Essential Marker Research Articles

Production and characterization of monoclonal antibodies against hepatitis B e-antigen and their potential application for development of HBeAg detection ELISA.

Despite global vaccination efforts, hepatitis B virus (HBV) infection remains a major health threat, causing over a million deaths annually. Hepatitis B e-antigen (HBeAg) is an indicator of HBV replication and high infectivity. HBeAg is an essential serological marker for monitoring response to treatment and/or determining the stage of chronic HBV infection. Here, we produced a panel of mouse hybridomas secreting monoclonal antibodies (MAbs) to HBeAg by fusing a mouse myeloma cell line with splenocytes from mice immunized with recombinant HBeAg. Anti-HBe MAbs were then characterized by competition ELISA and Western blotting. We designed and optimized an in-house sandwich ELISA using HBeAg-specific rabbit polyclonal and mouse monoclonal antibodies. The diagnostic performance of the assay was then compared to a commercial HBeAg detection ELISA kit using 176 HBeAg[-] and 44 HBeAg[+] serum samples, showing a significant positive correlation (r=0.8250; P<0.0001). The in-house ELISA showed reasonable sensitivity (97.56%) and specificity (99.40%), with a cut-off value and area under the curve of 0.193 and 0.9884, respectively. Additionally, the assay showed high repeatability, with intra- and inter-assay coefficients of variation of 2.46% and 11.38%, respectively. Our designed HBeAg-detecting sandwich ELISA has the potential for use in clinical diagnosis.

The C-terminal structure of the N6-methyladenosine deaminase YerA and its role in deamination.

The N6-methyladenine (6mA) modification is an essential epigenetic marker and plays a crucial role in processes, such as DNA repair, replication, gene expression regulation, etc. YerA from Bacillus subtilis is considered a novel class of enzymes capable of catalyzing the deamination of 6mA to produce hypoxanthine. Despite the significance of this type of enzymes in bacterial self-defense systems and potential applications as a gene-editing tool, the substrate specificity, the catalytic mechanism and the physiological function of YerA are currently unclear due to the lack of structural information. In this study, we expressed the recombinant enzyme and conducted its reconstitution to yield the active form. Our deamination assays showed that N6-methyladenosine (N6-mAdo) served as a more favorable substrate than its base derivative 6mA. Here we report the high-resolution structure of the C-terminal region of YerA, which exhibited a compact architecture composed of two antiparallel b-sheets with no obvious close structural homologs in PDB. We also created docking models to investigate the ligand-binding pattern, and found that more favorable contacts of N6-mAdo with the enzyme binding pocket lead to its preference for 6mA. Lastly, structural comparison to the deaminase MAPDA allowed us to propose a plausible role for this C-terminal region: shielding the active site from solvent and protecting the intermediate during catalysis. Taken together, this study sheds light on the catalytic mechanism and evolutionary pathways of the promiscuous enzyme YerA, thereby contributing to our molecular understanding of epigenetic nucleoside metabolism.

Abundance of long-chain polyunsaturated fatty acids in European eel (Anguilla anguilla L.) is determined by diet rather than biosynthesis.

The European eel (Anguilla anguilla L.) exhibits a remarkable phenotypic plasticity by occupying both marine and freshwater habitats and transitional areas in between. Because these habitats are characterized by different food sources with different fatty acid compositions, it remains unclear how eels from different habitats obtain essential long-chain polyunsaturated fatty acids (LC-PUFAs) to integrate in their lipids. We studied whether the fatty acid composition of eels in three different habitats, that is, a marine lagoon, an estuary, and a river, could be related to the expression levels of genes involved in the LC-PUFA pathways. In general, there were no significant differences in gene expression between eels from marine and freshwater habitats; gene expression in marine and freshwater specimens significantly differed from eels caught in the estuary. However, levels of essential LC-PUFAs and fatty acid ratio markers differed significantly between eels from the river and the marine lagoon. Therefore, we conclude that the LC-PUFA composition of the European eel is likely defined by their food intake from the local environment they are living in and potentially affected by the prevailing conditions, such as food availability, temperature, and salinity.

Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer's disease in two independent study cohorts.

