Medical review (Berlin, Germany)最新文献

Alzheimer's disease (AD) is a gradually progressive neurodegenerative disease with tremendous social and economic burden. Therefore, early and accurate diagnosis is imperative for effective treatment or prevention of the disease. Cerebrospinal fluid and blood biomarkers emerge as favorable diagnostic tools due to their relative accessibility and potential for widespread clinical use. This review focuses on the AT(N) biomarker system, which includes biomarkers reflecting AD core pathologies, amyloid deposition, and pathological tau, as well as neurodegeneration. Novel biomarkers associated with inflammation/immunity, synaptic dysfunction, vascular pathology, and α-synucleinopathy, which might contribute to either the pathogenesis or the clinical progression of AD, have also been discussed. Other emerging candidates including non-coding RNAs, metabolites, and extracellular vesicle-based markers have also enriched the biofluid biomarker landscape for AD. Moreover, the review discusses the current challenges of biofluid biomarkers in AD diagnosis and offers insights into the prospective future development.

Our understanding of β-cell differentiation from pluripotent stem cells (PSCs) is rapidly evolving. Although progress has been made, challenges remain, particularly in achieving glucose-stimulated insulin secretion (GSIS). Human embryonic stem cells (hESCs) are valuable due to their pluripotent ability. A fixed protocol targeting master regulatory genes initiates stem cells into pancreatic lineage commitment. Due to the observations that a single stem cell can differentiate into multiple cell types depending on various factors and conditions, non-linear differentiation pathways exist. Co-expression of key factors remains essential for successful β-cell differentiation. The mature β-cell marker MAFA plays a critical role in maintaining the differentiation state and preventing dedifferentiation. Recapitulating pancreatic islet clustering enhances physiological responses, offering potential avenues for diabetes treatment. On the other hand, several enhanced differentiation protocols from induced pluripotent stem cells (iPSCs) have improved the functional insulin producing β-cells generated. These findings, with their potential to revolutionize diabetes treatment, highlight the complexity of β-cell differentiation and guide further advancements in regenerative medicine.

The therapeutic efficacy of anticancer drugs heavily relies on their concentration and retention at the corresponding target site. Hence, merely increasing the cellular concentration of drugs is insufficient to achieve satisfactory therapeutic outcomes, especially for the drugs that target specific intracellular sites. This necessitates the implementation of more precise targeting strategies to overcome the limitations posed by diffusion distribution and nonspecific interactions within cells. Consequently, subcellular organelle-targeted cancer therapy, characterized by its exceptional precision, have emerged as a promising approach to eradicate cancer cells through the specific disruption of subcellular organelles. Owing to several advantages including minimized dosage and side effect, optimized efficacy, and reversal of multidrug resistance, subcellular organelle-targeted therapies have garnered significant research interest in recent years. In this review, we comprehensively summarize the distribution of drug targets, targeted delivery strategies at various levels, and sophisticated strategies for targeting specific subcellular organelles. Additionally, we highlight the significance of subcellular targeting in cancer therapy and present essential considerations for its clinical translation.

Neurodevelopmental disorders (NDDs) are a group of highly heterogeneous diseases that affect children's social, cognitive, and emotional functioning. The etiology is complicated with genetic factors playing an important role. During the past decade, large-scale whole exome sequencing (WES) and whole genome sequencing (WGS) have vastly advanced the genetic findings of NDDs. Various forms of variants have been reported to contribute to NDDs, such as de novo mutations (DNMs), copy number variations (CNVs), rare inherited variants (RIVs), and common variation. By far, over 200 high-risk NDD genes have been identified, which are involved in biological processes including synaptic function, transcriptional and epigenetic regulation. In addition, monogenic, oligogenic, polygenetic, and omnigenic models have been proposed to explain the genetic architecture of NDDs. However, the majority of NDD patients still do not have a definitive genetic diagnosis. In the future, more types of risk factors, as well as noncoding variants, are await to be identified, and including their interplay mechanisms are key to resolving the etiology and heterogeneity of NDDs.

