Advances in experimental medicine and biology最新文献

Human embryonic stem cells (hESCs) play a critical role in advancing regenerative medicine, with significant potential in tissue engineering, disease modeling, and cell-based therapies. Following the derivation of the first hESC line and subsequent breakthroughs in induced pluripotent stem cell (iPSC) technology, global efforts have accelerated the progress of stem cell research and clinical applications. The development of high-standard stem cell banks worldwide has ensured the traceability, quality, and accessibility of these critical resources, enabling their safe translation to clinical use. The National Stem Cell Resource Center (NSCRC) advances the efforts in arranging and optimizing stem cell resources to support research and clinical needs. Through rigorous quality control system construction and encouraging innovation, the NSCRC has been accredited by ISO 20387 and ISO 17025. Now, the NSCRC has developed a broad spectrum of high-quality stem cell lines, securing independent intellectual property rights. These resources have facilitated clinical research, supported major scientific initiatives, and provided good practice experience for the international standardization of stem cells. Moreover, the focus on integrating organoid resources and establishing intelligent biobanks highlights the frontier correlation of stem cell research, promoting innovation, collaboration, and clinical translation to meet unmet medical needs.

Stem cells hold tremendous promise for regenerative medicine. With continuous development in this field, stem cell medicines are starting to enter mainstream drug development. Due to their distinct and complex characteristics, which are significantly different from those of traditional medicine, new opportunities and challenges are arising in stem cell medicine development. Therefore, to facilitate the clinical translation of stem cells and adapt to scientific and technological progress, it is important to formulate and update regulatory policies and standards that are specifically appropriate for cell therapy. In this section, we discuss the regulatory policies on stem cell medicine and drug standards in China, and review the ongoing development of international and Chinese standards related to stem cell medicine. Finally, we discuss the framework for establishing a standard system for stem cell medicine in the future.

At the level of secondary structure, circular RNAs (circRNAs) can be understood in terms of base pairing, base-pair stacking, and entropic loop contribution in the same way as linear RNAs and intermolecular RNA-RNA interactions. The folding problem of circular RNAs can thus be solved by dynamic programming algorithms in essentially the same manner. In this chapter, we review the similarities and differences between circular and linear RNAs with a focus on the software tools provided by the ViennaRNA package. Comparative analysis of RNA structures can also be generalized to circular RNA molecules. However, the task of constructing pairwise and multiple alignments of circular sequences is more difficult than those of their linear counterpart, whence fewer and less convenient software solutions are available. This chapter has also touched upon recent developments such as applications of chemical probing to circular RNAs and prediction of secondary structures on the interaction of circular RNAs with other molecules.

The diaphragm is the thin dome-shaped muscle that separates the thoracic cavity from the abdominal contents. Functionally, the diaphragm is the principal inspiratory muscle in humans and other mammals, and importantly, a healthy diaphragm is essential to achieve adequate pulmonary ventilation and gas exchange across the blood/gas interface. In addition to pulmonary gas exchange, the diaphragm also contributes to important non-breathing functions such coughing and sneezing. Compared to locomotor muscles, the diaphragm is anatomically unique and is the only skeletal muscle that is chronically active. This chapter provides a summary of diaphragm structure and function and examines the plasticity of diaphragm muscle fibers in response to both increased and decreased contractile activity. The impact of aging and chronic diseases on diaphragmatic function is also considered. The chapter concludes with a detailed discussion of the important clinical problem of ventilator-induced diaphragm dysfunction.

Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs), which has the formation of reverse splicing of mRNAs. Interest in their regulatory function has recently been increasing. The most important features are its stability between species, its high abundance, and its evolutionary conservation. As a cellular function, circular RNAs are involved in transcriptional modulation and splicing from miRNA and protein sponges. In addition, they are differentially expressed in pathological conditions occurring in diseases, creating their potential as biomarkers. Resistance to RNases makes circular RNAs a less invasive biomarker. Studies on human tumors and other diseases have confirmed the regulatory role and expression profiles of circular RNAs in disease progenesis. This article discusses in detail the properties, functions, and mechanisms of action of circRNAs in human diseases. We also discuss the possibility of using circRNAs as potential therapeutic targets and biomarkers for human diseases.

Genetic variants for hemochromatosis have been identified in human fossils that are over 4000 years old in Northern Ireland. Iron overload can lead to life-threatening complications, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. In this review, the emphasis is on developments in the diagnosis and treatment of C282Y-linked hemochromatosis. There is a need for earlier diagnosis leading to earlier treatment to prevent morbidity and mortality.

Iron is an essential nutrient for most organisms; however, it can also be toxic when present in excess. For this reason, life has evolved complex pathways to tightly control the amount of iron contained within body tissues. Unlike most other nutrients, mammals do not have a regulated excretory mechanism for iron and, therefore, must regulate body iron levels at the point of dietary iron absorption in the proximal small intestine. In this chapter, we will describe the molecules and pathways involved in this important process, including our current understanding of the mechanisms of both heme and non-heme iron absorption. The regulation of this process will also be discussed, with particular emphasis on local and systemic factors that affect how much iron is absorbed from the diet. We also highlight areas where our knowledge is incomplete and where more research is required to fully understand the molecular mechanisms responsible for this essential process.

Hepcidin is primarily secreted by the liver and functions as an endocrine hormone. However, a growing number of studies show that hepcidin can also be produced locally by other cells and organs, where it acts in an autocrine/paracrine manner to mediate important iron-dependent pathways. These pathways can operate under normal homeostatic conditions or become relevant in pathophysiological conditions (inflammation, infection, cancer, liver disease, myocardial infarction, etc.). This chapter will delve into the local roles of hepcidin, highlighting its unconventional functions in barrier maintenance, host defense, growth, tissue housekeeping, and injury repair.

The mutual relationship between iron and liver disease is highlighted by the fact that too much iron can cause liver disease, while hepatic iron overload can also result from acute or chronic liver diseases. As the principal storage site for iron, hepatic iron concentration is a reliable surrogate marker for total body iron in iron overload conditions. Assessment of hepatic iron is therefore important for the initiation and monitoring of treatment of iron overload by therapeutic phlebotomies or iron chelators. The present chapter reviews how the liver controls iron homeostasis, and discusses how liver iron can be assessed before primary and secondary liver diseases with iron overload.

Erythropoiesis is a process by which red blood cells (RBCs) are produced in the adult bone marrow. It involves the differentiation of erythroid progenitor cells into mature RBCs, which transport oxygen from the lungs to all cells in the body. Erythropoiesis is a complex process with a nuanced crosstalk of regulation involving hormones, cytokines, and growth factors. In recent years, multiple sources of evidence have increased our understanding of the molecular mechanisms that coordinate erythropoiesis to enable the daily production of approximately 200 billion RBCs. These advances have shed light on the pathophysiology in a variety of diseases, i.e., iron-loading anemias, and are paving the way for novel therapeutic strategies in preclinical and clinical development to treat such dyserythropoietic disorders. This chapter elucidates our current understanding of iron-loading anemias in general and specifically in β-thalassemia and myelodysplastic syndrome (MDS), describes the current cutting-edge understanding in pathophysiology, and delineates what novel therapies are currently being developed to target these disorders.