Multifunctional Microneedle Patch with Diphlorethohydroxycarmalol for Potential Wound Dressing.

BACKGROUND: Treatment of skin wounds with diverse pathological characteristics presents significant challenges due to the limited specific and efficacy of current wound healing approaches. Microneedle (MN) patches incorporating bioactive and stimulus materials have emerged as a promising strategy to overcome these limitations and integrating bioactive materials with anti-bacterial and anti-inflammatory properties for advanced wound dressing. METHODS: We isolated diphlorethohydroxycarmalol (DPHC) from Ishige okamurae and assessed its anti-inflammatory and anti-bacterial effects on macrophages and its antibacterial activity against Cutibacterium acnes. Subsequently, we fabricated polylactic acid (PLA) MN patches containing DPHC at various concentrations (0-0.3%) (PDPHC MN patches) and evaluated their mechanical properties and biological effects using in vitro and in vivo models. RESUTLS: Our findings demonstrated that DPHC effectively inhibited nitric oxide production in macrophages and exhibited rapid bactericidal activity against C. acnes. The PDPHC MN patches displayed potent antibacterial effects without cytotoxicity. Moreover, in 2,4-Dinitrochlorobenzene-stimulated mouse model, the PDPHC MN patches significantly suppressed inflammatory response and cutaneous lichenification. CONCLUSION: The results suggest that the PDPHC MN patches holds promise as a multifunctional wound dressing for skin tissue engineering, offering antibacterial properties and anti-inflammatory properties to promote wound healing process.

Antimicrobial, antibiofilm, and antivirulence properties of Eisenia bicyclis-extracts and Eisenia bicyclis-gold nanoparticles towards microbial pathogens.

Nanomaterials derived from seaweed have developed as an alternative option for fighting infections caused by biofilm-forming microbial pathogens. This research aimed to discover potential seaweed-derived nanomaterials with antimicrobial and antibiofilm action against bacterial and fungal pathogens. Among seven algal species, the extract from Eisenia bicyclis inhibited biofilms of Klebsiella pneumoniae, Staphylococcus aureus, and Listeria monocytogenes most effectively at sub-MIC levels. As a result, in the present study, E. bicyclis was chosen as a prospective seaweed for producing E. bicyclis-gold nanoparticles (EB-AuNPs). Furthermore, the mass spectra of E. bicyclis reveal the presence of a number of potentially beneficial chemicals. The polyhedral shape of the synthesized EB-AuNP with a size value of 154.74 ± 33.46 nm was extensively described. The lowest inhibitory concentration of EB-AuNPs against bacterial pathogens (e.g., L.monocytogenes, S. aureus, Pseudomonas aeruginosa, and K. pneumoniae) and fungal pathogens (Candida albicans) ranges from 512 to >2048 µg/mL. Sub-MIC of EB-AuNPs reduces biofilm formation in P. aeruginosa, K. pneumoniae, L. monocytogenes, and S. aureus by 57.22 %, 58.60 %, 33.80 %, and 91.13 %, respectively. EB-AuNPs eliminate the mature biofilm of K. pneumoniae at > MIC, MIC, and sub-MIC concentrations. Furthermore, EB-AuNPs at the sub-MIC level suppress key virulence factors generated by P. aeruginosa, including motility, protease activity, pyoverdine, and pyocyanin, whereas it also suppresses the production of staphyloxanthin virulence factor from S. aureus. The current research reveals that seaweed extracts and a biocompatible seaweed-AuNP have substantial antibacterial, antibiofilm, and antivirulence actions against bacterial and fungal pathogens.

Ishophloroglucin A-based multifunctional oxidized alginate/gelatin hydrogel for accelerating wound healing.

This study investigated the potential applicability of wound dressing hydrogels for tissue engineering, focusing on their ability to deliver pharmacological agents and absorb exudates. Specifically, we explored the use of polyphenols, as they have shown promise as bioactive and cross-linking agents in hydrogel fabrication. Ishophloroglucin A (IPA), a polyphenol not previously utilized in tissue engineering, was incorporated as both a drug and cross-linking agent within the hydrogel. We integrated the extracted IPA, obtained through the utilization of separation and purification techniques such as high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) into oxidized alginate (OA) and gelatin (GEL) hydrogels. Our findings revealed that the mechanical properties, thermal stability, swelling, and degradation of the multifunctional hydrogel can be modulated via intermolecular interactions between the natural polymer and IPA. Moreover, the controlled release of IPA endows the hydrogel with antioxidant and antimicrobial characteristics. Overall, the wound healing efficacy, based on intermolecular interactions and drug potency, has been substantiated through accelerated wound closure and collagen deposition in an ICR mouse full-thickness wound model. These results suggest that incorporating IPA into natural polymers as both a drug and cross-linking agent has significant implications for tissue engineering applications.

