Dynamic smoking patterns and risk of parkinson disease and all-cause mortality: a competing risk analysis approach.
Background and Objectives.
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Exercise, nutrition, physical agent therapy in older adults with sarcopenic obesity: a systematic review and network meta-analysis
Sarcopenic obesity (SO) is characterized by the co-existence of excess adiposity and low muscle performance, with a high prevalence and poor prognosis in the geriatric population.
This systematic review and network meta-analysis (NMA) aims to assess the most effective non-pharmacological interventions for SO patients, including nutrition, exercise, and physical agent therapy.
A systematic search of six electronic databases was conducted from their inception until July 5, 2025, for randomized controlled trials. The NMA utilized a random-effects model, pooled mean difference (MD) and standardized mean difference (SMD), with 95% credible intervals (CrI), accounting for correlations within multi-arm trials. Subgroup analyses and sensitivity analyses were also performed.
Potassium channels functionality is coupled to trafficking!
In a study published recently in PNAS, researchers have revealed the relationship between KCNQ2/3 channel functionality (i.e., how well they work to control electrical signals in neurons) and localization (i.e., where they are found inside a cell), with important implications for the treatment of these epileptic disorders.
For KCNQ2/3 channels to work properly in the brain, they must have full functionality and be located in the correct cellular region – specifically the axon initial segment (AIS), the site in neurons where electric signals are first triggered, controlling nerve cell activity. This led the research team to wonder: does the functionality of KCNQ2/3 channels affect their cellular localization, or are the two not linked at all?
To investigate this potential association, the research team first genetically engineered the functionality of the channels, and then used channel trafficking imaging to visualize whether the channels were taken to their location in the AIS. In this way, they demonstrated that KCNQ2/3 functionality was indeed linked to its trafficking to the correct cellular localization. What’s more, when they used single-molecule imaging, they could see that reduced KCNQ3 functionality actually reduced the AIS localization of KCNQ2/3 by altering the entire trafficking pathway.
“Because we already knew that the localization of KCNQ2/3 to the AIS is regulated by a protein known as ankyrinG, or ankG, we next decided to explore the interactions between full-length KCNQ3 and ankG,” explains lead author of the study. “We found that the active conformation of KCNQ3 was essential for its stable binding to ankG, further confirming that functional KCNQ2/3 is needed to ensure its proper accumulation at the AIS.”
Together, these findings highlight the mechanisms underlying the important link between KCNQ2/3 functionality and localization, and provide clues about how their alterations might affect neuronal excitability. ScienceMission sciencenewshighlights.
Potassium KCNQ2/3 channels are crucial for suppressing the excitability of brain cells, or neurons. When these channels don’t work properly, they can cause specific types of epilepsy like benign familial neonatal convulsions and early infantile epileptic encephalopathy.
Clinical and laboratory features of juvenile-onset anti-NF155 autoimmune nodopathy
Background Neurofascin 155 autoimmune nodopathy (NF155 AN) is a recently recognised immune-mediated neuropathy distinct from chronic inflammatory demyelinating polyneuropathy. While adult-onset cases have been increasingly reported, the juvenile-onset form remains poorly characterised.
Methods We retrospectively analysed 36 patients with NF155 AN, focusing on detailed characterisation of 16 juvenile-onset cases. Their clinical and laboratory data were reviewed.
Results Juvenile-onset patients presented with sensorimotor neuropathy characterised by distal predominant weakness, tremor and sensory ataxia. Motor symptoms were the presenting feature in 75% of patients, which significantly differed from the adult cases (p=0.0015). Postural tremor was more frequent in juvenile patients (94%), while cranial nerve involvement was less common (19%).
Abstract: These two transcription factors are required for regenerative lymphangiogenesis and repair following injury👇
Gou Young Koh & team establish ERG and Fli1 as core transcriptional regulators of lymphatic identity, integrity, and function, using human cells and mouse models:
The figure shows stasis of mesenteric lymphatic drainage for a tracer (red) in Prox1-GFP-mice lacking Erg/Fli1 specifically in lymphatic endothelial cells compared with Prox1-GFP-WT mice; with Prox1-GFP marking lymphatic structures (green).
1Center for Vascular Research, Institute for Basic Science, Daejeon, South Korea.
2Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
Address correspondence to: Hyuek Jong Lee or Gou Young Koh, Center for Vascular Research, Institute for Basic Science, Daejeon 34,141, South Korea. Email: hyuekjong.lee@gmail.com (HJL); gykoh@kaist.ac.kr (GYK).
Developmental reprogramming in melanocortin neurons modulates diet-induced obesity in mice
Reprogramming in melanocortin modulates diet-induced obesity.
