The efficacy of intradermal hyaluronic acid filler as a skin quality booster: A prospective, single-center, single-arm pilot study.

BACKGROUND: The use of "skin boosters" comprised of hyaluronic acid (HA)-based fillers to improve skin quality has gained popularity recently, especially in individuals interested in skin rejuvenation. AIM: This study aimed to evaluate the efficacy and safety of intradermal micropuncture injections of HA-based gel filler combined with lidocaine (BYRYZN® SKINBOOSTER HA, ACROSS Co., Ltd., Gangwon-do, Korea). PATIENTS/METHODS: A prospective, single-arm, open-label pilot study was conducted with study subjects who were aged between 30 and 60 years old and exhibited evidence of skin aging, such as wrinkles and loss of elasticity. They received three injections at 2-week intervals and were followed up for a total of 12 weeks. RESULTS: Twenty subjects with a mean age of 54.1 years were included. The mean Lemperle wrinkle scale demonstrated a 40% decrease from 2.60 ± 0.60 at baseline to 1.55 ± 0.51 at week 8. The improvement rate was maintained at about 33% until week 12. The average maximum height of the wrinkle (Rz, µm), average skin roughness (Ra, µm), skin elasticity (R2, AU), facial curved length (mm), skin pore size (mm2 ), skin hydration (AU), TEWL (g/hm2 ), and skin glossiness (gloss value, AU) exhibited statistically significant improvements over time compared with the baseline measurements. No serious adverse effects or persistent adverse effects were reported, except for a transient subcutaneous nodule in one subject. CONCLUSIONS: This study demonstrates that multiple microinjections of HA-based gel filler for facial skin aging are safe and effective in improving facial skin quality.

Evaluation of the Antiviral Activity of Tabamide A and Its Structural Derivatives against Influenza Virus.

Influenza viruses cause severe endemic respiratory infections in both humans and animals worldwide. The emergence of drug-resistant viral strains requires the development of new influenza therapeutics. Tabamide A (TA0), a phenolic compound isolated from tobacco leaves, is known to have antiviral activity. We investigated whether synthetic TA0 and its derivatives exhibit anti-influenza virus activity. Analysis of structure-activity relationship revealed that two hydroxyl groups and a double bond between C7 and C8 in TA0 are crucial for maintaining its antiviral action. Among its derivatives, TA25 showed seven-fold higher activity than TA0. Administration of TA0 or TA25 effectively increased survival rate and reduced weight loss of virus-infected mice. TA25 appears to act early in the viral infection cycle by inhibiting viral mRNA synthesis on the template-negative strand. Thus, the anti-influenza virus activity of TA0 can be expanded by application of its synthetic derivatives, which may aid in the development of novel antiviral therapeutics.

5-Methylthiopentyl Isothiocyanate, a Sulforaphane Analogue, Inhibits Pro-inflammatory Cytokines by Regulating LPS/ATP-mediated NLRP3 Inflammasome Activation.

BACKGROUND: Pro-inflammatory cytokines secreted from activated macrophages and astrocytes are crucial mediators of inflammation for host defense. Among them, the secretion of IL-1ß, a major pro-inflammatory cytokine, is especially mediated by the activation of NLRP3 inflammasome. Pro-IL-1ß, which is produced in response to the invaded pathogens, such as LPS, is cleaved and matured in the NLRP3 inflammasome by the recognition of ATP. Excessively activated IL-1ß induces other immune cells, resulting in the up-regulation of inflammation. Therefore, regulation of NLRP3 inflammasome can be a good strategy for alleviating inflammation. OBJECTIVE: Our study aimed to examine whether 5-methylthiopentyl isothiocyanate, a sulforaphane analogue (berteroin), has an anti-inflammatory effect on the NLRP3 inflammasome activation induced by LPS and ATP. METHODS: Primary bone marrow-derived macrophages (BMDMs) and astrocytes were stimulated by LPS and ATP with the treatment of 5-methylthiopentyl isothiocyanate, a sulforaphane analogue. The secretion of pro-inflammatory cytokines was measured by ELISA, and the expression level of NLRP3 inflammasome-associated proteins was detected by western blot. The association of NLRP3 inflammasome was assessed by co-immunoprecipitation, and the formation of ASC specks was evaluated by fluorescent microscope. RESULTS: 5-Methylthiopentyl isothiocyanate, a sulforaphane analogue (berteroin), decreased the release of pro-inflammatory cytokines, IL-1ß, and IL-6 in the BMDMs. Berteroin notably prevented the formation of both NLRP3 inflammasome and ASC specks, which reduced the secretion of IL-1ß. Additionally, berteroin reduced the IL-1ß secretion and cleaved IL-1ß expression in the primary astrocytes. DISCUSSION AND CONCLUSION: These results indicated the anti-inflammatory effects of 5-methylthiopentyl isothiocyanate (berteroin) by regulating NLRP3 inflammasome activation, suggesting that berteroin could be the potential natural drug candidate for the regulation of inflammation.

