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Alzheimer's disease is a neurodegenerative disorder with Amyloid-β plaques onset, synaptic damage, and cognitive decline. Aβ deposits cause pathological events including oxidative stress, mitochondrial dysfunction, and neuron death. In this study, APPswe/PSENΔ9 double transgenic mice model was used to imitate Alzheimer's disease and the effect and possible mechanism of Andrographolide sulfonate were examined. Andrographolide sulfonate was given to the mice for 7 months before the onset of Aβ plaque. Spatial memory test showed that Andrographolide sulfonate treatment prevented cognitive decline. Aβ deposits were not affected while hippocampus and synapse damage was significantly alleviated. Mechanism studies showed that oxidative stress and mitochondrial swelling was reduced after Andrographolide sulfonate administration. These findings suggest that Andrographolide sulfonate, which has been applied in clinical medicine, might be a promising therapeutic agent for AD therapy via mitochondria protection., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Aberrant activation of NLRP3 inflammasome has an important function in the pathogenesis of various inflammatory diseases. Although many components and mediators of inflammasome activation have been identified, how NLRP3 inflammasome is regulated to prevent excessive inflammation is unclear. Here we show NLRP3 inflammasome stimulators trigger Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) translocation to the mitochondria, to interact with and dephosphorylate adenine nucleotide translocase 1 (ANT1), a central molecule controlling mitochondrial permeability transition. This mechanism prevents collapse of mitochondrial membrane potential and the subsequent release of mitochondrial DNA and reactive oxygen species, thus preventing hyperactivation of NLRP3 inflammasome. Ablation or inhibition of SHP2 in macrophages causes intensified NLRP3 activation, overproduction of proinflammatory cytokines IL-1β and IL-18, and increased sensitivity to peritonitis. Collectively, our data highlight that, by inhibiting ANT1 and mitochondrial dysfunction, SHP2 orchestrates an intrinsic regulatory loop to limit excessive NLRP3 inflammasome activation.

Despite advances in treatment, malignant glioma commonly exhibits recurrence, subsequently leading to a poor prognosis. As manganese (Mn) compounds can be transported by the transferrin‑transferrin receptor system, the present study synthesized and examined the potential use of Adpa‑Mn as a novel antitumor agent. Adpa‑Mn time and dose‑dependently inhibited U251 and C6 cell proliferation; however, it had little effect on normal astrocytes. Apoptosis was significantly elevated following treatment with Adpa‑Mn, as detected by chromatin condensation, Annexin V/propidium iodide staining, cytochrome c release from mitochondria to the cytoplasm, and the activation of caspases‑9, ‑7 and ‑3 and poly (ADP‑ribose) polymerase. In addition, Adpa‑Mn enhanced fluorescence intensity of monodansylcadaverine and elevated the expression levels of the autophagy‑related protein microtubule‑associated protein 1 light chain 3. Pretreatment with the autophagy inhibitors 3‑methyladenine and chloroquine enhanced Adpa‑Mn‑induced cell inhibition, thus indicating that autophagy has an essential role in this process. Furthermore, evidence of mitochondrial dysfunction was detected in the Adpa‑Mn‑treated group, including disrupted membrane potential, elevated levels of reactive oxygen species (ROS) and depleted adenosine triphosphate. Conversely, treatment with the mitochondrial permeability transition inhibitor cyclosporin A reversed Adpa‑Mn‑induced ROS production, mitochondrial damage and cell apoptosis, thus suggesting that Adpa‑Mn may target the mitochondria. Taken together, these data suggested that Adpa‑Mn may be considered for use as a novel anti‑glioma therapeutic option.

In this study, we reported the complete mitochondrial DNA sequence of the hybrid of Siniperca chuatsi (♀)×Siniperca kneri (♂). The total length of the mitochondrial genome is 16,493 bp, with the base composition of 28.61% A, 29.21% C, 16.21% G, and 25.97% T. It contains 2 rRNA genes, 13 protein-coding genes, 22 tRNA genes, and a major non-coding control region (D-loop region). The composition and order of these genes are identical to most of other vertebrates. All the protein initiation codons are ATG, except for COX1 that begins with GTG. The complete mitogenome of the hybrid of Siniperca chuatsi (♀) × Siniperca kneri (♂) provides an important data set for the study in genetic mechanism.

