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Journal of the American Society of... Mar 2022Understanding nephron loss is a primary strategy for preventing CKD progression. Death of renal tubular cells may occur by apoptosis during developmental and... (Review)
Review
Understanding nephron loss is a primary strategy for preventing CKD progression. Death of renal tubular cells may occur by apoptosis during developmental and regenerative processes. However, during AKI, the transition of AKI to CKD, sepsis-associated AKI, and kidney transplantation ferroptosis and necroptosis, two pathways associated with the loss of plasma membrane integrity, kill renal cells. This necrotic type of cell death is associated with an inflammatory response, which is referred to as necroinflammation. Importantly, the necroinflammatory response to cells that die by necroptosis may be fundamentally different from the tissue response to ferroptosis. Although mechanisms of ferroptosis and necroptosis have recently been investigated in detail, the cell death propagation during tubular necrosis, although described morphologically, remains incompletely understood. Here, we argue that a molecular switch downstream of tubular necrosis determines nephron regeneration versus nephron loss. Unraveling the details of this "switch" must include the inflammatory response to tubular necrosis and regenerative signals potentially controlled by inflammatory cells, including the stimulation of myofibroblasts as the origin of fibrosis. Understanding in detail the molecular switch and the inflammatory responses to tubular necrosis can inform the discussion of therapeutic options.
Topics: Acute Kidney Injury; Apoptosis; Female; Humans; Kidney; Kidney Cortex Necrosis; Male; Necrosis; Nephrons; Renal Insufficiency, Chronic
PubMed: 35022311
DOI: 10.1681/ASN.2021101293 -
Frontiers in Oncology 2022In recent years, various systemic immunotherapies have been developed for cancer treatment, such as monoclonal antibodies (mABs) directed against immune checkpoints... (Review)
Review
In recent years, various systemic immunotherapies have been developed for cancer treatment, such as monoclonal antibodies (mABs) directed against immune checkpoints (immune checkpoint inhibitors, ICIs), oncolytic viruses, cytokines, cancer vaccines, and adoptive cell transfer. While being estimated to be eligible in 38.5% of patients with metastatic solid or hematological tumors, ICIs, in particular, demonstrate durable disease control across many oncologic diseases (e.g., in melanoma, lung, bladder, renal, head, and neck cancers) and overall survival benefits. Due to their unique mechanisms of action based on T-cell activation, response to immunotherapies is characterized by different patterns, such as progression prior to treatment response (pseudoprogression), hyperprogression, and dissociated responses following treatment. Because these features are not encountered in the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), which is the standard for response assessment in oncology, new criteria were defined for immunotherapies. The most important changes in these new morphologic criteria are, firstly, the requirement for confirmatory imaging examinations in case of progression, and secondly, the appearance of new lesions is not necessarily considered a progressive disease. Until today, five morphologic (immune-related response criteria (irRC), immune-related RECIST (irRECIST), immune RECIST (iRECIST), immune-modified RECIST (imRECIST), and intra-tumoral RECIST (itRECIST)) criteria have been developed to accurately assess changes in target lesion sizes, taking into account the specific response patterns after immunotherapy. In addition to morphologic response criteria, 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/computed tomography (F-FDG-PET/CT) is a promising option for metabolic response assessment and four metabolic criteria are used (PET/CT Criteria for Early Prediction of Response to Immune Checkpoint Inhibitor Therapy (PECRIT), PET Response Evaluation Criteria for Immunotherapy (PERCIMT), immunotherapy-modified PET Response Criteria in Solid Tumors (imPERCIST5), and immune PERCIST (iPERCIST)). Besides, there is evidence that parameters on F-FDG-PET/CT, such as the standardized uptake value (SUV)max and several radiotracers, e.g., directed against PD-L1, may be potential imaging biomarkers of response. Moreover, the emerge of human intratumoral immunotherapy (HIT-IT), characterized by the direct injection of immunostimulatory agents into a tumor lesion, has given new importance to imaging assessment. This article reviews the specific imaging patterns of tumor response and progression and available imaging response criteria following immunotherapy.
PubMed: 36387133
DOI: 10.3389/fonc.2022.982983 -
Cell Mar 2024Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG...
Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging with existing tools. Here, we develop and curate a mouse genetic toolkit that allows for interrogating the properties and functions of distinct cutaneous targeting DRG neuron subtypes. These tools have enabled a broad morphological analysis, which revealed distinct cutaneous axon arborization areas and branching patterns of the transcriptionally distinct DRG neuron subtypes. Moreover, in vivo physiological analysis revealed that each subtype has a distinct threshold and range of responses to mechanical and/or thermal stimuli. These findings support a model in which morphologically and physiologically distinct cutaneous DRG sensory neuron subtypes tile mechanical and thermal stimulus space to collectively encode a wide range of natural stimuli.
