Superoxide Dismutase-Mimetic Polyphenol-Based Carbon Dots for Multimodal Bioimaging and Treatment of Atopic Dermatitis.

Polyphenols have been investigated for their potential to mitigate inflammation in the context of atopic dermatitis (AD). In this study, epigallocatechin-3-gallate (EGCG)-based carbon dots (EGCG@CDs) were developed to enhance transdermal penetration, reduce inflammation, recapitulate superoxide dismutase (SOD) activity, and provide antimicrobial effects for AD treatment. The water-soluble EGCG@CDs in a few nanometers size exhibit a negative zeta potential, making them suitable for effective transdermal penetration. The fluorescence properties, including an upconversion effect, make EGCG@CDs suitable imaging probes for both in vitro and in vivo applications. By mimicking the SOD enzyme, EGCG@CDs scavenge reactive oxygen species (ROS) and actively produce hydrogen peroxide through a highly catalytic capability toward the oxygen reduction reaction, resulting in the inhibition of bacterial growth. The enhanced antioxidant properties, high charge mobility, and various functional groups of EGCG@CDs prove effective in reducing intracellular ROS in an in vitro AD model. In the mouse AD model, EGCG@CDs incorporated into a hydrogel actively penetrated the epidermal layer, leading to ROS scavenging, reduced mast cell activation, and histological recovery of skin barriers. This research represents the versatile potential of EGCG@CDs in addressing AD and advancing tissue engineering.

Comparative analysis of supercritical fluid-based and chemical-based decellularization techniques for nerve tissue regeneration.

Axon regeneration and Schwann cell proliferation are critical processes in the repair and functional recovery of damaged neural tissues. Biomaterials can play a crucial role in facilitating cell proliferative processes that can significantly impact the target tissue repair. Chemical decellularization and supercritical fluid-based decellularization methods are similar approaches that eliminate DNA from native tissues for tissue-mimetic biomaterial production by using different solvents and procedures to achieve the final products. In this study, we conducted a comparative analysis of these two methods in the context of nerve regeneration and neuron cell differentiation efficiency. We evaluated the efficacy of each method in terms of biomaterial quality, preservation of extracellular matrix components, promotion of neuronal cell differentiation and nerve tissue repair ability in vivo. Our results indicate that while both methods produce high-quality biomaterials, supercritical fluid-based methods have several advantages over conventional chemical decellularization, including better preservation of extracellular matrix components and mechanical properties and superior promotion of cellular responses. We conclude that supercritical fluid-based methods show great promise for biomaterial production for nerve regeneration and neuron cell differentiation applications.

Decellularized brain extracellular matrix based NGF-releasing cryogel for brain tissue engineering in traumatic brain injury.

Traumatic brain injuries(TBI) pose significant challenges to human health, specifically neurological disorders and related motor activities. After TBI, the injured neuronal tissue is known for hardly regenerated and recovered to their normal neuron physiology and tissue compositions. For this reason, tissue engineering strategies that promote neuronal regeneration have gained increasing attention. This study explored the development of a novel neural tissue regeneration cryogel by combining brain-derived decellularized extracellular matrix (ECM) with heparin sulfate crosslinking that can perform nerve growth factor (NGF) release ability. Morphological and mechanical characterizations of the cryogels were performed to assess their suitability as a neural regeneration platform. After that, the heparin concnentration dependent effects of varying NGF concentrations on cryogel were investigated for their controlled release and impact on neuronal cell differentiation. The results revealed a direct correlation between the concentration of released NGF and the heparin sulfate ratio in cryogel, indicating that the cryogel can be tailored to carry higher loads of NGF with heparin concentration in cryogel that induced higher neuronal cell differentiation ratio. Furthermore, the study evaluated the NGF loaded cryogels on neuronal cell proliferation and brain tissue regeneration in vivo. The in vivo results suggested that the NGF loaded brain ECM derived cryogel significantly affects the regeneration of brain tissue. Overall, this research contributes to the development of advanced neural tissue engineering strategies and provides valuable insights into the design of regenerative cryogels that can be customized for specific therapeutic applications.

