Clinical Application Research Articles

Phosphatase LHPP confers prostate cancer ferroptosis activation by modulating the AKT-SKP2-ACSL4 pathway

LHPP, a novel, recognized tumor suppressor, exerts a critical influence on the regulation of tumor cell proliferation and survival by modulating various signaling pathways with its phosphatase activity. Here, we unveil a robust correlation between reduced LHPP expression and adverse prognosis in prostate cancer. We demonstrate that LHPP interacts with AKT, thereby dampening AKT phosphorylation and subsequently inhibiting ACSL4 phosphorylation at the T624 site. This interaction impedes phosphorylation-dependent ubiquitination, thwarting SKP2 from recognizing and binding to ACSL4 at the K621 site. As a result, ACSL4 is spared from lysosomal degradation, leading to its accumulation and the promotion of lipid peroxidation, and ferroptosis. Moreover, our findings reveal that Panobinostat, a potent histone-deacetylase inhibitor, intricately regulates LHPP expression at multiple levels through the inhibition of HDAC3. This complex modulation enhances the ferroptosis pathway, offering a novel mechanism for curtailing the growth of prostate tumors and highlighting its significant translational potential for clinical application.

Small Molecule-Mediated Stage-Specific Reprogramming of MSCs to Hepatocyte-Like Cells and Hepatic Tissue for Liver Injury Treatment.

Derivation of hepatocytes from stem cells has been established through various protocols involving growth factor (GF) and small molecule (SM) agents, among others. However, mesenchymal stem cell-based derivation of hepatocytes still remains expensive due to the use of a cocktail of growth factors, and a long duration of differentiation is needed, thus limiting its potential clinical application. In this study, we developed a chemically defined differentiation strategy that is exclusively based on SM and takes 14days, while the GF-based protocol requires 23-28days. We optimized a stage-specific differentiation protocol for the differentiation of rat bone marrow-derived mesenchymal stem cells (MSCs) into functional hepatocyte-like cells (dHeps) that involved four stages, i.e., definitive endoderm (DE), hepatic competence (HC), hepatic specification (HS) and hepatic differentiation and growth. We further generated hepatic tissue using human decellularized liver extracellular matrix and compared it with hepatic tissue derived from the growth factor-based protocol at the transcriptional level. dHep, upon transplantation in a rat model of acute liver injury (ALI), was capable of ameliorating liver injury in rats and improving liver function and tissue damage compared to those in the ALI model. In summary, this is the first study in which hepatocytes and hepatic tissue were derived from MSCs utilizing a stage-specific strategy by exclusively using SM as a differentiation factor.

Treating Sickle Cell Disease: Gene Therapy Approaches.

Sickle cell disease (SCD) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin molecules and thus distortion (sickling) of the red blood cells. SCD causes chronic pain and organ damage and shortens life expectancy. Gene therapy emerges as a potentially curative approach for people with SCD who lack a matched sibling donor for hematopoietic stem cell transplantation. Here, we review recent progress in gene therapy for SCD and focus on innovative technologies that target the genetic roots of the disease. We also review the challenges associated with gene therapy, including oncogenic risks, and the need for refined delivery methods. Despite these hurdles, the rapidly evolving landscape of gene therapy for SCD raises hope for a paradigm shift in the treatment of this debilitating disease. As research progresses, a deeper understanding of the molecular mechanisms involved and continuous improvements in gene-editing technologies promise to bring gene therapy for SCD closer to mainstream clinical application, offering a transformative, curative option for patients with this genetic disorder.

Inscription of Complex Stent Profiles on the Polished Surfaces of NiTiCo Shape Memory Alloys by Fiber Lasers: Examining the Impact of Diffuse Reflectance

