Skin Tissue Research Articles

Role of spexin and DARS2 as potential biomarkers in basal cell carcinoma and cutaneous malignant melanoma diagnosis, and as therapeutic targets.

Basal cell carcinoma (BCC) is a slowly progressive, locally aggressive and rarely metastasizing cancer, and although its mortality is low, its morbidity and cost of disease are high. While BCC is more common, cutaneous malignant melanoma (CMM) is significant due to its higher mortality rate. These patients can be treated, but recurrence, metastasis and mortality may occur in such patients. Various environmental, phenotypic and genotypic factors, especially ultraviolet (UV) radiations, play a role in the etiology of BCC and CMM. Histopathological examination continues to be the "gold standard" in their diagnosis. Spexin (SPX) and DARS2 are newly discovered proteins linked to many diseases, including cancer. These proteins may have an effect on the development and expression of skin cancers such as BCC and CMM. In this study, we evaluated the potential of SPX and DARS2 expressions as immunohistochemical biomarkers in the differential diagnosis of BCC and CMM. This study was conducted retrospectively using samples taken from the pathology laboratory. A total of 180 patient samples were used. The control group consisted of healthy skin tissues of the patients, and the other groups consisted of BCC and CMM tissues of the same patients. Tissue samples of all three groups were evaluated immunohistochemically with SPX and DARS2. The immunoreactivity of SPX was found to be higher in BCC and CMM tissue samples than in healthy skin tissues in the control group. DARS2 immunoreactivity was found to be higher in CMM tissues compared to the other two groups, and statistically significant in BCC tissues when compared with healthy control group tissues. SPX can be used as an immunohistochemical biomarker in the diagnosis of BCC and CMM. Since DARS2 expression is statistically more significant in CMM tissues than in BCC tissues, it can be used in differential diagnosis.

Validation of MEWS, NEWS, NEWS-2 and qSOFA for different infection foci at the emergency department, the acutelines cohort.

Sepsis is a leading cause of morbidity and mortality globally. The lack of specific prognostic markers necessitates tools for early risk identification in patients with suspected infections in emergency department (ED). This study evaluates the prognostic accuracy of various Early Warning Scores (EWS)-MEWS, NEWS, NEWS-2, and qSOFA-for in-hospital mortality, 30-day mortality, and ICU admission, considering the site of infection. A retrospective analysis was conducted using data from the Acutelines cohort, which included data collected from patients admitted to the University Medical Centre Groningen ED between September 2020 and July 2023. Patients were included if they had an ICD-10 code for infection. EWS were calculated using clinical data within 8h post-admission. Predictive performance was assessed using AUC-ROC, calibration by the Hosmer-Lemeshow test and calibration curves, and operative characteristics like sensitivity and specificity. A total of 1661 patients were analyzed, with infections distributed as follows: lower respiratory tract (32.9%), urinary tract (30.7%), abdominal (12.5%), skin and soft tissue (9.5%), and others (8.2%). The overall in-hospital mortality was 6.7%, and ICU admission was 7.1%. The highest AUC-ROC for in-hospital mortality prediction was observed with NEWS and NEWS-2 in abdominal infections (0.86), while the lowest was for qSOFA in skin and soft tissue infections (0.57). Predictive performance varied by infection site. The study highlights the variability in EWS performance based on infection site, emphasizing the need to consider the source of infection in EWS development for sepsis prognosis. Tailored or hybrid models may enhance predictive accuracy, balancing simplicity and specificity.

Application of Modified Skin Stretching for Soft Tissue Defect Reconstruction in the Ankle and Foot: A Retrospective Report.

The failure rate of foot and ankle soft tissue defect reconstruction with flap is relatively high, often posing a significant burden on patients. The aim of this study is to explore the effectiveness of repeated stretch sutures in repairing skin and soft tissue defects of the ankle and foot. Twenty-three patients with ankle and foot skin and soft tissue defects were retrospectively analyzed between February 2016 and February 2019. Sutures were repeatedly stretched every 3-5 days. Local skin grafting was performed if necessary after wound surfaces disappeared or exposed tendons and bones were covered by soft tissue. Wound healing time, postoperative healing area, Vancouver Scar Assessment Scale, sensation, and function of the new skin were evaluated. Healing time was 17-35 (24.43 ± 5.29) days. Ten patients wholly healed, and 13 healed by approximately 70.08% ± 6.59%. The Vancouver Scar Assessment Scale average score was 2.83 ± 1.19 points, of which 15 cases were excellent (0-3 points) and 8 cases were good (4-7 points). The sensation and function of the new skin after repair were equivalent to those of normal skin after the last follow-up. Applying repeated tension sutures on the skin and soft defects of the ankle and foot reduced the skin graft area and decreased complex high-risk surgical flaps' use and transplantation area.

