The Tumor Stroma of Squamous Cell Carcinoma: A Complex Environment That Fuels Cancer Progression.

The tumor microenvironment (TME), a complex assembly of cellular and extracellular matrix (ECM) components, plays a crucial role in driving tumor progression, shaping treatment responses, and influencing metastasis. This narrative review focuses on the cutaneous squamous cell carcinoma (cSCC) tumor stroma, highlighting its key constituents and their dynamic contributions. We examine how significant changes within the cSCC ECM-specifically, alterations in fibronectin, hyaluronic acid, laminins, proteoglycans, and collagens-promote cancer progression, metastasis, and drug resistance. The cellular composition of the cSCC TME is also explored, detailing the intricate interplay of cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, pericytes, adipocytes, and various immune cell populations. These diverse players modulate tumor development, angiogenesis, and immune responses. Finally, we emphasize the TME's potential as a therapeutic target. Emerging strategies discussed in this review include harnessing the immune system (adoptive cell transfer, checkpoint blockade), hindering tumor angiogenesis, disrupting CAF activity, and manipulating ECM components. These approaches underscore the vital role that deciphering TME interactions plays in advancing cSCC therapy. Further research illuminating these complex relationships will uncover new avenues for developing more effective treatments for cSCC.

First Reported Case of a Clinically Nonresponsive-to-Itraconazole Alternaria alternata Isolated from a Skin Infection of a Nonimmunocompromised Patient from Romania.

BACKGROUND: Alternaria alternata is a melanic fungus capable of causing a wide variety of infections, some of which have lethal potential. It is a ubiquitous fungus and a well-known plant pathogen. Cutaneous infections with Alternaria alternata most often occur in the extremities of patients who perform conventional agriculture, thus being exposed to occupational hazards leading to the disruption of the skin barrier. METHODS: This paper presents the first case report from Romania of an itraconazole nonresponsive cutaneous alternariosis in a patient without any type of immunosuppression. RESULTS: After an initial misdiagnosis regarding the etiology of the patient's skin infection, two successive punch biopsies, followed by mycologic examination, lead to the final diagnosis of cutaneous alternariosis. Treatment guided by antifungal susceptibility testing has been instituted, leading to the gradual healing of the patient's skin ulcerations. CONCLUSIONS: The ability of Alternaria alternata to infect immunocompetent human hosts and to develop resistance to antifungal drugs highlight the importance of correctly diagnosing the etiology of skin ulcerations and instituting appropriate treatment guided by antifungal susceptibility testing whenever the suspicion of a fungal skin infection is plausible.

Digital histological morphometry of the human pineal gland in a postmortem study, with endocrine and neurological clinical implications.

The pineal gland is a small-sized, photo neuroendocrine organ in the midline of the brain that synthesises and secretes melatonin and serotonin. Chords and islands of pinealocytes constitute the secretory parenchyma, while glial tissue and calcifications represent degenerative changes. This study examined human postmortem pineal glands to microscopically assess morphological changes possibly associated with clinical data, by using digital techniques. A retrospective autopsy study has been performed on 72 paediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with synaptophysin (SYN), neuron-specific enolase (NSE), and neurofilament (NF). Slides were digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. The comorbidities used for correlation with morphometric data were obesity, type 2 diabetes, adrenal gland adenoma, goitre, chronic pancreatitis, arterial hypertension, and mixed dementia. Thirty-three females and 39 males were included in the study. Increased secretory parenchyma was found in patients with chronic pancreatitis, arterial hypertension, and adrenal gland adenoma. Reduced activity was found in patients with type 2 diabetes, obesity, advanced pineal calcification, mixed dementia, and old age. There were no changes associated with goitre, cachexia, or Willis's polygon atherosclerosis. No significant differences between gender were found. The activity of the pineal gland can be assessed by quantitative immunohistochemistry of neuroendocrine and structural pinealocyte markers and observation of glial tissue and calcifications. There is a need for further research to evaluate the clinical impact of these morphological changes on the neuroendocrine systems, with clinical implications in endocrinology, neurology, and even psychiatry. Digital techniques offer a more exact analysis of histological data.

Nodular and Micronodular Basal Cell Carcinoma Subtypes Are Different Tumors Based on Their Morphological Architecture and Their Interaction with the Surrounding Stroma.

