Epidermal Layer Research Articles

Human Leukocyte Antigen Markers for Distinguishing Pustular Psoriasis and Adult-Onset Immunodeficiency with Pustular Reaction.

Pustular skin diseases, with pustular psoriasis (PP) being the prototype, are immune-mediated diseases characterized by the presence of multiple pustules, resulting from neutrophil accumulation in the layer of epidermis. Sterile skin pustular eruption, like PP, is also observed in 20-30% of patients with adult-onset immunodeficiency syndrome (AOID) and anti-interferon γ autoantibodies (IFN-γ), leading to challenges in classification and diagnosis. While the mechanism underlying this similar phenotype remains unknown, genetic factors in relation to the immune system are suspected of playing an important role. Here, the association between human leukocyte antigen (HLA) genes, which play essential roles in antigen presentation, contributing to immune response, and the presence of skin pustules in AOID and PP was revealed. HLA genotyping of 41 patients from multiple centers in Thailand who presented with multiple sterile skin pustules (17 AOID patients and 24 PP patients) was conducted using a next-generation-sequencing-based approach. In comparison to healthy controls, HLA-B*13:01 (OR = 3.825, 95%CI: 2.08-7.035), C*03:04 (OR = 3.665, 95%CI: 2.102-6.39), and DQB1*05:02 (OR = 2.134, 95%CI: 1.326-3.434) were significantly associated with the group of aforementioned conditions having sterile cutaneous pustules, suggesting a common genetic-related mechanism. We found that DPB1*05:01 (OR = 3.851, p = 0.008) and DRB1*15:02 (OR = 3.195, p = 0.033) have a significant association with pustular reaction in AOID patients, with PP patients used as a control. A variant in the DRB1 gene, rs17885482 (OR = 9.073, p = 0.005), was observed to be a risk factor for PP when using AOID patients who had pustular reactions as a control group. DPB1*05:01 and DRB1*15:02 alleles, as well as the rs17885482 variant in the DRB1 gene, were proposed as novel biomarkers to differentiate PP and AOID patients who first present with multiple sterile skin pustules without known documented underlying conditions.

First Report of Sclerotinia Rot Caused by Sclerotinia sclerotiorum on Artemisia capillaris in China.

Artemisia capillaris (Asteraceae) is an annual herb found in ˃10 provinces in China. It is cultivated on ˃670 ha, with annual production around 2,500 tons. Its shoot is used in traditional Chinese medicine (Liu et al. 2021). From April to May 2023, Sclerotinia rot symptoms were seen at the Institute of Medicinal Plant Development (40.04°N, 116.28°E), Beijing, China. Disease incidence was up to 10% in the field through investigation of 300 plants. Initial symptoms were irregular tan-brown lesions (0.5 to 5.0 mm) that expended to circumferential necrosis on the roots and basal stem, aerial mycelia and sclerotia were developed on them. The leaves and stem tips were withered and droopy in severe cases. Twelve symptomatic primary roots of 12 plants from two sites were cut into 5 × 5 mm pieces, surface sterilized with 75% ethanol for 30 s and 5% NaClO for 60 s, rinsed with distilled water for three times, dried with sterile filter paper, put on potato dextrose agar (PDA), and incubated at 25°C in the dark for 2 days. Two Sclerotinia-like isolates were obtained using the hyphaltip method. White aerial mycelia were sparse and appressed for isolate YC1-3 and dense for isolate YC1-7. After incubated at 25°C in the dark for 15 days, 10 to 25 sclerotia were developed near the colony margin. Sclerotia of isolate YC1-3 were 1.0 to 3.9 × 1.2 to 4.5 (mean 1.8 × 2.2) mm (n = 60), ovoid or arc-shaped. Sclerotia of isolate YC1-7 were 1.5 to 3.4 × 2.7 to 9.2 (mean 2.3 × 4.3) mm (n = 60), ovoid, dumbbell shaped or curved. The isolates were identified as Sclerotinia sclerotiorum based on morphology (Maas 1998). To further identify the pathogens, molecular identification was performed with isolates YC1-3 and YC1-7. DNA of the two isolates were extracted by the cetyltrimethylammonium bromide (CTAB) method. Polymerase chain reaction was performed with primers ITS1/ITS4 for the internal transcribed spacer (ITS) region (Choi et al. 2020; White et al. 1990) and primers G3PDHfor/G3PDHrev for the glyceraldehyde 3-phosphate dehydrogenase (G3PDH) gene (Garfinkel. 2021). BLAST search analysis revealed that the ITS sequence (GenBank OR229758 and OR229762) was ≥99% similar to S. sclerotiorum (MN099281, MZ379265, KX781301, etc.), and the G3PDH sequence (OR778388 and OR761975) was too (MZ493894, JQ036048, OQ790148, etc.). Phylogenetic trees were computed with ITS and G3PDH sequences using the Maximum Likelihood in MEGA 11. Nine two-month-old seedlings of A. capillaris were used to test pathogenicity. The epidermis layer of each primary root was slightly wounded (2 × 2 mm, 1 mm deep) using a sterile dissecting blade. Three plants were inoculated with mycelial plugs (5 mm in diameter) of YC1-3 and YC1-7 that cultured on PDA for 7 days. Control plants were inoculated with sterile PDA plugs. All seedlings were then incubated at 25oC and 90% relative humidity. After isolate YC1-7 inoculation 3 days and isolate YC1-3 inoculation 5 days, inoculated roots had symptoms like those in the field, controls had no symptoms. S. sclerotiorum was consistently re-isolated from diseased roots, fulfilling Koch's postulates. Diseases caused by S. sclerotiorum have been reported threatens several important economical crops (Marin and Peres 2020; Guan et al. 2022). To our knowledge, this is the first report of S. sclerotiorum causes Sclerotinia rot on A. capillaris. To avoid of significant economic losses, it is urgent to establish an effective disease-management strategy.

