Skin Samples Research Articles

Assessment of NB-UVB Effects on Skin of Atopic Dermatitis Patients: A Network Analysis.

Introduction: Atopic dermatitis is a common inflammatory skin disease which is treated with narrowband ultraviolet B (NB-UVB). Exploring the critical targeted genes in patients by UV radiation is the main aim of this study. Methods: Gene expression profiles of lesional and non-lesional skin samples of atopic dermatitis patients after treatment with NB-UVB and the non-irradiated samples were extracted from the Gene Expression Omnibus (GEO) database and analyzed via protein-protein interaction (PPI) network analysis to find the critical targeted genes. Results: A total of 357 significant differentially expressed genes (DEGs) were included in the PPI network. CTNNB1, SRSF1, YWHAB, SMC3, GNB2, ARF3, UBL7, RAB2A, YWHAE, EIF5B, SNRPE, PPIG, RC3H2, CFL1, SMARCB1. LAPTM5, PRPF40A, and RBBP4 were introduced as hub-bottlenecks. Conclusion: In conclusion, five central genes including SMC3, ARF3, EIF5B, SMARCB1, and LAPTM5 were highlighted as the critical genes in response to NB-UVB radiation in the skin of the treated atopic dermatitis patients. The introduced crucial genes are involved in essential cellular functions such as apoptosis, cell cycle, cell proliferation, and inflammation. It seems that applied NB-UVB radiation is a suitable therapeutic method for atopic dermatitis disease.

Keratinocytes drive the epithelial hyperplasia key to sea lice resistance in coho salmon

BackgroundSalmonid species have followed markedly divergent evolutionary trajectories in their interactions with sea lice. While sea lice parasitism poses significant economic, environmental, and animal welfare challenges for Atlantic salmon (Salmo salar) aquaculture, coho salmon (Oncorhynchus kisutch) exhibit near-complete resistance to sea lice, achieved through a potent epithelial hyperplasia response leading to rapid louse detachment. The molecular mechanisms underlying these divergent responses to sea lice are unknown.ResultsWe characterized the cellular and molecular responses of Atlantic salmon and coho salmon to sea lice using single-nuclei RNA sequencing. Juvenile fish were exposed to copepodid sea lice (Lepeophtheirus salmonis), and lice-attached pelvic fin and skin samples were collected 12 h, 24 h, 36 h, 48 h, and 60 h after exposure, along with control samples. Comparative analysis of control and treatment samples revealed an immune and wound-healing response that was common to both species, but attenuated in Atlantic salmon, potentially reflecting greater sea louse immunomodulation. Our results revealed unique but complementary roles of three layers of keratinocytes in the epithelial hyperplasia response leading to rapid sea lice rejection in coho salmon. Our results suggest that basal keratinocytes direct the expansion and mobility of intermediate and, especially, superficial keratinocytes, which eventually encapsulate the parasite.ConclusionsOur results highlight the key role of keratinocytes in coho salmon’s sea lice resistance and the diverged biological response of the two salmonid host species when interacting with this parasite. This study has identified key pathways and candidate genes that could be manipulated using various biotechnological solutions to improve Atlantic salmon sea lice resistance.

Next generation mycological diagnosis: Artificial intelligence-based classifier of the presence of Malassezia yeasts in tape strip samples.

Malassezia yeasts are almost universally present on human skin worldwide. While they can cause diseases such as pityriasis versicolor, their implication in skin homeostasis and pathophysiology of other dermatoses is still unclear. Their analysis using native microscopy of skin tape strips is operator dependent and requires skill, training and significant amounts of hands-on time. To standardise and improve the speed and quality of diagnosis of Malassezia in skin tape strip samples, we sought to create an artificial intelligence-based algorithm for this image classification task. Three algorithms, each using different internal architectures, were trained and validated on a manually annotated dataset of 1113 images from 22 samples. The Vision Transformer-based algorithm performed the best with a validation accuracy of 94%, sensitivity of 94.0% and specificity of 93.5%. Visualisations providing insight into the reasoning of the algorithm were presented and discussed. Our image classifier achieved very good performance in the diagnosis of the presence of Malassezia yeasts in tape strip samples of human skin and can therefore improve the speed and quality of, and access to this diagnostic test. By expanding data sources and explainability, the algorithm could also provide teaching points for more novice operators in future.