Opportunities and Challenges of Application of Cytosorb Therapy in Sepsis Management

Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. In 2017, an estimated 48·9 million incident cases of sepsis were recorded worldwide, and 11·0 million sepsis-related deaths were reported, representing 19·7% of all global deaths.1 Though overall data related to sepsis is poor but it is also a major health care challenge for resource limited countries. Severe sepsis is a significant & common health problem in ICU patients of Bangladesh2. A continuum of severity from sepsis to septic shock and multi-organ dysfunction syndrome (MODS) exists. MODS is a clinical syndrome characterized by the development of progressive and potentially reversible physiologic dysfunction in 2 or more organs or organ systems that is induced by a variety of acute insults, including sepsis. Sepsis leads to malignant intravascular inflammation, coagulopathy, circulatory derangement, tissue hypoxia, cytotoxicity and apoptosis. As a result, dysfunction of vital organ systems occur. Host response and other factors influenc outcome. Patients with sepsis must be treated with-timely, appropriate antibiotics, intravenousfluids, vasopressor and inotropic support & oxygen therapy.3 Other additional treatments including extracorporeal blood purification techniques (BPT). These techniques include hemofiltration, hemoperfusion, intermittent or continuous high-volume hemofiltration (HVHF), plasmapheresis or adsorption.4 The rationale behind such an approach is to achieve “immune homeostasis” which theoretically reduces the potential damage caused by dysregulation of the host response to infection. Given the pivotal role of cytokine production in sepsis, it follows that removal of these substances, through such BPT, may attenuate the response particularly in the early phase of sepsis.5 Indications include 1) Rhabdomyolysis resulting from Reperfusion syndrome, Trauma, Malignant Hyperthermia. 2) External injuries including Sepsis/Septic shock, Hemorrhagic shock, Trauma, Ruptured aortic aneurysm, Post-Cardiac Arrest Syndrome, Cardio-pulmonary resuscitation, Extensive surgery, Organ transplantation, Cardiosurgical intervention, Severe skin and soft tissue damage, Burns, Necrotizing fasciitis, Post-Cardiotomy Syndrome, Acute Respiratory Distress Syndrome. 3) Diseases: Pancreatitis, Liver insufficiency, Renal insufficiency, Stroke, Myocardial infarction, Cardiogenic shock/Heart failure, Tumor Lysis Syndrome, Hemophagocytosis Syndrome. Liver failure/Hyperbilirubinemia bridging to transplant or to recovery, Life-threatening bleeding under Direct Oral Anticoagulants (DOAC)6. Bangladesh Crit Care J September 2024; 12 (2): 79-80

New therapeutic approaches for S.aureus infections treatment

Staphylococcus aureus (S. aureus) is an opportunistic pathogen that causes a range of diseases, from mild skin and soft tissue infections and food poisoning to serious conditions such as pneumonia, endocarditis, sepsis, and hospital-acquired infections. Due to the aggressive nature of the disease, limitations of existing treatments, and the spread of antibiotic-resistant strains, the development of alternative strategies to combat bacterial infections has progressed faster than the development of new antibiotics. In this review, we analyze the epidemiological situation of morbidity and mortality associated with S. aureus infection, as well as antimicrobial resistance of this organism on a global scale. We reviewed the pathogenesis and virulent factors of S. aureus, their mechanisms of antibiotic resistance, and the importance of diagnosing staphylococcal infections to ensure timely intervention. This review also discusses the latest approaches to combating antibiotic resistance in Staphylococcus aureus, including preventive and therapeutic antimicrobial strategies. Such methods as the use of bacteriophages in treatment, antimicrobial peptides, probiotic microorganisms and their metabolites, and the use of inhibitors to suppress bacterial communication are considered.

Population pharmacokinetics/pharmacodynamics of minocycline plus rifampicin in patients with complicated skin and skin structure infections caused by MRSA.

