Faculty reviews最新文献

Cancer is a multi-step process where normal cells become transformed, grow, and may disseminate to establish new lesions within the body. In recent years, the physical properties of individual cells and the tissue microenvironment have been shown to be potent determinants of cancer progression. Biophysical tools have long been used to examine cell and tissue mechanics, morphology, and migration. However, exciting developments have linked these physical traits to gene expression changes that drive metastatic seeding, organ selectivity, and tumor growth. Here, we present some vignettes to address recent studies to show progress in harnessing biophysical tools and concepts to gain insights into metastasis.

Palmoplantar pustulosis (PPP) is a chronic inflammatory condition where crops of sterile pustules with erythematous keratotic lesions causing bleeding and pain appear on the palms and soles. Recently, the European Rare and Severe Expert Network considered PPP as a variant of pustular psoriasis with or without psoriasis vulgaris. The prevalence of PPP varies from 0.050 to 0.12%. PPP occurs more frequently in women and the highest prevalence occurred between the ages of 50 and 69 years. Nail psoriasis seems to be frequent in PPP, ranging from 30 to 76%, and psoriatic arthritis in 8.6 to 26% of PPP patients. Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome and pustulotic arthro-osteitis are considered PPP-associated disorders. PPP has been reported with other co-morbidities such as psychiatric disorders, thyroid-associated disease, altered calcium homeostasis, gluten sensitivity diabetes, obesity, and dyslipidemia, but larger studies are required to prove such associations. Environmental exacerbating factors might contribute to the onset or worsening of PPP such as cigarette smoking, stress, focal infections, metal allergies, and drug intake. Genetic predisposition plays an important role in PPP. In PPP, both the innate and the adaptive immune systems are activated. The acrosyringeal expression of IL-17 has been demonstrated, indicating that the eccrine sweat gland is an active component of the skin barrier and an immune-competent structure. Increased levels of several inflammatory molecules, including IL-8, IL-1α, IL-1β, IL-17A, IL-17C, IL-17D, IL-17F, IL-22, IL-23A, and IL-23 receptor, have been detected in PPP biopsies. Increased serum levels of TNF-α, IL-17, IL-22, and IFN-γ have been detected in patients with PPP in comparison to healthy subjects, suggesting a similar inflammatory pattern to psoriasis vulgaris. Oral and tonsillar infections serve as trigger factors for PPP. Long-term therapy is required for many patients, but high-quality data are limited, contributing to uncertainty about the ideal approach to treatment.

Minimally invasive surgery continues to transform the field of gynecological surgery and is now the standard of care for the surgical treatment of many diseases in gynecology. Owing to minimally invasive surgery's clear advantages, new advances in technology are being employed rapidly and enabling even the most complicated procedures to be performed less invasively. We examine recent literature on minimally invasive surgical innovations, advances, and common practices in benign gynecology that, from our point of view, made an impact on the way laparoscopic surgery is performed and managed in the last decade.

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder characterized by neurodevelopmental regression between 6 and 18 months of life and associated with multi-system comorbidities. Caused mainly by pathogenic variants in the MECP2 (methyl CpG binding protein 2) gene, it is the second leading genetic cause of intellectual disability in girls after Down syndrome. RTT affects not only neurological function but also a wide array of non-neurological organs. RTT-related disorders involve abnormalities of the respiratory, cardiovascular, digestive, metabolic, skeletal, endocrine, muscular, and urinary systems and immune response. Here, we review the different aspects of RTT affecting the main peripheral groups of organs and sometimes occurring independently of nervous system defects.

Stroke affects millions of people worldwide each year, and stroke survivors are often left with motor deficits. Current therapies to improve these functional deficits are limited, making it a priority to better understand the pathophysiology of stroke recovery and find novel adjuvant options. The excitation-inhibition balance undergoes significant changes post-stroke, and the inhibitory neurotransmitter γ-aminobutyric acid (GABA) appears to play an important role in stroke recovery. In this review, we summarise the most recent studies investigating GABAergic inhibition at different stages of stroke. We discuss the proposed role of GABA in counteracting glutamate-mediated excitotoxicity in hyperacute stroke as well as the evidence linking decreased GABAergic inhibition to increased neuronal plasticity in early stroke. Then, we discuss two types of interventions that aim to modulate the excitation-inhibition balance to improve functional outcomes in stroke survivors: non-invasive brain stimulation (NIBS) and pharmacological interventions. Finding the optimal NIBS administration or adjuvant pharmacological therapies would represent an important contribution to the currently scarce therapy options.

