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Sarcopenia, the progressive decline of muscle mass and function, has traditionally been viewed as an age-related process leading to a broad range of adverse outcomes. However, it has been widely reported that sarcopenia can occur earlier in life in association with various conditions (i.e. disease-related sarcopenia), including neuromuscular disorders. As early as 2010, the European Working Group on Sarcopenia in Older People included neurodegenerative diseases characterised by motor neuron loss among the mechanisms underlying sarcopenia. Despite some differences in pathogenetic mechanisms, both amyotrophic lateral sclerosis (ALS) and age-related sarcopenia share common characteristics, such as the loss of motor units and muscle fibre atrophy, oxidative stress, mitochondrial dysfunction and inflammation. The histology of older muscle shows fibre size heterogeneity, fibre grouping and a loss of satellite cells, similar to what is observed in ALS patients. Regrettably, the sarcopenic process in ALS patients has been largely overlooked, and literature on the condition in this patient group is very scarce. Some instruments used for the assessment of sarcopenia in older people could also be applied to ALS patients. At this time, there is no approved specific pharmacological treatment to reverse damage to motor neurons or cure ALS, just as there is none for sarcopenia. However, some agents targeting the muscle, like myostatin and mammalian target of rapamycin inhibitors, are under investigation both in the sarcopenia and ALS context. The development of new therapeutic agents targeting the skeletal muscle may indeed be beneficial to both ALS patients and older people with sarcopenia. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic stem cells residing in many tissues, including the lung. MSCs have long been regarded as a promising tool for cell-based therapy because of their ability to replace damaged tissue by differentiating into the resident cell and repopulating the injured area. Their ability to release soluble factors and extracellular vesicles has emerged as crucial in the resolution of inflammation and injury. There is a growing literature on the use of MSCs and MSC secretome to hamper inflammation in different lung pathologies, including: asthma, pneumonia, acute lung injury (ALI), pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). However, their potential therapeutic role in the context of Cystic Fibrosis (CF) lung inflammation is still not fully characterized. CF morbidity and mortality are mainly due to progressive lung dysfunction. Lung inflammation is a chronic and unresolved condition that triggers progressive tissue damage. Thus, it becomes even more important to develop innovative immunomodulatory therapies aside from classic anti-inflammatory agents. Here, we address the main features of CF and the implications in lung inflammation. We then review how MSCs and MSC secretome participate in attenuating inflammation in pulmonary pathologies, emphasizing the significant potential of MSCs as new therapeutic approach in CF. [ABSTRACT FROM AUTHOR]

We focused on transcription factors and epigenetic marks that regulate the B3GALT5 gene through its retroviral long terminal repeat (LTR) promoter. We compared the expression levels of the B3GALT5 LTR transcript, quantitated by competitive RT-PCR, with those of the candidate transcription factors HNF1α/β and Cdx1/2, determined by Western blot analysis, in colon cancer biopsies, various cell lines, and cell models serving as controls. We found that HNF1α/β were easily detected, irrespective of the amount of LTR transcript expressed by the source, whereas Cdx1/2 were undetectable, and no sample lacking HNF1α/β expressed the LTR transcript. On transfection in proper host cells, both HNFlα and HNF1β provided detectable LTR transcript, where shRNA-mediated silencing of HNF1β impaired transcription. Treating cells with 5'-aza-2'-deoxycytidine (5AZA) strongly reduced expression, without affecting HNFlα/β, despite the lack of CpG islands in the LTR and proximal sequences. By electrophoresis mobility shift and luciferase reporter assays, the LTR promoter binding and activity did not correlate with the amounts of LTR transcript expressed in the cells and depended on the levels of the transcription factors. We conclude that HNFlα/β are necessary but insufficient to activate and regulate B3GALT5 LTR transcription, which depends on unknown regulatory elements that are active when methylated and located outside of and far from the LTR promoter. [ABSTRACT FROM AUTHOR]