A major challenge in the development of more effective therapeutic strategies for Alzheimer's disease (AD) is the identification of molecular mechanisms linked to specific pathophysiological features of the disease. Importantly AD has a two-fold higher incidence in women than men and a protracted prodromal phase characterized by amnestic mild-cognitive impairment (aMCI) suggesting that biological processes occurring early can initiate vulnerability to AD. Here, we used a sample of 125 subjects from two independent study cohorts to determine the levels in plasma (the most accessible specimen) of two essential mitochondrial markers acetyl-L-carnitine (LAC) and its derivative free-carnitine motivated by a mechanistic model in rodents in which targeting mitochondrial metabolism of LAC leads to the amelioration of cognitive function and boosts epigenetic mechanisms of gene expression. We report a sex-specific deficiency in free-carnitine levels in women with aMCI and early-AD compared to cognitively healthy controls; no change was observed in men. We also replicated the prior finding of decreased LAC levels in both women and men with AD, supporting the robustness of the study samples assayed in our new study. The magnitude of the sex-specific free-carnitine deficiency reflected the severity of cognitive dysfunction and held in two study cohorts. Furthermore, patients with the lower free-carnitine levels showed higher β-amyloid(Aβ) accumulation and t-Tau levels assayed in cerebrospinal fluid (CSF). Computational analyses showed that the mitochondrial markers assayed in plasma are at least as accurate as CSF measures to classify disease status. Together with the mechanistic platform in rodents, these translational findings lay the groundwork to create preventive individualized treatments targeting sex-specific changes in mitochondrial metabolism that may be subtle to early cognitive dysfunction of AD risk.

How the brain differentiates human and monkey faces: Neuromagnetic evidence from spatiotemporal dynamics

Face recognition is an important aspect of human non-verbal communication. Event-related potentials or magnetic fields, such as the N170/M170 component, are considered essential neural markers of face processing. Compared to upright human faces, inverted human faces and upright but not inverted animal faces cause longer latencies and larger amplitudes of these components. However, the mechanisms underlying this factor remain unclear. To elucidate the spatiotemporal dynamics of the processing of inverted human and animal faces, we recorded face-selective responses (M170) to upright and inverted human and monkey faces using a 306-channel whole-head magnetoencephalography. Sensor analysis showed an increased M170 latency and amplitude for inverted human and upright animal faces. However, in the source analysis, the observed modulations of the estimated spatiotemporal dynamics were different from the sensor results: irrespective of species, upright faces activated wider areas in the ventral and dorsal visual regions compared with inverted faces. Additionally, face orientation differentially modulated the anterior region of the fusiform gyrus (FG) in both face categories. These results suggest that spatiotemporal dynamics differ in face orientation regardless of category and that the FG contributes little or nothing to the M170 modulation recorded in the scalp sensor. Furthermore, we demonstrated that inverted human and animal faces are processed via different mechanisms.

Elucidating postoperative dynamics in tractional retinal detachment: a systematic review and meta-analysis of structural and functional outcomes following diabetic vitrectomy, including an analysis of postoperative complications.

This meta-analysis aims to evaluate the efficacy and safety of diabetic vitrectomy for treating tractional retinal detachment (TRD) by assessing visual acuity improvements, retinal reattachment success rates, and the frequency of postoperative complications. A comprehensive literature search identified 1,211 studies, 30 of which met the inclusion criteria and were analyzed. The meta-analyses were conducted via random effects models to account for heterogeneity. The primary outcomes were visual acuity improvement and retinal reattachment success, whereas postoperative complications were analyzed as secondary outcomes. Funnel plots, trim-and-fill methods, and Egger's regression tests were employed to assess and adjust for publication bias. The meta-analysis included data from 1,844 eyes across 30 studies. The pooled mean difference (MD) in visual acuity following diabetic vitrectomy was 0.80 logMAR (95% CI: 0.58-1.01, p < 0.0001), with significant heterogeneity (I² = 95%). The trim-and-fill method adjusted the MD to 1.15 (95% CI: 0.85-1.45), indicating potential publication bias. The pooled proportion of retinal reattachment success was 94.63% (95% CI: 90.88-96.89%), with substantial heterogeneity (I² = 82.2%). Egger's regression test confirmed publication bias in the retinal reattachment data (t = 6.07, df = 25, p < 0.0001). The most common postoperative complications were vitreous hemorrhage (8.2%, 0-41%), elevated intraocular pressure (7.3%, 0-25%), and cataract formation (10.3%, 0-43%). Diabetic vitrectomy significantly improves visual acuity and achieves high retinal reattachment success rates in patients with TRD despite considerable heterogeneity across studies. However, a critical limitation of the current literature is the lack of comprehensive reporting of essential markers of perfusion, such as the choroidal vascularity index and choriocapillaris flow area, which are crucial for a thorough understanding of the impact of vitrectomy on ocular perfusion and its correlation with structural and functional outcomes. These findings also highlight the need for vigilant postoperative management to mitigate common complications. Adjustments for publication bias via the trim-and-fill method suggest that the initial estimates of efficacy may be optimistic, but the overall benefits of the procedure remain substantial. Further research is warranted to standardize surgical techniques, include detailed perfusion outcomes, and enhance the reliability of future meta-analyses. Trial registration: Retrospectively registered.

