Softening implantable bioelectronics: Material designs, applications, and future directions.

Implantable bioelectronics, integrated directly within the body, represent a potent biomedical solution for monitoring and treating a range of medical conditions, including chronic diseases, neural disorders, and cardiac conditions, through personalized medical interventions. Nevertheless, contemporary implantable bioelectronics rely heavily on rigid materials (e.g., inorganic materials and metals), leading to inflammatory responses and tissue damage due to a mechanical mismatch with biological tissues. Recently, soft electronics with mechanical properties comparable to those of biological tissues have been introduced to alleviate fatal immune responses and improve tissue conformity. Despite their myriad advantages, substantial challenges persist in surgical handling and precise positioning due to their high compliance. To surmount these obstacles, softening implantable bioelectronics has garnered significant attention as it embraces the benefits of both rigid and soft bioelectronics. These devices are rigid for easy standalone implantation, transitioning to a soft state in vivo in response to environmental stimuli, which effectively overcomes functional/biological problems inherent in the static mechanical properties of conventional implants. This article reviews recent research and development in softening materials and designs for implantable bioelectronics. Examples featuring tissue-penetrating and conformal softening devices highlight the promising potential of these approaches in biomedical applications. A concluding section delves into current challenges and outlines future directions for softening implantable device technologies, underscoring their pivotal role in propelling the evolution of next-generation bioelectronics.

Antimicrobial and anti-inflammatory effects of BenTooth: A natural product blend of burdock root, persimmon leaf extracts, and quercetin on periodontal disease.

Periodontal disease represents a condition that exhibits substantial global morbidity, and is characterized by the infection and inflammation of the periodontal tissue effectuated by bacterial pathogens. The present study aimed at evaluating the therapeutic efficacy of BenTooth, an edible natural product mixture comprising burdock root extract, persimmon leaf extract and quercetin, against periodontitis both in vitro and in vivo. BenTooth was examined for antimicrobial properties and its impact on cellular responses related to inflammation and bone resorption. Its effects were also assessed in a rat model of ligature-induced periodontitis. BenTooth demonstrated potent antimicrobial activity against P. gingivalis and S. mutans. In RAW264.7 cells, it notably diminished the expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as reduced interleukin-6 and tumor necrosis factor-α levels triggered by P. gingivalis-derived lipopolysaccharide. Furthermore, BenTooth inhibited osteoclastogenesis mediated by the receptor activator of nuclear factor κB ligand. In the rat model, BenTooth consumption mitigated the ligature-induced expansion in distance between the cementoenamel junction and the alveolar bone crest and bolstered the bone volume fraction. These results present BenTooth as a potential therapeutic candidate for the prevention and remediation of periodontal diseases.

A temperature-responsive intravenous needle that irreversibly softens on insertion.

The high stiffness of intravenous needles can cause tissue injury and increase the risk of transmission of blood-borne pathogens through accidental needlesticks. Here we describe the development and performance of an intravenous needle whose stiffness and shape depend on body temperature. The needle is sufficiently stiff for insertion into soft tissue yet becomes irreversibly flexible after insertion, adapting to the shape of the blood vessel and reducing the risk of needlestick injury on removal, as we show in vein phantoms and ex vivo porcine tissue. In mice, the needles had similar fluid-delivery performance and caused substantially less inflammation than commercial devices for intravenous access of similar size. We also show that an intravenous needle integrated with a thin-film temperature sensor can monitor core body temperature in mice and detect fluid leakage in porcine tissue ex vivo. Temperature-responsive intravenous needles may improve patient care.

Animal efficacy study of a plant extract complex (BEN815) as a potential treatment for COVID-19.

In a short time, several types of injectable and oral therapeutics have been developed and used to effectively manage patients with coronavirus disease 2019 (COVID-19). BEN815 is an improved mixture of three extracts (Psidium guajava, Camellia sinensis, and Rosa hybrida) recognized by the Ministry of Food and Drug Safety of Korea as a health food ingredient that alleviates allergic rhinitis. The current animal efficacy study was performed to assess its probability of improving COVID-19 symptoms. BEN815 treatment significantly increased the survival of K18-hACE2 transgenic mice and reduced viral titers in the lungs at 5 days post infection (DPI). Furthermore, the lungs of the treated mice showed mild tissue damage at 5 DPI and nearly complete recovery from COVID-19 at 14 DPI. BEN815 appears to be an effective and minimally toxic anti-SARS-CoV-2 agent in mice and has potential for clinical applications.

