Search Results (28)

Androgenetic alopecia (AGA) is a common form of hair loss characterized by androgen-driven tissue remodeling, including progressive follicular miniaturization and dermal fibrosis, which is accompanied by low-grade immune activation. However, the molecular mechanisms underlying this fibroimmune dysfunction remain poorly understood. Dermal fibroblasts (DFs) have been suggested as androgen-responsive stromal cells and a potential source of CXCL12, a chemokine implicated in fibroimmune pathology, but their precise role in AGA has not been fully established. In this study, we performed single-cell transcriptomic profiling of a testosterone-induced mouse model of AGA, with or without treatment of CXCL12-neutralizing antibody, to elucidate the pathological role of CXCL12 in mediating stromal-immune interactions. Our analysis suggested that DFs are the primary androgen-responsive population driving CXCL12 expression. Autocrine CXCL12-ACKR3 signaling in DFs activated TGF-β pathways and promoted fibrotic extracellular matrix deposition. In parallel, paracrine CXCL12-CXCR4 signaling reprogrammed Sox2⁺Twist1⁺ dermal papilla cells (DPCs) and promoted the accumulation of pro-fibrotic Trem2⁺ macrophages, contributing to impaired hair follicle regeneration. Notably, CXCL12 blockade attenuated these stromal and immune alterations, restored the regenerative capacity of DPCs, reduced pro-fibrotic macrophage infiltration, and promoted hair regrowth. Together, these findings identify CXCL12 as a central mediator of androgen-induced fibroimmune remodeling and highlight its potential as a therapeutic target in AGA. Full article

Canine mammary tumors (CMTs) constitute one of the most prevalent malignancies in female canines, whereas the functional involvement of gonadotropin receptors—luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR)—in these neoplasms remains uncharacterized. This study investigated LHR and FSHR expression in 79 CMTs and 14 normal mammary tissues collected from 59 female dogs (ethical approval AW82903202-2-3), using immunohistochemistry (IHC) and quantitative real-time PCR, specifically examining their association with tumor malignancy and spay status. Relative to normal mammary tissue, CMTs exhibited statistically significant downregulation of both LHR and FSHR transcripts and corresponding proteins (p < 0.01), with expression progressively decreasing as tumor malignancy increased, and with grade 3 tumors showing almost undetectable levels. Notably, spayed dogs displayed higher LHR levels in tumors (p < 0.05), whereas intact dogs showed higher FSHR levels than spayed dogs. These findings suggest that the expression of LHR and FSHR in CMTs may correlate with tumor malignancy and be influenced by the spay status. Our findings provide the first evidence of gonadotropin receptor dysregulation in CMTs, offering novel insights into their molecular mechanisms and potential applications in hormone-related diagnostic or therapeutic strategies. Full article

Background/Objectives: Hair loss (alopecia or effluvium) can significantly affect the self-esteem and psychosocial well-being of patients, resulting in a reduced quality of life. It may herald a systemic disease, nutritional deficiency, or side effects of pharmacotherapy. Current therapeutic options for hair loss are not always satisfactory and may be associated with considerable side effects; therefore, new solutions are still sought. Caffeine seems to be an effective agent against hair loss thanks to its stimulating effects on cell growth and good penetration into the hair follicle. The aim of this study was to systematically review published clinical trials of topical caffeine preparations against hair loss. Methods: We searched PubMed, Scopus, and Web of Science for clinical trials investigating the efficacy of topical caffeine products in hair loss, published until 29 November 2024. The quality of evidence was assessed using the GRADE classification. Results: The query returned 1121 articles, of which 9 ultimately met the inclusion criteria. In total, 684 people with androgenetic alopecia, excessive hair loss, or hair thinning were included in these trials. In all studies, conclusions were in favor of topical caffeine treatment; however, the level of scientific evidence was medium in 3 studies, low in 1, and very low in the remaining 5. Their major flaws included the lack of randomization and placebo and control groups, as well as the lack of information on the caffeine concentration in the topical products. Conclusions: Results from studies published to date suggest that topical caffeine preparations are safe and effective against hair loss. Nevertheless, better-designed clinical trials of well-defined caffeine products are required for an ultimate statement. Commercial hair products with caffeine offered on the market nowadays may be worth a try, but due to incomplete scientific data and product information, satisfactory outcomes are not guaranteed. Full article

