The first FDA-approved drug for frostbite can save limbs from amputation, and researchers are working on “coldscreen” preventatives.

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27 1月 2025

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Author : 伤口世界

The first FDA-approved drug for frostbite can save limbs from amputation, and researchers are working on “coldscreen” preventatives.

This article is excerpted from the ACS Cent. Sci. 2024, 10, 1976−1979 by Wound World.

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Latest from 伤口世界

Hypercholesterolemia Duration and Brain Area Determine Inflammatory Response Intensity and Apoptotic Mediator Activation in Apo E−/−/LDLR−/− Double‑Knockout Mice
Salt‑sensitive hypertension in GR mutant rats is associated with altered plasma polyunsaturated fatty acid levels and aortic vascular reactivity
Nutritional Interventions for Pressure Ulcer Prevention in Hip Fracture Patients: A Systematic Review and Meta-Analysis of Controlled Trials
CB-MNCs@ CS/HEC/GP promote wound healing in aged murine pressure ulcer model
The association between obesity indicators and mortality among individuals with hyperlipidemia: evidence from the NHANES 2003–2018

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Hypercholesterolemia Duration and Brain Area Determine Inflammatory Response Intensity and Apoptotic Mediator Activation in Apo E−/−/LDLR−/− Double‑Knockout Mice 2025-08-05 00:00

Ewelina Czuba‑Pakuła1 · Jolanta Ochocińska2 · Sebastian Głowiński3 · Alicja Braczko4 · Ryszard T. Smoleński4 · Grażyna Lietzau1 · Przemysław Kowiański1,3

Received: 14 August 2024 / Accepted: 7 May 2025 © The Author(s) 2025

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1 Division of Anatomy and Neurobiology, Faculty of Medicine, Medical University of Gdansk, Dębinki 1, 80-211 Gdańsk, Poland

2 Department of Conservative Dentistry, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland

3 Institute of Health Sciences, Pomeranian University in Słupsk, Słupsk, Poland

4 Department of Biochemistry, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland

Abstract

Hypercholesterolemia (Hch) is a risk factor for cerebrovascular and neurodegenerative diseases, manifesting with symptoms that vary depending on damage to specific brain regions. Hch triggers inflammatory responses and cell death. However, the progression of these processes in relation to the duration of Hch and the location of pathology in the central nervous system remains unclear. Therefore, we aimed to investigate (1) the impact of age and duration of Hch on neuroinflammatory responses and programmed cell death in the brain and (2) the intensity of these processes in various brain areas during Hch. In this study, we used 3-, 6-, and 12-month-old male Apo E−/−/LDLR−/− double-knockout mice and age-matched wild-type C57BL/6 mice (control group). Concentrations of cytokines IL-1β, IL-4, and IL-6, as well as apoptotic mediators AIF and Cas-3, were measured using enzyme-linked immunosorbent assay in the whole brain and separately in the prefrontal cortex (PFCx), hippocampus (HIP), and striatum (STR). The results showed that the Hch-induced release of cytokines IL-1β and IL-6, decreased expression of IL-4, and elevated level of apoptotic markers AIF and Cas-3 correlated with Hch duration. The inflammatory response and expression of apoptotic markers were more pronounced in the HIP and STR compared to the PFCx. Our results indicate a correlation between the neurodegenerative effects of Hch and its duration and highlight the varying susceptibility of different brain areas to Hch-induced damage.

Graphical Abstract

Hypercholesterolemia (Hch)-induced inflammatory response and programmed cell death activation in the prefrontal cortex (PFCx), hippocampus (HIP), and striatum (STR) of 3-, 6-, and 12-month-old, Apo E−/−/LDLR−/− double-knockout mice. In three age-groups the Hch-induced response involved release of inflammatory cytokines (IL-1ß and IL-6), a decrease of anti-inflammatory (IL-4) cytokine level, and activation of programmed cell death markers (AIF and Cas-3). The inflam matory response and expression of apoptotic markers were more pronounced in the HIP and STR, compared to the PFCx.