Comparative Study of Epidermal Grafting (Blister graft) versus STSG (Split-thickness skin grafting) in wound healing. Our experience

Abstract Background: Split-thickness skin grafting (STSG) is one of the basic modalities for wound cover. Sometimes donor site becomes painful and leaves a second wound or scar which may take longer time to cure than the primary graft site itself. Epidermal grafting (Blister graft/Suction graft) is an alternative method of skin grafting in which we apply continuous negative pressure on the skin to harvest the epidermal layer of the skin. This procedure leaves minimal donor site morbidity or scar and is relatively less painful. It can be done on an outpatient basis. In our study, we try to compare STSG and Epidermal grafts and the mechanism by which each technique achieves wound healing.

Chemical and Transcriptomic Analyses of Leaf Cuticular Wax Metabolism in Ammopiptanthus mongolicus under Osmotic Stress.

Plant cuticular wax forms a hydrophobic structure in the cuticle layer covering epidermis as the first barrier between plants and environments. Ammopiptanthus mongolicus, a leguminous desert shrub, exhibits high tolerances to multiple abiotic stress. The physiological, chemical, and transcriptomic analyses of epidermal permeability, cuticular wax metabolism and related gene expression profiles under osmotic stress in A. mongolicus leaves were performed. Physiological analyses revealed decreased leaf epidermal permeability under osmotic stress. Chemical analyses revealed saturated straight-chain alkanes as major components of leaf cuticular wax, and under osmotic stress, the contents of total wax and multiple alkane components significantly increased. Transcriptome analyses revealed the up-regulation of genes involved in biosynthesis of very-long-chain fatty acids and alkanes and wax transportation under osmotic stress. Weighted gene co-expression network analysis identified 17 modules and 6 hub genes related to wax accumulation, including 5 enzyme genes coding KCS, KCR, WAX2, FAR, and LACS, and an ABCG transporter gene. Our findings indicated that the leaf epidermal permeability of A. mongolicus decreased under osmotic stress to inhibit water loss via regulating the expression of wax-related enzyme and transporter genes, further promoting cuticular wax accumulation. This study provided new evidence for understanding the roles of cuticle lipids in abiotic stress tolerance of desert plants.