Predicting the severity of postoperative scars using artificial intelligence based on images and clinical data.

Evaluation of scar severity is crucial for determining proper treatment modalities; however, there is no gold standard for assessing scars. This study aimed to develop and evaluate an artificial intelligence model using images and clinical data to predict the severity of postoperative scars. Deep neural network models were trained and validated using images and clinical data from 1283 patients (main dataset: 1043; external dataset: 240) with post-thyroidectomy scars. Additionally, the performance of the model was tested against 16 dermatologists. In the internal test set, the area under the receiver operating characteristic curve (ROC-AUC) of the image-based model was 0.931 (95% confidence interval 0.910‒0.949), which increased to 0.938 (0.916‒0.955) when combined with clinical data. In the external test set, the ROC-AUC of the image-based and combined prediction models were 0.896 (0.874‒0.916) and 0.912 (0.892‒0.932), respectively. In addition, the performance of the tested algorithm with images from the internal test set was comparable with that of 16 dermatologists. This study revealed that a deep neural network model derived from image and clinical data could predict the severity of postoperative scars. The proposed model may be utilized in clinical practice for scar management, especially for determining severity and treatment initiation.

The Molecular Mechanisms of Neuroinflammation in Alzheimer's Disease, the Consequence of Neural Cell Death.

Alzheimer's disease (AD) is accompanied by neural cell loss and memory deficit. Neural cell death, occurring via apoptosis and autophagy, is widely observed in the AD brain in addition to neuroinflammation mediated by necroptosis and the NLRP3 inflammasome. Neurotoxicity induced by amyloid-beta (Aß) and tau aggregates leads to excessive neural cell death and neuroinflammation in the AD brain. During AD progression, uncontrolled neural cell death results in the dysregulation of cellular activity and synaptic function. Apoptosis mediated by pro-apoptotic caspases, autophagy regulated by autophagy-related proteins, and necroptosis controlled by the RIPK/MLKL axis are representative of neural cell death occurred during AD. Necroptosis causes the release of cellular components, contributing to the pro-inflammatory environment in the AD brain. Inordinately high levels of neural cell death and pro-inflammatory events lead to the production of pro-inflammatory cytokines and feed-forward hyper neuroinflammation. Thus, neural cell death and neuroinflammation cause synaptic dysfunction and memory deficits in the AD brain. In this review, we briefly introduce the mechanisms of neural cell death and neuroinflammation observed in the AD brain. Combined with a typical strategy for targeting Aß and tau, regulation of neural cell death and neuroinflammation may be effective for the amelioration of AD pathologies.

Effectiveness of creating digital twins with different digital dentition models and cone-beam computed tomography.

