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Background Psoriasis vulgaris is the most common form of psoriasis, yet current treatments often lead to significant side effects, resulting in a high rate of therapy desertion. Here, we explored a novel therapeutic approach using the secretome from Wharton Jelly-derived mesenchymal stem cells, biologically stabilized and enhanced with hyaluronic acid (HA), its presentation is an easy-to-apply topical sponge. This formulation had previously demonstrated efficacy in vitro and in experimental psoriasis mouse models. Methods In vitro characterization studies included dynamic light scattering, nanoparticle tracking analysis, optical/electronic microscopy, microbiological experiments, and angiogenic capacity (HUVEC cells). In vivo studies included angiogenic capacity in chicken embryo chorioallantoic membrane (CAM), safety (hypersensitive and healthy volunteers), and efficacy (double-blinded and randomized patients). Results We demonstrated the presence of spherical exosomes (164 ± 87 nm, PDI of 0.38, and 1.5 × 10⁷ particles/mL) within the selected secretomes, which exhibited significant proangiogenic activity in HUVEC cells and in a CAM assay. The secretome-containing sponges displayed distinct physicochemical properties, such as the absence of nitrogen and reduced carbon and oxygen content, resulting in a more cross-linked material with thinner fibers. These characteristics extended the dispersion time in aqueous media. Microbiological testing confirmed sterility in the packed, ready-to-use secretome-HA sponges after 3 months of storage. To assess safety, we selected doses (based on total protein content) that were applied to three patients with atopic dermatitis (42 µg of protein, patch test, 5 days) and four healthy volunteers (210 µg, 15 days) with no observed adverse topical or systemic effects. In a 30-day efficacy study, 12 patients with bilateral psoriasis exhibited up to a 33% reduction in mPASI scores and a 41% decrease in plaque size. Additionally, transepidermal water loss (TEWL) was reduced by up to 30%, while skin elasticity/flexibility improved by 43%. Conclusions These findings suggest that the topical application of the secretome-HA sponge is a safe and effective therapeutic option for alleviating symptoms of psoriasis vulgaris . Trial registration SSMN, SSMN047/2021. Registered 27 October 2021, https://www.ssmn.cl/comite_etica.php . Graphical abstract

Quality skin has long been a symbol of health and attractiveness, reflecting both genetic and environmental influences. Multiple elements contribute to beautiful skin. This complex topic influences modern dermatological practices and skincare approaches. This article reviews and explores the characteristics that define beautiful skin, integrating physical attributes with the scientific foundations that underpin them. It also delves into the evolutionary significance of skin appearance and the impact of visible skin conditions on social and psychological well-being. Additionally, it reviews advances in dermatological treatments and preventive measures aimed at achieving beautiful skin.

Atypical teratoid/rhabdoid (AT/RT) tumor is a rare, highly malignant tumor of the central nervous system (CNS) most commonly found in children less than 5 years of age. Although the vast majority of cases are diagnosed in young children, there have been isolated case reports in adults. Since its histological appearance can be confused with other tumors, especially in adults, separating AT/RT from other neoplasms may be difficult. In many instances, a reliable diagnosis is not possible without demonstrating the lack of nuclear INI1 protein expression by immunohistochemical methods. The patients (three males and one female) ranged in age from 23 to 42 years (mean age, 32 years). Radiographically, two tumors were localized in the right fronto-parietal region, one was frontal and the other was found in the left temporal lobe. Varying degrees of hydrocephalus and heterogeneous enhancement were present on MRI. In all cases, diagnosis during intraoperative consultation and preliminary diagnosis was different from the final diagnosis after immunohistochemical analysis. Immunohistochemical staining showed that the tumor cells were positive for vimentin and reacted variably for keratin, epithelial membrane antigen (EMA), synaptophysin, neurofilament protein, CD34, and smooth muscle actin (SMA). All were negative for GFAP, S-100, desmin and CD99. Three of the four cases lacked nuclear expression of INI1. One patient is alive with no evidence of disease 17 years after the diagnosis. In adult examples of AT/RT, the diagnosis requires a high index of suspicion, with early tissue diagnosis and a low threshold for investigation with INI1 immunohistochemistry to differentiate this entity from other morphologically similar tumors. Although the prognosis is dismal in pediatric population, long term survival is possible in adult AT/RT cases after surgery and adjuvant radiotherapy and chemotherapy.