Drug eluting stents (DES) have become essential to alleviate stenosis with minimally invasive procedures. Nickel-titanium (NiTi) based shape memory alloys (SMAs) are the most suitable materials for self-expanding stents due to their good stability and superior thermo-mechanical properties. This work explains the inscription of complex DES profiles by fiber laser micro-cutting (FLMC) on Nickel-Titanium-Cobalt (NiTiCo) SMA surfaces polished with various grits (1000P, 1500P, 2000P, 2500P, 3000P, and cloth polished) of abrasive sheets. The impact of the SMA surface diffuse reflectance on laser micromachining characteristics was investigated. The Fuzzy PROMETHEE II multi-criteria decision-making (FP II-MCDM) technique was employed to find the best-polished surface that provides the most desired responses (kerf quality, surface roughness, and depth of penetration) for clinical applications. The cloth-polished surface responds better in laser machining without compromising the kerf quality and surface roughness. A significant variation of 18% in kerf quality was found between the 3000P and the cloth-polished surfaces. This indicates that the surface diffuse reflectance has maximum impact when the surfaces are highly polished. For applications where surface roughness and kerf width are not a criterion, then polished surfaces between 1500P and 2000P give the maximum machining rate.

Analysis of clinical application effects of Esketamine combining Sufentanil in labor analgesia and their impacts on postpartum depression

Analysis of clinical application effects of Esketamine combining Sufentanil in labor analgesia and their impacts on postpartum depression

Chinese Verbal Fluency Deficiency in Temporal Lobe Epilepsy with and without Hippocampal Sclerosis: A Multiscale Study.

To test a Chinese character version of the phonemic verbal fluency task in patients with temporal lobe epilepsy (TLE) and assess the verbal fluency deficiency pattern in TLE with and without hippocampal sclerosis, a cross-sectional study was conducted including 30 patients with TLE and hippocampal sclerosis (TLE-HS), 28 patients with TLE and without hippocampal sclerosis (TLE-NHS), and 29 demographically matched healthy controls (HC). Both sexes were enrolled. Participants finished a Chinese character verbal fluency (VFC) task during functional MRI. The activation/deactivation maps, functional connectivity, degree centrality, and community features of the left frontal and temporal regions were compared. A neural network classification model was applied to differentiate TLE-HS and TLE-NHS using functional statistics. The VFC scores were correlated with semantic fluency in HC while correlated with phonemic fluency in TLE-NHS. Activation and deactivation deficiency was observed in TLE-HS and TLE-NHS (p < 0.001, k ≥ 10). Functional connectivity, degree centrality, and community features of anterior inferior temporal gyri were impaired in TLE-HS and retained or even enhanced in TLE-NHS (p < 0.05, FDR-corrected). The functional connectivity was correlated with phonemic fluency (p < 0.05, FDR-corrected). The neural network classification reached an area under the curve of 0.90 in diagnosing hippocampal sclerosis. The VFC task is a Chinese phonemic verbal fluency task suitable for clinical application in TLE. During the VFC task, functional connectivity of phonemic circuits was impaired in TLE-HS and was enhanced in TLE-NHS, representing a compensative phonemic searching strategy applied by patients with TLE-NHS.

Expert consensus on the clinical application of efficient intelligent chromosomal karyotyping precise auxiliary diagnosis system

Chromosomal karyotyping analysis has been considered as the gold standard for cytogenetic diagnosis and an effective measure for preventing birth defects. However, conventional karyotyping analysis relies heavily on manual recognition, which is time-consuming and labor-intensive. The application of an efficient intelligent chromosomal karyotyping precise auxiliary diagnosis system in clinical practice can significantly reduce the analysis time and greatly improve the efficiency, increase the detection rate for low-percentage mosaicisms, and promote homogenization between laboratories. This can effectively enhance the capacity and level of cytogenetic diagnosis. With the continuous application of such system in the field of karyotyping analysis, a substantial amount of clinical application data and experience has been accumulated. This consensus has been formulated after multiple rounds of discussion by experts from the clinical application collaboration group of the efficient intelligent chromosomal karyotyping precise auxiliary diagnosis system. It aims to provide a reference for peers to better utilize intelligent auxiliary diagnosis systems during chromosomal karyotyping analysis and promote the standardized development of karyotyping analysis technology.

