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Traumatic brain injury (TBI) is a global public-health problem. Astrocytes, and their mitochondria, are important factors in the pathogenesis of TBI-induced secondary injury. Mitochondria extracted from healthy tissues and then transplanted have shown promise in models of a variety of diseases. However, the effect on recipient astrocytes is unclear. Here, we isolated primary astrocytes from newborn C57BL/6 mice, one portion of which was used to isolate mitochondria, and another was subjected to stretch injury (SI) followed by transplantation of the isolated mitochondria. After incubation for 12 h, cell viability, mitochondrial dysfunction, calcium overload, redox stress, inflammatory response, and apoptosis were improved. Live-cell imaging showed that the transplanted mitochondria were incorporated into injured astrocytes and fused with their mitochondrial networks, which was in accordance with the changes in the expression levels of markers of mitochondrial dynamics. The astrocytic IKK/NF-κB pathway was decelerated whereas the AMPK/PGC-1α pathway was accelerated by transplantation. Together, these results indicate that exogenous mitochondria from untreated astrocytes can be incorporated into injured astrocytes and fuse with their mitochondrial networks, improving cell viability by ameliorating mitochondrial dysfunction, redox stress, calcium overload, and inflammation., 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.)

Sarcopenia is a common skeletal muscle degenerative disease characterized by decreased skeletal muscle mass and mitochondrial dysfunction that involves microRNAs (miR) as regulatory factors in various pathways. Exercise reduces age-related oxidative damage and chronic inflammation and increases autophagy, among others. Moreover, whether aerobic exercise can regulate mitochondrial homeostasis by modulating the miR-128/insulin-like growth factor-1 (IGF-1) signaling pathway and can improve sarcopenia requires further investigation. Interestingly, zebrafish have been used as a model for aging research for over a decade due to their many outstanding advantages. Therefore, we established a model of zebrafish sarcopenia using d-galactose immersion and observed substantial changes, including reduced skeletal muscle cross-sectional area, increased tissue fibrosis, decreased motility, increased skeletal muscle reactive oxygen species, and notable alterations in mitochondrial morphology and function. We found that miR-128 expression was considerably upregulated, where as Igf1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were significantly downregulated; moreover, mitochondrial homeostasis was reduced. Four weeks of aerobic exercise delayed sarcopenia progression and prevented the disruption of mitochondrial function and homeostasis. The genes related to atrophy and miR-128 were downregulated, Igf1 expression was considerably upregulated, and the phosphorylation levels of Pi3k, Akt, and Foxo3a were upregulated. Furthermore, mitochondrial respiration and homeostasis were enhanced. In conclusion, aerobic exercise improved skeletal muscle quality and function via the miR-128/IGF-1 signaling pathway, consequently ameliorating mitochondrial homeostasis in aging skeletal muscle., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aims to investigate the value of diffusion kurtosis imaging (DKI) in assessing microstructural changes associated with cognitive impairment in chronic traumatic brain injury (TBI). At 7 months, six TBI rats and six control rats underwent Morris water maze (MWM) tests, followed by DKI examinations. DKI parameters were measured in bilateral cortex, hippocampus, and callosum. Brain immunohistochemistry (IHC) analysis of neuron [neuron-specific nuclear protein (NeuN)], astroglia [glial fibrillary acidic protein (GFAP)], microglia [ionized calcium binding adaptor molecule 1 (Iba-1)], and myelin [myelin basic protein (MBP)] was performed in the same area as DKI parameter. The DKI parameters, IHC results, and MWM results were compared between TBI and control groups. Correlation analysis was performed to analyze the relationship between DKI parameters and IHC and MWM results. TBI group had worse performance in MWM test. DKI showed higher mean diffusion (MD) in all ipsilateral regions of interest (ROIs), and lower mean kurtosis (MK) in ipsilateral cortex and callosum in TBI group (P < 0.05). TBI group also showed lower IHC staining of NeuN, and higher staining of Iba-1 and MBP in all ipsilateral ROIs (P < 0.05). Further correlational study showed a positive relationship between MK and NeuN, MD and MBP in ipsilateral cortex, and a negative relationship between MK and Iba-1, MBP in ipsilateral cortex and hippocampus (P < 0.05). The MK in ipsilateral cortex and hippocampus were also correlated with MWM test results (P < 0.05). Our study suggests that DKI could be used to assess the microstructural changes associated with cognitive impairment in chronic TBI., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