Distortion of dentition may occur in cone-beam computed tomography (CBCT) scans due to artifacts, and further imaging is frequently required to produce digital twins. The use of a plaster model is common; however, it has certain drawbacks. This study aimed to assess the feasibility of different digital dentition models over that of plaster casts. Plaster models, alginate impressions, intraoral scan (IOS) images, and CBCT images of 20 patients were obtained. The desktop model scanner was used to scan the alginate impression twice, five minutes and two hours after impression-making. Using an IOS, the full arch was scanned in segments using CS 3600 and simultaneously with i700 wireless. The digital twins obtained from the alginate impression and IOS were superimposed with those obtained from the plaster cast. The differences and distances at each reference point were measured. Scans of alginate impressions after two hours showed the greatest discrepancies, but these were all less than the CBCT voxel size of 0.39 mm. Alginate impression scans and IOS are suitable supplements to CBCT compared to the plaster model. Accuracy can be improved by scanning the alginate impression within five minutes or by intraoral scanning of the entire arch with segmentation.

NXP032 ameliorates cognitive impairment by alleviating the neurovascular aging process in aged mouse brain.

Vascular aging is well known to be associated with the breakdown of the neurovascular unit (NVU), which is essential for maintaining brain homeostasis and linked to higher cognitive dysfunction. Oxidative stress is believed to be a significant cause of the vascular aging process. Vitamin C is easily oxidized under physiological conditions, so it loses its potent antioxidant activity. We developed a DNA aptamer that enhances the function of vitamin C. NXP032 is the binding form of the aptamer and vitamin C. In this study, we investigated the effect of NXP032 on neurovascular stabilization through the changes of PECAM-1, PDGFR-ß, ZO-1, laminin, and glial cells involved in maintaining the integrity of the blood-brain barrier (BBB) in aged mice. NXP032 was orally administered daily for 8 weeks. Compared to young mice and NXP032-treated mice, 20-month-old mice displayed cognitive impairments in Y-maze and passive avoidance tests. NXP032 treatment contributed to reducing the BBB damage by attenuating the fragmentation of microvessels and reducing PDGFR-ß, ZO-1, and laminin expression, thereby mitigating astrocytes and microglia activation during normal aging. Based on the results, we suggest that NXP032 reduces vascular aging and may be a novel intervention for aging-induced cognitive impairment.

The Derivatives of Cromolyn Ameliorate the Abnormal Misfolding of Amyloid Proteins and Neuroinflammation in the Neural Cells.

BACKGROUND: The representative symptom of Alzheimer's Disease (AD) has mainly been mentioned to be misfolding of amyloid proteins, such as amyloid-beta (Aß) and tau protein. In addition, the neurological pathology related to neuroinflammatory signaling has recently been raised as an important feature in AD. Currently, numerous drug candidates continue to be investigated to reduce symptoms of AD, including amyloid proteins misfolding and neuroinflammation. OBJECTIVE: Our research aimed to identify the anti-AD effects of two chemical derivatives modified from cromoglicic acid, CNU 010 and CNU 011. METHODS: CNU 010 and CNU 011 derived from cromoglicic acid were synthesized. The inhibitory effects of Aß and tau were identified by thioflavin T assay. Moreover, western blots were conducted with derivates CNU 010 and CNU 011 to confirm the effects on inflammation. RESULTS: CNU 010 and CNU 011 significantly inhibited the aggregation of Aß and tau proteins. Moreover, they reduced the expression levels of mitogen-activated protein (MAP) kinase and nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB) signaling proteins, which are representative early inflammatory signaling markers. Also, the inhibitory effects on the lipopolysaccharide (LPS)-induced cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expression referring to late inflammation were confirmed. CONCLUSION: Our results showing multiple beneficial effects of cromolyn derivatives against abnormal aggregation of amyloid proteins and neuroinflammatory signaling provide evidence that CNU 010 and CNU 011 could be further developed as potential drug candidates for AD treatment.

A randomized split-face comparative study of long-pulsed alexandrite plus low-fluence Nd:YAG laser versus pulsed-dye laser in the treatment of rosacea.