The population pharmacokinetics/pharmacodynamics (PK/PD) of minocycline, rifampicin and linezolid in patients with complicated skin and soft tissue infections (cSSTIs) caused by MRSA are described. Samples were collected in a Phase 4 study of oral minocycline plus rifampicin versus linezolid showing minocycline plus rifampicin to be non-inferior to linezolid. Antibiotics were assayed by HPLC or LC-MS, and a population PK model was developed using Pmetrics. The association between PK/PD indices and patient outcomes was explored. A three-compartment model (with an absorption compartment) with first-order input and elimination best described the data for the three drugs. No covariates were included in the final model. The population median values (95% credibility limits) of the clearance and volume of distribution were 7.412 L/h (5.121-8.361) and 14.155 L (6.799-33.901) for minocycline, 5.683 L/h (3.703-7.726) and 7.736 L (6.031-8.948) for rifampicin, and 1.970 L/h (1.326-2.499) and 20.169 L (12.857-32.629) for linezolid, respectively. Maximum a posteriori probability-Bayesian estimation plots of observed versus predicted had a slope of 0.999 r20.967 for minocycline, slope 0.998 r20.769 for rifampicin and slope 0.998 r20.895 for linezolid. PK/PD indices were not related to clinical outcome. Taking a translational minocycline fAUC24h/MIC target of >0.5 for minocycline in the presence of rifampicin, 96% (49/51) of patients reached the target. Population PK models of minocycline, rifampicin and linezolid were developed in patients with MRSA cSSTI and almost all patients reached the predefined PD index targets. As a result, neither AUC, MIC nor the AUC/MIC ratio could be related to clinical outcome.

Glioblastoma multiforme recurrence on skin and subcutaneous tissue: a case report

Glioblastoma multiforme (GBM) is the most common malignant primary central nervous system (CNS) tumor. It presents an aggressive pattern, with a tendency for intracranial progression despite optimal treatment. On the other hand, metastases and manifestations outside the CNS are exceptional, and very few cases have been described. The authors submitted a case of a 48-year-old male diagnosed with a left parietooccipital GBM isocitrate dehydrogenase (IDH) wild-type, non-methylated O6-methylguanine-DNA methyltransferase (MGMT). Six months after surgical treatment, followed by a chemotherapy (CT) and radiotherapy scheme, he developed a few subcutaneous erythematous nodules within the surgical scar. A punch biopsy confirmed the histopathology of GBM. The CT scan showed concomitant intracranial progression. We ruled out systemic metastases. As the performance status was good [Karnofsky Performance Status 90 (KPS 90)] and the subcutaneous implants were growing rapidly, limiting the quality of life, we decided to perform palliative surgery to remove the implants. The result was good. Unfortunately, the patient worsened during the following week, after ruling out medical complications, we attributed the worsening to cerebral tumor swelling, revealed in the CT scan, as unresponsive to steroids. He passed away a few days later. Based on the analysis of our case, we intend to provide useful information for the approach to this peculiar manifestation of GBM.

Spatial proteomics identifies JAKi as treatment for a lethal skin disease.

Toxic epidermal necrolysis (TEN) is a fatal drug-induced skin reaction triggered by common medications and is an emerging public health issue1-3. Patients with TEN undergo severe and sudden epidermal detachment caused by keratinocyte cell death. Although molecular mechanisms that drive keratinocyte cell death have been proposed, the main drivers remain unknown, and there is no effective therapy for TEN4-6. Here, to systematically map molecular changes that are associated with TEN and identify potential druggable targets, we utilized deep visual proteomics, which provides single-cell-based, cell-type-resolution proteomics7,8. We analysed formalin-fixed, paraffin-embedded archived skin tissue biopsies of three types of cutaneous drug reactions with varying severity and quantified more than 5,000 proteins in keratinocytes and skin-infiltrating immune cells. This revealed a marked enrichment of type I and type II interferon signatures in the immune cell and keratinocyte compartment of patients with TEN, as well as phosphorylated STAT1 activation. Targeted inhibition with the pan-JAK inhibitor tofacitinib in vitro reduced keratinocyte-directed cytotoxicity. In vivo oral administration of tofacitinib, baricitinib or the JAK1-specific inhibitors abrocitinib or upadacitinib ameliorated clinical and histological disease severity in two distinct mouse models of TEN. Crucially, treatment with JAK inhibitors (JAKi) was safe and associated with rapid cutaneous re-epithelialization and recovery in seven patients with TEN. This study uncovers the JAK/STAT and interferon signalling pathways as key pathogenic drivers of TEN and demonstrates the potential of targeted JAKi as a curative therapy.

