Progress in Biophysics & Molecular Biology最新文献

One of the central regulators of cell growth, proliferation, and metabolism is the mammalian target of rapamycin, mTOR, which exists in two structurally and functionally different complexes: mTORC1 and mTORC2; unlike m TORC2, mTORC1 is activated in response to the sufficiency of nutrients and is inhibited by rapamycin. mTOR complexes have critical roles not only in protein synthesis, gene transcription regulation, proliferation, tumor metabolism, but also in the regulation of the programmed cell death mechanisms such as autophagy and apoptosis. Autophagy is a conserved catabolic mechanism in which damaged molecules are recycled in response to nutrient starvation. Emerging evidence indicates that the mTOR signaling pathway is frequently activated in tumors. In addition, dysregulation of autophagy was associated with the development of a variety of human diseases, such as cancer and aging. Since mTOR can inhibit the induction of the autophagic process from the early stages of autophagosome formation to the late stage of lysosome degradation, the use of mTOR inhibitors to regulate autophagy could be considered a potential therapeutic option. The present review sheds light on the mTOR and autophagy signaling pathways and the mechanisms of regulation of mTOR-autophagy.

With a Nobel Prize for Physics widely viewed as only given for ‘settled’ science, the award then essentially accepts the validity of universal nonlocality. Other key discoveries and insights in recent years are also progressively pointing to the appearance of our Universe, its energy-matter and space-time, as not being foundational but emerging from deeper, discarnate realms of causation. as digitized and meaningful, in-formation, its manifestation pixelated at the so-named Planck scale of existence. Extending from studies of black holes to the entire Universe, a growing number of cosmologists have also developed the so-named holographic principle, to model the four-dimensional appearance of our Universe (three dimensions of space and one of time) as a holographic projection of its two- dimensional boundary. In framing the emergent cosmology of a nonlocally unified, meaningfully in-formed and holographically manifested Universe, an expansion of the three universal Laws of Thermodynamics to three Laws of Information, or Infodynamics also points the way to reconciling Quantum Theory that describes energy-matter and Relativity Theory that describes space-time and offers too an understanding of how the lifecycle of our Universe flows from its first moment until its last. Treating gravity as an emergent consequence of the in-formational and holographic structure of space- time and describing it as the consequence of the intropy associated with the positions in space-time of massive bodies, also points to the findings of the loss of phenotype identity in zero gravity and the role between gravity and cellular identity and the emergence of symbiogenesis.

The convergence of biology and computational science has ushered in a revolutionary era, revolutionizing our understanding of biological systems and providing novel solutions to global problems. The field of genetic engineering has facilitated the manipulation of genetic codes, thus providing opportunities for the advancement of innovative disease therapies and environmental enhancements. The emergence of bio-molecular simulation represents a significant advancement in this particular field, as it offers the ability to gain microscopic insights into molecular-level biological processes over extended periods. Biomolecular simulation plays a crucial role in advancing our comprehension of organismal mechanisms by establishing connections between molecular structures, interactions, and biological functions. The field of computational biology has demonstrated its significance in deciphering intricate biological enigmas through the utilization of mathematical models and algorithms. The process of decoding the human genome has resulted in the advancement of therapies for a wide range of genetic disorders, while the simulation of biological systems contributes to the identification of novel pharmaceutical compounds. The potential of biomolecular simulation and computational biology is vast and limitless. As the exploration of the underlying principles that govern living organisms progresses, the potential impact of this understanding on cancer treatment, environmental restoration, and other domains is anticipated to be transformative. This review examines the notable advancements achieved in the field of computational biology, emphasizing its potential to revolutionize the comprehension and enhancement of biological systems.