Antiseptic, Hemostatic, and Wound Activity of Poly(vinylpyrrolidone)-Iodine Gel with Trimethyl Chitosan.

Wound management practices have made significant advancements, yet the search for improved antiseptics persists. In our pursuit of solutions that not only prevent infections but also address broader aspects of wound care, we investigated the impact of integrating trimethyl chitosan (TMC) into a widely used poly(vinylpyrrolidone)-iodine gel (PVP-I gel). Our study assessed the antimicrobial efficacy of the PVP gel with TMC against Escherichia coli, Staphylococcus aureus, multidrug-resistant S. aureus MRSA, and Candida albicans. Additionally, we compared hemostatic effects using a liver puncture bleeding model and evaluated wound healing through histological sections from full-thickness dermal wounds in rats. The results indicate that incorporating TMC into the commercially available PVP-I gel did not compromise its antimicrobial activity. The incorporation of TMC into the PVP-I gel markedly improves its hemostatic activity. The regular application of the PVP-I gel with TMC resulted in an increased blood vessel count in the wound bed and facilitated the development of thicker fibrous tissue with a regenerated epidermal layer. These findings suggest that TMC contributes not only to antimicrobial activity but also to the intricate processes of tissue regeneration. In conclusion, incorporating TMC proves beneficial, making it a valuable additive to commercially available antiseptic agents.

Transcription factors and plant hormones mediate wax metabolism in response to drought stress.

Plants have, throughout evolution, developed a hydrophobic cuticle to protect them from various stresses in the terrestrial environment. The cuticle layer is mainly composed of cutin and cuticular wax, a mixture of very-long-chain fatty acids and their derivatives. With the progress of transcriptome sequencing and other research methods, the key enzymes, transporters and regulatory factors in wax synthesis and metabolism have been gradually identified, especially the study on the regulation of wax metabolism by transcription factors and others in response to plant stress has become a hot topic. Drought is a major abiotic stress that limits plant growth and crop productivity. Plant epidermal wax prevents non-stomatal water loss and improves water use efficiency to adapt to arid environments. In this study, the ways of wax synthesis, transport, metabolism and regulation at different levels are reviewed. At the same time, the regulation of wax by different transcription factors and plant hormones in response to drought is elaborated, and key research questions and important directions for future solutions are proposed to enhance the potential application of epidermal wax in agriculture and the environment.

Advancements in non-invasive skin sampling: Clinical conditions characterization via the assessment of skin surface cytokine biomarkers.

The skin is increasingly recognized as a biological active organ interacting with the immune system. Given that the epidermal skin layer actively releases various cytokines, non-invasive skin sampling methods could detect these cytokines, offering insights into clinical conditions. This study aims non-invasively measuring cytokine levels directly from the skin surface to characterize different inflammatory chronic disorders in the adult and elderly population: psoriasis, diabetes type 2, rosacea, chronic kidney disease (CKD) and aging. Cytokines IL-1β, IL-8 and IL-10 were sampled from healthy subjects and patients aged 18-80 using skin surface wash technique. A well with sterile phosphate-buffered saline solution was placed on the skin for 30 min, and the extracted solution was collected from the well for further cytokine levels analysis using ELISA assay. Results show distinct cytokine profiles in different pathological processes, healthy controls, affected and unaffected areas. Aging was associated with increased IL-1β, IL-8, and IL-10 levels in skin. In diabetes, IL-1β and IL-8 levels were elevated in lesional areas, while IL-10 levels were decreased in non-lesional skin. Psoriatic lesions showed elevated levels of IL-1β and IL-8. Rosacea patients had lower IL-10 levels in both lesional and non-lesional areas. CKD patients exhibited significantly lower IL-10 levels compared to healthy individuals. In conclusion, skin surface wash-derived cytokine profiles could serve as "alert biomarkers" for disease prediction, enabling early detection. Additionally, this method's cost-effectiveness allows pre-screening of molecules in clinical studies and holds potential as a tool for biomarkers and omics analysis, enhancing disorder characterization and disease management.

Conditions of acceleration and deceleration of the cancer cell growth under osmotic pressure.