OBJECTIVES: To compare the effectiveness of long-pulsed alexandrite laser (LPAL) with that of pulsed-dye laser (PDL) for rosacea. METHODS: This was a single-blind randomized controlled trial on 27 patients who were clinically diagnosed with rosacea. Randomly assigned split face in each patient received four times monthly treatment of LPAL plus low-fluence Nd:YAG with the contralateral side serving as the control treated with PDL. At every visit, the erythema index (EI) was measured with skin analysis systems, and two independent dermatologists evaluated digital photographs for five-point global aesthetic improvement scale (GAIS). RESULTS: The EI significantly decreased on both treated sides (LPAL 366.5 ± 101.0 vs. 295.8 ± 90.2, p < 0.001, PDL 369.0 ± 124.3 vs. 302.7 ± 92.1, p < 0.001) 1 month after fourth treatment (visit 5). Also 3 months after the fourth treatment (visit 6), the reduction in the EI was well maintained on both sides (LPAL 360.3 ± 96.8 vs. 282.0 ± 89.2, p < 0.001, PDL 364.3 ± 121.6 vs. 281.6 ± 97.8, p < 0.001). When comparing the improvement in the EI between the two groups, the percentage reduction in the EI on the LPAL-treated side was not inferior to the PDL-treated side (visit 5: LPAL 18.7 ± 15.7% vs. PDL 16.4 ± 12.9%, p = 0.501 and visit 6: LPAL 21.7 ± 13.9% vs. PDL 21.9 ± 15.2%, p = 0.943). The GAIS and patient satisfaction were comparable between the LPAL and PDL sides and did not show any significant difference. No serious adverse events occurred on either of the treated sides. CONCLUSION: This study showed that the decrease in EI in the treatment of rosacea was comparable between PDL and LPAL. Therefore, LPAL could be a promising alternative treatment option with good merits for rosacea, considering no consumables are required for device maintenance.

NXP031 prevents dopaminergic neuronal loss and oxidative damage in the AAV-WT-α-synuclein mouse model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by inclusions of aggregated α-synuclein (α-Syn). Oxidative stress plays a critical role in nigrostriatal degeneration and is responsible for α-Syn aggregation in PD. Vitamin C or ascorbic acid acts as an effective antioxidant to prevent free radical damage. However, vitamin C is easily oxidized and often loses its physiological activity, limiting its therapeutic potential. The objective of this study was to evaluate whether NXP031, a new compound we developed consisting of Aptamin C and Vitamin C, is neuroprotective against α-synucleinopathy. To model α-Syn induced PD, we stereotactically injected AAV particles overexpressing human α-Syn into the substantia nigra (SN) of mice. One week after AAV injection, NXP031 was administered via oral gavage every day for eight weeks. We found that oral administration of NXP031 ameliorated motor deficits measured by the rotarod test and prevented the loss of nigral dopaminergic neurons caused by WT-α-Syn overexpression in the SN. Also, NXP031 blocked the propagation of aggregated α-Syn into the hippocampus by alleviating oxidative stress. These results indicate that NXP031 can be a potential therapeutic for PD.

Positivity of Rapid Antigen Testing for SARS-CoV-2 With Serial Followed-up Nasopharyngeal Swabs in Hospitalized Patients due to COVID-19.

Despite the accuracy of nucleic acid amplification tests (NAATs), rapid antigen tests (RATs) for severe acute respiratory syndrome coronavirus-2 are widely used as point-of-care tests. A total of 282 pairs of reverse transcription-polymerase chain reaction and Standard Q COVID-19 Ag tests were serially conducted for 68 patients every 3-4 days until their discharge. Through a field evaluation of RATs using direct nasopharyngeal swabs, the sensitivities were 84.6% and 87.3% for E and RNA-dependent RNA polymerase (RdRp) genes, respectively, for specimens with cycle thresholds (Cts) < 25. The Ct values of E and RdRp genes for 95% detection rates by RATs were 16.9 and 18.1, respectively. The sensitivity of RAT was 48.4% after the onset of symptoms, which was not sufficient. RAT positivity gradually decreased with increased time after symptom onset and had continuously lower sensitivity than NAATs.

Unclogged Janus Mesh for Fog Harvesting.