Background/Objectives: This systematic review and meta-analysis aimed to investigate the effect of prebiotics, alone or as part of synbiotics, on cardiometabolic parameters in polycystic ovary syndrome (PCOS) women. Methods: Databases, including PubMed, Scopus, ISI Web of Science, Embase, and the Cochrane Central Register of Controlled Trials, were searched for relevant randomized-controlled trials (RCTs) until 12 December 2024. Changes in mean ± standard deviations were extracted and combined using a random-effects model. Bias was assessed using Cochrane risk of bias and evidence quality with GRADE. Results: Twenty RCTs with 1271 participants were included. Results showed high-quality evidence supporting prebiotics’ effects, alone or as part of synbiotics, in reducing body-mass index [n = 853; weighted-mean difference (WMD): −0.510, 95%CI: −0.669, −0.351 kg/m²] and diastolic blood pressure (WMD: −2.218, 95%CI: −4.425, −0.010 mmHg), moderate-quality evidence for weight, waist-to-hip ratio, and triglycerides improvements, and low or very-low-quality evidence for waist circumference (WC), fat mass, fasting plasma glucose, fasting insulin, low-density lipoprotein (LDL), total cholesterol (TC), high sensitive-C reactive protein, total testosterone, follicle-stimulating hormone and free androgen index improvements. Subgroup analyses revealed possible reduction in LDL with prebiotics, as well as possible decreases in WC, TC, and total testosterone with synbiotics. Dietary approaches to stop hypertension diet improved insulin sensitivity. Conclusions: This study suggests that prebiotics may beneficially affect several cardiometabolic parameters in PCOS women. Approximately one-third of the results were based on moderate-to-high-quality evidence. This study highlights the need for future well-designed, larger RCTs with longer treatment duration to strengthen the evidence base and guide clinical decision-making. Full article

The objective of this study was to measure the different redox biomarker levels within the follicular fluid (FF) and evaluate correlations with embryo quality using the one follicle–one oocyte/embryo approach. The prospective study included 54 women (average age 34.6 ± 3.0 years). Out of the 235 mature metaphase II cells that underwent intracytoplasmic sperm injection, fertilization was achieved in 177 cells, producing 92 Grade I embryos, 26 Grade II embryos, 39 Grade III embryos, and 20 Grade IV embryos. The activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and glutathione transferase were significantly higher in the group consisting of lower-quality (Grades II–IV) embryos in comparison with top-quality (Grade I) embryos (p = 0.011; p = 0.021; p = 0.008, respectively). The concentration of oxidative stress markers, malondialdehyde, 8-hydroxy-2′-deoxyguanosine, and thiol groups was significantly increased in the group with lower-quality embryos (Grades II–IV) compared to top-quality embryos (0.027; 0.018; 0.021, respectively). Furthermore, a significant positive correlation between each oxidative marker and the activities of antioxidant enzymes was observed (p < 0.001). According to our findings, the best embryos and, consequently, better in vitro fertilization outcomes are linked to low levels of oxidative stress and low antioxidant enzyme activity. Full article

