Interleukin-24: A molecular mediator of particulate matter's impact on skin aging.

Air pollution, a global health concern, has been associated with adverse effects on human health. In particular, particulate matter (PM), which is a major contributor to air pollution, impacts various organ systems including the skins. In fact, PM has been suggested as a culprit for accelerating skin aging and pigmentation. In this study, using single-cell RNA sequencing, IL-24 was found to be highly upregulated among the differentially expressed genes commonly altered in keratinocytes and fibroblasts of ex vivo skins exposed to PM. It was verified that PM exposure triggered the expression of IL-24 in keratinocytes, which subsequently led to a decrease in type I procollagen expression and an increase in MMP1 expression in fibroblasts. Furthermore, long-term treatment of IL-24 induced cellular senescence in fibroblasts. Through high-throughput screening, we identified chemical compounds that inhibit the IL-24-STAT3 signaling pathway, with lovastatin being the chosen candidate. Lovastatin not only effectively reduced the expression of IL24 induced by PM in keratinocytes but also exhibited a capacity to restore the decrease in type I procollagen and the increase in MMP1 caused by IL-24 in fibroblasts. This study provides insights into the significance of IL-24, illuminating mechanisms behind PM-induced skin aging, and proposes IL-24 as a promising target to mitigate PM-associated skin aging.

Foxp3+ Treg control allergic skin inflammation by restricting IFN-γ-driven neutrophilic infiltration and NETosis.

BACKGROUND: Atopic dermatitis (AD), a chronic inflammatory skin disease with T cell activation as a key feature, in which Th2 cell-mediated responses play a pivotal role. Regulatory T cells (Treg) are central immune cells that restrict autoimmunity and inflammation in the body. Patients with immune dysregulation, polyendocrinopathy, or enteropathy X-linked syndrome, an immune disease characterized by a deficiency in Treg, develop skin inflammation and allergic disorders, indicating that Treg play a crucial role in the development of allergic skin inflammation. OBJECTIVE: we investigated the underlying mechanisms by which Treg control cutaneous allergic inflammation. METHODS: An allergic skin inflammation mouse model was constructed using MC903, and Treg-depleted mouse model was constructed using diphtheria toxin. Neutralization of IFN-γ was constructed using anti-mouse-IFN-γ mouse antibody. Neutrophil infiltration was analyzed by flow cytometry and immunohistochemistry. Neutrophil extracellular traps (NETs), a process called NETosis, were detected using immunofluorescence. In vitro neutrophil stimulation and immunocytochemistry was conducted to demonstrate the effect of IFN-γ on NETosis. RESULTS: The depletion of Foxp3+ Treg led to significantly exacerbated AD-like skin inflammation, including increased recruitment of neutrophils and expression of Th1 cytokine IFN-γ. Neutrophil infiltrating in skin of Treg-depleted mice released more NETs than wild type. Neutralization of IFN-γ abolished neutrophil infiltration and NETosis in Treg-depleted mice. Neutrophils stimulated with IFN-γ were more prone to release NETs in vitro. Finally, Foxp3+ Treg control cutaneous allergic inflammation by regulating IFN-γ-driven neutrophilic infiltration and NETosis. CONCLUSION: Our results highlight the previously underestimated Treg-IFN-γ-neutrophil inflammatory axis.

Effect of Corticosteroid Use on the Occurrence and Progression of Osteonecrosis of the Femoral Head: A nationwide Nested Case-Control Study.