Janus membranes with asymmetric surface wettability have been extensively utilized in various fields, including fog harvesting, because of their novel liquid transport properties. However, Janus membranes have an inherent disadvantage in terms of aerodynamic efficiency in harvesting fog because of the clogged water bridges caused by the small pore size. In the present work, we applied Janus wettability to mesh geometry with systematically varying hole sizes. For a clogged mesh with a small hole size, capillary water transport to the mesh back via the wettability gradient in the direction of fog flow helps harvest more fog by enhancing water drainage, similarly to the Janus membrane. The advantage of the capillary water transport extends to a clog-free mesh with larger hole sizes but more preferably to a Janus mesh with a superhydrophilic back, which presents the highest level of fog-harvesting yield because of the fast shedding frequency and short onset time. In contrast, a Janus mesh with a superhydrophobic front, which also has a wettability gradient along the fog flow, produces a lower fog-harvesting performance, particularly at slow fog speeds, because of the dropwise deposition of large water drops that locally disturb fog flow around a protruding water surface. On the other hand, the other type of Janus mesh with a superhydrophilic front is observed to minimize this disadvantage in the local fog flow by virtue of the filmwise deposition. It is also found that some Janus treatments can help protect mesh holes from clogging up by either forming a thin water meniscus or resisting water transport through the mesh holes.

Blockade on Lin28a Prevents Cognitive Impairment and Disruption of the Blood-Brain Barrier Induced by Chronic Cerebral Hypoperfusion.

Lin28a is an RNA-binding protein involved in the translation and regulation of multiple mRNAs. Lin28a is overexpressed in animal models of brain injury. Similarly, our preliminary study found increased Lin28a expression levels in the animal models four to seven days after chronic cerebral hypoperfusion. Therefore, this current study aimed to evaluate the effects of modulating Lin28a on cognition and brain functions. Vascular dementia (VaD) was induced in 12-week-old male Wistar rats using permanent bilateral common carotid artery occlusion (BCCAO), and these rats were treated with Lin28a siRNA on the fourth and seventh day after BCCAO. From the 42nd day after BCCAO, cognitive behavioral experiments were performed for two weeks. VaD induced by BCCAO resulted in cognitive impairment and microglial activation. Lin28a expression was upregulated after BCCAO. Lin28a siRNA treatment alleviated cognitive impairment and overexpression of GFAP and Iba-1 in the brain. Furthermore, the treatment ameliorated the VaD-induced damage to the blood-brain barrier (BBB) components, including PECAM-1, PDGFRß, occludin, claudin-9, and ZO-1. CCR6 activation after VaD, associated with BBB disruption, was diminished by treatment with Lin28a siRNA. The treatment inhibited VaD-induced microglial activity and alleviated BBB damage. Thus, blocking Lin28a may alleviate cognitive impairment caused by VaD.

Efficacy of Constructing Digital Hybrid Skull-Dentition Images Using an Intraoral Scanner and Cone-Beam Computed Tomography.

Cone-beam computed tomography (CBCT) can distort dentition, and additional imaging is often required. A plaster model to help digitize dental images has been widely used in clinical practice, but there are some inconveniences such as complexity of the process and the risk of damage. The aim of this study was to evaluate the potential for improving dentition imaging with CBCT scans using an intraoral scanner instead of a plaster model. The study used laser model-scanned images of plaster models, imaging from two intraoral scanners, and CBCT images from 20 patients aged 12-18 years. CS 3600 (Carestream Dental, Atlanta, USA) and i700 (Medit, Seoul, Korea) were used as intraoral scanners. The full arch was scanned at once or in three sections using intraoral scanners. The segmented scans were merged to obtain full-arch images. With i700, full-arch images were additionally acquired using its "smart stich" function. The virtual skull-dentition hybrid images obtained from intraoral scanners were superimposed with images obtained using a plaster cast. The difference and distance of coordinate values at each reference point were measured. The average distances from the images obtained with the plaster cast were smaller than 0.39 mm, which is the voxel size of CBCT. Scanning the complete or partial arch using CS 3600 or i700 satisfactorily complemented the CBCT when compared to the plaster model. The virtual skull-dentition hybrid image obtained from intraoral scanners will be clinically useful, especially for patients and surgeons who have difficulty in scanning the complete arch at once.