The association between urinary bisphenol A levels and nonalcoholic fatty liver disease in Korean adults: Korean National Environmental Health Survey (KoNEHS) 2015-2017.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is becoming a global health problem. Bisphenol A (BPA), one of most widely used environmental chemicals, is suspected to be a contributor to the development NAFLD. This study was performed to examine the relationship between human BPA levels and risk of NAFLD. METHODS: The data (n = 3476 adults: 1474 men and 2002 women) used in this study were obtained from the Korean National Environmental Health Survey III (2015-2017). BPA levels were measured in urine samples. NAFLD was defined using hepatic steatosis index after exclusion of other causes of hepatic diseases. RESULTS: There was a significant linear relationship between the elevated urinary BPA concentrations and risk of NAFLD. In a univariate analysis, odds ratio (OR) of the highest quartile of urinary BPA level was 1.47 [95% confidence interval (CI) 1.11-1.94] compared to the lowest quartile. After adjusted with covariates, the ORs for NAFLD in the third and fourth quartiles were 1.31 [95% CI 1.03-1.67] and 1.32 [95% CI 1.03-1.70], respectively. CONCLUSIONS: Urinary BPA levels are positively associated with the risk of NAFLD in adults. Further experimental studies are needed to understand the molecular mechanisms of BPA on NAFLD prevalence.

Association between Blood Mercury Levels and Non-Alcoholic Fatty Liver Disease in Non-Obese Populations: The Korean National Environmental Health Survey (KoNEHS) 2012-2014.

Mercury is widely distributed in the environment, and a plausible association between mercury exposure and hepatic damage has been reported. Non-alcoholic fatty liver disease (NAFLD), which comprises a spectrum of liver diseases, has recently been recognized in non-obese subjects. However, there have been no studies on the relationship between internal mercury levels and NAFLD in non-obese individuals. Therefore, we investigated the association between blood mercury levels and NAFLD in non-obese subjects. Cross-sectional data (n = 5919) were obtained from the Korean National Environmental Health Survey (2012-2014). NAFLD was defined using the hepatic steatosis index (HSI). Blood mercury levels were log-transformed and divided into quartiles based on a weighted sample distribution. The association between blood mercury levels and NAFLD was analyzed using a multivariate logistic analysis after body mass index stratification. The geometric mean of blood mercury in the overweight group was significantly higher than that of the non-obese group (p < 0.001). The weighted frequencies of patients with NAFLD based on the HSI were 3.0-7.2% for the non-obese subjects and 52.3-63.2% for the overweight subjects. In the multivariate analysis, blood mercury levels were positively associated with NAFLD for both the overweight and non-obese groups (all p for trend < 0.001). Increased blood mercury levels are closely associated with NAFLD. In particular, mercury could be a risk factor for NAFLD in the non-obese population.

The potential of BEN815 as an anti-inflammatory, antiviral and antioxidant agent for the treatment of COVID-19.

Background: The corona virus disease 2019 (COVID-19) pandemic has highlighted the fact that there are few effective antiviral agents for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although the very recent development of vaccines is an extremely important breakthrough, it remains unclear how long-lived such vaccines will be. The development of new agents therefore remains an important goal. Purpose: Given the multifaceted pathology of COVID-19, a combinatorial formulation may provide an effective treatment. BEN815, a natural nutraceutical composed of extracts from guava leaves (Psidium guajava), green tea leaves (Camellia sinensis), and rose petals (Rosa hybrida), had previously shown to have a therapeutic effect on allergic rhinitis. We investigated whether BEN815 possesses anti-inflammatory, antiviral and antioxidant activities, since the combination of these effects could be useful for the treatment of COVID-19. Study design: We examined the anti-inflammatory effects of BEN815 and its principal active components quercetin and epigallocatechin gallate (EGCG) in lipopolysaccharide (LPS)-induced RAW264.7 cells and in an LPS-challenged mouse model of endotoxemia. We also assessed the antioxidant activity, and antiviral effect of BEN815, quercetin, and EGCG in SARS-CoV-2-infected Vero cells. Methods: The principal active ingredients in BEN815 were determined and quantified using HPLC. Changes in the levels of LPS-induced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured by ELISA. Changes in the expression levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were analyzed using western blotting. Antioxidant assay was performed using DPPH and ABTS assay. SARS-CoV-2 replication was measured by immunofluorescence staining. Results: BEN815 significantly suppressed the induction of IL-6 and TNF-α as well as COX-2 and iNOS in LPS-induced RAW264.7 cells. In addition, BEN815 protected against LPS-challenged endotoxic shock in mice. Two major constituents of BEN815, quercetin and EGCG, reduced the induction of IL-6 and TNF-α as well as COX-2 and iNOS synthase in LPS-induced RAW264.7 cells. BEN815, quercetin, and EGCG were also found to have antioxidant effects. Importantly, BEN815 and EGCG could inhibit SARS-CoV-2 replications in Vero cells. Conclusion: BEN815 is an anti-inflammatory, antiviral, and antioxidant natural agent that can be used to prevent and improve inflammation-related diseases, COVID-19.

Isolation and molecular characterizations of canine distemper virus from a naturally infected Korean dog using Vero cells expressing dog signaling lymphocyte activation molecule.

