Search Results (87)

This study aimed to comprehensively review surgical interventions for ocular surface diseases (OSDs), including dry eye syndrome (DES), exposure keratopathy, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and ocular graft versus host disease (oGVHD), and to highlight the indications, contraindications, outcomes, and complications of various oculoplastic procedures used in their management. A narrative review was performed based on expert-guided selection of relevant studies retrieved from PubMed, Scopus, and Web of Science. Relevant keywords included “ocular surface disease”, “dry eye syndrome”, “exposure keratopathy”, “thyroid eye disease (TED)”, “neurotrophic keratopathy (NK)”, “Stevens-Johnson syndrome”, “toxic epidermal necrolysis”, “punctal occlusion”, “tarsorrhaphy”, “botulinum toxin”, “eyelid loading”, “retractor weakening”, “corneal neurotization (CN)”, “amniotic membrane transplantation (AMT)”, “conjunctival flap”, “ocular graft versus host disease”, and “salivary gland transplantation (SGT)”. Studies addressing surgical approaches for OSDs were included. In conclusion, surgical options for OSDs offer significant benefits when non-invasive treatments fail. Surgical techniques such as punctal occlusion, eyelid fissure narrowing, AMT, and conjunctival flap procedures help stabilize the ocular surface and alleviate symptoms. Advanced methods like CN and SGT target the underlying pathology in refractory cases such as oGVHD. The outcomes vary depending on the disease severity and surgical approach. Each procedure carries specific risks and requires individualized patient selection. Therefore, a tailored approach based on clinical condition, anatomical involvement, and patient factors is essential to achieve optimal results. Ongoing innovations in reconstructive surgery and regenerative medicine are expected to further improve outcomes for patients with OSDs. Full article

SARS-CoV-2, a β-coronavirus, primarily affects the lungs, with non-specific lesions and no cytopathic viral effect in the skin. Cutaneous antiviral mechanisms include activation of TLR/IRF pathways and production of type I IFN. We evaluated the antiviral mechanisms involved in the skin of COVID-19 patients, including skin samples from 35 deceased patients who had contracted COVID-19 before the launch of the vaccine. Detection of SARS-CoV-2 in the skin was performed using transmission electron microscopy and RT-qPCR. Microscopic and molecular effects of the virus in skin were evaluated by histopathology, RT-qPCR, and immunohistochemistry (IHC). The results revealed the presence of SARS-CoV-2 and microscopic changes, including microvascular hyaline thrombi, perivascular dermatitis, and eccrine gland necrosis. There was increased transcription of TBK1 and a reduction in transcription of TNFα by RT-qPCR in the COVID-19 group. IHC revealed reduced expression of ACE2, TLR7, and IL-6, and elevated expression of IFN-β by epidermal cells. In the dermis, there was decreased expression of STING, IFN-β, and TNF-α and increased expression of IL-6 in sweat glands. Our results highlight the role of type I IFN in the skin of COVID-19 patients, which may modulate the cutaneous response to SARS-CoV-2. Full article

Squalane (SQ, a saturated, sebum-mimetic hydrocarbon), oleic acid (OA, a monounsaturated fatty acid), and linoleic acid (LA, a polyunsaturated essential fatty acid) belong to the category of “lipids and fats” in cosmetic materials, and are widely employed as skin-conditioning emollients. However, they present differences in UV stress. In this study, we compared their effects on UV-induced oxidative damage, inflammation, and lipid metabolism using a mouse model and human sebaceous gland cells (SZ95). Results showed that 10% SQ did not worsen oxidative damage or inflammation after 6 weeks of UV exposure. In contrast, the 5% and 10% OA/LA groups showed increased skin wrinkling (p < 0.01), epidermal thickening (p < 0.05), and sebaceous gland atrophy. Transcriptome analysis indicated OA/LA upregulated arachidonic acid-related cytokine pathways (PTGS2/IL-1β; p < 0.001). In SZ95 cells, 0.006% OA/LA significantly increased lipid droplet formation (p < 0.001), free fatty acid (FFA) levels (p < 0.001), and pro-inflammatory gene expression (p < 0.001). Conversely, SQ neither promoted lipid droplet/FFA secretion nor induced oxidative stress. These findings suggest that high concentrations of unsaturated fatty acids in skincare may worsen lipid dysregulation and inflammation, while formulations based on saturated hydrocarbons like SQ could provide superior photoaging management by stabilizing skin barrier function. Full article