The mechanical environment is important for tumorigenesis and progression. Tumor cells can sense mechanical signals by mechanosensitive receptors, and these mechanical signals can be converted to biochemical signals to regulate cell behaviors, such as cell differentiation, proliferation, migration, apoptosis, and drug resistance. Here, we summarized the effects of the mechanical microenvironment on breast cancer cell activity, and mechanotransduction mechanism from cellular microenvironment to cell membrane, and finally to the nucleus, and also relative mechanosensitive proteins, ion channels, and signaling pathways were elaborated, therefore the mechanical signal could be transduced to biochemical or molecular signal. Meanwhile, the mechanical models commonly used for biomechanics study in vitro and some quantitative descriptions were listed. It provided an essential theoretical basis for the occurrence and development of mechanosensitive breast cancer, and also some potential drug targets were proposed to treat such disease.

The risk of discovering an intracranial aneurysm during the initial screening and follow-up screening are reported as around 11%, and 7% respectively (Zuurbie et al., 2023) to these mass effects, unruptured aneurysms frequently generate symptoms, however, the real hazard occurs when an aneurysm ruptures and results in a cerebral hemorrhage known as a subarachnoid hemorrhage. The objective is to study the multiple kinds of hemorrhage and aneurysm detection problems and develop machine and deep learning models to recognise them. Due to its early stage, subarachnoid hemorrhage, the most typical symptom after aneurysm rupture, is an important medical condition. It frequently results in severe neurological emergencies or even death. Although most aneurysms are asymptomatic and won't burst, because of their unpredictable growth, even small aneurysms are susceptible. A timely diagnosis is essential to prevent early mortality because a large percentage of hemorrhage cases present can be fatal. Physiological/imaging markers and the degree of the subarachnoid hemorrhage can be used as indicators for potential early treatments in hemorrhage. The hemodynamic pathomechanisms and microcellular environment should remain a priority for academics and medical professionals. There is still disagreement about how and when to care for aneurysms that have not ruptured despite studies reporting on the risk of rupture and outcomes. We are optimistic that with the progress in our understanding of the pathophysiology of hemorrhages and aneurysms and the advancement of artificial intelligence has made it feasible to conduct analyses with a high degree of precision, effectiveness and reliability.

Periodontitis, the sixth most prevalent epidemic disease globally, profoundly impacts oral aesthetics and masticatory functionality. Hypoxia-inducible factor-1α (HIF-1α), an oxygen-dependent transcriptional activator, has emerged as a pivotal regulator in periodontal tissue and alveolar bone metabolism, exerts critical functions in angiogenesis, erythropoiesis, energy metabolism, and cell fate determination. Numerous essential phenotypes regulated by HIF are intricately associated with bone metabolism in periodontal tissues. Extensive investigations have highlighted the central role of HIF and its downstream target genes and pathways in the coupling of angiogenesis and osteogenesis. Within this concise perspective, we comprehensively review the cellular phenotypic alterations and microenvironmental dynamics linking HIF to periodontitis. We analyze current research on the HIF pathway, elucidating its impact on bone repair and regeneration, while unraveling the involved cellular and molecular mechanisms. Furthermore, we briefly discuss the potential application of targeted interventions aimed at HIF in the field of bone tissue regeneration engineering. This review expands our biological understanding of the intricate relationship between the HIF gene and bone angiogenesis in periodontitis and offers valuable insights for the development of innovative therapies to expedite bone repair and regeneration.

Fibrosis is a pathological process that occurs in various organs, characterized by excessive deposition of extracellular matrix (ECM), leading to structural damage and, in severe cases, organ failure. Within the fibrotic microenvironment, mechanical forces play a crucial role in shaping cell behavior and function, yet the precise molecular mechanisms underlying how cells sense and transmit these mechanical cues, as well as the physical aspects of fibrosis progression, remain less understood. Piezo1, a mechanosensitive ion channel protein, serves as a pivotal mediator, converting mechanical stimuli into electrical or chemical signals. Accumulating evidence suggests that Piezo1 plays a central role in ECM formation and hemodynamics in the mechanical transduction of fibrosis expansion. This review provides an overview of the current understanding of the role of Piezo1 in fibrosis progression, encompassing conditions such as myocardial fibrosis, pulmonary fibrosis, renal fibrosis, and other fibrotic diseases. The main goal is to pave the way for potential clinical applications in the field of fibrotic diseases.