Hypothalamic proopiomelanocortin (POMC) neurons promote satiety, while agouti-related peptide (AgRP) neurons drive hunger and maintain energy balance.
However, it is not clear how the system is diversified developmentally.
The researchers in this study show that transcription factor Otp act as a developmental ‘‘switch’’ in the hypothalamus and determines whether immature neurons become appetite suppressing (POMC) or appetite stimulating (AgRP).
Disrupting this switch reshapes feeding behavior and protects mice from obesity, revealing how early life programming shapes lifelong metabolic health. sciencenewshighlights ScienceMission https://sciencemission.com/melanocortin-neurons-modulates-diet-induced-obesity
Xu et al. show that a developmental “switch” in the hypothalamus determines whether immature neurons become appetite suppressing or appetite stimulating. Disrupting this switch reshapes feeding behavior and protects mice from obesity, revealing how early-life programming shapes lifelong metabolic health.
Setd4-expressing cells drive regenerative recovery in chronic liver injury
Liver regeneration in chronic disease is incompletely understood. In this issue, Jia and coworkers identify a distinct population of hepatocytes expressing Setd4 as key contributors to liver regeneration after chronic injury. Using lineage-tracing and ablation strategies in mouse models of chronic liver damage due to thioacetamide or 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet, the authors show that Setd4+ cells are a long-lasting, dormant, injury-resistant hepatocyte population that survives chronic insults and get activated to support de novo regeneration. Quiescent Setd4+ cells show suppressed metabolic activity maintained by a chromatin state that promotes cellular dormancy and survival (H4K20me3-enriched heterochromatin). After chronic injury, chromatin accessibility remodelling occurs, leading to activation of the cells and initiating regeneration. Selective ablation of Setd4+ cells markedly impaired regenerative recovery, leading to increased fibrosis, higher transaminases, and shorter survival. Interestingly, Setd4+ cells appeared to be essential to initiate de novo regeneration under chronic but not acute conditions. Given the presented data, this newly identified dormant Setd4+ hepatocyte population might hold therapeutic potential to restore regeneration in chronic liver disease.
Full text here: https://www.journal-of-hepatology.eu/article/S0168-8278(…4/fulltext.
EASL — the home of hepatology.
Chronic liver injury and its progression to disease often extend beyond exposure to toxic metabolites or xenobiotics. Recovery from chronic injury, when achieved, depends on de novo regeneration, the underlying mechanisms of which remain poorly understood. Herein, we investigate a specific cell population proposed to be fundamental for de novo regeneration and recovery following chronic injury, aiming to elucidate its regulatory mechanisms.
Immune cells in the brain may tune fertility hormones, animal study suggests
The kick-off signal for puberty begins in the brain. Specifically, in the hypothalamus, where specific neurons release a hormone that activates the hypophysis, at the base of the skull, which then releases other hormones to start gonad—ovaries or testicles—maturation. This mechanism leading to a fertile organism is the hypothalamic-pituitary-gonadal (HPG) axis.
A study by Spain’s National Cancer Research Center (CNIO) has discovered in animal models that two previously unsuspected elements are also involved in this hormone regulating system: microglia—defensive cells of the nervous system—and the protein RANK, which contributes to bone remodeling and is essential in the functioning of the mammary glands.
The work is published in the journal Science. It is led by Eva González-Suárez, head of the CNIO Transformation and Metastasis Group, who discovered in 2010 the key role played by RANK in the development of breast cancer. The first author is Alejandro Collado, a researcher from the same group and co-corresponding author.
Pluripotent stem-based screening uncovers sildenafil as a mitochondrial disease therapy
Now online! Leigh syndrome is a severe and untreatable mitochondrial disease. Using patient-derived models in 2D and 3D, Zink and colleagues identify the PDE5 inhibitor sildenafil as a repurposable drug candidate, leading to lifespan extension in mammalian models and clinical improvement in six individuals with Leigh syndrome.
Insulin Receptor Signaling in Normal and Insulin-Resistant States
In the wake of the worldwide increase in type-2 diabetes, a major focus of research is understanding the signaling pathways impacting this disease. Insulin signaling regulates glucose, lipid, and energy homeostasis, predominantly via action on liver, skeletal muscle, and adipose tissue. Precise modulation of this pathway is vital for adaption as the individual moves from the fed to the fasted state. The positive and negative modulators acting on different steps of the signaling pathway, as well as the diversity of protein isoform interaction, ensure a proper and coordinated biological response to insulin in different tissues. Whereas genetic mutations are causes of rare and severe insulin resistance, obesity can lead to insulin resistance through a variety of mechanisms.