergency departments between September 2021 and October 2022. The accuracy of renin activity, renin, and lactate concentrations in predicting 28-day mortality, acute kidney injury (AKI), and renal replacement requirement was assessed using the area under the ROC curve (AUC) analysis. Results: The AUCs of initial renin activity, renin, and lactate concentrations for predicting 28-day mortality were 0.66 (95% confidence interval [CI], 0.55-0.77), 0.63 (95% CI, 0.52-0.75), and 0.65 (95% CI, 0.53-0.77), respectively, and those at 24 hrs were 0.74 (95% CI, 0.62-0.86), 0.70 (95% CI, 0.56-0.83), and 0.67 (95% CI, 0.54-0.79). Renin concentrations and renin activity outperformed initial lactate concentrations in predicting AKI within 14 days. The AUCs of renin and lactate concentrations were 0.71 (95% CI, 0.61-0.80) and 0.57 (95% CI, 0.46-0.67), respectively (P=0.030). The AUC of renin activity (0.70; 95% CI, 0.60-0.80) was also higher than that of lactate concentration (P=0.044). Conclusions: Renin concentration and renin activity show comparable performance to lactate concentration in predicting 28-day mortality in patients with septic shock but superior performance in predicting AKI.

Hierarchical Chitin Nanocrystal-Based 3D Printed Dual-Layer Membranes Hydrogels: A Dual Drug Delivery Nano-Platform for Periodontal Tissue Regeneration.

Periodontitis, a prevalent chronic inflammatory disease caused by bacteria, poses a significant challenge to current treatments by merely slowing their progression. Herein, we propose an innovative solution in the form of hierarchical nanostructured 3D printed bilayer membranes that serve as dual-drug delivery nanoplatforms and provide scaffold function for the regeneration of periodontal tissue. Nanocomposite hydrogels were prepared by combining lipid nanoparticle-loaded grape seed extract and simvastatin, as well as chitin nanocrystals, which were then 3D printed into a bilayer membrane that possesses antimicrobial properties and multiscale porosity for periodontal tissue regeneration. The constructs exhibited excellent mechanical properties by adding chitin nanocrystals and provided a sustained release of distinct drugs over 24 days. We demonstrated that the bilayer membranes are cytocompatible and have the ability to induce bone-forming markers in human mesenchymal stem cells, while showing potent antibacterial activity against pathogens associated with periodontitis. In vivo studies further confirmed the efficacy of bilayer membranes in enhancing alveolar bone regeneration and reducing inflammation in a periodontal defect model. This approach suggests promising avenues for the development of implantable constructs that not only combat infections, but also promote the regeneration of periodontal tissue, providing valuable insights into advanced periodontitis treatment strategies.

Multifunctional vitamin D-incorporated PLGA scaffold with BMP/VEGF-overexpressed tonsil-derived MSC via CRISPR/Cas9 for bone tissue regeneration.

Guiding endogenous regeneration of bone defects using biomaterials and regenerative medicine is considered an optimal strategy. One of the effective therapeutic approaches involves using transgene-expressed stem cells to treat tissue destruction and replace damaged parts. Among the various gene editing techniques for cells, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is considered as a promising method owing to the increasing therapeutic potential of cells by targeting specific sites. Herein, a vitamin D-incorporated poly(lactic-co-glycolic acid) (PLGA) scaffold with bone morphogenetic protein 2 (BMP2)/vascular endothelial growth factor (VEGF)-overexpressed tonsil-derived MSCs (ToMSCs) via CRISPR/Cas9 was introduced for bone tissue regeneration. The optimized seeding ratio of engineered ToMSCs on the scaffold demonstrated favorable immunomodulatory function, angiogenesis, and osteogenic activity in vitro. The multifunctional scaffold could potentially support stem cell in vivo and induce the transition from M1 to M2 macrophage with magnesium hydroxide and vitamin D. This study highlights the improved synergistic effect of a vitamin D-incorporated PLGA scaffold and a gene-edited ToMSCs for bone tissue engineering and regenerative medicine.

Injectable Microparticle-containing hydrogel with controlled release of bioactive molecules for facial rejuvenation.