Current results identified 4-substituted 2-phenylaminoquinazoline compounds as novel Mer tyrosine kinase (Mer TK) inhibitors with a new scaffold. Twenty-one 2,4-disubstituted quinazolines (series 4-7) were designed, synthesized, and evaluated against Mer TK and a panel of human tumor cell lines aimed at exploring new Mer TK inhibitors as novel potential antitumor agents. A new lead, 4b, was discovered with a good balance between high potency (IC50 0.68μM) in the Mer TK assay and antiproliferative activity against MV4-11 (GI50 8.54μM), as well as other human tumor cell lines (GI50<20μM), and a desirable druglike property profile with low logP value (2.54) and high aqueous solubility (95.6μg/mL). Molecular modeling elucidated an expected binding mode of 4b with Mer TK and necessary interactions between them, thus supporting the hypothesis that Mer TK might be a biologic target of this kind of new active compound., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Artesunate, a remarkable antimalarial agent, also reveals profound cytotoxic activity. In the present investigation, we compared the anticancer effects of artesunate on three colorectal cancer cell lines and analyzed the relationship between drug sensitivity and malignant phenotype of the tumor cells. The findings are as follows: poorly-differentiated was colorectal cancer cell line CLY showing nuclear beta-catenin accumulation and loss of E-cadherin; moderately-differentiated were Lovo cells with cytoplasmic distribution of the two proteins; and well-differentiated were HT-29 cells with membranous localization of them. Also, both in vitro and in vivo, poorly- or moderately-differentiated CLY and Lovo were more susceptible to artesunate treatment than well-differentiated HT-29. Furthermore, the sensitive response of CLY and Lovo to artesunate was associated with membranous translocation of beta-catenin and increased expression of E-cadherin, which indicated the inhibition of hyperactive Wnt signaling pathway and the reversion of the epithelial to mesenchymal transition, respectively. Due to the vital roles of Wnt pathway and the epithelial to mesenchymal transition in tumor differentiation, we thought artesunate could promote the re-differentiation and apoptosis of colorectal cancer cells by inhibition of hyperactive Wnt pathway and reversion of the epithelial to mesenchymal transition.

A new hexaaza macrocyclic ligand (L) bearing two 2-hydroxypropyl pendants, 6,19-bis(2-hydroxypropyl)-3,6,9,16,19,22-hexaaza-tricyclo-[22.2.2.2(11,14)]triaconta-11,13,24,26,27,29-hexaene has been synthesized and characterized. The macrocyclic ligand was isolated as a colorless crystal, monoclinic, P2(1)/n, with a=10.757(2), b=14.214(3), c=13.746(3) A, beta=101.40(3) degrees, V=2060.3(7) A3, Z=2, R1=0.0695, and wR2=0.1538 [I>2sigma(I)]. Potentiometric studies of the macrocyclic ligand and three types of amino acids, glycine (equal numbers of carboxylate and amino groups), aspartic acid (more carboxylate groups than amino group), and lysine (more amino groups than carboxylate group) have been performed. The stability constants for the new macrocycle and binary complexes of the amino acid with the macrocyclic ligand are reported. Binary complexes are formed in aqueous solution as a result of hydrogen bonding interaction and electrostatic attraction between the host and the guest. The binding Schemes for the recognition of amino acids are suggested. From the results, it seems that this new macrocyclic ligand is able to bind three different amino acids with selectivity in aqueous solution, and the strength of binding is of the order lysine < glycine < aspartic acid.