BACKGROUND: Although it is very well known that corticosteroids cause osteonecrosis of the femoral head (ONFH), it is unclear as to which patients develop ONFH. Additionally, there are no studies on the association between corticosteroid use and femoral head collapse in ONFH patients. We aimed to investigate the association between corticosteroid use and the risk of ONFH among the general population and what factors affect ONFH occurrence. Additionally, we aimed to demonstrate which factors affect femoral head collapse and total hip arthroplasty (THA) after ONFH occurrence. METHODS: A nationwide, nested case-control study was conducted with data from the National Health Insurance Service Physical Health Examination Cohort (2002 to 2019) in the Republic of Korea. We defined ONFH (N = 3,500) using diagnosis and treatment codes. Patients who had ONFH were matched 1:5 to form a control group based on the variables of birth year, sex, and follow-up duration. Additionally, in patients who have ONFH, we looked for risk factors for progression to THA. RESULTS: Compared with the control group, ONFH patients had a low household income and had more diabetes, hypertension, dyslipidemia, and heavy alcohol use (drinking more than 3 to 7 drinks per week). Systemic corticosteroid use (≥ 1,800 mg) was significantly associated with an increased risk of ONFH incidence. However, lipid profiles, corticosteroid prescription, and cumulative doses of corticosteroid did not affect the progression to THA. CONCLUSION: The ONFH risk increased rapidly when cumulative prednisolone use was ≥ 1,800 mg. However, oral or high-dose intravenous corticosteroid use and cumulative dose did not affect the prognosis of ONFH. Since the occurrence and prognosis of ONFH are complex and multifactorial processes, further study is needed.

Oral consumption of Bonito fish-derived elastin peptide (VGPG Elastin® ) improves biophysical properties in aging skin: A randomized, double-blinded, placebo-controlled study.

BACKGROUND: Recent in vitro and in vivo studies have suggested that the elastin peptide improves the skin's biophysical properties, enhancing the proliferation of fibroblasts and elastin synthesis, resulting in anti-aging properties. Therefore, we conducted a randomized, double-blinded, placebo-controlled study to clinically evaluate the effect of elastin peptide intake on human skin. MATERIALS AND METHODS: Healthy adult participants (N = 100) were randomly assigned to receive a test product containing 100 mg of Bonito elastin peptide (VGPG Elastin® ) or placebo. In this study, all participants were Asian from Korea. The parameters of skin wrinkles, hydration, and brightening (melanin index) were measured at baseline and 4, 8, and 12 weeks after intervention. RESULTS: The average skin roughness, maximum peak-to-valley values, maximum peak height of the wrinkle, maximum valley depth of the wrinkle, average maximum height of the wrinkle, and eye wrinkle volume improved considerably in the test group compared with the placebo after 12 weeks of intervention. Skin hydration was enhanced, and the melanin index was significantly lower in the test group than in the placebo group. No participant experienced adverse events related to the test product. CONCLUSION: Oral consumption of Bonito elastin peptide (VGPG Elastin®) reduced fine wrinkles, enhanced skin moisture, and decreased melanin index without significant adverse effects and may be a promising anti-wrinkle, anti-dryness, and anti-pigmentation treatment.

Evaluation of the anti-aging effects of Zinc-α2-glycoprotein peptide in clinical and in vitro study.

BACKGROUND: Skin aging, characterized by the deterioration of skin density and elasticity, is a common concern among individuals seeking to maintain a youthful appearance. Zinc-α2-glycoprotein (ZAG) is secreted by various body fluids, and is associated with lipolysis and identified as an atopic dermatitis biomarker. This study evaluated the potential of ZAG peptides, which exert multiple benefits such as anti-aging. MATERIALS AND METHODS: We conducted a 4-week clinical trial on patients with noticeable periorbital wrinkles (n = 22) using a ZAG peptide-containing product. The effects of the products on skin density, elasticity, and the depth of periorbital wrinkles were evaluated using Cutometer Dual MPA580, Ultrascan, and Antera 3D CS, respectively. The effect of ZAG peptides on UVB-treated keratinocyte cells was evaluated in vitro to understand the mechanisms underlying its effects against impaired skin barrier function, collagen degradation, and senescence. In addition, the effects of ZAG peptides on cell viability and expression of aging and skin barrier-related genes were assessed using cell counting kit assay and quantitative reverse transcription-polymerase chain reaction, respectively. RESULTS: The patients demonstrated improved skin density, elasticity, and reduced periorbital wrinkles. Further, more than 85% patients scored the product as satisfactory regarding anti-aging effects. Furthermore, ZAG peptides reduced SA-ß-gal staining, downregulated the senescence-related genes, and upregulated the skin barrier function-related genes in UVB-irradiated keratinocyte cells. CONCLUSIONS: Our clinical and in vitro findings showed that ZAG peptides exert anti-aging effects and improve skin barrier functions, suggesting their promising potential as therapeutic agents to combat skin aging and improve skin health.