Basal cell carcinoma (BCC) is the most frequent cancer of the skin and comprises low-risk and high-risk subtypes. We selected a low-risk subtype, namely, nodular (N), and a high-risk subtype, namely, micronodular (MN), with the aim to identify differences between them using a classical morphometric approach through a gray-level co-occurrence matrix and histogram analysis, as well as an approach based on deep learning semantic segmentation. From whole-slide images, pathologists selected 216 N and 201 MN BCC images. The two groups were then manually segmented and compared based on four morphological areas: center of the BCC islands (tumor, T), peripheral palisading of the BCC islands (touching tumor, TT), peritumoral cleft (PC) and surrounding stroma (S). We found that the TT pattern varied the least, while the PC pattern varied the most between the two subtypes. The combination of two distinct analysis approaches yielded fresh insights into the characterization of BCC, and thus, we were able to describe two different morphological patterns for the T component of the two subtypes.

A Flavonoid-Rich Extract of Sambucus nigra L. Reduced Lipid Peroxidation in a Rat Experimental Model of Gentamicin Nephrotoxicity.

The use of gentamicin (GM) is limited due to its nephrotoxicity mediated by oxidative stress. This study aimed to evaluate the capacity of a flavonoid-rich extract of Sambucus nigra L. elderflower (SN) to inhibit lipoperoxidation in GM-induced nephrotoxicity. The HPLC analysis of the SN extract recorded high contents of rutin (463.2 ± 0.0 mg mL-1), epicatechin (9.0 ± 1.1 µg mL-1), and ferulic (1.5 ± 0.3 µg mL-1) and caffeic acid (3.6 ± 0.1 µg mL-1). Thirty-two Wistar male rats were randomized into four groups: a control group (C) (no treatment), GM group (100 mg kg-1 bw day-1 GM), GM+SN group (100 mg kg-1 bw day-1 GM and 1 mL SN extract day-1), and SN group (1 mL SN extract day-1). Lipid peroxidation, evaluated by malondialdehyde (MDA), and antioxidant enzymes activity-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX)-were recorded in renal tissue after ten days of experimental treatment. The MDA level was significantly higher in the GM group compared to the control group (p < 0.0001), and was significantly reduced by SN in the GM+SN group compared to the GM group (p = 0.021). SN extract failed to improve SOD, CAT, and GPX activity in the GM+SN group compared to the GM group (p > 0.05), and its action was most probably due to the ability of flavonoids (rutin, epicatechin) and ferulic and caffeic acids to inhibit synthesis and neutralize reactive species, to reduce the redox-active iron pool, and to inhibit lipid peroxidation. In this study, we propose an innovative method for counteracting GM nephrotoxicity with a high efficiency and low cost, but with the disadvantage of the multifactorial environmental variability of the content of SN extracts.

High-Frequency Ultrasound Assessment of Skin and Oral Mucosa in Metabolic Syndrome Patients-A Cross-Sectional Study.

BACKGROUND: Exogenous factors (such as sun exposure, smoking habits, and diet) and endogenous (inflammatory status, general diseases) have a direct influence on skin and soft tissue characteristics. The study's objective was to assess the impact of metabolic syndrome (MS) on characteristics of skin layers in sun-exposed and non-exposed maxillofacial tissues evaluated by high-frequency ultrasound (HFU), as a potential diagnosis and monitoring tool for the aging process. MATERIAL AND METHODS: The present study included 102 subjects (24 with MS; 78 without MS). Anthropometric parameters and disease history were recorded, and blood samples were harvested in order to assess biochemical parameters of MS. Sun-exposed skin (zygomatic region) and non-exposed oral mucosa of the lower lip were assessed using HFU (DUB® cutis, Taberna Pro Medicum) with a 22 MHz probe. RESULTS: Patients with cardiac disease had significantly lower values for epidermis density (p = 0.002). Gender was independently linked to the aged dermis depth (p < 0.001), aged dermis no. of px (pixels) (p < 0.001), dermis depth (p < 0.001), dermis no. of px (p < 0.001), and subcutaneous tissue density (p < 0.001). Patients with MS had thinner epidermis (p = 0.008) and thinner aged dermis (p = 0.037) when compared to non-MS subjects. CONCLUSION: Patients with MS had thinner epidermis and a lower epidermis number of pixels in sun-exposed skin. Women had lower epidermis density and thicker dermis in sun-exposed skin. Our study showed that HFU, as a non-invasive investigation approach, is useful to diagnose and monitor the aging process in skin and oral mucosa, correlated with skin phenotype pathological conditions.

Age-Related Changes of the Pineal Gland in Humans: A Digital Anatomo-Histological Morphometric Study on Autopsy Cases with Comparison to Predigital-Era Studies.