Salivary gland cancers (SGCs) pose a therapeutic challenge due to their aggressive nature and limited treatment options. Ion transporters, particularly the sodium/iodide symporter (SLC5A5), which transport iodine in the form of iodide anion (I⁻) into cells, have emerged as potential therapeutic targets in tumors of glandular origin. Our research indicates that SLC5A5 is expressed predominantly in ductal cells of human and murine SGC cells. We assessed the effects of potassium iodide (KI), a source of iodide ions. KI treatment reduced SGC cell proliferation and viability without impacting migration. KI increased ROS levels and triggered caspase-dependent apoptosis, as indicated by the upregulation of the pro-apoptotic protein BAX, downregulation of the anti-apoptotic protein Bcl-2, and induction of SGC cell shrinkage. KI did not affect NF-κB or TNF-α and SLC5A5 expression. Adding the antioxidant N-acetylcysteine reversed KI-induced growth inhibition, underscoring ROS-induced oxidative stress’s crucial role in growth inhibition. While KI administered in drinking water to mice increased epidermal growth factor (EGF) expression in non-malignant salivary gland tissues, KI decreased EGF receptor (EGFR) expression in malignant SGC cell cultures, where EGFR signaling is frequently dysregulated in SGCs but promoted AKT phosphorylation. Combining KI and anti-EGFR treatment did not yield synergistic anti-SGC cell effects. The study underscores the therapeutic potential of KI as a standalone treatment in vitro for SGC cells. However, the upregulation of EGF in non-malignant tissues and, therefore, the possibility to enhance EGFR-driven signals and AKT phosphorylation after KI treatment in cancer patients could indicate a risk of rendering SGC cells more drug resistant, warranting further investigation to optimize its clinical application. Full article

The Qinling giant panda has a high susceptibility to skin damage, which affects its survival. Although their healing efficacy in panda injuries remains unexplored, extracellular vesicles from adipose-derived mesenchymal stem cells (ADMSC-EVs) have shown promise in regenerative medicine. In this study, ADMSC-EVs were successfully obtained from Qinling giant pandas using ultracentrifugation, and proteomic techniques were used to analyze their composition and function. Primary skin fibroblasts from Qinling giant pandas were isolated and cultured to explore the effects of ADMSC-EVs on cell proliferation and migration. Additionally, a mouse model of skin injury was used to assess their wound healing effects. The ADMSC-EVs contained various substances, particularly proteins, with fifty unique proteins involved in transport, catabolism, and signal transduction identified. The application of ADMSC-EVs in a mouse model accelerated wound healing and promoted the regeneration of the epidermal and dermal layers. It facilitated the repair of skin appendages, including hair follicles and sebaceous glands. Additionally, ADMSC-EVs enhanced collagen deposition, stimulated angiogenesis, and reduced inflammation. Our findings confirm that ADMSC-EVs significantly improve skin healing, thus supporting the theoretical framework for the clinical use of giant panda extracellular vesicles and underscoring their potential for preserving the genetic resources of the Qinling giant panda. Full article

This review systematically examines the oral complications associated with conventional and novel anti-cancer therapies. It highlights that while molecularly targeted agents including monoclonal antibodies targeting the vascular endothelial growth factor and its receptor, the epidermal growth factor receptor, tyrosine kinase inhibitors, and immune checkpoint inhibitors tend to exhibit a lower overall toxicity profile compared to traditional cytotoxic chemotherapeutics, they are nonetheless linked to significant oral adverse events. These complications encompass inflammatory mucosal reactions known as mucositis, salivary gland dysfunction leading to a sensation of dryness in the mouth, taste alterations referred to as dysgeusia, and, critically, medication-related osteonecrosis of the jaw. In particular, bone-modifying agents such as bisphosphonates and denosumab disrupt bone remodeling and the formation of new blood vessels, thereby increasing the susceptibility to osteonecrosis of the jaw, especially following invasive dental procedures. The review delineates the multifactorial pathogenesis underlying these toxicities, which involves direct cell toxicity, impaired wound healing, and secondary infections. Furthermore, it emphasizes the importance of pre-treatment dental evaluation and preventive strategies including patient education, prophylactic dental care, and the integration of adjunctive therapies such as laser therapy and autologous platelet concentrates to mitigate these adverse effects. The analysis advocates for interdisciplinary collaboration between oncologists and dental professionals to optimize management protocols, enhance treatment adherence, and ultimately improve the quality of life for oncology patients undergoing anti-cancer therapy. Full article