In this paper, we study a pattern formation in the epidermal layer of skin during tumor development and appearance of a binary surface consisting of healthy and cancer cells forming Turing patterns under external osmotic pressure. The basic methodology of introducing the external influences, for example, time-targeted drug therapy or radiation exposure, influence of electromagnetic fields, laser radiation or other tumor-targeting physical influences act differently in different phases of the cell cycle. In some cases, this can lead to a slowdown in the growth of cancer cells, and sometimes vice versa. Therefore, it is of particular interest to choose the right parameters such as starting time of external pressure, its magnitude and duration depending on the cell cycle of developing cancer cells. We propose a biologically inspired model that allows us to simulate the growth of cancer cells under conditions of osmotic pressure. We divide this growth into two phases. The first is characterized by active cell division, and the second by their growth. In this article, we introduce two types of pressure: short-term and long-term, and looked at what this leads to in different phases. We have found an interesting result, that there are some resonant points in time both in the first and second phases, when the introduction of additional pressure leads to the most significant slowdown in the growth of cancer cells.

Dermatologic Changes in Experimental Model of Long COVID.

The coronavirus disease-19 (COVID-19) pandemic, declared in early 2020, has left an indelible mark on global health, with over 7.0 million deaths and persistent challenges. While the pharmaceutical industry raced to develop vaccines, the emergence of mutant severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains continues to pose a significant threat. Beyond the immediate concerns, the long-term health repercussions of COVID-19 survivors are garnering attention, particularly due to documented cases of cardiovascular issues, liver dysfunction, pulmonary complications, kidney impairments, and notable neurocognitive deficits. Recent studies have delved into the pathophysiological changes in various organs following post-acute infection with murine hepatitis virus-1 (MHV-1), a coronavirus, in mice. One aspect that stands out is the impact on the skin, a previously underexplored facet of long-term COVID-19 effects. The research reveals significant cutaneous findings during both the acute and long-term phases post-MHV-1 infection, mirroring certain alterations observed in humans post-SARS-CoV-2 infection. In the acute stages, mice exhibited destruction of the epidermal layer, increased hair follicles, extensive collagen deposition in the dermal layer, and hyperplasticity of sebaceous glands. Moreover, the thinning of the panniculus carnosus and adventitial layer was noted, consistent with human studies. A long-term investigation revealed the absence of hair follicles, destruction of adipose tissues, and further damage to the epidermal layer. Remarkably, treatment with a synthetic peptide, SPIKENET (SPK), designed to prevent Spike glycoprotein-1 binding with host receptors and elicit a potent anti-inflammatory response, showed protection against MHV-1 infection. Precisely, SPK treatment restored hair follicle loss in MHV-1 infection, re-architected the epidermal and dermal layers, and successfully overhauled fatty tissue destruction. These promising findings underscore the potential of SPK as a therapeutic intervention to prevent long-term skin alterations initiated by SARS-CoV-2, providing a glimmer of hope in the battle against the lingering effects of the pandemic.

The Mechanism of 5-Fluorouracil-Induced Hyperpigmentation in HRM-2 Hairless Mice: Focus on the Increase of Blood Vessels.

5-Fluorouracil (5-FU), an effective chemotherapeutic agent for many solid tumors, has long been reported to cause pigmentation in patients treated intravenously, which occurs with increasing frequency of administration and decreases the QOL of the patients. Although melanin accumulation is thought to be the cause, the mechanism of pigmentation induced by 5-FU administration remains unclear, and there is no effective treatment for this problem. In this study, we investigated the mechanism of pigmentation induced by continuous 5-FU administration in 9-week-old male HRM-2 hairless mice for 8 weeks by focusing on the blood vessels for basic verification. In the auricular skin of 5-FU-administered mice, hyperpigmentation caused by melanin accumulation was observed macroscopically and by Fontana-Masson Staining. In addition, the expression of tyrosinase, melanin synthase, and blood vessel markers in the auricular skin was increased by 5-FU-administration in mice auricular skin. Other anticancer agents, cytarabine (Ara-C) and irinotecan (CPT-11), were also administered, and the differences between them and 5-FU were investigated; these changes were not observed in the auricles of these mice. These results suggest that tyrosinase is associated with 5-FU-induced melanin production and that an increase in blood vessels may be involved. Furthermore, pigmentation with melanin accumulation in the basal epidermal layer is a characteristic finding of 5-FU compared with Ara-C and CPT-11. In conclusion, this study indicates that 5-FU causes hyperpigmentation by melanin accumulation in a characteristic manner, including an increase in blood vessels.