Photobiomodulation ameliorates inflammatory parameters in fibroblast-like synoviocytes and experimental animal models of rheumatoid arthritis.

Introduction: Rheumatoid arthritis (RA) is a chronic destructive inflammatory disease that afflicts over one percent of the world's population. Current pharmacological treatments remain relatively ineffective. In this context, photobiomodulation (PBM) is a potential resource for the treatment of RA. This study investigates investigate the anti-arthritic effects and related mechanisms of PBM on fibroblast-like synoviocytes (FLSs) from RA patients and a mouse model of collagen-induced arthritis (CIA). Methods: The RA-FLSs were irradiated with a light emitting diode (LED) at a wavelength of 610 nm for 20 min, and the corresponding power intensities were 5 and 10 mW/cm2. After the LED irradiation, cell viability, proliferation, migration, and invasion assays were performed. Male DBA/1J mice were used to establish an animal model of CIA. Light stimulation with 10 mW/cm2 was applied to the ankle joints via direct contact with the skin for 40 min, daily for 2 weeks. Results and Discussion: PBM significantly reduced tumor necrosis factor (TNF)-α-induced increase in proliferation, migration, and invasion in RA-FLSs, and downregulated the activation of nuclear factor-κappa B (NF-κB) and NLRP3 inflammasome by TNF-α. Moreover, PBM greatly inhibited the induction and development of CIA, resulting in the inhibition of synovial inflammation and cartilage degradation. PBM therapy decreased the serum levels of pro-inflammatory cytokines, while increasing the anti-inflammatory cytokines. PBM suppressed the translocation of NF-κB and activation of NLRP3 inflammasome in the ankle joint. Furthermore, PBM showed a more pronounced anti-arthritic effect when combined with methotrexate (MTX), a disease-modifying anti-rheumatic drug (DMARD). The results showed that the effectiveness of MTX + PBM in CIA is superior to that of either MTX or PBM and that both work synergistically. Therefore, PBM with LED may be a potential therapeutic intervention for against RA.

One-point versus two-point fixation in the management of zygoma complex fractures.

BACKGROUND: The treatment of zygoma complex fractures is of crucial importance in the field of plastic surgery. However, surgical methods to correct zygoma complex fractures, including the number of fixation sites, differ among operators. Although several studies have compared two-point and three-point fixation, no comparative research has yet been conducted on one-point versus two-point fixation using computed tomography scans of surgical results. Therefore, the present study aimed to address this gap in the literature by comparing surgical results between one-point and two-point fixation procedures. METHODS: In this study, we randomly selected patients to undergo surgery using one of two surgical methods. We analyzed patients with unilateral zygoma complex fractures unaccompanied by other fractures according to whether they underwent one-point fixation of the zygomaticomaxillary buttress or two-point fixation of the zygomaticomaxillary buttress and the zygomaticofrontal suture. We then made measurements at three points-the zygomaticofrontal suture, inferior orbital wall, and malar height-using 3-month postoperative computed tomography images and performed statistical analyses to compare the results of the two methods. RESULTS: All three measurements (zygomaticofrontal suture, inferior orbital wall, and malar height) showed significant differences (p < 0.05) between one-point and two-point fixation. Highly significant differences were found for the zygomaticofrontal suture and malar height parameters. The difference in the inferior wall measurements was less meaningful, even though it also reached statistical significance. CONCLUSION: Using three parameters in a statistical analysis of imaging findings, this study demonstrated significant differences in treatment outcomes according to the number of fixations. The results indicate that bone alignment and continuity can be achieved to a greater extent by two-point fixation instead of one-point fixation.

Effects of Photobiomodulation on Changes in Cognitive Function and Regional Cerebral Blood Flow in Patients with Mild Cognitive Impairment: A Pilot Uncontrolled Trial.