BACKGROUND: Canine distemper virus (CDV) infection results in high morbidity and mortality in dogs. There has been no report about isolation of Korean CDV since 1980 in Korea. OBJECTIVES: To investigate the biological properties and the genetic characterization of Korean CDV. METHODS: Vero cells expressing dog signaling lymphocyte activation molecule (dSLAM) gene named as Vero/dSLAM were used to isolate CDV using 17 samples. Diagnostic methods such as cytopathic effects, immunofluorescence assay, peroxidase linked assay, electron microscopy, rapid immunodiagnostic assay, and reverse transcription polymerase chain reaction were used to confirm the Korean CDV isolate as a CDV. The genetic analysis was performed through cloning and sequencing of hemagglutinin gene of CDV isolate. RESULTS: A virus propagated in Vero/dSLAM cell was confirmed as CDV (CD1901 strain) based on the above methods. The CD1901 strain showed the highest viral titer (105.5 50% tissue culture infectious dose [TCID50]/mL) in the Vero/dSLAM cells at 4 days post inoculation, but did not form a fork on chorioallantoic membrane of 7-day-old egg. Ribavirin, a nucleotide analogue anti-viral agent, inhibits moderately the Korean CDV propagation in the Vero/dSLAM cells. The nucleotide and amino acid sequences of the H gene of CD1901 strain were compared with those of other CDV strains. The CD1901 strain belonged to Asia 1 group and had the highest similarity (99.9%) with the BA134 strain, which was isolated in China in 2008. CONCLUSIONS: We constructed successfully Vero/dSLAM and isolated one Korean CDV isolate (CD1901 strain) from a naturally infected dog. The CD1901 strain belonged to Asia 1 genotype.

Immunogenicity of a new, inactivated canine adenovirus type 2 vaccine for dogs.

PURPOSE: We constructed a new canine adenovirus type 2 (CAV-2) vaccine candidate using the recently isolated Korean CAV-2 strain; we termed the vaccine APQA1701-40P and evaluated its safety and immunogenicity in dogs. MATERIALS AND METHODS: To generate the anti-CAV-2 vaccine, APQA1701 was passaged 40 times in MDCK cells growing in medium containing 5 mM urea and the virus was inactivated using 0.05% (volume per volume) formaldehyde. Two vaccines were prepared by blending inactivated APQA1701-40P with two different adjuvants; both were intramuscularly injected (twice) into guinea pigs. The safety and immunogenicity of the Cabopol-adjuvanted vaccine were evaluated in seronegative dogs. The humoral responses elicited were measured using an indirect enzyme-linked immunosorbent assay (I-ELISA), and via a virus neutralization assay (VNA). RESULTS: The new, inactivated CAV-2 vaccine strain, APQA1701-40P, lacked six amino acids of the E1b-19K protein. In guinea pigs, the Cabopol-adjuvanted vaccine afforded a slightly higher VNA titer and I-ELISA absorbance than an IMS gel-adjuvanted vaccine 4 weeks post-vaccination (p>0.05). Dogs inoculated with the former vaccine developed a significantly higher immune titer than non-vaccinated dogs. CONCLUSION: The Cabopol-adjuvanted, inactivated CAV-2 vaccine was safe and induced a high VNA titer in dogs.

Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder.

BACKGROUND: Creatine monohydrate (creatine) augmentation has the potential to accelerate the clinical responses to and enhance the overall efficacy of selective serotonin reuptake inhibitor treatment in women with major depressive disorder (MDD). Although it has been suggested that creatine augmentation may involve the restoration of brain energy metabolism, the mechanisms underlying its antidepressant efficacy are unknown. METHODS: In a randomized, double-blind, placebo-controlled trial, 52 women with MDD were assigned to receive either creatine augmentation or placebo augmentation of escitalopram; 34 subjects participated in multimodal neuroimaging assessments at baseline and week 8. Age-matched healthy women (n = 39) were also assessed twice at the same intervals. Metabolic and network outcomes were measured for changes in prefrontal N-acetylaspartate and changes in rich club hub connections of the structural brain network using proton magnetic resonance spectroscopy and diffusion tensor imaging, respectively. RESULTS: We found MDD-related metabolic and network dysfunction at baseline. Improvement in depressive symptoms was greater in patients receiving creatine augmentation relative to placebo augmentation. After 8 weeks of treatment, prefrontal N-acetylaspartate levels increased significantly in the creatine augmentation group compared with the placebo augmentation group. Increment in rich club hub connections was also greater in the creatine augmentation group than in the placebo augmentation group. CONCLUSIONS: N-acetylaspartate levels and rich club connections increased after creatine augmentation of selective serotonin reuptake inhibitor treatment. Effects of creatine administration on brain energy metabolism and network organization may partly underlie its efficacy in treating women with MDD.