Clinical Activity of TGF-ß Inhibitor Vactosertib in Combination with Imatinib in Desmoid Tumors: A Multicenter Phase Ib/II Study.

PURPOSE: The study was to determine the activity and safety of the TGF-ß inhibitor vactosertib in combination with imatinib in patients with desmoid tumors. PATIENTS AND METHODS: In this investigator-initiated, open-label, multicenter, phase Ib/II trial, patients with desmoid tumors not amenable to locoregional therapies (surgery and/or radiotherapy) or with disease progression following at least one treatment were enrolled. Participants were administered 400 mg imatinib daily in combination with vactosertib (5 days on and 2 days off, twice a day) every 28 days. In phase Ib, the vactosertib dose was set at 100 mg (level -1) and 200 mg (level 1) to determine the recommended phase II dose (RP2D). Phase II assessed the efficacy, with the primary endpoint being progression-free rate (PFR) at 16 weeks. RESULTS: No dose-limiting toxicities were observed during phase Ib; therefore RP2D was defined at doses of 400 mg imatinib daily in combination with 200 mg vactosertib. Of the 27 patients evaluated, 7 (25.9%) achieved a confirmed partial response and 19 (70.4%) were stable. The PFR at 16 weeks and 1 year were 96.3% and 81.0%, respectively. Most toxicities were mild to moderate myalgia (n = 10, 37%), anemia (n = 10, 37%), and nausea (n = 9, 33.3%). Common grade 3 to 4 toxicities included neutropenia (n = 6, 22.2%) and anemia (n = 5, 18.5%). CONCLUSIONS: The vactosertib and imatinib combination was well tolerated, with promising clinical activity in patients with progressive, locally advanced desmoid tumors. This is the first study investigating a novel target agent, a TGF-ß inhibitor, in this rare and difficult-to-treat desmoid tumor.

Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial.

We aimed to determine the activity of the anti-VEGF receptor tyrosine-kinase inhibitor, pazopanib, combined with the anti-PD-L1 inhibitor, durvalumab, in metastatic and/or recurrent soft tissue sarcoma (STS). In this single-arm phase 2 trial (NCT03798106), treatment consisted of pazopanib 800 mg orally once a day and durvalumab 1500 mg once every 3 weeks. Primary outcome was overall response rate (ORR) and secondary outcomes included progression-free survival (PFS), overall survival, disease control rate, immune-related response criteria, and safety. The ORR was 30.4% and the trial met the pre-specified endpoint. The median PFS was 7.7 months (95% confidence interval: 5.7-10.4). The common treatment-related adverse events of grades 3-4 included neutropenia (9 [19.1%]), elevated aspartate aminotransferase (7 [14.9%]), alanine aminotransferase (5 [10.6%]), and thrombocytopenia (4 [8.5%]). In a prespecified transcriptomic analysis, the B lineage signature was a significant key determinant of overall response (P = 0.014). In situ analysis also showed that tumours with high CD20+ B cell infiltration and vessel density had a longer PFS (P = 6.5 × 10-4) than those with low B cell infiltration and vessel density, as well as better response (50% vs 12%, P = 0.019). CD20+ B cell infiltration was identified as the only independent predictor of PFS via multivariate analysis. Durvalumab combined with pazopanib demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile.

Low-molecular-weight collagen peptides supplement promotes a healthy skin: A randomized, double-blinded, placebo-controlled study.