A systematic review of post-stroke fatigue measurement scale based on COSMIN guidelines

ObjectiveThis study aimed to evaluate the methodological quality and measurement attribute quality of the post-stroke fatigue measurement scale, so as to provide some basis for the clinical application and promotion of related scales.MethodsThe Chinese National Knowledge Infrastructure, the Wanfang Data Knowledge Service Platform, the China Science and Technology Journal Database, the Chinese Medical Journal Full-text Database, the Chinese Biology Medicine, PubMed, Embase, Medline, the Cochrane Library, the Web of Science, CINAHL, and PsycINFO databases were searched for literature on the post-stroke fatigue measurement scale up to June 2022. Literature screening and data extraction were carried out independently by two researchers, and in the case of disagreement, discussions were held with a third investigator to reach an agreement, and the COSMIN checklist and criteria were used to systematically evaluate the attributes of the measurement scale.ResultsA total of 17 studies were included, involving 10 post-stroke fatigue measurement scales. The content validity of FSS-7, FACIT-F, NRS-FRS, and MFI-20 was “not mentioned,” and the remaining scales were “uncertain.” In terms of construct validity, MFS was “adequate”; FSS-7, FACIT-F, and NRS-FRS were “not mentioned”; and the remaining scales were “uncertain.” In terms of internal consistency, NRS-FRS was “not mentioned”; FSS and MFS were “adequate”; and the remaining scales were “uncertain.” In terms of hypothesis testing, CIS and FACIT-F were “not mentioned,” NRS-FRS was “adequate,” and the remaining scales were “uncertain.” The stability of FSS-7, CIS, FACIT-F, and MFI-20 was “not mentioned,” and the remaining scales were “adequate.” The cross-cultural validity of FSS-7 was “adequate,” and the remaining scales were “not mentioned.” All 10 scales were given a recommendation grade of “B”.ConclusionFor the time being, the FSS can be recommended to measure post-stroke fatigue, but it still needs to be tested for more relevant measurement properties in order to gain more support from high-quality evidence. For a more comprehensive assessment of post-stroke fatigue, the FIS, FAS, and NFI-stroke should perhaps be considered, as the FSS is a one-dimensional scale that can only measure physical fatigue in patients; however, these scales also need to be tested for more relevant measurement properties to verify their clinical applicability.

A Qualitative Assessment of Reasons for Living and Dying in the Context of Feeling Trapped Among Adults in the United Kingdom

Objective Contemporary approaches to suicide assessment and treatment incorporate reasons for living (RFL) and reasons for dying (RFD). This study qualitatively explored individuals’ self-described RFL and RFD in the context of suicidal thinking and behaviors. Method Within a community United Kingdom (UK) sample, adults (N = 331, aged 16+) responded to eight open-ended questions probing their experiences of suicide, defeat, and entrapment. Utilizing these data, which were collected from a larger online survey examining risk and protective factors for suicidal behaviors, this study explored RFL and RFD within these narratives. After the research team established an initial code book, RFL and RFD codes were subsequently analyzed through inductive and deductive thematic analyses. Results The present study identified five complimentary RFD-RFL themes: (1) Hopelessness-Hopefulness, (2) Stress of Responsibilities-Duty to Responsibilities, (3) Social Disconnection-Social Connection, (4) Death as Sin-Desire for an Afterlife, and (5) Temporary Escapes as Coping-Entrapment (i.e., a lack of escape). Three subthemes within the RFD theme Entrapment were General/Unspecified, By Feelings, and Within Self. Conclusions Identified themes reflect the existing quantitative RFL and RFD literature. The identified RFL and RFD themes are discussed with reference to their clinical applications in advancing suicide-specific assessments and interventions. We propose a dimensional framework for RFD and RFL which informs future suicidal behaviors research and practice.

Maglev-fabricated long and biodegradable stent for interventional treatment of peripheral vessels

While chronic limb-threatening ischemia is a serious peripheral artery disease, the lack of an appropriate stent significantly limits the potential of interventional treatment. In spite of much progress in coronary stents, little is towards peripheral stents, which are expected to be both long and biodegradable and thus require a breakthrough in core techniques. Herein, we develop a long and biodegradable stent with a length of up to 118 mm based on a metal-polymer composite material. To achieve a well-prepared homogeneous coating on a long stent during ultrasonic spraying, a magnetic levitation is employed. In vivo degradation of the stent is investigated in rabbit abdominal aorta/iliac arteries, and its preclinical safety is evaluated in canine infrapopliteal arteries. First-in-man implantation of the stent is carried out in the below-the-knee artery. The 13 months’ follow-ups demonstrate the feasibility of the long and biodegradable stent in clinical applications.