Bioengineered skin-substitutes incorporating rete-ridges using a bioprinting process

Abstract Bioprinting is a widely used technique for creating three-dimensional, complex, and heterogeneous artificial tissue constructs that are biologically and biophysically similar to natural tissues. The skin is composed of several layers including the epidermis, basement membrane (BM), and dermis. However, the unique undulating structure of basement membranes (i.e., rete ridges) and the function of BM have not been extensively studied in the fabrication of engineered skin substitutes. In this study, a novel engineered skin substitute incorporating an artificially designed rete ridge (i.e., mogul-shape) was developed using bioprinting and bioinks prepared using collagen and fibrinogen. To mimic the structure of the rete ridges of skin tissue, we developed a modified bioprinting technique, controlling rheological property of bioink to create a mogul-shaped layer. In vitro cellular activities, including the expression of specific genes (those encoding vimentin, laminin-5, collagen IV, and cytokeratins), demonstrated that the engineered skin substitute exhibited more potent cellular responses than the normally bioprinted control owing to the favorable biophysical BM structure and the bioink microenvironment. Additionally, the feasibility of utilizing the bioprinted skin-structure was evaluated in a mouse model, and in vivo results demonstrated that the bioprinted skin substitutes effectively promoted wound healing capabilities. Based on these results, we suggest that bioprinted skin tissues and the bioprinting technique for mimicking rete ridges can be used not only as potential lab-chip models for testing cosmetic materials and drugs, but also as complex physiological models for understanding human skin.

Efficacy and Potential Mechanisms of Naringin in Atopic Dermatitis

Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin diseases. Topical treatments are recommended for all patients regardless of severity, making it essential to develop an effective topical AD treatment with minimal side effects; We investigated the efficacy of topical application of naringin in AD and explored the possible mechanisms using an AD mouse model induced by 1-chloro-2,4-dinitrobenzene (DNCB). Clinical, histological, and immunological changes related to AD and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling proteins in the skin tissues were measured as outcomes; Naringin treatment resulted in a significant improvement in dermatitis severity score and reduced epidermal thickness and mast cell count in the skin (p < 0.05). Naringin also demonstrated the ability to inhibit DNCB-induced changes in interleukin (IL) 4, chemokine (C-C motif) ligand (CCL) 17, CCL22, IL1β, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) levels by quantitative real-time polymerase chain reaction (qRT-PCR) and IL13 by enzyme-linked immunosorbent assay (ELISA) (p < 0.05). Western blot results exhibited the decreased JAK1, JAK2, STAT1, STAT3, phospho-STAT3, and STAT6 expression in the naringin-treated groups (p < 0.05); The findings of this study suggest that topical naringin may effectively improve the symptoms of AD and could be used as a therapeutic agent for AD.

Local Delivery of Ginger Extract via a Nanofibrous Membrane Suppresses Human Skin Melanoma B16F10 Cells Growth via Targeting Ras/ERK and PI3K/AKT Signaling Pathways: An In vitro Study.

Metastatic melanoma poses a significant threat globally, with a distressingly low ten-year survival rate of only 10%. While FDA-approved treatments such as dacarbazine and high-dose IL-2 have been employed in clinical settings, their limitations underscore the urgent need for more effective therapies. This study aimed to develop a potential anticancer local treatment through the extraction of various amounts of ginger extract loaded unto Poly(vinyl alcohol) (PVA) nanofibers. The anticancer activity of the produced membranes was studied on human skin melanoma B16F10 cells. Other in vitro experiments such as cell migration assay, cell proliferation assay, cell viability assay, scanning electron microscopy assay, real-time PCR assay, and ant-inflammatory assay were performed for the in vitro characterization of the delivery system. Tissue toxicity of the developed patches was studied in a rat model. The study showed that scaffolds loaded with 2%, 4%, 6%, 8%, and 0% of ginger extract had around 784.98 ± 202.31 nm, 771.86 ± 219.07 nm, 820.65 ± 242.43 nm, 785.19 ± 203.99 nm, and 671.29 ± 184.09 nm of mean fiber size, respectively. The ginger extract-loaded membranes suppressed the growth and migration activity of human skin melanoma B16F10 cells in a dose and time-dependent manner. Real-time PCR assay showed that the developed membranes modulated the expression levels of Ras/ERK and PI3K/AKT signaling pathways. Animal study results showed that our developed patches were not toxic against liver or skin tissues. Ginger extract-loaded PVA nanofibers exhibited promising anticancer potential against melanoma cells, suggesting a viable localized treatment option.