BACKGROUND: Oral collagen peptides supplementation was reported to improve skin integrity and counteract skin aging. AIMS: A randomized, double-blinded, placebo-controlled study was conducted to clinically evaluate the impact of low-molecular-weight collagen peptides on the human skin. PATIENTS/METHODS: Healthy adult participants (n = 100) were randomly assigned to receive a test product containing low-molecular-weight collagen peptides or a placebo. Parameters of skin wrinkles, elasticity, hydration, and whitening (melanin and erythema indexes) were measured at baseline and after 4, 8, and 12 weeks. RESULTS: Compared with the placebo group, the average skin roughness, maximum of all peak-to-valley values, maximum peak height of the wrinkle, and average maximum height of the wrinkle were significantly improved in the test group. Parameters of skin elasticity, including overall elasticity, net elasticity, and biological elasticity, were also significantly improved in the test group at Week 12 as compared with the placebo group. Moreover, skin hydration and whitening parameters changed more significantly in the test group than in the placebo group. None of the participants experienced adverse events related to the test product. CONCLUSIONS: Taken together, these findings suggest that low-molecular-weight collagen peptides supplementation can safely ehance human skin wrinkling, hydration, elasticity, and whitening properties.

Combination of Fractional Microneedling Radiofrequency and Ablative Fractional Laser versus Ablative Fractional Laser Alone for Acne and Acne Scars.

PURPOSE: Fractional microneedle radiofrequency (FMR) systems are used to treat inflammatory acne and scarring. Nonetheless, few controlled studies have combined this treatment with the traditional ablative fractional laser (AFL). We aimed to assess the safety and efficacy of the combination of FMR and AFL versus AFL alone in treating acne and acne scars. MATERIALS AND METHODS: In this 20-week, randomized, split-face study, 23 Korean patients with facial acne and acne scars underwent FMR and AFL treatments. One half of each patient's face was randomly assigned to receive FMR+AFL, whereas the other half received AFL alone. Treatments were administered in three consecutive sessions at 4-week intervals. This study investigated the severity of inflammatory acne, acne scars, individual lesion counts, depressed scar volumes, as well as patient and physician satisfaction. In addition, five patients underwent skin biopsy, and sebum output was measured. RESULTS: The FMR+AFL treatment demonstrated superior efficacy compared to AFL alone in terms of inflammatory acne and acne scar grading, lesion counts, and subjective satisfaction. The side effects were minimal and well-tolerated in both groups. Immunohistochemical findings from skin biopsy samples revealed that the application of FMR+AFL could induce an inhibitory effect on sebum secretion at the molecular level. CONCLUSION: FMR combined with AFL is a well-tolerated and effective treatment modality for inflammatory acne and acne scarring.

Highly accelerated knee magnetic resonance imaging using deep neural network (DNN)-based reconstruction: prospective, multi-reader, multi-vendor study.

In this prospective, multi-reader, multi-vendor study, we evaluated the performance of a commercially available deep neural network (DNN)-based MR image reconstruction in enabling accelerated 2D fast spin-echo (FSE) knee imaging. Forty-five subjects were prospectively enrolled and randomly divided into three 3T MRIs. Conventional 2D FSE and accelerated 2D FSE sequences were acquired for each subject, and the accelerated FSE images were reconstructed and enhanced with DNN-based reconstruction software (FSE-DNN). Quantitative assessments and diagnostic performances were independently evaluated by three musculoskeletal radiologists. For statistical analyses, paired t-tests, and Pearson's correlation were used for image quality comparison and inter-reader agreements. Accelerated FSE-DNN reduced scan times by 41.0% on average. FSE-DNN showed better SNR and CNR (p < 0.001). Overall image quality of FSE-DNN was comparable (p > 0.05), and diagnostic performances of FSE-DNN showed comparable lesion detection. Two of cartilage lesions were under-graded or over-graded (n = 2) while there was no significant difference in other image sets (n = 43). Overall inter-reader agreement between FSE-conventional and FSE-DNN showed good agreement (R2 = 0.76; p < 0.001). In conclusion, DNN-based reconstruction can be applied to accelerated knee imaging in multi-vendor MRI scanners, with reduced scan time and comparable image quality. This study suggests the potential for DNN-accelerated knee MRI in clinical practice.

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.

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.

Direct comparison of diagnostic and clinical values between Tc-99 m DPD and Tc-99 m PYP scintigraphy in patients with cardiac amyloidosis.

