Smart Contact Lens for Colorimetric Visualization of Glucose Levels in the Body Fluid.

Frequent blood glucose monitoring is a crucial routine for diabetic patients. Traditional invasive methods can cause discomfort and pain and even pose a risk of infection. As a result, researchers have been exploring noninvasive techniques. However, a limited number of products have been developed for the market due to their high cost. In this study, we developed a low-cost, highly accessible, and noninvasive contact lens-based glucose monitoring system. We functionalized the surface of the contact lens with boronic acid, which has a strong but reversible binding affinity to glucose. To achieve facile conjugation of boronic acid, we utilized a functional coating layer called poly(tannic acid). The functionalized contact lens binds to glucose in body fluids (e.g., tear) and releases it when soaked in an enzymatic cocktail, allowing for the glucose level to be quantified through a colorimetric assay. Importantly, the transparency and oxygen permeability of the contact lens, which are crucial for practical use, were maintained after functionalization, and the lenses showed high biocompatibility. Based on the analysis of colorimetric data generated by the smartphone application and ultraviolet-visible (UV-vis) spectra, we believe that this contact lens has a high potential to be used as a smart diagnostic tool for monitoring and managing blood glucose levels.

Thymosin Beta 4 Inhibits LPS and ATP-Induced Hepatic Stellate Cells via the Regulation of Multiple Signaling Pathways.

Risk signals are characteristic of many common inflammatory diseases and can function to activate nucleotide-binding oligomerization (NLR) family pyrin domain-containing 3 (NLRP3), the innate immune signal receptor in cytoplasm. The NLRP3 inflammasome plays an important role in the development of liver fibrosis. Activated NLRP3 nucleates the assembly of inflammasomes, leading to the secretion of interleukin (IL)-1ß and IL-18, the activation of caspase-1, and the initiation of the inflammatory process. Therefore, it is essential to inhibit the activation of the NLRP3 inflammasome, which plays a vital role in the immune response and in initiating inflammation. RAW 264.7 and LX-2 cells were primed with lipopolysaccharide (LPS) for 4 h and subsequently stimulated for 30 min with 5 mM of adenosine 5'-triphosphate (ATP) to activate the NLRP3 inflammasome. Thymosin beta 4 (Tß4) was supplemented to RAW264.7 and LX-2 cells 30 min before ATP was added. As a result, we investigated the effects of Tß4 on the NLRP3 inflammasome. Tß4 prevented LPS-induced NLRP3 priming by inhibiting NF-kB and JNK/p38 MAPK expression and the LPS and ATP-induced production of reactive oxygen species. Moreover, Tß4 induced autophagy by controlling autophagy markers (LC3A/B and p62) through the inhibition of the PI3K/AKT/mTOR pathway. LPS combined with ATP significantly increased thee protein expression of inflammatory mediators and NLRP3 inflammasome markers. These events were remarkably suppressed by Tß4. In conclusion, Tß4 attenuated NLRP3 inflammasomes by inhibiting NLRP3 inflammasome-related proteins (NLRP3, ASC, IL-1ß, and caspase-1). Our results indicate that Tß4 attenuated the NLRP3 inflammasome through multiple signaling pathway regulations in macrophage and hepatic stellate cells. Therefore, based on the above findings, it is hypothesized that Tß4 could be a potential inflammatory therapeutic agent targeting the NLRP3 inflammasome in hepatic fibrosis regulation.

Antioxidation and anti-inflammatory effects of gamma-irradiated silk sericin and fibroin in H2O2-induced HaCaT Cell.

Oxidative stress in skin cells can induce the formation of reactive oxygen species (ROS), which are critical for pathogenic processes such as immunosuppression, inflammation, and skin aging. In this study, we confirmed improvements from gamma-irradiated silk sericin (I-sericin) and gamma-irradiated silk fibroin (I-fibroin) to skin cells damaged by oxidative stress. We found that I-sericin and I-fibroin effectively attenuated oxidative stress-induced ROS generation and decreased oxidative stress-induced inflammatory factors COX-2, iNOS, tumor necrosis factor-α, and interleukin-1ß compared to the use of non-irradiated sericin or fibroin. I-sericin and I-fibroin effects were balanced by competition with skin regenerative protein factors reacting to oxidative stress. Taken together, our results indicated that, compared to non-irradiated sericin or fibroin, I-sericin, and I-fibroin had anti-oxidation and anti-inflammation activity and protective effects against skin cell damage from oxidative stress. Therefore, gamma-irradiation may be useful in the development of cosmetics to maintain skin health.

