NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism.

Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes.

Non-epitaxial single-crystal 2D material growth by geometric confinement.

Two-dimensional (2D) materials and their heterostructures show a promising path for next-generation electronics1-3. Nevertheless, 2D-based electronics have not been commercialized, owing mainly to three critical challenges: i) precise kinetic control of layer-by-layer 2D material growth, ii) maintaining a single domain during the growth, and iii) wafer-scale controllability of layer numbers and crystallinity. Here we introduce a deterministic, confined-growth technique that can tackle these three issues simultaneously, thus obtaining wafer-scale single-domain 2D monolayer arrays and their heterostructures on arbitrary substrates. We geometrically confine the growth of the first set of nuclei by defining a selective growth area via patterning SiO2 masks on two-inch substrates. Owing to substantial reduction of the growth duration at the micrometre-scale SiO2 trenches, we obtain wafer-scale single-domain monolayer WSe2 arrays on the arbitrary substrates by filling the trenches via short growth of the first set of nuclei, before the second set of nuclei is introduced, thus without requiring epitaxial seeding. Further growth of transition metal dichalcogenides with the same principle yields the formation of single-domain MoS2/WSe2 heterostructures. Our achievement will lay a strong foundation for 2D materials to fit into industrial settings.

Brown fat-specific mitoribosomal function is crucial for preventing cold exposure-induced bone loss.

This study examines the interplay between ambient temperature, brown adipose tissue (BAT) function, and bone metabolism, emphasizing the effects of cold exposure and BAT mitochondrial activity on bone health. Utilizing ovariectomized (OVX) mice to model primary osteoporosis and BAT-specific mitochondrial dysfunction (BKO) mice, we evaluated the impact of housing temperature on bone density, immune modulation in bone marrow, and the protective role of BAT against bone loss. Cold exposure was found to universally reduce bone mass, enhance osteoclastogenesis, and alter bone marrow T-cell populations, implicating the immune system in bone remodeling under cold stress. The thermogenic function of BAT, driven by mitochondrial oxidative phosphorylation, was crucial in protecting against bone loss. Impaired BAT function, through surgical removal or mitochondrial dysfunction, exacerbated bone loss in cold environments, highlighting BAT's metabolic role in maintaining bone health. Furthermore, cold-induced changes in BAT function led to systemic metabolic shifts, including elevated long-chain fatty acids, which influenced osteoclast differentiation and activity. These findings suggest a systemic mechanism connecting environmental temperature and BAT metabolism with bone physiology, providing new insights into the metabolic and environmental determinants of bone health. Future research could lead to novel bone disease therapies targeting these pathways.

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.

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.

Characteristics According to Frailty Status Among Older Korean Patients With Hypertension.

BACKGROUND: As the prevalence of hypertension increases with age and the proportion of the older population is also on the rise, research on the characteristics of older hypertensive patients and the importance of frailty is necessary. This study aimed to identify clinical characteristics of older hypertension in Korea and to investigate these characteristics based on frailty status. METHODS: The HOW to Optimize eLDerly systolic BP (HOWOLD-BP) is a prospective, multicenter, open-label, randomized clinical trial that aims to compare intensive (target systolic blood pressure [SBP] ≤ 130 mmHg) with standard (target SBP ≤ 140 mmHg) treatment to reduce cardiovascular events in older hypertensive Korean patients aged ≥ 65 years. Data were analyzed through a screening assessment of 2,085 patients recruited from 11 university hospitals. Demographic, functional (physical and cognitive), medical history, laboratory data, quality of life, and medication history of antihypertensive drugs were assessed. RESULTS: The mean age was 73.2 years (standard deviation ± 5.60), and 48.0% (n = 1,001) were male. Prevalent conditions included dyslipidemia (66.5%), obesity (body mass index ≥ 25 kg/m², 53.6%), and diabetes (28.9%). Dizziness and orthostatic hypotension were self-reported by 1.6% (n = 33) and 1.2% (n = 24), respectively. The majority of patients were on two antihypertensive drugs (48.4%), while 27.5% (n = 574) and 20.8% (n = 433) were on 1 and 3 antihypertensive medications, respectively. Frail to pre-frail patients were older and also tended to have dependent instrumental activities of daily living, slower gait speed, weaker grip strength, lower quality of life, and lower cognitive function. The frail to pre-frail group reported more dizziness (2.6% vs. 1.2%, P < 0.001) and had concerning clinical factors, including lower glomerular filtration rate, more comorbidities such as diabetes, stroke, and a history of admission. Frail to pre-frail older hypertensive patients used slightly more antihypertensive medications than robust older hypertensive patients (1.95 vs. 2.06, P = 0.003). Pre-frail to frail patients often chose beta-blockers as a third medication over diuretics. CONCLUSION: This study described the general clinical characteristics of older hypertensive patients in Korea. Frail hypertensive patients face challenges in achieving positive clinical outcomes because of multifactorial causes: they are older, have more morbidities, decreased function, lower quality of life and cognitive function, and take more antihypertensive medications. Therefore, it is essential to comprehensively evaluate and monitor disease-related or drug-related adverse events more frequently during regular check-ups, which is necessary for pre-frail to frail older patients with hypertension. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0003787.