Calcium transients trigger switch-like discharge of prostaglandin E2 in an extracellular signal-regulated kinase-dependent manner.

Prostaglandin E2 (PGE2) is a key player in a plethora of physiological and pathological events. Nevertheless, little is known about the dynamics of PGE2 secretion from a single cell and its effect on the neighboring cells. Here, by observing confluent Madin-Darby canine kidney (MDCK) epithelial cells expressing fluorescent biosensors, we demonstrate that calcium transients in a single cell cause PGE2-mediated radial spread of PKA activation (RSPA) in neighboring cells. By in vivo imaging, RSPA was also observed in the basal layer of the mouse epidermis. Experiments with an optogenetic tool revealed a switch-like PGE2 discharge in response to the increasing cytoplasmic Ca2+ concentrations. The cell density of MDCK cells correlated with the frequencies of calcium transients and the following RSPA. The extracellular signal-regulated kinase (ERK) activation also enhanced the frequency of RSPA in MDCK and in vivo. Thus, the PGE2 discharge is regulated temporally by calcium transients and ERK activity.

Calcium transients trigger switch-like discharge of prostaglandin E2 in an extracellular signal-regulated kinase-dependent manner

Prostaglandin E2 (PGE2) is a key player in a plethora of physiological and pathological events. Nevertheless, little is known about the dynamics of PGE2 secretion from a single cell and its effect on the neighboring cells. Here, by observing confluent Madin–Darby canine kidney (MDCK) epithelial cells expressing fluorescent biosensors, we demonstrate that calcium transients in a single cell cause PGE2-mediated radial spread of PKA activation (RSPA) in neighboring cells. By in vivo imaging, RSPA was also observed in the basal layer of the mouse epidermis. Experiments with an optogenetic tool revealed a switch-like PGE2 discharge in response to the increasing cytoplasmic Ca2+ concentrations. The cell density of MDCK cells correlated with the frequencies of calcium transients and the following RSPA. The extracellular signal-regulated kinase (ERK) activation also enhanced the frequency of RSPA in MDCK and in vivo. Thus, the PGE2 discharge is regulated temporally by calcium transients and ERK activity.

Photobiomodulation and conditioned medium of adipose-derived stem cells for enhancing wound healing in rats with diabetes: an investigation on the proliferation phase.

This investigation tried to evaluate the combined and solo effects of photobiomodulation (PBM) and conditioned medium derived from human adipose tissue-derived stem cells (h-ASC-CM) on the inflammatory and proliferative phases of an ischemic infected delayed healing wound model (IIDHWM) in rats with type I diabetes mellitus (TIDM). The present investigation consisted of four groups: group 1 served as the control, group 2 treated with h-ASC-CM, group 3 underwent PBM treatment, and group 4 received a combination of h-ASC-CM and PBM. Clinical and laboratory assessments were conducted on days 4 and 8. All treatment groups exhibited significantly higher wound strength than the group 1 (p = 0.000). Groups 4 and 3 demonstrated significantly greater wound strength than group 2 (p = 0.000). Additionally, all therapeutic groups showed reduced methicillin -resistant Staphylococcus aureus (MRSA) in comparison with group 1 (p = 0.000). While inflammatory reactions, including neutrophil and macrophage counts, were significantly lower in all therapeutic groups rather than group 1 on days 4 and 8 (p < 0.01), groups 4 and 3 exhibited superior results compared to group 2 (p < 0.01). Furthermore, proliferative activities, including fibroblast and new vessel counts, as well as the measurement of new epidermal and dermal layers, were significantly increased in all treatment groups on 4 and 8 days after the surgery (p < 0.001). At the same times, groups 4 and 3 displayed significantly higher proliferative activities compared to group 2 (p < 0.001). The treatment groups exhibited significantly higher mast cell counts and degranulation phenotypes in comparison with the group 1 on day 4 (p < 0.05). The treatment groups showed significantly lower mast cell counts and degranulation phenotypes than group 1 on day 8 (p < 0.05).The combined and individual application of h-ASC-CM and PBM remarkably could accelerate the proliferation phase of wound healing in the IIDHWM for TIDM in rats, as indicated by improved MRSA control, wound strength, and stereological evaluation. Furthermore, the combination of h-ASC-CM and PBM demonstrated better outcomes compared to the individual application of either h-ASC-CM or PBM alone.