Radiation dermatitis (RD) is a common side effect in patients receiving radiotherapy. Currently, clinical skincare approaches for acute RD vary widely among institutions and lack consensus. Hydrogen molecules, acting as radioprotective agents by selectively scavenging free radicals, have the potential to protect against RD. In this study, we demonstrate that hydrogen reduces double-strand breaks, mitochondrial depolarization, and inflammatory cytokines induced by irradiation damage in HaCaT cells. Furthermore, in vivo experiments reveal that exposing irradiated skin areas to a hydrogen gas environment alleviates RD. Assessment of skin appearance grade and histology staining revealed that direct transdermal application of hydrogen can prevent radiation-induced follicle damage, dermal thickening, and leukocyte infiltration, thereby reducing the severity of RD. In addition, hydrogen enhances the skin’s antioxidant capacity, leading to a reduction in the Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) ratio, the number of apoptotic cells, and the expression of pro-inflammatory cytokines. Our data demonstrate that hydrogen possesses antioxidant, anti-inflammatory, and anti-apoptotic properties, and could be a preventive strategy for RD. Full article

Background: Recent studies indicate that vitamin D impacts male reproductive function, with deficiency linked to infertility. This review evaluates the effect of vitamin D supplementation on male fertility, focusing on total testosterone, free testosterone, the free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex-hormone-binding globulin (SHBG), and estradiol. Methods: We systematically searched Medline, Web of Science, Cochrane Library, and Scopus from their inception until July 2024 for randomized controlled trials (RCTs) involving adult males. The primary focus of these studies was on reproductive hormone parameters, analyzed using a random-effects meta-analysis and weighted mean difference (WMD). Evidence quality was assessed using ROB2 and GRADE. Meta-regression and dose–response analyses were performed. Results: Seventeen studies met the criteria for quantitative analysis. Vitamin D supplementation significantly increased total testosterone levels (WMD 0.38, 95% CI 0.06–0.70, n = 15, I² = 67.03). However, it had no significant effect on other hormone parameters: free testosterone (WMD 0.00, 95% CI −0.02–0.03, n = 9, I² = 48.12), FSH (WMD −0.02, 95% CI −0.57–0.53, n = 7, I² = 48.72), LH (WMD −0.09, 95% CI −0.30–0.12, n = 8, I² = 0.00), SHBG (WMD 0.73, 95% CI −1.14–2.61, n = 10, I² = 69.05), FAI (WMD −0.92, 95% CI −2.12–0.27, n = 6, I² = 0.00), and estradiol (WMD −0.02, 95% CI −2.95–2.92, n = 5, I² = 20.63). Conclusion: This meta-analysis shows that vitamin D supplementation may increase total testosterone levels in men. However, further well-designed RCTs are needed to determine vitamin D’s effects on other reproductive hormone parameters. Full article

Fixatives and fixation protocol have a profound effect on both the morphology and epitope sensitivity of ovarian tissue, which hampers accurate ovarian tissue evaluation. We aimed to establish the most suitable fixation protocol for feline (Felis catus) ovarian tissue. Fragments (1.5 mm diameter) were punched from 1 mm-thick feline ovarian tissue, divided into three groups then fixed with three different fixatives (Bouin, neutral buffered formalin [NBF] and form acetic acid [new compound fixative formulation for ovarian tissue composed of 5% acetic acid in NBF]) for five fixation periods. Subsequently, fragments were processed and evaluated for the morphology and intensity of immunohistochemical signals against three antigens (Ki-67, MCM-7 and activated caspase-3). Proportions of grade 1 or morphologically intact follicles were significantly lower in NBF when compared with Bouin and form acetic acid fixatives. However, Bouin fixative had the lowest mean DAB intensity (p < 0.05) in all three antigen targets, while NBF had the highest (p < 0.05) in Ki-67 and caspase-3, but in MCM-7, it was no different from form acetic acid. In conclusion, form acetic acid maintained ovarian tissue architecture with excellent follicular morphology in the same manner as Bouin fixative, and it also maintained reasonable DAB signals similar to NBF, thus providing a better alternative for feline ovarian tissue studies. Full article