Efficacy and safety of a home-use handheld multi-energy-based device for skin rejuvenation: clinical, ex vivo, and histological studies.

Alongside increases in the average lifespan and a growing interest in anti-aging remedies, the demand for at-home skincare devices is rapidly expanding in the cosmetic market. This study aimed to assess the safety and efficacy of a novel home-use handheld multi-energy-based device for skin rejuvenation that simultaneously emits low level light, low-dose radiofrequency, low-energy microcurrent, and low-intensity ultrasonic wave. This prospective, randomized, split-face clinical trial enrolled 36 healthy Korean women. After 8 weeks of device use, parameters associated with skin aging were assessed. Additionally, a preliminary ex vivo study and skin biopsy following device use were performed to confirm safety and efficiency of the device. Parameters associated with skin aging including skin hydration, elasticity, roughness, skin pore size, and eye wrinkle volume showed significant improvements after 8 weeks of the device use, relative to baseline measurements and the control side. No adverse effects were observed during the follow-up period. Results of ex vivo and in vivo skin tissue studies correlated with clinical findings, which showed an increase in the expression of type 1 collagen and a decrease in the expression of matrix metalloproteinase-1, which is related to the skin aging phenotype. The expression of loricrin and involucrin, major components of the epidermal skin barrier, also increased after the use of the device. Multi-energy-based device is effective for skin rejuvenation and tolerable, without any considerable adverse effects.

The Protective Role of Magnoliae Flos in Preventing Ovotoxicity and Managing Ovarian Function: An In Vitro and In Vivo Study.

Magnoliae Flos (MF) is a medicinal herb widely employed in traditional medicine for relieving sinusitis, allergic rhinitis, headaches, and toothaches. Here, we investigated the potential preventive effects of MF extract (MFE) against 4-vinylcyclohexene diepoxide (VCD)-induced ovotoxicity in ovarian cells and a mouse model of premature ovarian insufficiency (POI). The cytoprotective effects of MFE were assessed using CHO-K1 or COV434 cells. In vivo, B6C3F1 female mice were intraperitoneally injected with VCD for two weeks to induce POI, while MFE was orally administered for four weeks, beginning one week before VCD administration. VCD led to a significant decline in the viabilities of CHO-K1 and COV434 cells and triggered excessive reactive oxygen species (ROS) production and apoptosis specifically in CHO-K1 cells. However, pretreatment with MFE effectively prevented VCD-induced cell death and ROS generation, while also activating the Akt signaling pathway. In vivo, MFE increased relative ovary weights, follicle numbers, and serum estradiol and anti-Müllerian hormone levels versus controls under conditions of ovary failure. Collectively, our results demonstrate that MFE has a preventive effect on VCD-induced ovotoxicity through Akt activation. These results suggest that MFE may have the potential to prevent and manage conditions such as POI and diminished ovarian reserve.

Quantitative Analysis of Hair Luster in a Novel Ultraviolet-Irradiated Mouse Model.