Objectives: Recently, a subset of patients affected by cerebral amyloid angiopathy (CAA) distinguished by atypical juvenile onset and a hypothesized iatrogenic origin (iatrogenic CAA, iCAA) has emerged. β-Amyloid (Aβ) accumulation evidenced by amyloid PET positivity or CSF Aβ decrease was included in the iCAA diagnostic criteria. Conversely, diagnostic criteria for sporadic CAA (sCAA) do not involve biomarker analysis. The aim of this study was to assess CSF and plasma levels of Aβ and tau in iCAA and sCAA cohorts., Methods: Patients affected by probable or possible CAA according to established criteria (Boston 2.0) were prospectively recruited at Fondazione IRCCS Carlo Besta and San Gerardo dei Tintori from May 2021 to January 2024. Patients with probable and possible iCAA or sCAA with available plasma and/or CSF samples were included. Clinical and neurologic data were collected, and levels of Aβ40, Aβ42, total tau, and phospho-tau (p-tau) were assessed in CSF and plasma by SiMoA and Lumipulse., Results: 21 patients with iCAA (72% male, mean age at symptom onset 50 years [36-74]) and 32 patients with sCAA (44% male, mean age at symptom onset 68 years [52-80]) were identified. Cognitive impairment and cardiovascular risk factors in the sCAA cohort were more common compared with the iCAA cohort. Patients with sCAA and iCAA showed similar CSF levels for Aβ40 ( p = 0.5 [sCAA, 95% CI 2,604-4,228; iCAA, 95% CI 1,958-3,736]), Aβ42 ( p = 0.7 [sCAA, 95% CI 88-157; iCAA, 95% CI 83-155]), and total tau ( p = 0.08 [sCAA, 95% CI 80-134; iCAA, 95% CI 37-99]). Plasma levels of Aβ40 ( p = 0.08, 95% CI 181-222), Aβ42 ( p = 0.3, 95% CI 6-8), and total tau ( p = 0.4, 95% CI 3-6) were not statistically different in patients with sCAA compared with iCAA ones (Aβ40, 95% CI 153-193; Aβ42, 95% CI 6-7 and total tau, 95% CI 2-4)., Discussion: Despite presenting with a younger age at onset, fewer cardiovascular risk factors, and lower cognitive impairment, patients with iCAA demonstrated Aβ and tau levels comparable with elderly patients with sCAA, supporting a common molecular paradigm between the 2 CAA forms.

Background: CA19.9 is the unique marker recommended for the preoperative staging and the follow-up of patients suffering from pancreatic ductal adenocarcinoma (PDAC) but up to 30% of PDAC patients maintain normal CA19.9 values and cannot be monitored in this way. Lewis a (Lea Galβ1,3[Fucα1,4]GlcNAc) and b (Leb, Fucα1,2Galβ1,3[Fucα1,4]GlcNAc) are antigens which are structurally similar to sialyl-Lewis a (Siaα2,3Galβ1,3[Fucα1,4]GlcNAc), the epitope of CA19.9., Methods: We set an ELISA procedure determining the levels of Lea, Leb, and CA19.9 in the blood of healthy individuals or PDAC patients. Moreover, such antigens were also detected in cancer resections by immunofluorescence microscopy, and the levels of glycosyltransferase transcripts involved in Lewis antigen biosynthesis were determined by RT-qPCR., Results: In our cohort of 116 healthy individuals, the distribution of circulating Lea and Leb was similar to that of CA19.9, allowing us to set putative cutoff values for both antigens. In a cohort of 115 PDAC patients, the differential distribution with respect to the controls was statistically significant for both antigens (p < 0.001). Out of 37 patients presenting normal CA19.9 values, 15 patients presented Lea or Leb above the cutoffs. By immunofluorescence, Lea, Leb and CA19.9 were all detected in cancer resections and expression levels were heterogeneous among patients in terms of intensity, localization and diffusion. The levels of relevant glycosyltransferase transcripts were found to be heterogeneous between cancers of different patients and no association was detectable with the levels of any circulating antigen., Conclusions: The concurrent quantification of Lea and Leb together with CA19.9 improves the management of PDAC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)