Cold atmospheric plasma devices generate reactive oxygen and nitrogen species that can be anti-microbial but also promote cell migration, differentiation, and tissue wound healing. This report investigates the healing of surgical incisions created using cold plasma generated by the J-Plasma scalpel (Precise Open handpiece, Apyx Medical, Inc.) compared to a steel scalpel in in vivo porcine and rat models. The J-Plasma scalpel is currently FDA approved for the delivery of helium plasma to cut, coagulate, and ablate soft tissue during surgical procedures. To our knowledge, this device has not been studied in creating surgical incisions but only during deeper dissection and hemostasis. External macroscopic and histologic grading by blinded reviewers revealed no significant difference in wound healing appearance or physiology in incisions created using the plasma scalpel as compared with a steel blade scalpel. Incisions created with the plasma scalpel also had superior hemostasis and a reduction in tissue and blood carryover. Scanning electron microscopy (SEM) and histology showed collagen fibril fusion occurred as the plasma scalpel incised through the tissue, contributing to a sealing effect. In addition, when bacteria were injected into the dermis before incision, the plasma scalpel disrupted the bacterial membrane as visualized in SEM images. External macroscopic and histologic grading by blinded reviewers revealed no significant difference in wound healing appearance or physiology. Based on these results, we propose additional studies to clinically evaluate the use of cold plasma in applications requiring hemostasis or when an increased likelihood of subdermal pathogen leakage could cause surgical site infection (i.e., sites with increased hair follicles). Full article

The evaluation of acne-prone skin and absent-to-mild acne is difficult because this condition is not associated with a clinically definable situation. Previous studies showed that apparently healthy skin in patients with previous episodes of acne shows microcomedos and infundibular hyperkeratosis upon reflectance confocal microscopy (RCM) evaluation. Our aim was to characterize the subclinical and microscopic characteristics of acne-prone skin by means of RCM and dynamic optical coherence tomography (D-OCT) and evaluate microscopic changes induced by treatment. A group of 20 patients received a daily combined treatment over a period of 3 months, consisting of probiotic supplementation with three strains of 10⁹ colony-forming units of Lactobacillus (Lactobacillus reuteri, Lactobacillus casei subsp. rhamnosus, Lactobacillus plantarum) and a combined topical product of azelaic and hydroxypinacolone retinoate (HPR). Clinical evaluations and non-invasive imaging acquisitions using VISIA^® System, RCM, and D-OCT were performed at baseline, and after 4 and 12 weeks. The total number of clinically evident non-inflammatory lesions decreased during treatment from 11.5 to 7.3 (p < 0.05). There was also an evident reduction in microscopic acne features at RCM and D-OCT, such as the number of small bright follicles, large bright follicles and vascular threshold density at 300 μm and 500 μm depths. The types and extent of microscopic alterations in acne-prone skin patients may not be evident by clinical scores. Patients with low investigator global assessment (IGA) grades are a heterogeneous population, characterized by different microscopic skin features. Acne-prone skin is susceptible to treatment, and RCM and D-OCT imaging are sensitive tools to objectively monitor subclinical skin changes. Full article

