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The integrity of stratified epithelia depends on the ability of progenitor cells to maintain a balance between proliferation and differentiation. While much is known about the transcriptional pathways underlying progenitor cells’ behavior in the epidermis, the role of posttranscriptional regulation by mRNA binding proteins—a rate-limiting step in sculpting the proteome—remains poorly understood. Here we report that the RNA binding protein YBX1 (Y-box binding protein-1) is a critical effector of progenitors’ function in the epidermis. YBX1 expression is restricted to the cycling keratinocyte progenitors in vivo and its genetic ablation leads to defects in the architecture of the skin. We further demonstrate that YBX1 negatively controls epidermal progenitor senescence by regulating the translation of a senescence-associated subset of cytokine mRNAs via their 3′ untranslated regions. Our study establishes YBX1 as a posttranscriptional effector required for maintenance of epidermal homeostasis. The integrity of the stratified epithelia relies on controlled cell turnover but it is unclear how mRNA binding proteins regulates this. Here, the authors show that the RNA binding protein Y-box binding protein-1 translationally represses cytokines, so preventing senescence and maintaining epidermal homeostasis.

Background and Aims Acupuncture is a widely used therapeutic practice that targets specific points on or beneath the skin, known as acupoints. While acupoints are thought to exhibit low electrical resistance, their underlying biophysical and molecular characteristics remain incompletely understood. This study investigates the presence and properties of high‐conductivity regions in surgically isolated human skin. Methods High‐conductivity points (HCPs) were identified on human skin explants using a clinical conductivity‐based acupoint detector. Histological, transcriptomic, and metabolomic analyses were performed on HCP and control regions, with and without needle stimulation. To probe mechanistic pathways, human keratinocytes and fibroblasts were cultured under biotin‐deficient conditions, mimicking stimulation‐induced metabolic changes. Results No significant structural differences were observed between HCPs and control skin. However, RNA sequencing revealed that needled HCPs activated gene programs resembling those of anatomically defined murine acupoints. Metabolomic profiling showed a stimulation‐specific decrease in biotin levels at HCPs. In vitro, biotin deficiency altered acetyl‐CoA carboxylase regulation and increased ATP production via mitochondrial respiration and glycolysis. Conclusion These findings suggest that biotin‐dependent metabolic reprogramming occurs at electrically distinct skin regions in response to physical stimulation. While the relationship between HCPs and classical acupoints remains to be fully established, this study provides novel insights into the local biochemical responses associated with acupuncture.

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) syndrome is a rare genetic disorder caused by mutations in the TP63 gene, which encodes a transcription factor essential for epidermal gene expression. A key feature of AEC syndrome is chronic skin erosion, for which no effective treatment currently exists. Our previous studies demonstrated that mutations associated with AEC syndrome lead to p63 protein misfolding and aggregation, exerting a dominant-negative effect. By performing a high-throughput screening of epigenetic and FDA-approved compounds in a co-transfection model of wild-type and mutant p63, we found that two compounds, Doxorubicin and Epirubicin, alleviate protein aggregation and restore p63 transactivation function. Moreover, treatment with these compounds reduced protein aggregation and restored the expression of keratinocyte-specific p63 target genes in primary keratinocytes derived from a conditional ΔNp63αL514F knock-in AEC mouse model, which mimics the ectodermal defects and skin erosions characteristic of AEC syndrome. A chemical analog of Doxorubicin, diMe-Doxorubicin, which exhibits lower tissue and organ toxicity, was also found to be effective in promoting the disaggregation of mutant p63 and rescuing its transcriptional activity. Our findings identify compounds that can partially resolve mutant p63 aggregation, increase its monomeric isoform, and reactivate its transcriptional function. These results suggest potential therapeutic efficacy for treating skin erosions in AEC syndrome.

Background Our Thyroid-Multidisciplinary Clinic is a large referral site for thyroid diseases. Thyroid biopsies are mainly performed for thyroid cancer screening. Yet, Hashimoto thyroiditis (HT) is being too frequently diagnosed. The prevalence of HT is reported as 0.3-1.2% or twice the prevalence of type 1 diabetes. However, the prevalence of HT confirmed by cytology is still uncertain. To evaluate different aspects of thyroid physiopathology including prevalence of Hashimoto's, a database of clinical features, ultrasound images and cytology results of patients referred for FNA of thyroid nodules was prospectively developed. Methods We retrospectively studied 811 consecutive patients for whom ultrasound guided thyroid FNA biopsies were performed at our clinic over 2.5 year period (Mar/2006-Sep/2008). Results The analysis of our database revealed that from 761 patients, 102 (13.4%) had HT, from whom 56 (7.4%) were euthyroid or had sub-clinical (non-hypothyroid) disease, and 46 (6%) were clinically hypothyroid. Conclusions This is the first study to show such a high prevalence of HT diagnosed by ultrasound-guided FNA. More strikingly, the prevalence of euthyroid HT, appears to be >5% similar to that of type 2 diabetes. Based on our results, there might be a need to follow up on cytological Hashimoto's to monitor for thyroid failure, especially in high risk states, like pregnancy. The potential risk for thyroid cancer in patients with biopsy-proven inflammation of thyroid epithelium remains to be established prospectively. However, it may explain the increased risk for thyroid cancer observed in patients with elevated but within normal TSH.

Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide. Skin exposure is the leading risk factor for initiating NMSC. Ultraviolet (UV) light induces various genomic aberrations in both tumor-promoting and tumor-suppressing genes in epidermal cells. In conjunction with interactions with a changed stromal microenvironment and local immune suppression, these aberrations contribute to the occurrence and expansion of cancerous lesions. Surgical excision is still the most common treatment for these lesions; however, locally advanced or metastatic disease significantly increases the chances of morbidity or death. In recent years, numerous pharmacological targets were found through extensive research on the pathogenic mechanisms of NMSCs, leading to the development of novel treatments including Hedgehog pathway inhibitors for advanced and metastatic basal cell carcinoma (BCC) and PD-1/PD-L1 inhibitors for locally advanced cutaneous squamous cell carcinoma (cSCC) and Merkel cell carcinoma (MCC). Despite the efficacy of these new drugs, drug resistance and tolerability issues often arise with long-term treatment. Ongoing studies aim to identify alternative strategies with reduced adverse effects and increased tolerability. This review summarizes the current and emerging therapies used to treat NMSC.

Giant aneurysms arising from the cavernous internal carotid artery (ICA) can mimic pituitary adenomas and may cause pituitary dysfunction due to their mass effect on the pituitary gland. We report a case of a 56-year-old man presenting with impotence, fatigue and panhypopituitarism who was found to have a giant unruptured aneurysm arising from the right cavernous ICA with severe mass effect on the pituitary gland. The patient underwent endovascular treatment of the giant aneurysm using two telescoping Surpass flow-diverting stents. At 6-month follow-up, repeat cerebral angiography showed Raymond grade II occlusion of the aneurysm with a small neck remnant. At the 10-month follow-up the patient showed full recovery of his pituitary function and clinical resolution of impotence and fatigue. This is the first report of occlusion of a giant cavernous carotid aneurysm using next generation Surpass flow-diverting stents leading to complete recovery of pituitary function.

Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression.

According to Rinker (2017), Pleurotus species are grown on wood sawdust and plant fibers supplemented with locally available proteins and carbohydrates. The main application of mushroom residues in vegetable production is as a component of growing media (Charles Heuser et al., 2007; Younis et al., 2023 ) for seedling production of crops such as tomato (Medina et al, 2009; Eudoxie and Alexander, 2011; Zhang et al., 2012; Ünal, 2015; Priadi et al., 2016; Collela et al., 2019; Alves et al., 2024), pepper (Medina et al., 2009; Demir, 2017), lettuce (Kwack et al., 2012; Marques et al., 2014; Liu et al., 2018), eggplant (So nmez et al., 2016), cucumber (Zhang et al., 2012), melon (Van Tam and Wang, 2015) and zucchini (Medina et al., 2009). Furthermore, spent mushroom substrate can enhance microbial diversity (Huang et al., 2023), aid in disease control (Mwangi et al., 2024), support biogas production (Kumar et al., 2022), contribute to bioremediation efforts (Rinker, 2017), and serve as a material for biodegradable containers in horticulture (Postemsky et al., 2016). MATERIAL AND METHODS In order to achieve the first objective a detailed analysis of the physical and chemical properties of a spent mushroom substrate of oyster mushroom (Pleurotus ostreatus) was conducted at the accredited Laboratory for Soil and Fertilizer Analysis (L-04), Faculty of Agricultural Sciences and Food - Skopje.

Giant aneurysms arising from the cavernous internal carotid artery (ICA) can mimic pituitary adenomas and may cause pituitary dysfunction due to their mass effect on the pituitary gland. We report a case of a 56-year-old man presenting with impotence, fatigue and panhypopituitarism who was found to have a giant unruptured aneurysm arising from the right cavernous ICA with severe mass effect on the pituitary gland. The patient underwent endovascular treatment of the giant aneurysm using two telescoping Surpass flow-diverting stents. At 6-month follow-up, repeat cerebral angiography showed Raymond grade II occlusion of the aneurysm with a small neck remnant. At the 10-month follow-up the patient showed full recovery of his pituitary function and clinical resolution of impotence and fatigue. This is the first report of occlusion of a giant cavernous carotid aneurysm using next generation Surpass flow-diverting stents leading to complete recovery of pituitary function.

The function of the kinase p38α in inflammation is unclear. Park and colleagues show that p38α exerts pro- or anti-inflammatory effects depending on the cell type in which it is expressed and the stimulus eliciting its activation. The mitogen-activated protein kinase p38 mediates cellular responses to injurious stress and immune signaling. Among the many p38 isoforms, p38α is the most widely expressed in adult tissues and can be targeted by various pharmacological inhibitors. Here we investigated how p38α activation is linked to cell type–specific outputs in mouse models of cutaneous inflammation. We found that both myeloid and epithelial p38α elicit inflammatory responses, yet p38α signaling in each cell type served distinct inflammatory functions and varied depending on the mode of skin irritation. In addition, myeloid p38α limited acute inflammation via activation of anti-inflammatory gene expression dependent on mitogen- and stress-activated kinases. Our results suggest a dual function for p38α in the regulation of inflammation and show mixed potential for its inhibition as a therapeutic strategy.