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Intercellular mitochondrial transfer (IMT) is an intriguing biological phenomenon where mitochondria are transferred between different cells and notably, cell types. IMT is physiological, occurring in normal conditions, but also is utilized to deliver healthy mitochondria to cells in distress. Transferred mitochondria can be integrated to improve cellular metabolism, and mitochondrial function. Research on the mitochondrial transfer axis between astrocytes and brain capillaries <i>in vivo</i> is limited by the cellular heterogeneity of the neurovascular unit. To this end, we developed an inducible mouse model that expresses mitochondrial Dendra2 only in astrocytes and then isolated brain capillaries to remove all intact astrocytes. This method allows the visualization of <i>in vivo</i> astrocyte- endothelial cell (EC) and astrocyte-pericyte IMT. We demonstrate evidence of astrocyte-EC and astrocyte-pericyte mitochondrial transfer within brain capillaries. We also show that healthy aging enhances mitochondrial transfer from astrocytes to brain capillaries, revealing a potential link between brain aging and cellular mitochondrial dynamics. Finally, we observe that astrocyte-derived extracellular vesicles transfer mitochondria to brain microvascular endothelial cells, showing the potential route of <i>in vivo</i> IMT. These results represent a breakthrough in our understanding of IMT in the brain and a new target in brain aging and neurovascular metabolism.

ObjectiveThe genomic effects of biomechanical loading on human growth plate cartilage are unknown so far. To address this, we used rare human growth plate biopsies obtained from children undergoing epiphysiodesis and exposed them to precisely controlled mechanical loading using a microloading device. The biopsies were cultured 24 hours after mechanical loading, followed by RNA-sequencing analyses to decipher the genomic regulation.DesignWe conducted RNA-seq analysis of human growth plate cartilage obtained from three patients cultured <i>ex vivo</i> and subjected to cyclical mechanical loading with peak 0.4 N with frequency 0.77 Hz during a 30-second duration, using a specialized microloading device.ResultsGene ontology analysis revealed novel data showing three significantly upregulated signaling pathways, including notch, oxytocin, and tight junction, and three significantly downregulated signaling pathways, including lysosome, sphingolipid metabolism, and peroxisome proliferator-activated receptor (PPAR) in human growth plate cartilage. Moreover, we found 15 significantly regulated genes within these signaling pathways from all three patients. These genes included PSEN2, HEY1, and NCOR2 from the notch signaling; CACNB1 and PPP3R2 from the oxytocin signaling; ACTR3C, WHAMM, and ARHGEF18 from the tight junction signaling; ARSA, SMPD1, and CD68 from the lysosome signaling; ARSA and SMPD1 from the sphingolipid metabolism signaling; and SLC27A4 and AQP7 from the PPAR signaling pathway. In addition, 20 significantly upregulated genes and six significantly downregulated genes shared between two patient samples were identified.ConclusionOur study provides the first-ever transcriptomic data of mechanical loading of human growth plate cartilage. These findings can potentially provide genetic targets for future investigations in physiological and pathological bone growth conditions.

<h4>Background and aim</h4>Skeletal muscle is the largest organ of the human body. It affects body metabolism and cooperates with other organs to maintain various physiological functions. Gan-Mai-Da-Zao-Tang (, gān mài dà zǎo tāng, GMDZ) is a traditional Chinese medicine consisting of licorice, wheat, and jujube. GMDZ is commonly used to treat anxiety and depression. Increasing evidence shows a correlation exists between sarcopenia and depression. Muscle wasting, particularly in older individuals, increases the risk of depressive symptoms. The study aims to explore the effects of GMDZ water extract (WE) on age-induced muscle wasting and mitochondrial dysfunction in 25-week-old and 82-week-old mice.<h4>Experimental procedure</h4>Exercise capacity was assessed through locomotor activity, rotarod performance, and grid-hanging tests. Grip strength was measured to assess muscle strength, while histological analysis and immunofluorescence staining were used to evaluate muscle mass and myofiber cross-sectional area. Protein expression, mRNA, and ATP levels were determined using western blots, real-time PCR, and ATP bioluminescence assays.<h4>Results and conclusion</h4>GMDZ-WE significantly improved motor performance, grip strength, muscle mass, and myofiber cross-sectional area in aging mice. These enhancements were associated with increased MyHC expression and the IGF-1R/Akt protein synthesis pathway in skeletal muscle. In addition, GMDZ-WE decreased age-related protein degradation and inflammatory signaling, enhanced mitochondrial biogenesis signaling, increased GSH levels, SOD activity, and reduced lipid oxidation in the skeletal muscle of aging mice. In conclusion, GMDZ-WE reduces age-related skeletal muscle wasting, motor impairment, oxidative stress, inflammation, and mitochondrial dysfunction, demonstrating anti-aging potential on skeletal muscles.

Non-transfusional iron overload (IOL) in hereditary spherocytosis (HS) is poorly documented compared with other red blood cell disorders. We studied 13 HS adults with confirmed IOL to identify potential genetic factors. Using a next-generation sequencing panel of 46 genes related to HS, anaemia and iron metabolism, we found no association between IOL and the genes involved in HS nor the HFE:p.(Cys282Tyr) variant responsible for hereditary haemochromatosis. However, potential genetic factors contributing to IOL were identified in some patients, including variants in HJV (haemojuvelin), SLC40A1 (ferroportin), PKLR (pyruvate kinase), ABCG5 and ABCB8, highlighting the need for larger studies.