Reliable indicators of cancer advancement have actively been sought recently. The detection of colorectal cancer progression markers is essential in improving diagnostic and therapeutic protocols. The aim of the study was to investigate the profile of E-cadherin expression in colorectal cancer tissue depending on the TNM staging and its correlation with several clinical and histopathological features. The study included 55 colorectal cancer patients admitted to the surgical ward for elective surgery. Tissue samples were obtained from resected specimens. Different distributions of E-cadherin expression within tumors were observed; the highest percentage of positive E-cadherin expression was found in the invasive front and in the tumor center. Additionally, the different cellular distribution of E-cadherin expression was noticed; weak membranous E-cadherin expression was the highest in the invasive front and in the budding sites, but a strong membranous pattern was most frequent in the tumor center. Various distributions of E-cadherin expression depending on cancer progression were also found; E-cadherin expression in node-positive patients was lower in the tumor center and in the tumor invasive front, whereas, in patients with distant metastases, the expression of E-Cadherin was lower in the budding sites. In patients with higher TNM stages, E-cadherin expression was lower within the tumor (in the budding sites, tumor center, and invasive front). In tumors with lymphoid follicles, E-cadherin expression was higher in all localizations within the primary tumor. E-cadherin expression in the tumor center was also lower in tumors with some higher tumor budding parameters (areas of poorly differentiated components and poorly differentiated clusters). E-cadherin expression was found to be lower at the tumor center in younger individuals, at the budding sites in men, and at the surrounding lymph nodes in rectal tumors. Low E-cadherin expression appears to be a reliable indicator of higher cancer staging and progression. When assessing the advancement of cancer, apart from the TNM classification, it is beneficial to also consider the expression of E-cadherin. High tumor budding, the poverty of lymphoid follicles, and low E-cadherin expression analyzed simultaneously may contribute to a reliable assessment of colorectal cancer staging. These three histopathological features complement each other, and their investigation, together with conventional tumor staging and grading, may be very helpful in predicting the prognosis of colorectal cancer patients and qualifying them for the best treatment. The role of E-cadherin in the diagnosis and treatment of colorectal cancer, as a part of a personalized medicine strategy, still requires comprehensive, prospective clinical evaluations to precisely target the optimal therapies for the right patients at the right time. Full article

Purpose: This study aims to compare dry eye parameters before and after COVID-19 infection in dry eye patients. Methods: We included 44 dry eye patients (88 eyes) from our existing dry eye cohort, with 22 belonging to the post-COVID-19 group due to a prior COVID-19 infection and the other 22 forming the non-COVID-19 group as they had no history of COVID-19. We examined and compared the dry eye parameters of the post-COVID-19 group, including the ocular surface disease index (OSDI), Schirmer’s test results (ST), non-invasive Keratography tear break-up time (NIKBUT), lipid layer thickness (LLT), Meibomian gland dysfunction (MGD), and the grading of papillae and follicles, both before and after the COVID-19 infection. We also compared the dry eye parameters difference of the post-COVID-19 group with the non-COVID-19 group. Results: The post-COVID-19 group was comprised of individuals with an average age of 38.36 ± 14.99 years, of which 82% were female. The time interval between the two tests was 16.92 ± 5.40 months, which did not differ significantly from the non-COVID-19 group. Compared to the pre-COVID-19 eyes, the post-COVID-19 eyes showed a significant decrease in the average LLT (52.86 ± 18.00 nm vs. 63.00 ± 22.40 nm, p < 0.001), as well as the maximum LLT (67.89 ± 20.81 nm vs. 78.48 ± 20.55 nm, p < 0.001). The MGD in both the upper (1.75 ± 0.84) and lower eyelids (1.43 ± 0.73) worsened after a COVID-19 infection. Additionally, the grading of papillae was worse following a COVID-19 infection (0.61 ± 0.69 vs. 0.16 ± 0.37, p < 0.001). The multivariate linear regression model revealed a negative association between COVID-19 infection and NIKBUT-average (β = −2.98, 95%CI: (−5.82, −0.15), p = 0.039), LLT-average (β = −14.12, 95%CI: (−22.66, −5.59), p = 0.001), and LLT max (β = −15.65, 95%CI: (−23.09, −8.20), p < 0.001). Conclusion: From preliminary results, we concluded that dry eye patients who have been infected with COVID-19 appear to have a more severe dry eye condition, as evidenced by lower LLT, worse papillae and MGD, and shorter NIKBUT. It is important to raise awareness of this potential long-term symptom of COVID-19, especially among existing dry eye patients. Full article

