Fig 1: Clinical images of the patient. (A) Axial CT images of the first stroke-like episode revealed cerebral edema and brain herniation in the right occipital (i), temporal (ii), and parietal (iii) lobes (red arrows). The green arrow indicated basal ganglia calcification (i). (B) Perimetry showed left-side hemianopsia. (C) Axial CT images of the second stroke-like episode revealed more severe cerebral infarction and cerebral edema in the right occipital (i), temporal (ii), and parietal (iii) lobes, and in the right cerebellar hemisphere (i) (red arrows). The green arrow indicated basal ganglia calcification (i). (D) Axial CT images at 12 years of age showed cerebral atrophy (i–iii), an enlarged lateral cerebroventricle (i–ii) and multiple calcifications (i). (E) Image i showed several subsarcolemmal basophilic substance (red arrow; HE staining). Image ii showed several RRFs (red arrow; MGT staining). Image iii showed ragged blue fibers (red arrow; SDH reaction). Images iv and v showed general COX-deficient fibers (COX-SDH reaction and COX reaction, respectively). The red arrow in image iv and v indicated a COX-positive fiber. Image vi showed a normal muscle sample from an age matched control (COX reaction).
Fig 2: CSA markedly relieved compression-induced mitophagy in rat NPCs. The rat NPCs were cultured under 1.0 MPa compression for 0, 24 and 48 h with CSA, or the same volume of DMSO (the control). A, The levels of p62, LC3-I, LC3-II, PINK1, PARKIN and COX IV were detected by Western blotting. B, A quantitative analysis of Western blotting shown by the p62/ß-actin, LC3-II/ß-actin, PINK1/ß-actin, PARKIN/ß-actin and COX IV/ß-actin ratios. C, The MMP was monitored using a JC-1 assay kit by flow cytometry. D, Quantitative and statistical analysis of MMP in rat NPCs; the data are expressed as the ratio of red over green fluorescence intensity, as assessed by flow cytometry. E, TEM was performed to observe the swollen mitochondria and autophagosomes with double membranes. Scale bars, 5 µm (a, c, h), 2 µm (f, j) or 0.5 µm (b, d, e, g, I, k); single thin arrowhead indicated normal mitochondria; double thin arrowheads indicated swollen mitochondria; single thick arrowhead indicated autophagic bodies. Data are presented as the mean ± SD (n = 3); *indicates a significant difference (P < .05) and **indicates a significant difference (P < .01) between the CSA treatment group and the control at the same durations of compression. CSA, cyclosporine A; TEM, transmission electron microscopy
Fig 3: Hypo-EVs rescued mitochondrial homeostasis in vivo. a Representative TEM images of kidneys on D 14 after I/R injury. Scale bar represents 500 nm. b, c Western blot was used to detect the protein expression of mitochondrial OXPHOS proteins (ATPB?SDHB and COX IV). The relative expression of ATPB, SDHB and COX IV were evaluated (n = 5–6). d Mitochondrial membrane potential was determined through a JC-1 probe in HK-2 cells after incubated with TGF-ß1. Scale bar represents 100 µm. e Mito-SOX Red was used to observe the levels of intracellular ROS in the HK-2 cells after incubated with TGF-ß1. Scale bar represents 100 µm. Data are expressed as mean ± SEM. *P < 0.05,** < 0.01
Fig 4: Nano-PSO treatment restored mitochondrial COX IV1 expression in all mice: (A) Coronal sections through the temporal cortex of brains from treated and untreated controls, as well as from untreated TBI, treated with Nano-PSO before TBI and treated with Nano-PSO post-TBI were immunostained for COX IV1 (red) and DAPI (blue) [scale bar 50 µm]; (B) Quantitative assessment of COX IV1 immunostaining for all sections (bregma temporal cortex -1.06 nm) at the end point of each experiment was quantified by One-way ANOVA (F (4, 12) = 45.101, p = 0.000 Fisher’s LSD post hoc, ** p < 0.01, *** p < 0.001, n = 3–4). NS = Not significant. Values are presented as mean ± SEM.
Fig 5: Tat-SabKIM1 peptide tracheal injection could inhibit JNK-mitochondrial activation during acute lung injury/acute respiratory distress syndrome. (A) Representative western blotting images of p-JNK and JNK expression in the mitochondrial protein. Relative (B) p-JNK and (C) JNK protein content in the mitochondrial protein. (D) Normalized ratio of p-JNK/JNK in the mitochondrial protein. (E) Representative western blotting images of p-JNK and JNK expression in the cytosol/nucleus protein. Relative (F) p-JNK and (G) JNK protein content in the cytosol/nucleus protein. (H) Normalized ratio of p-JNK/JNK in the cytosol/nucleus protein. Data are presented as the mean ± SEM. n=4/group. *P<0.05. TS, Tat-SabKIM1; p-, phosphorylated; COX IV, cytochrome c oxidase IV.
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