In the present study, the effect of asiatic acid, a natural triterpenoid compound, on murine experimental colitis induced by dextran sulfate sodium (DSS) and its possible mechanism were examined in vivo and vitro. Oral administration of asiatic acid dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco and myeloperoxidase activity were also significantly reduced by asiatic acid treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-α, IL-1β, IL-6 and IFN-γ, were markedly suppressed by asiatic acid. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in asiatic acid-treated mice, which suggested that the NLRP3 inflammasome activation was suppressed. In addition, we also found that asiatic acid dose-dependently inhibited IL-1β secretion, caspase-1 activation as well as inflammasome assembling in vitro. Furthermore, the mechanism of asiatic acid was related to the inhibition of mitochondrial reactive oxygen species generation and prevention of mitochondrial membrane potential collapse. Taken together, our results demonstrate the ability of asiatic acid to inhibit NLRP3 inflammasome activation and its potential usage in the treatment of inflammatory bowel diseases., (Copyright © 2014 Elsevier B.V. All rights reserved.)

We previously identified a novel synthesized metal compound, LMnAc ([L2Mn2(Ac)(H2O)2](Ac) (L=bis(2-pyridylmethyl) amino-2-propionic acid)). This compound exhibited significant inhibition on cancer cell proliferation and was more selective against cancer cells than was the popular chemotherapeutic reagent cisplatin. In this study, we further investigated the underlying molecular mechanisms of LMnAc-induced cancer cell death. We found that LMnAc achieved its selectivity against cancer cells through the transferrin-transferrin receptor system, which is highly expressed in tumor cells. LMnAc triggered cancer cells to commit autophagy and apoptosis, which was mediated by the mitochondrial pathway. Moreover, LMnAc disrupted mitochondrial function, resulting in mitochondrial membrane potential collapse and ATP reduction. In addition, LMnAc induced intracellular Ca(2+) overload and reactive oxygen species generation. Interestingly, its anticancer effect was significantly reduced following pretreatment with the antioxidant N-acetyl cysteine, indicating that reactive oxygen species triggered cell death. Altogether, our data suggest that LMnAc appears to be a selectively promising anticancer drug candidate.

Selectively facilitating apoptosis of activated T cells is essential for the clearance of pathogenic injurious cells and subsequent efficient resolution of inflammation. However, few chemicals have been reported to trigger apoptosis of activated T cells for the treatment of hepatitis without affecting quiescent T cells. In the present study, we found that asiatic acid, a natural triterpenoid, selectively triggered apoptosis of concanavalin A (Con A)-activated T cells in a mitochondria-dependent manner indicated by the disruption of the mitochondrial transmembrane potential, release of cytochrome c from mitochondria to cytosol, caspases activation, and cleavage of PARP. In addition, asiatic acid also induced the cleavage of caspase 8 and Bid and augmented Fas expression in Con A-activated T cells. However, following activation of T cells from MRL(lpr/lpr) mice with mutation of Fas demonstrated a similar susceptibility to asiatic acid-induced apoptosis compared with normal T cells, suggesting that Fas-mediated death-receptor apoptotic pathway does not mainly contribute to asiatic acid-induced cell death. Furthermore, asiatic acid significantly alleviated Con A-induced T cell-dependent fulminant hepatitis in mice, as assessed by reduced serum transaminases, pro-inflammatory cytokines, and pathologic parameters. Consistent with the in vitro results, asiatic acid also induced apoptosis of activated CD4(+) T cells in vivo. Taken together, our results demonstrated that the ability of asiatic acid to induce apoptosis of activated T cells and its potential use in the treatment of T-cell-mediated inflammatory diseases.

Mitochondrial homoplasmy is essential for normal development, as its heteroplasmy usually leads to abnormal or diseased phenotypes in mammals. So far, diverse mechanisms have been proposed to play roles in ensuring uniparental inheritance of mitochondria in many organisms. In recent years, hybrid yellow catfish from mating female yellow catfish (Pelteobagrus fulvidraco) with male darkbarbel catfish (Pelteobagrus vachelli) has been widely cultured in China due to its fast-growing. However, a high rate of abnormal and defective embryos was observed in the offsprings of hybrid yellow catfish. In this study, we systematically investigated the elimination process of paternal mitochondrial DNA (mtDNA) in yellow catfish and hybrid yellow catfish. The mtDNA contents significantly decreased in the isolated mature sperm compared with the semen. Different from the elimination of paternal mtDNA after fertilization in yellow catfish, paternal mtDNA was retained in the developmental embryos of hybrid yellow catfish as later as gastrula stage, indicating a delay of elimination for paternal mtDNA and mitochondrial heteroplasmy during embryogenesis in hybrid yellow catfish. Altogether, the present study suggests that mitochondrial heteroplasmy may affect embryonic development of hybrid progeny between catfish species. • Maternal inheritance of mitochondrial DNA is shown in yellow catfish. • A delayed elimination of paternal mtDNA in hybrid yellow catfish • A high malformation rate is observed in hybrid yellow catfish. [ABSTRACT FROM AUTHOR]