The skin is the largest organ and a crucial barrier for protection against various intrinsic and extrinsic factors. As we age, the skin's components become more vulnerable to damage, forming wrinkles. Among different procedures, hyaluronic acid-based hydrogel has been extensively utilized for skin regeneration and reducing wrinkles. However, it has limitations like low retention and weak mechanical properties. In this study, we suggested the poly(l-lactic acid) (PLLA) microparticles containing alkaline magnesium hydroxide and nitric oxide-generating zinc oxide and rejuvenative hyaluronic acid (HA) hydrogels including these functional microparticles and asiaticoside, creating a novel delivery system for skin rejuvenation and regeneration. The fabricated rejuvenative hydrogels have exhibited enhanced biocompatibility, pH neutralization, reactive oxygen species scavenging, collagen biosynthesis, and angiogenesis capabilities in vitro and in vivo. Additionally, an excellent volume retention ability was demonstrated due to the numerous hydrogen bonds that formed between hyaluronic acid and asiaticoside. Overall, our advanced injectable hydrogel containing functional microparticles, with controlled release of bioactive molecules, has a significant potential for enhancing the regeneration and rejuvenation of the skin.

Therapeutic potential of luteolin-loaded poly(lactic-co-glycolic acid)/modified magnesium hydroxide microsphere in functional thermosensitive hydrogel for treating neuropathic pain.

Neuropathic pain (NP) is a debilitating condition stemming from damage to the somatosensory system frequently caused by nerve injuries or lesions. While existing treatments are widely employed, they often lead to side effects and lack specificity. This study aimed to alleviate NP by developing an innovative sustained-release thermosensitive hydrogel system. The system incorporates hyaluronic acid (HA)/Pluronic F127 injectable hydrogel and bupivacaine (Bup, B) in combination with poly(lactic-co-glycolic acid; PLGA)/modified magnesium hydroxide (MH)/luteolin (Lut; PML) microspheres (PML@B/Gel). The PML@B/Gel was designed for localized and prolonged co-delivery of Bup and Lut as an anesthetic and anti-inflammatory agent, respectively. Our studies demonstrated that PML@B/Gel had exceptional biocompatibility, anti-inflammatory, and antioxidant properties. In addition, it exhibited efficient pain relief in in vitro cellular assays. Moreover, this functional hydrogel showed substantial sustained drug release while diminishing microglial activation. Consequently, it effectively mitigated mechanical allodynia and thermal hyperalgesia in in vivo rat models of chronic constriction injury (CCI). Based on our research findings, PML@B/Gel emerges as a promising therapeutic approach for the protracted treatment of NP.

Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease.

INTRODUCTION: With prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function via tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging. OBJECTIVES: To exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds. METHODS: Hybrid PMEZ scaffolds incorporating essential bioactive components, such as ricinoleic acid grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) based on biodegradable porous PLGA (P) platform was successfully manufactured. Consecutively, for functional improvements, melatonin-modulated extracellular vesicles (mEVs), derived from the human umbilical cord MSCs in chemically defined media without serum impurities, were also loaded onto PMEZ scaffolds to construct the multiplexed PMEZ/mEV scaffold. RESULTS: With functionalities of Mg(OH)2 and extracellular matrix-loaded PLGA scaffolds, the continuous nitric oxide-releasing property of modified ZnO and remarkably upregulated regenerative functionalities of mEVs showed significantly enhanced kidney regenerative activities. Based on these, the structural and functional restoration has been practically achieved in 5/6 nephrectomy mouse models that mimicked severe human CKD. CONCLUSION: Our study has proved the combinatory bioactivities of the biodegradable PLGA-based multiplexed scaffold for kidney tissue regeneration in 5/6 nephrectomy mouse representing a severe CKD model. The optimal microenvironments for the morphogenetic formations of renal tissues and functional restorations have successfully achieved the combinatory bioactivities of remarkable components for PMEZ/mEV, which could be a promising therapeutic alternative for CKD treatment.

Synergistic effect of Hypoxic Conditioning and Cell-Tethering Colloidal Gels enhanced Productivity of MSC Paracrine Factors and Accelerated Vessel Regeneration.