BACKGROUND: Technetium-99 m 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) and technetium-99 m sodium pyrophosphate (PYP) are the two most commonly used radiotracers for cardiac amyloidosis (CA), but no studies have directly compared them. Therefore, in this study, we directly compared the diagnostic and clinical utility of DPD and PYP scintigraphy in patients with CA. METHODS: Ten patients with CA were enrolled. Eight clinical variables and 12 scintigraphic parameters were used. Clinical variables were age, sex, estimated glomerular filtration rate (eGFR), N-terminal pro brain natriuretic peptide (NT-proBNP), and the results of electromyography (EMG), a sensory test, electrocardiogram, and echocardiography (EchoCG). Four heart retention ratios (heart/whole-body profile, heart/pelvis, heart/skull, and heart/contralateral lung) were calculated from the DPD and PYP scans and two visual scoring systems (Perugini and Dorbala systems) were used. Comparative analyses were performed between radiotracers and between visual scoring systems using clinical variables and scintigraphic parameters. RESULTS: Twenty DPD parameters and nine PYP parameters had significant associations with age, eGFR, NT-proBNP, EchoCG, and EMG. DPD parameters had more frequent significant associations with clinical variables than PYP parameters. Compared to visual scores in the DPD scan, the proportion of patients with higher visual scores in the PYP scan was relatively greater than those with lower visual scores, and there were more patients with a visual score of 2 or higher in PYP scans than DPD scans. CONCLUSIONS: DPD scintigraphy may reflect the disease severity of CA better than PYP scintigraphy, whereas PYP scintigraphy may be a more sensitive imaging modality for identifying CA involvement.

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.

Preliminary study for prediction of benign vertebral compression fracture age by quantitative water fraction using modified Dixon sequences: an imaging biomarker of fracture age.

PURPOSE: This study aimed to evaluate whether quantitative water fraction parameters could predict fracture age in patients with benign vertebral compression fractures (VCFs). METHODS: A total of 38 thoracolumbar VCFs in 27 patients imaged using modified Dixon sequences for water fraction quantification on 3-T MRI were retrospectively reviewed. To calculate quantitative parameters, a radiologist independently measured the regions of interest in the bone marrow edema (BME) of the fractures. Furthermore, five features (BME, trabecular fracture line, condensation band, cortical or end plate fracture line, and paravertebral soft-tissue change) were analyzed. The fracture age was evaluated based on clear-onset symptoms and previously available images. A correlation analysis between the fracture age and water fraction was evaluated using a linear regression model, and a multivariable analysis of the dichotomized fracture age model was performed. RESULTS: The water fraction ratio was the only significant factor and was negatively correlated with the fracture age of VCFs in multiple linear regression (p = 0.047), whereas the water fraction was not significantly correlated (p = 0.052). Water fraction and water fraction ratio were significant factors in differentiating the fracture age of 1 year in multiple logistic regression (odds ratio 0.894, p = 0.003 and odds ratio 0.986, p = 0.019, respectively). Using a cutoff of 0.524 for the water fraction, the area under the curve, sensitivity, and specificity were 0.857, 85.7%, and 87.1%, respectively. CONCLUSIONS: Water fraction is a good imaging biomarker for the fracture healing process. The water fraction ratio of the compression fractures can be used to predict the fracture age of benign VCFs.

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.

Efficacy and safety of silymarin containing antioxidant serum as an adjuvant treatment of mild-to-moderate acne vulgaris: A prospective, open-label pilot study.