Role of the Immune System and Stem Cells in Dental Conservation

Background: Dental conservation aims to maintain teeth's appearance and functionality through various procedures. Recent advancements in stem cell research and immune system roles in tooth tissue regeneration highlight their crucial roles in oral health. The immune system is essential for healing after dental treatments and helps maintain oral health. A robust immune response can expedite the healing of damaged oral tissues and prevent further infections, enhancing the outcomes of dental conservation therapies. Purpose: This literature review examines immune system modulation and stem cell therapy in dental conservation, highlighting their potential benefits and challenges in tissue regeneration and treatment outcomes. Methodology: This review analyzes literature on the immune system and stem cell roles in dental tissue regeneration, assessing the effectiveness of immunomodulatory substances and their synergy in healing processes and tissue integration. Result: The review highlights that immunomodulatory substances effectively reduce inflammation and support regeneration, improving dental conservation outcomes. Stem cells, particularly mesenchymal stem cells from dental pulp, show promising results in clinical applications such as pulp regeneration and alveolar bone repair. The combination of immune system modulation and stem cell therapy offers superior outcomes compared to traditional methods, enhancing the quality of tissue regeneration and accelerating healing. However, challenges such as preventing adverse immune responses and ensuring proper integration of transplanted cells with host tissue remain. Ongoing research and technological advancements are expected to enhance dental conservation techniques' effectiveness and efficiency.

Advanced Nanotechnological Approaches for Biofilm Prevention and Control

Biofilm-associated infections present a significant challenge in modern medicine, primarily due to their resilience and resistance to conventional treatments. These infections occur when bacteria form biofilms, protective layers formed by bacterial communities, which are notoriously resistant to traditional antibiotics on surfaces such as medical implants and biological surfaces, making eradication with standard antibiotics difficult. This resilience leads to persistent infections, imposing a substantial economic burden on healthcare systems. The urgency to find alternative treatments is critical as current methods are insufficient and costly. Innovative approaches, such as nanotechnology-based therapies, offer promising alternatives by targeting biofilms more effectively and reducing the need for invasive procedures. Nanocarriers hold significant promise in the fight against biofilm-associated infections. Nanocarriers can penetrate biofilms more effectively than conventional treatments, delivering higher concentrations of antibiotics or other antimicrobial agents precisely where they are needed. This targeted approach not only enhances the efficacy of treatments but also minimizes potential side effects. The development of nanocarrier-based therapies is crucial for overcoming the limitations of current treatments and ultimately improving patient outcomes and reducing the economic burden of biofilm-associated infections on healthcare systems. In this review, nanotechnology-based systems, their characteristics, limitations, and potential benefits are explored to address biofilms-related infections. Additionally, biofilm evaluation models and the tests necessary for the preclinical validation of these nanosystems to facilitate their clinical application are addressed.

Early Experience and Perioperative Risk of GammaTile® for Upfront Brain Metastases: Report from a Prospective Multicenter Study

Abstract Background GammaTile (GT), a form of brachytherapy utilizing cesium-131 seeds in a bioresorbable collagen tile, has gained popularity for treatment of recurrent intracranial tumors and more recently for newly diagnosed metastases. This study reports early experience utilizing GT in upfront brain metastases with a focus on clinical applications and perioperative safety. Methods The STaRT Registry (NCT04427384) was queried for all patients receiving GT for upfront metastases from August 2021 to August 2023. Data regarding patient demographics, procedure details, and adverse events (AEs) were extracted and analyzed. Results Twenty-eight patients, median age 65 years (range 28-81), with 30 treated metastases were reported from 6 institutions. Patients had 2.8 metastases on average (range 1-15) at time of surgery; however, most patients had a single metastasis (60.7%). Mean diameter of treated metastases was 3.4 cm (range 1.5-4.7). A median of 4.0 tiles (range 1-10) were used per tumor. The median follow-up was 3.0 months (range 1.0-11.2) with 6 attributed AEs (21.4%), including one Grade ≥3 (infection). In the immediate postoperative period (&amp;lt;14 days), two patients reported pain or headache, and one reported facial edema. One patient developed seizures on postoperative day 8 requiring medication. At one-month follow-up, there was one superficial wound infection, in a previously colonized patient, requiring surgical intervention without explantation of tiles. At three-month follow-up, one patient reported facial pain not requiring treatment. There were no symptomatic hematomas. Conclusions GammaTile demonstrates a favorable safety profile in upfront brain metastases with a 3.6% rate of serious AEs (Grade ≥3) within 90 days of the procedure.