IRAK4 Is Overexpressed in Hidradenitis Suppurativa Skin and Correlates with Inflammatory Biomarkers

Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting as painful dermal nodules, abscesses, and tunnels. Activation of the IL-1R/toll-like receptor (TLR) pathway is strongly implicated in the pathogenesis of HS; thus, the role of a key signaling node, IL-1R-associated kinase 4 (IRAK4), was investigated in a noninterventional study (NCT04440410) that enrolled 30 patients with HS. IRAK4 expression was evaluated in blood and lesional, perilesional, and nonlesional skin biopsies. Peripheral blood mononuclear cells (PBMCs) expressed IRAK4, with significantly higher levels in monocytes (P ≤ 0.0001). Ex vivo treatment of PBMCs with KT-474, a targeted degrader of IRAK4, robustly decreased IRAK4 in all immune cell types from healthy volunteers and patients with HS. Ex vivo treatment of TLR-stimulated healthy donor monocytes with KT-474 decreased IRAK4 protein levels and inhibited inflammatory cytokine production. In HS skin samples, IRAK4 protein levels were significantly higher in lesional versus nonlesional tissue (P ≤ 0.0001), and IRAK4-positive immune infiltrate increased with greater disease severity. Multiple inflammatory mediators were upregulated in HS lesional skin, correlating with IRAK4 overexpression. These data confirm the significance of the IL-1R/TLR pathway in the pathogenesis of HS and provide support for ongoing clinical studies evaluating KT-474 in the treatment of HS.

The fibroblast heterogeneity across keloid, normal and tumor samples from single-cell resolution.

Keloids are defined as a benign dermal fibroproliferative disorder, with excessive fibroblast proliferation, and excessive overproduction of collagen. Although the heterogeneity during keloid development has been extensively studied, the heterogeneity across different skin states is still unclear. So, a global comparison across skin states is needed. In this study, we collected samples from 5 states of skin, including melanoma, cutaneous squamous cell carcinoma, keloid skin, scar skin, and healthy control samples. The heterogeneity of cell types and subtypes was analyzed and compared across 5 states, and we observed significant differences among them. Our results showed a cancer-like fibroblast, which is not in normal samples, may play an important role in antigen processing and presentation. We also noticed that the mesenchymal fibroblast increased in keloid samples, which highly expressed POSTN. And POSTN may participate in epithelial-mesenchymal transition and collagen overexpression to promote keloid growth. These findings help to understand the alteration among different skin states and provide potential genetic basis for keloid therapies.

The value of immunohistochemical expression of SOX9 and CD34 in alopecia areata

ABSTRACT Background Alopecia areata (AA), an immune-mediated disorder, is marked by temporary, nonscarring hair loss. The bulge area is protected from immune attacks by immune privilege; however, recent studies demonstrated immune cells infiltrating the bulge area. Objective This study aims to investigate the immunohistochemical expression of the sex-determining region Y-box 9 (SOX9) and cluster of differentiation 34 (CD34) in AA patients as markers of hair follicle stem cells (HFSCs) and progenitor cells, respectively. Methods Immunohistochemical staining of SOX9 and CD34 was applied on skin samples of 20 AA patients and 20 healthy controls. Results SOX9 and CD34 were significantly lower in lesional samples of cases compared to perilesional and control skin biopsies. Furthermore, SOX9 level was negatively correlated with the severity of alopecia tool score (SALT score) among the studied AA patients. Moreover, lowered SOX9 expression was present in patients with recurrent attacks. Conclusions The significant reduction of stem cell markers (SOX9 and CD34) in our studied AA cases signifies the pathological affection of HFSCs and their progeny in AA. This is thought to cause a loss of competence in generating new hair in some AA cases, which needs to be validated in further research. Limitations of the study This study has a small sample size.