Topics: Animals; Mice; Ganglia, Spinal; Sensory Receptor Cells; Single-Cell Gene Expression Analysis; Skin
PubMed: 38442711
DOI: 10.1016/j.cell.2024.02.006 -
BioRxiv : the Preprint Server For... Apr 2023Mechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG)....
Mechanical and thermal stimuli acting on the skin are detected by morphologically and physiologically distinct sensory neurons of the dorsal root ganglia (DRG). Achieving a holistic view of how this diverse neuronal population relays sensory information from the skin to the central nervous system (CNS) has been challenging with existing tools. Here, we used transcriptomic datasets of the mouse DRG to guide development and curation of a genetic toolkit to interrogate transcriptionally defined DRG neuron subtypes. Morphological analysis revealed unique cutaneous axon arborization areas and branching patterns of each subtype. Physiological analysis showed that subtypes exhibit distinct thresholds and ranges of responses to mechanical and/or thermal stimuli. The somatosensory neuron toolbox thus enables comprehensive phenotyping of most principal sensory neuron subtypes. Moreover, our findings support a population coding scheme in which the activation thresholds of morphologically and physiologically distinct cutaneous DRG neuron subtypes tile multiple dimensions of stimulus space.
PubMed: 37131664
DOI: 10.1101/2023.04.22.537932 -
The Bone & Joint Journal Oct 2023The aim of this study was to investigate the agreement in interpretation of the quality of the paediatric hip ultrasound examination, the reliability of geometric and...
AIMS
The aim of this study was to investigate the agreement in interpretation of the quality of the paediatric hip ultrasound examination, the reliability of geometric and morphological assessment, and the relationship between these measurements.
METHODS
Four investigators evaluated 60 hip ultrasounds and assessed their quality based the standard plane of Graf et al. They measured geometric parameters, described the morphology of the hip, and assigned the Graf grade of dysplasia. They analyzed one self-selected image and one randomly selected image from the ultrasound series, and repeated the process four weeks later. The intra- and interobserver agreement, and correlations between various parameters were analyzed.
RESULTS
In the assessment of quality, there a was moderate to substantial intraobserver agreement for each element investigated, but interobserver agreement was poor. Morphological features showed weak to moderate agreement across all parameters but improved to significant when responses were reduced. The geometric measurements showed nearly perfect agreement, and the relationship between them and the morphological features showed a dose response across all parameters with moderate to substantial correlations. There were strong correlations between geometric measurements. The Graf classification showed a fair to moderate interobserver agreement, and moderate to substantial intraobserver agreement.
CONCLUSION
This investigation into the reliability of the interpretation of hip ultrasound scans identified the difficulties in defining what is a high-quality ultrasound. We confirmed that geometric measurements are reliably interpreted and may be useful as a further measurement of quality. Morphological features are generally poorly interpreted, but a simpler binary classification considerably improves agreement. As there is a clear dose response relationship between geometric and morphological measurements, the importance of morphology in the diagnosis of hip dysplasia should be questioned.
Topics: Humans; Child; Reproducibility of Results; Observer Variation; Hip Dislocation, Congenital; Hip Dislocation; Physical Examination
PubMed: 37777201
DOI: 10.1302/0301-620X.105B10.BJJ-2023-0143.R1 -
Handbook of Clinical Neurology 2020The central noradrenergic system comprises multiple brainstem nuclei whose cells synthesize and release the catecholamine transmitter norepinephrine (NE). The largest of... (Review)
Review
The central noradrenergic system comprises multiple brainstem nuclei whose cells synthesize and release the catecholamine transmitter norepinephrine (NE). The largest of these nuclei is the pontine locus coeruleus (LC), which innervates the vast majority of the forebrain. NE interacts with a number of pre- and postsynaptically expressed G protein-coupled receptors to affect a wide array of functions, including sensory signal processing, waking and arousal, stress responsiveness, mood, attention, and memory. Given the myriad functions ascribed to the locus coeruleus-noradrenergic (LC-NE) system, it is unsurprising that it is implicated in many disease states, including various mood, cognitive, neuropsychiatric, and neurodegenerative diseases. The LC-NE system is also notably sexually dimorphic with regard to its morphologic and anatomical features as well as how it responds to the peptide transmitter corticotropin releasing hormone (CRH), a major mediator of the central stress response. The sex-biased morphology and signaling that is observed in the LC could then be considered a potential contributor to the differential prevalence of various diseases between men and women. This chapter summarizes the primary differences between the male and female LC, based primarily on preclinical observations and how these disparities may relate to differential diagnoses of several diseases between men and women.
Topics: Attention; Brain Stem; Corticotropin-Releasing Hormone; Female; Humans; Locus Coeruleus; Male; Norepinephrine
PubMed: 33008523
DOI: 10.1016/B978-0-444-64123-6.00012-6 -
Science Advances May 2022The healthy functioning of the plants' vasculature depends on their ability to respond to environmental changes. In contrast, synthetic microfluidic systems have rarely...