The attention to treatment-related toxicity has increased since the survival of children with acute lymphoblastic leukemia (ALL) has improved significantly over the past few decades. Intensive ALL treatment schedules including corticosteroids and asparaginase have been shown to give rise to skeletal abnormalities such as osteonecrosis and low bone mineral density (BMD), which may lead to debilitating sequelae in survivors. Although osteonecrosis and low BMD are different entities with suggested separate pathophysiological mechanisms, recent studies indicate that osteonecrosis is associated with accelerated BMD decline. Common underlying mechanisms for osteonecrosis and BMD decline are considered, such as an enhanced sensitivity to corticosteroids in children who suffer from both osteonecrosis and low BMD. In addition, restriction of weight-bearing activities, which is generally advised in patients with osteonecrosis, could aggravate BMD decline. This induces a clinical dilemma, since bone stimulation is important to maintain BMD but alternative interventions for osteonecrosis are limited. Furthermore, this recent finding of accelerated BMD decline in children with osteonecrosis emphasizes the need to develop effective preventive measures for osteonecrosis, which may include targeting BMD decline.

In this review, we consider how the association between adherens junctions and the actomyosin cytoskeleton influences collective cell movement. We focus on recent findings which reveal different ways for adherens junctions to promote the locomotion of cells within tissues: through lamellipodia and junctional contraction. These contributions reflect how classic cadherins establish sites of cortical actin assembly and how adherens junctions couple to contractile actomyosin, respectively. The diverse interplay between cadherin adhesion and the cytoskeleton thus provides different ways for adherens junctions to support epithelial locomotion.

Fertility preservation is the process of saving gametes, embryos, gonadal tissues and/or gonadal cells for individuals who are at risk of infertility due to disease, medical treatments, age, genetics, or other circumstances. Adult patients have the options to preserve eggs, sperm, or embryos that can be used in the future to produce biologically related offspring with assisted reproductive technologies. These options are not available to all adults or to children who are not yet producing mature eggs or sperm. Gonadal cells/tissues have been frozen for several thousands of those patients worldwide with anticipation that new reproductive technologies will be available in the future. Therefore, the fertility preservation medical and research communities are obligated to responsibly develop next-generation reproductive technologies and translate them into clinical practice. We briefly describe standard options to preserve and restore fertility, but the emphasis of this review is on experimental options, including an assessment of readiness for translation to the human fertility clinic.

Stimulator of interferon genes (STING) functions in the cytosolic DNA-sensing pathway of innate immunity in mammals. It is activated upon binding the cyclic dinucleotide 2'3'-cGAMP, a second messenger produced by the enzyme cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), which acts as the receptor for DNA in this pathway, and triggers the expression of interferons and other viral stress-induced genes. The ancient origin of STING in the evolution of animals had been noted, but its primitive function was speculative. We review here recent advances in the remarkable history of cGAS-STING signaling, which establish that cGAS is a member of the family of cGAS/DncV-like nucleotidyltransferases (CD-NTases). In bacteria, CD-NTases synthesize a wide range of cyclic oligonucleotide second messengers in response to bacteriophage infections, which in turn activate a variety of effector proteins to abort phage infection. Among these effectors, some are related to STING, revealing an ancestral function for the cGAS-STING cassette in antiviral host defense. Study of STING signaling in invertebrate animals is consistent with an early acquisition in the history of metazoans of CD-NTase- and STING-encoding genes to counter the universal threat of viruses. In particular, STING-dependent immunity appears to play a previously unsuspected important role in some insects. These discoveries open up interesting perspectives for the use of model organisms to decipher emerging aspects of cGAS-STING biology in mammals, such as the activation of interferon-independent responses or the function and regulation of cGAS in the nucleus.

While widespread imitation of the productivity of the land biosphere by nutrients, like nitrogen and phosphorus, was demonstrated many decades ago, representation of nutrient cycles in global land models has been relatively recent. Over the last three years, significant progress has been made in understanding some of the key processes and their representation in global land models. They include the significance of plant-microbial interaction in affecting nutrient cycles, inorganic soil phosphorus transformation, and nitrogen release from rocks. As a result, our understanding of the linkages among geology, biology, and climate controlling nutrient cycles is improving. However, progress in modelling nutrient cycles at a global scale is still confronted with large uncertainties in representing key processes owing to lack of data at the relevant scales for evaluating coupled carbon and nutrient cycles. Here we recommend two approaches to advance modelling of land nutrient cycles: the application of machine learning techniques to bridge the gap between global modelling and scattered site-level information and the use of optimality principles to identify key mechanisms driving spatial and temporal patterns of nutrients.