Regeneration Status of Pterocarpus santalinus L.f. (Red Sanders) Dominated Tropical Dry Deciduous Forest of Eastern Ghats in Andhra Pradesh, India

Tropical dry deciduous forest regeneration dynamics are essential markers of biodiversity and ecological health. This study assesses the regeneration state of tree species in the Rajampet range, identifying a variety of patterns impacted by both natural and man-made influences. The study documented a total of 1391 adult individuals, 617 saplings, and 1646 seedlings from 67 species. Pterocarpus santalinus and Chloroxylon swietenia, two dominant species, showed "fair" regeneration potential, while Phyllanthus emblica and Azadirachta indica showed "good" regeneration potential. Nevertheless, a few species showed no regeneration, such as Bauhinia racemosa and Albizia amara. Overall Rajampet range regeneration is classified as 32.31 percent of species as "fair," 9.28 percent as "new," 15.38 percent as having "good" regeneration, and 43.08 percent as lacking.

Tertiary lymphoid structures in pancreatic cancer are structurally homologous, share gene expression patterns and B-cell clones with secondary lymphoid organs but show increased T-cell activation.

Tertiary lymphoid structures (TLS) in cancer are considered ectopic hotspots for immune activation that are similar to lymphoid follicles in secondary lymphoid organs (SLO). This study elucidates shared and TLS/SLO-specific features in pancreatic ductal adenocarcinoma (PDAC). TLS abundance was related to superior survival and T-cell abundance in 110 treatment-naïve PDAC samples, underlining their clinical relevance. Immunofluorescence microscopy identified structural homologies between TLS and SLO. In RNA-expression analyses of laser-microdissected TLS and paired SLOs, we observed largely overlapping expression patterns of immune-related gene clusters, but distinct expression patterns of T-cell and complement-associated genes. Immune cells in TLS expressed essential markers of germinal center formation. Increased activation of tumor-draining lymph nodes in patients with high numbers of TLS highlights the relevance of these tumor-related structures to systemic immune response. In line with this, we identified an overlap of expanded B-cell receptor clonotypes in TLS and SLO, which suggests a vivid cross-talk between the two compartments. . We conclude that combined therapeutic approaches exploiting TLS-mediated antitumor immune responses may improve susceptibility of PDAC to immunotherapy.

Evaluation of carp sperm respiration: fluorometry with optochemical oxygen sensor versus polarography

The primary function of spermatozoa is to fertilize the oocyte, which depends on their motility and is directly associated with their metabolic state. The oxygen consumption rate (OCR) of spermatozoa reflects the respiratory capacity of sperm mitochondria under various physiological conditions and is an essential marker of sperm quality. We determined the OCR of common carp (Cyprinus carpio) sperm using two respirometry methods: the conventionally used polarographic method with a Clark-type electrode and fluorometric assay with an Oxo Dish optochemical oxygen sensor. The latter was used for the first time to evaluate spermatozoa oxygen consumption in various metabolic states (under different treatments) at different dilution rates. These two methods were compared using Bland–Altman analysis, and the applicability of the optochemical oxygen sensor for evaluating carp sperm oxygen consumption was discussed. Sperm motility and progressive velocity parameters were also assessed to evaluate the effect of sperm respiration under different metabolic states and dilution rates and preincubation period on the physiological status of spermatozoa. The comparison of these respirometry methods clearly shows that while the polarographic method allows immediate measurement of oxygen levels after adding a sperm sample, the optochemical oxygen sensor has a priority in the amount of data obtained due to simultaneous measurements of several samples (e.g., different males, different fish species, repetitions of the same sample or various experimental conditions), even at a later time after adding sperm to the measuring chamber. However, the compared methods are complementary, and the proposed methodology can be applied to other fish species.

Clinical Diagnosis of Acute Noma: Essential Infection Markers and Clinical Presentations.