Ultrasensitive detection of aggregated α-synuclein using quiescent seed amplification assay for the diagnosis of Parkinson’s disease

BackgroundSeed amplification assays (SAA) enable the amplification of pathological misfolded proteins, including α-synuclein (αSyn), in both tissue homogenates and body fluids of Parkinson’s disease (PD) patients. SAA involves repeated cycles of shaking or sonication coupled with incubation periods. However, this amplification scheme has limitations in tracking protein propagation due to repeated fragmentation.MethodsWe introduced a modified form of SAA, known as Quiescent SAA (QSAA), and evaluated biopsy and autopsy samples from individuals clinically diagnosed with PD and those without synucleinopathies (control group). Brain biopsy samples were obtained from 14 PD patients and 6 controls without synucleinopathies. Additionally, skin samples were collected from 214 PD patients and 208 control subjects. Data were analyzed from April 2019 to May 2023.ResultsQSAA successfully amplified αSyn aggregates in brain tissue sections from mice inoculated with pre-formed fibrils. In the skin samples from 214 PD cases and 208 non-PD cases, QSAA demonstrated high sensitivity (90.2%) and specificity (91.4%) in differentiating between PD and non-PD cases. Notably, more αSyn aggregates were detected by QSAA compared to immunofluorescence with the pS129-αSyn antibody in consecutive slices of both brain and skin samples.ConclusionWe introduced the new QSAA method tailored for in situ amplification of αSyn aggregates in brain and skin samples while maintaining tissue integrity, providing a streamlined approach to diagnosing PD with individual variability. The integration of seeding activities with the location of deposition of αSyn seeds advances our understanding of the mechanism underlying αSyn misfolding in PD.

Host Species and Environment Shape the Skin Microbiota of Mexican Axolotls

Skin microbiomes in amphibians are complex systems that can be influenced by biotic and abiotic factors. In this study, we examined the effect of host species and environmental conditions on the skin bacterial and fungal microbiota of four obligate paedomorphic salamander species, commonly known as axolotls (Ambystoma andersoni, A. dumerilii, A. mexicanum, and A. taylori), all of them endemic to the Trans-Mexican Volcanic Belt. We found that despite their permanent aquatic lifestyle, these species present a host-specific skin microbiota that is distinct from aquatic communities. We identified skin-associated taxa that were unique to each host species and that differentiated axolotl species based on alpha and beta diversity metrics. Moreover, we identified a set of microbial taxa that were shared across hosts with high relative abundances across skin samples. Specifically, bacterial communities were dominated by Burkholderiales and Pseudomonadales bacterial orders and Capnodiales and Pleosporales fungal orders. Host species and environmental variables collectively explained more microbial composition variation in bacteria (R2 = 0.46) in comparison to fungi (R2 = 0.2). Our results contribute to a better understanding of the factors shaping the diversity and composition of skin microbial communities in Ambystoma. Additional studies are needed to disentangle the effects of specific host associated and environmental factors that could influence the skin microbiome of these endangered species.

Clinical study of common bacterial, fungal and parasitic skin diseases in cats

Background: The skin is a big, metabolically active organ that has a significant need for other nutrients and protein in its body. The study pointed high significant infection with fungal, scabies, alopecia, bacterial and wounds in the white color cats more than the others because it is represented the better color choice for the families then the orange and grey colors while the black color is the less in number of domestic cats. The aim of present study was investigated of some skin disease in cats in Basrah, Iraq.Methods: The present study includes two hindered animals of both sexes with different ages, colors, weights and sizes were studied clinically in Basrah veterinary hospital and the private veterinary clinics in Basrah. The study extended from October 2022 to March 2023 during the winter season. Clinical signs were reported carefully, and the initial diagnosis of skin diseases was confirmed by apparent lesions on the skin, the skin samples of the cases were collected for laboratory diagnosis in veterinary medicine college ̸ Basrah University and Basrah veterinary hospital laboratories to confirmed diagnosis.Results: Clinical signs were reported carefully and the initial diagnosis of skin diseases. The two hindered sample cases were divided according to cases in Basrah veterinary hospital and Basrah private clinic: 60 Cases fungal infection, 40 cases scabies, 10 case alopecia, 50 cases of bacterial infection and 40 cases of wound. Conclusion: The present study shows the fungal diseases were common causes for skin diseases in Cats follow by Bacterial, Parasitic and Alopecia respectively.Keywords: Cat infection; Skin diseases in cat; Scabies; Fungal disease

Comparison of the full-length sequence and sub-regions of 16S rRNA gene for skin microbiome profiling.