Taxonomic characteristics of &lt;i&gt;Spinacia oleracea&lt;/i&gt; L.

The research focused on the taxonomic study and proximate analysis of Spinacia oleracea L. The samples were fixed in formaldehyde acetic acid alcohol, dehydrated in alcohol solutions of 50%, 70% and 90%, sectioned, stained in 2% of Safranin O, counter stained in Alcian blue for 5 minutes, mounted in glycerine and photo-micrographed using Leica WILD MPS 52 camera on Leitz Draplan microscope. The proximate analysis was done using the Association of Official Analytical Chemists’ methods. The result revealed that spinach is glabrous and reach up to 4 to 8ft in length. The foliar organs are simple, ovate to ovate-triangular and alternate to rosette phyllotaxy. Margins are entire to slightly serrated, reticulate veined, up to 5 ± 4 cm in length and 3 ± 2 cm in width. The basal leaves are far larger than the ones towards the apical meristem. The inflorescence has spikelet of actinomorphic flowers pollinated by wind. The fruit is a berry/ drupe. The foliar epidermal study revealed presence of simple elongated, linear and glandular trichomes, and amphistomatic diacytic stomata. Anatomical study showcased a layer of epidermis, hypodermis of 2 to 3 rolls of collenchyma, general cortex of 7 to 10 rolls of parenchyma and the pith of parenchyma. The node is unilacunar with 2 lateral leaf traces and 1 leaf trace median. The proximate compositions of: 0.19 ± 0.00 Carbohydrate (%); 3.75 ± 0.00 Protein (%); 0.02 ± 0.00 Lipid (%); 94.74 ± 0.36 Moisture (%) content; 0.62 ± 0.32 Fiber (%) and 1.18 ± 0.03 Ash (%). These information would assist for further delimitation of the species.

Fusarium Induced Anatomical and Biochemical Alterations in Wild Type and DPA-treated Wheat Seedlings

Wheat (Triticum aestivum) employs various strategies to defend against Fusarium oxysporum, a soil-borne vascular fungal pathogen that disrupts structural integrity and metabolism. The purpose of this research was to ascertain the alterations of anatomical and biochemical responses in wild-type (WT) and DPA-treated wheat (T. aestivum) seedlings exposed to F. oxysporum. The WT and DPA-treated seedlings showed disorganization of parenchyma cells, sclerenchyma cells, vascular bundles (VBs), and lower numbers of xylem (Xy) and phloem (Ph) cells, and reduced thickness of the cuticle layer (C) at the epidermal layer of shoots. The content of chlorophyll (Chl), carbohydrate, and nucleic acid was reduced in WT and DPA-treated seedlings during infection. Enhanced defense responses through peroxidase (POD), and polyphenol oxidase (PPO) was observed to be high in WT as compared to DPA-treated seedlings under stress condition. In addition, the content of salicylic acid (SA) and phenolics was increased in WT than DPA under stress condition. However, the DPA-treated seedlings showed enhanced growth of fungal mycelia compared to WT during stress condition. Hence, the anatomical and biochemical aspects of DPA-treated seedlings decreased as compared to WT when exposed to F. oxysporum.