Keywords Apoptosis · Atherosclerosis · Cytokines · Hypercholesterolemia · Neurodegeneration · Neuroinflammation
Salt‑sensitive hypertension in GR mutant rats is associated with altered plasma polyunsaturated fatty acid levels and aortic vascular reactivity 2025-08-04 00:00

S.Verouti1,2,3 · G. Aeschlimann1 · Q. Wang4 · D. Ancin Del Olmo1 · A. C. Peyter5 · S. Menétrey5 ·D.V. Winter6 · A. Odermatt6 · D. Pearce7 · E. Hummler1,2 · P. E. Vanderriele1,2

Received: 30 April 2024 / Revised: 22 August 2024 / Accepted: 23 August 2024 / Published online: 10 September 2024 © The Author(s) 2024

* P. E. Vanderriele 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

1 Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland

2 National Center of Competence in Research, Kidney.CH, Lausanne, Switzerland

3 Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland

4 Division of Nephrology and Hypertension, Lausanne University Hospital (CHUV), Lausanne, Switzerland

5 Neonatal Research Laboratory, Clinic of Neonatology, Department Woman-Mother-Child, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland

6 Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland

7 Department of Medicine and Cellular & Molecular Pharmacology, University of California, San Francisco, USA

Abstract

In humans, glucocorticoid resistance is attributed to mutations in the glucocorticoid receptor (GR). Most of these mutations result in decreased ligand binding, transactivation, and/or translocation, albeit with normal protein abundances. However, there is no clear genotype‒phenotype relationship between the severity or age at disease presentation and the degree of functional loss of the receptor. Previously, we documented that a GR+/− rat line developed clinical features of glucocorticoid resistance, namely, hypercortisolemia, adrenal hyperplasia, and salt-sensitive hypertension. In this study, we analyzed the GR+/em4 rat model heterozygously mutant for the deletion of exon 3, which encompasses the second zinc finger, including the domains of DNA binding, dimerization, and nuclear localization signals. On a standard diet, mutant rats exhibited a trend toward increased corticosterone levels and a normal systolic blood pressure and heart rate but presented with adrenal hyperplasia. They exhibited increased adrenal soluble epoxide hydroxylase (sEH), favoring an increase in less active poly unsaturated fatty acids. Indeed, a significant increase in nonactive omega-3 and omega-6 polyunsaturated fatty acids, such as 5(6)-DiHETrE or 9(10)-DiHOME, was observed with advanced age (10 versus 5 weeks old) and following a switch to a high-salt diet accompanied by salt-sensitive hypertension. In thoracic aortas, a reduced soluble epoxide hydrolase (sEH) protein abundance resulted in altered vascular reactivity upon a standard diet, which was blunted upon a high-salt diet. In conclusion, mutations in the GR affecting the ligand-binding domain as well as the dimerization domain resulted in deregu lated GR signaling, favoring salt-sensitive hypertension in the absence of obvious mineralocorticoid excess.

Keywords Adrenal gland hyperplasia · Hypertension · Glucocorticoid receptor · Soluble epoxide hydrolase · Chrousos syndrome

Abbreviations

ACTH Adrenocorticotropic hormone DiHETrE Dihydroxyeicosatrienoic acid DiHOME Dihydroxy-9Z-octadecenoic acid EET Epoxyeicosatrienoic acid EpETrE Epoxyeicosatrienoic acid GR Glucocorticoid receptor HETE Hydroxyeicosatetraenoic acid KODE Ketooctadecenoic acid sEH Soluble epoxide hydrolase

◂Fig.1 GR+/em4 rats presented adrenal hyperplasia of the cortex and the medulla accompanied by a trend toward an increase in the plasma glucocorticoid concentration under standard diet. A Scheme of the wild-type (GR+, upper panel) and the mutated GRem2 (middle) and GRem4 (lower panel) structure of the GR. B Representation of the zinc finger domain of the GR with the deleted amino acids in red. C Rep resentative macroscopic images (scale bar, 1 mm) and D hematoxy lin/eosin-stained sections of whole adrenal glands (left panels; scale bar, 1 mm) and cortex (right panels; scale bar, 300 µm) from 3- to 4-week-old male GR+/+ and GR+/em4 rats (n=3) fed a standard salt diet; zf, zona fasciculata; zg, zona glomerulosa. E Measurement of the adrenal weight/body weight ratio (GR+/+, n=12; GR+/em4, n=14) and F cortex (left) and medulla (right panel) size (GR+/+ (n=3) and GR+/em4 (n=4)). G Determination of plasma concentrations of the glucocorticoids corticosterone, 11-dehydrocorticosterone and the corticosterone/11-dehydrocorticosterone ratio and H the mineralo corticoid aldosterone and its precursor 11-deoxycorticosterone in the morning (7–8 am) and afternoon (6–7 pm) of GR+/+ and GR.+/em4 (n=4 – 16) rats. The size measurements were evaluated using QuPath (vO.4.4), and the plasma concentrations were evaluated by two-way ANOVA and subsequently compared with an unpaired two tailed t test with Welch’s correction. The values are presented as the mean±SEMs. Differences were assessed at *P<0.05 and **P<0.01
Nutritional Interventions for Pressure Ulcer Prevention in Hip Fracture Patients: A Systematic Review and Meta-Analysis of Controlled Trials 2025-08-01 00:00