Hair luster is a key attribute of healthy hair and a crucial aspect of cosmetic appeal, reflecting the overall health and vitality of hair. Despite its significance, the advancement of therapeutic strategies for hair luster enhancement have been limited due to the absence of an effective experimental model. This study aimed to establish a novel animal model to assess hair gloss, employing ultraviolet (UV) irradiation on C57BL/6 mice. Specifically, UVB irradiation was meticulously applied to the shaved skin of these mice, simulating conditions that typically lead to hair luster loss in humans. The regrowth and characteristics of the hair were evaluated using a dual approach: an Investigator's Global Assessment (IGA) scale for subjective assessment and an image-based pixel-count method for objective quantification. These methods provided a comprehensive understanding of the changes in hair quality post-irradiation. To explore the potential reversibility of hair luster changes, oral minoxidil was administered, a treatment known for its effects on hair growth and texture. Further, to gain insights into the underlying biological mechanisms, bulk RNA transcriptomic analysis of skin tissue was conducted. This analysis revealed significant alterations in the expression of keratin-associated protein (KRTAP) genes, suggesting modifications in hair keratin crosslinking due to UV exposure. These changes are crucial in understanding the molecular dynamics affecting hair luster. The development of this new mouse model is a significant advancement in hair care research. It not only facilitates the evaluation of hair luster in a controlled setting but also opens avenues for the research and development of innovative therapeutic strategies. This model holds promise for the formulation of more effective hair care products and treatments, potentially revolutionizing the approach towards managing and enhancing hair luster.

Age-Dependent Clinicopathological Characteristics of Patients with T1b Papillary Thyroid Carcinoma: Implications for the Possibility of Active Surveillance.

BACKGROUND: Active surveillance (AS) of low-risk T1a papillary thyroid carcinoma (PTC) is generally accepted as an alternative to immediate surgery. The cut-off in the size criterion for AS has recently been extended in select individuals, especially older patients. We evaluated the clinicopathological differences of T1b PTC according to age to investigate the possibility of AS in older patients. PATIENTS AND METHODS: From a cohort study of 1269 patients undergoing lobectomy for PTC, 1223 PTC patients with T1 stage disease (tumor ≤ 2 cm) were enrolled. The clinicopathological characteristics between T1a and T1b patients according to age were analyzed. RESULTS: Among the 1223 T1 cases, 918 (75.1%) were T1a (≤ 1 cm) and 305 (34.9%) T1b (> 1 and ≤ 2 cm). T1b PTC was associated with male sex, minimal extrathyroidal extension, lymphovascular invasion, occult central lymph node (LN) metastasis, and a higher number of metastatic LNs than T1a. However, in patients over 55 years of age, the clinicopathological features of the patients with T1a and T1b PTC were not significantly different except for minimal extrathyroidal extension, although many clinicopathological differences were observed in patients under 55 years of age. CONCLUSION: The clinicopathological features of patients with T1b PTC over 55 years of age are similar to those with T1a PTC and less aggressive than those with T1b PTC under 55 years of age. These findings suggest that AS may be possible in patients with T1b PTC over 55 years of age without high-risk features on preoperative examinations.

Efficacy and safety of persimmon leaf formulated with green tea and sophora fruit extracts (BLH308) on hair growth: A randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Recent research suggests that persimmon leaf extract (PLE) has an effect on inflammatory skin diseases. Previously, PLE is revealed to inhibit not only nitric oxide production but also inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels in mouse macrophages in vitro. Moreover, it significantly reduced IL-6 production and 5α-reductase expression in human follicle dermal papilla cells (HFDPCs). This study aimed to determine whether the PLE-containing BLH308 complex improves hair growth in clinical trials. MATERIALS AND METHODS: A total of 88 participants were recruited, and were instructed to orally take BLH308 or the placebo twice a day for 24 weeks. The mean age of the test group was 38.52 ± 7.98 years and that of placebo group was 38.98 ± 8.80 years. The study was conducted for 24 weeks, and hair density, thickness, and gloss were evaluated. All participants completed a satisfaction survey questionnaire. RESULTS: The test group showed significantly increased hair density and hair diameter at week 24 compared with the placebo group (p = 0.0015 and p = 0.0001, respectively). Although not statistically significant, the degree of gloss also showed higher improvement in the test group compared to the placebo group. CONCLUSIONS: Our data demonstrated that oral consumption of the BLH308 complex containing PLE significantly increased hair density and thickness compared to the placebo group, showing its possible role in promoting hair growth.