Asiatic acid (AA), a pentacyclic triterpene found in Centella asiatica , displays significant anti-proliferative effects on cancer cells in vitro although the underlying mechanism of this effect remains unknown. This study investigated the efficacy and mechanism of action of AA against lung cancer both in vivo and in vitro . Using the MTT assay, AA was found to induce apoptosis in a dose- and time-dependent manner, an effect enhanced by pretreatment with an autophagy inhibitor. It also elevated expression of microtubule-associated protein 1 light chain 3 (LC3) and decreased the expression of p62. Furthermore, exposure to AA resulted in collapse of the mitochondrial membrane potential and generation of reactive oxygen species (ROS), suggesting mitochondria are the target of AA. In the mouse lung cancer xenograft model, oral administration of AA significantly inhibited tumor volume and weight accompanied by significant apoptosis of lung cancer cells. In addition, it led to a significant decrease in the expression of proliferating cell nuclear antigen (PCNA). In summary, the results show that AA significantly reduces lung cancer cell growth both in vitro and in vivo and that the associated apoptosis is mediated through mitochondrial damage. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome sequence of the hybrid ofSiniperca kneri(♀) × Siniperca chuatsi(♂) is described in this study. The 16,488 bp long circular molecule consisted of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a control region, showed a typical vertebrate pattern. The overall base composition of the heavy strand is 28.59% A, 29.20% C, 16.25% G, and 25.96% T, with a slight AT bias of 54.55%. Except for eight tRNA and ND6 genes, all other mitochondrial genes are encoded on the heavy strand. There are 5 regions of gene overlap totaling 14 bp and 20 intergenic spacer regions totaling 91 bp. The complete mitogenome of the hybrid ofS. kneri(♀) × S. chuatsi(♂) could provide an important data set for the study in mitochondrial inheritance mechanism. [ABSTRACT FROM AUTHOR]

In the present study, the complete mitogenome of the hybrid ofSiniperca scherzeri(♀) × Siniperca chuatsi(♂) is determined to be 16,504 bp long and showed a typical vertebrate pattern with 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and a control region. The base composition of heave strand in descending order is C (29.61%), A (28.31%), T (25.61%) and G (16.47%), with a slight AT bias of 53.92%. All the protein-coding genes are initiated by typical ATG codon, except for COX1 gene with the initiation codon GTG. Nine genes end with the complete stop codon TAA or TAG, while the COX1, COX2, ND4 and CYTB genes terminate with an incomplete stop codon T. The complete mitogenome of the hybrid ofS. scherzeri(♀) × S. chuatsi(♂) could provide an important data set for the study in mitochondrial inheritance mechanism. [ABSTRACT FROM AUTHOR]

In this study, we determined the complete mitochondrial DNA sequence of the hybrid ofSiniperca chuatsi(♀) × Siniperca scherzeri(♂). The total length of the hybrid mitogenome is 16,497 bp, with the base composition of 28.61% A, 29.16% C, 16.23% G, and 26.00% T. It contains 2 rRNA genes, 13 protein-coding genes, 22 tRNA genes, and 1 control region. The composition and order of these genes are identical to most of other vertebrates. All the protein-coding genes start with ATG, except for COX1 with the initiation codon GTG. Three types of stop codons are used by the coding genes, including complete stop codons (TAA and TAG) and an incomplete stop codon (T). Three conserved domains were observed in the control region. The complete mitogenome of the hybrid ofS. chuatsi(♀) × S. scherzeri(♂) could contribute to a better solution of the study in mitochondrial inheritance mechanism. [ABSTRACT FROM AUTHOR]

In this study, we reported the complete mitochondrial DNA sequence of the hybrid ofSiniperca chuatsi(♀)×Siniperca kneri(♂). The total length of the mitochondrial genome is 16,493 bp, with the base composition of 28.61% A, 29.21% C, 16.21% G, and 25.97% T. It contains 2 rRNA genes, 13 protein-coding genes, 22 tRNA genes, and a major non-coding control region (D-loop region). The composition and order of these genes are identical to most of other vertebrates. All the protein initiation codons are ATG, except for COX1 that begins with GTG. The complete mitogenome of the hybrid ofSiniperca chuatsi(♀) ×Siniperca kneri(♂) provides an important data set for the study in genetic mechanism. [ABSTRACT FROM AUTHOR]