In clinical settings, understanding the markers and clinical signs of infection is critical for timely diagnosis and treatment. However, a point-of-care diagnostic test is lacking for noma, a debilitating orofacial infectious disease. This retrospective study reviewed electronic medical records (EMRs) and paper medical records (PMRs) of noma patients from Facing Africa (235 EMRs), Yekatit 12 Hospital (68 PMRs), and Project Harar (33 PMRs) in Ethiopia to identify essential infection markers and clinical presentations of acute noma. The review identified seven acute noma patients aged 4-9 years. The patients presented with facial edema, pain, anorexia, ecchymosis, excessive salivation, and drooling, as well as specific symptoms such as visual disturbances, high fever, foul odor, halitosis, and local tenderness. Laboratory findings included elevated white blood cell counts (13,500-14,500 cells/mcL), C-reactive protein levels (107-148 mg/L), and erythrocyte sedimentation rates (65-90 mm/hour). At >85 ng/mL, procalcitonin levels were particularly high. Accurate diagnosis of noma requires a comprehensive approach that includes thorough clinical examination, appropriate disease stage classification, medical history review, and laboratory testing. The study highlights the critical infection markers and clinical presentations associated with acute noma that may aid in early diagnosis of the disease. Further research with a much larger number of participants is needed. However, given the difficulty in identifying acute noma cases due to the rapid progression and very high mortality of the disease and the challenge of accessing acute noma cases owing to various socioeconomic barriers, the results of this small study are still relevant.

Ruxolitinib Treatment Ameliorates Clinical, Immunological, and Transcriptomic Aberrations in Patients with STAT3 Gain-of-Function Disease

BackgroundSTAT3 gain-of-function (GOF) disease presents with lymphoproliferation, autoimmunity, and failure to thrive. While JAK inhibitors have alleviated symptoms, their effects on disease pathogenesis remain unclear. ObjectiveWe prospectively investigated the clinical, immunological, and transcriptomic responses of four STAT3 GOF patients under long-term ruxolitinib treatment. MethodsWe conducted clinical and immunological evaluations at baseline and after ruxolitinib treatment at 3, 8, 12, and over 12 months. Our assessments included circulating T follicular helper cells (cTFH), regulatory T (Treg) cells, cytokine levels, and proliferation assays. Furthermore, we investigated the transcriptomic changes with treatment and conducted T-cell receptor sequencing. ResultsRuxolitinib achieved substantial control over the clinical manifestations. Post-treatment evaluations demonstrated a notable increase in naive CD4+ and CD8+ T cell populations, alongside a significant reduction in effector memory T cells. Additionally, there was a decrease in cTFH cells and double-negative T cells. Treg cell percentages and their canonical markers, already reduced before treatment, further declined with ruxolitinib. The treatment did not alter IFN-γ, IL-17A, IL-10, IL-4 cytokine productions of CD4+ T cells. Importantly, ruxolitinib effectively normalized the previously dysregulated transcriptome profile in peripheral blood mononuclear cells, bringing it closer to that of healthy controls. This normalization was most striking in the downregulation of STAT3-targeted genes, interferon-related genes, myeloid cell activation, and cytotoxic effector CD8+ T-cell genes, with effects persisting for up to 12 months. Self-reactive T-cell indices based on TCR repertoire analysis revealed potential auto-reactive cell clones in the patient samples. ConclusionRuxolitinib reversed cellular and transcriptomic signatures, enhancing our understanding of the disease's pathophysiology and highlighting essential immunological markers for precise monitoring.

Machine Learning-Based Cardiac Output Estimation Using Photoplethysmography in Off-Pump Coronary Artery Bypass Surgery.

Background/Objectives: Hemodynamic monitoring is crucial for managing critically ill patients and those undergoing major surgeries. Cardiac output (CO) is an essential marker for diagnosing hemodynamic deterioration and guiding interventions. The gold standard thermodilution method for measuring CO is invasive, prompting a search for non-invasive alternatives. This pilot study aimed to develop a non-invasive algorithm for classifying the cardiac index (CI) into low and non-low categories using finger photoplethysmography (PPG) and a machine learning model. Methods: PPG and continuous thermodilution CO data were collected from patients undergoing off-pump coronary artery bypass graft surgery. The dataset underwent preprocessing, and features were extracted and selected using the Relief algorithm. A CatBoost machine learning model was trained and evaluated using a validation and testing phase approach. Results: The developed model achieved an accuracy of 89.42% in the validation phase and 87.57% in the testing phase. Performance was balanced across low and non-low CO categories, demonstrating robust classification capabilities. Conclusions: This study demonstrates the potential of machine learning and non-invasive PPG for accurate CO classification. The proposed method could enhance patient safety and comfort in critical care and surgical settings by providing a non-invasive alternative to traditional invasive CO monitoring techniques. Further research is needed to validate these findings in larger, diverse patient populations and clinical scenarios.