Sprayable Ti3C2 MXene hydrogel for wound healing and drug release system.

Wound healing is a critical process that facilitates the body's recovery from injuries and helps prevent infections, thereby maintaining overall tissue and organ functionality. However, delayed wound healing owing to various factors can lead to bacterial infections and secondary complications. In this study, a ciprofloxacin (CIP)-loaded MXene/sodium alginate (SA) hydrogel was fabricated to inhibit bacterial infections and enhance wound healing. The hydrogel was formulated in a sprayable state by blending CIP-loaded MXene (CIP-MX) with SA. This hydrogel was found to exhibit excellent photothermal conversion capability and biocompatibility under near-infrared (NIR) irradiation. In addition, the hydrogel enabled controlled drug release based on NIR irradiation, ultimately enabling improved antibacterial activity. Based on the in vitro and in vivo experiments, the CIP-loaded MXene/SA hydrogel (CIP-MX@Gel) accelerated wound healing. Overall, the CIP-MX@Gel has excellent potential as an effective wound healing material.

Δ8(14)-Ergostenol Glycoside Derivatives Inhibit the Expression of Inflammatory Mediators and Matrix Metalloproteinase.

Arthritis is a chronic inflammatory disease accompanied by pathological reactions such as swelling, redness, fever, and pain in various joint areas. The drugs currently available to treat arthritis are associated with diverse side-effects. Therefore, there is a need for safer and more effective treatments to alleviate the inflammation of arthritis with fewer side-effects. In this study, a new sterol, Δ8(14)-ergostenol, was discovered, and its glycosides were synthesized and found to be more efficient in terms of synthesis or anti-inflammatory activity than either spinasterol or 5,6-dihydroergosterol is. Among these synthetic glycosides, galactosyl ergostenol inhibited the expression of inflammatory mediators in TNF-α-stimulated FLS and TNF-α-induced MMPs and collagen type II A1 degradation in human chondrocytes. These results suggest the new galactosyl ergostenol as a treatment candidate for arthritis.

Supercritical Fluid-Based Decellularization Technologies for Regenerative Medicine Applications.

Supercritical fluid-based extraction technologies are currently being increasingly utilized in high purity extract products for food industries. In recent years, supercritical fluid-based extraction technology is transformed in biomaterials process fields to be further utilized for tissue engineering and other biomedical applications. In particular, supercritical fluid-based decellularization protocols have great advantage over the conventional decellularization as it may allow preservation of extracellular matrix components and structures. In this review, the latest technological development utilizing the supercritical fluid-based decellularization for regenerative medicine is introduced.

Effect of Surface Modifications and Their Reaction Conditions on Multi-Walled Carbon Nanotubes for Thermal Conductive Composite Material.

Thermally conductive composite materials were fabricated using Al2O3 and surface-modified MWCNTs on an ETDS matrix. The MWCNT surfaces were modified using a solution containing H2O2 and H2SO4/HNO3 and examined at various reaction times. After surface modification, the ratios of the functional groups introduced were compared. The changes in MWCNT morphology and thermal conductivity were also investigated for various reaction times. It was observed from the results that the MWCNTs exposed to 1 h acid treatment had the highest thermal conductivity without any decrease in their length. Based on the optimum oxidization of MWCNTs, further surface modification was performed using APTES, a silane coupling agent, using two different reactions. After the reaction, large particle aggregations were observed on the amine-terminated MWCNTs, which reacted with a mixture of EtOH and DI water. These agglomerates did not re-disperse after long-time sonication. However, the silanol-terminated MWCNTs were easily dispersed in EtOH via sonication, and their composite materials had outstanding thermal conductivities. Moreover, more amount of MWCNTs were processable using the same Al2O3 and ETDS concentrations, which also led to enhanced thermal conductivities compared to the other surface modification methods.