Nursing Experience of New Nurses Caring for COVID-19 Patients in Military Hospitals: A Qualitative Study.

This qualitative study explored the experiences of new nurses with less than one year of clinical experience in caring for COVID-19 patients in a military hospital. In-depth interviews were conducted with six new nurses working in a negative-pressure isolation unit of the Armed Forces Capital Hospital. Data were analyzed using the phenomenological method proposed by Colaizzi, and 12 themes were derived and classified into four clusters: burden of nursing in isolation units; hardship of nursing critically ill patients; efforts to perform nursing tasks; positive changes through patient care. The participants were anxious while caring for COVID-19 patients with severe illness due to a lack of clinical experience. Furthermore, the wearing of heavy personal protective equipment impeded communication with patients, leading to physical and psychological exhaustion. However, they tried to utilize their own know-how and provide the best nursing care, resulting in them gaining confidence. Participants were able to think critically and took pride in being military nursing professionals. This study is meaningful as it provides insight into the experiences of new military nurses who were rapidly dispatched during a national medical crisis. The results can be applied to develop future strategies aimed at improving new nurses' competency in military hospitals.

Systematic Approach to Mimic Phenolic Natural Polymers for Biofabrication.

In nature, phenolic biopolymers are utilized as functional tools and molecular crosslinkers to control the mechanical properties of biomaterials. Of particular interest are phenolic proteins/polysaccharides from living organisms, which are rich in catechol and/or gallol groups. Their strong underwater adhesion is attributed to the representative phenolic molecule, catechol, which stimulates intermolecular and intramolecular crosslinking induced by oxidative polymerization. Significant efforts have been made to understand the underlying chemistries, and researchers have developed functional biomaterials by mimicking the systems. Owing to their unique biocompatibility and ability to transform their mechanical properties, phenolic polymers have revolutionized biotechnologies. In this review, we highlight the bottom-up approaches for mimicking polyphenolic materials in nature and recent advances in related biomedical applications. We expect that this review will contribute to the rational design and synthesis of polyphenolic functional biomaterials and facilitate the production of related applications.

Immature Persimmon Suppresses Amyloid Beta (Aß) Mediated Cognitive Dysfunction via Tau Pathology in ICR Mice.

This study confirmed the ameliorating effect of immature persimmon (Diospyros kaki) ethanolic extract (IPEE) on neuronal cytotoxicity in amyloid beta (Aß)1-42-induced ICR mice. The administration of IPEE ameliorated the cognitive dysfunction in Aß1-42-induced mice by improving the spatial working memory, the short-term and long-term memory functions. IPEE protected the cerebral cholinergic system, such as the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity, and antioxidant system, such as the superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) contents. In addition, mitochondrial dysfunction against Aß1-42-induced toxicity was reduced by regulating the reactive oxygen species (ROS), mitochondrial membrane potential and ATP contents. In addition, IPEE regulated the expression levels of tau signaling, such as TNF-α, p-JNK, p-Akt, p-GSK3ß, p-tau, p-NF-κB, BAX and caspase 3. Finally, gallic acid, ellagic acid and quercetin 3-O-(6″-acetyl-glucoside) were identified as the physiological compounds of IPEE using ultra-performance liquid chromatography ion mobility separation quadrupole time-of-flight/tandem mass spectrometry (UPLC IMS Q-TOF/MS2).

Immune-enhancing effects of gamma-irradiated sericin.