Establishment of a CPAMD8-GFP reporter human embryonic stem cell line, IBBDe001-B, using CRISPR/Cas9 editing

The human CPAMD8 gene encodes proteins in the A2M/C3 (alpha-2-macroglobulin/complement 3) family, predominantly expressed in the distal tips of the retinal neuroepithelium that form the iris and ciliary body. Mutations in CPAMD8 have been linked to anterior segment dysplasia and congenital glaucoma. Using CRISPR/Cas9 editing, we inserted a 3*EAAAK-EGFP fluorescent tag into the CPAMD8 gene, enabling real-time observation of its expression and providing insights into its biological functions. The resulting gene-edited cell line retained normal stem cell morphology and karyotype, expressed essential pluripotency markers, and exhibited differentiation potential.

Rational integration of fluorogenic and quenching activity of dopamine for reversed ratiometric and semi-quantitative visual detection of tyramine

A facile and efficient reversed ratiometric fluorescence (RF) method has been developed for the sensitive and accurate detection of tyramine (Tyr), an essential marker for food spoilage in fermented or aged foods. This method utilizes an “activation-quenching integration” strategy involving the fluorogenic reactivity and quenching capacity of dopamine (DA), the tyrosinase (TYR) catalyzed products of Tyr. Under alkaline conditions, DA reacts with resorcinol to form azamonardine, exhibiting strong blue emission. Additionally, DA is oxidized to o-dopaquinone by TYR, which quenches the red fluorescence of CdTe quantum dots (QDs). Under optimized conditions, a Tyr-specific RF sensor was established, featuring a linear detection range from 0.1 to 6 mg/mL and a detection limit of 8.50 × 10−3 mg/L. The fabricated reversed RF sensing system was successfully applied for quantitative analysis of Tyr in real samples and semi-quantitative visual detection of Tyr in fermented food samples upon integration with a pseudo-color-assisted approach.

What are microsatellites and how to choose the best tool: a user-friendly review of SSR and 74 SSR mining tools.

Microsatellites, also known as SSR or STR, are essential molecular markers in genomic research, playing crucial roles in genetic mapping, population genetics, and evolutionary studies. Their applications range from plant breeding to forensics, highlighting their diverse utility across disciplines. Despite their widespread use, traditional methods for SSR analysis are often laborious and time-consuming, requiring significant resources and expertise. To address these challenges, a variety of computational tools for SSR analysis have been developed, offering faster and more efficient alternatives to traditional methods. However, selecting the most appropriate tool can be daunting due to rapid technological advancements and the sheer number of options available. This study presents a comprehensive review and analysis of 74 SSR tools, aiming to provide researchers with a valuable resource for SSR analysis tool selection. The methodology employed includes thorough literature reviews, detailed tool comparisons, and in-depth analyses of tool functionality. By compiling and analyzing these tools, this study not only advances the field of genomic research but also contributes to the broader scientific community by facilitating informed decision-making in the selection of SSR analysis tools. Researchers seeking to understand SSRs and select the most appropriate tools for their projects will benefit from this comprehensive guide. Overall, this study enhances our understanding of SSR analysis tools, paving the way for more efficient and effective SSR research in various fields of study.

Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295 HR + HER2- breast cancer: a retrospective analysis

BackgroundHER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay.MethodsA retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX® test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed.ResultsOf these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172–1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups.ConclusionWithin HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.

UNESCO heritage, remembrance, and contemporary identity: festivities of Jewish culture in small towns in the Czech Republic

ABSTRACT Třebíč is the only Czech town, but one of several in the world, to have its Jewish quarter separately listed on the UNESCO World Heritage List. For more than twenty years, this small town has held not one but two events related to Jewish culture: Shamayim Jewish Culture Festival and Jewish Town Revived, a cultural and historical festivity. Based on long-term and repeated fieldwork from 2017 to the present, the article explains how the acquisition of the UNESCO World Heritage status of the local Jewish quarter determined the reinterpretation and appropriation of the tangible monuments and immaterial references to Jewish culture from a more or less tolerated and dilapidated relic of the past into an essential and prestigious identity marker of today’s completely non-Jewish Třebíč. What elements other than Jewish material cultural heritage do the Třebíč festivities refer to, and how do today’s music/dance/theatre performers – who are overwhelmingly non-Jewish – present them? How do the festivities relate to the local Jewish past and where are the limits of imagination and reference to historical realia? What other purposes do the festivities serve today and how do they affect the revitalization of the quarter?