Paradigm for diagnosing mycobacterial disease: direct detection and differentiation of Mycobacterium tuberculosis complex and non-tuberculous mycobacteria in clinical specimens using multiplex real-time PCR.

AIMS: Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) are clinically different, and the rapid detection and differentiation of M. tuberculosis complex (MTBC) and NTM is crucial for patient management and infection control. Given the slow growth of most pathogenic mycobacteria, nucleic acid amplification assays are excellent tools for direct identification of mycobacteria in clinical specimens. Recently, a multiplex real-time PCR assay was developed that can directly detect 20 mycobacterial species in clinical specimens. Here, we evaluated the diagnostic performance of the assay for diagnosing mycobacterial disease under routine laboratory conditions. METHODS: A total of 3334 specimens collected from 1437 patients suspected of tuberculosis infection were subjected to acid-fast bacilli staining, conventional culture and the multiplex real-time PCR assay. To evaluate the sensitivity and specificity of the assay, the overall diagnosis of tuberculosis was defined by positive culture plus medical history, and the 2007 American Thoracic Society and Infectious Disease Society of America diagnostic criteria for NTM disease were applied. RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value were 87.5%, 99.6%, 96.1% and 98.5%, respectively, for the detection of MTBC isolates and 53.3%, 99.9%, 95.2%, and 98.9%, respectively, for detecting NTM isolates. CONCLUSIONS: Thus, the assay can correctly differentiate between MTBC and NTM isolates in clinical specimens and would be a useful tool for the rapid differentiation of tuberculosis and NTM disease, despite its limited sensitivity for the diagnosis of NTM disease.

Vitamin D receptor polymorphisms and Parkinson's disease in a Korean population: Revisited.

Recently, the effect of genetic variants in the Vitamin D receptor (VDR) gene on Parkinson's disease (PD) has gained interest. However, the precise relationship between VDR polymorphisms and PD remains unclear. In Korea, one study reported an association between VDR gene polymorphisms and PD. However, this study was conducted with a small sample size, and only the Bsml locus was evaluated. Therefore, further investigations about the relationship between VDR polymorphisms and PD are necessary in a Korean population. A total of 300 subjects were included in this study. One hundred and forty-six PD patients were diagnosed according to the United Kingdom Parkinson's Disease Society Brain Bank (UKPDBB) criteria with abnormal dopamine transporter imaging, and 154 healthy control subjects were also enrolled. We used a TaqMan genotyping assay to identify four SNPs of the VDR gene, including BsmI, FokI, ApaI, and TaqI (rs731236, rs2228570, rs7976091, and rs731236). A significant association was not noted between the risk of PD and genetic polymorphisms in the four loci in a Korean population. However, when the genetic variants of the VDR gene were analyzed after adjusting for the serum 25-OH vitamin D3 level, the TaqI and BsmI minor allele increased the risk of PD. Our data suggest no correlation between PD and the VDR polymorphisms, including BsmI, FokI, ApaI, and TaqI, in a Korean population; however, the results should be interpreted carefully because gene-environment interactions may exist. Further investigations of the VDR and its relationship with PD are required to identify the role of vitamin D in the pathogenesis of PD.

Direct identification of mycobacteria from liquid media using a triplex real-time PCR coupled with pyrosequencing method.