BACKGROUND: Photobiomodulation (PBM) affects local blood flow regulation through nitric oxide generation, and various studies have reported on its effect on improving cognitive function in neurodegenerative diseases. However, the effect of PBM in the areas of the vertebral arteries (VA) and internal carotid arteries (ICA), which are the major blood-supplying arteries to the brain, has not been previously investigated. OBJECTIVE: We aimed to determine whether irradiating PBM in the areas of the VA and ICA, which are the major blood-supplying arteries to the brain, improved regional cerebral blood flow (rCBF) and cognitive function. METHODS: Fourteen patients with mild cognitive impairments were treated with PBM. Cognitive assessment and single-photon emission computed tomography were implemented at the baseline and at the end of PBM. RESULTS: Regarding rCBF, statistically significant trends were found in the medial prefrontal cortex, lateral prefrontal cortex, anterior cingulate cortex, and occipital lateral cortex. Based on the cognitive assessments, statistically significant trends were found in overall cognitive function, memory, and frontal/executive function. CONCLUSION: We confirmed the possibility that PBM treatment in the VA and ICA areas could positively affect cognitive function by increasing rCBF. A study with a larger sample size is needed to validate the potential of PBM.

Wound healing properties of triple cross-linked poly (vinyl alcohol)/methacrylate kappa-carrageenan/chitooligosaccharide hydrogel.

To develop an effective and mechanically robust wound dressing, a poly (vinyl alcohol) (PVA)/methacrylate kappa-carrageenan (κ-CaMA) composite hydrogel encapsulated with a chitooligosaccharide (COS) was prepared in a cassette via repeated freeze/thaw cycles, photo-crosslinking, and chemical cross-linking. The chemical, physical, mechanical, in vitro biocompatibility, in vivo wound-healing properties, and antibacterial activity of triple-crosslinked hydrogel were subsequently characterized. The results showed that the PVA/κ-CaMA/COS (Pκ-CaC) hydrogel had a uniformly thick, highly porous three-dimensional architecture with uniformly distributed pores, a high fluid absorption, and retention capacity without disturbing its mechanical stability, and good in vitro biocompatibility. Macroscopic images from the full-thickness skin wound model revealed that the wounds dressed with the proposed Pκ-CaC hydrogel were completely healed by day 14, while the histomorphological results confirmed full re-epithelization and rapid skin-tissue remodeling. This study thus indicates that the composite Pκ-CaC hydrogel has significant potential for use as a wound dressing.

Light-emitting diode irradiation induces AKT/mTOR-mediated apoptosis in human pancreatic cancer cells and xenograft mouse model.

The beneficial effects of light-emitting diode (LED) irradiation have been reported in various pathologies, including cancer. However, its effect in pancreatic cancer cells remains unclear. Herein, we demonstrated that blue LED of 460 nm regulated pancreatic cancer cell proliferation and apoptosis by suppressing the expression of apoptosis-related factors, such as mutant p53 and B-cell lymphoma 2 (Bcl-2), and decreasing the expression of RAC-ß serine/threonine kinase 2 (AKT2), the phosphorylation of protein kinase B (AKT), and mammalian target of rapamycin (mTOR). Blue LED irradiation also increased the levels of cleaved poly-(ADP-ribose) polymerase (PARP) and caspase-3 in pancreatic cancer cells, while it suppressed AKT2 expression and inhibited tumor growth in xenograft tumor tissues. In conclusion, blue LED irradiation suppressed pancreatic cancer cell and tumor growth by regulating AKT/mTOR signaling. Our findings indicated that blue LEDs could be used as a nonpharmacological treatment for pancreatic cancer.

Quality of life of patients with nasal bone fracture after closed reduction.

BACKGROUND: Closed reduction is the standard treatment for nasal bone fractures, which are the most common type of facial bone fractures. We investigated the effect of closed reduction on quality of life. METHODS: The 15-dimensional health-related quality of life survey was administered to 120 patients who underwent closed reduction under general anesthesia for nasal bone fractures from February 2018 to December 2019, on both the day after surgery and 3 months after surgery. Three months postoperatively, the presence or absence of five nasal symptoms (nose obstruction, snoring, pain, nasal secretions, and aesthetic dissatisfaction) was also evaluated. RESULTS: The quality of life items that showed significant changes between immediately after surgery and 3 months postoperatively were breathing, sleeping, speech, excretion, and discomfort. Low scores were found at 3 months for breathing, sleeping, and distress. There were 31 patients (25.83%) with nose obstruction, 25 (20.83%) with snoring, 12 (10.00%), with pain, 11 (9.17%) with nasal secretions, and 29 (24.17%) with aesthetic dissatisfaction. CONCLUSION: Closed reduction affected patients' quality of life, although most aspects improved significantly after 3 months. However, it was not possible to rule out deterioration of quality of life due to complications and dissatisfaction after surgery.

Point-of-care testing for COVID-19 using SHERLOCK diagnostics.