The skin microbiome plays a pivotal role in human health by providing protective and functional benefits. Furthermore, its inherent stability and individual specificity present novel forensic applications. These aspects have sparked considerable research enthusiasm among scholars across various fields. However, the selection of specific 16S rRNA hypervariable regions for skin microbiome studies is not standardized and should be validated through extensive research tailored to different research objectives and targeted bacterial taxa. Notably, third-generation sequencing (TGS) technology leverages the full discriminatory power of the 16S gene and enables more detailed and accurate microbial community analyses. Here, we conducted full-length 16S sequencing of 141 skin microbiota samples from multiple human anatomical sites using the PacBio platform. Based on this data, we generated derived 16S sub-region data through an in silico experiment. Comparisons between the 16S full-length and the derived variable region data revealed that the former can provide superior taxonomic resolution. However, even with full 16S gene sequencing, limitations arise in achieving 100% taxonomic resolution at the species level for skin samples. Additionally, the capability to resolve high-abundance bacteria (TOP30) at the genus level remains generally consistent across different 16S variable regions. Furthermore, the V1-V3 region offers a resolution comparable with that of full-length 16S sequences, in comparison to other hypervariable regions studied. In summary, while acknowledging the benefits of full-length 16S gene analysis, we propose the targeting of specific sub-regions as a practical choice for skin microbial research, especially when balancing the accuracy of taxonomic classification with limited sequencing resources, such as the availability of only short-read sequencing or insufficient DNA.IMPORTANCESkin acts as the primary barrier to human health. Considering the different microenvironments, microbial research should be conducted separately for different skin regions. Third-generation sequencing (TGS) technology can make full use of the discriminatory power of the full-length 16S gene. However, 16S sub-regions are widely used, particularly when faced with limited sequencing resources including the availability of only short-read sequencing and insufficient DNA. Comparing the 16S full-length and the derived variable region data from five different human skin sites, we confirmed the superiority of the V1-V3 region in skin microbiota analysis. We propose the targeting of specific sub-regions as a practical choice for microbial research.

Skin locations inference and body fluid identification from skin microbial patterns for forensic applications

Given that microbiological analysis can be an alternative method that overcomes the shortcomings of traditional forensic technology, and skin samples may be the most common source of cases, the analysis of skin microbiome was investigated in this study. High-throughput sequencing targeting the V3-V4 region of 16S rRNA gene was performed to reveal the skin microbiome of healthy individuals in Guangdong Han. The bacterial diversity of the palm, navel, groin and plantar of the same individual was analyzed. The overall classification based on 16S rRNA gene amplicons revealed that the microbial composition of skin samples from different anatomical parts was different, and the dominant bacterial genus of the navel, plantar, groin and palm skin were dominated by Cutibacterium, Staphylococcus, Corynebacterium and Staphylococcus, respectively. PCoA analysis showed that the skin at these four anatomical locations could only be grouped into three clusters. A predictive model based on random forest algorithm showed the potential to accurately distinguish these four anatomical locations, which indicated that specific bacteria with low abundance were the key taxa. In addition, the skin microbiome in this study is significantly different from the dominant microbiome in saliva and vaginal secretions identified in our previous study, and can be distinguished from these two tissue fluids. In conclusion, the present findings on the community and microbial structure details of the human skin may reveal its potential application value in assessing the location of skin samples and the type of body fluids in forensic medicine.

Topical naltrexone potentiates cutaneous wound healing in blackbelt cichlids (Vieja maculicauda).

To evaluate the effects of topical naltrexone on wound healing in freshwater fish. 25 blackbelt cichlids (Vieja maculicauda). A randomized, controlled, experimental trial was performed, with each individual serving as its own control. Bilateral 6-mm periepaxial cutaneous wounds were created in the body-wall skin of each fish under anesthesia. Three treatment groups were as follows: topical 0.04% naltrexone in administration vehicle (iLEX ointment; iLEX Health Products) at day 0 only (n = 10), topical 0.04% naltrexone in iLEX every 72 to 96 hours (n = 10), or iLEX only every 72 to 96 hours (n = 5) for 10 total treatments. The contralateral wound was left untreated as a control. Fish were maintained in a common enclosure at 24.7 to 25.4 °C for 35 days. Macroscopic wound assessment and image collection were performed every 72 to 96 hours. On day 35, fish were humanely euthanized, and skin samples were collected for histopathology. Time to complete visual resolution of wound healing was faster (P = .002) in wounds treated every 72 to 96 hours with topical 0.04% naltrexone in iLEX (day 19.4) compared to untreated wounds (day 23.3). An interaction between treatment and day was observed (P = .002), with fish treated with 0.04% naltrexone in iLEX every 72 to 96 hours having reduced (P < .05) wound area compared to both controls and fish treated with topical 0.04% naltrexone in iLEX once. No significant differences were noted in histologic sections of wound sites examined at day 35. Fish improved earlier postsurgery and time to complete wound resolution was faster in wounds treated with topical 0.04% naltrexone in iLEX every 72 to 96 hours.