A sustainable strategy for generating highly stable human skin equivalents based on fish collagen

Tissue engineered skin equivalents are increasingly recognized as potential alternatives to traditional skin models such as human ex vivo skin or animal skin models. However, most of the currently investigated human skin equivalents (HSEs) are constructed using mammalian collagen which can be expensive and difficult to extract. Fish skin is a waste product produced by fish processing industries and identified as a cost-efficient and sustainable source of type I collagen. In this work, we describe a method for generating highly stable HSEs based on fibrin fortified tilapia fish collagen. The fortified fish collagen (FFC) formulation is optimized to enable reproducible fabrication of full-thickness HSEs that undergo limited contraction, facilitating the incorporation of human donor-derived skin cells and formation of biomimetic dermal and epidermal layers. The morphology and barrier function of the FFC HSEs are compared with a commercial skin model and validated with immunohistochemical staining and transepithelial electrical resistance testing. Finally, the potential of a high throughput screening platform with FFC HSE is explored by scaling down its fabrication to 96-well format.

Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice

BackgroundCDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, a persistently high level of CISD2 promotes longevity and ameliorates an age-related skin phenotype in transgenic mice. Here we translate the genetic evidence into a pharmaceutical application using a potent CISD2 activator, hesperetin, which enhances CISD2 expression in HEK001 human keratinocytes from an older person. We also treated naturally aged mice in order to study the activator’s anti-aging efficacy.MethodsWe studied the biological effects of hesperetin on aging skin using, firstly, a cell-based platform, namely a HEK001 human keratinocyte cell line established from an older person. Secondly, we used a mouse model, namely old mice at 21-month old. In the latter case, we investigate the anti-aging efficacy of hesperetin on ultraviolet B (UVB)-induced photoaging and naturally aged skin. Furthermore, to identify the underlying mechanisms and potential biological pathways involved in this process we carried out transcriptomic analysis. Finally, CISD2 knockdown HEK001 keratinocytes and Cisd2 knockout mice were used to study the Cisd2-dependent effects of hesperetin on skin aging.ResultsFour findings are pinpointed. Firstly, in human skin, CISD2 is mainly expressed in proliferating keratinocytes from the epidermal basal layer and, furthermore, CISD2 is down-regulated in the sun-exposed epidermis. Secondly, in HEK001 human keratinocytes from an older person, hesperetin enhances mitochondrial function and protects against reactive oxygen species-induced oxidative stress via increased CISD2 expression; this enhancement is CISD2-dependent. Additionally, hesperetin alleviates UVB-induced damage and suppresses matrix metalloproteinase-1 expression, the latter being a major indicator of UVB-induced damage in keratinocytes. Thirdly, transcriptomic analysis revealed that hesperetin modulates a panel of differentially expressed genes that are associated with mitochondrial function, redox homeostasis, keratinocyte function, and inflammation in order to attenuate senescence. Intriguingly, hesperetin activates two known longevity-associated regulators, namely FOXO3a and FOXM1, in order to suppress the senescence-associated secretory phenotype. Finally, in mouse skin, hesperetin enhances CISD2 expression to ameliorate UVB-induced photoaging and this occurs via a mechanism involving CISD2. Most strikingly, late-life treatment with hesperetin started at 21-month old and lasting for 5 months, is able to retard skin aging and rejuvenate naturally aged skin in mice.ConclusionsOur results reveal that a pharmacological elevation of CISD2 expression at a late-life stage using hesperetin treatment is a feasible approach to effectively mitigating both intrinsic and extrinsic skin aging and that hesperetin could act as a functional food or as a skincare product for fighting skin aging.

Umbilical therapy for promoting transdermal delivery of topical formulations: Enhanced effect and underlying mechanism