Culture in enriched broth, as well as on a solid medium, is recommended for primary isolation of mycobacteria. With the introduction of liquid mycobacterial culture methods, a substantial workload regarding the identification of culture-recovered mycobacterial species, particularly Mycobacterium tuberculosis complex (MTC), has been imposed on our laboratory. We thus developed a triplex, real-time PCR coupled with pyrosequencing assay that can directly identify mycobacterial species from liquid media, which can reduce the workload. In this assay, real-time PCR simultaneously detects MTC and Mycobacterium xenopi, and amplifies the region of 16S rRNA gene containing hypervariable region A for pyrosequencing analysis; subsequent, pyrosequencing identifies many other nontuberculous mycobacteria. The assay was evaluated using 333 DNA samples directly prepared from liquid media, including 24 reference strains and 309 clinical isolates. Three hundred and twenty-eight (98.5%) of the 333 samples were correctly identified. The remaining five were determined as indeterminate. In conclusion, this coupled assay would be an alternative method for rapid identification of mycobacteria directly from liquid media in a clinical laboratory with a high workload in regions where tuberculosis is endemic.

An energy efficient distance-aware routing algorithm with multiple mobile sinks for wireless sensor networks.

Traffic patterns in wireless sensor networks (WSNs) usually follow a many-to-one model. Sensor nodes close to static sinks will deplete their limited energy more rapidly than other sensors, since they will have more data to forward during multihop transmission. This will cause network partition, isolated nodes and much shortened network lifetime. Thus, how to balance energy consumption for sensor nodes is an important research issue. In recent years, exploiting sink mobility technology in WSNs has attracted much research attention because it can not only improve energy efficiency, but prolong network lifetime. In this paper, we propose an energy efficient distance-aware routing algorithm with multiple mobile sink for WSNs, where sink nodes will move with a certain speed along the network boundary to collect monitored data. We study the influence of multiple mobile sink nodes on energy consumption and network lifetime, and we mainly focus on the selection of mobile sink node number and the selection of parking positions, as well as their impact on performance metrics above. We can see that both mobile sink node number and the selection of parking position have important influence on network performance. Simulation results show that our proposed routing algorithm has better performance than traditional routing ones in terms of energy consumption.

Direct identification of mycobacteria from culture media using a multiplex real-time PCR assay: report on its application in a clinical laboratory in a region of high tuberculosis endemicity.

There are few commercial assays that easily and correctly identify the mycobacteria from culture in a clinical laboratory with a high workload. Thus, we developed and evaluated a scheme for the identification of mycobacteria using a multiplex real-time PCR assay and report on its application in our laboratory. The scheme consisted of 3 stepwise PCRs. Mycobacterium tuberculosis complex (MTC) and nontuberculous mycobacteria (NTM) were differentially detected in the step 1 PCR, and the NTM species were identified in the step 2 and 3 PCRs. Over the 1.5-year study period, 1136 isolates of MTC and 618 isolates of NTM were detected, and the species of 608 (98.4%) of the 618 NTM isolates were identified. We conclude that the established scheme is a very useful diagnostic approach for the rapid and accurate identification of MTC and clinically relevant NTM in a clinical laboratory in a region where tuberculosis is endemic.

Multiplex real-time PCR assay for detection of methicillin-resistant Staphylococcus aureus (MRSA) strains suitable in regions of high MRSA endemicity.

A multiplex real-time PCR assay that simultaneously detects the mecA, staphylococcal cassette chromosome (SCCmec)-open reading frame X (orfX) junction, and staphylococcal 16S rRNA genes was developed and evaluated using 444 staphylococcal strains. We demonstrated that this assay resulted in fewer false-positive results than a single-locus real-time PCR assay that amplified the SCCmec-orfX junction. This assay would be useful in a clinical laboratory in a region of high endemicity for methicillin-resistant Staphylococcus aureus (MRSA) infections.

Rho-associated kinase 2 polymorphism in patients with vasospastic angina.