Facile Rebridging Conjugation Approach to Attain Monoclonal Antibody-Targeted Nanoparticles with Enhanced Antigen Binding and Payload Delivery.

Adopting conventional conjugation approaches to construct antibody-targeted nanoparticles (NPs) has demonstrated suboptimal control over the binding orientation and the structural stability of monoclonal antibodies (mAbs). Hitherto, the developed antibody-targeted NPs have shown proof of concept but lack product homogeneity, batch-to-batch reproducibility, and stability, precluding their advancement toward the clinic. To circumvent these limitations and advance toward clinical application, herein, a refined approach based on site-specific construction of mAb-immobilized NPs will be appraised. Initially, the conjugation of atezolizumab (anti-PDL1 antibody, Amab) with polymeric NPs was developed using bis-haloacetamide (BisHalide) rebridging chemistry, followed by click chemistry (NP-Fab BisHalide Ab and NP-Fc BisHalide Ab). For comparison purposes, mAb-immobilized NPs developed utilizing conventional conjugation methods, namely, N-hydroxysuccinimide (NHS) coupling and maleimide chemistry (NP-NHS Ab and NP-Mal Ab), were included. Next, flow cytometry and confocal microscopy experiments evaluated the actively targeted NPs (loaded with fluorescent dye) for cellular binding and uptake. Our results demonstrated the superior and selective binding and uptake of NP-Fab BisHalide Ab and NP-Fc BisHalide Ab into EMT6 cells by 19-fold and 13-fold, respectively. To evaluate the PDL1-dependent cell uptake and the selectivity of the treatments, a blocking step of the PDL1 receptor with Amab was performed prior to incubation with NP-Fab BisHalide Ab and NP-Fc BisHalide Ab. To our delight, the binding and uptake of fluorescent NPs were reduced significantly by 3-fold for NP-Fab BisHalide Ab, demonstrating the PDL1-mediated uptake. Moreover, NP-Fab BisHalide Ab and NP-Fc BisHalide Ab were entrapped with the paclitaxel payload, and their cytotoxicity was evaluated. They showed significant enhancements compared to free paclitaxel and NP-NHS Ab. Overall, this work will provide a facile conjugation method that could be implemented to actively target NPs with a plethora of therapeutic mAbs approved for various malignancies.

Small Extracellular Vesicles and Oral Mucosa: The Power Couple in Regenerative Therapies?

Although ongoing debates persist over the scope of phenomena classified as regenerative processes, the most up-to-date definition of regeneration is the replacement or restoration of damaged or missing cells, tissues, organs, or body parts to full functionality. Despite extensive research on this topic, new methods in regenerative medicine are continually sought, and existing ones are being improved. Small extracellular vesicles (sEVs) have gained attention for their regenerative potential, as evidenced by existing studies conducted by independent research groups. Of particular interest are sEVs derived from the oral mucosa, a tissue renowned for its rapid regeneration and minimal scarring. While the individual regenerative potential of both sEVs and the oral mucosa is somewhat understood, the combined potential of sEVs derived from the oral mucosa has not been sufficiently explored and highlighted in the existing literature. Serving as a broad compendium, it aims to provide scientists with essential and detailed information on this subject, including the nature of the materials employed, isolation and analysis methodologies, and clinical applications. The content of this survey aims to facilitate the comparison of diverse methods for working with sEVs derived from the oral mucosa, aiding in the planning of research endeavors and identifying potential research gaps.

