Biology subjects

Ghiarone, T.

Publications and source records attributed to Ghiarone, T..

3 recordsLinked to original sources

bioRxiv2026

Short-Term Combined Tat-Beclin1 and Endurance Training Improves Age-Related Decline in Physical Function in Male Mice

Autophagy is a hallmark of aging, but autophagy-related proteins have not been exclusively targeted to attenuate the progressive decline in physical function associated with aging. Here, we combined Tat-Beclin1, an autophagy agonist, and endurance training to determine whether Tat-Beclin1 enhances exercise adaptation in old male mice. Tat-Beclin1 was administered intraperitoneally (TB group, 15 mg/kg, 2x/week) as a standalone therapy, or in combination with endurance training (TB+Exe group, 70% of maximal running speed 3x/week) for 1 month in 23-month-old male C57BL/6J mice. Control groups were age-matched cage controls and exercise-only groups. Animals were assessed for grip strength, endurance capacity on a treadmill, and balance and coordination on a rotarod. Gastrocnemius/plantaris (G/P) and tibialis anterior muscles were harvested for western blotting, myofiber typing, and proteomic profiling (G/P only). TB+Exe led to significant increases in grip strength, endurance capacity, and balance and coordination performance beyond those observed in the TB and Exe groups alone. Autophagy markers, including Beclin1, the LC3B-II/I ratio, and p62, did not differ among groups. A proteomic analysis of the G/P muscle revealed that TB upregulated biological processes involved in muscle contraction and adaptation, whereas TB+Exe increased mitochondrial bioenergetic processes and, surprisingly, upregulated acute inflammatory responses, including proteins such as haptoglobin and orosomucoid-1. We conclude that combining Tat-Beclin1 and endurance training may represent a new approach to attenuate aging-related decline in physical function. New & NoteworthyWe show evidence that combining Tat-Beclin1 and endurance training (TB+Exe) resulted in greater improvements in physical function in 24-month-old male mice than either standalone therapy. We also show that TB+Exe upregulates traditional exercise-like biological processes and unexpectedly upregulates acute-inflammatory proteins (e.g., orosomucoid-1), which are thought to improve physical function in preclinical studies. Our study suggests that TB may be a new drug enhancing physical function, especially when combined with endurance training in old male mice.

physiology↗

bioRxiv2025

Emerin expression stratification across breast cancer subtypes

Nuclear dysmorphism is a critical indicator of tumor aggressiveness, influencing cancer cell invasion and metastasis. Emerin, an integral nuclear envelope protein involved in nuclear architecture, is important for maintaining nuclear integrity. Our previous work demonstrated an inverse correlation between nuclear envelope-localized emerin expression and breast cancer aggressiveness. However, it failed to have the power to assess whether emerin loss correlates with cancer stage, grade, proliferation, or molecular phenotype. Here we analyzed emerin expression at the nuclear envelope across 243 breast cancer patient samples encompassing various tumor grades, stages, and molecular phenotypes. We found significantly reduced emerin expression in invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and ductal carcinoma in situ (DCIS), compared to normal breast tissue. Notably, emerin loss correlated with advanced tumor stage, higher Ki-67 proliferation rates, elevated human epidermal growth factor receptor 2 (HER2) levels, and decreased estrogen receptor (ER) and progesterone receptor (PR) expression--markers associated with more aggressive breast cancers. Emerin expression was consistently reduced in triple-negative breast cancer (TNBC) and other receptor-negative subtypes, underscoring its potential role in tumor dedifferentiation and progression. These findings highlight emerin as a promising prognostic biomarker and therapeutic target for aggressive breast cancer subtypes.

cancer biology↗

bioRxiv2019

Exercise twice-a-day potentiates skeletal muscle signalling responses associated with mitochondrial biogenesis in humans, which are independent of lowered muscle glycogen content

Endurance exercise begun with reduced muscle glycogen stores seems to potentiate skeletal muscle protein abundance and gene expression. However, it is unknown whether this greater signalling responses is due to low muscle glycogen per se or to performing two exercise sessions in close proximity - as a first exercise session is necessary to reduce the muscle glycogen stores. In the present study, we manipulated the recovery duration between a first muscle glycogen-depleting exercise and a second exercise session, such that the second exercise session started with reduced muscle glycogen in both approaches but was performed either two or 15 h after the first exercise session (so-called "twice-a-day" and "once-daily" approaches, respectively). We found that exercise twice-a-day increased the nuclear abundance of transcription factor EB (TFEB) and nuclear factor of activated T cells (NFAT) and potentiated the transcription of peroxisome proliferator-activated receptor-coactivator 1 alpha (PGC-1), peroxisome proliferator-activated receptor alpha (PPAR) and peroxisome proliferator-activated receptor beta/delta (PPAR{beta}/{delta}) genes, in comparison with the once-daily exercise. These results suggest that the elevated molecular signalling reported with previous "train-low" approaches can be attributed to performing two exercise sessions in close proximity rather than the reduced muscle glycogen content per se. The twice-a-day approach might be an effective strategy to induce adaptations related to mitochondrial biogenesis and fat oxidation.

molecular biology↗