Jose M. Moran 1,* , Laura Trigo-Navarro 2 , Esther Diestre-Morcillo 3 , Elena Pastor-Ramon 4 and Luis M. Puerto-Parejo 5

1 Nursing and Occupational Therapy College, University of Extremadura, 10001 Caceres, Spain

2 Área de Salud de Badajoz, Supervisora del Bloque Quirúrgico, Hospital Materno Infantil de Badajoz, Calle Violeta 3, 06010 Badajoz, Spain; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

3 Área de Salud de Badajoz, Banco de Sangre, Hospital Universitario de Badajoz, Av. de Elvas, s/n, 06080 Badajoz, Spain

4 Biblioteca Virtual de ciencias de la Salud de las Illes Balears (Bibliosalut), Ctra. De Valldemossa, 79, mòdul L+1, 07120 Palma, Spain; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

5 Gerencia del Área de Salud de Badajoz, Supervisor del Área de Investigación, Proyectos y Gestión, Av. de Huelva, 8, 06005 Badajoz, Spain; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

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Academic Editor: Yi-Chia Huang

Received: 22 January 2025

Revised: 6 February 2025

Accepted: 8 February 2025

Published: 11 February 2025

Citation: Moran, J.M.; Trigo-Navarro, L.; Diestre-Morcillo, E.; Pastor-Ramon, E.; Puerto-Parejo, L.M. Nutritional Interventions for Pressure Ulcer Prevention in Hip Fracture Patients: A Systematic Review and Meta-Analysis of Controlled Trials. Nutrients 2025, 17, 644. https://doi.org/10.3390/ nu17040644

Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/

Abstract: Background/Objective: Pressure ulcers represent a significant complication in patients with reduced mobility, such as those recovering from hip fractures. In the present study, we aimed to comprehensively assess the impact of oral nutritional interventions on the development of pressure ulcers in hip fracture patients via a systematic review and meta analysis of controlled studies evaluating the effectiveness of oral nutritional supplements compared with standard care. Methods: In accordance with PRISMA standards, this systematic review and meta-analysis of controlled studies evaluated the effectiveness of any type of oral nutritional supplements compared with standard care in hip fracture patients. The risk of bias was evaluated using the Cochrane ROB2 tool for randomized controlled trials and the ROBINS-1 tool for nonrandomized trials. Results: Fourteen studies (10 randomized controlled trials and 4 controlled trials) published since 1990 (n = 1648) were included. Oral nutritional supplementation was associated with a statistically significant decrease in the odds ratio of developing pressure ulcers in hip fracture patients (OR 0.54, 95% CI: 0.40–0.73, p < 0.001). Conclusions: The incidence and evolution of pressure ulcers can be improved by oral dietary supplementation in patients who have undergone hip fracture surgery. Accordingly, we propose that oral nutritional supplementation should be considered an essential component of comprehensive post-hip-fracture care.

Keywords: hip fracture; pressure ulcers; oral nutritional supplement; pressure sores; meta-analysis; wound healing; nutritional intervention

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The first FDA-approved drug for frostbite can save limbs from amputation, and researchers are working on “coldscreen” preventatives.

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主任医师、教授、博导，南方医科大学第三附属医院（广东省骨科医院）院长

The first FDA-approved drug for frostbite can save limbs from amputation, and researchers are working on “coldscreen” preventatives.

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