A Literature Review of Adhesive Systems in Dentistry: Key Components and Their Clinical Applications

The central aim of adhesive dentistry is to improve the compatibility between current adhesives and a range of substrates by employing diverse application techniques. Therefore, the overarching objective of this review is to offer a comprehensive analysis of dentin bonding systems, starting with an introduction to adhesion and a detailed overview of enamel and dentin structures, their histology, and the impact of dentin structure on resin–dentin bonding. It covers the mechanisms of resin–dentin bonding, including resin adhesive application, bonding mechanisms, and factors influencing efficacy. Further, this review explores the composition of resin adhesive systems, including acidic components, cross-linking monomers, solvents, and other critical elements. It also examines various adhesive strategies—etch-and-rinse, self-etch, and universal adhesives—highlighting their applications and advantages. The review extends to clinical applications of dental adhesion, including direct restorations, indirect restorations, and immediate dentin sealing (IDS), demonstrating the practical implications of adhesive systems in enhancing restoration longevity and performance. In conclusion, despite significant advancements, no gold-standard method for optimal adhesion exists. Each adhesive system has distinct strengths and limitations. The review emphasizes the importance of evaluating methods for achieving durable adhesion and staying current with technological advancements in adhesive systems. Summary: This review provides a thorough analysis of dentin bonding systems, delving into the structures and bonding mechanisms of both enamel and dentin. By exploring various adhesive systems and their components, it highlights the ongoing challenges in achieving optimal resin–dentin adhesion. The review also addresses the clinical applications of dental adhesion, including direct restorations, indirect restorations, and immediate dentin sealing (IDS), illustrating how different adhesive techniques impact clinical outcomes. It underscores the necessity for continuous innovation and assessment of adhesive systems to enhance long-term bonding effectiveness in clinical practice.

Natural pachypodol integrated, lung targeted and inhaled lipid nanomedicine ameliorates acute lung injury via anti-inflammation and repairing lung barrier

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a high-mortality disease caused by multiple disorders such as COVID-19, influenza, and sepsis. Current therapies mainly rely on the inhalation of nitric oxide or injection of pharmaceutical drugs (e.g., glucocorticoids); however, their toxicity, side effects, or administration routes limit their clinical application. In this study, pachypodol (Pac), a hydrophobic flavonol with anti-inflammatory effects, was extracted from Pogostemon cablin Benth and intercalated in liposomes (Pac@liposome, Pac-lipo) to improve its solubility, biodistribution, and bioavailability, aiming at enhanced ALI/ARDS therapy. Nanosized Pac-lipo was confirmed to have stable physical properties, good biodistribution, and reliable biocompatibility. In vitro tests proved that Pac-lipo has anti-inflammatory property and protective effects on endothelial and epithelial barriers in lipopolysaccharide (LPS)-induced macrophages and endothelial cells, respectively. Further, the roles of Pac-lipo were validated on treating LPS-induced ALI in mice. Pac-lipo showed better effects than did Pac alone on relieving ALI phenotypes: It significantly attenuated lung index, improved pulmonary functions, inhibited cytokine expression such as TNF-α, IL-6, IL-1β, and iNOS in lung tissues, alleviated lung injury shown by HE staining, reduced protein content and total cell number in bronchoalveolar lavage fluid, and repaired lung epithelial and vascular endothelial barriers. As regards the underlying mechanisms, RNA sequencing results showed that the effects of the drugs were associated with numerous immune- and inflammation-related signaling pathways. Molecular docking and western blotting demonstrated that Pac-lipo inhibited the activation of the TLR4-MyD88-NF-κB/MAPK signaling pathway. Taken together, for the first time, our new drug (Pac-lipo) ameliorates ALI via inhibition of TLR4-MyD88-NF-κB/MAPK pathway-mediated inflammation and disruption of lung barrier. These findings may provide a promising strategy for ALI treatment in the clinic.