Quercetin ameliorates lupus symptoms by promoting the apoptosis of senescent Tfh cells via the Bcl-2 pathway

Systemic lupus erythematosus (SLE) is an autoimmune disorder that commonly affects the skin, kidneys, joints, and various other systemic tissues, with its development intricately linked to the process of immunosenescence. Quercetin (QC), a phytochemical that occurs naturally, demonstrates many different biological capabilities, such as antibacterial, antioxidant, and anti-inflammatory activities. Our investigation found that QC effectively reduced kidney damage and relieved mesenteric lymph nodes (mLNs) swelling in MRL/lpr lupus mice. Moreover, QC has been found to decrease the number of senescent follicular helper T (Tfh) cells, a pivotal kind of T cells that contribute to the progression of SLE. In vitro, QC exhibited the capacity to modulate mRNA expression levels, with the downregulation of IL-6, IL21-AS1, IL-27, BCL6, and BCL2L12, and the upregulation of FOXP1 and BIM. This modulation resulted in the suppression of Tfh cells differentiation and the enhancement of apoptosis in senescent CD4+ T cells. In addition, the HuProtTM Human Proteome Microarray revealed that QC can directly bind to BCL-2 protein and therefore promote the apoptosis of senescent CD4+ T cell. As a result, our investigative elucidate the potent inhibitory action of QC on the ontogeny of Tfh cells, along with its capacity to abrogate the immunosenescent phenotype. This positions QC as a promising therapeutic strategy for treating SLE.

Suppurative Granulomatous Osteomyelitis with Microcystic Changes Due to Mycobacterium chelonae- abscessus Complex

Abstract Introduction/Objective Mycobacterium chelonae and Mycobacterium abscessus are rapidly growing non-tuberculous mycobacterium found in soil and water, and represent rare causes of skin and soft tissue infection. Treatment typically involves an extended course of antimicrobial therapy and occasionally surgical debridement. Previous reports have described a distinctive pattern of suppurative granulomatous inflammation with microcystic changes in skin biopsies; however, the morphologic changes of M. chelonae-abscessus complex as a cause of osteomyelitis have not been well-documented in the literature. Methods/Case Report We searched our database from 2013 to 2024 for bone samples diagnosed as granulomatous inflammation in which M. chelonae or M. abscessus were identified on concurrent microbiology studies. Patient demographics, risk factors for infection, and treatment data were collected. Results (if a Case Study enter NA) Three patients with culture- or PCR-confirmed M. chelonae (2) or M. abscessus (1) were identified. All infections involved bones of the distal extremities. Patients were 57 years and older with risk factors for infection that included: diabetes (1), intravenous drug use (1), and long-term immunosuppressive therapy (1). All patients presented with osteomyelitis refractory to antibiotic therapy for which bone biopsy, bone resection, or amputation was performed. All cases showed suppurative granulomatous inflammation with microcystic changes. Cystic spaces were markedly enriched for acid-fast bacilli on Fite and/or Ziehl-Neelsen stains. In two patients, the antimicrobial regimen was changed as a result of the pathologic findings and microbiologic testing that provided additional information about speciation and susceptibilities. Conclusion Suppurative granulomatous inflammation has a broad differential that includes blastomycosis, sporotrichosis, cat scratch disease, non-tuberculous mycobacterial infection, and granulomatosis with polyangiitis, for which there are substantial treatment differences. When this pattern of microcystic suppurative granulomatous inflammation is encountered, it is important to perform special stains for acid-fast bacilli, particularly when seen in distal extremity lesions from patients with infections that are refractory to empiric antibiotic therapy.