Analysis of the Efficacy of Universal Screening of Coronavirus Disease with Antigen-Detecting Rapid Diagnostic Tests at Point-or-Care Settings and Sharing the Experience of Admission Protocol-A Pilot Study.

AIMS: To introduce the admission protocol of a COVID-19 specialized hospital outlined by the government, including the assessment of reverse transcription polymerase chain reaction (RT-PCR), low dose chest computed tomography (CT) and antigen-detecting rapid diagnostic test (Ag-RDT) for patient screening. MATERIALS AND METHODS: This was a retrospective cohort study of 646 patients who were admitted between December 2020, and February 2021, during the third wave of COVID-19 in Korea. Ag-RDT and RT-PCR were routinely performed on all patients who required admission, and low-dose chest CT was performed on high-risk patients with associated symptoms. Any patients with high-risk COVID-19 infection according to the Ag-RDT test were quarantined alone in a negative pressured room, and those with low-risk COVID-19 infection remained in the preemptive quarantine room with or without negative pressure. The diagnostic values of the Ag-RDT test and associated cycle threshold (Ct) values of the RT-PCR test were subsequently evaluated. RESULTS: In terms of the diagnostic value, the Ag-RDT for COVID-19 had a sensitivity of 68.3%, specificity of 99.5%, positive predictive value (PPV) of 90.3%, and negative predictive value (NPV) of 97.9%. For the 355 symptomatic patients with low-dose chest CT, the diagnostic values of combined evaluations had a sensitivity of 90.2%, specificity of 99.0%, PPV of 86.1%, and NPV of 99.3%. The cut-off Ct value for positive Ag-RDT was ≤25.67 for the N gene (sensitivity: 89.3%, specificity: 100%), which was regarded as a high viable virus in cell culture. There were no patients or medical staff who had COVID-19 in the hospital. CONCLUSION: Appropriate patient care was possible by definitive triage of the area, according to the symptoms and using diagnostic tests. Screening protocols, including the Ag-RDT test and low-dose chest CT, could be helpful in emergency point-of-care settings.

NXP032 Ameliorates Aging-Induced Oxidative Stress and Cognitive Impairment in Mice through Activation of Nrf2 Signaling.

Aging is a neurodegenerative disease that leads to cognitive impairment, and an increase in oxidative stress as a major cause is an important factor. It has been reported that aging-related cognitive impairment is associated with increased oxidative damage in several brain regions during aging. As a powerful antioxidant, vitamin C plays an important role in preventing oxidative stress, but due to its unstable chemical properties, it is easily oxidized and thus the activity of antioxidants is reduced. In order to overcome this easily oxidized vulnerability, we developed NXP032 (vitamin C/DNA aptamer complex) that can enhance the antioxidant efficacy of vitamin C using an aptamer. We developed NXP032 (vitamin C/DNA Aptamin C320 complex) that can enhance the antioxidant efficacy of vitamin C using an aptamer. In the present study, we evaluated the neuroprotective effects of NXP032 on aging-induced cognitive decline, oxidative stress, and neuronal damage in 17-month-old female mice. NXP032 was orally administered at 200 mg/kg of ascorbic acid and 4 mg/kg of DNA aptamer daily for eight weeks. Before the sacrifice, a cognitive behavioral test was performed. Administration of NXP032 alleviated cognitive impairment, neuronal damage, microglia activity, and oxidative stress due to aging. We found that although aging decreases the Nrf2-ARE pathway, NXP032 administration activates the Nrf2-ARE pathway to increase the expression of SOD-1 and GSTO1/2. The results suggest that the new aptamer complex NXP032 may be a therapeutic intervention to alleviate aging-induced cognitive impairment and oxidative stress.