Investigating the molecular mechanisms of Fuzheng Yiliu Shenji prescription in SH-SY5Y neuroblastoma cells

BackgroundNeuroblastoma is the most common extracranial solid tumor in childhood. Fuzheng Yiliu Shenji Prescription (FYSP) has shown potential in treating malignant pediatric tumors in clinical settings. This study aims to explore the molecular mechanisms behind its effects, specifically in the context of neuroblastoma cell lines.ObjectiveTo elucidate the active compounds in FYSP and their mechanisms of action in inhibiting neuroblastoma cell viability, inducing apoptosis, and affecting the cell cycle in SH-SY5Y cells through network pharmacology and empirical validation.Materials and methodsWe identified the major compounds in FYSP and their predicted targets, constructing a protein-protein interaction (PPI) network and performing GO and KEGG pathway analyses. The effects of FYSP were empirically validated through assays on cell viability, cell cycle, apoptosis, and protein expression in SH-SY5Y cells.ResultsThe study identified 172 active chemical components in FYSP, with 188 common targets related to neuroblastoma. Network analysis highlighted the PI3K-Akt pathway as a significant target. Experimental validation in SH-SY5Y cells confirmed that FYSP could inhibit cell viability, induce G2/M cell cycle arrest, and promote apoptosis through modulation of the PI3K-Akt pathway, specifically upregulating caspase-3 and downregulating Bcl-2/Bax expression.ConclusionThe study elucidates the molecular basis of FYSP’s effects on neuroblastoma cells in vitro, demonstrating its ability to modulate key pathways involved in cell cycle and apoptosis. While these findings suggest a potential therapeutic role for FYSP, they are limited to in vitro observations, and further research, including in vivo studies, is necessary to explore its clinical applicability.

Recent updates on the influence of iron and magnesium on vascular, renal, and adipose inflammation and possible consequences for hypertension.

The inflammatory status of the kidneys, vasculature, and perivascular adipose tissue (PVAT) has a significant influence on blood pressure and hypertension. Numerous micronutrients play an influential role in hypertension-driving inflammatory processes, and recent reports have provided bases for potential targeted modulation of these micronutrients to reduce hypertension. Iron overload in adipose tissue macrophages and adipocytes engenders an inflammatory environment and may contribute to impaired anticontractile signalling, and thus a treatment such as chelation therapy may hold a key to reducing blood pressure. Similarly, magnesium intake has proven to greatly influence inflammatory signalling and concurrent hypertension in both healthy animals and in a model for chronic kidney disease, demonstrating its potential clinical utility. These findings highlight the importance of further research to determine the efficacy of micronutrient-targeted treatments for the amelioration of hypertension and their potential translation into clinical application.

Beyond labs: unveiling dynamics of dental students’ transition from pre-clinical to clinical training in a Saudi dental school

Objective To assess the factors affecting the transition of dental students from pre-clinical to clinical courses in an outcome-based curriculum. Methods This cross-sectional study surveyed dental students in the third and fourth academic years of the Bachelor of Dental and Oral Surgery (BDS) program at the College of Dentistry, Jouf University. Ethically approved and powered by the G Power software, the study employed a modified questionnaire validated through a pilot test to assess five domains. Likert scale responses were analyzed using SPSS v.25, revealing insights into clinical workload, patient interaction, and learning experiences. Multiple regression analysis was used to assess the impact of clinical skill application, workload, transition to clinics, and patient interaction on learning experience as well as CGPA. The Mann-Whitney U test compared the ranks of two independent samples, making it less sensitive to outliers and more suitable for data with non-normal distributions. Results In this study, the response rate of the participants was 70%. A total of 44 dental students in their third and fourth years of the program completed the survey. The multiple regression analysis showed that the predictors collectively explained 36.1% of the variance in the learning experience (Adjusted R2 = 0.361). “Transition to Clinics” had a significant positive effect on learning experience (β = 0.292, p = 0.012), “Workload” (β = −0.203, p = 0.393) and “Patient Interaction” (β = 0.443, p = 0.168) were not significant predictors. The Mann-Whitney U test revealed no significant gender differences in transition to clinics, workload, patient interaction, application of clinical skills, and learning experience (U = 33.09 to −40.33, p &gt; 0.05), but a significant difference in transition to clinics between third- and fourth-year students (U = 31.56 to −43.24, p &lt; 0.05). Conclusion The results of this study demonstrate that the transition to clinical training can be intricate, and that multiple elements have an impact on this process. It is crucial to have support systems that facilitate the transition into the clinical learning environment.