The healthy functioning of the plants' vasculature depends on their ability to respond to environmental changes. In contrast, synthetic microfluidic systems have rarely demonstrated this environmental responsiveness. Plants respond to environmental stimuli through nastic movement, which inspires us to introduce transformable microfluidics: By embedding stimuli-responsive materials, the microfluidic device can respond to temperature, humidity, and light irradiance. Furthermore, by designing a foldable geometry, these responsive movements can follow the preset origami transformation. We term this device TransfOrigami microfluidics (TOM) to highlight the close connection between its transformation and the origami structure. TOM can be used as an environmentally adaptive photomicroreactor. It senses the environmental stimuli and feeds them back positively into photosynthetic conversion through morphological transformation. The principle behind this morphable microsystem can potentially be extended to applications that require responsiveness between the environment and the devices, such as dynamic artificial vascular networks and shape-adaptive flexible electronics.
PubMed: 35507654
DOI: 10.1126/sciadv.abo1719 -
Hamostaseologie Apr 2021Aside from their canonical role in hemostasis, it is increasingly recognized that platelets have inflammatory functions and can regulate both adaptive and innate immune... (Review)
Review
Aside from their canonical role in hemostasis, it is increasingly recognized that platelets have inflammatory functions and can regulate both adaptive and innate immune responses. The main topic this review aims to cover is the proinflammatory effects and side effects of platelet transfusion. Platelets prepared for transfusion are subject to stress injury upon collection, preparation, and storage. With these types of stress, they undergo morphologic, metabolic, and functional modulations which are likely to induce platelet activation and the release of biological response modifiers (BRMs). As a consequence, platelet concentrates (PCs) accumulate BRMs during processing and storage, and these BRMs are ultimately transfused alongside platelets. It has been shown that BRMs present in PCs can induce immune responses and posttransfusion reactions in the transfusion recipient. Several recent reports within the transfusion literature have investigated the concept of platelets as immune cells. Nevertheless, current and future investigations will face the challenge of encompassing the immunological role of platelets in the scope of transfusion.
Topics: Humans; Platelet Count; Platelet Transfusion
PubMed: 33711849
DOI: 10.1055/a-1347-6551 -
Histopathology Jan 2020Vulval squamous cell carcinoma (VSCC) can arise through two distinct pathways [human papillomavirus (HPV)-associated and HPV-independent], and these VSCC variants are... (Review)
Review
Vulval squamous cell carcinoma (VSCC) can arise through two distinct pathways [human papillomavirus (HPV)-associated and HPV-independent], and these VSCC variants are recognised as different disease entities on the basis of different aetiologies, morphological features, molecular events during oncogenesis, precursor lesions, prognosis, and response to treatment. The precursor of HPV-associated VSCC, variously referred to as high-grade squamous intraepithelial lesion (HSIL) [vulvar intraepithelial neoplasia (VIN) 2/3] or usual-type VIN, is morphologically identical to the more common HSIL (cervical intraepithelial neoplasia 2/3) of the cervix. The precursor lesions of HPV-independent VSCC include differentiated VIN, differentiated exophytic vulvar intraepithelial lesion, and vulvar acanthosis with altered differentiation; these have been under-recognised by pathologists in the past, leading to delays in treatment. This review will discuss the recent advances in diagnostic surgical pathology of VSCC and its precursors, and how these diagnoses can impact on patient management.
Topics: Carcinoma, Squamous Cell; Female; Humans; Papillomaviridae; Papillomavirus Infections; Precancerous Conditions; Vulva; Vulvar Neoplasms
PubMed: 31846523
DOI: 10.1111/his.13989 -
International Journal of Molecular... Nov 2021Drought stress causes changes in the morphological, physiological, biochemical and molecular characteristics of plants. The response to drought in different plants may... (Review)
Review
Drought stress causes changes in the morphological, physiological, biochemical and molecular characteristics of plants. The response to drought in different plants may vary from avoidance, tolerance and escape to recovery from stress. This response is genetically programmed and regulated in a very complex yet synchronized manner. The crucial genetic regulations mediated by non-coding RNAs (ncRNAs) have emerged as game-changers in modulating the plant responses to drought and other abiotic stresses. The ncRNAs interact with their targets to form potentially subtle regulatory networks that control multiple genes to determine the overall response of plants. Many long and small drought-responsive ncRNAs have been identified and characterized in different plant varieties. The miRNA-based research is better documented, while lncRNA and transposon-derived RNAs are relatively new, and their cellular role is beginning to be understood. In this review, we have compiled the information on the categorization of non-coding RNAs based on their biogenesis and function. We also discuss the available literature on the role of long and small non-coding RNAs in mitigating drought stress in plants.
Topics: Droughts; Gene Expression Regulation, Plant; MicroRNAs; Plant Development; Plants; RNA, Long Noncoding; RNA, Untranslated; Stress, Physiological
PubMed: 34830399
DOI: 10.3390/ijms222212519