The recent outbreak of the novel coronavirus SARS-CoV-2, which causes COVID-19, can be diagnosed using RT-qPCR, but inadequate access to reagents and equipment has slowed disease detection and impeded efforts to mitigate viral spread. Alternative approaches based on combinations of isothermal amplification and CRISPR-mediated detection, such as the SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) technique, offer reduced dependence on RT-qPCR equipment, but previously reported methods required multiple fluid handling steps, complicating their deployment outside clinical labs. Here we developed a simple test chemistry called STOP (SHERLOCK Testing in One Pot) for detecting SARS-CoV-2 in one hour that is suitable for point-of-care use. This simplified test, STOPCovid, provides sensitivity comparable to RT-qPCR-based SARS-CoV-2 tests and has a limit of detection of 100 copies of viral genome input in saliva or nasopharyngeal swabs per reaction. Using lateral flow readout, the test returns result in 70 minutes, and using fluorescence readout, the test returns result in 40 minutes. Moreover, we validated STOPCovid using nasopharyngeal swabs from COVID-19 patients and were able to correctly diagnose 12 positive and 5 negative patients out of 3 replicates. We envision that implementation of STOPCovid will significantly aid "test-trace-isolate" efforts, especially in low-resource settings, which will be critical for long-term public health safety and effective reopening of the society.

Photobiomodulation Using a Low-Level Light-Emitting Diode Improves Cognitive Dysfunction in the 5XFAD Mouse Model of Alzheimer's Disease.

Photobiomodulation using low-level light-emitting diode can be rapidly applied in neurological and physiological disorders safely and noninvasively. Photobiomodulation is effective for chronic diseases because of fewer side effects than drugs. Here we investigated the effects of photobiomodulation using light-emitting diode on amyloid plaques, gliosis, and neuronal loss to prevent and/or recover cognitive impairment, and optimal timing of photobiomodulation initiation for recovering cognitive function in a mouse model of Alzheimer's disease. 5XFAD mice were used as an Alzheimer's disease model. Animals receiving photobiomodulation treatment were divided into two groups: an early group starting photobiomodulation at 2 months of age (5XFAD+Early), and a late group starting photobiomodulation at 6 months of age (5XFAD+Delay). Both groups received photobiomodulation 20 minutes per session three times per week for 14 weeks. The Morris water maze, passive avoidance, and elevated plus maze tests were performed at 10 months of age. Immunohistochemistry and Western blot were performed after behavioral evaluation. The results showed that photobiomodulation treatment at early stages reduced amyloid accumulation, neuronal loss, and microgliosis and alleviated the cognitive dysfunction in 5XFAD mice, possibly by increasing insulin degrading enzyme related to amyloid-beta degradation. Photobiomodulation may be an excellent candidate for advanced preclinical Alzheimer's disease research.

Immediate regraft of the remnant skin on the donor site in split-thickness skin grafting.

BACKGROUND: Skin defects of head and neck need reconstruction using various local flaps. In some cases, surgeons should consider skin graft for large skin defect. It is important to heal skin graft and donor sites. The authors investigated wound healing mechanisms at the donor sites with split-thick-ness skin graft (STSG). In this study, the authors compared two types of immediate regraft including sheets and islands for the donor site after facial skin graft using remnant skin. METHODS: The author reviewed 10 patients who underwent STSG, from March 2015 to May 2017, for skin defects in the craniofacial area. The donor site was immediately covered with the two types using remnant skin after harvesting skin onto the recipient site. Depending on the size of the remnant skin, we conducted regraft with the single sheet (n= 5) and island types (n= 5). RESULTS: On postoperative day 1 and 3 months, the scar formation was evaluated using the Patient and Observer Scar Assessment Scale (POSAS) and Vancouver Scar Scale (VSS). Total POSAS and VSS scores for the island type were lower than in single sheet group after 3 months postoperatively. There was significant difference in specific categories of POSAS and VSS. CONCLUSION: This study showed a reduction in scar formation following immediate regrafting of the remnant skin at the donor site after STSG surgery. Particularly, the island type is useful for clinical application to facilitate healing of donor sites with STSG.

Cell contact and Nf2/Merlin-dependent regulation of TEAD palmitoylation and activity.