The conceptual description of Follicular lymphoma (FL) in the 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumors (WHO-HAEM5) has undergone significant revision. The vast majority of FL (85%) with a follicular growth pattern are composed of centrocytes and centroblasts, harbor the t(14;18)(q32;q21) translocation and are now termed classic FL (cFL). They are set apart from three related subtypes, FL with predominantly follicular growth pattern, FL with unusual cytological features (uFL) and follicular large B-cell lymphoma (FLBCL). In contrast to the revised 4th edition of the WHO classification of haematolymphoid tumors (WHO-HAEM4R), grading of cFL is no longer mandatory. FL with a predominantly diffuse growth pattern had been previously recognized in WHO-HAEM4R. It frequently occurs as a large tumor in the inguinal region and is associated with CD23 expression. An absence of the IGH::BCL2 fusion and frequent STAT6 mutations along with 1p36 deletion or TNFRSF14 mutation is typical. The newly introduced subtype of uFL includes two subsets that significantly diverge from cFL: one with “blastoid” and one with “large centrocyte” variant cytological features. uFL more frequently displays variant immunophenotypic and genotypic features. FLBCL is largely identical to WHO-HAEM4R FL grade 3B and renaming was done for reasons of consistency throughout the classification. In-situ follicular B-cell neoplasm, pediatric-type FL, duodenal-type FL and primary cutaneous follicle center lymphoma are categorized as discrete entities. In addition, novel findings concerning underlying biological mechanisms in the pathogenesis of early and systemic follicular lymphoma will be presented. Full article

The Wnt signaling pathway is important in the normal development and regulation of ovarian follicles throughout the lifecycle of females. Dysregulation of the Wnt signaling pathway, genetically or epigenetically, with subsequent activation of β-catenin has been implicated in tumorigenesis of a spectrum of ovarian neoplasms, from benign to malignant. We review the recent findings of the Wnt signaling pathway involved in regulating normal physiologic processes of the ovarian follicle cycle. We also review the β-catenin mutations in a family of low-grade ovarian stromal tumors, focusing on characterizing their shared morphological features and the utility of immunohistochemistry of β-catenin in facilitating the accurate diagnosis of these ovarian stromal tumors. The Wnt signaling pathway is one of the most critical mechanisms in regulating cell proliferation, differentiation, and morphogenesis. The Wnt signaling pathway comprises a diverse group of glycoproteins that serve as ligands and bind to transmembrane Frizzled family receptors. The ligand-receptor interactions activate the pathway and govern the downstream signaling cascades, ultimately affecting the transcriptional control of the cellular cytoskeleton, organelle dynamics, epithelial-mesenchymal interaction, and tissue remodeling in the ovary. Wnt signaling consists of two major pathways: a canonical pathway that is β-catenin-dependent and a non-canonical Wnt pathway that is β-catenin-independent. Canonical Wnt signaling is governed by the interaction of β-catenin with other molecules to regulate cellular decisions related to proliferation and differentiation. Recent studies have demonstrated that the Wnt signaling pathway plays important roles in the development and regulation of ovarian folliculogenesis and oogenesis. Full article

Neoplastic progression is influenced by the expression of tumour antigens that activate an anti-tumour immune response. Human medical studies show that this body defence is carried out in secondary lymphoid organs (SLOs) but also directly in the tumour through organized cellular aggregates that are called tertiary lymphoid structures (TLSs). However, their occurrence has different meanings in different tumour types. For example, the presence of TLSs in breast cancer is associated with the most aggressive subtypes. This paper aimed to study TLSs in canine mammary simple carcinomas. A morphological assessment of the inflammatory infiltrate was performed on H&E sections of fifty cases. Immunohistochemistry was then carried out to typify the inflammatory cells in the tumour microenvironment. Results showed that, sometimes, inflammatory infiltrates were organized in follicles close to high-grade carcinomas, simulating a lymphoid organization, as in breast cancer. Therefore, we can assume that even in canine mammary tumours, TLSs exist and they are entities to consider due to their presence in the most aggressive histotypes or tumours with a high degree of malignancy. Full article