An idiosyncratic reaction to the synthetic biologic membrane on a surgical wound

Abstract Introduction/Objective Biodegradable temporizing matrix (BTM) is a synthetic polymer used to temporarily close wounds and aid the body in generating new tissue. BTM is applied to a debrided wound.BTM acts as a scaffold aiding the migration of granulation tissue into the matrix. Once the tissue is fully integrated throughout the BTM, the sealing membrane is removed. The matrix slowly deteriorates until fully absorbed at approximately 18 weeks. Methods/Case Report An 80-year-old woman with a past medical history of eczema, rheumatoid arthritis and gout presented with swelling of the left third metatarsal. Imaging showed an abscess which was eventually drained and cultured to show mycobacterium chelone. The patient was started on antibiotics for mycobacterium. On follow up she reported a nodule on left forearm recently increased in size. MRI on 9/28 showed abscess of the dorsal aspect of phalanx. She underwent surgical debridement 10/31 on her finger and the forearm nodule. After debridement a polynovo BTM graft was placed. Histopathology showed skin and subcutaneous tissue with necrotizing granulomas of the finger and the forearm. Cultures and stains for mycobacterium returned negative.The patient was subsequently followed up for wound healing. She reported nodules on the left forearm at the scar from previous surgical site which were biopsied. Histopathology showed granulomatous inflammation, rare foreign body giant cells, and birefringent material. The stains for Ziehl-Neelsen, Fite and Gomori’s Methenamine Silver for Urate Crystals were all negative excluding the possibility of gouty tophi or mycobacterium. Results (if a Case Study enter NA) NA Conclusion The complex history of the patient with mycobacterium, gout, the giant cell reaction and the unique appearing birefringent crystals presented a puzzling problem. Given the negative stain results for mycobacteria and the presence of birefringent (foreign) material, we deem these granulomas most likely an idiosyncratic reaction to the synthetic biologic membrane applied during her prior procedure. There are no known cases of giant cell reaction and similar morphology of birefringent (foreign) material in literature.

Pre-expanded Local Flaps: Optimal Choice for Repairing Defects Following Extensive Benign Tumor Resection in the Head and Face.

Treating extensive benign tumors of the head and face presents a longstanding challenge, necessitating efficacy at the lesion site, and postoperative esthetic considerations for the donor area. This study aims to explore the clinical outcomes of pre-expanded local flap reconstruction for extensive benign tumors of the head and face post resection. From March 2018 to March 2023, a total of 18 patients with extensive benign tumors of the head and face were admitted, including 13 cases of nevus, 2 cases of hemangioma, 2 cases of neurofibroma, and 1 case of verruca. Based on the location and size of the lesions, suitable local areas were selected for tissue expansion, and expanders were implanted for regular saline injections over 8 to 16 weeks. After reaching the desired expansion, resection of the head and facial tumors and local flap reconstruction were performed. Postoperatively, data on patients' information, tumor types, tumor area, expansion volume, postexpander complications, vascular condition after flap transfer, and donor site condition were collected. In this series of 18 patients, benign tumors of the head and face were completely repaired through 1 to 2 stages of tissue expansion surgeries. Postimplantation complications included hematoma in 1 case and infections in 2 cases, with one instance of expander infection leading to surgical failure. However, all other patients achieved adequate expansion, successful flap survival post-transfer, and experienced no other complications. Follow-up over 6 to 24 months showed no recurrence at the lesion sites, with flaps maintaining consistent color, texture, and thickness matching surrounding skin tissue. In addition, donor site healing was excellent, with no obvious surgical scars. Pre-expanded local flap reconstruction is an ideal method for repairing extensive benign tumors of the head and face postresection.

The molecular anatomy of cashmere goat hair follicle during cytodifferentiation stage

BackgroundCashmere, named as “soft gold”, derives from the secondary hair follicles (SHFs) of cashmere goat which is vital to Northwest China’s economy. The cytodifferentiation stage (E120), mirroring the complete hair follicle (HF) structure of adult goats and marking a critical phase in SHF development. Therefore, this study aims to enhance the understanding of SHF development and its impact on fiber quality, informing breeding strategies.ResultsFrom the scRNA-seq data analysis, the intricate processes and transcriptional dynamics of inner layer cell differentiation of HFs were unveiled in this study. we identified nine cell populations during cytodifferentiation and key structures such as the hair shaft and inner root sheath. And we discovered three main inner layer lineages and seven subpopulations, clarifying their roles in specialization and signaling. Pseudotime mapping analysis showed cell evolution from early stage to mature stages marked by unique gene expressions, and the intermediate stage on the differentiation of each lineage was revealed. The identification and spatial localization of specific transcription factors, such as GATA3, LEF1 and PRDM1, as well as keratin genes highlight regulatory pathways involved in HF development, which was further validated by immunofluorescence. These findings suggested the potential strategies to improve fiber quality, and the discovery of diverse cell types and their developmental molecular mechanisms, particularly in this species-specific context, offered a nuanced view of the regulatory mechanisms driving HF development in cashmere goats.ConclusionOverall, these findings provide a systematic molecular atlas of skin, defining three major branches and cell states of inner layer cells of HF, and determining how the branch-specific transcription factors, keratins, and signals coordinate HF morphogenesis during cytodifferentiation stage. This research not only advances skin tissue research in goats but also holds broader implications for the understanding of HF regeneration and development across various species.