Microporous hydrogels have been widely used for delivering therapeutic cells. However, several critical issues, such as the lack of control over the harsh environment they are subjected to under pathological conditions and rapid egression of cells from the hydrogels, have produced limited therapeutic outcomes. To address these critical challenges, cell-tethering and hypoxic conditioning colloidal hydrogels containing mesenchymal stem cells (MSCs) are introduced to increase the productivity of paracrine factors locally and in a long-term manner. Cell-tethering colloidal hydrogels that are composed of tyramine-conjugated gelatin prevent cells from egressing through on-cell oxidative phenolic crosslinks while providing mechanical stimulation and interconnected microporous networks to allow for host-implant interactions. Oxygenating microparticles encapsulated in tyramine-conjugated colloidal microgels continuously generated oxygen for 2 weeks with rapid diffusion, resulting in maintaining a mild hypoxic condition while MSCs consumed oxygen under severe hypoxia. Synergistically, local retention of MSCs within the mild hypoxic-conditioned and mechanically robust colloidal hydrogels significantly increased the secretion of various angiogenic cytokines and chemokines. The oxygenating colloidal hydrogels induced anti-inflammatory responses, reduced cellular apoptosis, and promoted numerous large blood vessels in vivo. Finally, mice injected with the MSC-tethered oxygenating colloidal hydrogels significantly improved blood flow restoration and muscle regeneration in a hindlimb ischemia (HLI) model.

Nature-Inspired Chiral Structures: Fabrication Methods and Multifaceted Applications.

Diverse chiral structures observed in nature find applications across various domains, including engineering, chemistry, and medicine. Particularly notable is the optical activity inherent in chiral structures, which has emerged prominently in the field of optics. This phenomenon has led to a wide range of applications, encompassing optical components, catalysts, sensors, and therapeutic interventions. This review summarizes the imitations and applications of naturally occurring chiral structures. Methods for replicating chiral architectures found in nature have evolved with specific research goals. This review primarily focuses on a top-down approach and provides a summary of recent research advancements. In the latter part of this review, we will engage in discussions regarding the diverse array of applications resulting from imitating chiral structures, from the optical activity in photonic crystals to applications spanning light-emitting devices. Furthermore, we will delve into the applications of biorecognition and therapeutic methodologies, comprehensively examining and deliberating upon the multifaceted utility of chiral structures.

Level of Psychological and Somatic Symptoms Predict Perimenopausal Syndrome Severity Better Than Obstetric and Psychiatric History Do Among Korean Women.

OBJECTIVE: Menopause symptoms can vary in type, duration, and severity. The purpose of this study was to investigate the key factors predicting severe symptoms among Korean perimenopausal women with various demographic data, obstetric and psychiatric histories, and menopausal symptoms screening scale scores. METHODS: Data were collected from 1,060 women, and 4 latent classes were identified using latent profile analysis, with 6 major categories of menopausal complaints. Among the 4 classes, we selectively used data from the "all unimpaired" and "all impaired" groups. Menopause rating scale (MRS), sociodemographic, obstetric, and psychiatric factors were assessed, and hierarchical logistic regression analyses were conducted with the "all impaired" group as a dependent variable. RESULTS: Marital status and scores on the psychological and somatic subscales of the MRS were statistically related to being in the "all impaired" group. Otherwise, family history of menopausal symptoms, menarche age, and history of other psychiatric disorders were not statistically significant predictors of being in the "all impaired" group. CONCLUSION: The psychological and somatic subscales of the MRS predict the severity of perimenopausal syndrome better than obstetric and psychiatric history do among Korean perimenopausal women. Psychological and somatic symptoms as well as genitourinary symptoms in menopausal patients should be closely evaluated.

Nitric Oxide-Releasing Bioinspired Scaffold for Exquisite Regeneration of Osteoporotic Bone via Regulation of Homeostasis.