BACKGROUND AND OBJECTIVES: Recent studies indicate that in response to vasoconstrictor stimuli, the small GTPase RhoA and its down-stream effector, Rho-associated kinase 2 (ROCK)/Rho-kinase, are associated with hypercontraction of the vascular smooth muscle of coronary arteries through augmentation of myosin light chain phosphorylation and Ca(2+) sensitization. Expression of ROCK/Rho-kinase mRNA was significantly increased and up-regulated in the spastic coronary artery in a porcine model, and a specific inhibitor of ROCK/Rho-kinase inhibited coronary artery spasm in humans. We therefore explored the role of ROCK2 polymorphisms in the pathogenesis of vasospastic angina (VA). SUBJECTS AND METHODS: We studied 106 patients with VA who exhibited spontaneous or provoked coronary spasm during coronary angiography and compared the prevalence of ROCK2 polymorphisms between this group of patients with VA and controls whose angiograms were normal, and in whom the ergonovine test did not cause spasm (n=107). Five single nucleotide polymorphisms (SNPs) of the ROCK2 gene were selected. SNPs were genotyped by high-resolution melting. Linkage disequilibrium and haplotype analyses were performed using the SHEsis program. RESULTS: The prevalence of genotypes of the 5 interesting SNPs in patients with VA was not different from that in the control group. In haplotype analysis, the haplotype G-T-C-T-G (in order of rs978906, rs2271621, rs2230774, rs1515210, and rs3771106) was significantly associated with a decreased risk of VA (p=0.007). CONCLUSION: The haplotype G-T-C-T-G in the ROCK2 gene had a protective effect against VA, suggesting the involvement of ROCK2 in VA pathogenesis.

Multiplex real-time PCR assay and melting curve analysis for identifying Mycobacterium tuberculosis complex and nontuberculous mycobacteria.

A multiplex real-time PCR assay and melting curve analysis for identifying 23 mycobacterial species was developed and evaluated using 77 reference strains and 369 clinical isolates. Concordant results were obtained for all 189 (100%) isolates of the Mycobacterium tuberculosis complex and 169 (93.9%) isolates of nontuberculous mycobacteria. Our results showed that this multiplex real-time PCR assay is an effective tool for the mycobacterial identification from cultures.

A Distance-based Energy Aware Routing algorithm for wireless sensor networks.

Energy efficiency and balancing is one of the primary challenges for wireless sensor networks (WSNs) since the tiny sensor nodes cannot be easily recharged once they are deployed. Up to now, many energy efficient routing algorithms or protocols have been proposed with techniques like clustering, data aggregation and location tracking etc. However, many of them aim to minimize parameters like total energy consumption, latency etc., which cause hotspot nodes and partitioned network due to the overuse of certain nodes. In this paper, a Distance-based Energy Aware Routing (DEAR) algorithm is proposed to ensure energy efficiency and energy balancing based on theoretical analysis of different energy and traffic models. During the routing process, we consider individual distance as the primary parameter in order to adjust and equalize the energy consumption among involved sensors. The residual energy is also considered as a secondary factor. In this way, all the intermediate nodes will consume their energy at similar rate, which maximizes network lifetime. Simulation results show that the DEAR algorithm can reduce and balance the energy consumption for all sensor nodes so network lifetime is greatly prolonged compared to other routing algorithms.

Association of endothelin-1 gene polymorphisms with variant angina in Korean patients.

BACKGROUND: The incidence of variant angina in oriental patients is higher than in patients from the Western world. Endothelin-1 (ET-1) seems to be associated with coronary vasospasm in variant angina, suggesting that ET-1 gene variants may be important in coronary vasospasm in variant angina. We wanted to assess potential association between Korean variant angina and three polymorphisms of the ET-1 gene, which include the +138delA polymorphism in exon 1, G8002A polymorphism in intron 4 and Lys198Asn polymorphism in exon 5. METHOD: A total of 97 patients with variant angina and 111 healthy controls were studied. Analyses of the +138delA, G8002A and Lys198Asn polymorphisms were carried out by polymerase chain reaction-restriction fragment length polymorphism and haplotype techniques. RESULTS: The frequency of mutant 138delA allele was lower in the angina group than in controls [p=0.003, odds ratio (OR)=0.42] and the frequencies of A8002 or Asn198 were significantly higher in the variant angina group than in controls (p=0.005, OR=2.17 or p=0.009, OR=1.75, respectively). According to haplotype analysis, 4A/A8002/Asn198 haplotype was significantly associated with the disease (p=0.0162, OR=2.33) and 3A/G8002/Lys198 haplotype was protective against the disease (p=0.0043, OR=0.54). CONCLUSIONS: The ET-1 gene polymorphisms, such as +138delA, G8002A and Lys198Asn polymorphisms, seem to be associated with variant angina in Korean patients.