Adipose-derived mesenchymal stem cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) have shown great potential in clinical applications. However, the similarities and differences between these two cell types have not been fully elucidated. Recent advances in transcriptomic and metabolomic research have provided valuable insight into the characteristics and functions of ADSCs and BMSCs. In this perspective article, we review the key findings from these studies, including cellular heterogeneity as well as differences in metabolic and secretory properties. We discuss how these insights can help guide the selection of the most suitable cell source for the clinic, and the optimization of preconditioning strategies prior to clinical deployment. Furthermore, we analyze the current landscape of products and clinical trials involving ADSCs and BMSCs, highlighting their therapeutic potential. We propose that the integration of multi-omics datasets will be crucial for establishing a comprehensive understanding of ADSC and BMSC identity and potency, and the provision of quality-assured stem cell-derived products for the clinic.

Chronic Mountain Sickness (CMS), characterized by increased red blood cells above average values traditionally attributed to chronic hypobaric hypoxia exposure, is being redefined in light of recent research and clinical experience. We propose a shift in perspective, viewing CMS not as a singular entity but as Poly-erythrocythemia (PEH), as the Hematocrit/Hemoglobin/Red Blood Cells (Ht/Hb/RBCs) increase constitutes a sign, not a disease reflecting a spectrum of oxygen transport alterations in multiple diseases in the chronic hypoxia environment in high-altitude populations. Drawing on over five decades of experience at the High Altitude Pulmonary and Pathology Institute (HAPPI-IPPA) in Bolivia, we advocate for altitude-specific blood parameter norms and emphasize the importance of correct etiological diagnosis for effective management. This updated understanding not only aids in managing chronically hypoxemic patients at various altitudes but also offers valuable insights into global health challenges, including the recovery from COVID-19.

Dental caries, driven by plaque biofilm, poses a major oral health challenge due to imbalance in mineralization and demineralization. The primary objective in caries management is to maintain biofilm homeostasis while facilitating the repair and regeneration of dental hard tissues, thus restoring both structural integrity and functionality of affected teeth. Though antimicrobial and remineralization approaches haven shown promise, their standalone utilization without concurrent bacterial control or rebalancing lacks an integrated strategy to effectively arrest caries progression. Furthermore, according to the principles of minimally invasive dentistry, treatment materials should exhibit high permeability to ensure optimal sealing of demineralized tooth surfaces. The concept of interrupting dental caries (IDC) has emerged as a holistic approach, drawing upon extensive research encompassing three pivotal techniques: antibacterial strategies, remineralization therapies, and infiltration mechanisms, all of which are indispensable components in combating the progression of dental caries. In this review, we provide a comprehensive overview of the mechanisms and applications of antibacterial, remineralization, and infiltration technologies within the context of caries management. Additionally, we summarize advanced materials that align with the IDC concept, aiming to offer valuable insights for designing next-generation materials adept at preventing or halting caries progression efficiently.

Mechanical forces control a multitude of biological responses in various cells and tissues. The periodontal ligament, located between the tooth's root and alveolar bone, is a major tissue compartment that is incessantly subjected to such mechanical stimulation through either normal or abnormal oral functionality. It is now known that mechanical stimulation activates periodontal ligament stem cells (PDLSCs) to modulate periodontal immunity and regulate inflammation - a basic feature of periodontal disease that affects virtually every human during their lifetime. For instance, shear stress induces the expression of immunomodulatory-related gene, indoleamine 2,3-dioxygenase (IDO). IDO cleaves l-tryptophan, resulting in increased l-kynurenine levels that, in turn, further promote regulatory T-cell differentiation and inhibit T cell proliferation. These and other related data reinforce the notion that mechanical stimulation plays a crucial role in controlling inflammation and immunomodulation of periodontal tissues. Further investigations, however, are warranted to evaluate the immunomodulatory features of PDLSCs so as to understand the pathological basis of periodontal disease and translate these into clinical interventions.