Gamma radiation changes the molecular structure and activity of proteins, which in turn changes their physiological effects. Sericin, one of the silk peptides, has beneficial effects to humans such as inducing apoptosis, acting as an anti-oxidant. The effects of gamma irradiation on the physiological activity of fibroin have been studied, but its effects on sericin alone have not yet been established. In this study, we assessed the effects of gamma irradiation on sericin (I-sericin) in regard to its inflammatory effects in vitro and in vivo. Our results showed that I-sericin (5 kGy) significantly increased nitric oxide production, proliferation of immune cells, and effectively attenuated lipopolysaccharide (LPS)-induced inflammation. The mice were fed I-sericin for 4 weeks and treated with LPS; they exhibited significantly increased proliferation of lymphocytes, activation of NK cells and decreased secretion of inflammatory cytokines These results suggest gamma-irradiated I-sericin as a valuable functional food supplement by immune-enhancing and anti-inflammation effects.

Thymosin beta 4 attenuates PrP(106-126)-induced human brain endothelial cells dysfunction.

The blood-brain barrier (BBB) is a highly selective permeability barrier that separates the circulating blood from the brain and extracellular fluid in the central nervous system (CNS). The BBB is formed by cerebral endothelial cells connected by tight junctions. Prion diseases are neurodegenerative pathologies characterized by the accumulation of altered forms of the prion protein (PrP), named PrPSc. Thymosin beta 4 (Tß4) is an actin-sequestering peptide known to bind monomeric actin and inhibit its polymerization, and it is known to have a neuroprotective effect. However, the effect of Tß4 on prion disease has not yet been investigated. Therefore, in this study, we investigated the effect of Tß4 on prion-induced BBB dysfunction in hCMEC/D3 human cerebral endothelial cells. We found that Tß4 increased the expression of tight junction protein, but reduced the ratio of F-actin to G-actin. Moreover, we showed that Tß4 significantly improved PrP (106-126)-induced vascular permeability dysfunction in hCMEC/D3 cells. Through human BBB in vitro model, we found that PrP (106-126) could disrupt tight junctions and cytoskeleton arrangement. These results suggest that Tß4 may play a critical role in barrier stabilization. Furthermore, Tß4 may prevent neurodegenerative diseases caused by prion-induced BBB dysfunction.

Ulmus macrocarpa Hance modulates lipid metabolism in hyperlipidemia via activation of AMPK pathway.

Ulmus macrocarpa Hance as an oriental medicinal plant has shown enormous potential for the treatment of several metabolic disorders in Korea. Hyperlipidemia, which is characterized by the excess accumulation of lipid contents in the bloodstream, may lead to several cardiovascular diseases. Therefore, in this study, anti-hyperlipidemic potential of U. macrocarpa water extract (UME) was examined in vitro and in vivo using HepG2 cells and experimental rats, respectively. The hyperlipidemia in experimental rats was induced by the high-cholesterol diet (HCD) followed by oral administration of various concentrations (25, 50 and 100 mg/kg) of UME for 6 weeks. As a result, the UME significantly improved the biochemical parameters such as increased the level of triglyceride, total cholesterol, and low-density lipoprotein cholesterol as well as reduced the high-density lipoprotein cholesterol in the HCD-fed rats. In addition, UME also prevented lipid accumulation through regulating AMPK activity and lipid metabolism proteins (ACC, SREBP1 and HMGCR) in the HCD-fed rats as compared to the controls. Moreover, similar pattern of gene expression levels was confirmed in oleic acid (OA)-treated HepG2 cells. Taken together, our results indicate that UME prevents hyperlipidemia via activating the AMPK pathway and regulates lipid metabolism. Thus, based on the above findings, it is estimated that UME could be a potential therapeutic agent for preventing the hyperlipidemia.

Thymosin beta 4-Induced Autophagy Increases Cholinergic Signaling in PrP (106-126)-Treated HT22 Cells.