Metastatic prostate cancer occurs when the tumor spreads from the prostate gland to other parts of the body. Previous studies have shown that Gα_i2, a subunit of the heterotrimeric G protein complex, plays a critical role in inducing cell migration and invasion in prostate cancer cells in response to diverse stimuli. Rac1 is a small rho-GTPase, which is activated by the phosphoinositide 3-kinase (PI3K)/AKT pathway and plays an essential role during cell migration. Previous studies have shown that the knockdown of Gα_i2 attenuates cell migration without causing any reduction in basal Rac1 activity in both PC3 and DU145 cells, and has only marginal effects on the epidermal growth facotor (EGF)-induced increase in Rac1 activity. Therefore, Gα_i2 may be involved in the regulation of cell motility and invasion independently or downstream of Rac1 activation. In this study, we investigated the possible mechanism of Gα_i2 at the level of the Rac1-dependent activation of Wiskott-Aldrich Syndrome Protein)-family verprolin homologous protein2 (Wave2) and actin related protein 2/3 (Arp 2/3) proteins, downstream effectors of activated Rac1. PC3 cells with a stable overexpression of constitutively active Rac1 were transfected with control siRNA or Gα_i2 siRNA to knockdown endogenous Gα_i2 expression. Western blot analysis showed that the Rac1-dependent activation of Wave2 was impaired in the absence of Gα_i2. The overexpression of constitutively active Gα_i2 (Gα_i2-Q205L) in PC3 cells significantly increased cell migration compared to cells transfected with control plasmids. In the parallel experiments, a specific Gα_i2 inhibitor blocked G_iα2-Q205L-induced cell migration in PC3 cells. Furthermore, the Rac1 inhibitor did not block increased cell migration in PC3 cells overexpressing constitutively active Gα_i2. We conclude that activated Gα_i2 plays a crucial role in cell migration in prostate cancer cells independent of Rac1 activation. Full article

Scaled integument of six species of the genus Acanthocercus and Laudakia nupta, family Agamidae was studied using light and scanning electron microscopy. Gross observation revealed the presence of two types of modified scales in the males. The enlarged scales covered with an extremely thick β-corneous layer were detected in the dorsal and ventral surfaces of the tail base and on the palmar and plantar limb surfaces of all species. After detachment of the β-layer, the surface of such scales was covered with high papillae (“papillary scales”). The callous scales were found in the precloacal region of Acanthocercus species and in both precloacal and mid-ventral regions of L. nupta. Modified scales were found in some females and subadut specimens, and absent in juveniles. A prominent papillary layer characterized the dermis of both scale types. It was assumed that well-developed dermal papillae in such scales expended the total surface area of stratum germinativum and created a pool of proliferated cells in the interpapillary loops to increase the production of differentiating keratinocytes. These processes were undoubtedly associated with the formation of a thick and resistant corneous layer that distinguished both types of scales. Functional role, a taxonomic value, and analogies with normal and pathological epidermis in birds and mammals are discussed. Full article

Breast cancer is the most clinically relevant pathology of the mammary gland and is currently the most diagnosed malignant disease among women worldwide. In breast cancer prevention, it is important to consider that the risk of developing the disease is not the same for the entire population. This pathology presents heterogeneous clinical manifestations and the most common classification is related to the following hormonal receptors: estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and triple-negative (TNBC). Currently, a new class of therapy is being used for cancer treatment: anti-body-drug conjugates. A bibliographic search was performed by establishing keywords and then combining them using Boolean operators OR and AND. Thus, the search equation was formulated according to the PICO search question to be used in the PubMed database. Results: Fifteen studies that met the established inclusion criteria were analyzed, and their methodological quality was assessed using the Joanna Briggs Institute approach, demonstrating high reliability in the results obtained, the analyzed studies focus on the combination of adjuvant Pertuzumab + Trastuzumab with chemotherapy for the treatment of HER2-positive breast cancer. Scientific evidence suggests that the combination of pertuzumab and trastuzumab not only improves the survival of patients with HER2-positive breast cancer but also provides a safe and flexible treatment option. Full article