BACKGROUND: Silymarin is the active component of milk thistle, which has antioxidant properties by scavenging free radicals and potential comedolytic properties. AIMS: This study aimed to assess the efficacy and safety of 0.5% silymarin-loaded antioxidant serum (SAS) used to treat mild-to-moderate acne. PATIENTS AND METHODS: A prospective, open-label pilot study was conducted. We enrolled 22 Korean acne patients who applied the 0.5% SAS on the whole face twice daily while continuing the current anti-acne medications. Grade of acne severity, individual lesion counts, sebum output levels, skin erythema, and melanin pigmentation were assessed. RESULTS: After a 4-week application, the modified Global Acne Grading Score (mGAGS), Global Evaluation Acne (GEA) scale, and the acne lesion counts were significantly decreased. Sebum secretion, skin pigmentation, and erythema were also reduced during the study period, yet only the melanin pigmentation index reached statistical significance. Subgroup analysis revealed that the patients who took the low-dose oral isotretinoin during the study period showed more noticeable improvements in skin sebum output and melanin pigmentation. Additionally, no adverse event was associated with using the 0.5% SAS. CONCLUSION: The 0.5% silymarin-containing antioxidant formulation improved acne's clinical severity and related skin biophysical parameters.

Therapeutic Implications of TGF-ß Pathway in Desmoid Tumor Based on Comprehensive Molecular Profiling and Clinicopathological Properties.

(1) Background: Desmoid tumors have a relatively high local failure rate after primary treatment using surgery and/or radiotherapy. Moreover, desmoid tumors recur at the primary site for many patients. An effective therapeutic strategy for the desmoid tumor is needed to maintain quality of life and prolong survival. (2) Method: First of all, we collected desmoid tumor tissues and investigated the status of protein expression for beta-catenin and alpha-SMA through immunohistochemistry. Then, we performed targeted sequencing and whole RNA sequencing. To compare the data with other cancer types, we used NGS data from sarcoma patients at Yonsei Cancer Center (YCC-sarcoma cohort, n = 48) and The Cancer Genome Atlas (TCGA, n = 9235). Secondly, we established the novel patient-derived preclinical models (n = 2) for the validation of treatment strategy. The same gene alteration of primary tissue was demonstrated. (3) Results: We discovered specific gene sets related to the TGF-ß signaling pathway. Moreover, we selected the combination treatment comprising TGF-ß inhibitor, vactosertib, and imatinib. In screening for the anti-proliferation effect, the combination treatment of TGF-ß inhibitor was more effective for tumor suppression than monotherapy. (4) Conclusion: We found preclinical indications that TGF-ß inhibitors could prove useful as a potential treatment for patients with desmoid tumors. Moreover, we could find some examples in clinical trials.

Oral Supplementation of Low-Molecular-Weight Collagen Peptides Reduces Skin Wrinkles and Improves Biophysical Properties of Skin: A Randomized, Double-Blinded, Placebo-Controlled Study.

Orally administered collagen peptides could contribute to antiaging by replacing the degraded extracellular matrix proteins caused by photoaging. This study aimed to evaluate the efficacy and safety of low-molecular-weight collagen peptides for treating photoaged and dry skin. In this randomized, placebo-controlled, parallel-group, double-blinded trial, we randomly assigned study participants (n = 100) to either the test product group or placebo group at a 1:1 ratio for 12 weeks. The wrinkle scale score, eye wrinkle volume, roughness parameters, such as the average maximum height of the wrinkle (Rz), arithmetic average within the total measuring length of the wrinkle (Ra), maximum profile valley depth of the wrinkle (Rv), and skin hydration, transepidermal water loss (TEWL), overall elasticity (R2), and ratio of elastic recovery to total deformation (R7) were evaluated at baseline, 6 weeks, and 12 weeks. Safety assessments with serial blood tests were also conducted. Efficacy assessments of data from 84 participants were conducted as the per-protocol analysis. After 12 weeks, the 10-grade crow's feet photo scale score, eye wrinkle volume, skin roughness parameters (Rz, Ra, and Rv), skin elasticity (R2 and R7), skin hydration, and TEWL were significantly improved in the test product group compared to the placebo group. There were no adverse events or abnormalities according to laboratory analysis associated with using the test material during the study period. This study showed that the oral supplementation of low-molecular-weight collagen peptides could improve the wrinkles, elasticity, hydration, and barrier integrity of photoaged facial skin. This clinical study was registered with the Korean Clinical Research Information Service and International Clinical Trials Registry Platform (No: KCT0006500).