Age-related changes in scalp biophysical parameters: A comparative analysis of the 20s and 50s age groups.

BACKGROUND: Age-related changes in scalp parameters affect hair quality and scalp condition. However, detailed data on biophysical parameters of the scalp across age groups remain scarce. We aimed to investigate the differences in scalp parameters between individuals in their 20s and 50s and analyze their sex-specific variations. MATERIALS AND METHODS: Two hundred participants (160 women and 40 men) were equally divided into 20s and 50s age groups. Biophysical parameters of the scalp, including elasticity, pH, trans-epidermal water loss (TEWL), sebum production, desquamation, firmness, redness, and yellowness, were measured in the vertex, occipital, and temporal regions. Hair density and thickness were measured in the temporal region. The accumulation of advanced glycation end products (AGEs) in the skin was noninvasively measured in a subset of 60 women. RESULTS: Skin firmness and redness increased with age in women, whereas yellowness increased with age in both sexes. Sebum production and pH levels were significantly lower in the 50s age group than in the 20s age group, particularly in women. TEWL was lower in men in their 50s than in those in their 20s, particularly in the occipital region. A significant reduction in hair density was observed in the 50s age group in both sexes. AGE accumulation in the skin increased with age and was correlated with scalp skin yellowness. CONCLUSION: Age-related changes in scalp parameters have important implications for hair health and scalp condition. These findings emphasize the importance of considering age and sex when developing hair care strategies.

Cutaneous neurogenic inflammation mediated by TRPV1-NGF-TRKA pathway activation in rosacea is exacerbated by the presence of Demodex mites.

BACKGROUND: Rosacea is a common chronic inflammatory skin condition that is often refractory to treatment, with frequent relapses. Alterations in the skin immunological response and Demodex mite infestation are the primary aetiologic factors targeted for treatment. Transient receptor potential cation channel subfamily V member 1 (TRPV1) is a nociceptive cation channel that plays a role in cutaneous neurogenic pain and can be activated by various rosacea triggers. OBJECTIVES: We investigated the effects of TRPV1 modulation in rosacea, focussing on Demodex mite colonization and cutaneous neurogenic inflammation. METHODS: We examined mRNA expression levels according to Demodex population counts. An in vitro study using capsazepine as a TRPV1 antagonist was performed to assess the influence of TRPV1 in keratinocytes. A rosacea-like mouse model was generated by the injection of the 37-amino acid C-terminal cathelicidin peptide (LL37), and changes in the skin, dorsal root ganglion (DRG) and ears were examined. RESULTS: Increased Demodex mite population counts were associated with increased expression levels of TRPV1, tropomyosin receptor kinase A (TrkA) and nerve growth factor (NGF), and these levels could be reduced by capsazepine treatment in keratinocytes. In an in vivo study, the downstream effects of TRPV1 activation were investigated in the skin, DRG and ears of the rosacea-like mouse model. CONCLUSIONS: The findings of this study are instrumental for understanding the underlying causes of rosacea and could potentially lead to the development of new treatments targeting the NGF-TrkA-TRPV1 pathway. The identification of this pathway as a therapeutic target could represent a major breakthrough for rosacea research, potentially resulting in more effective and targeted rosacea treatments. This study contributes to an improved understanding of rosacea pathophysiology, which may lead to the development of more effective treatments in the future.

Needs Assessment for the Development of Training Curricula for Internal Medicine Residents.