Immunohistochemical examination of immunoreactivity of transient receptor potential melastatin 2, glutathione peroxidase 4 and spexin in lichen planus.

In this study, we aimed to investigate the potential contributions to the disease by examining the immunoreactivities of SPX in LP-affected skin tissue using immunohistochemical methods, in light of its recent prominence as a molecule related to diabetes mellitus, along with apoptosis and ferroptosis mediated by GPX4 and TRPM2 channels facilitating oxidative stress-induced cell death. This research explored the immunohistochemical expressions of TRPM2, GPX4, and SPX in Lichen Planus (LP) patients compared to healthy individuals. Forty skin samples were collected, split equally between LP patients and healthy controls, excluding those with other conditions. Samples underwent immunohistochemical staining for TRPM2, SPX, and GPX4, using secondary antibodies and chromogens AEC or DAB. Histoscores were calculated based on staining diffusiveness and severity. Statistical analyses were performed with SPSS 22.0, using t-tests and ANOVA, with significance set at p < 0.05. There were no demographic differences between groups (p > 0.05). LP patients showed significantly lower TRPM2 and GPX4 histoscores and higher SPX histoscores compared to controls (TRPM2 and GPX4: p < 0.001, SPX: p < 0.001). Gender and age did not affect histoscores significantly. Findings suggest TRPM2, GPX4, and SPX play roles in LP pathogenesis, indicating a need for further molecular studies to clarify their involvement. This contributes to understanding LP beyond the traditional apoptosis perspective.

Visualizing the transdermal delivery of berberine loaded within chitosan microneedles using mass spectrometry imaging.

Berberine (BR), an alkaloid isolated from theChinese traditional medicine Coptidis rhizoma, exhibits therapeutic effects on several diseases including bacterial infections, diabetes, and hyperlipidemia, but the oral availability is poor. In this work, we prepared the chitosan microneedle array-loaded BR (BR-CS MNAs) to transdermally deliver BR, and the spatial distribution of BR in heterogeneous skin tissues was analyzed and imaged by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Some endogenous phospholipids with specific spatial distribution were used to differentiate the epidermis and dermis regions of the skin. The results showed that BR was effectively delivered and could permeate to both epidermis and dermis regions of the skin. This demonstrated the feasibility of MALDI-MSI to evaluate the transdermal delivery efficiency of microneedle arrays and suggested BR could be transdermally delivered by CS MNAs.

N-butanol extract of Broussonetia papyrifera (L.) L′Hér. ex Vent root bark alleviates atopic dermatitis by targeting E3 ubiquitin ligase WWP1 to promote NLRP3 degradation