Identification of tumor‐derived proteins in the circulation may allow for early detection of cancer and evaluation of therapeutic responses. To identify circulating tumor‐derived proteins, mice were immunized with concentrated culture medium conditioned by human breast cancer cells. Antibodies generated by hybridomas were screened against conditioned media from both normal epithelial cells and tumor cells. Antibody selectively reacting with tumor cell–conditioned media was further characterized. This led to the development of a monoclonal antibody (Alper‐p280) that reacts with a newly identified 280‐kDa secreted variant of human filamin‐A. Circulating filamin‐A was detected in patient plasma samples using Alper‐p280 in an ELISA assay. Human plasma samples from 134 patients with brain, breast, or ovarian cancer, 15 patients with active arthritis, and 76 healthy controls were analyzed. Filamin‐A protein levels in human cell lines and tissues were analyzed by western blotting, immunohistochemistry, and electron and confocal microscopy. Circulating filamin‐A was detected in the plasma of 109 of 143 patients with breast cancer and primary brain tumors. Plasma levels of filamin‐A showed 89.5% sensitivity (95% confidence interval [CI] = 0.67% to 0.99%) and 97.8% specificity (95% CI = 0.88% to 0.99%) for glioblastoma at a cut‐off of 21.0 ng/mL. Plasma levels of filamin‐A (>36.0 ng/mL) had 96.7% sensitivity (95% CI = 0.80% to 0.99%) and 67.8% specificity (95% CI = 0.54% to 0.79%) for metastatic breast cancer. Filamin‐A levels were increased in malignant breast or brain tissues, but not in normal control tissues. Filamin‐A localized to lysosomes in MDA.MB.231 breast cancer cells, but not in normal human mammary epithelial cells, suggesting that filamin‐A may undergo cancer‐specific processing. Plasma filamin‐A appears to be a specific and sensitive marker for patients with high‐grade astrocytoma or metastatic breast cancer. Additional novel cancer biomarkers have been identified and are being developed alongside Alper‐p280 for use in diagnosis of breast carcinoma and high‐grade astrocytoma, and for use in the evaluation of therapeutic responses. (Cancer Sci 2009; 100: 1748–1756)

Previous attempts to classify flow units in Iranian carbonate reservoirs, based on porosity and permeability, have faced challenges in correlating the rock's pore size distribution with the capillary pressure profile. The innovation of this study highlights the role of clustering techniques, such as Discrete Rock Type, Probability, Global Hydraulic Element, and Winland's Standard Chart in enhancing the reservoir's rock categorization. These techniques are integrated with established flow unit classification methods. They include Lucia, FZI, FZI*, Winland R35, and the improved stratigraphic modified Lorenz plot. The research accurately links diverse pore geometries to characteristic capillary pressure profiles, addressing heterogeneity in intricate reservoirs. The findings indicate that clustering methods can identify specific flow units, but do not significantly improve their classification. The effectiveness of these techniques varies depending on the flow unit classification method employed. For instance, probability-based methods yield surpassing results for low-porosity rocks when utilizing the FZI* approach. The discrete technique generates the highest number of flow unit classes but provides the worst result. Not all clustering techniques reveal discernible advantages when integrated with the FZI method. In the second part, the study creatively suggests that rock classification can be achieved by concurrently clustering irreducible water saturation (SWIR) and porosity in unsuccessful flow unit delineation cases. The SWIR log was estimated by establishing a smart correlation between porosity and SWIR in the pay zone, where water saturation and SWIR match. Then, the estimated saturation was dispersed throughout the reservoir. Subsequently, the neural network technique was employed to cluster and propagate the three finalized flow units. This methodology is an effective recommendation when conventional flow unit methods fail. The study also investigates influential factors causing the failure of flow unit classification methods, including pore geometry, oil wettability, and saturation in heterogeneous reservoirs.

We encountered a child with an intraosseous small round cell tumor that was negative for LCA, CD20 (L26), and CD3 and positive for vimentin, CD99 (MIC-2), and periodic acid-Schiff. The tumor exhibited rosette-like formations. This case was initially interpreted as Ewing's sarcoma (ES); however, additional studies revealed positivity for CD79a, CD43, and TdT expression, and an immunoglobulin heavy chain gene rearrangement (IgH-R) by polymerase chain reaction (PCR) established this to be a precursor B-lymphoblastic lymphoma. Because the differential diagnosis of ES and lymphoblastic lymphoma can be difficult and the differential diagnostic value of leukocyte antigens and immunoglobulin heavy chain gene rearrangement studies have not been fully evaluated, we conducted a more extensive investigation on 33 (21 soft tissue and 12 intraosseous) ES cases. Cases were retrieved from the files of the Department of Pathology at Georgetown University and from the Soft Tissue Registry of the Armed Forces Institute of Pathology. The cases were studied by light microscopy, immunohistochemistry, and PCR for IgH-R and T cell receptor gamma chain gene rearrangement (Tγ-R). There were 17 females and 16 males; the mean age was 29.3 years. Locations included the extremities (n = 17) and trunk (n = 16). All cases fit the ES spectrum by light microscopy and immunohistochemistry, as previously determined, and were negative for lymphoid markers (LCA, CD3, CD20, CD43, CD79a, and TdT), CD10 and CD34. CD99 was positive in 31/33 and bcl-2 was weakly positive in 13/33 cases. All 21 cases studied for gene rearrangements by PCR were negative for IgH-R and Tγ-R. Distinction of intraosseous lymphoblastic lymphoma from ES may be difficult because lymphomas may occasionally exhibit unexpected morphologic and immunophenotypic properties including LCA, CD3 and CD20 negativity and cytokeratin positivity. Additional analysis using CD79a, CD43, TdT, and PCR should be performed to avoid misdiagnosis. True ES is negative for lymphoid markers including CD79a, CD43, and TdT, as well as for IgH-R and Tγ-R.