Melanoma Detection and Classification using Deep Learning

Melanoma is a type of carcinoma with a notably high mortality rate. Accurate diagnosis of this aggressive cancer is crucial due to its severe implications. Key diagnostic indicators include asymmetrical shape, heterogeneous color, diameter greater than 6 mm, and irregular borders, which dermatologists typically identify through visual examination. The conventional method for carcinoma detection is biopsy, involving the removal or scraping of skin samples for extensive laboratory testing. This process is both painful and time- consuming. To improve patient experience and enhance diagnostic efficiency, computer-based detection using image processing techniques and deep learning algorithms, specifically Convolutional Neural Networks (CNNs), has been developed to accurately identify melanoma. Keywords: Deep learning, CNN, Computer- based detection

An integrated bioinformatics approach for unravelling the molecular insights into psoriasis pathology and therapeutics

Psoriasis is a chronic relapsing inflammatory disease of the skin that affects almost 2–3 % population worldwide. The current treatment strategies include palliative therapeutics targeting the inflammatory pathways that do not completely cure the lesioned skin. The molecular cues in the hyper-proliferative and aberrantly differentiated keratinocytes of the psoriatic lesioned skin remain unknown. Through an integrative in-silico approach, we have analyzed human psoriatic skin samples from 3 RNA-Seq and 3 microarray datasets to identify 340 differentially expressed genes (DEGs). Further, these DEGs were analyzed using gene ontology enrichment, KEGG pathways, and protein-protein interaction networks for their role in disease pathology and the identification of hub genes. The expression of the hub genes was validated in a preclinical murine model of psoriasiform dermatitis. Finally, the ten hub genes were assessed for their drugability, which revealed 74 drugs targeting 7 hub genes (CCNA2, TOP2A, BIRC5, RRM2, CDK1, AURKA, and CCNB1) that can be repurposed for psoriasis treatment. This study provides an understanding of psoriasis pathophysiology and suggests key molecular biomarkers as therapeutic targets for effective mitigation of the disease.

Analysis of granulysin expression in vitiligo and halo-nevus

Vitiligo and halo nevus are immune-mediated skin diseases that have a similar pathogenesis and involve cellular cytotoxicity mechanisms that are not yet fully understood. In this study, we investigated the expression patterns of the cytolytic molecule granulysin (GNLY) in different cytotoxic cells in skin samples of vitiligo and halo nevus. Skin biopsies were taken from perilesional and lesional skin of ten vitiligo patients, eight patients with halo nevus and ten healthy controls. We analysed the expression of GNLY by immunohistochemistry in CD8+ and CD56+ NK cells. A significantly higher accumulation of GNLY+, CD8+ GNLY+ and fewer CD56+ GNLY+ cells was found in the lesional skin of vitiligo and halo nevus than in the healthy skin. These cells were localised in the basal epidermis and papillary dermis, suggesting that GNLY may be involved in the immune response against melanocytes. Similarly, but to a lesser extent, upregulation of GNLY+ and CD8+ GNLY+ cells was observed in the perilesional skin of vitiligo and halo nevus compared to healthy controls. In this study, we demonstrated for the first time an increased expression of CD8+ GNLY+ T lymphocytes and CD56+ GNLY+ NK cells in lesions of vitiligo and halo nevus, indicating the role of GNLY in the pathogenesis of both diseases.