Osteoporotic bone regeneration is a challenging process which involves the occurrence of sophisticated interactions. Although various polymeric scaffolds have been proposed for bone repair, research on osteoporotic bone regeneration remains practically limited. In particular, achieving satisfactory bone regeneration when using osteoporotic drugs is challenging including bisphosphonates. Here, a novel nitric oxide-releasing bioinspired scaffold with bioactive agents for the exquisite regeneration of osteoporotic bone is proposed. The bone-like biomimetic poly(lactic-co-glycolic acid) scaffold is first prepared in combination with organic/inorganic ECM and magnesium hydroxide as the base implant material. Nanoparticles containing bioactive agents of zinc oxide (ZO), alendronate, and BMP2 are incorporated to the biomimetic scaffold to impart multifunctionality such as anti-inflammation, angiogenesis, anti-osteoclastogenesis, and bone regeneration. Especially, nitric oxide (NO) generated from ZO stimulates the activity of cGMP and protein kinase G; in addition, ZO downregulates the RANKL/osteoprotegerin ratio by suppressing the Wnt/ß-catenin signaling pathway. The new bone is formed much better in the osteoporotic rat model than in the normal model through the regulation of bone homeostasis via the scaffold. These synergistic effects suggest that such a bioinspired scaffold could be a comprehensive way to regenerate exceptionally osteoporotic bones.

Endogenous stimulus-responsive nitric oxide releasing bioactive liposome for a multilayered drug-eluting balloon.

Drug-eluting balloon (DEB) system has been widely utilized for percutaneous coronary intervention (PCI), treating atherosclerosis to overcome the limitations of cardiovascular stents. With the anti-proliferative drug, everolimus (EVL), nitric oxide (NO) plays a key bioregulator role to facilitate the angiogenesis of endothelial cells (ECs) and inhibit the cell proliferation of smooth muscle cells (SMCs) in the lesions of cardiovascular diseases. Due to the very short lifetime and limited exposure area of NO in the body, the continuous release and efficient delivery of NO must be carefully considered. In this respect, a liposome-containing disulfide bonding group was introduced as a delivery vehicle of EVL and NO with the continuous release of NO via successive reaction cycles with GSH and SNAP in the blood vessel without the need for exogenous stimulations. With a multilayer coating platform consisting of a polyvinylpyrrolidone (PVP)/EVL-laden liposome with NO (EVL-NO-Lipo)/PVP, we precluded the loss of the EVL-encapsulated liposome with NO release during the transition time and maximized the transfer rate from the surface of DEB to the tissues. The sustained release of NO was monitored using a nitric oxide analyzer (NOA), and the synergistic bioactivities of EVL and NO were proved in EC and SMC with angiogenesis and cell proliferation-related assays. From the results of hemocompatibility and ex vivo studies, the feasibility was provided for future in vivo applications of the multilayer-coated DEB system.

Obstetric and psychiatric history as predictors for psychosomatic symptoms among Korean perimenopausal women.

OBJECTIVES: Menopause presents various physical and psychological disturbances for women and comes at a high financial cost. Therefore, this study aimed to identify factors influencing menopause symptoms. STUDY DESIGN: Data of Korean perimenopausal women aged 40-60 (n = 1060; mean age, 46.03 ± 4.08) were collected by a research company. Participants were classified into a "functional" group (n = 716) or a "dysfunctional" group (n = 344) according to the severity of their perimenopausal psychosomatic symptoms. To investigate the association of obstetric and psychiatric history with membership of the "dysfunctional" group, a hierarchical logistic regression analysis was conducted. RESULTS: The outcomes of all three hierarchical logistic regression models presented significant overall model fit. Among the independent variables, family history of menopausal symptoms, menarcheal age, number of pregnancies, history of postpartum depression, postpartum psychosis, and other psychiatric disorders were positively associated with being in the "dysfunctional" group, whereas age and number of deliveries were negatively associated with being in the "dysfunctional" group. CONCLUSION: A short reproductive period and short exposure to estrogen due to late menarche and early menopausal transition may be related to severe perimenopausal symptoms. The relationship between the history of postpartum mental illness and severe perimenopausal symptoms may be associated with heightened sensitivity to hormonal triggers when a woman is exposed to fluctuating ovarian sex steroid levels. The relationship between parity or gravidity and the severity of menopausal symptoms in Korean women differed from that in studies conducted in other countries, possibly due to the low birth rate in Korea.