The Hippo pathway is involved in regulating contact inhibition of proliferation and organ size control and responds to various physical and biochemical stimuli. It is a kinase cascade that negatively regulates the activity of cotranscription factors YAP and TAZ, which interact with DNA binding transcription factors including TEAD and activate the expression of target genes. In this study, we show that the palmitoylation of TEAD, which controls the activity and stability of TEAD proteins, is actively regulated by cell density independent of Lats, the key kinase of the Hippo pathway. The expression of fatty acid synthase and acetyl-CoA carboxylase involved in de novo biosynthesis of palmitate is reduced by cell density in an Nf2/Merlin-dependent manner. Depalmitoylation of TEAD is mediated by depalmitoylases including APT2 and ABHD17A. Palmitoylation-deficient TEAD4 mutant is unstable and degraded by proteasome through the activity of the E3 ubiquitin ligase CHIP. These findings show that TEAD activity is tightly controlled through the regulation of palmitoylation and stability via the orchestration of FASN, depalmitoylases, and E3 ubiquitin ligase in response to cell contact.

Smartphone-Driven Low-Power Light-Emitting Device.

Low-level light (laser) therapy (LLLT) has been widely researched in the recent past. Existing LLLT studies were performed based on laser. Recently, studies using LED have increased. This study presents a smartphone-driven low-power light-emitting device for use in colour therapy as an alternative medicine. The device consists of a control unit and a colour probe. The device is powered by and communicates with a smartphone using USB On-The-Go (OTG) technology. The control unit controls emitting time and intensity of illumination with the configuration value of a smartphone application. Intensity is controlled by pulse width modulation (PWM) without feedback. A calibration is performed to resolve a drawback of no feedback. To calibrate, intensity is measured in every 10 percent PWM output. PWM value is linearly calibrated to obtain accurate intensity. The device can control the intensity of illumination, and so, it can find application in varied scenarios.

Cutaneous Leiomyosarcoma of the Face.

Cutaneous leiomyosarcoma is an uncommon superficial soft tissue sarcoma and mainly found in the middle aged to elderly males. It can occur in any part of the body, mostly affecting the extremities and rarely affecting the face. It grows relatively slowly, can be diagnosed by biopsy and is treated by surgical excision. It needs to be distinguished from other spindle cell neoplasms, and immunohistochemical markers are usually required to attain an accurate diagnosis. We report a case of cutaneous leiomyosarcoma appeared on the left cheek within 6 month of a 73-year-old female patient suspected with malignant melanoma before surgery.

Cutaneous Basal Cell Carcinoma Arising in Odontogenic Cutaneous Fistula.

An odontogenic cutaneous fistula is a pathological communication between the outer skin surface of the face and the oral cavity. Facial cutaneous fistula is a complication of odontogenic infection that is often misdiagnosed with skin infection. We report a rare case, which was diagnosed as basal cell carcinoma based on the biopsy of skin lesions in the patient who had been diagnosed with odontogenic cutaneous fistula. A 64-year-old male patient presented with a cutaneous odontogenic fistula. The patient had undergone surgical extraction of fistula tract and loose tooth before dermatology or plastic surgery consultation. With the biopsy and computed tomography, it was confirmed that fistula and basal cell carcinoma. However, the connection between the fistula and skin cancer was not clear. Positron emission tomography-computed tomography scan was performed and was not detected as other local or distant metastasis. After that, wide excision of the skin lesion was performed. Although skin cancer is not commonly observed, it is necessary to rule out this disease entity by performing biopsy of skin lesions.

Low-level light emitting diode therapy promotes long-term functional recovery after experimental stroke in mice.

We aimed to investigate the effects of low-level light emitting diode therapy (LED-T) on the long-term functional outcomes after cerebral ischemia, and the optimal timing of LED-T initiation for achieving suitable functional recovery. Focal cerebral ischemia was induced in mice via photothrombosis. These mice were assigned to a sham-operated (control), ischemic (vehicle), or LED-T group [initiation immediately (acute), 4 days (subacute) or 10 days (delayed) after ischemia, followed by once-daily treatment for 7 days]. Behavioral outcomes were assessed 21 and 28 days post-ischemia, and histopathological analysis was performed 28 days post-ischemia. The acute and subacute LED-T groups showed a significant improvement in motor function up to 28 days post-ischemia, although no brain atrophy recovery was noted. We observed proliferating cells (BrdU+ ) in the ischemic brain, and significant increases in BrdU+ /GFAP+ , BrdU+ /DCX+ , BrdU+ /NeuN+ , and CD31+ cells in the subacute LED-T group. However, the BrdU+ /Iba-1+ cell count was reduced in the subacute LED-T group. Furthermore, the brain-derived neurotrophic factor (BDNF) was significantly upregulated in the subacute LED-T group. We concluded that LED-T administered during the subacute stage had a positive impact on the long-term functional outcome, probably via neuron and astrocyte proliferation, blood vessel reconstruction, and increased BDNF expression. Picture: The rotarod test for motor coordination showed that acute and subacute LED-T improves long-term functional recovery after cerebral ischemia.