Evaluation of Infected and Non-infected Wounds Healing Activity of Eriosema robustum Hydroethanolic Leaves Extract Ointments in Streptozotocin Induced Diabetic Rats

Untreated diabetic wounds provide an optimal environment for bacterial growth, which, over time, can develop resistance to common antibiotics and ultimately result in amputation. Therefore, it is necessary to search for new sources of antimicrobial molecules with wound healing activity owing to the presence of different secondary metabolites in medicinal plants. Aims: This study was to evaluate the in vivo antibacterial and diabetic wound healing capabilities of 70° hydroethanolic extract of Eriosema robustum leaves on non-infected and infected diabetic wound. Methodology: To do this, obese albino Wistar male rats (200–280 g) were divided into eleven groups and were made diabetic by intraperitoneal injection with a low dose of streptozotocin at 45 mg/kg of body weight. An excision wound with a surface area of 314 mm2 was created on the dorsal area of each animal, except in the uninjured diabetic group (UDG). The 70° hydroethanolic extract was used to prepare 1%, 5%, and 10% ointments, with L-Mesitran serving as the reference ointment. Healing potential was assessed by measuring wound contraction rates and determining serum and tissue hydroxyproline, serum lactate deydrogenase (LDH) and total protein levels (TP). The antibacterial power evaluated in vivo of Eriosema robustum leaves was also assessed by culturing the skin after healing. Results: The results demonstrated a significantly faster healing rate in the non-infected groups (5%,10% and L-Mesitran) compared to the infected groups. The levels of tissue hydroxyproline and total proteins were significantly (p &lt; 0.05) elevated in all treated groups compared to infected and negative controls, unlike serum hydroxyproline levels. LDH levels were significantly (p &lt; 0.05) elevated in both negative control group compared to the treated groups. The culture of different skin samples on previously injured areas on the 20th day of treatment showed no growth of S. aureus on completely healed areas and a low rate in the groups treated during the healing process. Conclusion: 70° Hydroethanolic leaves extract of Eriosema robustum possess in vivoantibacterial activities and diabetic wound healing potential.

Analysis of the Skin and Brain Transcriptome of Normally Pigmented and Pseudo-Albino Southern Flounder (Paralichthys lethostigma) Juveniles to Study the Molecular Mechanisms of Hypopigmentation and Its Implications for Species Survival in the Natural Environment.

Southern flounder skin pigmentation is a critical phenotypic characteristic for this species' survival in the natural environment. Normal pigmentation allows rapid changes of color for concealment to capture prey and UV light protection. In contrast, highly visible hypopigmented pseudo-albinos exhibit a compromised immune system and are vulnerable to predation, sensitive to UV exposure, and likely have poor survival in the wild. Skin and brain tissue samples from normally pigmented and hypopigmented individuals were analyzed with next-generation RNA sequencing. A total of 1,589,613 transcripts were used to identify 952,825 genes to assemble a de novo transcriptome, with 99.43% of genes mapped to the assembly. Differential gene expression and gene enrichment analysis of contrasting tissues and phenotypes revealed that pseudo-albino individuals appeared more susceptible to environmental stress, UV light exposure, hypoxia, and osmotic stress. The pseudo-albinos' restricted immune response showed upregulated genes linked to cancer development, signaling and response, skin tissue formation, regeneration, and healing. The data indicate that a modified skin collagen structure likely affects melanocyte differentiation and distribution, generating the pseudo-albino phenotype. In addition, the comparison of the brain transcriptome revealed changes in myelination and melanocyte stem cell activity, which may indicate modified brain function, reduced melanocyte migration, and impaired vision.

Integrative Analysis of Lactylome and Proteome of Hypertrophic Scar To Identify Pathways or Proteins Associated with Disease Development.

Lactylation (Kla), a recently discovered post-translational modification derived from lactate, plays crucial roles in various cellular processes. However, the specific influence of lactylation on the biological processes underlying hypertrophic scar formation remains unclear. In this study, we present a comprehensive profiling of the lactylome and proteome in both hypertrophic scars and adjacent normal skin tissues. A total of 1023 Kla sites originating from 338 nonhistone proteins were identified based on lactylome analysis. Proteome analysis in hypertrophic scar and adjacent skin samples revealed the identification of 2008 proteins. It is worth noting that Kla exhibits a preference for genes associated with ribosome function as well as glycolysis/gluconeogenesis in both normal skin and hypertrophic scar tissues. Furthermore, the functional enrichment analysis demonstrated that differentially lactyled proteins are primarily involved in proteoglycans, HIF-1, and AMPK signaling pathways. The combined analysis of the lactylome and proteome data highlighted a significant upregulation of 14 lactylation sites in hypertrophic scar tissues. Overall, our investigation unveiled the significant involvement of protein lactylation in the regulation of ribosome function as well as glycolysis/gluconeogenesis, potentially contributing to the formation of hypertrophic scars.