BACKGROUND: Patient-centered outcomes can be achieved when common core and specialist competencies are achieved in a balanced manner. This study was conducted to assess the need to fill the gap between the defined competencies and learners' achievement, in order to improve the internal medicine (IM) training education curriculum for promoting patient-centered outcomes. METHODS: A cross-sectional online survey was conducted. The participants were 202 IM specialists who obtained board certification in 2020-2021. We developed a questionnaire to investigate the self-evaluation of common core competencies and achievement level of IM essential competencies. For analysis, frequency tests, paired t-test, Borich priority formula, and χ² were performed. RESULTS: In common core competencies, IM specialists recognized that their achievement levels in all competency categories were lower than their importance level (P < 0.001), and the highest educational demands were related to self-management. They assessed their five essential procedure skill levels as novice or advanced beginner status. The achievement level for the essential symptoms and signs that IM specialists should be able to manage was predominantly competent level. However, on average, 34.9% answered that they had never assessed during training for essential skills, and 29.7% answered the same for essential symptoms and signs. CONCLUSION: We identified the priorities of core competencies, the level of achievement in essential procedures and patient care with essential symptoms and signs for IM training, and the related educational methods and assessment status. This study is expected to be used as basic data for developing and revising IM training educational curriculum.

Risk Factors Related to COVID-19 Reinfection and Fatality During the Omicron (BA.1/BA.2) Period in Korea.

BACKGROUND: This study aimed to investigate the deaths due to coronavirus disease 2019 (COVID-19) reinfection and related risk factors. METHODS: National cohort data were collected for a six-month period when omicron BA.1/BA.2 variant was dominant in South Korea. RESULTS: The long-term care facility residents (adjusted odds ratio, 3.11; 95% confidence interval [CI], 2.98-3.25) had significantly higher risk of reinfection than the general population. The risk of reinfection was significantly lower for persons with 2 or more vaccine doses compared to the unvaccinated. The risk of death was significantly higher in the reinfection group than in the primary infection group for persons in the 60-74 years age group (adjusted relative risk [aRR], 1.62; 95% CI, 1.19-2.20), and immunocompromised group (aRR, 4.56; 95% CI, 2.34-8.90). CONCLUSION: In these data, vaccination history was significantly related to reduced COVID-19 reinfection and severe progression, and scheduled vaccinations were important even with a history of infection.

Shape Memory Alloys in Textile Platform: Smart Textile-Composite Actuator and Its Application to Soft Grippers.

In recent years, many researchers have aimed to construct robotic soft grippers that can handle fragile or unusually shaped objects without causing damage. This study proposes a smart textile-composite actuator and its application to a soft robotic gripper. An active fiber and an inactive fiber are combined together using knitting techniques to manufacture a textile actuator. The active fiber is a shape memory alloy (SMA) that is wire-wrapped with conventional fibers, and the inactive fiber is a knitting yarn. A knitted textile structure is flexible, with an excellent structure retention ability and high compliance, which is suitable for developing soft grippers. A driving source of the actuator is the SMA wire, which deforms under heating due to the shape memory effect. Through experiments, the course-to-wale ratio, the number of bundling SMA wires, and the driving current value needed to achieve the maximum deformation of the actuator were investigated. Three actuators were stitched together to make up each finger of the gripper, and layer placement research was completed to find the fingers' suitable bending angle for object grasping. Finally, the gripping performance was evaluated through a test of grasping various object shapes, which demonstrated that the gripper could successfully lift flat/spherical/uniquely shaped objects.

Silibinin Downregulates Types I and III Collagen Expression via Suppression of the mTOR Signaling Pathway.

Keloid scars are fibro-proliferative conditions characterized by abnormal fibroblast proliferation and excessive extracellular matrix deposition. The mammalian target of the rapamycin (mTOR) pathway has emerged as a potential therapeutic target in keloid disease. Silibinin, a natural flavonoid isolated from the seeds and fruits of the milk thistle, is known to inhibit the mTOR signaling pathway in human cervical and hepatoma cancer cells. However, the mechanisms underlying this inhibitory effect are not fully understood. This in vitro study investigated the effects of silibinin on collagen expression in normal human dermal and keloid-derived fibroblasts. We evaluated the effects of silibinin on the expressions of collagen types I and III and assessed its effects on the suppression of the mTOR signaling pathway. Our findings confirmed elevated mTOR phosphorylation levels in keloid scars compared to normal tissue specimens. Silibinin treatment significantly reduced collagen I and III expressions in normal human dermal and keloid-derived fibroblasts. These effects were accompanied by the suppression of the mTOR signaling pathway. Our findings suggest the potential of silibinin as a promising therapeutic agent for preventing and treating keloid scars. Further studies are warranted to explore the clinical application of silibinin in scar management.