Background and objectives: The pineal gland is a photoneuroendocrine organ in the midline of the brain, responsible primarily for melatonin synthesis. It is composed mainly of pinealocytes and glial tissue. This study examined human postmortem pineal glands to microscopically assess age-related changes using digital techniques, and offers a perspective on evolutionary tendencies compared to the past. Materials and Methods: A retrospective autopsy study has been performed on 72 pediatric and adult autopsy cases. The glands have been processed for histological analysis and immunohistochemical staining with glial fibrillary acidic protein (GFAP). Slides were assessed under polarized light and digitally scanned. Morphometric data were obtained using CaseViewer and ImageJ. Results: Thirty-three females and 39 males were included in the study, grouped under three age groups: 0-25, 46-65, and 66-96 years of age. The peak gland volume was found within the 46-65 age group, the overall mean volume was 519 mm3, the main architectural types were lobular and insular, and the mean percentage of pineal calcification was 15% of the gland, peaking within the 66-96 age group, with a predominantly globular shape. Glial cysts were found in 20.8% of cases. The intensity of GFAP stain was maximal in the pediatric age group, but the extent of glial tissue was much larger in elderly patients. Discussion: The degenerative process of the pineal gland can be quantified by measuring normal parenchyma, calcifications, glial tissue, and glial cysts. Morphometric differences have been observed and compared to a similar studies performed in the published literature. The current study, unfortunately, lacks a 26-45 age group. Digital techniques seemed to offer a more exact analysis, but returned similar results to studies performed over 40 years ago, therefore offering important information on evolutionary tendencies. Conclusions: Increase in glial tissue, calcifications, and glial cysts have a defining role as age-related changes in the pineal gland.

Retrospective Analysis of Complication Rates Associated With Auricular Reconstruction After Skin Cancer Surgery.

BACKGROUND: There is limited data regarding postoperative complications after microtia surgery or tympanoplasty; however, complication rates after pinna reconstruction following tumor resection and comorbidities associated with suboptimal outcomes have not been investigated so far. OBJECTIVE: To examine the incidence of postoperative complications after auricular reconstruction surgery following tumor resection and determine the association between postoperative complications and defect size, patients' comorbidities, and reconstruction type. METHODS AND MATERIALS: In a retrospective case series (n = 146, January 2014 to October 2018), we examined the surgical outcome and amount of postoperative complications following auricular surgery as well as the association with different comorbidities. SPSS 16.0 was used for statistical analyses. RESULTS: The following early postoperative complications were identified: pain (29.5%), hematoma (4.1%), flap congestion (4.8%), infection (3.4%), and flap/graft necrosis (2.7%). Late complications including cartilage step-offs, helical rim sulcus alteration, granulomas, or ear deformities occurred only in 3.6% of subjects. Reconstructions of large defects (>1 cm2) were associated with a higher incidence of early postoperative complications compared to small defects (<1 cm2) (P < .001). Neither the presence of smoking or diabetes nor immunosuppression was significantly linked to an increased incidence of early complications. Immunosuppression, however, was associated with a higher incidence of postoperative infection (P < .001). CONCLUSION: The incidence of early and late postoperative complications after skin tumor resection and external ear reconstruction is low. The occurrence of postoperative infection was not linked with smoking or the presence of diabetes, but strongly associated with a state of immunosuppression, which is why a perioperative antibiotic prophylaxis in immune-compromised patients may be considered.

Preliminary study on the development of an antistretch marks water-in-oil cream: ultrasound assessment, texture analysis, and sensory analysis.

PURPOSE: Striae distensae represent the result of the failure of the dermis to sustain intrinsic mechanical forces. Intensive moisturization of the lesions and use of emollient oils have been recommended for the prevention and treatment of striae distensae rubra. The aim of this research was to formulate an emollient water-in-oil cosmetic cream containing argan oil, which may be helpful in the prevention or early treatment of striae distensae. PATIENTS AND METHODS: Sensory evaluation of the consistency, firmness, adhesiveness, oiliness, spreadability, and rapidity of penetration into the skin was evaluated by 22 volunteers using 10-point scales for each descriptor. The instrumental characterization of the cream was performed using Brookfield(®) CT3 Texture Analyzer. The cutaneous changes induced by the topical use of the cream were evaluated by assessing the thickness of the epidermis, hydration, and elasticity of the skin using DermaLab(®) Combo scanner. RESULTS: Ultrasound measurements showed an improvement in the elasticity of the epidermis following the application of cream. The product was well tolerated and appreciated by the consumers in terms of its spreadability, penetration ability, and lack of stickiness. The values recorded for texture analysis were firmness 10.16±0.15 mJ, adhesiveness 30.94±6.87 g, consistency 1229.50±119.78 g, spreadability 481.50±39 g, and stringiness 0.56±0.09 mJ. CONCLUSION: A water-in-oil cream containing argan oil and emollient ingredients with appropriate physical characteristics was obtained. In vivo study of clinical efficacy revealed a positive effect on increasing the skin elasticity, suggesting that the cream may be helpful in the prevention or early treatment of striae distensae.