Biomechanical and biochemical changes in murine skin during development and aging

Aging leads to biochemical and biomechanical changes in skin, with biological and functional consequences. Despite extensive literature on skin aging, there is a lack of studies which investigate the maturation of the tissue and connect the microscopic changes in the skin to its macroscopic biomechanical behavior as it evolves over time. The present work addresses this knowledge gap using multiscale characterization of skin in a murine model considering newborn, adult and aged mice. Monotonic uniaxial loading, tension relaxation with change of bath, and loading to failure tests were performed on murine skin samples from different age groups, complemented by inflation experiments and atomic force microscopy indentation measurements. In parallel, skin samples were characterized using histological and biochemical techniques to assess tissue morphology, collagen organization, as well as collagen content and cross-linking. We show that 1-week-old skin differs across nearly all measured parameters from adult skin, showing reduced strain stiffening and tensile strength, a thinner dermis, lower collagen content and altered crosslinking patterns. Surprisingly, adult and aged skin were similar across most biomechanical parameters in the physiologic loading range, while aged skin had lower tensile strength and lower stiffening behavior at large force values. This correlates with altered collagen content and cross-links. Based on a computational model, differences in mechanocoupled stimuli in the skin of the different age groups were calculated, pointing to a potential biological significance of the age-induced biomechanical changes in regulating the local biophysical environment of dermal cells. Statement of significanceSkin microstructure and the emerging mechanical properties change with age, leading to biological, functional and health-related consequences. Despite extensive literature on skin aging, only very limited quantitative data are available on microstructural changes and the corresponding macroscopic biomechanical behavior as they evolve over time. This work provides a wide-range multiscale mechanical characterization of skin of newborn, adult and aged mice, and quantifies microstructural correlations in tissue morphology, collagen content, organization and cross-linking. Remarkably, aged skin retained normal hydration and normal biomechanical function in the physiological loading range but showed significantly reduced properties at super-physiological loading. Our data show that age-related microstructural differences have a profound effect not only on tissue-level properties but also on the cell-level biophysical environment.

Shh Gene Regulates the Proliferation and Apoptosis of Dermal Papilla Cells to Affect Its Differential Expression in Secondary Hair Follicle Growth Cycle of Cashmere Goats.

Sonic hedgehog (Shh) is a component of the Hedgehog signaling pathway, playing an important role in regulating cell proliferation, differentiation, apoptosis, and the repair of damaged organisms. To further clarify the expression pattern of Shh gene in the secondary hair follicle growth cycle of cashmere goats and its mechanism of action on secondary hair follicle papilla cells, and improve cashmere quality, in this study, we took Inner Mongolia Albas white cashmere goats as the research objects and collected skin samples at different growth stages to obtain secondary hair follicles, detected Shh and its gene expression by RT-qPCR, Western blot, immunohistochemistry, and other techniques, while we also cultured DPCs in vitro. Shh gene overexpression and interference vectors were constructed, and the effects of Shh gene on the proliferation and apoptosis of DPCs were studied through cell transfection technology. The results showed that there are significant differences in Shh and its gene expression in the secondary hair follicle growth cycle skins of cashmere goats, with the highest expression level in anagen, followed by catagen, and the lowest expression level in telogen. Shh was mainly expressed in the inner root sheath, outer root sheath, and secondary hair follicle papilla. After the overexpression of Shh gene, the proliferation and vitality of the hair papilla cells were enhanced compared to the interference group. After Shh gene interference, the apoptosis rate of the cells increased, indicating that Shh gene can regulate downstream Ptch, Smo, and Gli2 gene expression to promote the proliferation of DPCs, and thus form its expression pattern in the secondary hair follicle growth cycle of cashmere goats.