Hair follicle stem cells, located in the bulge region of the outer root sheath, are multipotent epithelial stem cells capable of differentiating into epidermal, sebaceous gland, and hair shaft cells. Efficient culturing of these cells is crucial for advancements in dermatology, regenerative medicine, and skin model development. This investigation aimed to develop a protocol for isolating enriched bulge-derived epithelial cells from scalp specimens to produce tissue-engineered substitutes. The epithelium, including hair follicles, was separated from the dermis using thermolysin, followed by microdissection of the bulge region. Epithelial stem cells were isolated using enzymatic dissociation to create a single-cell suspension and compared with the direct explant culture and a benchmark method which isolates cells from the epidermis and pilosebaceous units. After 8 days of culture, the enzymatic digestion of microdissected bulges yielded 5.3 times more epithelial cells compared to explant cultures and proliferated faster than the benchmark method. Cells cultured from all methods exhibited comparable morphology and growth rates. The fully stratified epidermis of tissue-engineered skin was similar, indicating comparable differentiation potential. This enzymatic digestion method improved early-stage cell recovery and expansion while maintaining keratinocyte functionality, offering an efficient hair bulge cell-extraction technique for tissue engineering and regenerative medicine applications. Full article

The ultrastructure of submandibular gland (SMG) of Bactrian camels was observed by a transmission electron microscope. Routine HE staining, special staining combined with immunohistochemistry, and immunofluorescence techniques were used to study the histochemical characteristics of the submandibular gland and the localisation and distribution characteristics of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR). HE results showed that the submandibular gland of Bactrian camels was composed of mixed serous and mucinous acini glands. The submandibular striated duct was highly developed and connected with intercalated ducts with larger diameter. Intercalated ducts are shorter and directly connected to acini. In AB-PAS staining, it was observed that the inner wall of striated tube was strongly positive for AB staining. The distribution of the reticular fibres around the follicles and ducts of the submandibular gland is distinct, with collagen fibres distributed mainly in the periphery of the ducts and sparse collagen fibres in the periphery of the acini. Immunohistochemistry and fluorescence show that EGF is strongly positive in striated and intercalated ducts, and EGFR is weakly positive in striated and intercalated ducts. Bactrian camel SMGs secrete more acidic mucins, and EGF and EGFR were mainly secreted and play a role in the pipeline system of SMGs. Full article

The Utricularia (bladderworts) species are carnivorous plants that prey mainly on invertebrates using traps (bladders) of leaf origin. On the outer surfaces of the trap, there are dome-shaped glands (capitate trichomes). Each such trichome consists of a basal cell, a pedestal cell, and a terminal cell. During the maturation of these external glands, there are changes in the cell wall of the terminal cell of the gland (deposited layers of secondary wall material). Thus, due to changes in the cell wall, these glands are excellent models for studying the specialization of cell walls. The main aim of this study was to check whether different cell wall layers in terminal gland cells have a different composition in the case of homogalacturonans (low-methylesterified HGs, fully de-esterified HGs, and galactan) and hemicelluloses (galactoxyloglucan, xyloglucan, and xylan). The antibodies were used against cell wall components (anti-pectins JIM5, JIM7, LM19, CCRC-M38, and LM5 and anti-hemicelluloses LM25, LM15, CCRC-M1, and CCRC-M138). The localization of the examined compounds was determined using immunohistochemistry techniques, Carbotrace 680, and Calcofluor White. Our study showed the presence of various components in the cell walls of external gland cells: methylesterified and demethylesterified homogalacturonans, galactan, xylan, galactoxyloglucan, and xyloglucan. In the terminal cell, the primary cell wall contains different pectins in contrast to the secondary wall material, which is rich in cellulose and hemicelluloses. We also found that the basal cell differs from the other gland cells by the presence of galactan in the cell wall, which resembles the epidermal cells and parenchyma of traps. A particularly noteworthy part of the cell wall functions as a Casparian strip in the pedestal cell. Here, we found no labeling with Carbotrace 680, possibly due to cell wall modification or cell wall chemical composition variation. We have shown that the apoplastic space formed by the cell walls of the terminal cell is mainly composed of cellulose and hemicelluloses (galactoxyloglucan and xyloglucan). This composition of the cell walls allows the easy uptake of components from the external environment. Our research supports the external glands’ function as hydropotens. Full article