Prion protein peptide (PrP) has been associated with neurotoxicity in brain cells and progression of prion diseases due to spongiform degeneration and accumulation of the infectious scrapie prion protein (PrPSc). Autophagy has been shown to provide protective functions for neurodegenerative diseases, including prion disease. Thymosin beta 4 (Tß4) plays a key role in the nervous system, providing a neuronal growth effect that includes motility, neurite outgrowth, and proliferation. However, the effect of Tß4 on autophagy in prion disease has not been investigated. In this study, we investigated the neuroprotective effects of Tß4, an activator of autophagy, in cholinergic signaling activation in PrP (106-126)-treated HT22 cells. We found that Tß4-induced autophagy markers, LC3A/B and Beclin1, were protective against PrP-induced neurotoxicity. Interestingly, a balance between autophagy markers and autophagy pathway factors (AKT, p-AKT, mTOR, and p-mTOR) was maintained by Tß4 competitively against each protein factors reacted to PrP (106-126). The cholinergic signaling markers ChTp and AChE, which play an important role in the brain, were maintained by Tß4 competitively against each protein factors reacted to PrP (106-126). However, these results were reversed by 3-MA, an autophagy inhibitor. Taken together, our results indicate that Tß4 has cholinergic signaling activities through the induction of autophagy. Thus, Tß4 may be to a potential therapeutic agent for preventing neurodegenerative diseases.

Murine γδ T Cells Render B Cells Refractory to Commitment of IgA Isotype Switching.

γδ T cells are abundant in the gut mucosa and play an important role in adaptive immunity as well as innate immunity. Although γδ T cells are supposed to be associated with the enhancement of Ab production, the status of γδ T cells, particularly in the synthesis of IgA isotype, remains unclear. We compared Ig expression in T cell receptor delta chain deficient (TCRδ-/-) mice with wild-type mice. The amount of IgA in fecal pellets was substantially elevated in TCRδ-/- mice. This was paralleled by an increase in surface IgA expression and total IgA production by Peyer's patches (PPs) and mesenteric lymph node (MLN) cells. Likewise, the TCRδ-/- mice produced much higher levels of serum IgA isotype. Here, surface IgA expression and number of IgA secreting cells were also elevated in the culture of spleen and bone marrow (BM) B cells. Germ-line α transcript, an indicator of IgA class switch recombination, higher in PP and MLN B cells from TCRδ-/- mice, while it was not seen in inactivated B cells. Nevertheless, the frequency of IgA+ B cells was much higher in the spleen from TCRδ-/- mice. These results suggest that γδ T cells control the early phase of B cells, in order to prevent unnecessary IgA isotype switching. Furthermore, this regulatory role of γδ T cells had lasting effects on the long-lived IgA-producing plasma cells in the BM.

Antioxidant Activity of Royal Jelly Hydrolysates Obtained by Enzymatic Treatment.

Recently, research on the processing of raw functional materials with the aim of improving various physiological activities has been conducted. In this study, we investigated the antioxidant activity of royal jelly (RJ) hydrolysates obtained from three commercial proteases. Enzyme-treated royal jelly (ERJ), in which the RJ hydrolysates were converted into easy-to-absorb shorter chain monomers through the removal of two known allergen proteins, showed no difference in the content of (E)-10-hydroxydec-2-enoicacid (10-HDA) or the freshness parameter and showed a significant increase in total free amino acid content. The antioxidant activity of ERJ was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and chemical assays. The ERJ showed about 80% DPPH-radical scavenging activity at same concentration of ascorbic acid. The antioxidant effect of ERJ was confirmed to be due to reduction of intracellular reactive oxidative species (ROS) and nitric oxide (NO) production in LPS-treated macrophages. Moreover, ERJ significantly increased the activity of the antioxidant enzyme superoxide dismutase (SOD) and the level of the antioxidant glutathione (GSH) in a dose-dependent manner. Interestingly, these antioxidant activities of ERJ were stronger than those of non-treated RJ. These findings indicate that ERJ has high potential as an antioxidant agent for use in human and animal diets.

Effects of 7-MEGATM 500 on Oxidative Stress, Inflammation, and Skin Regeneration in H2O2-Treated Skin Cells.