Differentiating oligodendroglioma from extraventricular neurocytoma by conventional light microscopy alone can present a diagnostic challenge. We report pathologic findings of an unusual spinal cord tumor from a 33-year-old male patient which showed hybrid features of oligodendroglioma and extraventricular neurocytoma. Magnetic resonance imaging (MRI) showed an enhancing intramedullary mass in the cervicothoracic region (C7 through T6). Histologic examination revealed a clear cell neoplasm containing ganglion-like cells and calcifications, prompting the differential diagnosis of oligodendroglioma and extraventricular neurocytoma. The immunohistochemical analysis disclosed neural differentiation of the neoplastic cells with strong synaptophysin and neurofilament staining consistent with extraventricular neurocytoma, as well as strong S-100 and glial fibrillary acidic protein (GFAP) expression. Molecular studies with fluorescent in situ hybridization (FISH) revealed chromosome 1p/(partial) 19q deletions, a finding commonly observed in oligodendroglioma. The proliferation index (using antibody MIB1) of the tumor was approximately 30%. The morphologic findings and these results strengthen the hypothesis that these tumors may share a common progenitor cell, which has also been observed by others. Because there are differences in patient management and long-term prognosis, it is important to attempt to distinguish between oligodendroglioma and neurocytoma. This unusual case and similar rare reported cases support the need to reclassify tumors showing pathologic features common to both neurocytoma and oligodendroglioma as a unique entity, while the effort continues to identify the cell of origin.

Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://www.nature.com/group/journalclub

Using conditional cell reprogramming, we generated a stable cell culture of an extremely rare and aggressive neuroendocrine cervical cancer. The cultured cells contained HPV-16, formed colonies in soft agar and rapidly produced tumors in immunodeficient mice. The HPV-16 genome was integrated adjacent to the Myc gene, both of which were amplified 40-fold. Analysis of RNA transcripts detected fusion of the HPV/Myc genes, arising from apparent microhomologous recombination. Spectral karyotyping (SKY) and fluorescent- in-situ hybridization (FISH) demonstrated coordinate localization and translocation of the amplified Myc and HPV genes on chromosomes 8 and 21. Similar to the primary tumor, tumor cell cultures expressed very high levels of the Myc protein and, in contrast to all other HPV-positive cervical cancer cell lines, they harbored a gain-of-function mutation in p53 (R273C). Unexpectedly, viral oncogene knockdown had no effect on the growth of the cells, but it did inhibit the proliferation of a conventional HPV-16 positive cervical cancer cell line. Knockdown of Myc, but not the mutant p53, significantly inhibited tumor cell proliferation. On the basis of these data, we propose that the primary driver of transformation in this aggressive cervical cancer is not HPV oncogene expression but rather the overexpression of Myc.

Despite intensive investigation, no clearly defined mechanism explaining human immunodeficiency virus (HIV)-induced cell killing has emerged. HIV-1 infection is initiated through a high-affinity interaction between the HIV-1 external envelope glycoprotein (gp120) and the CD4 receptor on T cells. Cell killing is a later event intimately linked by in vitro genetic analyses with the fusogenic properties of the HIV envelope glycoprotein gp120 and transmembrane glycoprotein gp41. In this report, we describe aberrancies in cell cycle regulatory proteins initiated by cell-cell contact between T cells expressing HIV-1 envelope glycoproteins and other T cells expressing CD4 receptors. Cells rapidly accumulate cyclin B protein and tyrosine-hyperphosphorylated p34cdc2 (cdk1) kinase, indicative of cell cycle arrest at G2phase. Moreover, these cells continue to synthesize cyclin B protein, enlarge and display an abnormal ballooned morphology, and disappear from the cultures in a pattern previously described for cytoxicity induced by DNA synthesis (S phase) inhibitors. Similar changes are observed in peripheral blood mononuclear cells infected in vitro with pathogenic primary isolates of HIV-1.