BackgroundBroussonetia papyrifera (L.) L′Hér. ex Vent (B. papyrifera) is a deciduous tree widely distributed in Asia. Previous studies have revealed that leaves of B. papyrifera ameliorated atopic dermatitis (AD)-like symptoms and inflammatory response. However, the impact and underlying mechanism of other parts of B. papyrifera on AD remain elusive. MethodsThe AD mice induced by 1-Chloro-2,4-dinitrochlorobenzene were used to observe the histopathological alterations in the skin tissues using hematoxylin-eosin staining and toluidine blue staining techniques. Serum levels of inflammatory factors were quantified utilizing ELISA. Pyroptosis was analyzed by lactate dehydrogenase release and flow cytometry in human keratinocytes. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome was analyzed by western blots. Furthermore, the mechanism underlying the inhibition of NLRP3 inflammasome by N-butanol extracts of B. papyrifera root bark (NE-BPRB) was investigated using cellular thermal shift assay and surface plasmon resonance techniques. ResultsTreatment with NE-BPRB significantly ameliorated symptoms of AD mice and reduced serum levels of pro-inflammatory factors. NE-BPRB intervention exhibited inhibitory effects on NLRP3 inflammasome activation and pyroptosis in vitro and in vivo. NE-BPRB and its primary bioactive constituent chlorogenic acid (CA) promote the K48-linked ubiquitination of NLRP3, leading to its proteasomal degradation by binding WW domain containing E3 ubiquitin protein ligase 1 (WWP1). ConclusionsThe NE-BPRB and its primary bioactive constituent, CA, effectively inhibit the formation of the NLRP3 inflammasome and impede cell pyroptosis by promoting K48-linked ubiquitin-dependent proteasomal degradation of NLRP3 through binding to the E3 ubiquitin ligase WWP1, thereby resulting in improved AD.

Infectious Complications in Pediatric Hematopoietic Stem Cell Transplantation Recipients in Northeast Mexico

Abstract Background Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for an increasing number of neoplastic and hematological diseases. However, these patients are at high risk of acquiring infections due to a complex interaction involving organ dysfunction, tissue damage, pathogen exposure, pathogen virulence, and the overall state of dynamic immunosuppression varying according to different phases of immunologic reconstitution after HSCT, and the need for immunosuppressants to prevent and treat non-infectious complications such as graft-versus-host disease (GVHD). Methods All patients under 16 years old who underwent HSCT at the “Dr. José Eleuterio González” University Hospital, a referral center in Northeast Mexico, from March 2019 to October 2023, were included. Clinical, epidemiological, and analytical characteristics of the patients and infectious episodes during pre-engraftment, early engraftment, and late engraftment periods were analyzed. Results In the studied period, a total of 75 patients underwent HSCT, of whom 52 (69%) experienced infectious events (IEs). A total of 136 IEs were documented, averaging 2.5 IEs per patient. Among these, 40% were viral infections, 33% bacterial, 6.6% fungal, 0.7% parasitic, and 19.3% were indeterminate. The most prevalent baseline diagnoses were acute lymphoblastic leukemia (52%), acute myeloid leukemia (19%), and aplastic anemia (12%). Seventy-two percent of the patients underwent a haploidentical stem cell transplantation, and the graft was sourced from peripheral blood stem cells in 75% of the population. Bacterial infections were predominant in the pre-engraftment period, whereas viral infections were more frequent in early and late engraftment. The distribution of these IEs by period is shown in Figure 1. Among bacterial infections, bloodstream infections (BSIs) accounted for 56%, followed by skin and soft tissue infections (14%) and gastroenteritis (13%). Of the 26 BSI events, 73% were caused by Gram-negative bacilli, including 8 cases of Escherichia coli (42%), 6 cases of Pseudomonas aeruginosa (32%), 2 cases of Klebsiella pneumoniae (11%), and 1 case each of Acinetobacter calcoaceticus, Salmonella enterica and Stenotrophomonas maltophilia (5%). 44% of these exhibited extended-spectrum beta-lactamase (ESBL), and 19% were carbapenem-resistant. The remaining 27% of BSI were caused by Gram-positive cocci: Staphylococcus epidermidis (43%), Streptococcus viridans group (29%), Staphylococcus aureus, and Rothia mulcilaginosa (14% each). 17% of all BSI were central line associated bloodstream infection (CLABSI). Among viral infections, cytomegalovirus (CMV) was the most frequent agent at 46%, followed by SARS-CoV-2 and BK virus at 14% and 11%, respectively. Among the fungal infections, we identified 9 cases of invasive fungal disease (IFD), four cases of possible IFD, two of probable IFD and three cases of proven IFD were identified, including one case each of mucormycosis (zygomycetes), Candida tropicalis fungemia, and Aspergillus niger pneumonia. Additionally, one case of intestinal giardiasis, was identified, accounting for 0.7% of the total. Conclusion Infections represent one of the major adverse events in patients undergoing HSCT. It is essential to understand the local epidemiology in each hospital center to tailor international guidelines to the available resources in each institution, which is crucial in improving strategies for preventing, detecting, and providing timely treatment for these infectious complications and their clinical outcomes. Figure 1. Distribution of infectious events among the post-HSTC periods.