Umbilical paste therapy is a promising method to promote transdermal drug delivery of topical formulations. This work investigated the effect and mechanism of transdermal drug delivery through the umbilical skin. The transdermal permeation studies showed the phenomenon of higher cumulative penetration and faster penetration rates for drug through the umbilical skin compared with non-umbilical skin, namely umbilical pro-permeability. This special transdermal permeability of drugs is influenced by their molecular weight, logP value, ability to form hydrogen bonds, and molecular volume. The underlying mechanism of umbilical pro-permeability was elucidated from unique structure and regulation the effect of drugs on microcirculation in the umbilical skin. Mechanistic studies revealed that this phenomenon was not only associated with the structural and physiological properties of the skin but also to the interactions between drugs and different skin layers. The umbilical pro-permeation is attributed to the thinner stratum corneum layer, differences in stratum corneum lipid composition and keratin structure, and lower levels of intercellular tight junction proteins in the viable epidermis and dermis layer of the skin. Our research indicated that umbilical paste therapy enhanced the transdermal delivery and absorption of drugs by stimulating local blood flow through mast cell activation. Surprisingly, skin temperature modulation and calcitonin gene-related peptide and substance P levels did not appear to significantly affect this process. In conclusion, umbilical drug administration, as a straightforward and non-invasive approach to enhance transdermal drug delivery, presents novel concepts for continued investigation and practical implementation of transdermal drug delivery systems.

Insecticidal activity and possible modes of action of secondary metabolites of some fungal strains and wild plants as natural pesticides against Spodoptera frugiperda

BackgroundThe fall armyworm (FAW), Spodoptera frugiperda, is an invasive and destructive pest to certain strategic crops, especially maize in Egypt. This research was conducted mainly to obtain secondary metabolites from some wild plants and fungal strains, use them in controlling FAW, and investigate their mode of action.ResultsThe ethyl acetate extracts of Cladosporium cladosporioides and Verticillium lecanii, as well as the alkaloid extracts of Ricinus communis and Nicotiana glauca, were extracted to obtain their secondary metabolites. The secondary metabolite contents were identified by gas chromatography mass spectrometry and NMR. The toxicity of all extracts against the 3rd-instar larvae of FAW was evaluated. The possible mode of action of the extracts was studied via their effects on larval enzyme activities and larval tissue. The toxicity results illustrated that, the extract of C. cladosporioides was more effective with LC50 229 ppm, followed by the extract of V. lecanii with LC50 341 ppm and N. glauca with LC50 404 ppm, while the least effective extract was R. communis with LC50 1110 ppm after 72 h of treatment. While, the results of larval enzyme activities showed that C. cladosporioides, V. lecanii, and R. communis extracts led to significant activity of AST, ALT, ACP, and ALP enzymes, but GST and AchE were inhibited in treated larvae compared with control. While N. glauca alkaloid extract caused significant inhibition of AST, ALT, ACP, AchE, and GST enzymes, ALP was activated in the treated larvae compared with control. The results of larval tissue slides indicated that the most affected tissues were the cuticle layer and the membrane lining of the midgut, in addition to the fatty bodies.ConclusionThus, natural pesticides would have a promising role in terms of controlling the FAW and according to this study, it was recommended that, alkaloid extracts of tested wild plants and ethyl acetate extracts of fungal strains be used as natural pesticides to control the fall armyworm, S. frugiperda.

Low-velocity impact response of a novel bionic turtle shell back armor sandwich structure

Turtle shell dorsal armor comprises a typical lightweight laminated composite structural material, which is constructed by cuticle and bone layer, with high specific strength and high fracture toughness. The red-eared slider turtle, a widely studied species of turtle, has a rich hierarchical structure. In this paper, according to the structure of red-eared slider turtle shell dorsal armor and the characteristics of each layer as well as by taking into full consideration of the fine structure of cuticle and ventral cortex of the shell dorsal armor, two bionic foam silicone rubber sandwich structures of different levels were prepared. Low-velocity impact test and finite element simulation analysis were carried out to study the mechanical response, specific absorbed energy, and damage mode of the two bionic sandwich structures under different impact energies, hammerhead shapes, and hammerhead radii. By comparing the mechanical response and specific energy absorption with the existing ordinary sandwich structure, we find that the two sandwich structures modeled in this paper exhibit better impact resistance than the ordinary sandwich structure. The shape and radius of the hammer head have a significant effect on the energy absorption characteristics of the sandwich structure, and the damage mode under the hemispherical hammer head is mainly dominated by tensile tearing damage, while the damage mode of extrusion fracture is more obvious under the impact of the conical hammer head. With the increase of the radius of the hammer head, the absorbed energy and specific energy absorption of the sandwich structure increases.