Efficacy and Safety of Epidermidibacterium Keratini EPI-7 Derived Postbiotics in Skin Aging: A Prospective Clinical Study.

The present study investigated the effect of topical application of Epidermidibacterium Keratini (EPI-7) ferment filtrate, which is a postbiotic product of a novel actinobacteria, on skin aging, by performing a prospective randomized split-face clinical study on Asian woman participants. The investigators measured skin biophysical parameters, including skin barrier function, elasticity, and dermal density, and revealed that the application of the EPI-7 ferment filtrate-including test product resulted in significantly higher improvements in barrier function, skin elasticity, and dermal density compared to the placebo group. This study also investigated the influence of EPI-7 ferment filtrate on skin microbiome diversity to access its potential beneficial effects and safety. EPI-7 ferment filtrate increased the abundance of commensal microbes belonging to Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Clostridium, Rothia, Lactobacillus, and Prevotella. The abundance of Cutibacterium was significantly increased along with significant changes in Clostridium and Prevotella abundance. Therefore, EPI-7 postbiotics, which contain the metabolite called orotic acid, ameliorate the skin microbiota linked with the aging phenotype of the skin. This study provides preliminary evidence that postbiotic therapy may affect the signs of skin aging and microbial diversity. To confirm the positive effect of EPI-7 postbiotics and microbial interaction, additional clinical investigations and functional analyses are required.

No Interference of H9 Extract on Trastuzumab Pharmacokinetics in Their Combinations.

Trastuzumab is used to treat breast cancer patients overexpressing human epidermal growth factor receptor 2, but resistance and toxicity limit its uses, leading to attention to trastuzumab combinations. Recently, the synergistic effect of trastuzumab and H9 extract (H9) combination against breast cancer has been reported. Because drug exposure determines its efficacy and toxicity, the question of whether H9 changes trastuzumab exposure in the body has been raised. Therefore, this study aimed to characterize trastuzumab pharmacokinetics and elucidate the effect of H9 on trastuzumab pharmacokinetics at a combination dose that shows synergism in mice. As a result, trastuzumab showed linear pharmacokinetics after its intravenous administration from 1 to 10 mg/kg. In the combination of trastuzumab and H9, single and 2-week treatments of oral H9 (500 mg/kg) did not influence trastuzumab pharmacokinetics. In the multiple-combination treatments of trastuzumab and H9 showing their synergistic effect (3 weeks of trastuzumab with 2 weeks of H9), the pharmacokinetic profile of trastuzumab was comparable to that of 3 weeks of trastuzumab alone. In tissue distribution, the tissue to plasma ratios of trastuzumab below 1.0 indicated its limited distributions within the tissues, and these patterns were unaffected by H9. These results suggest that the systemic and local exposures of trastuzumab are unchanged by single and multiple-combination treatments of H9.

A Novel Multi-Component Formulation Reduces Inflammation In Vitro and Clinically Lessens the Symptoms of Chronic Eczematous Skin.

Long-term treatments for inflammatory skin diseases like atopic dermatitis or eczema can cause adverse effects. Super Protein Multifunction (SPM) was investigated as a potential treatment for managing skin inflammation by monitoring the expression of pro-inflammatory cytokines induced using LPS and poly(I:C)/TNFα in HaCaT keratinocytes and Hs27 fibroblasts as measured via RT-PCR. SPM solution was also assessed for its effect on cytokine release, measured using ELISA, in a UVB-irradiated 3D human skin model. To evaluate the efficiency of SPM, 20 patients with mild eczematous skin were randomized to receive SPM or vehicle twice a day for three weeks in a double-blind controlled trial. In vitro studies showed SPM inhibited inflammation-induced IL-1ß, IL-6, IL-33, IL-1α, TSLP, and TNFα expression or release. In the clinical study, the SPM group showed significant improvements in the IGA, PA, and DLQI scores compared to the vehicle group. Neither group showed significant differences in VAS (pruritus). Histological analysis showed reduced stratum corneum thickness and inflammatory cell infiltration. The results suggest that SPM may reduce inflammation in individuals with chronic eczematous skin.