The epidermis of the skin and skin appendages, such as nails, hair and sebaceous glands, depend on a balance of cell proliferation and terminal differentiation in order to fulfill their functions at the interface of the body and the environment. The differentiation of epithelial cells of the skin, commonly referred to as keratinocytes, involves major remodeling processes that generate metabolically inactive cell remnants serving as building blocks of the epidermal stratum corneum, nail plates and hair shafts. Only sebaceous gland differentiation results in cell disintegration and holocrine secretion. A series of studies performed in the past decade have revealed that the lysosome-dependent intracellular degradation mechanism of autophagy is active during keratinocyte differentiation, and the blockade of autophagy significantly alters the properties of the differentiation products. Here, we present a model for the autophagy-mediated degradation of organelles and cytosolic proteins as an important contributor to cellular remodeling in keratinocyte differentiation. The roles of autophagy are discussed in comparison to alternative intracellular degradation mechanisms and in the context of programmed cell death as an integral end point of epithelial differentiation. Full article

This literature review looks at Sjogren’s Syndrome (SS), a chronic autoimmune disorder affecting exocrine glands, particularly the lacrimal and salivary glands. SS manifests as ocular and oral dryness, with severe complications like visual dysfunction and corneal perforation, as well as systemic implications, such as interstitial lung disease and lymphoma. This review explores the use of tear film biomarkers to diagnose SS, emphasizing the significance of their identification in aiding clinical diagnosis and differentiation from other diseases. This study identified and analyzed 15 papers, encompassing 1142 patients and employing various tear sample collection methods. Tear biomarkers were categorized by function and explored in-depth. Categories include (1) antimicrobials, antivirals, and antifungals; (2) components of immune regulation; (3) components that regulate metabolic processes; and (4) inflammatory markers. Noteworthy findings include the potential diagnostic values of tear lysozyme, lactoferrin, dinucleoside polyphosphates, cathepsin, defensin, antibodies, epidermal fatty acid-binding protein, HLA-DR, ADAM10, aquaporin 5, and various miRNAs and mRNAs. Overall, our understanding of SS tear film composition is enhanced, providing valuable insights into the pathogenesis of SS and offering a foundation for future diagnostic and therapeutic advancements in autoimmune conditions affecting the ocular surface. Full article

The use of tyrosine kinase inhibitors (TKI) has been growing in veterinary oncology and in the past few years several TKI have been tested in dogs. However, different from human medicine, we lack strategies to select patients to be treated with each TKI. Therefore, this study aimed to screen different tumor subtypes regarding TKI target immunoexpression as a predictor strategy to personalize the canine cancer treatment. It included 18 prostatic carcinomas, 36 soft tissue sarcomas, 20 mammary gland tumors, 6 urothelial bladder carcinomas, and 7 tumors from the endocrine system. A total of 87 patients with paraffin blocks were used to perform immunohistochemistry (IHC) of human epidermal growth factor receptor 2 (HER-2), epidermal growth factor receptors 1 (EGFR1), vascular endothelial growth factor receptor 2 (VEGFR-2), platelet derived growth factor receptor beta (PDGFR-β), c-KIT, and extracellular signal-regulated kinase 1/2 (ERK1/ERK2). The immunohistochemical screening revealed a heterogeneous protein expression among histological types with mesenchymal tumors showing the lowest expression level and carcinomas the highest expression. We have demonstrated by IHC screening that HER2, EGFR1, VEGFR-2, PDGFR-β and ERK1/ERK2 are commonly overexpressed in dogs with different carcinomas, and KIT expression is considered relatively low in the analyzed samples. Full article