Molecular epidemiological profile of rotavirus in South Korea, July 2002 through June 2003: emergence of G4P[6] and G9P[8] strains.

To determine the distribution of rotavirus strain genotypes in South Korea, rotavirus-positive stool specimens were collected from July 2002 through June 2003 at 8 hospitals in the Korean Rotavirus Strain Surveillance Network, and they were genotyped by means of reverse-transcription polymerase chain reaction. The globally uncommon G4P[6] type was the most prevalent type identified among strains (27% of strains), the newly emerging G9P[8] strain accounted for 11% of strains, and the globally common genotypes (i.e., G1P[8], G2P[4], G3P[8], and G4P[8]) constituted 55% of the strains characterized. Ninety percent of G4P[6] strains were detected in specimens obtained from neonates. Common genotypes were responsible for the rotavirus epidemic that began in January 2003 and ended in May 2003; however, an early peak in infections with the G4P[6] strain occurred from August through October 2002, and infections with this strain were detected throughout the remaining study period. G4P[6] strains were most commonly identified at 6 urban health care centers, but they were absent from 2 rural health care centers. The newly emerging strain G9P[8] represented a relatively greater proportion of strains identified at a hospital in the central region of Korea and at 2 hospitals in the southern region. The identification of novel rotavirus genotypes in this laboratory-based surveillance study underscores the importance to public health of continued strain surveillance among children for whom prevention of rotavirus infection by vaccination might be considered.

Carvedilol reduces plasma 8-hydroxy-2'-deoxyguanosine in mild to moderate hypertension: a pilot study.

The purpose of this pilot study was to test whether carvedilol has a protective effect against oxidative deoxyribonucleic acid (DNA) damage in human hypertension in vivo. Carvedilol's antioxidant effect has mostly focused on lipid or amino acid so far. However, there has been no data that carvedilol reduces DNA damage in human hypertension. Never-treated mild to moderate hypertension patients and age- and sex-matched control subjects volunteered for the study. The hypertension subjects were given 12.5 or 25 mg of carvedilol or hydrochlorothiazide orally for 2 months and controls were not given any. Fasting blood samples were collected before and after carvedilol. Plasma highly sensitive 8-hydroxy-2'-deoxyguanosine (hs8-OHdG) and high-sensitivity C-reactive protein (hsCRP) were checked with the samples. There were no statistical differences in clinical characteristics in 3 groups. The hs8-OHdG declined from 9.07+/-4.23 ng/mL to 5.74+/-3.89 ng/mL (P=0.002) after carvedilol. However, it did not show significant reduction after hydrochlorothiazide (9.01+/-3.89 versus 8.23+/-4.12 ng/mL; P=NS). In the control group, the hs8-OHdG concentration was 3.41+/-2.03 ng/mL and 3.01+/-2.65 ng/mL at baseline and 2 months later, respectively (P=NS). The baseline hs8-OHdG levels were higher in hypertension groups compared with control (P=0.000). The hsCRP had no significant difference before and after the tested drugs in 2 hypertension groups (group A: 0.21+/-0.51 versus 0.19+/-0.37 mg/dL; group B: 0.20+/-0.45 versus 0.18+/-0.42 mg/dL). In conclusion, DNA damage caused by reactive oxygen species occurs more in the hypertension patients than normals. Carvedilol significantly reduces DNA damage in the hypertension patients.