Environmental stimuli can lead to the excessive accumulation of reactive oxygen species (ROS), which is one of the risk factors for premature skin aging. Here, we investigated the protective effects of 7-MEGATM 500 (50% palmitoleic acid, 7-MEGA) against oxidative stress-induced cellular damage and its underlying therapeutic mechanisms in the HaCaT human skin keratinocyte cell line (HaCaT cells). Our results showed that treatment with 7-MEGA prior to hydrogen peroxide (H2O2)-induced damage significantly increased the viability of HaCaT cells. 7-MEGA effectively attenuated generation of H2O2-induced reactive oxygen species (ROS), and inhibited H2O2-induced inflammatory factors, such as prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). In addition, cells treated with 7-MEGA exhibited significantly decreased expression of matrix metalloproteinase-1 (MMP-1) and increased expression of procollagen type 1 (PCOL1) and Elastin against oxidative stress by H2O2. Interestingly, these protective activities of 7-MEGA were similar in scope and of a higher magnitude than those seen with 98.5% palmitoleic acid (PA) obtained from Sigma when given at the same concentration (100 nL/mL). According to our data, 7-MEGA is able to protect HaCaT cells from H2O2-induced damage through inhibiting cellular oxidative stress and inflammation. Moreover, 7-MEGA may affect skin elasticity maintenance and improve skin wrinkles. These findings indicate that 7-MEGA may be useful as a food supplement for skin health.

The Relation Between the Presence of Aspiration or Penetration and the Clinical Indicators of Dysphagia in Poststroke Survivors.

OBJECTIVE: To examine the relation between the presence of penetration or aspiration and the occurrence of the clinical indicators of dysphagia. The presence of penetration or aspiration is closely related to the clinical indicators of dysphagia. It is essential to understand these relationships in order to implement proper diagnosis and treatment of dysphagia. METHODS: Fifty-eight poststroke survivors were divided into two groups: patients with or without penetration or aspiration. Medical records and videofluoroscopic swallowing examinations were reviewed. The occurrence of clinical indicators of dysphagia between two groups was analyzed with Cross Tabulation and the Pearson chi-square test (p<0.05). RESULTS: Poststroke survivors with penetration or aspiration had significantly high occurrences of delayed initiation of the swallow (p=0.04) and reduced hyolaryngeal elevation (p<0.01) than those without penetration or aspiration. CONCLUSION: The results of this study indicate that delayed initiation of the swallow is a strong physiological indicator of penetration or aspiration during the oral stage of swallowing in poststroke survivors. For the pharyngeal stage of swallowing, hyoid and laryngeal elevation is a key event related to occurrence of penetration or aspiration. Clinical indicators should be investigated further to allow appropriate implementation of treatment strategies for stroke survivors.

Retinoic acid acts as a selective human IgA switch factor.

Retinoic acid (RA) is known to have several functions that lead to a potent mucosal IgA response. Nevertheless, its exact role in human IgA synthesis has yet to be elucidated. Thus, we investigated the role of RA in promoting IgA isotype switching in human B cells. We found that RA increased IgA production and the expression of germ-line IgA1 and IgA2 transcripts (GLTα1 and GLTα2). This induction occurred alongside an increase in the frequency of IgA1-secreting B cell clones, as assessed by limiting dilution analysis. Under the same conditions, RA did not increase IgM and IgG production. Am80, an agonist of RA receptor α (RARα), increased IgA production. In addition, RA activity was abrogated by LE540, an antagonist of RAR, suggesting that the RAR pathway is involved in RA-induced IgA production. Taken together, these results indicate that RA induces IgA isotype switching mainly through RARα in human B cells.

Alum Directly Modulates Murine B Lymphocytes to Produce IgG1 Isotype.

Aluminum hydroxide (alum) is the most widely used adjuvant in human vaccines. Nevertheless, it is virtually unknown whether alum acts on B cells. In the present study, we explored the direct effect of alum on Ig expression by murine B cells in vitro. LPS-activated mouse spleen B cells were cultured with alum, and the level of isotype-specific Ig secretion, IgG1 secreting cell numbers, and Ig germ-line transcripts (GLT) were measured using ELISA, ELISPOT, and RT-PCR, respectively. Alum consistently enhanced total IgG1 production, numbers of IgG1 secreting cells, and GLTγ1 expression. These results demonstrate that alum can directly cause IgG1 isotype switching leading to IgG1 production.