Biochemical characterization of the feedforward loop between CDK1 and FOXM1 in epidermal stem cells

The complex network governing self-renewal in epidermal stem cells (EPSCs) is only partially defined. FOXM1 is one of the main players in this network, but the upstream signals regulating its activity remain to be elucidated. In this study, we identify cyclin-dependent kinase 1 (CDK1) as the principal kinase controlling FOXM1 activity in human primary keratinocytes. Mass spectrometry identified CDK1 as a key hub in a stem cell-associated protein network, showing its upregulation and interaction with essential self renewal-related markers. CDK1 phosphorylates FOXM1 at specific residues, stabilizing the protein and enhancing its nuclear localization and transcriptional activity, promoting self-renewal. Additionally, FOXM1 binds to the CDK1 promoter, inducing its expression.We identify the CDK1-FOXM1 feedforward loop as a critical axis sustaining EPSCs during in vitro cultivation. Understanding the upstream regulators of FOXM1 activity offers new insights into the biochemical mechanisms underlying self-renewal and differentiation in human primary keratinocytes.

Quercus glauca Acorn Seed Coat Extract Promotes Wound Re-Epithelialization by Facilitating Fibroblast Migration and Inhibiting Dermal Inflammation.

The skin, recognized as the largest organ in the human body, serves a vital function in safeguarding against external threats. Severe damage to the skin can pose significant risks to human health. There is an urgent requirement for safe and effective therapies for wound healing. While phytotherapy has been widely utilized for various health conditions, the potential of Quercus glauca in promoting wound healing has not been thoroughly explored. Q. glauca is a cultivated crop known for its abundance of bioactive compounds. This study examined the wound-healing properties of Quercus glauca acorn seed coat water extract (QGASE). The findings from the study suggest that QGASE promotes wound closure in HF cells by upregulating essential markers related to the wound-healing process. Additionally, QGASE demonstrates antioxidant effects, mitigating oxidative stress and aiding in recovery from injuries induced by H2O2. In vivo experiments provide additional substantiation supporting the efficacy of QGASE in enhancing wound healing. The collective results indicate that QGASE may be a promising candidate for the development of innovative therapeutic strategies aimed at enhancing skin wound repair.

Extracorporeal Photopheresis Enhances the Frequency and Function of Highly Suppressive FoxP3+ Treg Subsets in Heart Transplanted Individuals.

Extracorporeal photopheresis (ECP) has emerged as a prophylactic and therapeutic immunomodulatory option for managing acute rejection in heart transplants (HTx). The underlying mechanisms through which ECP exerts its immunomodulatory effects remain under investigation. Regulatory T cells (Treg) are a heterogeneous subset of immune lymphocytes that ensure the maintenance of tissue homeostasis, avoiding graft rejection. The transcription factor forkhead box protein 3 (FoxP3) is an essential molecular marker of Treg, acting as a "master regulator" of their genesis, stability, and functions. No study has investigated whether ECP impacts FoxP3 expression and its highly suppressive variants containing the exon 2 (FoxP3-E2), particularly in HTx. In the current study, we recruited 14 HTx participants who had undergone ECP therapy. We explored the effect of in vivo ECP on CD4+FoxP3+ Treg frequency and in vitro suppressive function in 8 HTx participants before (T0) and after 3 (T1), 6 (T2), and 12 (T3) mo of treatment. As a control group, we included 4 HTx individuals who had not undergone ECP therapy. We found that ECP increases the frequency of CD4+FoxP3+ Treg subset with highly suppressive phenotype, including CD4+FoxP3-E2+ Treg. At functional levels, we observed that ECP treatment in HTx individuals effectively improves Treg suppressive ability in controlling the proliferation of autologous conventional CD4+ T lymphocytes. Our findings collectively suggest that ECP exerts its immunomodulatory effects in HTx individuals by positively impacting the frequency and regulatory function of the FoxP3+ Treg compartment.